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“The way it moves between moments of wonder, humour and tragedy makes The Long Journey Home a rare pleasure among science fiction games.” Kotaku “Interacting with different alien races makes the universe in the game feel vivid and alive – that’s something The Long Journey Home does way better than other games in the past.” 90% – Gamereactor “The game can’t teach you everything in tutorial after tutorial. Thank goodness. You’d never start your doomed mission. But you’ll have to be patient with yourself. You know so little going into this.” 80% – GamingNexus

About This Game

System requirements.

OS *: Win 7, 8, 10, 64-bit
Processor: 3 GHz Dual Core CPU
Memory: 4 GB RAM
Graphics: NVIDIA GeForce 650 Ti / AMD Radeon HD 7790
DirectX: Version 11
Storage: 16 GB available space
Sound Card: DirectX 11 compatible sound card with latest drivers
Processor: 3GHz Quad Core CPU
Memory: 8 GB RAM
Graphics: NVIDIA GeForce 970 / AMD Radeon R9 380
Processor: i5 3GHz
Graphics: AMD R9 M380X
Storage: 15 GB available space
Additional Notes: SSD and Controller recommended
Graphics: AMD Radeon Pro 560

© Copyright 2017 Daedalic Entertainment Studio West GmbH and Daedalic Entertainment GmbH. The Long Journey Home is a trademark of Daedalic Entertainment Studio West GmbH. Daedalic and the Daedalic logo are trademarks of Daedalic Entertainment GmbH. All rights reserved.

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The Long Journey Home review

A punishing resource and repair system gets in the way of the long journey home's characterful exploration., our verdict.

A savage, sometimes frustrating space exploration game that succeeds because of beautiful design and a compelling universe.

PC Gamer's got your back Our experienced team dedicates many hours to every review, to really get to the heart of what matters most to you. Find out more about how we evaluate games and hardware.

What is it: A procedural space exploration and resource gathering game where everything will go wrong. Publisher: Daedalic Entertainment Developer Daedalic Studio West Reviewed on: Windows 10, 16GB RAM, Intel Core i7-7700, NVidia GeForce GTX 1070 Expect To Pay: £34 / $40 Multiplayer: No Link: Official site

One of my favourite moments in The Long Journey Home happens before I take off. I spend 15 minutes analysing the characters, picking the ones I’d tolerate being trapped with, trying to work out if there was a secret reason I should take a potted plant into the space. It didn’t matter. Three hours later they were all dead from burns and/or suffocation. This doesn’t mean that what came after was bad (apart from the deaths), but just that the game does a smart job of defining the gravitas of your mission. You’re going into space and, despite the name, you’re probably not coming back.

Your four adventurers are flung to the far side of universe and must navigate their way home by farming resources, maintaining their ship, and negotiating with a selection of distinct alien races. The journey is different each time, and their are loads of combinations of crew and craft, so there’s no ‘right’ way to play it. (Although I discovered multiple times there’s definitely a ‘wrong’ way.) The Long Journey Home largely delivers on the promise of grasping and desperate journey across space, but it’s deliberately tough. Your crew will die. Your equipment will break. Aliens will take your things.

I went into the game expecting the difficulty to be high, but there are times when the balance feels off. You gather resources by dropping your lander onto planets, drilling for metals, and sucking up gases like a vacuum cleaner. You’re given a description of each planet before you land, so you don’t have to be reckless, but it’s always a risk. Any errant bumps and crashes can cause injuries to your pilot which can only be cured with expensive medpacks. Each excursion only takes a few minutes, but it’s still a gruelling, repetitive way of gathering essential resources, and it isn’t always fun. Variables such as convection, which blows your lander off course, only compound the frustration. I pimped my lander to reduce the effect of wind, but I started to dread the threat of landing on a planet’s surface. Sometimes, you have no choice but to brave the most difficult planets, and it often results in disaster.

Gathering essential resources can be a chore, but it’s not the only way to play the game. The Long Journey home is full of alien encounters, which feel like the heart of the game. You could push through by just collecting resources, but interacting with the aliens and completing tasks feels like the more rewarding route. I searched for lost artifacts, located stranded explorers, and helped religious zealots wipe out alien infestation. It felt more righteous than that reads. Each encounter feels different and the aliens are all different, so you get real sense of the universe being inhabited by creatures who were there before you. Being able to actually talk to the aliens helps, too—it’s precisely the thing I felt No Man’s Sky lacked, and it brings this universe to life.

It’s a bright, interesting system to explore. Characters are crisply designed, and I got a strong sense of who everyone was just by looking at them. Planets are striking and varied. The music makes everything you do feel important—even asking a crewmate what they think about a medicinal slime takes on a cosmic significance. But it’s the story that stands out, adding definition and reason to a world that would otherwise seem soulless. It’s good enough, in fact, that sometimes I wished that I could enjoy it without all the broken bones, fuel ruptures, and suffocation. The unpredictability can feel punitive.

Likewise, some of the random, wear-and-tear problems your ship experiences feel mean-spirited. Mechanical failures are common, and they’re expensive to fix. There are also occasions where it feels like a solution should come quicker than it does. I foolishly accepted a gift from a suspiciously-friendly race of infectious plant monsters, because I didn’t want to seem rude—even in space, it’s important to remain civil—and I had to watch as my crew slowly became infested, aware of the issue but unable to fix it. Each playthrough is defined by the things that go wrong, which makes the game striking and memorable, but too often the resources needed to fix problems are too precious or too rare, and the game piles misery upon misery.

Despite this, I like the game enough to keep coming back, and I’m ready to start my fifth (certainly doomed) attempt to get home. Each journey is a learning experience, and the vague promise of success is enough to keep me interested, even if half the missions end up with me screaming at my lander as it blows around like a duckling on a windy day. If nothing else, I won’t rest until I find out what that bloody plant does.

Disclosure: PC Gamer contributor Richard Cobbett worked on The Long Journey Home.

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The Long Journey Home

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Endless Space - Explore a living, procedurally generated universe inspired by both classic and modern Science Fiction. Meet different aliens. Find different stories. Take different risks. Learn the secrets of the universe and with them, new possibilities.
Hidden stories - Raid alien tombs full of traps and treasure. Compete in the galaxy’s greatest combat tournament. Find and research strange artifacts, and use your crew’s skills to find out whether that old skull is just a piece of bone, or the Holy Grail of an aggressive new species.
A crew worth leading - Choose four out of ten experts, all with personality as well as specialties. Far from just stats, you’ll come to know them as they share their feelings, their fears, their excitement and their concerns on the trip and your decisions. Learn how best to use their skills to help the others… and who might be willing to sacrifice themselves to get the others back Home.

© Copyright 2016 Daedalic Entertainment Studio West GmbH and Daedalic Entertainment GmbH. The Long Journey Home is a trademark of Daedalic Entertainment Studio West GmbH. Daedalic and the Daedalic logo are trademarks of Daedalic Entertainment GmbH. All rights reserved.

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The Long Journey Home is a game of great ambition — an ambition that pulled me in before I realized the limited scope of its mechanics.

If you watch a trailer for The Long Journey Home or read the description on its Steam store page, you’ll get a sense for what this game wants to be: a procedurally generated science-fiction universe; a coherent, emergent sci-fi odyssey that players can shape through diplomacy, craft and skill. It’s a tantalizing idea, and one that got me immediately excited to discover more.

The reality is a lot less appealing than the pitch. The Long Journey Home contains some colorful ideas, but it’s dragged down by an overwhelming dependence on repetitive, discouraging tests of mechanical patience and skill.

The Long Journey Home stylizes itself as a more scientific, literary roguelike. You play as the guiding hand behind an expedition to test humanity's first jump drive. It malfunctions, of course, and deposits you on the other side of the galaxy, around a hundred jumps away from Earth. To get back, you'll have to meet alien races, conquer hostile terrain and upgrade your ship. At least, that's the framing idea.

The vast majority of my time with The Long Journey Home was spent controlling the velocity of a fragile spacecraft as I harvested resources from procedurally generated planets. On the primary star map, gravity is represented as a grid, folding and dipping as planets, moons and stars leave their gravitational indentations. And then there's the shuttle landing minigame, where you have to settle your lander down on a resource while managing approach vector, wind speed and escape velocity.

These are the overwhelmingly primary mechanics of the game. No matter what the page on the Steam store promises about diplomacy, trading and surprise encounters, eighty percent of the actual game is trying not to smash into the ground during these frustrating sequences.

It's extraordinarily difficult to navigate around mountains, planets and meteorites in The Long Journey Home . A small miscalculation of velocity when you're trying to achieve stable orbit, and you bounce off the atmosphere, damaging your ship, injuring your crew and forcing you to try again. Even after over a dozen hours familiarizing myself with the game and its controls, I found myself approaching each new planet three or four times, swinging wide, coming up short, too fast, too shallow.

The lander sequences are even more unforgiving and awkward. I routinely shaved off over half the lander's health just trying to perch it atop the meager resources the planet offers. Generally speaking, I did more damage to my lander trying to collect metal than I could ever repair with the metal harvested. Not to mention that bouncing your lander off the surface will seriously injure your pilot. A simple mistake can cause two or three semi-permanent damage conditions that you'll have to spend precious (and rare) items to repair.

The Long Journey Home is a game dependent on extremely miserly resource management, and any kind of deep progress is only made possible by planning your expeditions with care. The game gives you an impression like you don't have to land on dangerous planets, that you can pick and choose to only make dangerous landings in emergencies, but the math just never added up that way. It can take over five individual metal nodes to fix your ship, and a single mineral resource is almost never enough to allow a system-to-system jump. Being imprecise with velocity and skimming off a planet's atmosphere can give you a 30 percent penalty to filling up your jump drive, which can quickly leave you stranded.

So you have to hoover up everything you see to survive. But there are so many serious, long-lasting, deeply impactful penalties for even the simplest of navigation errors in the simplest conditions that it's hard to come out ahead. I routinely quit back to the main menu and reloaded over and over to ensure that I would pull off successful resource runs with minimal damage to my lander. The most intriguing elements of The Long Journey Home are the ones teased as being in the late game: discovering ancient relics, resolving major interstellar conflicts, grand arcs of plot that are only suggested in the early game. But the whole thing is so mechanically punitive, so quick to mire you in the simplest, least engaging mechanics, that actually arriving at those most complex levels seems as distant as Earth itself.

Combat adds a whole new dimension of pain to the experience: Your ship, at least to start, is only capable of firing broadsides. These sequences play out like top-down naval engagements where your puny human vessel, firing and moving as agonizingly slowly as a Spanish galleon, must spar off against alien ships with homing missiles and defensive fighters. After dozens of fights, I still couldn't pin down proper aiming technique. My only workable tactic was to ram the enemy vessel, hook on the geometry of their ship, and fire point-blank. Combat can be expected about once per star system after the first star cluster, with some systems holding a half dozen enemy ships who all ask for Blood or Coin.

The aggressive pace of the combat encounters further gates the narrative content behind a skill wall. There are complicated systems of allegiance with the aliens you meet, and they respond in complex ways to prompts and quests. For example, I accidently showed the leader of a pirate base the head of one of his lieutenants, whose ship I destroyed when they tried to rob me. At first, he screamed at the insult, then immediately offered me a job as a pirate for my bloodthirsty gall. Or consider an over-friendly race who offer helpful items, leaving you to realize too late that the items give your crew an infestation. Narratively speaking, this is engaging. But mechanically, it’s infuriating: insult on top of injury. The excitement of being offered a piracy job is dulled when you consider that it means you have to spend more time with the combat minigame.

I can tell that The Long Journey is a complicated game, but the narrative is the least complex thing about it. That's the fundamental frustration of the game: It's marketed to people exactly like me, sci-fi fans who want a video game that's grounded in the optimism and curiosity of the science fiction novels of yesteryear. Artistically, thematically, the game follows in those footsteps. But don't get the impression that it's a casual game by any means. It's a cruel and finicky physics puzzler. It requires absolute attention be paid to each one of its many mechanical systems, even on the easiest difficulty. It supposes the power of your imagination is enough to make micromanaging the curve and flight velocity of a cursor on a screen exciting.

The Long Journey Home may hold many secrets and wonders, but it's hard to hold on to the promise of them when the game's more likely to break both your legs as soon as you step off the front porch. The promise of a truly narrative-driven roguelike is tantalizing, but this isn’t that game. It's just as tied to your skill with the controller as any bullet hell — more so, really, because you carry the consequences of even the slightest mistake a long ways before finally seeing the game over screen. It promises to be a game about the wonder of unbound space; instead, it’s more about the infuriating heartbreak of high wind speeds in a low gravity environment.

The Long Journey Home was reviewed using a pre-release final Steam code provided by Daedalic Entertainment. You can find additional information about Polygon’s ethics policy here .

Featured Content / Reviews

The Long Journey Home Review

by Alex Fuller · November 30, 2018

Are We Nearly There Yet?

Originally released for PC last year before making its way onto consoles this November, The Long Journey Home is a different title from what many have come to expect from Daedalic Entertainment, a developer and publisher more renowned for its various adventure titles. Tasking players with guiding a ship across the far reaches of space, The Long Journey Home never attempts to make its journey particularly thrilling, but the deliberate pacing combines well with its risk-versus-reward elements and the simple enjoyment of travelling the stars.

The Long Journey Home begins with players selecting the crew, spaceship, and universe seed for a mission to test a new faster-than-light drive. There are ten potential members to fill out the four available crew slots, each with their own item and skill set, as well as three spaceship and lander options providing different attributes in terms of speed, cargo space, and so forth. As the title alludes to, the test does not go quite as planned, and the crew find themselves and the ship far, far away from home. Left to their own devices, the crew must try and find the way home while dealing with dangerous locations, limited resources, and aliens of the friendly and not-so-friendly varieties.

The universe seed is the primary factor that will affect a playthrough of The Long Journey Home . It determines what players will be able to encounter, from the alien species present to the general makeup of the stars and galaxies they will be roaming in. This leads to a wide variety in difficulty between playthroughs, with certain seeds being far more welcoming to new players than others. However, there is always an element of luck to things, and even on an easier seed and with the game’s story difficulty setting, there will be many opportunities for the journey to end prematurely.

Successfully slinging the ship between planets is highly satisfactory.

The structure of the game has players jumping from star system to star system, stopping off at planets, space stations, and asteroid fields to find resources, investigate points of interest, or take on small jobs. Gravity plays a big part in travelling between locations in the star system, and players are heavily encouraged to make use of gravitational slingshots wherever they can to ensure they don’t needlessly waste fuel. Once players have successfully gone into orbit around a planet or moon, they can send the lander down to the surface, where it will have resource points that can be gathered and maybe other points of interest such as an alien settlement or set of ruins to explore. The structure is decently paced, with planetary stopovers always being a quick in-and-out, and it makes for an engaging journey where it can be easy and enjoyable to get sucked into a mindset of “just one more system…”.

The game’s controls are nice and straightforward, but one of the few annoyances comes with controlling the lander. Some planets are more hostile and difficult to land on than others, some having high gravity or winds, others prone to earthquakes or lightning storms, with players able buy and attach modules to the lander to help against these. However, the game always seems to enjoy throwing the lander down at high speed, so that even a lander that has in theory been modified to cope with the conditions will still be flung onto the surface despite the player’s best attempts. In these cases all players can do is hope the damage isn’t too severe and just carry on. It’s understandable that the game is promoting a sense of risk-versus-reward on using the lander, but it’s nevertheless frustrating, particularly given how much more enjoyable and comparatively friendly interplanetary travel is.

Combat encounters are not worth actively seeking out.

Though there are some interesting quests and pieces of lore to discover, there isn’t much of a narrative to The Long Journey Home . Part of this is because quests and jobs often require that players go out of their way to complete them, which is generally a high risk to take considering the limited resources available and the propensity of the ship to be damaged through wear and tear when it jumps. Even on the friendly seeds, money needed for repairs can be hard to come by and so time spent going back and forth in one sector can be very costly in the long run. There are very few named characters in the game, and those that are named generally appear for a single quest before they disappear and are never heard from again. The Long Journey Home is undeniably more about trying to survive the journey above anything else, but there’s some interesting variety to the alien species that can appear, with some enjoyable writing and inconsequential banter between the crew that appears from time to time.

Crew members don’t gain any new skills on top of those they come with; anything they can do to help depends on items picked up throughout the voyage. The main concern is keeping them alive, as various things such as radiation from stars and heavy lander impacts can cause injuries, five of which will cause that crew member’s death. Instead, any progress comes from what helpful items players are able to attain, and crew members can be help get these. For example, Ash is able to turn alien flora into medical items, used to heal aforementioned injuries. Meanwhile, players can also buy new modules for the ship or lander that will provide bonuses such as improved radiation shielding. It all follows the theme of survival above anything else.

Combat is not very interesting and more often than not best avoided. Combat will see the ship come up against another ship, usually bigger, which may itself spawn additional smaller ships. The ships then fly around each other, shooting in pre-defined directions — the default weapon has the player ship fire up to four projectiles directly port and starboard, with players able to buy upgrades from a very limited selection of weapons and shields — then recharging before firing again. If players win, they may be lucky enough to receive a paltry set of credits or resources that may just about cover any repairs. If players lose, then it’s time to rewind back to the start of the star system or start the entire journey anew. The combat itself is straightforward, but is rarely worth the time and effort.

Some planets have very pretty backdrops, but be prepared to see similar ones elsewhere in the galaxy.

There’s not too much to say about the audio in The Long Journey Home . The best thing to say is that the atmospheric music tracks do a nice job combined with the gravitational simulation to make the journeys between planets nice and chilled out. Sound effects are fine, but there’s no voice acting, though given the general lack of narrative in the game, there isn’t much to be gained even if it was present. Visuals also do the job well, with a nice and clear UI, but the positives reduce out over time. Some planets are pleasing to look at, but by the time players are through they will have seen all the templates multiple times. The same goes for the alien species, there is good variation between them, but just one design for each species and nothing to distinguish individual encounters.

The Long Journey Home doesn’t outstay its welcome. A successful journey should take most players around ten hours, which is a good length for those who just want to get home and enjoy the accomplishment while the gameplay cycle remains enjoyable. Meanwhile, the way the universe is generated with seeds means that those who are interested in seeing everything the game has to offer as well as find new challenges have many reasons to keep coming back. It never offers the most in-depth or exciting gameplay moments, but the overall experience of The Long Journey Home is an enjoyable one.

Good at sucking players into the journey

Using gravity is fun

Combat feels like an afterthought

Some lander annoyances

Tags: Daedalic Entertainment PS4 The Long Journey Home

Alex Fuller

Alex joined RPGamer in 2011 as a Previewer before moving onto Reviews, News Director, and Managing Editor. Became Acting Editor-in-Chief in 2018.

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Wot I Think: The Long Journey Home

Star Trekkin'

It's not all that long, the journey, but it is very busy. About six hours might do the trick, but you're likely to get distracted along the way. Part Star Trek Voyager and part The Odyssey, The Long Journey Home [ official site ] puts you in charge of a small crew who have been stranded far from Earth due to a tech malfunction, and must make their way home, making friends and enemies along the way. Though it's clearly inspired by the likes of Star Control and Captain Blood, I've found myself thinking of No Man's Sky as I play. Here's wot I think.

TLJH is one of those games that feels like lots of mini-games stitched together. There's some basic resource management, Thrust-like planetary landings, conversations with alien races, combat, and star system navigation. It's a game that could easily end up being less than the sum of its parts, but the structure of the journey itself ties everything together and makes each decision and challenge important. Whether you're figuring out if a diversion to save a plague-ridden planet is worthwhile or even a realistic possibility given how limited the essential resources needed to keep your ship running might be.

There are four things to consider. Your crew are a primary resource and as they pick up injuries, your journey becomes more perilous. Those injuries come from rough landings, risky flying, certain encounters and ship-to-ship combat. People are your most precious resource, and are irreplaceable, though they can be healed if you find the appropriate items.

The other three resources you'll need to trek across the stars can all be picked up along the way and the core loop of the game involves ensuring you gather enough of each at each stop along the route.

First of all, you'll need fuel to move within systems, and to send your single-seater lander craft down to the surface of planets. It's planetside where you'll find the gases, metals and minerals that are used for refuelling and repair, but you might also want to visit some planets as part of a quest chain, or on the off-chance there'll be some mystery to uncover. But, yes, fuel is of vital importance, and you'll use it to move between planets and find it on planets.

And then there's a second kind of fuel that lets you jump between systems. The ingredients for that are found on planets as well, and you'll always have a fairly good idea what you're going to find once you settle into orbit. A scan tells you what kind of resources to expect, and what quantities they might be found in, and information about inhabitants, atmosphere, weather and overall threat level.

If a planet has firestorms, high winds and scarce supplies, it's probably not worth risking your lander and crew. You can repair both your ship and lander, and that's where the third resource, metal, comes into play.

On one level, that's how The Long Journey Home works; you travel from place to place, gathering enough resources to ensure you can make the next jump, or survive the next tricky landing in order to get the fuel to make the jump. That's where it reminds me of my hours with No Man's Sky, a game in which I never cared for the journey so much as the destination. The lure of discovering new species and biomes was powerful, for a few days, and part of the attraction was knowing that everything I saw mine and mine alone. Discoveries born of code and procedural design.

There is randomisation in The Long Journey Home as well, but it affects the order of things rather than the things themselves. The systems you'll pass through on your way back to our solar system are different each time, but the things within them are hand-crafted. There are several species to encounter, all with their own stories, dialogues and quest chains. Those quests range from delightfully silly interstellar quiz shows and tests of strength to genocide and flirtations with transcendental beings. What they all have in common is a sense of mischievous wit in the writing, which is courtesy of RPS columnist Richard Cobbett, a man who has forgotten more about RPGs and their tropes than most of us have ever known.

The combination of resource-gathering and wordy adventures is an odd one, but it's mostly successful. At worst, the actual business of scooping up fuel and minerals becomes busywork, interrupting the flow of a quest, and the limited number of encounters means that you'll start to see repetition after a few playthroughs. Thankfully, running into aliens you've already met on a previous journey doesn't mean you're in for an identical story – some encounters have fairly predictable outcomes, but some branch and twist, and there are even emergent qualities to some stories, which can be derailed or unexpectedly collide with one another.

There's a lot to like in those encounters but it's hard to escape from the feeling that the actual machinery driving the game is simpler than I'd like it to be. If you come for the stories, you still have to do the work in between them, as if visiting a library with a byzantine membership system that requires you to sign up again every time you want to borrow a book.

Take the lander sections: they're beautiful and simple enough, rarely taking more than five minutes to complete, even if you actually explore the surface and have a mini text adventure rather than just scooping up resources before jetting away. But they're also repetitive and a couple of mistakes can make the cost of landing heavier than rewards. I'd describe The Long Journey Home as a difficult game, given how hard it is to get home, but it's an oddly pitched difficulty. I'm more likely to peter out than to explode in a blaze of glory or perish in a calamitous misadventure.

Simply put, getting home is hard work and even though there are loads of amazing adventures to be had along the way, you'll also be carrying out a lot of maintenance. Think of this more as a warning than a condemnation because I'm still enjoying the game after thirty-five hours of playing. There's something quite soothing about the repetition that puts Long Journey Home into my Podcast Pile – which is to say, the pile of games that I play while listening to podcasts. That's not a bad pile to be in given how many podcasts I listen to every day.

And, yes, it still reminds me of No Man's Sky, but with these discrete mini-games instead of the arduous walking and gathering and crafting and inventory juggling. It also feels like a successor to Digital Eel's Weird Worlds: Return to Infinite Space, and a stronger one than the actual sequel. There's not quite enough here to win me over completely, but there's more than enough to make the numerous trips I've made worthwhile, and part of the charm is in never knowing if there's anything left to discover. The stars are strange and home to many mysteries and it's tempting to stick around until I've seen them all. But keep in mind that there's lots of work to do along the way.

The Long Journey Home is available now for Windows, via Steam and GOG .

Disclosure: Richard Cobbett wrote the words and has a regular column on RPS that I edit most weeks. The fact that I have to look at so many of his words as part of my day-job and actually enjoyed playing a game that was stuffed with even more of them could probably be seen as a compliment.

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From the bridge of your ship, you see a million points of light. Only one of them matters. Home.

It was only supposed to be a short trip. But when your jump drive malfunctions, you and a mismatched crew of specialists along for the ride find yourselves trapped and alone on the wrong side of the galaxy. The only way back is through. Forge alliances with strange Alien Races . Explore distant Planets for the Ruins , Artifacts and Resources they hide. Harness your crew’s Skills , from archeology to diplomacy. Make deals and moral decisions that change the universe. Do whatever it takes to survive.

And every game, enter a new galaxy. Will you find yourself welcomed by Traders and noble warrior knights... or surrounded by Pirates , psychopaths, and an unspeakable cosmic horror that threatens to snuff out the stars themselves. One destination. Endless adventures. Where will your Journey take you?

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The Long Journey Home

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It was supposed to be a short test run – a quick flight to Alpha Centauri and back. But when mankind’s first experimental jump drive goes wrong, you and your crew find yourselves trapped on the wrong side of the galaxy. Now, you are entirely on your own – and the only way back leads through the vast unknown of outer space. On your strange journey, you will encounter unforeseen obstacles and unimaginable treasures. You will fail and you will pick yourselves up again. You will suffer painful losses and also make new friends – in a vibrant universe that changes its design with every new journey. Your most important goal: Bring your crew back home to their families and friends. The Long Journey Home combines an open world full of galaxies, planets and anomalies with quests and mechanics of a rogue-like RPG. You have to make decisions – and choose to live with the consequences. One destination. Endless adventures. Where will this journey take you?

The Long Journey Home

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The Long Journey Home Media

THE LONG JOURNEY HOME Teaser

Critic Reviews for The Long Journey Home

When The Long Journey Home focuses on interactions with a diverse and entertaining cast of aliens across its procedurally generated star systems, it's possible to find a degree of wonder and personality that many roguelike seldom achieve. Unfortunately, such interactions take a back seat to a barrage of frustrating minigames with rewards that rarely match the risks. The experience as a whole suffers for it.

Read full review

A savage, sometimes frustrating space exploration game that succeeds because of beautiful design and a compelling universe.

The Long Journey Home promises much more than its punishing gameplay can deliver on

Areajugones

Daedalic has created a very brave space roguelike that features strategy elements and a huge universe to keep us in front of our screens.

Review in Spanish | Read full review

God is a Geek

The Long Journey Home has some great ideas. But ultimately it is a victim of its grand ambition. Repetitive, often frustrating gameplay further mar the experience.

COGconnected

The Long Journey Home is bound to drift to the far left side of my Switch home screen, but I hope it’s not forever. I will keep my eyes peeled for an announcement promising “drastic changes.” In the meantime, I will dream of a better game.

The Long Journey Home is a roguelike that tries to do things differently but it still fails to become accessible enough to a wider audience. While there are some interesting mechanics and features, the bad controls for both ship and lander and the lack of precise information will put more than a few players off.

Gaming Nexus

The Long Journey Home is a roguelike sci-fi survival simulator fueled on hope and hopelessness. Bring them home, commander. But be ready to die a hundred deaths before that ever happens.

A Long Journey Summary & Analysis by Musaemura Zimunya

Line-by-Line Explanation & Analysis
Poetic Devices
Vocabulary & References
Form, Meter, & Rhyme Scheme
Line-by-Line Explanations

"A Long Journey" is a free verse poem by the Zimbabwean poet Musaemura Zimunya. Zimunya included "A Long Journey" in his book Country Dawns and City Lights , published in 1985—just five years after Zimbabwe attained independence from Britain. In “A Long Journey,” a Zimbabwean speaker describes the effects of industrialization and the complex changes that their village undergoes during British colonial rule, appreciating the many comforts and conveniences of modern life while also struggling with the immense legacy of suffering and violence that preceded it.

Read the full text of “A Long Journey”

The Full Text of “A Long Journey”

“a long journey” summary, “a long journey” themes.

The Complicated Legacy of Colonialism

The Cost of Development

Line-by-line explanation & analysis of “a long journey”.

Through decades that ... ... long long journey

When the motor-car ... ... every village boy

With the arrival ... ... behind the horizons

Lines 12-13

Such a long ... ... bush to concrete

Lines 14-17

And now I ... ... my mother country

Lines 18-22

I fight in ... ... rain and cold

Lines 23-27

We have fled ... ... rattling around me

Lines 28-30

We moved into ... ... for our shirts

“A Long Journey” Symbols

City Lights

Line 25: “the halo of ,” “tower lights”
Line 28: “We moved into the lights”

“A Long Journey” Poetic Devices & Figurative Language

Lines 1-2: “decades that ran like rivers / endless rivers of endless woes”

Alliteration

Line 1: “ran,” “rivers”
Line 3: “jail”
Line 4: “journey”
Line 5: “car came”
Line 6: “cart”
Line 7: “but,” “bicycle,” “Britain”
Line 8: “boy”
Line 17: “capital,” “country”
Line 19: “road runs”
Line 23: “witches,” “wizards”
Line 26: “blood”
Line 27: “bones”
Line 1: “rivers”
Line 2: “endless rivers of endless woes”
Line 3: “pick and shovel sjambok and jail”
Line 4: “long long”
Line 12: “long travail”
Line 13: “long journey”
Line 22: “wind and rain and cold”
Line 24: “long long road”

Extended Metaphor

Line 4: “O such a long long journey”
Line 13: “a long journey from bush to concrete”
Lines 19-22: “but my road runs and turns into dusty gravel / into over-beaten foot tracks that lead / to a plastic hut and soon to a mud-grass dwelling / threatened by wind and rain and cold”
Lines 28-30: “We moved into the lights / but from the dark periphery behind / an almighty hand reaches for our shirts.”
Line 3: “through pick and shovel sjambok and jail”
Line 6: “the sledge and the ox-cart began to die”
Line 15: “eighteen ninety”
Lines 16-17: “new-found luxury / in this the capital city of my mother country”
Lines 19-22: “dusty gravel / into over-beaten foot tracks that lead / to a plastic hut and soon to a mud-grass dwelling / threatened by wind and rain and cold”
Line 23: “witches and wizards”
Lines 26-27: “I hear the cry from human blood / and wicked bones rattling around me”

“A Long Journey” Vocabulary

Select any word below to get its definition in the context of the poem. The words are listed in the order in which they appear in the poem.

Eighteen ninety
Over-beaten foot tracks
(Location in poem: Line 3: “through pick and shovel sjambok and jail”)

Form, Meter, & Rhyme Scheme of “A Long Journey”

Rhyme scheme, “a long journey” speaker, “a long journey” setting, literary and historical context of “a long journey”, more “a long journey” resources, external resources.

Zimbabwe's History — Read a brief history of Zimbabwe via the Encyclopedia Britannica.

Zimunya Sings — Watch a video of Zimunya performing.

A Brief Biography — Learn more about Zimunya's life and work.

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Retro find: pickles were stars long before tiktok trend of dipping them in dr pepper.

The journey from cucumber to pickle is long, arduous journey.

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Some stars only get their big break after putting in years of work.

Pedro Pascal played numerous bit parts before making it big on “Game of Thrones.” Bryan Cranston only became a household name after “Malcolm in the Middle.” Pickles, after struggling for decades, became a viral celebrity after starring in Dr Pepper.

Empty cans of Dr. Pepper soda sit stacked in the warehouse before being filled at the Dr. Pepper Snapple Group Inc. bottling plant in Louisville, Kentucky, U.S., on Tuesday, April 21, 2015.

This quirky video from 1980 explores how hard it is for a cucumber to break into stardom.

It follows one cucumber, fresh off the farm, as it tries to make it amongst the glitz and glamour. It is a difficult journey. The vegetable is just one of many hoping to make it to the big time. The path is long and arduous. Some find it too hard to handle, breaking under the pressure.

Our pickled protagonist survives and makes it to the big time — but is it truly what he wanted?

WATCH the hilarious video to discover if our briny buddy savored his slice of the limelight.

If you enjoyed this video, here are a few more blasts from the past.

Do you think soda belongs in baking? This retro find has recipes using Coke in everything

Coca-Cola muffins, Coca-Cola cobbler, Coca-Cola salad? Would you try these cola-infused recipes from 30 years ago?

RETRO FIND: 100-foot sandwich is 100x better than average

This colossal sandwich may not be a club, but it is in a league of its own.

WATCH: Man went way beyond cooking eggs on hot sidewalk

This chef took advantage of an '80s heatwave and a manhole cover to cook food in a crazy way.

California State University, Sacramento

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Dean’s award 2024 – after a long and challenging journey, manar tayeh graduates as one of sacramento state’s top students.

By Cynthia Hubert

May 13, 2024

It took her more than a decade, but Manar Tayeh never gave up on the idea of earning her college degree.

Not only is Tayeh graduating this month from Sacramento State, but she will do so as one of this year’s top students. She is the Dean’s Award winner for the College of Health and Human Services. Deans’ Awards are given at Commencement to the top graduating student from each of Sac State’s seven academic colleges.

Tayeh’s degree is in Communication Sciences and Disorders. She plans to return to Sac State in the fall to pursue her master’s, the next chapter in an educational journey that has been long and challenging.

She grew up in Brooklyn, part of a Middle Eastern culture in which girls were not encouraged to attend college. But she valued education, and wanted to pursue a degree.

“Communication is everything. I’m so excited at the idea of being part of changing someone’s life for the better.” -- Manar Tayeh

She enrolled at CUNY Brooklyn College, originally studying education, but after two years moved across the country to San Jose to be closer to her husband’s family. She soon discovered she was pregnant, and put her education on hold. The family grew to include three children.

“But college was always in the back of my mind,” Tayeh said. “I was afraid I would lose the drive the longer I waited, but I really didn’t. I saw the importance of education, and I wanted to show that to my son and my two daughters.”

In 2021, the family moved to Sacramento, and Tayeh set her sights on Sac State. By then, a cousin had been diagnosed with autism, which sparked her interest in speech and language pathology.

“At first I just wanted to get my degree and be done,” she said. But she found that she loved her classes, her professors and her chosen field.

“I made lots of friends who also were moms, and we lean on one another,” she said. “All of my professors were amazing.”

Her husband’s flexible schedule helped her spend quality time with her children, who are now 11, 8, and 5, while she juggled classes and studying.

As she got closer to finishing her degree, she began to contemplate graduate school.

“It really wasn’t in my mind when I started, but I just love school and I want to continue my journey,” she said.

In nominating Tayeh for the Dean’s Award, Associate Professor of Communication Sciences and Disorders Laura Gaeta cited her “unwavering perseverance, resiliency and determination.”

She is “highly engaged, motivated, and a collegial peer in her large, diverse cohort,” Gaeta wrote.

Eventually, Tayeh would like to work as a speech and language pathologist, helping people who have suffered health crises regain their ability to communicate.

“Communication is everything,” she said. “I’m so excited at the idea of being part of changing someone’s life for the better.”

Tayeh, who earned a 4.0 GPA at Sac State, never imagined that she would graduate as one of the most exceptional scholars at her University.

“It feels surreal,” she said. “I almost can’t believe it.”

“But I guess that’s what happens when you’re doing something because you want to do it,” said Tayeh. “It’s not so hard if you’re doing something you love.”

Share This Story

About Cynthia Hubert

Cynthia Hubert came to Sacramento State in November 2018 after an award-winning career writing for the Sacramento Bee. Cynthia believes everyone has a good story. She lives in East Sacramento with her two cats, who enjoy bird-watching from their perch next to the living-room window.

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Texas Tech Now

Media and communication graduate earns degree after decade-long journey.

May 10, 2024

Gini Wilbanks proves you can have it all, just not all at once.

Gini woke up, her heart mimicking the pulsing beat of her alarm.

It was another morning of a racing heart and a sick feeling in her stomach. She wondered if her family had made the right decision moving to Round Rock, Texas. She made her way to Elijah's crib, picking up her 6-month-old who was crying. She wanted to join him, but she was too exhausted to cry.

Gini and her husband Josh had moved from Lubbock so Josh could take a job near Austin. He had recently graduated from Texas Tech University, but Gini still had roughly 40 credit hours to finish. The move away from campus meant a change in major for Gini. The former Creative Media Industries student switched to Public Relations & Strategic Communication Management.

She was getting close to finishing her degree, but on this morning, the finish line felt far. Gini started making breakfast for herself and her two older children, Adeline and Charlotte.

“I was postpartum, and I got hit hard with depression and high anxiety,” Gini recalled. “My grades started to suffer.”

Gini had moved away from her family, friends and her entire support system. The couple had believed the move would set them up for a successful future but at this moment, Gini couldn't think past the next few hours.

A Future Red Raider

“Texas Tech has always been a huge part of my life,” Gini said.

Born and raised in Lubbock, Gini's parents both worked at the university. The family was active in their support of Red Raider athletics and the university's arts scene. They attended each Carol of Lights™ and befriended faculty and staff around campus.

Gini as a child at a Texas Tech University football game.

Growing up in the college town inspired Gini to attend Texas Tech one day.

Coming up through Tubbs Elementary, O.L. Slaton Middle School and Lubbock High School, Gini was active in theater, dance and choir. She involved herself in as many artistic events as she could, finding these endeavors energized her.

As high school graduation approached, though, she took stock of what would offer a consistent career.

“When I graduated in 2013, there were not as many jobs in communications,” Gini said. “There was a stigma around creative careers. I wanted to be seen as serious so I looked for something that would make good money.”

Multiple family members worked in the medical field, so Gini decided to study nursing.

Around this same time, she and her high school sweetheart were getting more serious. Gini met her now-husband Josh in biology during the ninth grade. The two became friends and started dating the following year. By the time they graduated, they both knew they'd found the one.

Josh and Gini in front of the Lubbock High School sign.

Josh enlisted in the Army and was sent to basic training the summer after graduation. The young couple couldn't talk much on the phone, so they wrote letters throughout the long, sweltering summer months. Gini would make her way to the mailbox in the dry West Texas heat, opening the latch to find something stamped from Fort Benning.

The couple kept every letter from that summer.

Meanwhile, Gini started pre-nursing courses at South Plains College (SPC). While the dream was still to attend Texas Tech, she knew she could get basic requirements out of the way at a lower cost at SPC.

“For a few semesters, I was very focused on my schoolwork,” Gini recalled. “Josh was getting his stuff done and I was taking care of my classes.”

In the following years, everything rapidly changed. In April 2016, the couple got married and Gini started work as a nurse's aide at Covenant Children's in the postpartum unit.

In 2017, the couple welcomed their first child, Adeline. By 2018, Josh enrolled full time at Texas Tech.

In the span of a few short years, Gini's life looked drastically different.

“When we had Adeline, I ended up having an emergency cesarian,” Gini said. “Because of the longer recovery, I ended up taking that whole semester off from school.”

Gini's classwork began to take a backseat during this time. Supporting Josh in his studies, working as a postpartum nurse's aide and taking care of a newborn was a full load.

“I decided to take a prolonged break from school,” she said. “I had a job I enjoyed and wanted to soak up being a new mom.”

While a break was the right choice for Gini at that time, it made going back to school that much tougher.

A Change in Direction

Josh and Gini had their second daughter, Charlotte, at the beginning of 2020. She was only a few weeks old when the pandemic started. Josh, Gini and their young children were home for months. While Gini did go back to work after her maternity leave was over, the restrictions gave her room to reflect.

“We were stuck at home for a while, and my need to express myself creatively came back out,” she said.

It was something she hadn't taken the time to do in years.

Gini came up with crafts to do with their eldest, and she started dabbling in photography. A light came on, and Gini started questioning the academic road she'd taken up until that point.

“The stress of working through the pandemic certainly added to it, but I think the pandemic showed me something I already knew deep down,” she said.

Gini had chosen to forego a creative career seven years prior, worried about appearances and stability. Now, a wife and mother, her priorities had changed.

“I'd grown up a lot in that short time, and I had different aspirations,” she said.

Not only had Gini changed, but the communications industry had changed as well. When she graduated from high school, some organizations were just beginning to use social media, and many weren't utilizing it at all. But with the progression of technology and the sudden boom of online activity during the pandemic, Gini decided to revisit a career in communications.

She met with Associate Director of Advising Don Ellis in the College of Media & Communication (CoMC), who became a mentor to Gini every step of the way.

“Gini came to us as a transfer student, and she had a level of maturity and diverse life experiences that seemed to enhance the quality of her academic career,” Ellis said. “Despite challenges posed by the pandemic, she consistently displayed a strong sense of determination and resilience, maintained her focus, and always actively participated in her own education.”

Gini had always wanted to help people; she thought nursing was the best way to do that. But as life changed, she realized she could make a difference while using her talents.

“I discovered Texas Tech had a program called creative media industries (CMI),” she said.

The program's focus on innovative storytelling was appealing to Gini, who was looking to grow her existing passion for visual communications. So, in the fall of 2020, Gini started her first semester as a Red Raider.

The moment was a long time coming.

While her first semester was completely online, Gini was able to be on campus in the spring of 2021.

“I have a photo of my first day on campus,” she said. “I have a mask on, so it'll always be easy to remember when that was.”

Gini wearing a COVID mask, standing in front of the College of Media and Communication.

Life had thrown her some curve balls, but Gini was zeroing in on what she wanted and remembering the dreams she had had as a young girl. She knew she would attend Texas Tech, the reality of that was just a whole lot different than she envisioned.

For the following year, both Josh and Gini were enrolled in the same college. Josh was a student in the Public Relations & Strategic Communication Management program, while Gini thrived in CMI. It was around this same time that the couple found out they were expecting another child, a son.

“I remember thinking, ‘Oh boy, here we go again,'” Gini laughed.

Thrilled to be welcoming a son, Gini struggled, wanting to focus on her growing family and her schoolwork at the same time. When she had her daughters, she was in a love-hate relationship with academia. That had changed this time around. She wondered how she would balance being a mom to three kids while finishing a program she genuinely loved.

It was a good problem to have, but it remained a problem. To make matters harder, Josh received a job offer in Round Rock after graduating from Texas Tech in the spring of 2022, only a few months after they had Elijah.

Josh was commissioned as an Army officer upon graduation and signed with the National Guard. His new reporting station was in central Texas and a marketing job became available nearby. However, that meant Gini and the kids would have to leave behind their support system in Lubbock. Both Gini's parents still lived in Lubbock, and she had friends in her hometown.

Unfortunately for the couple, they didn't have a lot of time to weigh their options. They wanted Josh to start work in six weeks. So, with three young children and virtually no community in Round Rock, Josh and Gini ventured into the unknown.

The Hardest Stretch

In the early morning hours, a few months later, Gini was at rock bottom. When classes started in fall of 2023, she had to go back to being an online student. Unfortunately, CMI was not a fully online program. But with the encouragement of her adviser, Gini realized the Public Relations & Strategic Communication Management program overlapped heavily with the courses she'd taken, and it was offered both in-person and online.

If she was going to complete her degree any time soon, she'd need to switch programs.

So, she did, and the coursework was comparable to what she'd been studying. However, it wasn't the change in major that was so difficult, it was the fact she was an online college student with three children, at home alone, and suddenly without her support system.

She also struggled with postpartum depression after the birth of her son.

“Honestly, I felt like finishing school just wasn't going to happen for me,” Gini said. “Like, maybe it wasn't in the cards.

“I was taking care of a five-month-old, a toddler, and a 5-year-old. I had no family or friends nearby and I was waking up every morning with a high heart rate, sick to my stomach. I stressed over finances, wondering if we'd made a mistake.”

During that semester, Gini's grades began to suffer. She knew that wasn't the way she wanted to finish her college career, so she sought help from her doctor and her adviser. Everyone worked with her, finding solutions to help her succeed.

Her doctor placed her on an anti-anxiety medication that helped her feel like herself again. Gini begin to create a new routine and even befriended other mothers in the area.

“I also made sure to reach out to my adviser and kept the line of communication open with each of my professors, letting them know my situation from the beginning,” she said.

By the end of the semester, she made the President's Honors List.

There were times, particularly that semester, that Gini was tempted to give up.

“Every time I was about ready to give up, I would think, ‘C'mon Gini, you have to do this for yourself. You've always wanted to be a Texas Tech graduate; you can do this.'”

In place of having family in town, Gini would get on the phone and get added support when she needed it most.

Gini's mother was her biggest cheerleader.

“She has watched me work toward this goal for a decade,” Gini said. “She's always been so encouraging. Whenever I've had a setback, she reminds me to get back up and get at it. She's always believed I can do this.”

And on the days when Gini didn't believe in herself, her family, her friends, and Josh have been there to help her cross the finish line.

“Both Gini and I were unique students,” Josh said. “Texas Tech does an amazing job catering to individuals who are in nontraditional situations.

“Gini has displayed such tenacity while finishing her degree, especially this past year. She doesn't let anything define or limit her. At no point has she looked at her circumstances and let them be a reason not to do something.”

The Horizon

After graduation, Gini hopes to work in public relations as a social media manager; particularly for brands geared toward mothers and children.

As proud as Gini is of finishing her degree, she is even prouder of being a mom. She wants to share that passion in an industry that has plenty of need for good public relations practitioners.

“In my experience, juggling the demands of being a fulltime public relations major and a mother of three, I've come to realize the critical importance of authenticity and connection,” she said. “Especially when it comes to brands marketing to mothers.”

The demographic Gini hopes to appeal to is focused on quality and safety, just as she is. Gini has found that parents do not just want to buy products, they want guidance and support. That's why it's important for a public relations campaign to educate and engage that demographic, she says.

Gini does not hide the fact she is a non-traditional student. Rather, she plays to her strengths.

“As a mom entering the PR world, I bring a unique perspective to the table,” she said. “I know firsthand the challenges and joys of parenting, and I believe our experience as mothers enriches the work we do.

“By sharing our stories and collaborating with influencers who share our values, we can create genuine connection with audiences.”

Gini has been in a campaign course this semester, which serves as a capstone for her degree program. To her delight, most of her team members also turned out to be parents. While she may have started out on campus as the older student in class, her online experience has partnered her up with colleagues who are on similar paths.

Gini hopes even more parents will consider going back to school and finishing their degrees.

“As fulltime parents and students, it's OK to take your time. School will still be there. The job market will still be there. But time with your kids, that's valuable,” she said.

Even though Gini knows it's not a race, it doesn't make commencement any less sweet. If anything, walking the stage this spring will be that much more special, as it marks her incredible perseverance over the last 11 years.

Gini wearing a graduation stoll and looking dreamily at the sky.

“There have been a lot of ups and downs,” Gini said. “But I can finally see the horizon, and it's a great view.”

The Journey Together Canoe FM

Society & Culture
MAY 7, 2024

Greg Roe & Sharon Kaasalianen On The Dementia Care Conference

Join host Greg Roe for an interview with Professor Sharon Kaasalainen of McMaster University, about the upcoming, June 3, Dementia Care Conference....and more...

MAY 6, 2024

Peter Ferri & John Middleton a Long Term Care Resident

Join hosts Lynn Higgs and Peter Ferri for an interview with a resident in a local Long-Term Care home on the Journey Together

APR 16, 2024

Lynn Higgs with Brigitte Gebauer, coordinator of volunteer services at HHHS

April is National Volunteer Appreciation month and April 14th to 20th is volunteer appreciation week. Join host Lynn Higgs talking to Brigitte Gebauer, coordinator of volunteer services at HHHS to discuss the state of volunteerism in Canada, the world and Haliburton County. As well, you’ll hear about some exciting interviews coming up in the weeks ahead on The Journey Together. Thanks

APR 2, 2024

Greg Roe & Barb Smith Morrison, Executive Director of the Abbey Retreat Centre

Join host Greg Roe and his guest Barb Smith- Morrison, the Executive Director of the Abbey Retreat Centre. Tune in to learn more about this wonderful facility for people living with cancer and for their care-givers as well. The centre has gained national recognition for its work and it is located right here in Haliburton County.

MAR 19, 2024

Peter Ferri and Greg Roe with Danielle Turpin of Home Care Workers Cooperative

Join hosts Peter Ferri and Greg Roe for a chat with Danielle Turpin, a Personal Support Worker and the founder and President of Home Care Workers Cooperative (HCWC) and the Executive Director of the Cooperative Care Alliance (CCA). Tune in to learn more about this interesting model of care delivery…and to hear about the Haliburton connection….. This podcast is hosted by ZenCast.fm

MAR 5, 2024

Episode 1-Preview of what's to come.

Join hosts Peter Ferri and Greg Roe and their guests Terry Hartwick from the Haliburton Highlands Long-Term Care Coalition and Bonnie Roe from Aging Together as Community. As well, listeners will learn more about the very eclectic topics that will be covered in upcoming episodes of The Journey Together. This podcast is hosted by ZenCast.fm

Top Podcasts In Society & Culture

Journey to the Himalayas - Exploring Nepal and its Trekking Destination

O ur Planet hides countless treasures ready to be discovered. One such treasure is the breathtaking beauty of Mountains, the rich life energy of lush green forests lining long trails, and the ever-changing vibrant hues of the sky with seasons in Nepal.

If you have the adventurous spirit to unveil the charm of such treasures, Welcome to the club!

Nepal: A Heaven on Earth

Located in the heart of the Himalayas, Nepal allows its visitors to create unforgettable memories of a journey through stunning landscapes, diverse cultures, and thrilling adventures.

The Himalayan mountain range provides the most exhilaration and life-long experiences. Nestling the soaring peaks of the world’s highest mountains makes this country a popular attraction for people worldwide.

But is that all to Nepal? Well, No!

This country appeals to every appreciative eye, from the highest peaks to tranquil valleys and spiritual ancient temples. It beckons visitors to immerse themselves in Nepal's unparalleled beauty and rich heritage.

Introduction to Trekking in Nepal

The diversity of trekking trails in Nepal is unmatched. The Himalayan mountain range offers a wealth of beautiful peaks and trails that can’t be spotted anywhere else in the world. In fact, even the minimum altitude of peaks in Nepal is 59 m above sea level. Not to mention the presence of Mt. Everest in this range. Everest stands tall around 8,848 m above sea level, making it the highest and coldest peak in the world.

Contrary to popular belief, trekking in Nepal has a relatively recent history. Even though that is true, it has evolved into a major industry and a famous to-go place for adventure seekers.

Tracing the history of trekking in Nepal, we see a sudden rise in the mid-20th century. Until 1949, Nepal was isolated and only accessible up to Kathmandu from India. By the beginning of 1962, tourism to this heavenly place started developing. To this year 2024, several thousand people have booked their treks to this country in every season.

Popular Trekking Destinations

Before we dive into the most popular trekking destination, there is something that you need to know. Although the treks are enthralling, there are several challenges that need to be considered before dialing into your trekking escapade in Nepal.

To begin with, you need to acclimate yourself, get into your best health and then get the necessary permits and other documentation required to be done.

A reliable trekking guide can help you in this regard and plan the complete itinerary to maximize your adventure. Mosaic Adventure is a famous name in this vertical. As a premier tour operator based in Nepal, Mosaic Adventure offers you the highest quality trekking experiences and commitment to responsible tourism. Their teams are expert in arranging treks for hundreds of groups throughout the year, you can also be one of them.

Here are the most popular trekking destinations that are go-to places for adventurers in cohorts with Mosaic Adventure:

Everest Base Circuit

Annapurna Circuit

Manaslu circuit.

Langtang Valley
Kanchenjunga Circuit

And more.

Unique Appeal of Nepal & Himalayas

Stunning landscapes.

Whether you are looking for snow-covered peaks, peaceful plains, still waters, vibrant forests, or jaw-dropping landscapes, Nepal offers a complete package. Stand at the edge of any trail of Manaslu or Everest base, and you are bound to be stunned by the captivating beauty of landscapes. These landscapes provide spiritual healing to calm your soul and open your mind.

Spiritual Retreats

Nepal offers a breath of fresh air amidst the chaos of modern life. If you are sick of your tiresome routines, make a sweet escape to this tranquil place and refresh your soul. The foothills of the Himalayas are perfect for meditation and yoga, where you can seek inner peace and self-reflection.

Rich and Diverse Culture

While the landscapes and peaks in Nepal are serene and tranquil, the air is thick with rich culture and lively spirits. Nepalese culture has been passed from generation to generation, making it richer down the line. The bright blend of ethnicity and religion of every culture makes Nepal a more exciting place to visit. This is even more true when you visit in the season of festivals. Each village exudes its unique charm.

World’s tallest mountain - Mt Everest

Besides everything, the most appealing aspect of Nepal is none other than Mount Everest and its legendary peaks that stay white throughout the year. Although the trekking to Everest base camp is arduous, it is safe for regular adventure seekers.

However, hiking enthusiasts and mountaineers wanting to conquer the mountain have challenged themselves to reach the peak, which is insane but not unbelievable altogether. After all, being able to conquer the world’s highest peak sparks an unimaginable spirit in mountaineers.

Most Popular Trekking Circuits to Explore

The Himalayan mountain range hides countless adventures, the most popular of which we will discuss today.

Everest Circuit

Without a doubt, Everest Base Circuit is the most sought-after trek for hikers and trekkers alike. The trek can take as much as 17 days and includes sections of Everest Base Camp Trek and stunning views of the giants in the center of the Himalayas as soon as you cross the Renjo la Pass, Cho La Pass, and Kongma La Pass.

The maximum elevation you will cover in this trek is 5545 m at Kala Pathar. The base camp has several lodges and tea houses to rest and revive your energy for the trek.

The itinerary begins with Kathmandu and proceeds as follows:

Kathmandu > Lukla > Phakding > Nance Bazaar > Thyangboche > Dingboche > Chhukung > Kongma La Pass > Lobuche > Gorak Shep > Everest Base Camp > Kalapathar > Gorakshep > Dzongla > Gokyo Lake > Renjo La > Lungden > Thame > Phakding > Lukla > Kathmandu

As much as Everest attracts trekkers, Annapurna doesn’t fall behind. The enchanting and exotic beauty of the Annapurna circuit is one to admire truly. The magical views of Annapurna, Dhaulagiri, Gangapurna, and other nearby mountains will turn your journey into an unforgettable adventure.

With the highest point reaching up to 4300 m, the trip to Annapurna trek only stretches to 8 days. Here’s what your journey will look like:

Kathmandu > Jagat > Dharapani > Chame > Pisang > Manang > Yak Kharka > Thorung Phedi > Muktinath > Marpha > Kalopani > Pokhara > Kathmandu

The eighth highest peak in the world, Manaslu, is surrounded by the charming Manaslu Conservation area . The trek to Manaslu is widely popular after the Everest Trek and offers a memorable journey to visitors.

Although it is not as high as the Annapurna Mount, It still provides stunning night views of the sky and jaw dropping landscapes in the day.

The trek spans over 13 days, Beginning from Soti Khola and strides as follows:

Sot Khola > Machhakhola > Jagat > Deng > Namrung > Samagaun > Samdo > Dharamsala > Larkya - la Pass > Bhimtang > Tilije > Dharapani > Tal > Syange > Besishahar > Dumre > Kathmandu

Langtang Trek

Another lively trek to breathtaking views is the Langtang Trek. This moderate-level trek travels you through the beautiful Langtang Valley. It rounds up in 11 days while offering you a thrilling experience through stunning landscapes of Langtang and Ganesh Himal.

The maximum trek height is 3870m, and it begins from Syabrubesi. The journey flows through surreal views of glaciers, mountains, forests, and rivers. Tropical lowland jungles, lush green forests, and high-altitude glaciers loop through the whole trek. If you are lucky, you can even come across some wildlife, such as red pandas or musk bears roaming the forests. Let’s say you have an encounter. Don’t forget to say hi.

So, Crank Up Your Adventurous Fun-o-Meter!

Nepal offers a plethora of stunning views for which words fall short. As an adventurous soul, Exploring Nepal and its magical peaks can be a lifetime experience to commemorate and relish in joy. So, take some days off your busy schedule and unwind amidst the pure air and breathtaking views.

Journey to the Himalayas - Exploring Nepal and its Trekking Destination

The Long Road to Graduation: Chelsea Harkins’ 14-year journey to a bachelor’s degree

May 13, 2024

On Saturday, May 11, at Enmarket Arena in Savannah, Chelsea Harkins completed a 14-year journey to receive her college degree from Georgia Southern University. It’s a quest she pursued with passion and perseverance, overcoming unimaginable obstacles along the way.

“It’s been something that I could never just step away from and just say, ‘I’m throwing my hands up and I just can’t do it,’” she said. “It was a need to continue doing this for myself.

“Now that I’m at the finish line, I can look back and see how unique it is. But at the time, when you’re in it, it’s a hard line between ‘Wow, I failed because I didn’t do it the way people normally do’ and ‘Wow, I did it even though people said I couldn’t.’”

Despite their opinions, few people could have traveled the road Harkins took to get her degree.

A native of Cincinnati, Harkins began her college education in 2009 at Miami University in Ohio, where she pursued an English education degree to become a teacher in an urban school district. Her passion was and still is helping people, and teaching students in difficult circumstances seemed a fulfilling way to spend a career.

Just a few semesters into her education, however, Harkins and her family were faced with the ultimate nightmare for any parent. Her oldest daughter, only 9 years old at the time, was diagnosed with severe mental health issues. She spent the next few years finding the right medications, receiving specialized therapy and joining groups for socialization and play.

In an effort to keep her education moving, and to learn more about what was going on with her daughter, Harkins changed her major and pursued courses to become a psychiatric nurse.

“You start digging really deep and doing as much research as you can to figure out what’s happening with your child,” she said. “It led me to want to work in the mental health field because I saw what was lacking and also what was good. But it was a lot of ‘Let me try to take a class here or there,’ but my daughter had to go to a lot of institutions and doctors and I just couldn’t keep up.”

It was several years before Harkins could commit to school at all again, but health setbacks required her to shift her life again.

Her youngest son was diagnosed with heart failure while still in the womb. When he was born, Harkins said he had a stroke and died in her hands. He was immediately airlifted to another hospital and brought back to life. It was years before he could experience the normal, healthy life he enjoys today.

“Those extra worries don’t really go away,” she said. “Even when doctors start saying things are better, they still sit in your mind as a mom.”

After years of upheaval, Harkins’ life began to get back to a semblance of normalcy when she and her family decided to move to Richmond Hill, Georgia, in 2018. She wanted to continue schooling when she arrived but had to wait two years to be able to get in-state tuition at Georgia Southern’s Armstrong Campus in Savannah.

When it was time to go back to school, however, Harkins wasn’t sure where to begin again.

“I changed my major a lot,” she said. “It’s actually a running joke in my family and circle of friends that I never know what I want to do when I grow up.”

She decided to pursue an Interdisciplinary Studies degree with concentrations in sociology and criminal justice, and a minor in psychology. The interdisciplinary degree would allow her to use the credits she’d gained in other programs, and her concentrations and minor would allow her to pursue her passion for helping others through such difficult circumstances as her own.

“It was hard because the mom guilt made me feel bad for doing it,” she said. “But personally, I loved doing it — every class I took. A lot of people say, ‘Man, you wasted a lot of time, though, changing majors or taking courses you didn’t need. And always my response is, ‘That’s not true! Because nobody can take this knowledge from me. I don’t have to give it back. It’s mine. I get to keep it so I don’t feel like it was a waste.’”

Harkins return to school was anything but easy. In order for her to become a full-time student again, she relied on her family to rely less on her. She was still helping keep family finances in the black, and she worked at The Crab Shack on Tybee Island as a waitress and bartender as well as an assistant at McNamara Law Firm in Savannah.

Despite the long hours, Harkins still found time to do hours of service-learning at a women’s shelter in Richmond Hill and take 18 credit hours for the last two semesters of her degree.

“This ending year is the hardest I’ve done, but I’m doing it,” she said. “We had a family meeting and we all agreed that I’m going to push through and do it. And they would try not to rely on me for as many things. So it was kind of a family affair by the end. Even my husband started cooking! It was great!

“Are there times I wanted to quit? Yes, today,” she added, laughing. “As I’m looking at how many papers are due, today is a good day if I wanted to quit.”

Though she faced difficulties and isolation as an older student, Harkins says she was motivated to keep going by her kids, who watched her persevere for years to reach this goal. She says they’re all thriving now, and some of them are now adults. But she wants them to remember how important education is — especially her daughters.

“I’m the first woman on my mother’s side to earn a college degree,” she said. “I think it’s important for women to be educated and to know that their education is worth it and that they can do anything. I tell my daughters one of the most dangerous things you can do is be completely dependent on somebody else.”

As Harkins reflects on her journey, she still wrestles with whether she should feel guilt for taking so long to finish or feel pride for pushing through and crossing the finish line. She faced personal doubts, guilt and occasional negativity from friends and family who thought she shouldn’t be in college at all.

At the end of this road, however, she’s happy they’ll all be there to see her do what seemed impossible.

“I tear up as I think about the people who are coming from all over the U.S. to watch me do this,” she said. “So I am just excited and ready to see everybody and let them see me do what some of them said I couldn’t.

“It’s a hard debate inside your brain of whether you should celebrate yourself or should you be mad at yourself because you didn’t already have it done. But the other side of being happy with myself is winning. It’s starting to win out.”

Being happy should win out for Harkins, who has crammed four years of college into 14 as the saying goes. And while she’s proud of her accomplishments, she knows there’s still some ribbing she’ll have to endure.

“I think people still don’t believe there’s actually a graduation party,” she said.

Posted in Graduate Stories , Press Releases

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Beyond oncology: selinexor’s journey into anti-inflammatory treatment and long-term management.

1 Respiratory Medicine Department, Wuhou District People's Hospital, Chengdu, China
2 Department of Pulmonary and Critical Care Medicine, Sichuan Provincial People's Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu, China
3 Department of Pulmonary and Critical Care Medicine, Mayo Clinic, MN, United States

Selinexor, a selective inhibitor of nuclear export (SINE), is gaining recognition beyond oncology for its potential in anti-inflammatory therapy. This review elucidates Selinexor’s dual action, highlighting its anti-tumor efficacy in various cancers including hematologic malignancies and solid tumors, and its promising anti-inflammatory effects. In cancer treatment, Selinexor has demonstrated benefits as monotherapy and in combination with other therapeutics, particularly in drug-resistant cases. Its role in enhancing the effectiveness of bone marrow transplants has also been noted. Importantly, the drug’s impact on key inflammatory pathways provides a new avenue for the management of conditions like sepsis, viral infections including COVID-19, and chronic inflammatory diseases such as Duchenne Muscular Dystrophy and Parkinson’s Disease. The review emphasizes the criticality of managing Selinexor’s side effects through diligent dose optimization and patient monitoring. Given the complexities of its broader applications, extensive research is called upon to validate Selinexor’s long-term safety and effectiveness, with a keen focus on its integration into clinical practice for a diverse spectrum of disorders.

1 Introduction

Selinexor, also known as KPT-330, is an oral small molecule drug that Selectively Inhibits Nuclear Export (SINE). It specifically inhibits exportin 1 (XPO1), which exports various proteins (including tumor suppressor proteins and growth regulators) from the nucleus to the cytoplasm ( 1 ). By inhibiting XPO1, Selinexor effectively traps these proteins in the nucleus, leading to the reactivation of tumor suppressor functions and induction of apoptosis in cancer cells. Selinexor’s mechanism of action distinguishes it from other oncology therapies, making it a viable clinical option for treating various tumor types, such as multiple myeloma and diffuse large B-cell lymphoma ( 1 ). Additionally, Selinexor has shown potential therapeutic applications beyond its initial approval for hematological malignancies, including breast cancer ( 2 ), lung adenocarcinoma ( 3 ), and gastric cancer ( 4 ), by inducing cell cycle arrest and promoting apoptosis.

However, Selinexor has emerged as a pivotal agent in the treatment of certain oncologic conditions, particularly demonstrating efficacy in scenarios where traditional therapies have failed. It is important to recognize that Selinexor is not intended as a first-line treatment option, nor is it recommended for direct comparison with standard treatment modalities. Its utility is specifically recognized in the treatment of drug-resistant or treatment-refractory cases, offering a novel avenue for patients who have exhausted other therapeutic options. This distinct role underscores the importance of understanding Selinexor’s unique mechanism of action, its therapeutic potential, and the need for precise patient selection criteria to optimize treatment outcomes.

But it is encouraging that Selinexor has demonstrated not only anti-tumor effects but also anti-inflammatory effects and protection against other inflammatory diseases, such as COVID-19 ( 5 ), sepsis ( 6 ), and Duchenne muscular dystrophy (DMD) ( 7 ). The applications of Selinexor will not be limited to oncology, and there may be broader areas that can be explored. The role of Selinexor will be explored in detail.

2 Selinexor in anti-cancer treatment

2.1 selinexor in hematologic malignancies.

Selinexor has shown effectiveness against blood cancers by inhibiting tumor growth and inducing the death of cancer cells, with a better safety profile for healthy cells compared to older treatments. Studies indicate its success as both a solo treatment and in combination with other therapies across various blood cancer types.

In significant research, the STORM trial investigated Selinexor in patients with advanced myeloma who had undergone numerous treatments, finding that approximately 26% experienced a reduction in cancer severity ( 8 ). The Boston trial examined the combination of Selinexor with bortezomib and dexamethasone in 402 patients, revealing that this regimen extended progression-free survival to nearly 14 months, offering notable benefits particularly to older individuals and those with renal issues ( 9 ).

The SADAL study evaluated Selinexor in individuals with advanced Large B-Cell Lymphoma after 2-5 prior treatments, reporting a 28% response rate and an average survival of 9 months with manageable side effects ( 10 ). An additional investigation into various Non-Hodgkin’s Lymphomas (NHL) in 70 patients showed a 31% response rate, supporting Selinexor’s role in treating relapsed or refractory cases ( 11 ).

Regarding other blood cancer types, a Phase I clinical trial combining Selinexor with chemotherapy for relapsed/refractory Acute Myeloid Leukemia (AML) reported a 70% overall response rate and a 50% complete remission rate ( 12 ). Another AML study with Selinexor, cytarabine, and idarubicin showed a 47.6% response rate and a median complete remission duration of 34 days, highlighting variable outcomes in such AML treatments ( 13 ). In chronic lymphocytic leukemia (CLL), Selinexor has been found to boost the effects of chemotherapeutic agents like Fludarabine and Bendamustine, or sustain the impact of PI3Kδ inhibitors, effectively overcoming resistance to single-agent therapies and preserving the drugs’ ability to kill tumor cells ( 14 ).

2.2 Selinexor in non-hematologic malignancies

Selinexor is broadening its horizons from blood cancers to include treatments for solid tumors, showcasing its versatility in oncology. This expansion reflects an active pursuit to uncover its full potential beyond hematologic applications, emphasizing the necessity for comprehensive clinical evaluations across various cancer types.

For advanced and metastatic malignancies, Selinexor has demonstrated a promising safety and efficacy profile. A Phase 1 study underscored its tolerability in patients with a range of advanced cancers, suggesting a potential for broader applicability ( 15 ).

In the realm of soft tissue sarcoma (STS), Selinexor’s combination with doxorubicin has yielded partial remission in 21% of patients, and stable disease in 63% ( 16 , 17 ). This finding is significant, particularly for a diverse and rare cancer like STS, highlighting Selinexor’s capacity to fill therapeutic gaps where targeted options are limited.

Gynecological cancers, too, have seen potential benefits from Selinexor, with a Phase I study indicating partial or complete remission in patients treated with a combination of Selinexor, paclitaxel, and carboplatin ( 18 ). This promising result opens up new avenues for treatment in ovarian and endometrial cancers.

Research has broadened Selinexor’s application to encompass a variety of solid tumors, addressing complex cases such as salivary gland tumors, recurrent glioblastoma, metastatic triple-negative breast cancer, and castration-resistant prostate cancer ( 19 – 22 ). Although the outcomes of these studies vary, they collectively indicate potential clinical benefits of Selinexor across diverse solid tumors. Notably, the integration of Selinexor with radiotherapy has been shown to enhance apoptosis and reduce proliferation in colorectal cancer cell lines and xenograft tumor models, compared to either treatment alone. This synergistic effect has led to decreased tumor sizes and improved responses to radiation ( 23 ).

This exploration into non-hematologic malignancies with Selinexor represents a significant stride in cancer treatment, hinting at a versatile and effective option for a range of solid tumors. The ongoing challenge is to fine-tune treatment protocols and deepen understanding of its optimal use, particularly in combination therapies and specific patient demographics, to maximize Selinexor’s therapeutic advantage.

2.3 Summary of Selinexor in anti-tumor treatment

Selinexor, typically not used as a standalone therapy in antitumor regimens, excels when combined with other treatments, especially for blood cancers. This strategy offers renewed hope for patients who have exhausted other therapeutic options. The drug’s ability to enhance the efficacy of combination therapy regimens is marked by its capacity to attenuate the harsh effects of chemotherapy and maintain cancer cell sensitivity to ongoing treatments ( 24 – 26 ). Moreover, the integration of Selinexor into treatment strategies not only improves outcomes for resistant cases but also aids in preparing patients for bone marrow or stem cell transplants. By reducing cancer burden pre-transplant, Selinexor increases the likelihood of successful chemotherapy preparatory regimens, broadening the eligibility for these life-extending procedures ( 27 – 29 ).

While Selinexor introduces significant therapeutic benefits, its administration is not without challenges. A primary concern is hematological toxicities such as thrombocytopenia, which affects approximately 54% of treated patients, necessitating close monitoring and potential dose adjustments to mitigate severe bleeding risks ( 30 ). Gastrointestinal side effects are prevalent, with nausea and vomiting reported frequently. These effects can substantially impact patient quality of life and adherence to the therapy regime. Effective management strategies often involve supportive care measures, including the use of antiemetics and dietary adjustments to help patients better tolerate treatment ( 30 ). Concerns about hepatotoxicity are underscored by instances of elevated ALT levels, signaling potential liver injury. Though relatively rare, regular monitoring of liver function is essential for detecting any hepatic injury early, allowing for timely medical intervention ( 30 ). Additionally, Selinexor treatment has been associated with a heightened risk of infections, particularly upper respiratory tract infections, observed in about 17.8% of patients in clinical trials. This necessitates rigorous monitoring and preemptive management strategies to mitigate the risk and manage any infections promptly ( 30 ).

The use of biomarkers plays a critical role in monitoring Selinexor’s efficacy and managing resistance. Studies such as the BOSTON and STORM trials have uncovered a three-gene signature (WNT10A, DUSP1, and ETV7) that predicts Selinexor’s efficacy in treating multiple myeloma, in terms of both depth and duration of response ( 31 ). ABCC4, or ATP-binding cassette subfamily C member 4, has emerged as a significant biomarker for Selinexor sensitivity in multiple myeloma, with varying expression levels correlating with the drug’s effectiveness. This suggests ABCC4’s potential as a novel indicator of drug response, highlighted by weighted gene co-expression network analysis demonstrating its predictive value ( 32 ). Further, CRISPR-Cas9 screening has identified ASB8 as a critical element enhancing Selinexor sensitivity in various cancer types through the modulation of XPO1 proteasomal degradation. Additionally, the TGFβ-SMAD4 pathway has been identified as a significant factor in resistance to multiple myeloma, suggesting its potential as a biomarker for predicting therapeutic outcomes and devising strategies to overcome resistance ( 33 ). Monitoring the activity or expression of XPO1 and NF-kB, which are directly tied to Selinexor’s mechanism of action, can provide valuable insights into treatment effectiveness. These biomarkers are instrumental in adjusting therapeutic approaches to maximize patient benefits while minimizing adverse effects ( 34 – 36 ).

In summary, Selinexor’s role in overcoming chemotherapy resistance and facilitating bone marrow transplants underscores its value in treating blood cancers. This approach could significantly improve the chances of a cure for some patients.

3 Introduction to Selinexor and inflammation

The rationale for exploring Selinexor’s role in inflammatory pathways stems from its unique mechanism of action. By inhibiting XPO1, Selinexor effectively traps crucial regulatory proteins within the nucleus, thereby impeding their normal function in the cytoplasm. This action leads to the modulation of several cellular pathways involved in cell survival, inflammation, and immune responses. The nuclear retention of these proteins can result in the downregulation of pro-inflammatory cytokines and the modulation of other key components of inflammatory pathways.

This broad mechanism suggests a potential utility for Selinexor beyond oncology, targeting inflammatory and autoimmune diseases where dysregulation of cytokine signaling plays a significant role. The anti-inflammatory effects of Selinexor have been observed in various models of disease, providing a promising outlook for its application in treating chronic and acute inflammatory conditions.

3.1 Mechanism of action of Selinexor in inflammation

3.1.1 focusing on proteins involved in inflammation.

Selinexor targets several key pathways central to inflammation, notably the NF-κB and STAT3 signaling pathways. Under typical conditions, NF-κB is confined in the cytoplasm bound to IκB proteins. In response to inflammatory stimuli, IκB degrades, allowing NF-κB to enter the nucleus and activate genes that escalate the inflammatory response. Selinexor intervenes by stabilizing IκBα, thus hindering the nuclear translocation of NF-κB. This prevention reduces the transcription of pro-inflammatory cytokines and mediators, critical components that perpetuate inflammation. The suppression of these mediators is crucial for controlling inflammatory processes across various conditions ( 6 ).

Building on this mechanism, Selinexor also modulates the STAT3 signaling pathway, which plays a pivotal role in mediating inflammation. By retaining STAT3 in the nucleus, Selinexor limits its capability to activate downstream genes responsible for the inflammatory response. This containment reduces the overall inflammatory activity, providing therapeutic benefits especially in diseases where STAT3 is overly active ( 37 ).

Selinexor’s influence on immune regulation is primarily achieved through its action on NF-κB and STAT3, critical transcription factors involved in immune cell activation. By retaining these factors in the nucleus, Selinexor prevents them from promoting the expression of genes that drive the inflammatory and immune responses. This results in a reduction of immune cell activation and inflammatory signaling, making it beneficial for treating conditions with excessive immune activation ( 6 ).

3.1.2 Changes in cytokine profiles due to Selinexor treatment

Cytokines, small proteins crucial for cell signaling, play significant roles in the immune response during inflammation. Key cytokines like tumor necrosis factor-alpha (TNF-α), interleukins (IL-1β, IL-6), and interferons (IFNs) drive inflammatory responses, and their dysregulation can exacerbate disease severity and progression. Selinexor’s ability to modulate cytokine production largely stems from its inhibition of nuclear export. By blocking the nuclear export of transcription factors such as NF-κB and STAT3, Selinexor prevents them from activating genes responsible for pro-inflammatory cytokine production. This suppression leads to a notable reduction in cytokine levels, directly impacting the inflammatory process ( 6 ).

Clinically, Selinexor’s effect on cytokine levels has profound implications. It has been shown to significantly reduce concentrations of key pro-inflammatory cytokines, thereby alleviating symptoms and lessening disease severity. For instance, in diseases like rheumatoid arthritis or inflammatory bowel disease, where cytokine overproduction leads to tissue damage, Selinexor’s ability to modulate cytokine production can prevent tissue damage and reduce symptoms ( 38 ).

Furthermore, by altering cytokine profiles, Selinexor offers a new therapeutic approach for conditions inadequately managed by existing medications. This includes diminishing chronic disease flare-ups, reducing reliance on steroids or other immunosuppressants, and potentially improving patient quality of life. Additionally, the altered localization of signaling molecules through Selinexor’s action affects downstream signaling pathways essential for immune cell development and function, notably reducing the proliferation and differentiation of pro-inflammatory T cells crucial in autoimmune and inflammatory diseases.

3.1.3 Specific effects on T cells

Selinexor modulates T cell function primarily through the indirect effects of inhibiting nuclear export, which is crucial since T cells are central to both cell-mediated immunity and the modulation of other immune responses through cytokine production. By altering the localization and activity of key transcription factors such as NF-κB and STAT3, which are vital for T cell activation and proliferation, Selinexor prevents these factors from triggering the gene expression necessary for T cell responses. This retention within the nucleus significantly curtails the proliferation and activation of T cells, particularly those implicated in inflammatory responses ( 38 ).

Furthermore, T cells are prolific producers of cytokines like interleukin-2 (IL-2), interferon-gamma (IFN-γ), and tumor necrosis factor-alpha (TNF-α), which drive inflammation. By reducing the availability of transcription factors necessary for cytokine gene activation, Selinexor effectively diminishes cytokine production ( 39 ). This reduction is crucial for alleviating the inflammatory response, offering therapeutic benefits in diseases characterized by cytokine storms or persistent inflammation.

The suppression of inappropriate immune responses by Selinexor, especially in autoimmune diseases where T cells target self-antigens, alleviates symptoms associated with these conditions. By dampening T cell activation and reducing inflammatory cytokine levels, Selinexor aids in managing inflammatory diseases and contributes to maintaining immune homeostasis. These actions underscore Selinexor’s potential to modulate the immune system in ways fundamentally different from traditional immunosuppressive or immunostimulatory therapies, providing a novel approach to treating conditions where immune regulation is beneficial, such as autoimmune disorders and chronic inflammation.

Furthermore, Selinexor’s ability to prevent the creation of neutrophil extracellular traps (NETs) while maintaining neutrophil function provides strategic benefits in the treatment of illnesses defined by high NET activity ( 40 ). It affects cell death mechanisms, such as PANoptosis (pyroptosis, apoptosis, and necroptosis), by controlling the nuclear export of ADAR1-p150, highlighting its potential for treating cancer and inflammatory illnesses by modulating cell death pathways ( 41 ).

The therapeutic scope of Selinexor in anti-inflammatory therapy is complicated, encompassing nuclear output inhibition, cytokine production control, modulation of critical signaling pathways, and antiviral actions, as illustrated in Figure 1 . These features make Selinexor and other SINE compounds intriguing candidates for the treatment of chronic inflammatory disorders and viral infections, paving the way for further study into their broad therapeutic applications.

Figure 1 Illustration of Selinexor’s Mechanism of Action in Modulating Inflammatory Pathways. This diagram depicts the mechanism of action of Selinexor in inhibiting inflammation. It shows the stabilization of IκBα, which prevents the translocation of NF-κB to the nucleus and the subsequent reduction in pro-inflammatory cytokine transcription. The image outlines Selinexor’s effect on various components of the inflammatory pathway, highlighting its role in downregulating cytokine production and modulating immune responses.

3.2 Clinical implications of Selinexor’s anti-inflammatory actions

3.2.1 sepsis.

Clinical studies have established Selinexor’s efficacy in modulating key inflammatory pathways in sepsis. In animal models, treatment with Selinexor has been observed to significantly improve survival rates. Specifically, it reduces lung damage caused by lipopolysaccharide (LPS) and decreases the accumulation of inflammatory cells in the peritoneal area. These effects are linked to reduced levels of pro-inflammatory cytokines such as TNF-α, IL-6, and HMGB1 ( 6 ). Selinexor’s mechanism of action in sepsis involves the inhibition of crucial inflammatory pathways, notably NF-kB and MAPK p38, which are integral to the inflammatory cascade in sepsis. This inhibition is significant as it directly affects the pathways that exacerbate sepsis, providing a targeted approach to reducing acute inflammatory reactions ( 6 ).

3.2.2 Antiviral applications

Selinexor and Verdinexor, members of the SINE chemical family, demonstrate potent antiviral properties by inhibiting the nuclear export of viral proteins crucial for assembly and replication. In animal models, including ferrets in COVID-19 studies, Selinexor has effectively reduced viral loads and mitigated inflammatory damage, indicating its role in managing severe viral infections through immune modulation and cytokine storm reduction ( 37 ). Verdinexor disrupts the lifecycle of Respiratory Syncytial Virus (RSV) by sequestering RSV M proteins in the cell nucleus, inhibiting replication of both A and B strains. This action simultaneously enhances p53 activity and reduces XPO1 levels, offering a strategic advantage against RSV ( 42 ).

In the context of COVID-19, Selinexor blocks the nuclear export of essential viral proteins such as ORF3b, ORF9b, and the nucleocapsid N protein, crucial for SARS-CoV-2 replication. It also reduces the cell surface presence of the ACE-2 receptor, limiting viral entry. Furthermore, Selinexor modulates immune responses by controlling the release of inflammatory cytokines, potentially alleviating cytokine storms commonly associated with severe COVID-19 cases through the inhibition of NF-kB pathways and direct effects on STAT3 and IL-6 transcription ( 37 ). Conversely, research by Rahman et al. suggests that pretreatment with Selinexor may enhance coronavirus replication, including in SARS-CoV-2 and mouse hepatitis virus (MHV), illustrating the complex effects of Selinexor on viral replication and inflammation, and underscoring the necessity for precise administration timing ( 40 , 43 ).

These findings reveal the dual potential of Selinexor and KPT-335 in combating viral infections, showcasing their ability to control viral growth and inflammation. Despite promising initial results, the complexities and some contradictory findings underscore the need for further research to fully understand their therapeutic potential beyond cancer treatment and to integrate them into broader therapeutic frameworks.

3.2.3 Chronic inflammatory diseases

Selinexor, along with other SINE compounds such as KPT-8602, exhibits potential in treating both acute and chronic inflammatory diseases, spanning conditions like Duchenne Muscular Dystrophy (DMD), Parkinson’s Disease (PD), Calcific Aortic Valve Disease (CAVD), and pulmonary fibrosis. These compounds inhibit key inflammatory pathways, offering new therapeutic strategies across a spectrum of diseases.

In chronic conditions like DMD, Selinexor and KPT-8602 have shown promise by modulating inflammatory cytokines and pathways, improving muscle function, and slowing disease progression. Specifically, KPT-8602 not only enhances muscular architecture but also reduces serum levels of biomarkers associated with bone and muscle turnover, fostering conditions conducive to muscle healing and renewal ( 7 ). This dual approach targets both the structural damage and inflammatory underpinnings of DMD, making KPT-8602 a valuable therapeutic option. For PD, these compounds protect dopaminergic neurons by mitigating neuroinflammation, thereby potentially delaying the progression of the disease. The inhibition of critical pathways such as NF-kB and the NLRP3 inflammasome underscores their capacity to protect against neuronal degeneration, a hallmark of PD ( 44 ). In the realm of CAVD, Selinexor has demonstrated the ability to modulate inflammatory responses that contribute to pathological calcification, suggesting a role in managing diseases characterized by such calcifications ( 42 ). Recent insights into Selinexor’s impact on pulmonary fibrosis reveal its effectiveness through the inhibition of the XPO1 protein, influencing GBP5/NLRP3 inflammasome signaling pathways crucial in the inflammatory responses associated with fibrosis. This action suggests that Selinexor could be instrumental in treating conditions marked by widespread inflammation and fibrotic transformations ( 45 ).

Overall, the exploration of SINE compounds in treating benign diseases has garnered significant attention due to promising results that suggest a potential to control, if not decelerate, the progression of these conditions ( 42 , 44 ). The broad applicability of SINE compounds in diverse inflammatory and autoimmune conditions supports continued research into their comprehensive anti-inflammatory effects across various diseases.

4 Limitations and future directions

As Selinexor’s role in treating both cancerous and non-cancerous conditions continues to be explored, it is evident that while the drug offers promising results in managing inflammation, there are significant gaps and limitations in our understanding that necessitate further investigation. One primary concern is Selinexor’s specificity as an XPO1 inhibitor, which influences a broad spectrum of proteins and can lead to unintended consequences, including severe side effects. This broad activity presents challenges, especially in chronic conditions where long-term treatment is required, as balancing efficacy and safety becomes critical ( 46 , 47 ). The need for optimal dosing to achieve the desired anti-inflammatory effects without compromising safety is a significant hurdle, with higher doses potentially increasing the risk of adverse effects.

Additionally, while it is recognized that Selinexor modulates several key inflammatory pathways, the precise mechanisms by which it impacts specific conditions remain poorly understood. This incomplete mechanistic insight hampers the development of targeted therapies that could enhance Selinexor’s efficacy while minimizing side effects.

Looking ahead, future research should focus on developing targeted delivery systems that can localize Selinexor’s action to specific tissues or organs. This strategy would potentially reduce systemic side effects and enhance efficacy in localized inflammatory conditions, such as inflammatory bowel disease or rheumatoid arthritis. Exploring combination therapies that include Selinexor and other anti-inflammatory agents may also improve therapeutic effects and possibly reduce the necessary dosages, which could be tailored to specific pathways active in various inflammatory diseases.

Longitudinal studies are crucial for assessing the long-term effects and safety of Selinexor in chronic inflammation. Such studies would provide a more comprehensive understanding of its benefits and risks. Further research into identifying biomarkers that predict responses to Selinexor could improve patient selection and treatment monitoring, facilitating personalized treatment approaches that optimize therapeutic outcomes while minimizing adverse effects.

Moreover, expanding research to explore Selinexor’s effects in non-cancerous inflammatory diseases could uncover additional therapeutic uses and provide new insights into its anti-inflammatory properties, potentially opening new avenues for treatment across a broader range of inflammatory disorders. This ongoing research and the development of new clinical strategies are essential for fully realizing the potential of Selinexor in the management of both malignant and benign diseases, ensuring that treatments are both effective and safe for long-term use.

5 Conclusion

Selinexor is distinguished by its unique nuclear inhibition, exhibiting extensive effects. By trapping tumor suppressor proteins within the cell nucleus, Selinexor induces apoptosis in cancer cells, proving effective against various types of tumors, including hematologic malignancies and solid tumors. This positions it as a key therapeutic approach in oncology, especially valuable in cases resistant to conventional treatments.

Similarly, Selinexor demonstrates robust anti-inflammatory action through its key mechanism of XPO1 inhibition, which suppresses the activity of regulatory factors such as NF-kB and STAT3. This action effectively modulates immune responses and inflammatory pathways, enhancing its utility in treating both acute and chronic inflammatory diseases such as sepsis, DMD, and PD. This dual functionality not only broadens its therapeutic applications beyond oncology but also highlights its potential to manage a diverse array of diseases.

However, the transition of Selinexor from an anti-cancer to an anti-inflammatory agent has unveiled both its versatility and the complexities associated with its broader applications. Ongoing research is crucial in further unraveling its full potential, aiming to harness its capabilities while addressing any associated risks more effectively. The extensive clinical trials and continuous research efforts are essential to ensure the long-term safety and efficacy of Selinexor, optimizing its use in clinical practice.

As research advances, Selinexor continues to stand out not only for its significant therapeutic implications but also as a paradigm shift in the management of complex disorders. Its ability to concurrently address oncological and inflammatory diseases underscores its potential as a versatile therapeutic tool. This highlights the importance of continued investigations into its mechanisms and therapeutic applications to fully realize and utilize its extensive benefits.

Author contributions

DL: Writing – original draft, Investigation. HF: Writing – original draft, Data curation. RZ: Writing – review & editing, Resources. QX: Writing – review & editing. YY: Writing – original draft. LC: Writing – review & editing, Supervision, Conceptualization.

The author(s) declare financial support was received for the research, authorship, and/or publication of this article. This work is supported by Project of Sichuan Provincial Department of Science and Technology (2021YFS0373).

Acknowledgments

We express our sincere gratitude to Dr. Qingxiang Sun for his invaluable guidance and assistance throughout the research and preparation of this manuscript. His expertise in navigating complex literature and explaining intricate mechanisms has been essential to our work. Additionally, we acknowledge Bio-render for providing the tools necessary to illustrate mechanisms clearly and effectively. Special thanks to Shenzhen METSTR Technology Co., Ltd. for granting us access to cutting-edge literature, which significantly contributed to the depth and quality of this review.

Conflict of interest

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Publisher’s note

All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.

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Keywords: Selinexor, oncology, inflammatory diseases, nuclear export inhibition, therapeutic mechanisms

Citation: Li D, Fang H, Zhang R, Xie Q, Yang Y and Chen L (2024) Beyond oncology: Selinexor’s journey into anti-inflammatory treatment and long-term management. Front. Immunol. 15:1398927. doi: 10.3389/fimmu.2024.1398927

Received: 11 March 2024; Accepted: 25 April 2024; Published: 10 May 2024.

Reviewed by:

Copyright © 2024 Li, Fang, Zhang, Xie, Yang and Chen. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY) . The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

*Correspondence: Lin Chen, [email protected]

† These authors have contributed equally to this work

‡ ORCID : Lin Chen, orcid.org/0000-0002-9196-3640

Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.

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“A Long Journey” Poetic Devices & Figurative Language

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“A Long Journey” Vocabulary

Form, Meter, & Rhyme Scheme of “A Long Journey”

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