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Eldritch horrors may have a little s’mores…as a treat
Mild body horror version under the cut
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Doing another picrew chain
Support this beautiful picrew right now!!! /nf
Tags: @i-dont-eat-drywall @maple-chaos @skylerfumaniac @mattcat @fluffygiraffe @theauthor27 @ask-abstracted-kaufmo @raedioactive and all of my other moots I forgot to tag
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hello, hello!! could we perhaps have some zooble angst if you wouldn’t mind?? /nf
Here it is!! omg im so sorry ab the wait but i hope you like it!!
•Abstract Art•
TW: Heavy angst, Abstracting, identity loss/low sense of identity, Swearing, Very intense identity issues/please read with caution
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Zooble never knew exactly what they were.
They knew they were a circus member unwillingly, that they were doomed here indefinitely. They knew they didn’t like Caine’s adventures.
But they didn’t know how to be Zooble.
They stare at the full length mirror in their bright bedroom. Zooble stares back. The mirror in their room brought a cruel irony: they could barely recognize the mess of shapes simulating a reflection.
The flimsy and wavering sense of identity they had before was just that. The circus, this body didn’t help matters at all. It was like their memories, their life beforehand, was a sea of questions and inauthenticity. This body stripped away their last anchor.
They glanced at the box that became a permanent fixture in their room. The box of parts, chasing a high of finally finding something that fits. That feels fucking *okay* for once.
The only thing Zooble knew for certain about themselves, was that they knew absolutely nothing about themselves.
Their minds were so fragile here. Getting used to your new avatar and body took a long time, that was a given. But, most of the cast had gotten used to it. It wasn’t always a problem for them.
Zooble recalled when their digital body’s unwanted versatility sank in. They had been having the digital feast, everyone making mindless and meaningless small talk. Zooble shakily raised their arms. Then their legs. Then felt their antennae.
A dry, humorless chuckle came from them. Then another, raising in pitch. Then another, higher still. Before long, they were full on cackling.
Somehow, through a headset, into a game they had no say of being stuck in, with no memory of their names,
Their unstable identity managed to make it through.
Zooble stood now, still looking at the mirror. Charged silence hung in their room. Zooble shook slightly. Their fists, if they could be called that, clenched.
Then, they screamed.
Zooble screamed and screamed. Their rooms were soundproof, so no one would know.
Zooble shouted this time, and knocked everything down. Punching the mirror, ripping sheets off the bed, breaking their bedside table.
It wasn’t enough. Zooble needed to destroy everything. Everything that made up this lie. Zooble scanned the room in an angered and desperate haze, until something caught their eye.
That damned box.
Zooble flung it open. The endless mountain of parts and arms and legs greeted them.
They mocked Zooble, they were sure of it. A cruel joke. A solution, right here in front of them, that wouldn’t solve anything now matter how many times they tried it.
Zooble, breathing heavily, began flinging them out of the box. Part after part, shouting as they did so. Screaming.
Something good. Something had to work. Eventually. Eventually it would. Good. Something that fit. Something good. Something that didn’t make them scream. Something for Zooble. Who is zooble who is zooble who is ZOOBLE WHO IS-
Zooble barely stopped when the first eye appeared on them. Flicking around insanely fast with a neon pupil and sclera. Zooble shouted in pain, more eyes appearing.
Their room was covered in parts. It was never enough. It was never going to *be* enough. This was their fate.
Zooble was shocked to the ground again with another violent glitch. They fell back on the piles and piles of parts on their floor. The darkness spread up their body, around their neck. Up their torso.
Zooble let out another humorless laugh. They knew they weren’t too different from the abstractions, anyhow.
Maybe they’d like this form more.
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WOOOO!! I hope this was good! If i need to add more trigger warnings please lmk :)))
jesterdoll should be comin soon cus that won the poll! i may have something special w a new ship soon tho..
reblogs are appreciated! see u guys next time!
#tadc#the amazing digital circus#tadc fic#writers on tumblr#tadc zooble#zooble#the amazing digital circus zooble#tadc angst#tadc caine#zooble tadc#zooble fic#tadc gangle#gangle#tadc pomni
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LSOH x TADC AU designs!!
Ye ye some designs for my lsoh x tadc au I talked about a while back lol :3 btw I won't spoil but tadc ep 3 was pretty good IMO!! I can't guarantee I'll get back into tadc since I feel like the main reason I did after ep 2 was for Ribbun mostly lol but hey who knows? Speaking of, I don't ship them in this AU personally but idgaf what y'all ship with them, preferably not Pomni n Caine tho since this is going by the 1986 version of the movie where Mr. Mushnik acts more like a dad to Seymour.
First up, we have Pomni as Seymour and Queenie as Audrey 2!! I like to think she starts to abstract as she is "dying" of starvation :]
Next up we have Gangle as Audrey and Jax as Orin because OH BOY are they toxic...also added the bow cuz I didn't wanna give Gangle hair but I wanted to give her..something..so ye
Next up we have Bubble, Sun and Moon as the Chiffon girls cuz...idk. My only real thought is Bubble, Sun and Moon are all paired together for the Animiz figure & they're all just talking objects so..yeah
Then we got Caine as Mr. Mushnik and Ragatha as the radio host person thingy that Seymour talks to! For Caine, I decided to take more inspo from Mr. Mushnik's design from the cartoon Little Shop just to differnate this from regular Caine as much. For Ragatha, idk I wanted to make her look like a typical 80s' girl lol
Last, but not least, we got Kaufmo as Arthur Denton!! :3
Also, I didn't feel like drawing them cuz they would play such minor roles but I think Gummigoo would be the first guy to come in and notice Audrey 2 and buy a dozen roses(or two dozen..? i cant remember lol) since that guy already talks a bit like an NPC lol. And then Zooble would be the nurse that just wants to get the hell out of there during the Arthur Denton scene lol.
But yeah, lmk what y'all think!! :3 /nf
#lsoh#little shop of horrors#crossover#crossover au#lsoh x tadc au#tadc x lsoh au#pomni#queenie#gangle#jax#bubble#sun#moon#caine#ragatha#kaufmo#pomni tadc#queenie tadc#gangle tadc#jax tadc#bubble tadc#sun tadc#moon tadc#caine tadc#ragatha tadc#kaufmo tadc#tadc#the amazing digital circus#artists on tumblr#lucyartz
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hiii i hope you're doing well!! /gen
i just saw your post (it was from a few months ago) where you said that you're okay with asks about kin-related activities so i was wondering if you have any suggestions for angelkin/divinekin activities? (/nf)
if you don't have any ideas no worries!!!
-@aureatewings
hihi im SO sorry i dont know how i never saw this !! :0
im a demon lord myself so this is a little outside my realm, but ill do my best ! i feel like there must be some cross over anyway with divine kin :o
ANGEL/DIVINEKIN ACTIVITIES
🕊️ meditation! get in touch with the higher powers or simply allow the world to move around you. as a higher being, the constant stimulation of the human world can pull us in and distract us from our connection to the universe, the world, your deity, or even your own sense of self. allow yourself space to reflect and remember the scale of the universe and where you came from.
-> as an aside to this, cloud gazing can also be a good activity! it promotes the same kind of mindset, but if you are one who comes from the heavens or used to have wings, it can help to watch the sky above.
🕊️if you are a creature who is meant to help humans or command others, it may help to go into a leadership position. naturally we want to see our actions impact the world around us, and you can do this positively by engaging in your community, charities, or other groups around you like youth groups, churches, clubs, etc.! especially if you are an angel of a kind god, this may help you feel like your back in touch with your 'purpose' of aiding mortals.
🕊️ personally, i find it can help to get creative around more abstract/obscure kintypes to find ways to represent yourself. explore how you may express your sense of self - do you manifest as a wall of code, or a mixed media instillation with imagery and sound? are you a video? a sculpture? i find it fun to explore how the essence of my being feels when it is unable to be perfectly seen/experienced by the human mind.
thats all i can think of at the moment, but ill add onto this if i think of anything else! feel free to reblog with ur own ideas too ! ^^ apologies if this isnt quite what u wanted, i did my best coming from the perspective of a demon lord :>
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Im craving for my abstract au bestie... /nf /srs
here you go bestie! i’m sorry it took a while!
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My Babies (NF + LF) Headcannons
There's so much stuff I just... don't like too much about the LF, I think most everybody can agree with me, and since I'm back in my annual HTTYD phase, I'm developing my LF redesign further.
The grey version of the light Fury, that I'll be building off: (plus older redesign photos)
1. Invisibility/Skills
As shown in HTTYDTHW, LF has reflective scales when heated. This works with its own fire, but I like to think, also from the inside. Their body can consciously move internal bodily heat against their scales, so slowly able to become invisible within closed spaces. Also used to prolong reflectivity after using a plasma blast.
Plus, a nack for rock climbing, using their longer tail, as well as longer talons, allows them to scale up rocky walls.
2. Habitat/Camouflage
As shown in the hidden world, there are tide pools and large bodies of water. I like the idea the LF developed a grey top, to blend in with stone, and from any angle within the water, (like a killer whale.)
Also shown in my designs, their tail fins, are longer but thinner, with fins instead of spikes on the back, and this would be better for tight cramped spaces of a cave, and underwater manoeuvre. So semi-cave dweller, semi-aquatic.
3. Family/Pack roles
As shown in HTTYD Nine realms, Furies live in packs. There's obviously an order to that. I'm slightly taking inspiration from Lions, and comparing Toothless to the LF, Toothless is significantly bulkier. With this extra bulk, male LF are made to protect eggs and young. With white eggs, these furies often cover the eggs with their wings or bodies. While females, being less wide, allowing for tighter turning, are the hunters. Like a kingfisher, I think they may dive-bomb down into the water to quickly catch fish, being their main food-catching method, but with speed and agility, other larger prey can be caught.
I like to think with their destructive plasma blast, Males can often court females by carving out a hole in the rock walls or cliffs or claiming an already existing one. These home caves are often found by the water. Allowing for easy fishing, and allowing the kids to safely watch their mum while she hunts, to help them learn.
3. Courting
Being a thing Toothless didn't excel at, mating dances and other practices. intelligence and coordination seem to be the main two traits females look for.
I think mainly, having a good cave picked out, is something a female likes, showing intelligence. Also as shown in the Toothless sense where he dances with the LF after winning her over, swinging the tail, and spreading the wings are in the male's favour. Trotting, holding up the wings, and swishing the tail all at once, shows agility and coordination. The LF finally likes Toothless once he draws her, with the abstract show of intelligence, and so other things like that, solving puzzles, outsmarting other dragons in fights and such are other ways of showing off courting.
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⁎˚ ఎ Rin Itoshi Agere ໒ ˚⁎
Since you allow blue lock I was thinking little Rin Itoshi hcs? I know you get a ton of agere reqs but I see no blue lock agere ever :( /nf take your time and thank you!!
•Rin’s regression likely stems from his deeply rooted emotional struggles, such as his constant internal pressure to be the best
•Quiet Regression: Rin is a very quiet little. He doesn’t verbalize much, preferring to communicate through gestures, nods, or short phrases. This mirrors his usual personality but in a much softer, less guarded way
•He’d have one specific plushie (maybe a wolf or tiger) that he clings to. It represents the strength he feels he lacks as a little and brings him comfort during moments of vulnerability
•In his regressed state, Rin loves to draw. His sketches are simple but expressive, often depicting soccer scenes, family, or abstract shapes that mirror his emotions
•Comfort Items : Oversized hoodies or soft blankets become his go-to. He loves to cocoon himself in them, creating a small "safe zone" where he feels protected from the pressures of the outside world
•Even as a little, soccer is a grounding activity. He might kick around a soft, squishy ball indoors or play small games with himself, finding joy in the simplicity of the sport rather than its competitive aspects
•Isagi would likely be a gentle and patient caretaker, encouraging Rin to take breaks from overexerting himself. He’d play small soccer games with him or join him in his quiet activities
•Bachira would bring out Rin’s more playful side. He’d encourage him to finger paint, play silly games, or just laugh at goofy antics. Rin might find Bachira overwhelming at times but secretly enjoys the attention
•If Sae were ever to find out, he’d probably be confused but surprisingly protective. He’d awkwardly try to connect with Rin by sharing quiet moments, like reading together or just sitting in comfortable silence
•Rin's agere triggers : mention of failure or loss, especially in the context of soccer and conflict, particularly arguments or raised voices, even if they don’t involve him
•Rin might try to hide his regression by retreating to quieter spaces (his room or the corner of the training facility). However, observant teammates might notice his softer demeanor
•Unlike other age regressors who may seek social comfort, Rin might initially avoid group interactions during regression. Over time, though, he could warm up to one or two trusted teammates
•Rin thrives on routine even as a little. If his regression happens during training periods, he might follow his usual schedules but at a slower, less intense pace
•Chigiri: Rin and Chigiri could bond over their quiet tendencies. Chigiri might introduce Rin to calming activities like braiding string bracelets or light stretching routines
•Kunigami: Rin would view Kunigami as a safe "big brother" figure, often gravitating toward him for silent reassurance
•Reo & Nagi: Reo would try to spoil Rin, offering him toys or snacks, while Nagi would be the perfect nap buddy !
If you're in the basic criteria , are DSMP fans, vivziep0p fans , h0tel/h3lluva b0ss fans, Owl h0use fans, St4r butterfly fans, Ghibli fans, ddlg/abdl blogs, nsfw/k!nk blogs, anti-agere blogs, or anti Christians/Christianity blogs : just dont interact !
#ㅤ𐔌ྀ h e a d c a n o n s#edit#free to reblog#sfw post#sfw little one#agere#sfw regression#sfw agere#age regressor#sfw age regression#age re safe space#age regression#age re blog#age regressive#agere fandom#agere hcs#agere headcanons#agere little#agere boy#agere blog#agere community#agere blue lock#blue lock#rin itoshi#blue lock isagi#blue lock bachira#chigiri blue lock#bllk kunigami#nagi blue lock#reo blue lock
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This country (UK) is *consistently* so alarmingly, deliberately, obtuse and in denial when it comes to talking about race and racism. That a tory donor (who also has a number of NHS contracts because, of course), can talk about having a murderous hatred of Diane Abbott that is sufficiently strong enough to make him hate all Black women, and people are genuinely going 'it was rude, but was it racist?'... give me strength
MPs, commentators and donors will come out with the most vile, explicitly racist venom, and journalists will seriously entertain them saying 'I haven't got a racist bone in my body' or some such nonsense, all because people here have kidded themselves into believing that racism is strictly limited to a handful of Very Bad People™️, apartheid South Africa and the entire US Deep South.
And if they do manage to acknowledge that the most obvious explicitly racist rant is, indeed racist, they most certainly will not have the powers to reflect on their own behaviours to see if there's a pattern. Politicians and journalists playing fast and loose with 'culture wars' bs day and night, as if there'll be no casualties. And then falsely invoking concern over MPs' safety in order to sabotage a concensus vote against the genocide of Palestinians. Diane Abbott has been in the receiving end of the majority of the abuse faced by all MPs, and not only has she *never* received support from the likes of Dear Leader Keith, but the fucker actually gave her the boot for her troubles
And to think that Gove is currently presiding on a new definition of extremism to harass us with. Bitch, the call is coming from inside the house!
It's always been a problem that racism is so often framed as an individual making poor choices or being ignorant and 'doing a racism', rather than understanding it as being a fundamental factor in the socio political organisation of the world for some 500 odd years. Racism is seen as 'bad', but only in an abstract sense that absolves society at large of culpability and reduces it to a bothersome (but only if you - the individual- choose to let it bother you🙃), individual flaw
We've spoken up, written books, protested, 'debated', reminded the world that Black people did not invent or benefit from this racial hierarchy which now permeates everything and perhaps therefore cannot reasonablybe expected to be the ones to fux it, and yet here we are...
Meanwhile, an awful lot of people still seem convinced that because we have an Asian PM and the party in power is more ethnically diverse than snyone would have believed possible 20 years ago, we've got it sussed. Those people cannot begin to grasp that the entire tory party could be comprised of Black, Asian, muslim & women candidates, and it would still be upholding the white supremacist heteropatriarchy. When Sunak has to defend his dodgy premiership by invoking some 'protect our wimmin from dangerous migrants' like some retro NF dickhead, that should tell you everything you need to know if you have the range to understand
#uk politics#uk racism#a hotbed of denial duplicity mendacity and general foolishness#never tory#UK Labour are useless#misogynoir#diane abbott
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you do have oc’s yes. give the lore now. That is an order, mister /j /nf
BHSXHHDOBSOXBXBI HAVE TOO MANY
UHM
I GOT LIKE A MILLION ESSAYS OF LORE FOR MOST BUT HERE ARE THE INTRODUCTIONS:
For this show I wanted to write I have 3 main guys I love dearly, Lifen Heid who is the main dude and German- is secretly holding some kind of power and yet isn’t aware of it. This spirit guy Fhelix (quite OP but is so fed up with every being that he litterally does not use his powers at all except for his main goal) knows though and was set off on a journey to help him become a god like he once was but can’t say what he’s doing otherwise they would both die an agonising death. They got some chemistry and lore together plus I advanced the plot into a full blown book. Robin, a side character whom I love dearly, is a pathetic little kid who was forced to flee from his planet from false vigilante accusations and resides in the realm (this whole new world only accessible through a portal) with Fhelix, whole ordeal, and also some other people that also had the same fate, basically heroes turned sour and he got trapped into their little group (There’s this massive group and all got their individual relationship with one another and personality but in short they’re like 15-23 year old losers with some sort of dramatic past and incredible talents (lemme tell you about them..) ) So there’s Batrose - an emo shithead who is 99% a sadist and is a very good swordsman, and despite that, he is in a relationship with Florence, an absolute sweetheart who also is quite a dangerous individual. Basically that meme template where they both can absolutely kill you but one visibly has intention and the other is bubbly. Both dress somewhat goth. There’s also Dan, a daredevil cat hybrid who always looks for trouble and is a horrid influence on Robin but I still love him, not too much older then him. Westifer is this ginger kid the same age as Dan and yet is much more secluded than the rest and has an amulet passed down from generation to generation which allows him to practically bend water to his will, but he sort of struggles with it. He has a floating blob of water he can activate anytime and it’s somewhat sentient and has bubbles for eyes but mostly just helps him get to places sometimes as it’s body can act as a cushion. Also has a pet flamingo named fern. There are some other others but they’re not worthy enough of being saved in my mind.
one of my newest two is Neil Wolfman, he got a shitload of lore which I could copy and paste here in a second. Absolutely adore him but in short he’s a pathetic little soggy boy who has a car and out of paranoia spends most time out in the suburbs and owns an adorable German shepherd named Arc. also this mad scientist I haven’t bothered with making a name for that I do quite love and is my most attacked character for art fight!
also idk if it counts but just any variety of me whenever I draw myself, ranges from abstract concept to realistic depiction to absolute goofy doodle to entirely new creature or human.
I also realised like not lately that they almost all were some representation from me and I was incredibly surprised.
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✶ Welcome ✶
Ace ✶ 27 ✶ they/them
Please read my Carrd and the addendum in UT+ before following
Navigation
Tags ✶ UT+ ✶ reblogs @capricioussuns
Commissions: Open ✶ Art Trades: Open
Kofi ✶ Discord: @ CapriciousSuns ✶ Other socials linked in Carrd
Mostly undertale+au stuff here but other things show up from time to time ✶ Prosh/p dni ✶ "Boundaries"
Hand Status: the surgery haunts me still, doing exercises to build strength to mixed results
General Status: not good (festive edition 🎄(like this))
Upcoming Event(s): December 30th, UF Papyrus Monday 1 year anniversary 24h magma board, starting midnight EST
#yearly updated pinned post jumpscare#art tag ->#snow and hail#talk tag ->#sunny with clouds#hc tag ->#sun spots#pinned#cs comms#nf abstract
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Employee art idea or smh:
Employee abstragedy 👀 /nf
Like- abstracted....humans?
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Idk if you take requests, but if yes: does thou have any Loui hc’s? Or NY if not? 👁️👁️ /nf
Oh hello
I can indeed take requests, though I haven't in some time. Luckily for you I have headcanons for both of these delightful beings!
Let's go alphabetically and start with Louisiana :)
The most normal name of the states, and therefor the one who receives the most mail. He spells his 'name' Louis, of course, because that is how the person he was 'named' for spelled it. It's still pronounced Loui don't fret.
A lover of Odd Museums. Like dinosaurs are very cool, and history is very Important, but Niche Museums are his joy.
Because of the state's reputation for magic and similar practices, most people assume Louis knows magic. So they tell him about their local magic or cryptic or the traditions immigrants brought along with them, or even just interesting myths or folklore they found on the internet. Now don't get him wrong, Louis is 100% capable of some magic, but he isn't really as into it as the stereotype would have you believe. Luckily(?) He likes the conversation too much to stop people most of the time.
Louisiana loves big gatherings. Louisiana loves showing people his state. Louisiana is constantly inviting states outside of his region to parties/meals/events/hang out. The South thinks this is very weird and constantly tries to dissuade him from the habit. Louisiana does not stop.
Now let's see what we have for The World's Grumpiest Bodega Cat, New York
He is alarmingly short for his population and area. He's just slightly below average human height, maybe 5'9", but he *feels* bigger. If asked him about it, he'd say it's because you're looking at him from the wrong angle before punching you to the ground.
He has a deep love of hiking, nature walks, and bird watching. It is not unusual to find New York on a path or trail, just soaking in fresh air, listening to a different sort of background noise.
THE most ecclectic music taste in the house. His Playlists are entirely unpredictable and totally random to anyone but him. Good news is he's great at making a playlist for abstract vibes. He and California make tons of them.
He is the author of so many petitions to give the Jets to New Jersey. So very many. He's also first in line for destroying MetLife stadium.
#OOC#Welcome to the Table#WTTT New York#WTTT Louisiana#For those of you that didnt know#this is my RP blog#currently my primary#congratulations on bejng my first ask in AGES btw!#its so exciting!#have fun with these
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Another random TADC crossover AU?? Yea baby!! This time it's little shop of horrors :3
Note: I am a big Ribbuny shipper but in this AU I personally don't for reasons :3
Anyways here's who I think everybody would be:
Seymour --> Pomni
Mushnik --> Caine
Audrey --> Gangle
Orin --> Jax
Audrey 2 /Twoey --> idk who specifically but one of the characters that has abstracted perhaps
Arthur Denton --> maybe Kaufmo..cuz idk who else 😭
Anyways lemme know what y'all think! :3/nf
#little shop of horrors#the amazing digital circus#tadc#lsoh#crossover AU#gangle tadc#pomni tadc#jax tadc#kaufmo tadc#caine tadc#audrey lsoh#audrey 2 lsoh#mushnik lshoh#orin lsoh#seymour lsoh#tadc au#au#silly
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hellooo i heard that you help people figure out exactly what words are appropriate for their verbalness or lack thereof? i know ur not a professional but input from another would be really helpful. /nf. for reference we have DID and a lot of disorders associated with being bad at words (schizospec, autism, adhd) so we are, unshockingly, bad at words.
as a younger kid we were hyperverbal but kind of incoherent, and 90% of our coherent words were pulled from something else like a book or tv show. we only had verbal shutdowns if we were MAJORLY freaking out, and at age 12-13 managed to wayy tone down the garbled speech with something kind of similar to speech therapy.
then we had a heavy heavy environmental shift that caused a major skill regression. it knocked us down like a full support needs level (from level 1 to 2) and we're kind of just not very good at being a person anymore.
our speech has a 50/50 of making sense but our thoughts are clearly scattered, we're constantly forgetting words, and we have zero sense of tone. we can really only verbally communicate events, wants, or needs. feelings or abstract concepts get fried. it also takes insane anmounts of effort to make anything make sense. it gets worse on bad days or in nervewracking situations. we're a part time aac user and pretty reliant on it but even then sometimes we just cant, especially if it requires typing or writing :/
we've learned that for us, speech is very much on a "spoons" system where it is exhausting to speak to the point that we have less spoons to function through the day (ie; if we spend too much energy on words we can't brush our teeth later). we can kind of "save up" words, or have like a "verbal break" & different situations or sentences have different "costs." if we run low on spoons we also run out of words, but this takes shockingly little time on the average day. on the average day we can give one five minute presentation and then boom, no words. communicating complex thoughts is a solid no, our brain just scrambles it into incoherence. its really weird i hate it.
hi friend!
as i said, im just one guy on the internet (and not a professional) but i think its super valuable for people to share their experiences with differing levels in verbality!
i would definitely check out the word demiverbal! it kinda sounds like you struggle with speaking all the time, which is a hallmark of being semiverbal but as i said i can’t make that distinction for you.
also, while having a label to describe your experiences is useful, it’s not necessary and doesn’t make you more or less valid in your experience.
i totally get wanting one tho, and it’s really cool to hear about your experiences!
i hope this makes sense i’m a little brain fried ag the moment
i hope something good happens to you today!
chrome
ps - i get you about the whole going up a level thing! i’m leaning towards the MSN side of things every passing day due to autism/scz combo
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Progress in the Study of the Protective Effect and Mechanism of C-phycocyanin on Liver Injury
Abstract: C-phycocyanin (C-phycocyanin) is a pigment-containing protein from marine algae that has shown promising results in the treatment of many inflammatory diseases and tumors. C-alpha-cyanobilin is a pigment-containing protein from marine algae that has been shown to be effective in the treatment of various inflammatory diseases and tumors. C-alpha-cyanobilin has a protective effect on various liver diseases, such as drug-induced or toxic substance-induced liver damage, non-alcoholic fatty liver disease, hepatic fibrosis, and hepatic ischemia-reperfusion injury. The protective effect of C-alginin on liver injury is mainly realized through the regulation of signaling pathways such as nuclear factor (NF)-κB, phosphatidylinositol 3-kinase/protein kinase B (PI3K/Akt) and AMP-dependent protein kinase (AMPK), and the inhibition of oxidative stress, etc., and is not toxic to normal cells. Therefore, C-alginin has a broad application prospect as a potential natural hepatoprotective marine active substance. In recent years, the research progress of the protective effect of C-alginin on liver injury and its mechanism is summarized.
C-phycocyanin (C-phycocyanin) is a complex protein of cyanobacteria and a natural food protein pigment with pharmacological effects such as antioxidant, anti-inflammatory and anti-tumor effects, as well as fast-acting and low-toxicity, it can be used as a functional food [1-2]. C-Alginin can also enhance immunity and is safe, without causing acute and subacute toxic reactions [3]. Selenium-enriched PC has been shown to have stronger pharmacological effects [4]. Therefore, C-alginate has important research value both as a drug and a functional food, and has become a hot spot in the field of pharmaceutical research [5]. In this paper, we summarize the progress of research on the application and mechanism of C-alginin in liver diseases.
1 Ameliorative effect of C-phycocyanin on liver injury caused by drugs and toxic substances
The liver is the metabolic center of drugs and exogenous toxic substances, and metabolites are prone to liver injury. C-PC can inhibit the synthesis and release of inflammatory factors such as tumor necrosis factor (TNF)-α and interferon-γ, and increase the activities of catalase and superoxide dismutase (SOD), which can inhibit hepatic inflammation and alleviate hepatic injury [3]. It has been found that C-PC can significantly prevent thioacetamide-induced liver injury, significantly reduce the levels of alanine aminotransferase (ALT) and aliquot aminotransferase (AST), shorten the prothrombin time and reduce the hepatic histopathological damage, and improve the survival rate of rats with fulminant hepatic failure [6]. C-alginin also has a good effect on thioacetamide-induced hepatic encephalopathy, which can be seen in the reduction of tryptophan and lipid peroxidation indexes in different regions of the brain, and the enhancement of catalase and glutathione peroxidase activities in rats with fulminant hepatic failure [6].
Another study found that C-alginin not only attenuates the oxidative stress induced by 2-acetylaminofluorene and reduces the generation of reactive oxygen species (ROS) radicals, but also inhibits the phosphorylation of protein kinase B (Akt) and the nuclear translocation of nuclear factor (NF)-κB induced by 2-acetylaminofluorene, thus inhibiting the expression of multidrug resistance genes [7]. Osman et al. [8] also showed that C-alginin could normalize the levels of ALT, AST, catalase, urea, creatinine, SOD and glutathione-s-transferase in the livers of rats poisoned with carbon tetrachloride (CCl4). This result was also verified in human liver cell line (L02) [9]. C-phycocyanin can effectively scavenge ROS and inhibit CCl4-induced lipid peroxidation in rat liver [10], and C-PC can improve the antioxidant defense system and restore the structure of hepatocytes and hepatic enzymes in the liver of gibberellic acid-poisoned albino rats [11]. As a PC chromophore, phycocyanin can also significantly inhibit ROS generation and improve liver injury induced by a variety of drugs and toxic substances [10]. Liu et al. [12] found that phycocyanin showed strong anti-inflammatory effects in a CCl4-induced hepatic injury model in mice, which could significantly reduce the levels of ALT, AST, the expression of TNF-α and cytochrome C, increase the levels of albumin and SOD, and proliferate cytosolic nuclei. It can significantly reduce ALT and AST levels and the expression of TNF-α and cytochrome C, increase albumin levels and the expression of SOD and proliferating cell nuclear antigen, promote hepatocyte regeneration and improve the survival rate of mice with acute liver failure.
Gammoudi et al [13] used response surface method to optimize the extraction process of C-phycocyanin, and obtained high extraction recovery. C-phycocyanin extracted by the optimized method has the ability of scavenging hydroxyl, superoxide anion and nitric oxide radicals as well as the ability of metal chelating, and it has stronger antioxidant effect; C-PC significantly increased the activity of SOD and inhibited the increase of ALT, AST, and bilirubin in cadmium-poisoned rats. C-PC significantly increased the activity of SOD and inhibited the increase of ALT, AST and bilirubin in rats with cadmium poisoning. The above studies show that C-phycocyanin can effectively protect liver injury caused by drugs and toxic substances, and has the efficacy as the basis for drug development.
2 Preventive effect of C-alginin on hepatic fibrosis
Liver fibrosis is an inevitable process in the development of various chronic liver diseases and may be reversed with early and timely treatment. The key to liver fibrosis is the activation of hepatic stellate cells. Previous studies have found that low-dose C-alginin combined with soy isoflavones can inhibit hepatic stellate cell activation by inhibiting the activity of reduced nicotinamide adenine dinucleotide phosphate (NADPH) oxidase��14], but it is not clear whether C-alginin alone can inhibit the activity of NADPH oxidase. Therefore, the combination of C-algin and soy isoflavones at appropriate doses may have a preventive effect on liver fibrosis in high-risk groups. C-alginin may inhibit the progression of NADPH by suppressing oxidative damage, thereby inhibiting the development of hepatic fibrosis [15].
Epithelial mesenchymal transition (EMT) is one of the key mechanisms contributing to the development of fibrotic diseases. C-alginin inhibits transforming growth factor β1 (TGF-β1)-induced human EMT [16]. Although the effect of C-alginin on EMT in hepatic fibrosis has not been reported, it has been found that C-alginin can reduce pulmonary fibrosis by inhibiting epithelial mesenchymal transition [17]. Another study found that C-alginin could reduce the expression of α-smooth muscle actin (α-SMA) and connective tissue growth factor (CTGF) mRNA in human dermal fibroblasts and alleviate fibrous contracture [18]. The results of these studies also have significance for the inhibition of hepatic fibrosis, and provide a theoretical basis for the further study of C-PC as a potential antifibrotic drug.
3 Protective effect of C-alginin on hepatic ischemia-reperfusion injury
Liver ischemia/reperfusion injury is an important clinicopathophysiological phenomenon. It was found that the addition of two different doses (0.1 g/L and 0.2 g/L) of C-alginin to the Krebs Henseleit preservation solution significantly decreased hepatic ALT, AST and alkaline phosphatase activities, and reduced the rate of lipid peroxidation and malondialdehyde content in an isolated perfused rat liver model, and increased the activities of hepatic glutathione-s-transferase and glutathione peroxidase, as well as sulfhydryl groups in hepatic tissue. On the other hand, it can increase the activities of hepatic glutathione-s-transferase and glutathione peroxidase and the content of sulfhydryl groups in liver tissues, therefore, C-alginin can significantly reduce hepatic ischemia/reperfusion injury as an antioxidant [19]. In isolated perfused mouse livers, it was found that C-alginin significantly reduced the phagocytosis and respiratory burst activity of hepatic macrophages (Kupffer cells), attenuated cytotoxicity and inflammation induced by highly active Kupffer cells, and dose-dependently inhibited carbon phagocytosis and carbon-induced oxygen uptake by perfused livers, and then inhibited the increase of hepatic nitric oxide synthase activity induced by gonadotropins [20]. and thus inhibit the thyroid hormone-induced elevation of hepatic nitric oxide synthase activity [20].
However, C-alginin has a very short half-life in vivo, which limits its application in vivo. It was found that the use of polyethylene glycol-b-(polyglutamic acid-g-polyethyleneimine), a macromolecular material with good drug-carrying capacity and slow-release properties, as a nanocarrier of C-alginin could solve this problem, and the release of C-alginin could be delayed by subcutaneous injection into the abdominal region of rats, which could attenuate islet damage caused by hepatic ischemia/reperfusion and enhance the function of the islets [21]. This study broadens the scope of application of C-alginin in vivo and improves the therapeutic effect of C-alginin.
4 Inhibitory effect of C-alginin on hepatocellular carcinoma
It was found that C-alginin significantly reduced the expression of matrix metalloproteinase (MMP)-2 and MMP-9 and the expression of tissue inhibitor of metalloproteinase 2 (TIMP2) mRNA in human hepatocellular carcinoma cells (HepG2 cells) [22]. C-alginin is a natural photosensitizer, and photodynamic therapy (PDT) mediated by alginin microcystin induced a large accumulation of ROS in HepG2 cells, which promoted mitochondrial damage and cytochrome C release, and led to apoptosis of hepatocellular carcinoma cells [23].
Liu et al. [24] used nanoscale C-alginate particles prepared by lactobionic acid grafting and adriamycin loading to enhance the growth inhibition of HepG2 cells when combined with chemo-PDT, and the C-alginate particles could effectively accumulate and diffuse in tumor multicellular spheres. In vitro and in vivo studies on the effects of selenium-enriched PCs on PDT in hepatocellular carcinoma showed that selenium-enriched PCs could migrate from lysosomes to mitochondria in a time-dependent manner, and that selenium-enriched PCs could induce the death of tumor cells through the generation of free radicals in vivo, increase the activities of antioxidant enzymes in vivo, induce mitochondria-mediated apoptosis, and inhibit autophagy, thus offering a relatively safe pathway to tumor treatment and showing new development perspectives [4]. It can provide a relatively safe way to treat tumors and shows a new development prospect [4].
Lin et al. [25] combined C-phycocyanin with single-walled carbon nanohorns and prepared phycocyanin-functionalized single-walled carbon nanohorn hybrids, which enhanced the photostability of C-phycocyanin and protected the single-walled carbon nanohorns from adsorption of plasma proteins, and synergistically used with PDT and photothermal therapy (PTT) to treat tumors. C-phycocyanin covalently coupled with biosilica and PDT or non-covalently coupled with indocyanine green and PTT on tumor-associated macrophages can also increase the apoptosis rate of tumor cells [26-27]. The development of PDT and PTT synergistic methods for the treatment of cancer has broadened the application of C-PC and enhanced its value in the treatment of hepatocellular carcinoma.
In addition, C-phycocyanin can inhibit the expression of multidrug-resistant genes in HepG2 cells through NF-κB and activated protein-1 (AP-1)-mediated pathways, and C-phycocyanin increases the accumulation of adriamycin in HepG2 cells in a dose-dependent manner, which results in a 5-fold increase in the susceptibility of cells to adriamycin [28]. Even in adriamycin-resistant HepG2 cells, C-PC induced the activation of apoptotic pathways such as cytochrome C and caspase-3 [29], and the results of Prabakaran et al. [30] also confirmed the inhibitory effect of C-PC on the proliferation of HepG2 cells, mediated by the inactivation of BCR-ABL signaling and the downstream PI3K/Akt pathway. mediated by BCR-ABL signaling and inactivation of downstream PI3K/Akt pathway. In addition, C-phycocyanin modifies the mitochondrial membrane potential and promotes apoptosis in cancer cells [30]. Currently, C-phycocyanin is a synergistic molecule with other drugs that have been widely used in the treatment of cancer [31]. The above studies demonstrate that C-phycocyanin has good therapeutic potential in the field of hepatocellular carcinoma.
5 Amelioration of metabolic syndrome and non-alcoholic fatty liver disease by C-phycocyanin
It has been found that C-alginin can reduce ALT and AST levels, decrease ROS production and NF-κB activation, and attenuate hepatic fibrosis in rats induced by high-fat choline-deficient diets, and thus C-alginin has a protective effect on NAFLD rats through anti-inflammatory and antioxidant mechanisms [15].
Another study on the effects of aqueous extract of Spirulina (mainly C-alginin) on NAFLD induced by a high-calorie/high-fat Western diet in C57Bl/6J mice showed that aqueous extract of Spirulina significantly improved glucose tolerance, lowered plasma cholesterol, and increased ursodeoxycholic acid in bile in mice [32]. Kaspi-Chadli et al. Kasbi-Chadli et al. [33] showed that aqueous extract of Spirulina could reduce cholesterol and sphingolipid levels in the liver and aortic cholesterol levels in hamsters fed a high-fat diet by significantly decreasing the expression of hydroxy-3-methylglutaryl-coenzyme A reductase (HMG CoA) gene, a limiting enzyme for cholesterol synthesis, and TGF-β1 gene, and that ursodeoxycholic acid levels in the feces of hamsters fed high-fat diets were increased in the high Spirulina aqueous extract treatment group.
A daily dose of C-alginin-enriched Spirulina can reduce the harmful effects of oxidative stress induced by a diet rich in lipid peroxides [34]. Ma et al. [35] found that C-alginin promoted the phosphorylation of hepatocyte AMP-dependent protein kinase (AMPK) in vivo and ex vivo, and increased the phosphorylation of acetyl coenzyme A carboxylase. In the treatment of NAFLD in mice, C-alginin can improve liver inflammation by up-regulating the expression of phosphorylated AMPK and AMPK-regulated transcription factor peroxisome proliferator-activated receptor α (PPAR-α) and its target gene, CPT1, and by down-regulating the expression of pro-inflammatory factors such as TNF-α and CD36 [35]. This suggests that C-phycocyanin can also improve lipid deposition in the liver through the AMPK pathway.
Endothelial dysfunction is associated with hypertension, atherosclerosis and metabolic syndrome. Studies in animal models of spontaneous hypertension have shown that long-term administration of C-alginin may improve systemic blood pressure in rats by increasing aortic endothelial nitric oxide synthase levels, with a dose-dependent decrease in blood pressure, and thus C-alginin may be useful in preventing endothelial dysfunction-related diseases in the metabolic syndrome [36]. In the offspring of ApoE-deficient mice fed C-alginate during gestation and lactation, male littermates had an elevated hepatic reduced/oxidized glutathione ratio and significantly lower hepatic SOD and glutathione peroxidase gene expression.
C-PC is effective in preventing atherosclerosis in adult hereditary hypercholesterolemic mice [37]. In vitro, C-phycocyanin also improved glucose production and expression of phosphoenolpyruvate carboxykinase (PEPCK) and glucose-6-phosphatase (G-6-Pase) in high-glucose-induced insulin-resistant HepG2 cells [38]. C-alginin also increases glucose uptake in high glucose-induced insulin-resistant HepG2 cells through the insulin receptor substrate (IRS)/PI3K/Akt and Sirtuin-1 (SIRT1)/liver kinase B1 (LKB1)/AMPK signaling pathways, activates glycogen synthase, and increases the amount of glycogen [38]. C-phycocyanin can improve blood glucose and fasting serum insulin levels in tetracycline-induced diabetic mice [39]. Therefore, C-phycocyanin can maintain cellular glucose homeostasis by improving insulin resistance in hepatocytes.
6 Hepatoprotective role of C-phycocyanin in other liver diseases
Studies have shown that C-alginin can inhibit total serum cholesterol, triacylglycerol, LDL, ALT, AST, and malondialdehyde levels in mice modeled with alcoholic liver injury, significantly increase SOD levels in the liver, and promote the activation and proliferation of CD4+ T cells, which can have an ameliorative effect on alcoholic liver injury [40]. In addition, C-phycocyanin may enhance the intestinal barrier function, regulate the intestinal flora, reduce the translocation of bacteria and metabolites to the liver, and inhibit the activity of the Toll-like receptor 4 (TLR4)/NF-κB pathway, which may reduce the inflammation of the liver and prevent the occurrence of hepatic fibrosis in mice [41]. In mice with X-ray radiation-induced liver injury, C-phycocyanin can reduce radiation-induced DNA damage and oxidative stress injury by up-regulating the expression of nuclear factor (NF)-E2-related factor 2 (Nrf2) and downstream genes, such as HO-1, and play a hepatoprotective role by enhancing the activities of SOD and glutathione peroxidase [42].
7 Outlook
Liver fibrosis is the common final process of chronic liver diseases, and there is no effective therapeutic drug at present. Although some research progress has been made in the field of traditional Chinese medicine (TCM) on the reversal of liver fibrosis [43], its toxicological effects have not yet been clarified. Although the incidence of viral hepatitis has gradually decreased with the development and popularization of vaccines and antiviral drugs, the incidence of drug-induced liver injury (DILI) and liver diseases such as NAFLD has been increasing year by year with the improvement of people's living conditions [44]. Therefore, there is an urgent need to find drugs or nutrients that can help maintain normal hepatocyte function and effectively inhibit liver inflammation and fibrosis. C-alginin, with its anti-inflammatory, antioxidant, and antitumor effects, as well as good food coloring, has a wide range of applications in both the pharmaceutical and food industries.
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