#Fibrosis

[mindblowingscience]

Researchers at The University of Texas at El Paso are developing a new therapeutic approach that uses nanoparticles for the treatment of skin and lung fibrosis, conditions that can result in severe damage to the body's tissues. Md Nurunnabi, Ph.D., is an associate professor in UTEP's School of Pharmacy and the lead researcher on two studies published this June in the Journal of Controlled Release; one study focuses on skin fibrosis and the other on lung fibrosis. "We are closer than ever to developing a safe, effective and reliable approach to treating fibrosis," Nurunnabi said. Fibrosis is a condition in which the tissues in an organ—such as the skin, lungs, liver or kidneys—become thicker and stiffer, according to Nurunnabi. This can have multiple damaging effects, such as the lungs not being able to hold enough oxygen or blood vessels becoming narrower, leading to high blood pressure.

Continue Reading.

[bpod-bpod]

Essential for Marrow

Activity of a gene called LATS2 in the bone marrow's blood vessel cells is shown to be vital for normal functioning of the bone marrow, its loss leads to fibrosis – providing greater understanding of diseases such as leukaemia

Read the published research article here

Image from work by Kishor K. Sivaraj and Paul-Georg Majev, and colleagues

Department of Tissue Morphogenesis, Max Planck Institute for Molecular Biomedicine, Münster, Germany

Image originally published with a Creative Commons Attribution 4.0 International (CC BY 4.0)

Published in Nature Cardiovascular Research, July 2024

You can also follow BPoD on Instagram, Twitter and Facebook

[blueoaknx]

Mitochondrial Dysfunction in Endometriosis

 A Technical Overview of Cellular Mechanisms

Endometriosis, a common gynecological condition affecting approximately 10% of women during their reproductive years, is characterized by the presence of endometrial-like tissue outside the uterine cavity, most frequently in the ovaries, fallopian tubes, and peritoneal cavity. This ectopic tissue leads to a chronic inflammatory environment, pain, and infertility. While the pathophysiology of endometriosis is not fully understood, recent studies have increasingly highlighted mitochondrial dysfunction as a central feature of the disease. This technical article provides a detailed exploration of the role of mitochondria in endometriosis, examining the molecular and cellular mechanisms through which mitochondrial dysfunction contributes to disease progression.

Mitochondrial Function and Metabolism

Mitochondria are dynamic organelles responsible for numerous vital cellular processes, most notably ATP production through oxidative phosphorylation (OXPHOS). ATP is generated within the mitochondrial matrix by the electron transport chain (ETC), which involves the transfer of electrons from NADH and FADH2 to oxygen molecules, ultimately producing ATP. In addition to ATP production, mitochondria are involved in the regulation of calcium signaling, the maintenance of cellular redox balance, apoptosis, and the synthesis of key metabolites, including lipids and steroids. Mitochondria also contain their own genome (mitochondrial DNA or mtDNA), which encodes essential components of the ETC and mitochondrial protein synthesis machinery.

Mitochondria maintain their function through a balance of fusion and fission, processes that help ensure the organelle's shape, distribution, and response to stress. Mitochondrial dysfunction can arise from an imbalance in these processes, as well as from damage to mitochondrial DNA (mtDNA), excessive reactive oxygen species (ROS) production, and impaired bioenergetic functions. In the context of endometriosis, these disruptions have profound implications for cellular homeostasis and tissue function.

Mitochondrial Dysfunction in Endometriosis

In endometriosis, altered mitochondrial function contributes significantly to the disease's pathology. The following mechanisms are central to understanding how mitochondrial dysfunction drives the progression of endometriosis:

1. Altered Metabolic Shifts: The Warburg Effect

A hallmark of cancerous and proliferative cells is a shift in cellular metabolism, often referred to as the Warburg effect, in which cells preferentially utilize glycolysis over oxidative phosphorylation for ATP production, even in the presence of oxygen. This metabolic reprogramming is also observed in endometriotic cells, particularly in ectopic lesions, where cells exhibit increased glycolytic activity. In these lesions, endometrial cells rely less on mitochondrial OXPHOS and instead preferentially use glycolysis for ATP production, generating lactate as a byproduct.

This metabolic shift supports enhanced cell proliferation and survival under suboptimal conditions, characteristic of the hyperplastic nature of endometriosis. Glycolysis is less efficient in terms of ATP production compared to OXPHOS, yet it provides the necessary metabolic intermediates for cell division and biosynthesis. Additionally, the accumulation of lactate in the extracellular space lowers the local pH, which can exacerbate tissue inflammation and create a microenvironment conducive to the growth and persistence of ectopic lesions.

2. Mitochondrial DNA Damage and Instability

Mitochondria are highly susceptible to damage due to their proximity to ROS-producing processes in the electron transport chain. ROS, which are byproducts of cellular respiration, can damage mitochondrial lipids, proteins, and most notably, mitochondrial DNA (mtDNA). Unlike nuclear DNA, mtDNA is not protected by histones, making it particularly vulnerable to oxidative damage. In endometriosis, there is compelling evidence that mtDNA is significantly damaged in ectopic endometrial tissue. Studies have shown mtDNA deletions, mutations, and increased levels of mtDNA fragmentation in these tissues, which suggest a breakdown in the integrity of mitochondrial function.

The damaged mtDNA further exacerbates mitochondrial dysfunction, impairing the ability of mitochondria to generate ATP through OXPHOS. This, in turn, results in an increased reliance on anaerobic glycolysis, fueling the Warburg effect. Furthermore, mtDNA mutations can impair mitochondrial protein synthesis, leading to dysfunctional mitochondrial complexes and altered cellular bioenergetics, perpetuating a cycle of cellular dysfunction in endometriotic lesions.

3. Oxidative Stress and Inflammation

One of the critical roles of mitochondria is the regulation of cellular redox balance. Under normal conditions, mitochondria produce ROS as part of the electron transport chain. However, when mitochondrial function is compromised—whether due to damage, oxidative stress, or metabolic reprogramming—excess ROS are produced, leading to a state of oxidative stress. In endometriosis, ectopic endometrial tissue exhibits elevated levels of ROS, contributing to a persistent inflammatory environment.

Oxidative stress in endometriotic lesions is amplified by mitochondrial dysfunction and is further exacerbated by the Warburg effect, which generates additional ROS during glycolysis. ROS directly activate inflammatory pathways, particularly through the nuclear factor-kappa B (NF-κB) signaling pathway, leading to the production of pro-inflammatory cytokines such as IL-6, IL-1β, and TNF-α. These cytokines perpetuate the inflammatory response, recruiting immune cells to the site of ectopic lesions, which leads to pain, fibrosis, and the development of adhesions.

Moreover, ROS play a critical role in sensitizing nociceptors, contributing to the chronic pain experienced by women with endometriosis. The interplay between oxidative stress and inflammation forms a vicious cycle that fuels the progression of endometriosis and promotes the growth and persistence of ectopic lesions.

4. Impaired Mitochondrial Dynamics: Fragmentation and Dysfunction

Mitochondria undergo constant fusion and fission, processes that regulate mitochondrial morphology, quality control, and function. Fusion allows for the mixing of mitochondrial contents, which can help dilute damaged components, while fission helps eliminate dysfunctional mitochondria through mitophagy. In endometriosis, there is evidence of disrupted mitochondrial dynamics, particularly an increase in mitochondrial fragmentation. Fragmented mitochondria are less efficient at ATP production and more prone to accumulating damaged proteins and lipids, which further impairs mitochondrial function.

The imbalance between mitochondrial fusion and fission in endometriosis is linked to altered expression of key proteins such as mitofusins (MFN1/2) and dynamin-related protein 1 (DRP1). DRP1-mediated mitochondrial fission is upregulated in endometriotic lesions, contributing to the generation of fragmented mitochondria. These fragmented organelles are associated with increased oxidative stress, apoptosis resistance, and enhanced cell proliferation—features that contribute to the pathogenesis of endometriosis.

5. Apoptosis Resistance and Cell Survival

Mitochondria play a pivotal role in regulating apoptosis through the release of pro-apoptotic factors, such as cytochrome c, from the mitochondrial intermembrane space. These factors initiate the caspase cascade, leading to cell death. However, in endometriosis, ectopic endometrial cells exhibit resistance to apoptosis, allowing them to survive and proliferate abnormally.

Mitochondrial dysfunction in endometriosis leads to alterations in key apoptotic proteins, including Bcl-2 family members, which regulate mitochondrial outer membrane permeabilization (MOMP). The overexpression of anti-apoptotic proteins, such as Bcl-2 and Bcl-xL, and the downregulation of pro-apoptotic proteins, such as Bax and Bak, result in the persistence of damaged cells. This resistance to apoptosis allows for the survival of endometriotic lesions in hostile environments, contributing to the chronic nature of the disease and complicating treatment strategies.

Therapeutic Implications: Targeting Mitochondrial Dysfunction

Given the central role of mitochondrial dysfunction in endometriosis, therapeutic approaches targeting mitochondrial function hold promise for improving disease management. Several potential strategies include:

Antioxidant Therapies: Reducing oxidative stress through antioxidants such as N-acetylcysteine (NAC), Coenzyme Q10 (CoQ10), and vitamin E could help restore mitochondrial function and reduce inflammation in endometriotic tissues.

Modulation of Mitochondrial Dynamics: Targeting proteins involved in mitochondrial fusion and fission, such as DRP1 and MFN2, may help restore mitochondrial morphology and improve bioenergetic function in endometriotic lesions.

Inhibition of Glycolysis: Given the shift toward glycolysis in endometriotic cells, inhibiting key glycolytic enzymes, such as hexokinase or lactate dehydrogenase, may help reduce lesion growth and metabolic reprogramming.

Mitochondrial Biogenesis Stimulation: Activators of PGC-1α, a central regulator of mitochondrial biogenesis, could promote the generation of healthy mitochondria and improve overall cellular metabolism in endometriotic tissue.

Conclusion

Mitochondrial dysfunction is a key contributor to the pathogenesis of endometriosis. Alterations in mitochondrial metabolism, oxidative stress, mitochondrial DNA damage, and impaired apoptotic regulation are central to the disease's progression. Understanding the molecular mechanisms underlying mitochondrial dysfunction in endometriosis provides novel insights into potential therapeutic strategies. Targeting mitochondrial function and bioenergetics could lead to more effective treatments for endometriosis, alleviating its symptoms and improving outcomes for affected women.

[drmanishkumargupta]

Indications of Liver Biopsy | A liver biopsy is a medical procedure that involves taking a small sample of liver tissue for analysis.

Meet our Expert Contact Us: 📍 Dr. Manish Kumar Gupta 👨⚕ Gastroenterologist, Liver Specialist & Endoscopist ☎ +91-9560720171 Website: https://gastroliver.co.in/ Review Us: https://g.page/r/Ca-LQMsvgGypEB0/review

[pinkribboninc]

Fibrosis After Radiation Treatment: Challenges & Empowerment. Learn how survivors find support from Pink Ribbon Boutique. Click here to continue reading. . . . https://pinkribboninc.com/life-after-fibrosis-after-radiation-treatment/

[drpedi07]

AST to Platelet Ratio Index (APRI) Calculator

The AST to Platelet Ratio Index (APRI) predicts fibrosis and cirrhosis in hepatitis C patients. It offers a non-invasive way to predict which patients have cirrhosis without imaging or biopsy.

[smoov-criminal]

happy disability pride month to those with conditions no one talks about, online or in general:

multiple sclerosis (me lol)

marfans

cerebral palsy

bells palsy

hidradenitis suppurativa

cauda equina syndrome

mixed connective tissue disorder

hyperadrenergic pots

non hypermobile eds types

stickler syndrome

mitochondrial disease

cystic fibrosis

sickle cell disease

myasthenia gravis

post-cholecystectomy syndrome

SWAN (syndromes without a name)

...just to name a few. i see you and you deserve awareness and understanding.

this list is non exhaustive, rb with other conditions you want to see represented!!

[ID: a post banner with dark red background and medium grey bolded text in the center. it reads “This post is about physical disabilities, do not derail.” On each side there is the dynamic disability icon, a gray symbol of person in manual wheelchair leaning forward with arms bent behind them mid-push. /end ID]

[bpod-bpod]

Contact to Contract

Scarring after injury or fibrosis can be fatal as it renders tissue functionally useless. Cells called fibroblasts drive this kind of inappropriate repair, and this study reveals that contact with a kind of macrophage (large cells of the immune system, shown here in red) triggers the fibroblast (in green) – via interaction of two proteins, αvβ3 integrin on the macrophage with Piezo1 on the fibroblast – to contract ultimately leading to stiffened tissue

Read the published research article here

Image from work by Maya Ezzo and colleagues

Laboratory of Tissue Repair and Regeneration, Faculty of Dentistry, University of Toronto, Toronto, Ontario, Canada

Image originally published with a Creative Commons Attribution 4.0 International (CC BY 4.0)

Published in Science Advances, October 2024

You can also follow BPoD on Instagram, Twitter and Facebook

[dangerdust2]

‘Plasticosis’: Characterising macro- and microplastic-associated fibrosis in seabird tissues

Highlights

• Extensive scar tissue formation was associated with plastic exposure in seabirds.

• Plastic significantly altered collagen prevalence within stomach tissue structures.

• Pathology was caused directly by plastic, rather than natural items, such as pumice.

• First record of plastic-related fibrosis in seabird stomach tissues.

• Evidence for a new plastic-induced fibrotic disease, ‘Plasticosis’.

[drmanishkumargupta]

Discover the Advantages and Uses of Fibroscan! 🌟 Learn how this cutting-edge technology revolutionizes liver assessments, offering quick, non-invasive insights into liver health. If You Have any Gastric, Intestinal, or Liver Problems.

Book an appointment for the Test Now! Contact Us: 📍 Dr. Manish Kumar Gupta 👨⚕ Gastroenterologist, Liver Specialist & Endoscopist 🏥 Gastro, Liver & Endoscopy Center, plot no. 100, Shakti khand 2, Indirapuram Ghaziabad ☎ +91-9560720171 Website: https://gastroliver.co.in/ Review Us: https://g.page/r/Ca-LQMsvgGypEB0/review

[jcmarchi]

Adhesive coatings can prevent scarring around medical implants

New Post has been published on https://thedigitalinsider.com/adhesive-coatings-can-prevent-scarring-around-medical-implants/

Adhesive coatings can prevent scarring around medical implants

When medical devices such as pacemakers are implanted in the body, they usually provoke an immune response that leads to buildup of scar tissue around the implant. This scarring, known as fibrosis, can interfere with the devices’ function and may require them to be removed.

In an advance that could prevent that kind of device failure, MIT engineers have found a simple and general way to eliminate fibrosis by coating devices with a hydrogel adhesive. This adhesive binds the devices to tissue and prevents the immune system from attacking it.

“The dream of many research groups and companies is to implant something into the body that over the long term the body will not see, and the device can provide therapeutic or diagnostic functionality. Now we have such an ‘invisibility cloak,’ and this is very general: There’s no need for a drug, no need for a special polymer,” says Xuanhe Zhao, an MIT professor of mechanical engineering and of civil and environmental engineering.

The adhesive that the researchers used in this study is made from cross-linked polymers called hydrogels, and is similar to a surgical tape they previously developed to help seal internal wounds. Other types of hydrogel adhesives can also protect against fibrosis, the researchers found, and they believe this approach could be used for not only pacemakers but also sensors or devices that deliver drugs or therapeutic cells.

Zhao and Hyunwoo Yuk SM ’16, PhD ’21, a former MIT research scientist who is now the chief technology officer at SanaHeal, are the senior authors of the study, which appears today in Nature. MIT postdoc Jingjing Wu is the lead author of the paper.

Preventing fibrosis

In recent years, Zhao’s lab has developed adhesives for a variety of medical applications, including double-sided and single-sided tapes that could be used to heal surgical incisions or internal injuries. These adhesives work by rapidly absorbing water from wet tissues, using polyacrylic acid, an absorbent material used in diapers. Once the water is cleared, chemical groups called NHS esters embedded in the polyacrylic acid form strong bonds with proteins at the tissue surface. This process takes about five seconds.

Several years ago, Zhao and Yuk began exploring whether this kind of adhesive could also help keep medical implants in place and prevent fibrosis from occurring.

To test this idea, Wu coated polyurethane devices with their adhesive and implanted them on the abdominal wall, colon, stomach, lung, or heart of rats. Weeks later, they removed the device and found that there was no visible scar tissue. Additional tests with other animal models showed the same thing: Wherever the adhesive-coated devices were implanted, fibrosis did not occur, for up to three months.

“This work really has identified a very general strategy, not only for one animal model, one organ, or one application,” Wu says. “Across all of these animal models, we have consistent, reproducible results without any observable fibrotic capsule.”

Using bulk RNA sequencing and fluorescent imaging, the researchers analyzed the animals’ immune response and found that when devices with adhesive coatings were first implanted, immune cells such as neutrophils began to infiltrate the area. However, the attacks quickly quenched out before any scar tissue could form.

“For the adhered devices, there is an acute inflammatory response because it is a foreign material,” Yuk says. “However, very quickly that inflammatory response decayed, and then from that point you do not have this fibrosis formation.”

One application for this adhesive could be coatings for epicardial pacemakers — devices that are placed on the heart to help control the heart rate. The wires that contact the heart often become fibrotic, but the MIT team found that when they implanted adhesive-coated wires in rats, they remained functional for at least three months, with no scar tissue formation.

“The formation of fibrotic tissue at the interface between implanted medical devices and the target tissue is a longstanding problem that routinely causes failure of the device. The demonstration that robust adhesion between the device and the tissue obviates fibrotic tissue formation is an important observation that has many potential applications in the medical device space,” says David Mooney, a professor of bioengineering at Harvard University, who was not involved in the study.

Mechanical cues

The researchers also tested a hydrogel adhesive that includes chitosan, a naturally occurring polysaccharide, and found that this adhesive also eliminated fibrosis in animal studies. However, two commercially available tissue adhesives that they tested did not show this antifibrotic effect because the commercially available adhesives eventually detached from the tissue and allowed the immune system to attack.

In another experiment, the researchers coated implants in hydrogel adhesives but then soaked them in a solution that removed the polymers’ adhesive properties, while keeping their overall chemical structure the same. After being implanted in the body, where they were held in place by sutures, fibrotic scarring occurred. This suggests that there is something about the mechanical interaction between the adhesive and the tissue that prevents the immune system from attacking, the researchers say.

“Previous research in immunology has been focused on chemistry and biochemistry, but mechanics and physics may play equivalent roles, and we should pay attention to those mechanical and physical cues in immunological responses,” says Zhao, who now plans to further investigate how those mechanical cues affect the immune system.

Yuk, Zhao, and others have started a company called SanaHeal, which is now working on further developing tissue adhesives for medical applications.

“As a team, we are interested in reporting this to the community and sparking speculation and imagination as to where this can go,” Yuk says. “There are so many scenarios in which people want to interface with foreign or manmade material in the body, like implantable devices, drug depots, or cell depots.”

The research was funded by the National Institutes of Health and the National Science Foundation.

[aistobascistod]

Codified : Cystic Fibrosis :: Modified : Mystic Fibrosis

[gayaest]

[Description in Alt-Text]

Nekoma’s team is coming together! All that’s left is Lev and Inuoka! 🏐❤️🐈

[dandelionsresilience]

Good News - July 8-14

Like these weekly compilations? Tip me at $Kaybarr1735! And if you tip me and give me a way to contact you, at the end of the month I'll send you a link to all of the articles I found but didn't use each week!

1. Zoo welcomes birth of four endangered horse foals

“[The Marwell Zoo in GB] said it was "delighted" to welcome the arrivals to the endangered Przewalski’s horse herd. All four are female and said to be "doing well" after two were born in May and two in June. […] “These horses, that were previously listed extinct in the wild, are an example of how zoo breeding programmes can help restore threatened species around the world.” […] All the Przewalski’s horses alive today are descended from just 12 individuals. Current estimates suggest there are 178 mature individuals living in the wild.”

2. Restoring woodlands and planting trees for sustainability success

“In 2023, [the Marwell Zoo] planted 9,000 new trees […] both within the zoo and on our surrounding land. […] Marwell tries to encourage natural feeding behaviour and nutrition by including leafy material [in animals’ feed] as much as possible. […] Planting more trees and enhancing management of our existing woodlands, prepares the way to further self-sufficiency in browse production in the future. Plus, it creates new habitats for wildlife in our woodland areas.”

3. Inclusive Playgrounds Allow Children Of All Abilities To Play

“With ramps allowing children in wheelchairs to ascend the central play structure, as well as numerous other swings and apparatus usable for children of all abilities, the 16,000-square-foot P.K.’s Place is St. Paul’s first fully inclusive playground. […] To be universally accessible, a play area must have at least 70% of its play features fully accessible, far more than required by the Americans with Disabilities Act (ADA). […] Play areas should allow parents and grandparents with disabilities to participate as well.”

4. Combination treatment can increase human insulin-producing cells in vivo

“[Diabetes-model mice] were treated with the combination therapy [of a plant product called harmine and “a widely used class of type 2 diabetes therapy”] and their diabetes was rapidly reversed. Strikingly, human beta cell numbers increased by 700 percent over three months with this drug combination. "This is the first time scientists have developed a drug treatment that is proven to increase adult human beta cell numbers in vivo. This research brings hope for the use of future regenerative therapies to potentially treat the hundreds of millions of people with diabetes," said Dr. Garcia-Ocaña, the paper's corresponding author.”

5. Decades of Dedication: Australia’s Largest Ongoing Urban Restoration Project

“[Friends of Lake Claremont] has transformed the area into a thriving ecosystem, re-establishing native habitats and fostering biodiversity. This year, 800 native seedlings (100 trees, 350 shrubs and 350 ground covers) have been planted on the northwestern buffer of Lake Claremont. Volunteers replaced a large Port Jackson fig (Ficus rubiginosa) affected by [beetle] infestation with native plants to enhance the local wildlife habitat, thereby benefiting insects, frogs, birds and brown bandicoots. […] Overall, the project contributes to the area’s function as a regional ecological corridor, linking inland bushlands, the Swan River and the Indian Ocean.”

6. Important habitat for fish in Heart of the Fraser now conserved

“British Columbia’s iconic salmon now have more protected spawning habitat in the lower Fraser River, thanks to the Nature Conservancy of Canada’s (NCC’s) conservation acquisition of Carey Island. […] Carey Island and its gravel channels offer calm and crucial spawning and rearing habitat for the river’s fish and aquatic species. […] The Pelólxw Tribe […is also] actively working to restore the resilience of aquatic habitat within this stretch of the Lower Fraser. NCC is exploring opportunities to collaborate with the Pelólxw Tribe in support of their vision for stewardship of the area, which prioritizes both ecological and cultural values.”

7. Prime editing efficiently corrects cystic fibrosis mutation in human lung cells

“[R]esearchers have developed a gene-editing approach that efficiently corrects the most common mutation that causes cystic fibrosis, found in 85 percent of patients. With further development, it could pave the way for treatments that are administered only once and have fewer side effects. The new method precisely and durably corrects the mutation in human lung cells, restoring cell function to levels similar to that of Trikafta [the standard treatment since 2019].”

8. Montana’s High Court Considers a Constitutional Right to a Stable Climate

“At issue was the appeal of a decision last year, when a Montana judge blocked a state law that prohibited agencies from considering climate impacts when deciding whether to approve fossil fuel projects such as new power plants, pipelines or mining. The ruling, by District Judge Kathy Seeley, was prompted by a lawsuit filed by 16 youths who argued that the law violated Montana’s constitutional right to a “clean and healthful environment.” It was the first ruling in the United States to effectively establish constitutional rights to a stable climate[….]”

9. The US is about to get its first solar-covered canal

“The first canal-based solar project in the U.S. is nearing completion on tribal lands south of Phoenix, Arizona. […] The long, narrow solar array design would snake along the line of the canal and tap into the local electrical distribution grid every 1,000 feet, or every one megawatt. […] “Canal solar allows for greater power production per land size, cleaner water, less power transmission losses, and significant reduction in evaporation[….]” Covering the entire 8,000 miles of canals and waterways managed by the Bureau of Reclamation with solar panels could generate over 25 gigawatts of renewable energy and reduce water evaporation by tens of billions of gallons[….]”

10. Camera traps offer glimpse of first beaver born in Northumberland for 400 years

“"It’s such a relief that they have bred successfully and to see a new fluffy kit swimming with the family[….]” In just one year [since releasing the beavers], there has been a noticeable increase in resident trout, says the National Trust, along with more regular visits from kingfishers and grey herons. There are more insects at the site, too, thanks to the organic matter that builds up behind the dams, which in turn provides food for Daubenton’s bats. […] Beavers also play an important role in creating habitats that are more resilient to the effects of climate change[….]”

July 1-7 news here | (all credit for images and written material can be found at the source linked; I don’t claim credit for anything but curating.)