#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.

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[bpod-bpod]

Keep it Together

Picture a perky provincial postman enthusiastically delivering parcels from the edge of town into the centre, not realising that these are unwanted deliveries, amassing in an unhelpful mess. Such is the situation with immune cells from alveoli – the tiny air sacs at the edges of our lungs. Researchers knew they were involved in some way in the development of lung fibrosis, a chronic condition where lung tissue becomes scarred and thickened with excessive connective tissue. So in mice they tracked the disassembly and transport of this material (green), shepherded by the immune cells (red) from the junction between the pleura (a membrane surrounding the lungs) and alveoli towards the deep lungs, where it activated fibroblasts (pink) which prompt fibrosis development. Preventing the disassembly of material where the pleura and alveoli meet reversed fibrosis and regenerated chronically fibrotic lungs, revealing that targeting the pleura could be a new avenue for treatment.

Written by Anthony Lewis

Video from work by Adrian Fischer, Wei Han, Shaoping Hu, Martin Mück-Häusl and Juliane Wannemacher, and colleagues

Institute of Regenerative Biology and Medicine(IRBM), Helmholtz Zentrum München, Munich, Germany

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

Published in Nature Communications, January 2025

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[drmanishkumargupta]

Hepatitis-B is viral infection that affects the liver, transmitted through blood or bodily fluids, which can cause liver inflammation and damage if left untreated.

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

[thelovebudllc]

Health organizations collaborate to address idiopathic pulmonary fibrosis on Rare Disease Day 2025

The American College of Chest Physicians (CHEST), the PF Warriors, the Rare Disease Diversity Coalition (RDDC)-a program at the Black Woman’s Health Imperative-and the National Association of Community Health Workers (NACHW) announce their collaboration to address idiopathic pulmonary fibrosis (IPF) as a chronic disease on Rare Disease Day 2025. Together, the organizations will employ designated…

[biology-geology-beaches-india]

The Science Research Diaries of S. Sunkavally, p 462.

[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.

[eurofinsadvinus]

Tackle Idiopathic Pulmonary Fibrosis with Eurofins Advinus' disease specific preclinical models. Let's work together to advance research in IPF. Connect with us to learn more about our initiatives and explore potential collaborations. 📧 bd@advinus.eurofinsasia.com

[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/

[drmanishkumargupta]

GastroFacts: Gastroenterology focuses on digestive system health. Gastroenterologists diagnose and treat issues like reflux and liver diseases. A balanced diet and regular check-ups are essential for maintaining optimal digestive well-being.

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

[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.

[biology-geology-beaches-india]

The Science Research Diaries of S. Sunkavally, p425.

[chiwosays]

shoutout to other disabled people with constant and debilitating pain, people whose pain can't fade into the background or be ignored throughout the day.

[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’.

[gayaest]

[Description in Alt-Text]

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