Radically different
Microplastics have become a defining environmental signature of modern life, turning up in oceans, soil, food, drinking water, and even the air. But their biological fate inside the human body remains far less understood. A new study suggests that these particles may be doing more than simply passing through. Instead, they may be accumulating in one of the body’s most overlooked fluids—bile—and leaving behind measurable cellular damage that could shape future thinking about environmentally driven biliary injury and long‑term health effects. As the authors noted in their abstract, “the long-term accumulation patterns and chronic toxic effects of microplastics within the human biliary system are largely unknown,” underscoring the need for deeper investigation into how these particles behave in the enterohepatic circulation.
Researchers from the Tenth Affiliated Hospital of Southern Medical University (Dongguan People’s Hospital), Sun Yat-sen University, Guilin Medical University, and collaborating institutions reported the findings in Environmental Science and Ecotechnology. Their study, “Microplastics accumulate in human bile and drive cholangiocyte senescence,” provides the first direct evidence that microplastics are not only present in bile but may also contribute to mitochondrial dysfunction and premature aging in cholangiocytes, the epithelial cells that line the bile ducts.
The team collected bile from 14 surgical patients (five without gallstones and nine with gallstones) and used a multimodal analytical approach—pyrolysis–gas chromatography–mass spectrometry, laser direct infrared spectroscopy, and scanning electron microscopy—to characterize the particles. According to the paper, “we show the universal presence of microplastics in human bile,” identifying six polymer types dominated by polyethylene terephthalate and polyethylene, with most particles measuring 20–50 μm. Patients with gallstones carried substantially higher microplastic burdens, raising questions about whether biliary stasis or altered bile composition may influence microplastic retention.
To probe biological effects, the researchers exposed cultured human cholangiocytes to low-dose polystyrene nanoplastics for seven days, simulating chronic exposure. The cells exhibited mitochondrial dysfunction, elevated reactive oxygen species, reduced ATP, Drp1‑mediated mitochondrial fission, and G1 cell‑cycle arrest—hallmarks of senescence. As the authors wrote, chronic exposure “induces mitochondrial dysfunction-associated senescence in cholangiocytes,” suggesting a mechanistic link between environmental microplastics and biliary aging.
One of the most intriguing findings is that melatonin, a widely used antioxidant, partially reversed the mitochondrial and inflammatory damage. While far from a therapeutic recommendation, the result hints at a potential intervention point and gives the study translational relevance.
The work reframes the biliary system as something far more active than a simple transit channel. The data indicate that bile can serve as a reservoir for microplastics and that prolonged exposure may age cholangiocytes by driving mitochondrial dysfunction. The partial rescue with melatonin adds a mechanistic foothold for future intervention, even as the authors caution that broader human studies are essential.
For biotech, the implications are broad. The work highlights bile as a clinically accessible matrix for exposure assessment, opening the door to new diagnostics for environmental toxicology. The mitochondrial stress signature aligns with pathways already being targeted by companies developing senolytics, mitoprotective agents, and anti‑inflammatory therapeutics. The authors wrote that the research provides “a mechanistic foundation for assessing the health risks of plastic pollution and developing therapeutic interventions for environmentally driven biliary disorders.”
The post Microplastics in Human Bile Drive Mitochondrial Dysfunction and Senescence appeared first on GEN – Genetic Engineering and Biotechnology News.
– Rebecca Deusser, MS, MBA and Sanjaya Saxena, MD
“It took me years to find out that what I was dealing with was OCD!”
This is a phrase all too often repeated by people living with obsessive compulsive disorder. Currently, individuals live with OCD for an average of 7 years (Dell’Osso et al, 2019) before they even receive a diagnosis, all while symptoms may intensify and daily life often becomes increasingly constrained.
Clinicians, researchers, and advocates have long raised this concern. What has been missing is clear data behind how many people with OCD in the U.S. are missed in clinical settings or are not receiving the most effective treatment.
When the International OCD Foundation undertook this analysis, the scale of the problem became unmistakable. Millions of people in America are currently struggling with OCD without the most effective treatment.
The challenges we detail in our new white paper, America’s OCD Care Crisis: National Findings on the Failure of Effective OCD Treatment to Reach Patients, are significant, but fixable. They are symptoms of structural oversights that can be changed. Effective, evidence-based treatment for OCD exists, and through intentional action, we can dramatically change these unacceptable outcomes for people with OCD.
Well established prevalence rates for OCD indicate that nearly 10 million people in America — roughly 3% (Ruscio et al, 2010; Stein et al,2025; Ringeisen et al, 2025) — will have OCD at some point in their lives. Yet our findings suggest that 75% of them are never even identified, and up to 95% aren’t receiving the most effective treatment for the disorder.
In our analysis, we discovered significant systemic breakdowns at several key points of a patient’s journey: screening, diagnosis, referral, and treatment.
The breakdowns seen in each step of the care pathway reinforce the focus of IOCDF’s Vision 2030, our five-year strategy to address the systemic barriers that keep effective OCD treatment out of reach.
While the findings are stark, they illuminate many opportunities for change:
Vision 2030 outlines how the IOCDF is committing its resources, partnerships, and expertise toward advancing these priorities — by increasing awareness and community, expanding access to effective treatment, and advancing research. Together, these efforts are designed to work in concert, improving clinical training, implementing screening for early identification, strengthening pathways from diagnosis to care, and increasing the likelihood that people receive evidence-based treatment.
At the same time, the scale of the problem revealed in this report makes clear that progress depends on collective action across the field. Clinicians, health systems, educators, researchers, policymakers, advocates, and people with lived experience all have a role to play. Together, these efforts can help ensure that people with OCD reach effective treatment sooner, reducing years of unnecessary confusion and distress.
Join us in building better access to effective treatment for people with OCD:
The current state of treatment for OCD in the U.S. is sobering, but it is not the end of the story. OCD is treatable, recovery is possible, and change can happen as awareness grows and access expands. With continued effort, the gap between how many are struggling and how many receive effective care can begin to close. A brighter future is possible — and we can build it together.
References
When clinicians have easier access to best practices in OCD diagnosis and treatment, more people can receive effective care. The IOCDF’s Training Institute offers evidence-based programs for clinicians at every stage of practice, including:
The post The Most Effective OCD Treatment Reaches Almost No One: Here’s What We Can Do About It appeared first on International OCD Foundation.
Background: Periodontitis is a chronic gum disease affecting approximately 42% of adults aged 30 years and older in the United States. Training dental students to accurately diagnose and manage periodontitis is a critical component of dental education and clinical care. Recent advances in large language models offer new opportunities to support both domains, yet their performance in periodontal diagnosis remains largely unexplored, particularly for newer models such as GPT-5. Objective: This study conducted an exploratory evaluation of GPT-5’s ability to stage and grade periodontitis. Methods: A total of 25 publicly available clinical cases explicitly reporting periodontitis stage and grade were identified through Google and PubMed searches. Each case description was entered into GPT-5 using a zero-shot prompting approach to assess guideline-based reasoning without exemplar conditioning. The model’s predictions were compared with the published reference diagnoses. Performance was measured using accuracy, 95% CI, unweighted Cohen κ, and weighted Cohen κ. Results: Across these cases, GPT-5 showed marked class-dependent performance and a tendency to overestimate disease severity. Grading performance was notably imbalanced, with high recall for grade C but substantially lower discrimination for grade B. GPT-5 achieved a staging accuracy of 68% (95% CI 48.4%-82.8%) and a grading accuracy of 77.3% (95% CI 56.6%-89.9%), with corresponding Cohen κ values of 0.454 (95% CI 11.0%-75.6%) and 0.179 (95% CI −15.8% to 63.8%), respectively. While staging performance showed fair agreement beyond chance, the low κ for grading indicates poor agreement and limited reliability in distinguishing periodontal disease severity. Conclusions: These findings suggest that although GPT-5 demonstrates potential for guideline-based periodontitis staging and grading, its current diagnostic performance, particularly for periodontitis grading, limits its use in clinical assessment and educational training. Meaningful application in periodontal diagnosis and training will require substantial improvements in reliability and rigorous validation in larger, more diverse, and prospectively collected datasets.
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Large language models are rapidly becoming embedded in everyday life through artificial intelligence (AI) chatbots that people use for practical assistance and companionship, as well as for support with mental health and emotional wellbeing. Alongside clear benefits, clinicians and public reports increasingly describe a minority of users whose interactions seem to drift over days or weeks toward strongly questionable convictions, delusions or suicidal crises. Importantly, clinically meaningful deterioration can occur even without overtly unsafe text outputs, via more insidious processes such as compulsive use and sleep disruption, as well as withdrawal from human contact and progressive narrowing of attention around the chatbot relationship. In this Viewpoint, we argue that risk often arises not at a single tipping point but through trajectory effects that accumulate across extended dialogue, and that prevailing safety evaluation approaches are misaligned with this reality because they primarily score risk at discrete conversational endpoints often reached through scripted dialogues lasting just a single turn or several turns. Mental health benchmarks and safety suites (including clinician-informed efforts) have advanced the field by testing refusal behaviour, toxicity, and adversarial prompting, but they often treat the last message as the unit of analysis and therefore miss when risk-relevant relational cues, signs of validation, contradiction handling, and shifts in certainty first emerge and how they compound. We propose that mental health safety assessment should shift from endpoints to trajectories by 1) treating the whole dialogue, not just the end result, as the focus of evaluation; 2) reporting turn-by-turn dynamics such as delusion confirmation and harm enablement, as well as timing and persistence of safety interventions; and 3) calibrating short multi-turn tests against longer, clinically realistic interaction sequences that can reveal context-length effects and drift. We further argue that transcript-only evaluation is insufficient in mental health contexts. Similar language can reflect very different internal states, and the relationship between expressed psychopathology and real-world harm is non-linear. Safety research should therefore incorporate proximal human outcomes after interactions (e.g., shifts in certainty, openness to counterevidence, arousal, urge to continue, and subsequent sleep or behaviour) and build prospective clinical surveillance infrastructure that supports consented transcript donation and linkage to health outcomes. Together, these steps would enable benchmarks that are clinically relevant and better aligned with the kinds of harms now being observed in real-world chatbot use.
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Although immunoglobulin G (IgG) normally protects the body against pathogens, it can become problematic in many autoimmune diseases like lupus, rheumatoid arthritis, Graves’ disease, myasthenia gravis, and Sjögren’s disease.
“In these conditions, the immune system is creating defective IgGs—called autoantibodies—that are no longer fighting infections,” explained Eric Venker, MD, PharmD, CEO of Immunovant. “Instead, they are attacking a part of your normal functioning body and causing dysfunction.”
Historically, autoimmune conditions have been challenging to treat because therapies like steroids rely on broad immune suppression, noted Leonard L. Dragone, MD, PhD, disease area leader of autoantibody and rheumatology at Johnson & Johnson Innovative Medicine. These non-specific approaches are often inconsistently effective and lead to adverse side effects.
“For many autoimmune diseases, there is a need for more targeted strategies that address disease-causing autoantibodies directly, rather than broadly suppressing the immune system,” emphasized Dragone. Beginning in 1998, the U.S. Food and Drug Administration (FDA) approved infliximab, a tumor necrosis factor (TNF)-α inhibitor, for the treatment of Crohn’s disease. This marked the first approval of a monoclonal antibody for the treatment of a chronic condition. Since then, targeted therapies for autoimmune diseases have expanded to address cytokine signaling pathways (TNF-α, IL-6, IL-17, IL-23), Janus kinase (JAK–STAT) signaling, and immune cell surface markers (CD20).
Another such targeted strategy involves an emerging drug class called FcRn blockers, which are now showing considerable promise in the treatment of certain autoimmune diseases.
FcRn blockers, which typically consist of monoclonal antibodies or antibody fragments, work by blocking the function of a protein receptor called FcRn (neonatal Fc receptor). This prevents IgG recycling, thereby reducing IgG levels in the body.
Venker compares FcRn inhibitors to cholesterol-lowering drugs such as statins. “LDL is the disease-causing agent that healthcare providers target to prevent many cardiovascular diseases. Likewise, in the case of FcRn blockade, we are aiming to lower IgG. We believe that deeper IgG reduction may provide improved results.”
As of early 2026, the FDA has approved three FcRn inhibitors for the treatment of myasthenia gravis, a chronic autoimmune disorder affecting up to 100,000 people in the U.S. Efgartigimod (approved in 2021), rozanolixizumab-noli (approved in 2023), and nipocalimab-aahu (approved in 2025) all work by reducing pathogenic IgGs associated with the disease.
“With FcRn blockers, it is exciting to know that there is now a targeted mechanism for patients around the world with autoimmune diseases caused by an IgG autoantibody,” said Venker.
In Graves’ disease, an IgG autoantibody called thyrotropin receptor antibody (TRAb), which targets the thyroid-stimulating hormone (TSH) receptor of the thyroid, is produced. The condition, which is the most common cause of hyperthyroidism, causes elevated heart rate, shakiness, irritability, muscle weakness, and weight loss.
“TRAb is an IgG antibody, but it is a badly behaving one that is basically hijacking the thyroid system,” noted Venker. “It doesn’t serve any purpose that is normal at all.”
Unfortunately, the toolkit for treating Graves’ disease hasn’t changed much since 1950, when the FDA approved the drug methimazole, said Mark A. Lupo, MD, founder and medical director of the Thyroid & Endocrine Center of Florida.
Methimazole is an anti-thyroid drug that slows down the production of thyroid hormones. Although Graves’ patients benefit from anti-thyroid drugs, Lupo estimates a 50% relapse rate within two years of discontinuing these drugs.
Other options for treating Graves’ disease include surgical removal of the thyroid or the use of radioactive iodine to induce destruction of the thyroid gland. However, these approaches result in permanent hypothyroidism, and patients typically require lifelong thyroid hormone replacement after treatment.
Because TRAb is an IgG, FcRn drugs represent a potential autoimmune solution for Graves’ disease. Like all FcRn blockers, they may work by decreasing TRAb recycling and lowering TRAb levels.
Lupo highlights Immunovant’s recent proof-of-concept study of an FcRn inhibitor for Graves’ disease, the first such study for the condition. “Despite the small number of patients (around 25), the results from this study suggest a potential, durable remission six months off treatment,” said Lupo.
While study participants experienced an increase in total IgG levels following treatment, TRAb levels remained low over a six-month period. The thyroid also decreased in size. “To see TRAb levels down six months off the study drug caught the attention of the endocrine thyroid community,” noted Lupo.
“What was unexpected was that TRAb, the disease-causing antibody, stayed down for many months after stopping the investigational therapy,” added Venker.
“I think we are overdue for a new option in Graves’ disease that could help break some of these methimazole cycles and potentially address not the innocent thyroid gland but the underlying immune system issues,” concluded Lupo.
Venker recalls that safety was an initial concern with FcRn inhibition. After all, these drugs work by reducing IgG, an essential part of the immune system. “Any time you are using an autoimmune drug that potentially suppresses your immune system, you have to think about going too far. Am I going to cause an infection or weaken the immune system?
“So far, this investigational drug has demonstrated a safety profile we expected, and appears positive,” noted Venker. “That makes sense mostly because FcRn blockade is pretty targeted.”
“Although there are no head-to-head comparative safety trials yet, most clinicians and principal investigators view FcRn blockers as relatively safe,” added Lupo. “There are FcRn blockers on the market, and they have demonstrated a good safety record in patients.” The most common side effect tends to involve injection site reactions with either intravenous or subcutaneous delivery.
During pregnancy, maternal antibodies—called alloantibodies—can cross the placenta and attack the organs and tissues of the fetus, explained Dragone.
A distinguishing feature of Johnson & Johnson’s nipocalimab is its pH-independent binding to FcRn. This allows it to bind with high affinity in the placenta, a low-pH environment.
The drug is currently showing potential in the treatment of two alloimmune diseases of pregnancy: hemolytic disease of the fetus and newborn (HDFN) and fetal and neonatal alloimmune thrombocytopenia (FNAIT), said Dragone. These conditions can arise during alloimmunized pregnancies, when the pregnant person’s immune system forms alloantibodies against fetal red blood cells (HDFN) and/or fetal platelets (FNAIT). Importantly, published data on nipocalimab suggest minimal transfer of the drug to the fetus or infant. “Therapies like nipocalimab offer a blueprint for how precision medicine can expand to include pregnant people, a population that has historically been excluded from drug development,” noted Dragone. “Our approach with nipocalimab has the potential to change how we think about treating autoantibody-driven diseases in people of childbearing age.”
The FDA has granted a fast track designation to nipocalimab for both FNAIT and HDFN, and Phase III studies are underway to further investigate the drug in both diseases.
“There are probably 20 trials out there for FcRn blockers, and many are likely to work,” noted Venker. “There are a ton of potential new indications under investigation, including rare diseases that have been ignored historically.”
He notes that Immunovant’s pipeline alone includes potential indications in endocrinology (Graves’ disease), rheumatology (rheumatoid arthritis, Sjögren’s disease, and cutaneous lupus erythematosus), and neurology (myasthenia gravis and chronic inflammatory demyelinating polyneuropathy).
Venker stresses that no FDA-approved solutions exist for Sjögren’s disease, which affects as many as four million Americans. The condition causes severe dry eyes and mouth, fatigue, and joint and muscle pain. Immunovant and Johnson & Johnson are conducting clinical trials to evaluate FcRn blockers for the disease.
Meanwhile, argenx’s FcRn inhibitor efgartigimod has been used in 19,000 people worldwide for myasthenia gravis and other autoimmune conditions, said Hani Houshyar, PhD, FcRn asset strategy lead for argenx.
“However, we believe myasthenia gravis is just the beginning,” she said. As of 2026, the company has active clinical trials to test the drug’s effectiveness in additional autoimmune diseases with high unmet medical need, like myositis, Sjögren’s disease, ocular myasthenia gravis, systemic sclerosis, Graves’ disease, and autoimmune encephalitis.
UCB’s rozanolixizumab was the first FcRn blocker to be approved for the treatment of generalized myasthenia gravis in adults who are positive for anti-AChR or anti-MuSK antibodies, who together account for approximately 90% of cases, said Omar Sinno, MD, UCB’s U.S. medical strategy lead of rare disease. So far, the drug has been approved in the U.S., Canada, the EU, Australia, Switzerland, China, Turkey, and Korea.
Rozanolixizumab is administered via a convenient subcutaneous infusion rather than intravenously. The company’s long-term studies demonstrate robust IgG reductions (up to 75%) with sustained benefit across multiple treatment cycles. UCB is also investigating rozanolixizumab as a potential treatment for a rare autoimmune condition called myelin oligodendrocyte glycoprotein antibody-associated disease.
Finally, Johnson & Johnson’s nipocalimab is in mid-to-late-stage studies for Sjögren’s disease, lupus, warm autoimmune hemolytic anemia, and chronic inflammatory demyelinating polyneuropathy.
Viridian Therapeutics is currently investigating two FcRn inhibitors, VRDN-006 and VRDN-008, said Steve Mahoney, president and CEO. Both candidates are designed as subcutaneous products that can be conveniently self-administered by the patient.
VRDN-006 is an Fc fragment in Phase I trials, while VRDN-008 is made up of an Fc fragment and an albumin-binding domain designed to prolong IgG suppression. Mahoney notes that VRDN-008 showed a longer half-life and more sustained IgG reduction than efgartigimod in a high-dose, head-to-head study in non-human primates.
Clinical trial results of VRDN-008 in healthy volunteers are expected later in 2026. “What we believe differentiates VRDN-008 from other FcRn inhibitors is a longer half-life, which has the potential to support less frequent dosing for patients to enhance convenience,” said Mahoney.
Although three FcRn blockers are currently FDA-approved to treat myasthenia gravis in the U.S., Venker notes that Immunovant is continuing to investigate the condition with the company’s follow-on FcRn candidate, imeroprubart (IMVT-1402).
In Immunovant’s proof-of-concept study for Graves’ disease, TRAb stayed low even six months after the investigational treatment was discontinued. But how long will this effect last? “We don’t know that yet because our randomized trials with IMVT-1402 are ongoing,” Venker said. “However, Graves’ disease has given us the first hint that FcRn drugs may be able to put certain autoimmune conditions into permanent remission.”
“A key question for autoimmune disease, the holy grail, so to speak, is whether we can reset the immune system so the person can function normally without medication for the rest of their lives,” he added.
Finally, argenx is developing ARGX-213, a next-generation FcRn inhibitor engineered to extend half-life and sustain IgG reduction.
“Looking ahead, FcRn inhibition represents an increasingly important approach across IgG-driven disease,” noted Sinno. “By selectively reducing pathogenic IgG, these agents enable more targeted autoimmune care. And as clinical experience with FcRn inhibition grows, treatment paradigms may shift toward earlier intervention.”
Tiffany Yesavage, PhD is a freelance writer from Denver, Colorado.
The post FcRn Inhibition in Autoimmune Disease appeared first on Inside Precision Medicine.
Companies that sell Medicare Advantage plans will receive a 2.5% pay bump on average in 2027, up significantly from what was proposed and a win for an industry that has experienced higher medical costs and has opposed nearly all reforms to the lucrative taxpayer-financed program.
More importantly, the Trump administration scrapped a proposal that would have used more updated data in the payment process, ensuring that Medicare Advantage insurers retain billions of dollars.
The finalized rate is estimated to add $13 billion in revenue next year for insurers, according to the Centers for Medicare and Medicaid Services. During trading after the markets closed, the stock prices of UnitedHealth Group, Humana, and CVS Health each climbed by more than 8%. Those companies are the three largest Medicare Advantage insurers, and together cover almost 60% of all people enrolled in the program.
Rodolphe Barrangou, PhD, is the T. R. Klaenhammer Distinguished Professor at North Carolina State University, where he leads the CRISPR Lab. Rodolphe spent nine years at Danisco and DuPont, where he made seminal contributions in the functional characterization of CRISPR as a microbial immune system. He has been at NC State since 2013.
For his CRISPR work, Rodolphe has received several international awards, notably the Canada Gairdner International Award, and has been elected to the National Academy of Sciences, the National Academy of Engineering, and the National Academy of Inventors. Rodolphe is a scientific co-founder of Intellia Therapeutics, Locus Biosciences, TreeCo, Ancilia Biosciences, and CRISPR Biotechnologies, and an advisor to Inari and the IGI. He is also the founding Editor in Chief of The CRISPR Journal (published by Mary Ann Liebert, Inc., a Sage partner), which launched in 2018.
Rodolphe holds a degree from Paris Descartes University and a PhD in functional genomics from NC State.
It has been almost 25 years since the acronym “CRISPR” was first coined. Since then, CRISPR has become a household word, a star of books and films, and a Nobel Prize–winning discovery. This powerful and disruptive genome editing technology has transformed countless fields, including gene therapy, xenotransplantation, de-extinction and agbiotech. Researchers continue to build on the CRISPR chassis, devising new platforms for bespoke genome editing. But major questions remain around clinical safety, commercial development, ethical deployment, and regulatory oversight.
In the first of a new series of GEN Keynote Webinars, Professor Rodolphe Barrangou, PhD (North Carolina State; EIC, The CRISPR Journal) offers a front-row perspective of the CRISPR revolution, the seminal advances, clinical highlights, and rising applications. Almost two decades ago, Barrangou provided the first experimental demonstration of the functional role of CRISPR. With numerous advisory and entrepreneurial activities in the gene editing space, Barrangou is the ideal guide to discuss CRISPR’s progress in the clinic; the state of the CRISPR toolbox; and the regulatory roadblocks and ethical challenges that will shape the application of CRISPR in agbiotech, germline editing, and other arenas.
Registration for this GEN Keynote Webinar is free. Following this live presentation, Dr. Barrangou will answer audience questions.
Produced with support from:
The post CRISPR at 25: The Past, Present, and Future of Genome Editing appeared first on GEN – Genetic Engineering and Biotechnology News.
For the second time in two years, a bill is moving through the Colorado legislature that would exempt orphan drugs, which are used to treat rare diseases, from pricing caps that might be pursued by the state’s Prescription Drug Affordability Board — a panel whose work is being closely watched elsewhere in the country.
The effort reflects concerns that patients may lose access to these drugs if pharmaceutical companies halt sales of such treatments in the state. But opponents argue exemptions would unnecessarily extend to numerous big-selling medicines for common conditions that — thanks to regulatory endorsements — also happen to have an orphan designation.
As a result, consumer advocates complain the maneuver would only increase the risk that countless patients could have trouble paying for a wide variety of medicines. They further argue that the legislation would preserve profits for drug companies at the expense of the state government — and its taxpayers — as it tries to cope with budgetary strains.