Medical Bulletin 24/November/2025

The research used data from 7,256 UK adults in the Fenland Study, tracking physical activity energy expenditure via wearable heart rate and movement sensors over seven years, alongside dietary patterns measured by Mediterranean diet adherence.

Researchers assessed body fat distribution using DEXA scans and ultrasound to detect fatty liver. Improvements in either diet or physical activity independently correlated with less weight gain, reduced overall, subcutaneous, and visceral fat, and lower fatty liver incidence.

However, simultaneous positive changes in both diet and exercise yielded the greatest reductions—participants improving both behaviors gained nearly 1.9 kg less total fat and 150 g less visceral fat, reflecting significant health benefits.

Interestingly, changes in visceral fat, a dangerous fat surrounding internal organs linked to diabetes and heart disease, were especially responsive to lifestyle improvements, even after adjusting for BMI. This reinforces that fat loss location critically affects metabolic health.

First author Dr. Shayan Aryannezhad emphasized that focusing not only on weight but on fat distribution through both diet and exercise can better prevent chronic diseases and promote healthy ageing. Senior author Professor Nita Forouhi highlighted the importance of policy measures to create environments supporting healthier food and activity choices.

This study underscores the power of small, sustained lifestyle changes targeting both nutrition and physical activity. By adopting a Mediterranean-style diet and engaging in regular movement, individuals can substantially improve their body composition, reduce disease risk, and support longevity, even amid modern challenges promoting unhealthy habits.

REFERENCE: Aryannezhad, S., et al. (2025) Concurrent Changes in Diet Quality and Physical Activity and Association With Adiposity in Adults. JAMA Network Open. DOI: 10.1001/jamanetworkopen.2025.45232. https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2841742

New antibody breakthrough offers hope to slow polycystic kidney disease progression

A new frontier in treating polycystic kidney disease (PKD) has emerged from the labs at the University of California, Santa Barbara. Led by biologist Thomas Weimbs, the team has engineered specialized monoclonal antibodies capable of penetrating kidney cysts—tiny fluid-filled sacs that slowly erode kidney function, often leading to dialysis.

Published in Cell Reports Medicine, this innovative approach aims to function where current therapies fall short: inside the cysts themselves.

PKD cysts grow uncontrollably due to self-stimulating growth signals secreted into their fluid-filled interiors. Traditional immunoglobulin G (IgG) antibodies, successful in cancer therapies, can’t cross the cyst lining to halt this process.

However, the researchers redesigned an antibody to mimic dimeric immunoglobulin A (dIgA), naturally able to traverse epithelial barriers via polymeric immunoglobulin receptors. This allowed the antibody to enter cysts and target the cMET receptor, a key driver of cyst expansion.

The team first confirmed in-vitro that the engineered antibody retained its ability to bind cMET. Testing in mouse PKD models showed the antibody successfully penetrated cysts where it reduced cMET activity, dampening the growth signals. Notably, it triggered a striking increase in apoptosis (cell death) specifically in cyst-lining cells, without harming healthy kidney tissue.

While promising, this work remains preclinical. Challenges lie ahead, including collaboration to generate additional antibody variants and identification of other growth factor receptors to block. The researchers hope to explore combination antibody therapies and refine targets for maximizing disease slowing or reversal.

This breakthrough could open a new chapter in PKD treatment—offering a “magic bullet” to stop cyst growth at its source, delaying kidney failure and improving quality of life. Though clinical application is years away, these findings bring fresh hope to thousands battling this relentless disease.

REFERENCE: Margaret F. Schimmel, Bryan C. Bourgeois, Alison K. Spindt, Sage A. Patel, Tiffany Chin, Gavin E. Cornick, Yuqi Liu, Thomas Weimbs. Development of a cyst-targeted therapy for polycystic kidney disease using an antagonistic dimeric IgA monoclonal antibody against cMET. Cell Reports Medicine, 2025; 6 (9): 102335 DOI: 10.1016/j.xcrm.2025.102335

CRISPR breakthrough disables gene, reverses resistant lung cancer growth

A revolutionary breakthrough in cancer therapy could transform the treatment landscape for resistant lung tumors. Researchers at Christiana Care's Gene Editing Institute have demonstrated that using CRISPR technology to knockout the NRF2 gene restores lung cancer cells’ sensitivity to chemotherapy.

Published in Molecular Therapy Oncology, this study provides hope that overcoming drug resistance—a major barrier in cancer treatment—may soon be within reach.

The research focused on lung squamous cell carcinoma, a fast-progressing type of non-small cell lung cancer that accounts for 20-30% of lung cancer cases. Scientists engineered lung cancer cells carrying a tumor-specific NRF2 mutation called R34G.

Using CRISPR/Cas9, they selectively disrupted the mutated NRF2 gene, leaving healthy cells unaffected. This genetic knockout re-sensitized cancer cells to standard chemotherapy drugs like carboplatin and paclitaxel, slowing tumor growth in lab cultures and animal models.

Remarkably, editing just 20-40% of tumor cells yielded significant therapeutic effects, a promising feature for clinical application where complete gene modification is challenging. Tumors treated with CRISPR showed reduced NRF2 activity and better response to chemotherapy without detected off-target genetic damage.

Lead author Dr. Kelly Banas emphasized that targeting NRF2 through gene editing could augment existing therapies, reducing drug resistance and allowing patients to tolerate treatment longer with improved outcomes. Since NRF2 also mediates chemoresistance in liver, esophageal, and head and neck cancers, this approach may have broad implications.

While these preclinical results are compelling, clinical trials are necessary to confirm safety and effectiveness in humans. If successful, CRISPR-based NRF2 targeting could redefine cancer treatment by restoring the power of conventional chemotherapy and prolonging patient survival.

This study exemplifies how precision gene editing can tackle one of oncology’s toughest challenges—drug resistance—offering new hope to patients facing aggressive tumors.

REFERENCE: Kelly H. Banas, Pawel A. Bialk, Natalia Rivera-Torres, Katelynn Owens, Tori N. Reiner, Kristen M. Pisarcik, Nicole Haas, Emily Gielda, Komal Khan, Krishna Priya Narra, Eric B. Kmiec. Functional characterization of tumor-specific CRISPR-directed gene editing as a combinatorial therapy for the treatment of solid tumors. Molecular Therapy Oncology, 2025; 33 (4): 201079 DOI: 10.1016/j.omton.2025.201079