Medical Bulletin 21/January/2026

Globally, breast cancer strikes 2.3 million women yearly; adult recreational activity slashes odds by ~20%. Yet adolescence—a "window of susceptibility" with explosive mammary growth—remains underexplored for how exercise shapes density-linked biomarkers.

Non-invasive optical spectroscopy beamed red/near-infrared light into breasts, quantifying water/collagen (tied to high mammographic density and risk) versus lipids (protective). Participants self-reported prior-week recreational physical activity (RPA): "organized" like team sports or dance classes, versus "unorganized" such as biking or playground time. Urine tested oxidative stress via 15-F2t-isoprostane (lipid peroxidation marker); blood checked inflammation with high-sensitivity CRP, IL-6, and TNF-α.

Alarming baseline: 51% reported zero RPA; 73% avoided organized sports entirely. Breakthrough for the active minority—girls logging more than or just 2 hours organized RPA had significantly lower breast water content, persisting after body fat adjustment. This echoes lower adult density, a proven risk factor. They also showed reduced systemic oxidative stress. Notably, higher stress levels predicted elevated breast collagen, suggesting oxidative damage drives fibroglandular changes. No associations emerged for inflammation markers, lipid content, collagen directly, or unorganized activity.

Organized RPA's edge likely stems from structured intensity over casual play, though self-reports risk recall bias. These patterns held independent of adiposity, spotlighting biology beyond weight.

Inactivity prevalence demands public health pushes for equitable sports access. While causation awaits longitudinal confirmation, early organized exercise emerges as a promising, modifiable ally against breast cancer's roots.

REFRENCE: Kehm, R. D., et al. (2026). Recreational physical activity and biomarkers of breast cancer risk in a cohort of adolescent girls. Breast Cancer Research. DOI: 10.1186/s13058-025-02216-1, https://link.springer.com/article/10.1186/s13058-025-02216-1

New Study Uncovers Ketogenic Diet's Protection Mechanism Against Epilepsy Seizures

Keto diet's seizure-stopping secret finally cracked—University of Virginia researchers pinpoint a key brain receptor that unlocks its power, paving way for pill-based benefits without ditching carbs.

Published in Annals of Neurology, a team led by epileptologist Jaideep Kapur, co-director of UVA's Brain Institute, unraveled how the high-fat, low-carb ketogenic (keto) diet tames epilepsy—a use dating back to the 1920s for drug-resistant cases. Keto shifts the body from carbs to fat-burning, producing ketones like β-hydroxybutyrate (BHB) that fuel the brain. Beyond epilepsy, it shows promise against Alzheimer's, Parkinson's, and even autism by calming overexcitable neurons, but doctors needed the "how" to mimic it with easier treatments.

Researchers tested BHB's effects in lab mice prone to seizures, mapping its action via the hydroxycarboxylic acid receptor 2 (HCAR2) in the hippocampus—seizure hotspot. They found HCAR2 dense on excitatory neurons (seizure triggers) and microglia (brain's immune guards). Using genetic knockouts, electrophysiology, and imaging, they showed BHB binds HCAR2 to dial down neuron hyperactivity, curb glutamate release, and boost inhibition—slashing seizure severity without toxicity.

In knockout mice lacking HCAR2, BHB lost its anti-seizure punch, confirming the receptor's starring role. HCAR2 also tempered microglia overdrive, hinting at inflammation control relevant to neurodegeneration. Early tests flagged niacin (vitamin B3, an FDA-approved cholesterol drug) as a HCAR2 activator mimicking keto effects in mice, sidestepping diet side effects like gut woes or fat overload.

Kapur notes: "Many can't stomach keto's restrictions—this unlocks drugs delivering the same brain calm." Ongoing work probes HCAR2's microglia modulation for epilepsy, MS, and dementia therapies.

Backed by NIH grants, this breakthrough—free of conflicts—fuels UVA's Manning Biotechnology Institute push to fast-track brain cures. No more carb deprivation needed; targeted pills could soon protect brains universally.

REFERENCE: Naderi, S., et al. (2025). Hydroxycarboxylic Acid Receptor 2 Mediates β‐hydroxybutyrate’s Antiseizure Effect in Mice. Annals of Neurology. DOI: 10.1002/ana.78098. https://onlinelibrary.wiley.com/doi/10.1002/ana.78098

Research Reveals Vitamin A's Role in Cancer Immune Evasion

Vitamin A and cancer link? Is there any? —Princeton researchers unmask how tumors hijack this essential nutrient to sabotage immune attacks, and unveil the first drugs to slam the brakes.

In breakthrough papers from Nature Immunology and iScience, Ludwig Princeton researchers Yibin Kang and Mark Esposito reveal how all-trans retinoic acid (ATRA)—a vitamin A offshoot—lets tumors dodge destruction. Think of ATRA as a double agent: essential for vision and immunity in the gut, but hijacked by cancers via enzymes ALDH1a3 (in tumor cells) and ALDH1a2 (in dendritic cells, DCs). This creates "immune tolerance," where the body's defenders stand down, weakening natural attacks and even cancer vaccines.

Dendritic cells act like immune alarm systems—they snag tumor pieces, show them to T cells, and spark killer squads. But during vaccine prep, DCs crank out ATRA via ALDH1a2, halting their own growth, birthing weak macrophages, and recruiting regulator T cells that hush the fight. Tumors pump extra ATRA too, ignoring its cell-slowing effects while muting nearby T cells in the tumor zone.

The teams cracked this using mouse melanoma models, human cancer cell lines, and gene edits. They mapped ATRA receptors, confirmed enzyme must-haves with knockouts, and simulated vaccine conditions. Game-changer: computer modeling plus huge drug screens built KyA33—the first safe blocker of ALDH1a2/3 after 100 years of dead ends.

In mice, KyA33 revived DC maturity, supercharged vaccines to delay tumors, and solo shrank growths by unleashing T cells. It solved vitamin A’s paradox: lab tests show ATRA kills cancer cells, but high intake in people boosts cancer/death risk—tumors just tune it out, using excess to sabotage immunity instead.

Kang explains: "ATRA mutes key cancer defenses—we’ve got blockers proving preclinical power." New firm Kayothera targets trials for cancer, diabetes, heart issues. Funded by Ludwig, Komen, this unlocks immunotherapy 2.0.

REFERENCE:

1.Cao Fang, Mark Esposito, Ulrike Hars, Robert T. Byrne, Bokai Song, Jian Huang, Asael Roichman, Lawrence Shue, Xiaobing Cheng, John Proudfoot, Demin Zhao, Yong Wei, Ileana M. Cristea, Joshua D. Rabinowitz, Yibin Kang. Targeting autocrine retinoic acid signaling by ALDH1A2 inhibition enhances antitumor dendritic cell vaccine efficacy. Nature Immunology, 2026; DOI: 10.1038/s41590-025-02376-4

2.Mark Esposito, Cao Fang, Yong Wei, Alfonso Pozzan, Claudia Beato, Xiaoyang Su, Josiah E. Hutton, Tavis Reed, Xiang Hang, Enrico D. Perini, Wen Wang, Xiaobing Cheng, Yan Pan, Jianshi Yu, Maureen Kane, Malini Manoharan, John Proudfoot, Ileana M. Cristea, Yibin Kang. Development of retinoid nuclear receptor pathway antagonists through targeting aldehyde dehydrogenase 1A3. iScience, 2025; 28 (11): 113675 DOI: 10.1016/j.isci.2025.113675