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Researchers Discover a Blood-Pressure Drug May Stimulate “Healthy” Brown Fat
Losartan, a drug commonly prescribed for high blood pressure, boosts brown adipose tissue or “brown fat” activity and enhances its metabolism, according to a preclinical study by Weill Cornell Medicine, Rockefeller University and Memorial Sloan Kettering Cancer Center researchers.
Making pediatric cancer more ‘visible’ boosts immunotherapy response
A new preclinical study reveals that blocking a protein makes neuroblastoma cells easier to detect and more vulnerable to treatment.
U.S. Department of Health and Human Services (HHS) Recommends Science-Based Thresholds to Target Dangerous Enhanced Kratom Products
Kratom products credit: CDPH DEA takes action based on updated recommendation from HHS October 11, 2026 - WASHINGTON - On Friday, the U.S. Department of Health and Human Services relesed the following: The U.S. Department of Health and Human Services (HHS) provided a new recommendation to the Drug Enforcement Administration (DEA) that establishes science-based thresholds for 7-hydroxymitragynine (7-OH) and mitragynine pseudoindoxyl (MGPI), potent opioid compounds associated with products marketed as kratom. The Department of Justice today announced that DEA issued new Notices of Intent reflecting HHS’ updated scientific analysis and recommendations, including a new Notice of Intent for 7-OH and MGPI incorporating HHS’ recommended concentration and ratio thresholds. Following a review of available scientific data and comments, HHS Assistant Secretary for Health Admiral Brian Christine, M.D., recommended that DEA use concentration or ratio-based thresholds to determine which products containing 7-OH and MGPI are subject to Schedule I control for purposes of temporary scheduling of these substances under the Controlled Substances Act. The recommendation is designed to target concentrated or chemically altered products while distinguishing them from natural botanical kratom products, which may contain trace amounts of 7-OH and MGPI. “We are drawing a clear line between natural kratom and dangerous, enhanced opioid products,” said HHS Secretary Robert F. Kennedy, Jr. “We listened to the public, followed the science, and developed a clear recommended threshold for temporary scheduling that targets concentrated 7-OH and MGPI without sweeping natural botanical kratom into Schedule I. The Trump Administration will continue taking decisive action against dangerous products that fuel addiction while making sure our policies are grounded in rigorous science.” Under the recommendation, 7-OH and MGPI would be controlled in Schedule I for purposes of temporary scheduling when either substance alone, or their combined amount when both are present: Exceeds 1 milligram per gram in solid powders, encapsulated material, or other solid forms, or exceeds 1 milligram per milliliter in liquid preparations; or When the mass of mitragynine present divided by the mass of 7-OH, or MGPI, or the combined amount of 7-OH and MGPI if both present, is less than 100. The ratio-based approach reflects the alkaloid composition of natural kratom products and provides a way to identify products intentionally enhanced or concentrated with 7-OH or MGPI. Available scientific data indicate that 7-OH occurs naturally in botanical kratom at relatively low or trace levels, while some evidence reviewed by FDA suggests MGPI may also occur at trace levels in some natural or kratom-derived products. FDA's scientific review found that 7-OH is substantially more potent than morphine in preclinical studies, with available data indicating approximately two to nine times greater potency depending on the study. FDA also identified evidence supporting a meaningful risk of opioid-like physical dependence and withdrawal from MGPI. “Our recommendation gives DEA a scientifically supportable framework to distinguish natural botanical kratom from products that have been concentrated or manipulated to deliver dangerous levels of potent opioid compounds,” said Assistant Secretary for Health Admiral Brian Christine, M.D. “This approach allows us to focus on the products that pose the greatest threat to public health.” In July 2025, following an FDA scientific and medical evaluation, HHS recommended that 7-OH above a specified threshold be placed in Schedule I of the Controlled Substances Act. In July 2026, DEA announced its intent to temporarily schedule 7-OH above a specified threshold, and HHS simultaneously sought public comment on the proposed threshold. DEA subsequently temporarily placed MGPI and two synthetic 7-OH derivatives, MGM-15 and MGM-16, in Schedule I. Since then, questions have emerged about how scheduling could affect natural botanical kratom products potentially containing trace amounts of MGPI. The new HHS recommendation responds to those concerns by providing DEA with a more precise threshold based on both the concentration of 7-OH and MGPI and their relationship to mitragynine, the predominant alkaloid in kratom. HHS and FDA will continue working with DEA to protect Americans from dangerous concentrated and synthetic opioid products while ensuring federal policy is grounded in the best available science. Source: HHS
FDA-approved epilepsy drug may help reverse osteoarthritis damage
Researchers at Yale have identified a promising new approach to osteoarthritis that could do more than simply ease pain. The epilepsy drug lacosamide appears to block a protein involved in both pain signaling and cartilage destruction, helping damaged joints shift back toward repair in preclinical studies.
Why do we get sleepy? Uncovering the science of sleep drive
Why do we get sleepy? A new preclinical study sheds some light on the science of sleep drive.
SL Science: A $1.15 Billion Valuation Built On Preclinical Promises
SL Science Holding Limited is rated Sell due to an unsustainable $1.15B valuation built on a strictly preclinical pipeline. Click for this SLBT stock update.
Posts touting mebendazole as cancer treatment go beyond the science
The anti-parasitic drug mebendazole has shown preclinical efficacy in targeting multiple cancers, but experts say social media posts calling it a "cure" go too far. Additional clinical trials in humans are necessary to prove when, at what dosage, and in which treatment combinations it could make an impact.
Posts touting mebendazole as cancer treatment go beyond the science
The anti-parasitic drug mebendazole has shown preclinical efficacy in targeting multiple cancers, but experts say social media posts calling it a "cure" go too far. Additional clinical trials in human...
Scientists find a weak spot in one of the deadliest brain cancers
Researchers may have found a new way to weaken glioblastoma’s defenses against treatment. Blocking a protein called SET prevented tumors from forming in preclinical models, while targeting related proteins made cancer cells more vulnerable to radiation. The strategy works by restoring activity of PP2A, an enzyme that glioblastoma cells appear to suppress. Human testing will be needed to determine whether the approach is safe and effective.
Anthropic Wants to Make Its Own Drugs With Help from Claude
The AI company is launching preclinical drug programs for overlooked diseases.
Moderna highlights expanding mRNA platform at Science Day
Moderna's Horizon programme contains a variety of mRNA assets in varying stages of development, including a preclinical in vivo candidate.
Sullivan to lead basic and preclinical science at Duke School of Medicine
Beth A. Sullivan, PhD, has been appointed vice dean for basic and preclinical science at Duke University School of Medicine, effective July 1, 2026.
Common asthma drug helps fight hard-to-treat cancers, including aggressive breast cancers, early study finds
Scientists found that blocking a protein best known for its role in asthma enhances cancer immunotherapy in preclinical models.
Traws Pharma Reports Full Year 2025 Results and Provides Business Highlights
Tivoxavir marboxil advancing towards a human influenza challenge trial as a once-monthly prophylactic agent, building on broad preclinical antiviral activity, Ratutrelvir topline Phase 2a data show a differentiated profile versus PAXLOVID® in COVID patients, with good overall safety; final study analysis underway Private financing of up to $60M (with $10M of such amount upfront) offering of common stock and milestone-based and three-year warrants completed on April 15, 2026 supporting operations
Dean for Basic Science Colin Duckett tapped to serve as Boston University Provost
Duckett, executive vice dean for basic and preclinical science, will begin his tenure as chief academic officer at Boston University starting in July.
Your Thymus and Your Healthspan
Our thymus gland plays a central role in the development or our immune system, specifically for supporting T cell development (how these cells got their name, maturation and differentiation in the thymus) and discriminating between self and foreign, non-self antigen proteins with production of dendritic cells. As we age, our thymus gland shrinks—the process known as involution—with progressive change from spongy to fatty tissue, with loss of functionality. But this process, with respect to timeline and extent, markedly varies from one person to the next. And to make things even more complicated, our thymus gland anatomy and precise location in the chest also is highly variable. So the famous Frank Netter diagrams from the 1960s (such as at left below) don’t capture the remarkable heterogeneity that a random set of 12 chest CT scans (below at right). What I consider as 2 landmark papers in Nature this week (here and here) used AI to quantify health of the thymus in 2 large cohorts, and then correlate the metric to a broad array of health outcomes. In this edition of Ground Truths, I’m going to cover three questions: (1) How was thymus health determined by AI?; (2) How is thymus health linked to key clinical outcomes? and (3) Are there ways we can promote a healthy (aka rejuvenate) thymus gland in our later years? Subscribe 1. How was thymus health determined by AI? This was accomplished by extensive work developing and validating an AI pipeline for 2 stages, the first for localization and segmentation of the thymus bed, and the second to quantify a digital marker, termed the thymic health score. There’s a lot to this algorithmic development, so I won’t go into all the details, but just provide a rudimentary outline of what was done. The 1st stage used supervised learning with 2 radiologists reviewing 2,461 chest CT scans. That work trained a 3D U-Net model to automatically identify the thymic bed’s 3D cropped region using center of mass coordinates, which reached 99.8% accuracy. The 2nd stage used a foundation model that was pre-trained with SwAV (which stands for Swapping Assignment between multiple Views), a self-supervised model, that generated a high-dimensional thymus representation of 4,096 features. That compares to the radiology reductionist and subjective scoring of 0 to 3 where 0 means the thymus is fully degenerated and fatty, and 3 is considered dense, intact glandular soft tissue. Notably, the self-supervised learning (SSL) performance was superior to supervised (AUC ~0.75 vs 0.55, respectively) reflecting the shallowness of the 0-3 classifier vs SSL’s holistic, self-taught AI. The thymic health score ranged from 0 to 100, with the highest number indexed to fully preserved thymic health. The algorithmic work extended to explainability with both Shapely value distribution, meaning the model was holistic not relying on any “magic” pixel, and occlusion sensitivity, demonstrating the model’s performance was not affected by ribs, sternum, lung tissue, but rather focused on the thymic bed directly. Below are a few saliency maps from the occlusion sensitivity that indicate the thymic bed focus, not affected by neighboring structures, using the jet color scale. Now the AI was ready for processing ~25,000 CT scans, each over 30 MB files, from the 2 large participant cohorts to provide a thymic health score, it did so in less than 14 hours, which is less than 2 seconds per scan! Share 2. How is thymus health linked to key clinical outcomes? The two cohorts were the National Lung Screening Trial, NLST (N=25,031) and the Framingham Heart Study, FHS (N=2,581) each with baseline demographics and long term follow up of >12 years for health outcomes. From the NSLT, you can see below that increased age and body-mass index were correlated to reduced thymic health. And, overall, men had reduced thymic health scores compared with women. There are a lot of graphs in the paper for outcomes, for both the NLST and FHS cohorts. To simplify the major outcomes, below is a composite Figure with striking reduction of all-cause mortality and for the different causes of death. The results were consistent between the 2 cohorts. For example, the cardiovascular mortality hazard ratio average was 0.57 in NLST and 0.38 in FHS (weighted to be 0.53 for the aggregate). The reduction of mortality also extended to digestive diseases and pulmonary disease (data not shown below). Lung cancer incidence was reduced by 36% for high vs low thymic health (Figure below, with a panel -incidence and b panel-mortality, adjusted for age, sex, BMI, smoking status). Notably, there was a smoker’s paradox: lower incidence and improved survival for lung cancer in smokers who had a high thymus health score. Smoking was associated with lower thymic scores whereas alcohol was not. Higher thymic health was linked to higher HDL cholesterol, lower triglycerides, lower fasting blood glucose, and lower systolic and diastolic blood pressure. Inflammation biomarkers, such as C-reactive protein and interleukin-6, were elevated in the people with lower thymic health scores. In their second paper, the same team looked at the relationship between thymic score and outcomes for 3,476 patients receiving cancer immunotherapy. The non-small cell lung cancer progression-free survival was reduced in patients with low thymic health score. A parallel relationship for survival was seen for other types of cancer including melanoma, breast, and kidney with a 44% lower risk among high thymic scores (Figure). A similar pattern was seen with different immune checkpoint inhibitors. The thymus health score outperformed programmed death ligand-1 (PD-L1)and tumor mutation burden (TMB) assay of the tumor and was an independent prognostic marker of progression-free survival. In this dataset, a direct connect with thymus score and adaptive immune function was noted with a correlation before cancer treatment for both T-cell diversity and thymus T-cell production (a metric known as T cell receptor excision circles). Thymus Removal Study There is a highly relevant citation about thymus function before moving onto ways to rejuvenate it. In 2023, a very important study of thymus removal during cardiothoracic surgery was published, with 1146 patients undergoing thymus removal vs 1146 matched controls (mean age 55 years). The adverse outcomes for thymus removal were striking, with a 2.9 higher risk of all-cause mortality and doubling of cancer incidence, 1.5 fold increase in cancer mortality, and 1.5-fold increase in autoimmune diseases. The immune function showed marked compromise after thymus removal, as reflected by CD4+ and CD8+ T cells (Figure below) Share Ground Truths 3. Are there ways we can promote a healthy (aka rejuvenate) thymus gland in our later years? In recent months we’ve learned a lot about the process of thymus involution and the pathways by which this may be modulated. Thymus involution is primarily due to loss to thymus epithelial cells (TECs) and there are 2 subtypes with different functions: the cortical, responsible for positive selection of T cells, and the medullary, for negative selection. When adipose tissue infiltrates the thymus, thymic adipocytes are pro-inflammatory, knocking out T-cell output. Likewise, systemic inflammation, or “inflammaging,” from smoking, obesity, and chronic stress promote thymic adipocytes. Now, from preclinical studies, we know about key pathways that account for these processes. Historically, back in 2014, FOXN1 was recognized as a single master transcription factor essential for TEC function, with studies in mice with forced FOXN1 upregulation leading to thymus regeneration. That laid the foundation for potential regrowth of quiescent thymus cells. It took awhile to find pathways to accomplish this goal and to even refute its role as the master regulator. The Liver-Thymus Axis Feng Zhang and his team recently showed that injection of an mRNA vaccine to the liver encoding DLL1, IL-7 and FLT3-L in combination, factors known to support thymopoiesis (Figure), successfully enhanced immune function in aged mice. However, the effect was transient. The FGF21 Story Two reports in 2025 addressed the thymus gland’s production of FGF21, a growth factor (fibroblast growth factor 21) and its control of thymus involution. This growth factor is also produced by the liver, but it doesn’t have impact on the thymus in aged rodent models. In contrast, The liver’s hepatocyte growth factor (HGF) has been shown to reverse senescent TEC structural changes. Growth hormone stimulates production of insulin growth factor-1 (IGF-1) in the liver and the thymus. Two small studies in human participants (TRIIM, for Thymus Regeneration, Immunorestoration, and Insulin Mitigation) of 6 and 50 people, respectively, treated with combined human growth hormone, metformin and DHEA, suggested the potential of slowing epigenetic aging and improving thymus mass and function. But the combination of drugs, small sample, and lack of controls make conclusions murky. Increased thymus FGF21 led to increased CD8 T cells in old mice and extended healthspan and improved physical performance. Building on the previous FOXN1 data, ablation of β-klotho, the obligatory co-receptor for FOXN1, accelerated thymic aging. The benefit to FGF21 was confirmed in a companion paper using an FGF21 knock-in mouse model showing thymus enlargement and increased TECs throughout the lifespan. (schematic Figure below). The accompanying editorial for these 2 papers speculated: “The proposed link between age-associated thymus involution and organismal aging is intriguing, and suggests we might seek to achieve systemic rejuvenation by counteracting thymic involution.” Other Factors Lessons from the Axolotl (Mexican Salamander) In an elegant set of experiments of the axolotl (Figure), known for its complete thymus regeneration after total surgical removal, mediators were identified. Surprisingly FOXN1 was dispensable. But midkine, a growth factor, appeared to be the driver, the initiator of thymus cell growth, survival, and repair. Other components that contributed were Postn+ (periostin-expressing mesenchymal niches) and Ccl19, a chemokine protein from the bloodstream. RANK and RANKL RANK (receptor activator of nuclear factor κB its ligand (RANKL) have been considered key regulators of medullary TECs. In a study of both aged mice and human thymus cell cultures, their key role was confirmed, with multiple benefits of resorting TEC function, recruitment of progenitor cells, and T cell development. Subscribe Summing Up This body of work strongly supports the health of the thymus gland as a critical regulator of human healthspan, not just a correlate or link. The new landmark studies are reinforced by the regenerative biology experimental models that have shown, via an array of mediators, that healthspan of aged mice is at least in part dependent on thymus gland function and its critical role for maintaining adaptive immunity. It sure seems that we’d be better off having an immune reservoir of naive T cells instead of a profile in older adults of exhausted, low quality, memory T cells, with a senescent phenotype. It is striking that we ignored the importance of the thymus gland for many decades. A wake-up call was the results of the thymectomy matched control study reviewed here, with the opposite of high thymic health score improved health outcomes. The convergence of AI and healthspan here is notable. The exceptional and laborious work for developing and validating (no less explaining) the AI to quantify thymus health set the foundation for probing the connect the major health outcomes in two cohorts with extensive follow-up. We’ve never had a way to meaningfully quantify the thymus gland before, so this represents important leverage of supervised, self-supervised, and transformer models. The study wouldn’t have been possible without AI. And it begs the question as to whether there are ways we can maintain our thymus at a high health score. But it’s not so simple to rejuvenate our thymus. There are multiple risks including the induction of autoimmunity, increasing the risk of cancer, and inducing a pro-inflammatory state. For example, factors that increase TEC proliferation could compromise the medulllary negative selection process and leak out auto-reactive (self-attacking) T cells. Thymic cells could be induced to proliferate, but we know, for example, that growth hormone and IGF-1 are associated with an increase risk of cancer. If thymus rejuvenation doesn’t clear out the accumulated senescent cells in older adults, then inflammation within the gland could block the production of TECs. Keeping these risks in mind, we now have identified many ways to keep our thymus healthy as we age that undoubtedly will be tested in clinical trials going forward. Ultimately, the benefit-to-risk tradeoffs will be defined. In the meantime, we have desperately needed an immunome. As I’ve stressed in multiple prior Ground Truths, we have no test in the clinic to assess a patient’s immune status! It was very encouraging for me to get an email from Hugo Aerts, the senior author of the landmark papers in the days after they were published: “I also wanted to say that your Substack on “Why We Need an Immunome” was inspiring for this work. We found it a very compelling perspective and greatly enjoyed reading it.” Just having an assessment of a person’s immune status via a chest CT scan, with millions of these performed per year, might help in guiding the right immunotherapy for cancer (e.g. more intensive, combinations for those with low thymic health scores) and help define people who are increased risk for age-related diseases of cancer, cardiovascular, and neurodegenerative. The main theme of Super Agers is that we now have many layers of data (genetics, proteins, biomarkers, organ clocks that can be integrated via multimodal AI) for us to define a person’s specific risk decades before one of these age-related diseases leads to symptoms, enabling prevention. From the new studies this week, we can add thymus health score as yet another way to understand a person’s risk, a window into their adaptive immune system and healthspan. And perhaps someday we will be able to safely rejuvenate the thymus, or maintain its health through one’s life, and use the thymus health score to monitor. NB: I wrote this post (No A.I.) A Quick Poll Loading... ********************************************************************* Thanks to Ground Truths subscribers (now > 200,000) from every US state and 212 countries. Your subscription to these free essays and podcasts makes my work in putting them together worthwhile. Please join! If you found this interesting PLEASE share it! Share Ground Truths Paid subscriptions are voluntary and all proceeds from them go to support Scripps Research. They do allow for posting comments and questions, which I do my best to respond to. Please don’t hesitate to post comments and give me feedback. Let me know topics that you would like to see covered. Leave a comment Many thanks to those who have contributed—they have greatly helped fund our summer internship programs for the past two years. It enabled us to accept and support 47 summer interns in 2025! We aim to accept even more of the several thousand who will apply for summer 2026.
Maine’s wild blueberries deliver more than tradition. Research proves they support health.
Wild blueberries — the iconic Maine crop dotting hillsides, decorating sweatshirts and adding personality to local menus — is more than a cultural symbol. Over 20 years of preclinical and clinical studies suggest that regularly consuming wild blueberries supports gut and heart health and may reduce risk factors associated with…
Aveeno® announces research collaboration to advance skin health science and education as skin care brand celebrates 80 years of innovation
Collaboration to focus on preclinical and clinical research, professional education, and innovative strategies to amplify advancements in skin science
Aveeno® announces research collaboration to advance skin health science and education as skin care brand celebrates 80 years of innovation
Collaboration to focus on preclinical and clinical research, professional education, and innovative strategies to amplify advancements in skin science
START Appoints Dr. Frank Smith President of its XenoSTART Preclinical Research Business Unit
/PRNewswire/ -- The START Center for Cancer Research ("START") today announced the appointment of Frank Smith, PhD, MBA, as President of XenoSTART, its...
Five honored at Translational Science and Research Forum
Translational research brings discoveries from the laboratory and preclinical studies forward to clinical trials and studies in humans.
Five honored at Translational Science and Research Forum
Translational research brings discoveries from the laboratory and preclinical studies forward to clinical trials and studies in humans.
Assessing Suzhou Ribo Life Science’s Valuation After Recent Share Price Weakness
Recent share performance and business profile Suzhou Ribo Life Science (SEHK:6938) has drawn attention after a 5.4% one day decline to HK$70.05, extending a one month return of a 7.9% decline and a year to date return of a 14.7% decline. For context, the company focuses on researching and developing small nucleic acid drugs targeting cardiovascular, metabolic, renal, liver and other diseases, with several candidates in Phase I, Phase II and preclinical trials. See our latest analysis for...
CRISPR Therapeutics Provides Business Update and Reports Fourth Quarter and Full Year 2025 Financial Results
ZUG, Switzerland and BOSTON, Feb. 12, 2026 (GLOBE NEWSWIRE) -- CRISPR Therapeutics (Nasdaq: CRSP) today reported financial results for the fourth quarter and full year ended December 31, 2025. “As we close out the fourth quarter, CRISPR Therapeutics continues to make steady progress across a broad and increasingly mature pipeline,” said Samarth Kulkarni, Ph.D., Chairman and Chief Executive Officer of CRISPR Therapeutics. “We made meaningful advances across multiple clinical and preclinical progr
Endocrinology — Uniting the Legacy and Future of Basic Endocrine Science
Read the inaugural editorial from Endocrinology’s new Editor-in-Chief, Manuel Tena-Sempere, MD, PhD, outlining the vision for the journal to continue its high-quality standards spanning foundational, translational, and preclinical research investigating endocrine and metabolic function in health and disease while becoming more influential and attractive for a wider array of scientists worldwide.
Legend Biotech Highlights Recent Business Updates at 44th Annual J.P. Morgan Healthcare Conference
Exceeded 10,000 patients treated to date with CARVYKTI® (ciltacabtagene autoleucel; cilta-cel)Increased CARVYKTI® manufacturing capacity with the physical expansion of the Raritan facility, now the largest cell therapy manufacturing facility in the U.S.Profitability expected in 2026, driven by continued CARVYKTI® revenue growth and operating margin expansion Treated first patient with in vivo pipeline candidate in investigator-initiated trial Preclinical data from primates provided early validat