Animal only
This controlled animal trial investigated the comparative effects of three butyrate-based dietary supplements — tributyrin with copper and essential oils (TB-500), di- and tri-butyrin (TB-300), and coated sodium butyrate (SB-500) — versus a control diet in 1,000 Arbor Acres broiler chicks across four treatment groups (250 birds each, six replicates). Over 35 days, researchers measured growth performance, carcass traits, serum biochemistry, immune markers, gene expression (mTOR, TLR4, NBN), intestinal histomorphometry, caecal microbiota, and litter hygiene. The study found that TB-300 was associated with improved body weight (+4.6%), feed conversion ratio (–5.2%), and European Production Efficiency Factor (+14.9%). SB-500 was linked to reduced litter Clostridia and aerobic bacterial counts. All butyrate treatments were associated with improved intestinal villus morphology, elevated serum total proteins and digestive enzymes (lipase and protease), and upregulated TLR4 gene expression. TB-300 and SB-500 were associated with reduced serum lipids, urea, and AST, alongside enhanced mTOR and NBN gene expression. Limitations include that the study was conducted exclusively in broiler chickens, findings are not directly translatable to humans, and it did not include a blinded assessment of outcomes.
Scientific reports · Jul 2025DOI ↗ Review
This narrative review examines how rapidly advancing obesity pharmacotherapies — particularly GLP-1 receptor agonists, dual and triple incretin agonists, and amylin-based combination therapies — are challenging the longstanding criteria used to determine eligibility for bariatric surgery. The authors note that current surgical guidelines were established when effective medical alternatives were limited, and argue that newer agents achieving 15–25% body weight reduction now approach outcomes historically associated only with surgery. The review compares surgical and pharmacologic interventions across dimensions of efficacy, safety, metabolic benefit, and cost-effectiveness, and considers whether a stepwise, pharmacotherapy-first approach may be appropriate — particularly for individuals with a BMI of 30–40 kg/m². The authors also discuss potential roles for pharmacotherapy in perioperative care and long-term obesity management, and call for personalized treatment strategies. As a narrative review, the paper does not conduct a systematic search or meta-analysis, which limits its ability to make definitive comparative claims. It reflects the authors' interpretive synthesis of existing literature rather than new primary data, and is subject to selection bias inherent to the narrative format.
Medicina (Kaunas, Lithuania) · Jul 2025DOI ↗ Limited · human
This paper presents a case report of a man in his early 30s who developed transaminitis (elevated liver enzymes) after taking MK-677, an oral growth hormone secretagogue, for approximately two months. MK-677 has been growing in popularity as a performance-enhancing supplement. The patient was otherwise healthy, with no other apparent causes for liver injury identified. Following discontinuation of the supplement, liver function tests gradually returned to normal levels, suggesting a causal relationship between MK-677 use and the hepatotoxic event. The authors highlight that while known side effects of MK-677 include oedema, increased appetite, and muscle pain, reports of hepatotoxicity associated with its use are rare. This case adds to the limited literature on potential adverse hepatic effects of MK-677. Key limitations include the single-patient design, lack of a liver biopsy or formal causality assessment score (e.g., RUCAM), inability to fully exclude confounders such as contaminants in the supplement, and the inherent difficulty in establishing definitive causality from a single case report.
BMJ case reports · Jul 2025DOI ↗ Animal only
This study investigated the mechanisms underlying weight loss produced by CagriSema — a combination of cagrilintide (an amylin analogue) and semaglutide (a GLP-1 analogue) — in a rat model. Researchers quantified the contributions of reduced energy intake versus preserved energy expenditure to overall weight loss. Rats treated with CagriSema achieved approximately 12% body weight loss alongside a 39% reduction in food intake. To isolate the role of energy intake, the authors used two comparison conditions: pair-feeding (matching food intake to CagriSema-treated animals) and weight matching (determining how much food restriction alone would be needed to achieve equivalent weight loss, which required a 51% reduction in intake). The gap between these conditions suggested that roughly one-third of CagriSema's weight loss effect was attributable to blunting of metabolic adaptation — the phenomenon where the body typically reduces energy expenditure in response to caloric restriction. Limitations include that findings are from an animal model and may not directly translate to humans, and the study does not address long-term outcomes. The authors conclude that CagriSema's dual action on both energy intake and expenditure may contribute to its potential effectiveness as an obesity treatment.
Nature metabolism · Jul 2025DOI ↗ Moderate · human
This multicentre retrospective observational study used TriNetX, a global healthcare data platform, to examine real-world associations between semaglutide use and survival outcomes in adults with type 2 diabetes (T2D) and chronic kidney disease (CKD). Researchers identified over 1.1 million eligible patients, of whom 14,511 initiated semaglutide and 69,700 initiated sitagliptin between 2018 and 2020. After propensity score matching to balance baseline characteristics, 13,703 patients were included in each group. The study found that the semaglutide group had a significantly lower 3-year incidence of all-cause death (7.2% vs. 9.5%) compared with the sitagliptin group. Secondary outcomes including acute heart failure, acute myocardial infarction, and stroke also favored semaglutide. The authors note these findings are consistent with the randomized FLOW trial. Key limitations include the retrospective, non-randomized design, potential for residual confounding despite propensity score matching, reliance on administrative coding data, and the inability to account for medication adherence or dosing details. Findings should be interpreted as associative, not causal.
Open heart · Jul 2025DOI ↗ Limited · human
This pilot study investigated whether targeting estrogen-related receptors (ERRs) could help counteract muscle atrophy associated with physical inactivity in older women. Twenty women undergoing hip replacement surgery were divided into active (n=10) and inactive (n=10) groups based on self-reported activity levels. Muscle biopsies were collected during surgery and analyzed for key proteins involved in mitochondrial function and oxidative stress. Active women showed greater muscle fiber diameter, better handgrip strength, and lower pain scores. Inactive women's muscle tissue showed higher NOX4 (an oxidative stress marker) and lower levels of SIRT1, PGC-1α, ERRα, and FNDC5 compared to active women. In a separate cell-culture experiment, myoblasts isolated from inactive women's muscle tissue were treated with the ERR agonist SLU-PP-332. Treatment was associated with reduced NOX4, increased SIRT1, PGC-1α, ERRα, FNDC5, Akt, and Bcl-2 expression, decreased cytotoxicity, oxidative stress, and cellular senescence, increased glutathione levels, and enhanced myotube formation. The authors suggest ERR activation as a potential therapeutic strategy for muscle atrophy, while acknowledging that the small sample size, self-reported activity classification, and in vitro nature of the intervention data limit conclusions.
Frontiers in physiology · Jul 2025DOI ↗ Limited · human
This observational study investigated the relationship between serum Thymosin β4 (Tβ4) levels and Kawasaki disease (KD) in children, with a specific focus on coronary artery lesions (CALs). Researchers measured serum Tβ4 concentrations via ELISA in children diagnosed with KD and age-matched healthy controls, further subdividing the KD group into those with and without CALs. The study found that serum Tβ4 levels were significantly lower in children with KD compared to healthy controls, and were reduced even further in KD patients who developed CALs. Following intravenous immunoglobulin (IVIG) treatment, Tβ4 levels increased significantly. Correlation analyses revealed negative associations between Tβ4 and several cytokines, including pro-inflammatory markers (TNF-α, IL-1β) and anti-inflammatory markers (IL-4, IL-10). The authors suggest that Tβ4 may play a role in KD's inflammatory pathogenesis and the progression of coronary artery involvement, proposing it as a potential diagnostic or therapeutic target. Key limitations include the observational design, which precludes causal inference, the pediatric-specific and single-condition focus, and the reliance on serum biomarker associations without mechanistic validation in this population.
Journal of inflammation research · Jul 2025DOI ↗ Animal only
This study investigated the therapeutic potential of GHK-Cu (glycyl-l-histidyl-l-lysine-copper) in ulcerative colitis (UC) using a dextran sulfate sodium (DSS)-induced mouse model and complementary cell-based experiments. Researchers administered GHK-Cu to BALB/c mice with DSS-induced colitis and assessed disease activity, colon histology, goblet cell counts, tight junction proteins (ZO-1, Occludin), inflammatory cytokines (TNF-α, IL-6, IL-1β), and key signaling proteins (SIRT1, STAT3, p-STAT3, RORγt). Network pharmacology and molecular docking were used to predict SIRT1 as a core target. A co-culture model of mouse colonic epithelial cells (MCECs) and peritoneal macrophages confirmed GHK-Cu's role in mucosal healing. STAT3 silencing via siRNA revealed that STAT3 is required for GHK-Cu's promotion of epithelial healing and tight junction protein upregulation, but not for its anti-inflammatory effects, suggesting additional pathways are involved. The study found that GHK-Cu reduced disease severity, suppressed inflammation, enhanced mucosal repair via the SIRT1/STAT3 pathway, and decreased RORγt expression, suggesting reduced Th17 cell activity. Limitations include exclusive use of animal and in vitro models with no human data.
Frontiers in pharmacology · Jul 2025DOI ↗ In vitro
This study investigated the metabolic fate of alexamorelin — a synthetic peptide growth hormone secretagogue (GHS) with potential performance-enhancing properties — to identify biomarkers useful for doping control. Researchers used in silico metabolite prediction software (GLORYx) alongside in vitro incubations with pooled human hepatocytes from 10 donors, analyzing samples via liquid chromatography–high-resolution tandem mass spectrometry (LC-HRMS/MS). GLORYx predicted 21 possible single-reaction metabolites, with N-acetylation ranked highest in probability (98%), and other transformations such as hydroxylation, N-oxidation, and glucuronidation predicted at lower probabilities. However, after 3 hours of hepatocyte incubation, only one metabolite was experimentally detected: examorelin (hexarelin), produced by carboxypeptidase-mediated cleavage of the C-terminal alanine residue. The parent compound decreased approximately 150-fold over the incubation period, indicating rapid and extensive hepatic metabolism. A key limitation is that examorelin is itself a commercially available GHS compound, meaning it cannot serve as a specific biomarker for alexamorelin use. The authors conclude that direct detection of alexamorelin itself remains the most reliable strategy for confirming its consumption in anti-doping contexts. This study was conducted entirely in vitro and does not involve human subjects or animal models.
Journal of analytical toxicology · Jul 2025DOI ↗ Review
This review paper provides a comprehensive overview of the current and emerging pharmacological landscape for metabolic dysfunction-associated steatohepatitis (MASH), the progressive inflammatory form of metabolic dysfunction-associated steatotic liver disease (MASLD). The authors describe MASH as a growing global health burden, closely tied to obesity and type 2 diabetes, and carrying significant risks of cirrhosis, hepatocellular carcinoma, and liver failure. The review synthesizes evidence from advanced-stage clinical trials evaluating several therapeutic classes, including incretin-based therapies (GLP-1 receptor agonists, dual, and triple agonists such as semaglutide, tirzepatide, and survodutide), metabolic modulators (PPAR agonists like lanifibranor, FGF21 analogues like pegozafermin, and thyroid hormone receptor-beta agonists like resmetirom), and novel agents such as fatty acid synthase inhibitors. The authors note that regulatory endpoints currently rely on histological assessment, while noninvasive biomarkers and personalized approaches are gaining traction. Genetic factors, such as PNPLA3 polymorphisms, and artificial intelligence are highlighted as emerging tools for patient stratification and trial design. Key limitations acknowledged include unresolved questions about treatment duration, response heterogeneity, long-term adherence, and the evolving definition of therapeutic success.
The Journal of clinical investigation · Jul 2025DOI ↗ Limited · human
This retrospective observational study used the TriNetX database of de-identified electronic health records (January 2018–December 2020) to compare cardiovascular outcomes between semaglutide and dulaglutide in adults with type 2 diabetes. From a pool of nearly 4.7 million patients with type 2 diabetes, 231,075 semaglutide initiators and 189,103 dulaglutide initiators were identified. Propensity score matching yielded 171,105 patients per group. Over a 3-year follow-up, the study found that semaglutide was associated with statistically significantly lower rates of all-cause death (4.2% vs. 5.6%; HR 0.75, 95% CI 0.72–0.78), acute myocardial infarction (5.2% vs. 5.6%; HR 0.94), stroke (5.8% vs. 6.4%; HR 0.90), and acute heart failure hospitalization (5.3% vs. 6.1%; HR 0.88) compared with dulaglutide. Key limitations include the observational, non-randomized design, which is susceptible to residual confounding despite propensity score matching; reliance on administrative/EHR coding for outcome ascertainment; and the inability to distinguish between semaglutide formulations (oral vs. injectable) or account for dosing differences between agents.
Scientific reports · Jul 2025DOI ↗ Review
This review paper examines whether two major antihyperglycemic drug classes — sodium-glucose co-transporter-2 (SGLT2) inhibitors and glucagon-like peptide-1 receptor agonists (GLP-1 RAs) — may have a therapeutic role in gout management, particularly in patients who also have type 2 diabetes mellitus (T2DM). The authors describe gout as the most common form of inflammatory arthritis, driven by hyperuricemia that leads to monosodium urate crystal deposition in joints and tissues. The review summarizes evidence from multiple clinical studies suggesting that SGLT2 inhibitors lower serum urate (SU) levels, likely by promoting urinary uric acid excretion, which could benefit gout patients with comorbid T2DM. The paper also notes that SGLT2 inhibitors have demonstrated reductions in cardiovascular and renal events. By contrast, the effect of GLP-1 RAs on SU levels and urinary uric acid excretion in humans is described as unclear. The authors review mechanisms of action, structure-activity relationships, uricosuric effects, pharmacokinetic profiles, and adverse effects for both drug classes. Key limitations include the review design, reliance on studies conducted primarily in T2DM populations, and the absence of dedicated gout-specific clinical trials for either drug class.
Pharmaceutics · Jun 2025DOI ↗ Moderate · human
This systematic review and meta-analysis examined treatments for female sexual desire, arousal, and orgasmic (DAO) dysfunction, explicitly excluding patients with sexual pain conditions. Researchers searched six major databases through December 2024, screening 8,994 abstracts and ultimately including 36 studies (26 RCTs and 10 single-arm trials). Treatments evaluated included cognitive behavioral therapy (CBT, 10 studies), medications (24 studies), and devices (2 studies). Meta-analyses were feasible for three interventions: mindfulness-based CBT, flibanserin, and bremelanotide, all assessed using the Female Sexual Function Index (FSFI) and Female Sexual Distress Scale (FSDS). The study found that mindfulness-based CBT was associated with significant improvements in total FSFI and DAO subscales; flibanserin was associated with improvements in total FSFI and the desire subscale; and bremelanotide was associated with improvements in total FSFI and both the desire and arousal subscales. All three treatments were associated with reduced sexual distress. Key limitations include the absence of direct head-to-head comparisons between CBT and pharmacotherapy, heterogeneous terminology across studies, varying outcome measures, and insufficient data to draw conclusions about most other treatments reviewed.
Journal of minimally invasive gynecology · Jun 2025DOI ↗ Animal only
This review paper examines the proposed therapeutic mechanisms and safety profile of BPC 157, a synthetic 15-amino-acid peptide derived from a gastric protein. The authors argue, drawing on Robert and Szabo's cytoprotection concept, that BPC 157's protective effects on gastric epithelial and endothelial cells extend to other organ systems (cytoprotection → organoprotection). The paper addresses and disputes concerns that BPC 157 might promote tumorigenesis through angiogenesis, generate harmful free radicals via increased nitric oxide (NO) and eNOS activity, or contribute to neurodegenerative diseases such as Parkinson's and Alzheimer's. Instead, the authors contend that, based on reviewed animal and in vitro studies, BPC 157 modulates angiogenesis in a context-dependent manner—maintaining corneal transparency and opposing pathological neovascularization—while demonstrating anti-tumor effects both in vivo and in vitro per Folkman's framework. The paper also reports that BPC 157 counteracts Parkinson's- and Alzheimer's-like disturbances in rodent models and modulates NO levels without promoting damaging free radical formation. Key limitations include the heavy reliance on animal and in vitro data, the absence of human clinical trial data, and the authors' advocacy framing.
Pharmaceuticals (Basel, Switzerland) · Jun 2025DOI ↗ Moderate · human
This systematic review and meta-analysis evaluated the efficacy of Thymosin alpha 1 (Tα1), an immunomodulatory peptide, in patients with severe acute pancreatitis (SAP). Researchers searched five major databases through February 2025 and identified five randomized controlled trials encompassing 706 SAP patients, comparing Tα1 treatment against non-Tα1 controls. The pooled analysis found that Tα1 was associated with increased percentages of CD4+ T cells and improved CD4+/CD8+ ratios, suggesting a positive effect on immune cell balance and reduction of immune suppression. Lower-dose Tα1 was associated with significantly reduced C-reactive protein (CRP) levels, an inflammation marker. Tα1 was also associated with a potential reduction in extrapancreatic infection risk. The authors concluded that Tα1 may regulate immune cell balance and exert anti-inflammatory effects in SAP patients, potentially improving prognosis. Key limitations include the small number of included trials (n=5), the relatively modest total patient population, heterogeneity in dosing protocols, and the predominance of studies from a single country (China), which may limit generalizability. The authors noted that further research is needed to validate these findings.
Frontiers in immunology · Jun 2025DOI ↗ Animal only
This study developed a multifunctional injectable hydrogel platform — called Exo@Tβ4/HAMA — designed to accelerate bone repair by simultaneously promoting stem cell recruitment, angiogenesis, neurogenesis, and osteogenesis. The hydrogel was fabricated by grafting Thymosin β4 (Tβ4), a short tissue-repair peptide, onto methylmalonic anhydride-modified hyaluronic acid (HAMA) via photo-cross-linking, then loading it with bone marrow mesenchymal stem cell (BMSC)-derived exosomes. In vitro experiments showed the hydrogel had favorable mechanical properties, good biocompatibility, and could recruit BMSCs, enhance tube formation in human umbilical vein endothelial cells (HUVECs), and promote osteogenic differentiation. In vivo rat cranial defect models demonstrated that the hydrogel promoted new bone formation, vascularization, and nerve ingrowth. The study identified the ERK1/2-dependent RUNX2 signaling pathway as a likely mechanistic contributor to osteogenesis. Key limitations include exclusive use of rat models with no human data, a relatively short observation window, and lack of comparison to current clinical gold-standard grafts. The findings suggest promise as a cell-free, injectable bone regeneration scaffold, but clinical translation requires further validation.
Review
This paper systematically compares four major oncology and gynecology clinical practice guidelines — ASCO (2018), ESO-ESMO (2022), NCCN (2024), and SOGC (2024) — regarding the management of sexual health concerns in female cancer survivors. The authors grouped recommendations across five domains of sexual dysfunction: vaginal dryness, low sex drive, pain, orgasmic dysfunction, and psychological concerns. All four guidelines consistently recommend non-hormonal therapies (lubricants and moisturizers) as first-line treatment for vaginal dryness, with low-dose local estrogen as a second-line option. All guidelines endorse multidisciplinary care including psychosocial counseling, relationship counseling, specialist referral, and cognitive behavioral therapy. Three guidelines (ASCO, NCCN, SOGC) support vaginal dilators and pelvic floor physical therapy for pain. ASCO uniquely recommends any form of stimulation to improve sexual response, while NCCN and SOGC endorse sexual aids for arousal. Pharmacological agents for low libido — including androgens, bupropion, flibanserin, bremelanotide, and buspirone — are mentioned in all guidelines except ESO-ESMO, though the authors note the underlying evidence base is limited. A key limitation is that this is a narrative comparison of guidelines rather than a primary study. The authors conclude that while consensus exists in several areas, further research on pharmacological and counseling interventions is needed.
Supportive care in cancer : official journal of the Multinational Association of Supportive Care in Cancer · Jun 2025DOI ↗ Animal only
This study introduces a biodegradable buccal suction patch designed to improve the systemic delivery of therapeutic peptides by bypassing gastrointestinal degradation. The researchers replaced previously used non-degradable silicone materials with biodegradable copolyesters, which were thermally crosslinked via a scalable mold-casting process. Mechanical testing identified the best-performing polymer formulation, and degradation was confirmed in both aqueous media and simulated waste environments. An ex vivo model using porcine buccal tissue demonstrated enhanced permeation of a poorly permeable dye when a chemical permeation enhancer was co-applied. In a beagle dog in vivo model, the biodegradable patch substantially improved the bioavailability of semaglutide (4.11 kDa) compared to a commercially available oral tablet within a 10-minute application window. The patch also achieved a relative bioavailability of approximately 26% for bremelanotide (1.03 kDa) versus subcutaneous injection. Key limitations include the use of an animal model rather than human subjects, a relatively small study scope, and the need for further safety and efficacy validation before clinical translation. The work highlights a promising, more sustainable alternative to silicone-based buccal delivery devices for peptide therapeutics.
Journal of controlled release : official journal of the Controlled Release Society · Jun 2025DOI ↗ Animal only
This review paper examines pharmacotherapies for abdominal compartment syndrome (ACS) and intra-abdominal hypertension (IAH) through the lens of cytoprotection theory, framing these conditions as failures of cytoprotective mechanisms. The authors survey existing pharmacological agents used in ACS/IAH management, noting that most currently reported treatments are limited in scope—typically effective in only one organ, tested only in mild-to-moderate IAH, applied prophylactically rather than therapeutically, and lacking confirmed broad effectiveness. The review then focuses on stable gastric pentadecapeptide BPC 157 as a proposed cytoprotective agent with claimed pleiotropic effects. The authors argue that BPC 157 may address multiple simultaneous targets in ACS/IAH, including compression/ischemia and decompression/reperfusion injury across several organs (brain, heart, lung, liver, kidney, gastrointestinal tract). A proposed mechanism involving activation of collateral "bypassing" vascular pathways—particularly azygos vein blood flow—is described as a potential key to counteracting multiorgan failure, vascular dysfunction, thrombosis, and free radical damage. The paper is a narrative review drawing primarily on animal study data; it does not present original clinical trial data or human evidence. Conclusions about BPC 157 efficacy are therefore speculative in a human clinical context.
Pharmaceuticals (Basel, Switzerland) · Jun 2025DOI ↗ Animal only
This preclinical study investigated whether mazdutide — a dual glucagon-like peptide-1 receptor (GLP-1R) and glucagon receptor (GCGR) agonist — could improve cognition in a mouse model of type 2 diabetes mellitus (T2DM). Male db/db mice (a well-established T2DM model characterized by obesity and hyperglycemia) were treated with mazdutide and compared against dulaglutide, a GLP-1R-only agonist. Researchers assessed cognitive function via behavioral tests and examined brain pathology for neurodegenerative markers. They also applied transcriptomic, proteomic, and metabolomic (multi-omics) analyses to explore underlying molecular mechanisms. The study found that mazdutide-treated mice showed greater improvements in cognitive performance compared to dulaglutide-treated mice, along with better neuronal structure and brain tissue integrity. Multi-omics data implicated molecular pathways related to neuroprotection, energy metabolism, and synaptic plasticity as potential contributors to these effects. Key limitations include exclusive use of male mice, meaning results cannot be generalized to females, and the entirely preclinical nature of the study. No human data were collected, so whether these findings translate to people with T2DM remains unknown. The authors suggest mazdutide may warrant further investigation as a treatment for metabolic disorder-associated cognitive decline.
EBioMedicine · Jun 2025DOI ↗