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Comparison of Specific Glucagon-Like Peptide-1 Receptor Agonists on Kidney Outcomes Among Patients With Type 2 Diabetes.
Am J Kidney Dis
Joshua J Neumiller, Yihong Deng, Kavya Sindhu Swarna +9 more
Glucagon-like peptide-1 (GLP-1) receptor agonist treatment is associated with lower risk for incident chronic kidney disease (CKD) and death relative to treatment with a dipeptidyl peptidase-4 inhibitor or sulfonylurea. This study examined within class effects of GLP-1 receptor agonists on kidney outcomes in type 2 diabetes (T2D) and moderate cardiovascular risk.
Microfocused Ultrasound with Visualization for Skin Tightening: Clinical Applications, Safety, and Technical Considerations.
Dermatol Clin
Gabriela Marie Soza
Microfocused ultrasound with visualization (MFU-V) represents a noninvasive energy-based modality for skin tightening and lifting. This technology delivers precise ultrasound energy to dermal and subdermal tissues, creating thermal coagulation points that stimulate neocollagenesis and elastin regeneration. US Food Drug Administration-cleared for brow lifting, neck and submental tightening, and décolletage wrinkles, with recent 2025 clearance for abdomen and arms, MFU-V demonstrates efficacy across multiple anatomic regions with a favorable safety profile. The recent introduction of Ultherapy Prime offers enhanced visualization and processing capabilities, potentially improving treatment precision and patient comfort.
Tirzepatide for Obesity in Adults ≥ 65 Years: A Post Hoc Analysis of the SURMOUNT and SUMMIT Clinical Trials.
Diabetes Obes Metab
Nasreen Alfaris, Robert F Kushner, Jianghao Li +4 more
Tirzepatide is a once-weekly glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) receptor agonist (RA) approved for weight management in adults with obesity. Data on older adults remain limited, however. This study aimed to examine tirzepatide's safety and efficacy in adults aged ≥ 65 years with obesity across Phase 3 clinical trials.
Comparative Effects of Antidiabetic Drugs on Body Composition: A Systematic Review and Network Meta-Analysis.
Diabetes Obes Metab
Seyedeh Samira Rakhsha, Hossein Shahinfar, Sara Ebrahimi-Mousavi +9 more
Antidiabetic drugs differ in their effects on body composition, which may influence metabolic and functional outcomes. This systematic review and network meta-analysis aimed to quantify and compare effects of major antidiabetic drugs on key body composition parameters.
DMD-Null mice exhibit severe muscle weakness, impaired regeneration, and deficient satellite cell function.
Proc Natl Acad Sci U S A
Harry Wilton-Clark, Md Nur Ahad Shah, Jamie Leckie +7 more
Duchenne muscular dystrophy (DMD) is a debilitating and fatal X-linked disease affecting 1/5,000 males worldwide that currently has no cure [D. Duan, N. Goemans, S. Takeda, E. Mercuri, A. Aartsma-Rus, Nat. Rev. Dis. Primers 7, 1-19 (2021), 10.1038/s41572-021-00248-3]. Vast amounts of research have been conducted on DMD, and one of the most common animal models for DMD studies is the mouse muscular dystrophy (mdx) model [J. W. McGreevy, C. H. Hakim, M. A. McIntosh, D. Duan, DMM Dis. Model. Mech. 8, 195-213 (2015), 10.1242/DMM.018424/-/DC1]. Unfortunately, despite its shared genetic etiology, the mdx mouse shows a relatively mild dystrophic phenotype compared to affected humans, limiting its overall utility as a research model (G. Donen, N. Milad, P. Bernatchez, J. Neuromuscul. Dis. 10, 1003 (2023), 10.3233/JND-230126]. Notably, mdx mice have a mutation preventing the production of full-length dystrophin but are still able to produce numerous short isoforms of dystrophin. Here, we provide a comprehensive functional characterization of DMD-Null mice, which lack all dystrophin isoforms. Our studies demonstrate that DMD-Null mice show a more severe skeletal muscle phenotype than mdx mice, characterized by profound weakness, decreased exercise tolerance, and impaired muscle regeneration, while utrophin upregulation was similarly observed in DMD-Null and mdx mice. We identify a marked deficit in satellite cell proliferation and myogenic differentiation, accompanied by downregulation of regenerative gene programs. These findings suggest potential contributions of short dystrophin isoforms to muscle stem cell function, and establish DMD-Null mice as a unique model for investigating the pathogenesis of DMD and testing therapeutic interventions targeting satellite cell health and regeneration.
Glucagon-like peptide-1 receptor agonists and rotator cuff disease: a scoping review.
BMC Musculoskelet Disord
Dave Osinachukwu Duru, Andrew Kailin Zhou, David Kwan Ryung Ryung +2 more
Obesity and type 2 diabetes mellitus (T2DM) are associated with impaired rotator cuff tendon healing and inferior clinical outcomes following surgical repair. Glucagon-like peptide-1 receptor agonists (GLP-1RA) are increasingly used to manage obesity and T2DM. However, their influence on rotator cuff disease biology and outcomes following cuff repair remains unknown.
Evaluating the effects of aging on biodistribution and gene silencing activity of lipid-siRNA conjugates delivered into cerebrospinal fluid.
Mol Ther
Alexander P Ligocki, Alexander G Sorets, Adam M Abdulrahman +11 more
Aging is the primary risk factor for chronic neurodegenerative diseases and is associated with alterations to cerebrospinal fluid (CSF) flow and clearance. CSF delivery is currently the most clinically advanced route of administration for oligonucleotide therapeutics, but it remains poorly understood how aging, which is rarely incorporated into clinical trials, impacts biodistribution, gene silencing activity, and potential toxicity of these compounds. Here, we evaluated a lipid-siRNA conjugate (L2-siRNA) for potential age-related changes to CSF-mediated delivery, mRNA silencing, and safety. In the context of aging, we also studied how conjugate chemistry and siRNA structure impact delivery and activity by comparing L2-siRNA to an alternative lipid-siRNA conjugate design. We determined that age had minimal impact on the performance of L2-siRNA and that conjugates exhibit better activity when each lipid is paired with the siRNA structure and chemistry for which it was initially optimized. Collectively, these results provide valuable insight into siRNA conjugate biodistribution and activity in the CNS in the context of aging and further establish the performance of L2-siRNA under conditions relevant to the treatment of neurodegenerative diseases.
Pathological Interplay of ROS With Myofibroblasts: An Impediment to Corneal Restitution.
Oxid Med Cell Longev
Mohammad Yahya Karimi, Abasalt Hosseinzadeh Colagar
Myofibroblasts are morphologically similar cells with diverse origins that exhibit characteristics of both fibroblasts and smooth muscle cells. Following insults, myofibroblasts play critical roles in tissue reintegration and restitution. However, their prolonged presence and activity impede physiological recovery, leading to persistent or progressive tissue complications, as evidenced in corneal fibrosis and opacification. Reactive oxygen species (ROS) are key signaling intermediates in various cellular events, playing critical roles in the physiology of myofibroblasts. However, when dysregulated, these molecules can engage in misinstructive manners with myofibroblasts, directing these cells toward pathogenic states and behaviors. In brief, dysregulated ROS pathologically modulate myofibroblast differentiation, extracellular matrix (ECM) remodeling, and immune evasion, maintaining self-perpetuating cycles of myofibroblast survival. The mediation of ROS promotes maladaptive intra and extracellular responses that contribute to myofibroblast persistence by enhancing ECM stiffness, increasing resistance to apoptosis, inducing senescence, and impairing immune clearance. ROS-mediated alterations in ECM components, most notably in proteoglycans (PGs) and glycosaminoglycans (GAGs), further dysregulate the ECM and make it more conducive to myofibroblast persistence. Additionally, ROS-induced immune privilege mechanisms prevent the proper clearance of myofibroblasts. Therefore, targeting ROS collectively offers promising therapeutic potential for mitigating their pathological presence and behavior, thereby enhancing overall corneal recovery following insults.
Latilactobacillus sakei ZFM232 alleviates age-related lipid metabolism disorders and enhances antioxidant defense in Caenorhabditis elegans.
Food Funct
Gang Wang, Yubin Zhang, Fengxuan Wang +5 more
Lactic acid bacteria (LAB) are widely recognized as beneficial microorganisms within the human microbiome; however, the mechanisms underlying their health-promoting effects remain largely elusive. Here, we show that Latilactobacillus sakei ZFM232 (LS232) exhibits tolerance to acidic conditions and moderate salt stress, along with relatively stable antioxidant capacity in vitro. Using Caenorhabditis elegans as an in vivo model, we found that long-term intake of LS232 significantly improved nematode survival under oxidative, osmotic, and heavy-metal stress conditions, with increases of 40%, 36.5%, and 11.9%, respectively, compared to the control group. LS232 feeding also reduced age-related lipid droplet accumulation and triglyceride levels, indicating improved lipid metabolic status during aging. Concurrently, LS232 enhanced glutathione S-transferase 4 (GST-4) activity, promoted superoxide clearance, and improved redox balance in vivo. Moreover, LS232 feeding was associated with increased nhr-49 expression, enhanced nuclear enrichment of NHR-49, and upregulation of lipid metabolism-related genes, including fat-5, fat-6, fat-7, and acs-2. In the nhr-49 mutant background, the beneficial effects of LS232 on lipid accumulation and redox balance were significantly attenuated, further supporting the involvement of an NHR-49-associated regulatory program in mediating these responses. Overall, these results suggest that LS232 has potential applications in alleviating aging-related lipid metabolism disorders and oxidative damage.
First case report of the ARMC5 (c.2692C>T, p.Arg898Trp) variant in a Chinese family with adrenocorticotropic hormone-independent macronodular adrenal hyperplasia.
AME Case Rep
Ren Gai, Chunyang Shi, Zimeng Guo +3 more
Adrenocorticotropic hormone (ACTH)-independent macronodular adrenal hyperplasia (AIMAH) is a rare etiology of Cushing's syndrome (CS), frequently linked to germline mutations in the ARMC5 gene. These variants exhibit autosomal dominant inheritance with incomplete penetrance and are associated with bilateral adrenal nodularity and autonomous cortisol secretion. In this familial case, the proband's father carried the same heterozygous variant but remained asymptomatic, illustrating the incomplete penetrance characteristic of ARMC5-associated disorders.
Anshen Decoction Improves Synaptic Plasticity and Memory in Insomnia Rats by Regulating Hippocampal Mitochondrial Dysfunction via the AMPK/PGC-1α Pathway.
Comb Chem High Throughput Screen
Tiantian Tan, Biyong Liu, Shaojie Wan +8 more
This study investigated the effects of Anshen Decoction (ASD) on heart-kidney disharmony insomnia, focusing on the AMPK/PGC-1α pathway.
Refractory hyponatremia after traumatic brain injury unmasks adrenal insufficiency in a patient with remote steroid use.
CEN Case Rep
Toshikazu Ozeki, Seiya Ito, Yuna Muto +7 more
A man in his early 60 s developed persistent hyponatremia following lumbar spine surgery complicated by traumatic brain injury with subarachnoid hemorrhage. Initial evaluation demonstrated hypotonic hyponatremia with inappropriately concentrated urine, consistent with the syndrome of inappropriate antidiuretic hormone secretio. Standard therapy including hypertonic saline and oral sodium supplementation resulted in only transient improvement. Given a history of secondary adrenal insufficiency due to long-term topical corticosteroid use, adrenal function was reassessed. An adrenocorticotropic hormone stimulation test confirmed secondary adrenal insufficiency. Initiation of hydrocortisone therapy led to sustained normalization of serum sodium. This case highlights the diagnostic difficulty of post-TBI hyponatremia and underscores the importance of considering adrenal insufficiency, even years after apparent recovery from steroid-induced hypothalamic-pituitary-adrenal axis suppression.
Integrated bioinformatics analysis and experimental validation reveal circFoxO1 as a regulator of pathological cardiac hypertrophy.
3 Biotech
Huicong Yang, Jie Lin, Yongqing Yang +6 more
Pathological Cardiac Hypertrophy (CHT) is a maladaptive response that can lead to heart failure and increase the risk of severe cardiovascular events. However, the molecular mechanisms underlying CHT remain incompletely understood, and effective targeted therapies are still limited in clinical practice. Circular RNAs (circRNAs) emerge as important epigenetic regulators in cardiovascular biology, yet their roles in CHT remain insufficiently characterized. In this study, we combined transcriptomic analysis with in vitro and in vivo experimental models to identify functional circRNAs associated with CHT. Differential expression analysis of the GSE148602 dataset, coupled with machine-learning-assisted prioritization, highlighted circFoxO1 as a potential regulator. Angiotensin II (AngII)-induced hypertrophy models were established in HL-1 cardiomyocytes and C57BL/6 mice, revealing significant downregulation of circFoxO1 under hypertrophic conditions. Gain-of-function experiments demonstrated that circFoxO1 overexpression reduced the expression of classical hypertrophic markers, including atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP), and β-myosin heavy chain (β-MHC), and alleviated AngII-induced cardiomyocyte enlargement. Mechanistic analyses further suggested that circFoxO1 may influence hypertrophic responses through the canonical Wnt/β-catenin signaling pathway, as circFoxO1 overexpression restored Wnt3a and β-catenin expression levels, whereas pharmacological inhibition with FH535 attenuated its antihypertrophic effect. Collectively, these findings indicate that circFoxO1 may modulate AngII-induced CHT and provide additional insight into circRNA-mediated regulatory mechanisms during pathological cardiac remodeling.
The Effect of Semaglutide on Antipsychotic-Induced Weight Gain and Other Metabolic Parameters, among a Cohort of Inpatients.
Schizophr Bull
Riddhita De, Yasser Amin Alfatwa, Pruntha Kanagasundaram +8 more
Antipsychotic use in severe mental illnesses (SMI) is associated with metabolic dysregulation, including antipsychotic-induced weight gain (AIWG), type 2 diabetes (T2D), and dyslipidemia. In the case of non-response to metformin which is currently recommended for AIWG mitigation, no clear alternatives exist. Semaglutide, a weekly injectable glucagon like peptide-1 receptor agonist, represents a promising option. However, effectiveness and safety data in SMI are lacking. With initiation of semaglutide, we hypothesized weight loss, improvements in metabolic indices, and good tolerability.
Weight Changes With Lower Doses of Semaglutide in Clinical Practice: Findings From the Chinese HARMONY Cohort.
Diabetes Obes Metab
Shuang Liu, Baige Cao, Chuwen Lin +5 more
To evaluate 24-week weight changes with lower-dose semaglutide in routine care among Chinese adults with obesity and to examine whether diabetes and ectopic fat in the liver and pancreas are associated with heterogeneity in weight-loss response.
The Effect of Semaglutide on Quality of Life in Adults With Overweight or Obesity: A Brief Systematic Review and Meta-Analysis.
Diabetes Obes Metab
Naseem Eisa, Mira Khoury
Semaglutide 2.4 mg causes substantial weight loss, but its average effect on patient-reported physical function requires interpretation against clinically meaningful thresholds and routine clinical expectations. This systematic review and meta-analysis aimed to evaluate the effects of once-weekly subcutaneous semaglutide 2.4 mg on patient-reported physical functioning and weight-related quality-of-life outcomes in adults with overweight or obesity.
GLP-1 Receptor Agonists in Aesthetic Surgery: A Narrative Review on Perioperative Safety, Sarcopenic Morphologies, and Adapted Body Contouring Strategies.
Aesthetic Plast Surg
Mario Venza, Isabella Venza
GLP-1 receptor agonists (GLP-1 RAs) are increasingly used for obesity and for weight management in individuals seeking aesthetic improvement. Their pharmacologic effects (delayed gastric emptying and reduced appetite) and the rapidity of weight loss may create perioperative and morphologic challenges for aesthetic and body contouring surgery.
Tirzepatide monotherapy in Chinese patients with early type 2 diabetes: A randomized, double-blind, placebo-controlled phase 3 trial (SURPASS-CN-MONO).
Med
Yaqi Yin, Jianhua Ma, Dexue Liu +8 more
We report findings from the Chinese SURPASS-CN-MONO trial (ClinicalTrials.gov: NCT05963022) of tirzepatide monotherapy.
SURMOUNT-REAL UK: A Pragmatic Randomized Clinical Trial to Assess the Effectiveness of Tirzepatide in Adults With Obesity.
Obesity (Silver Spring)
Martin K Rutter, Julie Mount, J Martin Gibson +12 more
SURMOUNT-REAL UK will evaluate the effectiveness of tirzepatide when offered in addition to standard-of-care (SoC) in adults with Class I obesity (BMI ≥ 30 and ≤ 34.9 kg/m2) and without diabetes in a UK primary care setting.
Temporal Trends and Clinical Characteristics of Incretin-Based Therapy Use in Women With Polycystic Ovary Syndrome: A Real-World Cohort Study From a Polish Private Healthcare Network.
Diabetes Obes Metab
Artur Dziewierz, Natalia Kulicka, Kaja Stolarska +4 more
Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) and the dual GIP/GLP-1 receptor agonist tirzepatide are increasingly used for weight and cardiometabolic management, but real-world prescribing patterns in women with polycystic ovary syndrome (PCOS) remain poorly characterised.