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peptide science.

Approved weight loss drugs for obesity with a thorough emphasis on GLP-1 agonist medications: A systematic review.

Dis Mon

Praveen Gunasekaran, Pugazhendi Inban, Ashita Agrawal +5 more

Obesity is a worldwide health concern linked to cardiometabolic comorbidities such as type 2 diabetes, hypertension, dyslipidemia, and heart disease. The management of obesity using pharmacotherapy, especially with GLP-1 receptor agonists and dual incretin agents, has proven successful not only for weight loss but also for gaining control of the metabolic components of the disease. Thus, it is pertinent to analyse the GLP-1-based anti-obesity medications to examine cardiometabolic efficacy and safety using weight loss, glycemic control, cardiometabolic, gastro-intestinal tolerability, and serious adverse events as the primary variables.

Cardiometabolic Profiles of Oral and Subcutaneous Glucagon-Like Peptide-1 Receptor Mono-Agonists in Adults With Overweight or Obesity: A Systematic Review and Network Meta-Analysis.

Diabetes Obes Metab

Ying Lu, Jiajie Chen, Yuqing Guo +6 more

To characterize the cardiometabolic profiles of oral and subcutaneous glucagon-like peptide-1 (GLP-1) receptor mono-agonists in adults with overweight or obesity, with or without type 2 diabetes (T2D), using network meta-analysis (NMA).

Overcoming Challenges in Wound Infection: Biofilm and Antimicrobial Resistance.

Adv Wound Care (New Rochelle)

Markus Rothmaier, Matthew J Hardman, Bithi Chatterjee +3 more

Chronic wounds represent a growing clinical and economic burden, affecting 1-2% of the global population, with prevalence expected to rise due to aging and increasing rates of diabetes, obesity, and vascular diseases. Wound persistence is often driven by infection and compounded by antimicrobial resistance (AMR), resulting in poor patient outcomes. High prevalence of microbial biofilms, which shield pathogens from immune clearance and promote AMR, further promotes the chronicity of infected wounds.

Dapagliflozin for cardiorenal protection after intensive care unit discharge: a protocol for a randomised controlled trial evaluating dapagliflozin at ICU discharge for cardiorenal protection (DAPA-ICU).

BMJ Open

François Dépret, Benjamin Chousterman, Claire Roger +20 more

Patients discharged from intensive care units (ICUs) are at high risk of adverse long-term outcomes including cardiovascular and/or renal events and a 1-year mortality of approximately 22%. Plasma biomarkers measured at ICU discharge have demonstrated strong prognostic value, with elevated cardiac or renal biomarkers identifying patients at particularly high risk of poor outcomes. Sodium-glucose cotransporter 2 inhibitors are now widely recognised for their cardioprotective and nephroprotective effects in chronic conditions such as type 2 diabetes, heart failure or chronic kidney disease. These agents improve both morbidity and mortality across a range of high-risk populations. We hypothesise that a therapeutic strategy aimed at preventing the progression of cardiovascular and/or renal injury following ICU discharge may improve long-term outcomes in ICU survivors.

Machine learning-based risk stratification identifies heart failure with preserved ejection fraction as an independent predictor of adverse outcomes in hypertrophic cardiomyopathy.

Sci Rep

Weijie Zhang, Huan Zhao, Zhuchang Tian +16 more

Heart failure with preserved ejection fraction (HFpEF) is increasingly recognized in hypertrophic cardiomyopathy (HCM); however, its prognostic significance, phenotypic heterogeneity, and optimal risk stratification strategies remain incompletely defined. In this multicenter retrospective cohort study, 2802 patients with HCM were enrolled from three tertiary centers. HFpEF was diagnosed using established criteria, and H₂FPEF score-based risk subgrouping was performed to further stratify patients. Propensity score matching was applied to balance baseline characteristics between HFpEF and Non-HFpEF patients. Event-free survival was assessed using Kaplan-Meier and multivariable Cox analyses. Restricted cubic spline modeling evaluated non-linear associations between B-type natriuretic peptide (BNP) levels and outcomes. Four machine learning models were developed for individualized risk prediction, with model interpretability assessed using SHAP analysis. HFpEF was present in 47.8% of patients with HCM and was independently associated with worse event-free survival after propensity score matching (HR = 2.612, 95% CI 2.188-3.118, P < 0.001). Higher H₂FPEF scores conferred graded risk, with HFpEF-High patients exhibiting substantially poorer outcomes (HR 2.925, 95% CI 2.210-3.701; P < 0.001). BNP demonstrated a significant non-linear relationship with adverse events, with risk accelerating at higher concentrations. Among machine learning models, the random forest achieved the best discrimination (AUC = 0.856), with SHAP analysis identifying HFpEF status and BNP as dominant contributors to risk prediction. HFpEF represents a prevalent, heterogeneous, and high-risk phenotype in HCM. Integrating H₂FPEF score-based risk subgrouping, non-linear biomarker modeling, and interpretable machine learning enhances personalized risk stratification and may, pending external validation, inform precision management strategies in HCM.

Sex differences in corticotropin-releasing factor receptor-2α expressing neurons in acutely stressed mice.

Horm Behav

Jennifer J Lafrican, Katherine E Parra, Krystyna A Rybka +12 more

Females are 2-3 times more likely than males to be diagnosed with mood disorders, including depression and anxiety, yet the neurobiological mechanisms contributing to this sex difference are not fully understood. Corticotropin-releasing factor receptor 2 (CRFR2) plays a key role in regulating stress responses, with evidence suggesting it may dampen hypothalamic-pituitary-adrenal (HPA) axis activation and behavioral stress responses. Although CRFR2 has been implicated in stress buffering, little is known about how its expression and activation differs by sex, particularly in the mouse model. To address this gap, we used newly generated CRFR2-Cre-2α-TdTomato mice to investigate sex differences in CRFR2-expressing neurons and their activation across stress-regulating brain regions following an acute restraint. Males exhibited significantly more CRFR2-expressing neurons in the lateral septum, bed nucleus of the stria terminalis, paraventricular nucleus of the hypothalamus, and central amygdala, while females had more CRFR2-expressing neurons in the medial amygdala and ventromedial hypothalamus. Activation of CRFR2 neurons also showed region-specific sex differences, with males generally exhibiting greater CRFR2 colocalization with c-Fos, a marker for neural activation. Corticosterone levels following restraint were correlated with CRFR2 expression or activation in several brain regions, including the paraventricular hypothalamus, medial amygdala, and bed nucleus of the stria terminalis. These findings identify novel sex differences in CRFR2 expression and stress-induced activation of CRFR2 neurons across multiple stress-regulating brain areas. Together, these results suggest that sex differences in CRFR2 signaling may mediate sex differences in HPA axis responsivity as well as behavioral stress responses.

Cushing's Shadow: An Overlooked Diagnosis in Endocrinology.

Horm Metab Res

Lala Soltanova, Serdar Sahin, Yucel Erbilgin +5 more

The purpose of this study was to describe a novel heterozygous missense variant in the nuclear receptor subfamily 3 group C member 1 ligand-binding domain causing primary generalized glucocorticoid resistance and highlight diagnostic pitfalls that can mimic Cushing's disease.A 22-year-old woman was evaluated for suspected Cushing's disease after elevated cortisol levels and pituitary imaging findings. She underwent three transsphenoidal surgeries, but hypercortisolism and clinical symptoms including hirsutism, acne, menstrual irregularities, and weight gain persisted. The absence of classical Cushing's stigmata prompted genetic evaluation, which led to the diagnosis of primary generalized glucocorticoid resistance.Whole-exome sequencing was performed in the index case. The identified variant was validated by Sanger sequencing and segregation analysis was carried out in her sister. A novel heterozygous, likely pathogenic missense variant (NM_000176.3:c.1940T>C, p.(Leu647Pro)) in the nuclear receptor subfamily 3 group C member 1 gene was detected in two siblings. We describe a novel nuclear receptor subfamily 3 group C member 1 variant associated with primary generalized glucocorticoid resistance, expanding the mutational spectrum of glucocorticoid receptor defects. This case underscores the importance of considering primary generalized glucocorticoid resistance in patients with adrenocorticotropic hormone-dependent hypercortisolism lacking typical Cushing's features to prevent unnecessary invasive procedures and guide appropriate genetic counseling.

Carbonless amino acids and a carbonless GHK peptide.

Phys Chem Chem Phys

Piotr Skurski, Iwona Anusiewicz

Carbonless biomolecular design, in which carbon atoms are systematically replaced by boron and nitrogen under an isoelectronicity constraint, offers a route to carbon free analogues that retain the structural logic of familiar biochemistry. The concept is applied to amino acids and peptides, using glycine, histidine, lysine, and the tripeptide Gly-His-Lys (GHK) as a representative system. DFT(ωB97XD)/aug-cc-pVDZ calculations with aqueous PCM solvation, supported by CREST conformer sampling at the GFN2-xTB/ALPB level, identify unique low energy carbonless building blocks, cGly, cHis, and cLys, defined as carbonless analogues of Gly, His, and Lys among all isoelectronic BN constitutional isomers. These residues enable construction of cGHK, defined as the carbonless analogue of GHK, whose conformational landscape is predicted to be broader than that of GHK under physiological aqueous conditions, consistent with enhanced conformational plasticity. Cu(II) complexation is modeled with an experimentally supported 3N1O motif including one explicit water ligand, and an isodesmic ligand exchange thermodynamic cycle based on ensemble Gibbs free energies indicates stronger stabilization of Cu(II) by cGHK than by GHK (ΔGexch = -6.24 kcal mol-1 at 298 K), with only a minor ensemble correction. The results demonstrate the feasibility of carbonless amino acids and peptides and show that BN substitution can tune conformational behavior and metal binding thermodynamics in carbon free bioinspired scaffolds.

miR-449b-5p from adipose-derived mesenchymal stem cell-derived exosomes targets IGF1R to alleviate airway inflammation and improve airway smooth muscle cell dysfunction in children with asthma.

J Immunol

ShuXiang Sui, LiJuan Yang, DongMei Ji +1 more

This study investigated the protective effect of miR-449b-5p from adipose-derived mesenchymal stem cell-derived exosomes (ADSC-Exos) targeting type 1 insulin-like growth factor receptor (IGF1R) on airway smooth muscle cells (ASMCs) and further investigated its mechanism of action. ADSC-Exos were isolated and characterized. Cellular uptake of ADSC-Exos by ASMCs was observed. Differences in serum miR-449b-5p expression levels between healthy children and asthmatic children were detected by RT-qPCR. The possible binding sites of miR-449b-5p and IGF1R were identified and then verified. The proliferation of ASMCs was determined by MTT assay and EdU assay. Cell cycle of ASMCs was measured by flow cytometry. Cell contraction of ASMCs was evaluated by inverted microscopy. IL-4, IL-5, and IFN-γ were measured by ELISA to evaluate the inflammatory response of ASMCs. ADSC-Exos exerted therapeutic effects on ASMCs by effectively inhibiting proliferation, cell contraction, and inflammatory response. miR-449b-5p upregulation in ASMCs effectively inhibited the promoting effect of PDGF-BB on cellular proliferation and contraction, while IGF1R upregulation showed the opposite effect. miR-449b-5p in ADSC-Exos targeted IGF1R to alleviate airway inflammation in asthma and improve ASMC dysfunction. ADSC-Exos carrying miR-449b-5p improve ASMC dysfunction, excessive proliferation, and inflammatory responses by downregulating IGF1R.

Pharmacological Inhibition of N-terminal methyltransferase 1 promotes myogenic differentiation and muscle regeneration in a mouse model of Duchenne muscular dystrophy.

Stem Cell Res Ther

Haoyuan Zhang, Ming He, Muhammad Asif +3 more

Duchenne muscular dystrophy (DMD), caused by mutations of the DMD gene, is a lethal degenerative disease with no cure. Stimulating myogenesis of muscle stem cells (MuSCs) represents a promising strategy to ameliorate muscle pathology in DMD patients. Although previous work has revealed a role of N-terminal methyltransferase 1 (NTMT1) in myogenesis, its potential as a therapeutic target to ameliorate muscular dystrophy remains unexplored.

A Multicentre, Prospective, Non-Interventional Single-Arm Study Investigating the Impact of Once-Daily Oral Semaglutide in a Real-World Adult Population With Type 2 Diabetes in Mexico.

Endocrinol Diabetes Metab

Guillermo González-Gálvez, Juan C Garnica-Cuellar, Miguel Ángel Colín-García +5 more

To investigate the oral semaglutide use among Mexican adults with type 2 diabetes.

Complex clinical encounter series: Glucagon-like peptide-1 receptor agonists-induced weight loss: are we paying attention to bone health?

J Bone Miner Res

Elena Ambrogini

A sixty-five-year-old white woman with obesity class II, hypertension, hyperlipidemia, obstructive sleep apnea, osteoarthritis, and pre-diabetes was started on subcutaneous semaglutide, a glucagon-like peptide-1 receptor agonist (GLP-1 RA), for weight loss. Her DXA BMD 3 months prior to the initiation of semaglutide showed osteopenia. She did not have personal or family history of fractures. She had gone into menopause at the age of 52 with no other risk factors for osteoporosis. She maintains an adequate intake of calcium and cholecalciferol and she is active but does not exercise regularly. After 1 year on semaglutide, she lost ~15 % of her weight with improvement of blood pressure, lipid profile, and sleeping pattern. She reports two recent falls. The initial recommendation was to repeat DXA in two-three years. However, recent evidence suggests that in elderly patients experiencing ~ 9% weight loss with semaglutide, monitoring bone remodeling markers and BMD after 1 year of treatment is justified. Counseling on adequate protein intake and strengthening exercise to preserve muscle mass should also be provided.

Hemodynamic Changes in Response to GLP-1 Treatment in ICD and CRT Patients: Insights From HeartLogic Sensor Data.

Eur J Heart Fail

Frederik Holme Fussing, Lise Witten Davodian, Danny Witten Davodian +24 more

Glucagon-like peptide-1 receptor agonist (GLP-1RA) therapy is increasingly used, but the physiological effects in patients with heart failure and reduced ejection fraction (HFrEF) remain uncertain. Continuously collected data from implantable cardiac devices may enable evaluation of drug effects in a real-world setting.

Childhood Obesity, Medications, and Surgeries.

Cardiol Rev

Srinidhi Raghav, William H Frishman

The obesity pandemic continues to increase in prevalence in children and adolescents, with its increase outpacing the rate of adult obesity; the human developmental index, body mass index, and family income all display associations to childhood obesity. There are numerous adverse complications of childhood obesity, including cardiovascular, endocrine, and gastrointestinal manifestations. Obesity is thought to be an interaction of several different factors, such as leptin, proopiomelanocortin, glucose uptake in adipocytes, melanocortin receptor 4, protein convertase 1/3, brain-derived neurotrophic factor, fat-mass and obesity-associated gene, melanocortin receptor 4, tumor necrosis factor, interleukin-6, and long noncoding RNA. Epigenetic regulation, the unique gut microbiome role in contributing to obesity, environmental factors, and the social context of a child can precipitation of childhood obesity. In this review, we hope to explore the different medications for obesity, orlistat, glucagon-like peptide-1 agonists, liraglutide, semaglutide, exenatide, setmelanotide, metreleptin, naltrexone, lorcaserin, phentermine, metformin, fluoxetine, lisdexamfetamine, and zonisamide, while also reviewing surgeries such as the Roux-en-Y gastric bypass, laparoscopic or vertical sleeve gastrectomy, and adjustable gastric banding.

Efficacy and safety of novel antidiabetic drugs in patients with type 2 diabetes and chronic kidney disease: a network meta-analysis.

Front Endocrinol (Lausanne)

Xiaojian Zhu, Xingjia Wang, Peiru Zhang +6 more

A number of novel antidiabetic drugs have been developed. These drugs include sodium-glucose cotransporter 2 inhibitors (SGLT-2is), glucagon-like peptide-1 receptor agonists (GLP-1RAs), and dipeptidyl peptidase-4 inhibitors (DPP-4is). However, the optimal medication for individuals with type 2 diabetes mellitus (T2DM) and comorbid chronic kidney disease (CKD) has not been established. To this end, this study was conducted to compare specific novel antidiabetic drugs regarding efficacy and safety.

Neuroprotective Effect of Intraperitoneal Humanin-G in Retinal Degeneration of Royal College of Surgeons Rats.

bioRxiv

Bin Lin, Kevin Schneider, Mustafa Ozgul +2 more

This study aimed to examine whether Humanin-G (HNG), a mitochondrial derived peptide with cytoprotective properties, could improve the retinal function and gene expression profiles after intraperitoneal injections to Royal College of Surgeons (RCS) rats with Retinal Pigment Epithelium (RPE) dysfunction and retinal degeneration. Starting at postnatal day 21 (p21), RCS rats received twice a week intraperitoneal injections of either Low Dose HNG (0.4 mg/kg), High Dose HNG (4mg/kg), or sham-saline for 1 or 4 weeks. Visual function was tested with full field scotopic & photopic electroretinography (ERG) and optokinetic testing (OKT) 1 and 4 weeks after first injection (WAFI). The rats were euthanized after the ERG and OKT (1 or 4 WAFI) and the dissected retinas and RPE were collected for RNA, cDNA and Quantitative Real-time PCR (qRT-PCR) analysis. The results of our study showed that high dose (4mg/kg) HNG at 4 WAFI was associated with the largest change in gene expression in the RPE and retina of treated animals, altering expression of genes involved in apoptosis, oxidative stress, inflammation and retinal/RPE function. Analysis of a and b waves from scotopic and photopic ERG showed no difference between either low or high dose of HNG and sham injection at 4 WAFI. However, at 4 WAFI, the visual acuity in rats treated with high dose HNG showed significant improvement as compared to the rats treated with low dose of HNG or saline. Most significantly, our findings support that HNG administered IP can modulate RPE/neuroretina cells and improve vision, thus may be a potential treatment for retinal degeneration diseases.

Clinical Decision-Making in Laparoscopic Common Bile Duct Exploration: Choosing Between Primary Closure and T-Tube Drainage.

Ann Ital Chir

Kun Liu, Zhang Liu, Jie Gao +2 more

Choledocholithiasis, or common bile duct (CBD) stones, is increasingly prevalent in aging populations worldwide. Laparoscopic common bile duct exploration (LCBDE) is a well-established minimally invasive procedure; however, the optimal method for choledochotomy closure-primary closure (PC) versus T-tube drainage (TTD)-remains controversial.

Congenital Nephrogenic Diabetes Insipidus With the Leu44Phe Variant in Vasopressin Receptor 2 Managed With DDAVP.

Pediatr Int

Issei Takahashi, Makoto Ono, Takuro Yoshimoto +2 more

A Novel Marker in Hypogonadal Hypogonadism: Apelin.

Sisli Etfal Hastan Tip Bul

Alperen Akansel Caglar, Engin Sebin, Emine Kartal Baykan +1 more

Apelin is a recently identified adipokine with pleiotropic actions in cardiovascular regulation, metabolic homeostasis, bone remodeling, and reproductive physiology. Through binding to the apelin receptor (APJ), apelin has been shown to influence gonadotropin-releasing hormone (GnRH) secretion, which is essential for the production of follicle-stimulating hormone (FSH) and luteinizing hormone (LH). Given its potential role in the hypothalamic-pituitary-gonadal (HPG) axis, alterations in circulating apelin may contribute to hypogonadotropic hypogonadism (HH). This study aimed to investigate whether serum apelin concentrations are altered in patients with HH and to evaluate its potential relevance as a complementary biomarker in the diagnostic approach to HH.

Autoimmune Polyglandular Syndrome Type II Presenting with Severe Hyponatraemia and Autoimmune Bicytopaenia.

Eur J Case Rep Intern Med

Patrik Lecký, Martin Jozef Péč, Matej Turčan +4 more

Autoimmune polyglandular syndrome type II (APS II) is a rare, multifactorial disorder characterised by a combination of primary adrenal insufficiency with other autoimmune endocrinopathies, most commonly thyroid disease and type 1 diabetes mellitus. The clinical presentation is variable, and non-specific symptoms often lead to delayed diagnosis.