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peptide science.

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.

Comparative distribution of the hypothalamic neurons activated during wakefulness and paradoxical (REM) sleep using male TRAP2-red mice: contribution of orexin, MCH, Lhx6, and a new marker Meis2.

Sleep

Amarine Chancel, Patrice Fort, Renato M Maciel +5 more

Paradoxical sleep (PS) is a state involving numerous hypothalamic neuronal subpopulations, many remaining neurochemically uncharacterized. Our goal was to compare hypothalamic neurons active during wakefulness or PS rebound (PSR) and explore their potential overlap, with a focus on melanin-concentrating hormone (MCH), Orexin (Orx), Lhx6, and a new contingent of Meis2-expressing neurons.

The weight-loss-independent hepatoprotective benefits of semaglutide are orchestrated by intrahepatic sinusoidal endothelial GLP-1 receptors.

Cell Metab

Maria J Gonzalez-Rellan, Cristina Riobello, Susanna Fang +7 more

Glucagon-like peptide-1 (GLP-1) medicines improve metabolic liver disease through weight-loss-dependent and -independent actions. Here, we interrogated semaglutide's action in mice with metabolic dysfunction-associated steatohepatitis (MASH). In Glp1rWnt1-/- mice resistant to GLP-1RA-induced weight loss, semaglutide improved steatosis, fibrosis, and immune remodeling. GEM-X Flex-seq localized Glp1r expression to pericentral liver sinusoidal endothelial cells (ECs) (LSECs) and CD8+ T cells. EC Glp1r deletion in Glp1rTie2-/- mice or AAV8-Cre-mediated hepatic EC Glp1r knockdown substantially abrogated semaglutide's hepatic benefits despite preserved weight loss. Transcriptomic profiling revealed that Glp1r+ LSECs adopt a stress-responsive phenotype in MASH that is reversed by semaglutide. Glp1r+ LSECs function as dominant contributors to semaglutide-regulated circuits linked to injury and repair involving VWF, SELE, CEACAM, and BMP. Molecular profiling revealed semaglutide-coordinated transcriptional and protein-level reversal of disease signatures. Together, the data using mouse models of MASH reveal an EC-specific, weight-loss-independent, semaglutide-regulated, GLP-1R-dependent intrahepatic network for improving liver health.

Widespread exposure to GLP-1RAs and weight loss-related discourse: Considering potential public health implications.

Can J Public Health

Marilou Côté, Ximena Ramos Salas, Kimberly Carrière +1 more

Incretin-based therapies, including glucagon-like peptide-1 receptor agonists (GLP-1RAs), are approved for the treatment of type 2 diabetes, obesity, and related conditions, and have demonstrated significant benefits for individuals with these conditions. However, in recent years, public interest and demand for GLP-1RAs-often driven by media, social media influencers, advertising, and public discourse-have increased beyond the populations for whom these medications are medically indicated. The ripple effects of widespread public exposure to GLP-1RAs and weight-loss-related discourse on public health have received very little research attention and remain poorly understood. This widespread exposure may contribute to a perception that GLP-1RAs are intended as weight loss solutions for non-medical use, rather than an effective treatment for specific chronic conditions like obesity. Such perceptions could influence demand and affect equitable access for people with medical indications for these medications. Widespread exposure to discourse that highlights GLP-1RAs as weight loss solutions may inadvertently reinforce social desirability for thinness and body image concerns. Despite the established clinical efficacy of GLP-1RAs for medically indicated conditions, this commentary highlights the potential public health risks associated with their growing portrayal as weight loss solutions for non-medical use in the public sphere and calls for research to better understand these broader implications to inform balanced public health communication strategies.

The role of mast cells in simvastatin-induced myopathy and the possible protective role of omega-3 fatty acids in adult male albino rats: light and electron microscopic study.

Ultrastruct Pathol

Dalia Ahmed Baha Eldein, Shereen Hamed, Shireen Mazroa +1 more

Simvastatin is antihyperlipidemic drugs that inhibit hydroxy methylglutaryl CoA reductase to decrease cholesterol synthesis; however, it causes skeletal myopathy. Omega-3 are polyunsaturated fatty acids with anti-inflammatory and anti-oxidant effects. Mast cells have an important role in the response to tissue injury by secreting different mediators and cytokines. The current study was performed to assess the role of mast cells in simvastatin-induced myopathy and the possible protective role of omega-3 fatty acids. Forty adult male albino rats were divided into four main groups received the drugs orally for of 21 days. Group 1: 1 ml distilled water, group 2: 300 mg/kg/day omega-3, group 3: 88 mg/kg/day simvastatin, and group 4: 88 mg/kg/day simvastatin plus 300 mg/kg/day omega-3. Light and electron microscopic studies were done along with morphometric and statistical studies. Group 1 and 2 showed regular histological structure. By light microscope, group 3 revealed muscle fiber disorganization, splitting, loss of striations, and cytoplasmic fragmentation. Some nuclei were centrally displaced. Toluidine blue sections showed a large number of mast cells. By transmission electron microscope, there was loss of the regular banding pattern with irregular mitochondria, nuclei, and sarcolemma. The concurrent administration of simvastatin with omega-3 showed less myopathic changes, decrease in mast cell numbers and more activation of the satellite stem cells to accomplish the process of muscle regeneration. In conclusion, the administration of omega-3 can decrease the myopathic changes of simvastatin. Further studies are recommended to explore the mast cells' role in the progression and repair of statin-induced myopathy.

Isolation, Culture, and Differentiation of Bovine Muscle Resident Stem Cells.

Bio Protoc

Perri Gish, Madison W Stewart, Maykal Tsonov +4 more

Bovine muscle satellite cells (MuSC) and fibro-adipogenic progenitor cells (FAP) are muscle resident stem cells that are responsible for postnatal muscle growth, intramuscular fat deposition, and extracellular matrix generation. These cells are of increasing interest for the cultivated meat community due to their ability to generate all the major components of meat; additionally, these cells are of interest to conventional animal science research to elucidate mechanisms to improve meat quality. To use these cells for these goals, efficient and accurate cell isolation, culture, and differentiation are essential to evaluate their cell fate decisions and behaviors. In this protocol, we detail a simultaneous isolation of both MuSCs and FAPs with multiple intermediate stopping points, allowing for flexibility for day-of time constraints. We also detail improved growth conditions to maximize cell expansion and procedures to assess cell differentiation. This protocol provides a flexible isolation procedure that is compatible with sampling in modern slaughterhouses or from biopsies. Additionally, the differentiation procedures provide improved differentiation but still allow in vitro treatment and assessment. Key features • This protocol offers a flexible in-lab procedure to isolate bovine FAPs and MuSCs from tissue collected post-slaughter with multiple pause points. • The protocol demonstrates successful conditions to grow, expand, and differentiate bovine FAPs with an optimized adipogenic differentiation medium. • Strategies for planning your primary cell isolation, choosing the sampling location, and characterizing differentiation of bovine FAPs and MuSCs are included.

Glucagon-Like Peptide-1 Receptor Agonists: Their Potential Role in Prediabetes.

Diabetes Ther

Theodoros Panou, Evanthia Gouveri, Djordje S Popovic +2 more

Prediabetes is a frequently occurring condition with increased risk of type 2 diabetes mellitus (T2DM) and cardiovascular disease. Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are established antidiabetic agents, also used to treat obesity. There is limited, yet promising evidence on their use in prediabetes. T2DM was less frequent among subjects on liraglutide, semaglutide and tirzepatide compared with the control arm. Delayed progression to T2DM has also been observed. Furthermore, normoglycaemia was achieved for subjects on liraglutide (up to 66%), semaglutide (up to 81%) and tirzepatide (up to 93.3%). However, this effect was only partially sustained following drug withdrawal. GLP-1RAs have led to modest decreases in glycated haemoglobin (HbA1c), fasting glucose, weight and fat mass loss, as well as increased insulin sensitivity and improved β-cell glucose-insulin dynamics. Decreased risk for atherosclerotic cardiovascular disease and heart failure was also demonstrated, mostly for subjects on tirzepatide. There is experimental evidence on improvements in liver dysfunction, pointing to potential benefits for metabolic dysfunction-associated steatotic liver disease (MASLD) in prediabetes. The safety profile was acceptable with mild-to-moderate gastrointestinal adverse effects being mostly reported. Future large randomised controlled trials are needed to ascertain the exact role of GLP-1RAs in prediabetes.

Comparative Cardiovascular Effectiveness of Glucagon-Like Peptide 1 Receptor Agonists and Sodium-Glucose Cotransporter 2 Inhibitors in Diabetes Mellitus.

J Am Coll Cardiol

Fan Bu, Ruopeng Wu, Anna Ostropolets +18 more

Glucagon-like peptide 1 receptor agonists (GLP-1RAs) and sodium-glucose cotransporter 2 inhibitors (SGLT2Is) have established cardiovascular benefits for patients with type 2 diabetes mellitus (T2DM), with similar class-level effectiveness found in previous studies. However, real-world comparative effectiveness assessments of individual agents remain limited.

The Role of the Glymphatic System in Alzheimer's Disease: Mechanisms, Evidence, and Therapeutic Implications.

Rejuvenation Res

Yaran Li, Juan Li, Xinhong Liu +4 more

Alzheimer's disease (AD) is an aging-associated neurodegenerative disorder characterized by amyloid-β (Aβ) and tau accumulation and progressive cognitive decline. Increasing evidence implicates the glymphatic system, a brain-wide perivascular pathway involved in cerebrospinal fluid-interstitial fluid exchange and metabolic waste clearance, in the removal of Aβ, tau, and other solutes relevant to AD pathogenesis. Aging-related alterations in aquaporin-4 polarization, arterial pulsatility, sleep architecture, and cerebrovascular integrity may impair glymphatic transport and thereby promote protein retention and neurodegeneration. In this review, we summarize current knowledge of glymphatic anatomy and function and discuss its implications for AD, with particular emphasis on modifiable factors such as sleep, exercise, vascular health, and aging-associated decline. We further highlight emerging therapeutic and potential intervention strategies aimed at restoring glymphatic function, and critically evaluate current methods for assessing this system in humans together with the evidence obtained to date. Although human studies increasingly support the relevance of perivascular fluid transport to AD-related pathology and cognitive outcomes, mechanistic insights remain largely derived from animal models, and human assessment is still constrained by methodological and imaging limitations. Overall, the glymphatic system provides a useful framework for linking brain aging to impaired clearance in AD. Further refinement of human biomarkers and longitudinal translational studies will be essential for clarifying their clinical relevance and therapeutic potential.

Sleep-Dependent Clearance of Brain Metabolites via the Glymphatic System: Implications for Alzheimer's Pathophysiology.

Brain Behav

Farshad Zare, Gulnora Shakhmurova, Jasur Rizaev +4 more

This review aims to examine how sleep-dependent glymphatic function contributes to the clearance of brain metabolites involved in Alzheimer's disease (AD), with particular emphasis on amyloid-beta (Aβ), tau, astrocytic aquaporin-4 (AQP4), and emerging biomarkers of clearance-related dysfunction.