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Role of Oral Glucagon-Like Peptide-1 Receptor Agonists in Weight Management for Individuals With Overweight or Obesity Without Diabetes: A Network Meta-Analysis of Randomized Controlled Trials.
Obes Sci Pract
A B M Kamrul-Hasan, Hamid Ashraf, Lakshmi Nagendra +6 more
Oral GLP-1 receptor agonists (GLP-1 RAs) offer a non-injectable option for weight management in adults with overweight/obesity without diabetes. This network meta-analysis (NMA) evaluated their effects on body weight.
Projected budget impact of pharmacotherapy scenarios for obesity and related conditions in Peru: A national survey analysis of 76,819 participants.
Obes Pillars
Victor J Vera Ponce
The increasing prevalence of obesity is generating demand for chronic pharmacologic treatment, but Latin American evidence on population-level budget implications remains limited.
A GLP-1 receptor agonist enhances islet microvascular flow through nitric oxide-dependent mechanisms in a diabetic mouse model: investigation using intravital two-photon imaging.
Diabetologia
Tomohiko Kimura, Kengo Kidokoro, Yuichiro Iwamoto +10 more
Impaired regulation of islet microvascular blood flow has been implicated in beta cell dysfunction in diabetes; this dysregulation is linked to endothelial dysfunction with reduced nitric oxide bioavailability. However, dynamic regulation of islet microvascular flow has not been directly examined in vivo. We hypothesised that acute pharmacological activation of the glucagon-like peptide-1 receptor (GLP-1R) rapidly enhances islet microvascular flow through NO-dependent mechanisms under diabetic conditions.
Arterial Spin-Labeling MRI at the Cortical-CSF Interface: A Novel Biomarker in Alzheimer Disease.
Ann Clin Transl Neurol
Mona Asghariahmadabad, Pouya Metanat, Michael Thomas +20 more
Arterial spin-labeling (ASL) MRI can measure perfusion signal adjacent to CSF spaces and may provide information regarding CSF-adjacent water transport physiology. We developed an automated pipeline to extract cortical-CSF interface (IF) perfusion for comparison between Alzheimer disease (AD) and cognitively normal controls.
TrkB signaling modulates neuromuscular transmission in a frequency dependent manner in the mouse diaphragm muscle.
J Neurophysiol
Braydon A Crum, Robert C Martinez, Sepideh Jahanian +3 more
Signaling via tropomyosin-related kinase receptor B (TrkB) plays an important role in synaptic function and plasticity at the neuromuscular junction. Multiple conditions show selective effects on the most forceful and fatigable motor units that require high frequency activation and are necessary for maximal force generation. The goal of the present study is to investigate the effects of inhibiting TrkB kinase activity on neuromuscular transmission in mouse diaphragm muscle during repeated stimulation at frequencies that reflect the recruitment of different motor units (10 vs. 75 Hz). TrkBF616A mice, which possess a mutation that renders TrkB kinase activity susceptible to rapid inhibition by 1NMPP1, were used at 6-8 months old (n = 12; 6 females). Neuromuscular transmission failure (NMTF) was estimated in diaphragm-phrenic nerve preparations following 1 hour treatment with 1NMPP1 or vehicle by assessing the difference in forces evoked by 2 min of repetitive nerve and muscle stimulation at either 10 or 75 Hz. There was no effect of 1NMPP1 on muscle contractile properties, but there was a frequency-dependent effect of 1NMPP1 treatment on the extent of NMTF. At 10 Hz stimulation, 1NMPP1 decreased the extent of NMTF compared to vehicle by 35%. At 75 Hz, 1NMPP1 increased the extent of NMTF compared to vehicle by 28%. The greater negative effect of TrkB kinase inhibition during higher frequency stimulation suggests reliance on TrkB signaling for sustained activation predominantly at higher force, more fatigable motor units which are responsible for the high forces necessary for airway clearance (i.e., coughing and sneezing).
Structural brain injury on magnetic resonance imaging in heart failure and identifying patients at high-risk.
Cereb Circ Cogn Behav
Wenyi Tang, Qing Xie, Zihong Huang +10 more
Structural brain injury characteristics in heart failure (HF) and risk factors for such injury are poorly defined.
The diagnostic value and optimal cutoff of basal luteinizing hormone for central precocious puberty in premenarcheal girls stratified by weight status.
Front Endocrinol (Lausanne)
Xin Yuan, Jing Zhang, Ying Zhang +2 more
To investigate the diagnostic value and explore optimal cutoff value of the basal luteinizing hormone (LH) level for central precocious puberty (CPP) in premenarcheal girls with different weight status, so as to provide preliminary stratified reference thresholds and a basis for reducing unnecessary gonadotropin-releasing hormone (GnRH) stimulation tests in clinical screening.
Bioactive Hydrogels with D-Amino Acid RGD Mimics: A Therapeutic Strategy for Expeditious Infected Wound Closure.
Adv Healthc Mater
Akanksha Negi, Santosh Yadav, Megha Jain +7 more
Developing biomaterials that simultaneously support tissue repair while inhibiting infection remains a critical challenge in wound-healing research. Here, a novel series of D-amino acid and D/L-hybrid analogs has been synthesized to investigate the influence of stereochemistry on wound healing and antimicrobial activity. Self-assembly into a nanofibrous network enables these peptides to form hydrogels that serve as injectable, biomimetic scaffolds for drug delivery and antimicrobials, making them ideal for advanced wound-healing applications. Molecular docking revealed the strongest binding affinity of AN2D3 peptide toward integrin αvβ3, suggesting it as a promising lead candidate for targeting αvβ3-mediated pathways in cell adhesion and proliferation. Further, these peptides are systematically evaluated in methicillin-resistant Staphylococcus aureus (MRSA)-infected Balb/c mice to assess their antimicrobial activity, mechanical integrity, and regenerative potential. Remarkably, as the D-amino acid content increased in the sequences, antimicrobial efficacy and wound-healing also improved. Among peptide sequences, AN2D3 yielded the best results, highlighting the critical role of stereochemistry in peptide-based constructs. These hydrogels were designed to resist enzymatic degradation while promoting interactions with the extracellular matrix and innate antimicrobial activity. This inversion of stereochemistry is anticipated to influence the bioactivity of the peptide hydrogels, suggesting that even subtle shifts in chirality may affect biomaterial behavior.
Antiviral efficacy of Trappin-2/Elafin against Zika virus in the human keratinocyte HaCaT cell line.
Arch Virol
Víctor Javier Cruz-Holguín, José Manuel Ulloa-Aguilar, Rocío Yazmin Benítez-Zeferino +9 more
Zika virus (ZIKV) is primarily transmitted through mosquito bites, and the skin acts as the initial site of viral entry into the host. Consequently, resident skin cells are among the first targets of infection. The epidermis, mainly composed of keratinocytes, can mount an antiviral response against arboviruses through the production of interferons, interferon-stimulated genes, cytokines, and antimicrobial peptides (AMPs), including the Trappin-2/Elafin (Tr2/E) peptide. However, the antiviral activity of Tr2/E during ZIKV infection remains poorly understood, therefore, this study aimed to investigate the antiviral activity of Tr2/E in human keratinocytes during ZIKV infection. In this study, we evaluated the permissiveness of the human keratinocyte cell line HaCaT to infection with a Mexican isolate of ZIKV and observed that these cells support productive viral infection. We then assessed whether ZIKV infection induces endogenous expression of Tr2/E. Tr2/E transcripts were detected in infected cells and showed increased expression over time post-infection, which correlated with the presence of its corresponding protein. Furthermore, we evaluated the antiviral potential of this peptide through exogenous treatment of infected keratinocytes. A significant reduction in ZIKV infection following Tr2/E treatment was observed. Collectively, these findings provide additional insight into the involvement of AMPs in the antiviral response to ZIKV infection and highlight Tr2/E as a potential antiviral factor.
Integrating GLP-1 Receptor Agonists Into Dermatology Practice: Safety and Monitoring Strategies.
Clin Dermatol
Shanthi Narla, Radhika R Narla
Glucagon-like peptide-1 receptor agonists (GLP-1RAs) have rapidly expanded beyond the treatment of type 2 diabetes mellitus (T2DM) and obesity, with increasing relevance to dermatologic practice as more patients present while receiving these therapies. This medication class now includes oral formulations including oral semaglutide and the first non-peptide oral GLP-1RA, orforglipron as well as next-generation triple agonists such as retatrutide, which demonstrated up to 24.2% body weight reduction in phase 2 trials and a favorable body composition profile, with preferential fat over lean mass loss. Although GLP-1 RAs provide substantial metabolic and weight reduction benefits, their growing use has introduced a broad spectrum of systemic and cutaneous adverse effects that dermatologists must recognize and monitor. This review summarizes the current evidence regarding the safety profile of GLP-1RAs with emphasis on dermatologic implications and interdisciplinary monitoring considerations. Common adverse effects include gastrointestinal (GI) intolerance, nutritional deficiencies, gallbladder disease, pancreatitis, and loss of lean body mass. Other rarer potential side effects include anemia, neuropsychiatric, and sexual health effects. Emerging data also suggest associations with ophthalmologic complications, skeletal fragility in older adults, and alterations in body composition that may influence cosmetic and procedural outcomes. Dermatologic adverse events include alopecia, eczematous and hypersensitivity eruptions, bullous and pustular dermatoses, acneiform eruptions, hyperhidrosis, and significant facial volume loss ("Ozempic face"). Current evidence regarding GLP-1RA use in pregnancy remains limited and evolving, with recommendations generally advising discontinuation prior to conception. Given the increasing overlap between metabolic disease management and dermatologic care, dermatologists should understand contraindications, screening strategies, nutritional monitoring, and counseling considerations associated with GLP-1RA therapy. A multidisciplinary approach involving primary care physicians, endocrinologists, ophthalmologists, dietitians, and dermatologists is essential to optimize patient safety while maintaining the substantial therapeutic benefits of these medications.
Antrodia cinnamomea extract exhibits anti-melanogenic and anti-photoaging effects: potential for cosmetic and dermatological applications.
Sci Rep
I-Hsuan Huang, Tse-Kai Fu, Yu-Ting Chou
Skin pigmentation and photoaging are major dermatological concerns, underscoring the need for safe and effective topical agents. Antrodia cinnamomea, a medicinal mushroom native to Taiwan, is well known for its hepatoprotective, anti-cancer, and metabolic benefits; however, its anti-melanogenic and anti-photoaging potential remains insufficiently characterized. In this study, we demonstrate that A. cinnamomea ethanol extract (AC-EtOH) suppresses melanin production and tyrosinase activity in α-MSH-stimulated B16F10 melanocytes by downregulating the mRNA expression of tyrosinase, TRP-1, TRP-2, and microphthalmia-associated transcription factor (MITF). AC-EtOH also inhibits α-MSH-activated PKA/cAMP/CREB signaling, further contributing to melanogenesis suppression. In skin fibroblasts, AC-EtOH protects against UV-induced photoaging by reducing the accumulation of reactive oxygen species (ROS) and attenuating the expression of matrix metalloproteinases (MMP1 and MMP3) and pro-inflammatory cytokines (IL-1β and IL-6). To improve its suitability for cosmetic formulations, polyethylene glycol (PG)-a widely used solvent-was employed to generate an A. cinnamomea extract-PG mixture (AC-PG). AC-PG retained the biological efficacy of AC-EtOH, reducing melanin production and tyrosinase activity in α-MSH-induced cells, while exhibiting low sensitization and irritation potential, as per OECD Test Guidelines 439, 492, and 442E. Collectively, these findings identify AC-EtOH as a promising natural ingredient with potent anti-melanogenic and anti-photoaging activities, supporting its potential application in cosmetic and dermatological products for skin whitening, anti-wrinkle, and anti-photoaging purposes.
Fibrillin-1 Inhibits Early Adipogenic Commitment Via αvβ3 Integrin Signaling.
J Mol Biol
Iram Fatima S Siddiqui, Valentin Nelea, Kerstin Tiedemann +3 more
Extracellular fibrillin-1 is present in many tissues, including adipose tissue. Mutations in fibrillin-1 cause Marfan syndrome, paradoxically presenting with either low body fat at younger ages or frequently increased adiposity in older individuals. The latter correlated well with data obtained with the Fbn1mgR/mgR mice, which show that global fibrillin-1 deficiency leads to sex-dependent obesity by negatively regulating early adipogenic stem cell differentiation. However, the underlying cell receptors and mechanisms remained unknown. Here, we used recombinant fibrillin-1 fragments harboring either an active RGD integrin-binding motif (rFBN1-N-RGD) or an inactive RGA motif (rFBN1-N-RGA) and tested their roles in adipogenic differentiation with primary mesenchymal progenitors isolated from bone marrow or fat tissue, as well as with adipogenic 3T3-L1 cells. rFBN1-N-RGD inhibited adipogenic differentiation in all cell models when present during the early commitment phase but not during the maturation phase, whereas the rFBN1-N-RGA control was inactive. siRNA-mediated gene silencing or pharmacologic inhibition of integrin αvβ3, but not α5β1, rescued rFBN1-N-RGD-dependent inhibition of adipogenic differentiation. Fibrillin-1 engagement of integrin αvβ3 triggered activation of the downstream focal adhesion kinase (Fak)-Src kinase (Src) signaling cascade, driving extracellular signal-regulated kinase (Erk) activation. This cascade suppressed early adipogenic transcriptional programs by restraining Cebpα and Pparγ activation, thereby maintaining progenitor cells in a committed but undifferentiated state. Pharmacological inhibition of Fak, Src and Erk restored the anti-adipogenic effect of rFBN1-N-RGD. These data establish the integrin αvβ3-Fak-Src-Erk axis as an important signaling pathway by which fibrillin-1 imposes an adipogenic checkpoint during the early adipogenic commitment phase, thereby limiting excessive differentiation.
Obestatin and Its Fragment Analog Nt8U Influence Levels of Satiety Peptides in Diet-Induced Obese Mice.
Biochimie
Shilpa Talkad Shivashankara Murthy, Uma Venkateswaran Manjappara
Imbalance in energy intake and energy expenditure due to changes in lifestyle and genetic issues results in obesity, which is a serious health problem. Appetite-inducing signals and satiety peptides in the enteroendocrine system have a definite role in the management of obesity. To regulate food intake and digestive signals, gut-derived satiety peptides act in a coordinated network to regulate appetite and metabolic homeostasis. Among these peptides, obestatin has garnered interest for its role in modulating food intake and obesity-associated lipid parameters, as demonstrated in mouse models. This study investigates the interaction among major satiety peptides in the enteroendocrine system on administration of obestatin and its fragment analog, Nt8U, for 30 days. Obestatin and Nt8U, along with a positive control, Orlistat, were administered to high-fat fed mice. Circulating Cholecystokinin-8 (CCK-8) levels increased in obestatin-treated mice but decreased with Nt8U, while Oxyntomodulin (OXM) levels increased by 20% in the obestatin group. In contrast, glucagon-like peptide-1 (GLP-1) levels were reduced following obestatin and orlistat treatment. These alterations were accompanied by significant changes in intestinal mRNA expression of the corresponding peptide precursors, suggesting altered gene expression. Long-term indicators of energy stores, including leptin and adiponectin, were reduced across all treatment groups, while insulin levels were significantly decreased in obestatin-treated mice. These hormonal changes were associated with reductions in body weight, plasma total cholesterol, and triglycerides. Collectively, these findings indicate that obestatin and Nt8U administration altered circulating satiety peptide concentrations and the intestinal expression of genes encoding gut-derived satiety hormones. These coordinated changes suggest modulation of metabolic hormone networks associated with energy balance in diet-induced obesity.
Improved Outcomes with Early Aggressive Therapy in Pediatric Pulmonary Hypertension.
Eur Respir J
Benjamin S Frank, Maurice Beghetti, Rolf M F Berger +8 more
Pediatric pulmonary arterial hypertension (PAH) carries high mortality with 81% 5-year transplant-free survival. The global Tracking Outcomes and Practice in Pediatric Pulmonary Hypertension-2 (TOPP-2; NCT02610660) registry was created to assess the treatments and outcomes of newly diagnosed pediatric PAH patients. This study evaluates real-world treatment strategies and their relationship with outcomes.
Impact of semaglutide introduction on the use of triptans: an interrupted-time series.
J Headache Pain
Noémie Roland, Heidi Sonne, Lanfranco Pellesi +4 more
Emerging evidence suggests that glucagon-like peptide-1 receptor agonist (GLP-1RA) may be associated with reduced migraine burden. We aimed to evaluate whether semaglutide for weight management initiation is associated with changes in triptan consumption.
From Weight Loss to Organ-Specific Disease Modification: A Narrative Review of Incretin-Based Therapies in Obesity-Related Cardiometabolic Disease, Chronic Kidney Disease, Metabolic Dysfunction-Associated Steatohepatitis, and Obstructive Sleep Apnoea.
Cureus
Devarsh Joshi
Incretin-based therapies have changed the management of type 2 diabetes and obesity. Semaglutide acts through the glucagon-like peptide-1 receptor, while tirzepatide combines glucose-dependent insulinotropic polypeptide and glucagon-like peptide-1 receptor agonism. These therapies were initially used mainly for glycaemic control and weight reduction, but recent evidence suggests that their role now extends into obesity-related organ disease, including atherosclerotic cardiovascular disease, heart failure with preserved ejection fraction, chronic kidney disease, metabolic dysfunction-associated steatohepatitis, and obstructive sleep apnoea. This review summarizes evidence for semaglutide and tirzepatide across obesity-related cardiometabolic, renal, and hepatic outcomes, as well as obstructive sleep apnoea-related outcomes. A targeted literature search was conducted using PubMed, MEDLINE, major journal websites, and regulatory sources from database inception to May 16, 2026. Current evidence supports clinically important benefits in selected patients, although the strength of evidence varies by condition. Important limitations include treatment durability, weight regain after discontinuation, adverse effects, peri-procedural considerations, pregnancy avoidance, cost, drug supply, and unequal access. These therapies should therefore be viewed as potential components of chronic disease management for selected patients with obesity, type 2 diabetes, or obesity-related cardiometabolic, renal, hepatic, or sleep-disordered breathing complications, rather than as short-term weight-loss interventions.
Pharmacotherapy in obstructive sleep apnoea: a clinical guide.
Sleep Breath
Shashank Shastry, John R Kimoff, Lancelot Mark Pinto
Obstructive Sleep Apnoea (OSA) is a common, yet underdiagnosed disorder, with significant health implications. Continuous positive airway pressure (CPAP) remains the reference standard and first-line therapy. However, successful CPAP usage is influenced by factors such as access, cost, tolerance, patient education, early troubleshooting, and long-term adherence, all of which can be challenging and resource-demanding. Adding therapeutic options to the armamentarium is therefore welcome. There is a need for clinicians to be abreast of all the available therapeutic options for treatment of OSA.
The P2X7 Receptor in Cancer: From Functional Receptor to Non-Functional P2X7.
Carcinogenesis
Luyao Liu, Yoshiteru Kagawa, Colin L Masters +4 more
The ATP-gated P2X7 receptors are abundantly expressed in immune cells, neurons, glial cells, and cancer cells. The P2X7 receptor performs distinct functions, depending on the extracellular ATP concentration and the duration of exposure to ATP. With brief ATP stimulation, the P2X7 receptor acts as an ion channel, and the movement of ions is associated with the regulation of cell proliferation and differentiation. Prolonged ATP exposure induces a conformational change in P2X7, allowing large molecules to pass through the membrane via the formation of macropores, thereby contributing to cell death. A novel function of P2X7 as a scavenger receptor was recently reported in the absence of both serum and ATP. However, the discovery of non-functional P2X7 in cancer reveals that this group of isoforms of P2X7 fails to form macropores upon ATP stimulation and cannot initiate ATP-induced cell death, allowing malignant cells to evade this regulatory mechanism and continue proliferating. We discuss the multifaceted functions of the P2X7 receptor in regulating diverse cell types, including cell growth, death, and clearance, and how the non-functional form of P2X7 disrupts this balance in cancer. Furthermore, the review explores the potential targeting of this aberrant isoform of P2X7 in the development of novel cancer therapies.
CCR2 deficiency protects against doxorubicin-induced cardiac dysfunction through enhanced IL12B-dependent autophagy.
Theranostics
Lizhi Hu, Li Lin, Long Chen +6 more
Doxorubicin (DOX) is a potent chemotherapeutic agent whose antitumor benefits are limited by a well-recognized, dose-dependent cardiotoxicity. While previous studies have implicated inflammatory pathways in DOX-induced cardiomyopathy (DIC), the role of CCR2 in this process remains incompletely defined. This study aims to investigate whether CCR2 deficiency confers cardioprotection against DIC and to uncover the molecular mechanisms involved.
Cholesterol enhances lysosome-autophagosome fusion for better α-synuclein clearance in GBA L444P-mutated Parkinson disease.
Cell Rep
Mingjia Chen, Fengtao Liu, Yujie Yang +13 more
Mutations in lysosomal enzyme glucocerebrosidase (GBA), the most common genetic risk factor for Parkinson disease (PD), exacerbate α-synuclein pathology through unclear mechanisms. Here, we report, in a large cohort, that GBA-mutated PD patients exhibit lower serum cholesterol levels. By introducing the most common GBA variant in our cohort, L444P, into human α-synuclein knock-in mice, we noted that the mice exhibited behavioral and molecular pathological PD features at 12 months of age. Mechanistically, lysosomal proteomics identified the loss of lysosome-cytoplasmic vesicle interactions and cholesterol-containing lipid microdomains in both PD patients and mice. Autophagic flux monitoring revealed impaired autophagosome-lysosome fusion in GbaL444P/+ neurons. Gain- and loss-of-function experiments uncovered cholesterol synthesis impairment via glycosphingolipid-reduced SREBP2 levels. Importantly, cholesterol supplementation was found to enhance the autophagic flux and mitigate α-synuclein accumulation in vitro, whereas AAV-Srebp2 delivery increased α-synuclein clearance in GbaL444P/+ mice. Our study provides animal models and mechanistic insights into GBA-associated PD and offers a therapeutic paradigm by facilitating cholesterol-associated α-synuclein autophagic clearance.