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peptide science.

GLP-1, GIP, and Glucagon Excursions During a Mixed Meal Tolerance Test in Young and Lean South Asians Versus Europids.

Diabetes Obes Metab

Carlijn A Hoekx, Lisa B D Brinkman, Robin van Eenige +6 more

South Asians exhibit an unfavourable metabolic phenotype characterized by visceral obesity, insulin resistance and dyslipidemia. While various hormones play a critical role in regulating postprandial energy metabolism, it remains unclear whether they respond differently to food intake. We aimed to compare the meal-induced excursion of incretin hormones (GLP-1 and GIP) and glucagon between South Asians and Europids.

Case report and literature review: isolated ACTH deficiency induced by combined nivolumab and trastuzumab therapy in gastric adenocarcinoma.

Front Endocrinol (Lausanne)

Liwei Shi, Jinrong Wang, Xiaohong Xie +1 more

Isolated adrenocorticotropic hormone (ACTH) deficiency (IAD) is an uncommon endocrine disorder characterised by the selective reduction or absence of pituitary ACTH secretion, resulting in secondary adrenal insufficiency while other pituitary hormone axes remain functional. The clinical manifestations of this condition are frequently non-specific, and may include symptoms such as fatigue, decreased appetite, weight loss, hypotension, and hyponatremia. These symptoms can be easily confused with those of other diseases, resulting in either missed diagnoses or misdiagnoses. Glucocorticoid replacement therapy is generally considered to provide effective symptom relief and a favourable prognosis. In recent years, the widespread use of immune checkpoint inhibitors (ICIs) in cancer treatment has resulted in a significant increase in immune-related adverse events (irAEs). Isolated ACTH deficiency has been reported as a rare yet severe endocrine-type irAE, potentially arising from immune-mediated pituitary injury. In view of the nonspecific nature of its clinical presentation, early recognition and timely intervention are of critical importance.

Neuroprotective Effects of Carnosine Against Corticosterone-Induced Depression and Memory Impairment.

Food Sci Nutr

Muneezah Elahi, Noreen Samad, Ali Irfan +4 more

Corticosterone (Crt) is reported to induce oxidative stress in experimental animals. Carnosine (Crn), a well-known dipeptide antioxidant synthesized endogenously from β-alanine and L-histidine, neutralizes oxidative stress. The current study examines the influences of Crn on Crt-induced behavioral alterations (depressive-like behaviors and cognitive performance), oxidative damage, antioxidant enzymes activity, inflammatory markers, serotonin metabolism, and histopathology in female rats. Thirty-six animals were allocated to six groups (n = 6): (i) vehicle (vh) + vh (1 mg/kg) (ii) vh + Crn (20 mg/kg), (iii) vh + Crn (50 mg/kg), (iv) vh + Crt (20 mg/kg) (v) Crt + Crn (20 mg/kg), and (vi) Crt + Crn (50 mg/kg). All respective doses were given intraperitoneally (i.p) for 2 weeks. After treatment, behavioral testing was done via the Tail suspension test (TST) for depressive-like behavior and the Morris Water Maze (MWM) for spatial memory. Crn treatment had significant effects on Crt-induced behavioral impairments, such as depressive-like behavior and cognitive dysfunction. After completing behavioral tests, the rats underwent decapitation, and the hippocampus was separated for further biochemical and neurochemical analyses. Outcomes revealed that Crn mitigates depressive-like behaviors and cognitive dysfunction. Crn reduces oxidative stress and inflammatory cytokine levels while improving antioxidant enzyme activity, restoring cholinergic and serotonergic transmission, and brain (hippocampus) morphology following Crt-administration. The in silico analyses also demonstrate its strong binding affinity with monoamine oxidases (MAO) A and B, with an energy of -7.1 and -6.7 kcal/mol, respectively. In conclusion, the present results showed that Crn possesses strong antioxidant properties and reduced Crt-induced depressive-like behavior and memory impairment due to its effective abilities as antioxidant and neuromodulator. Supplementation with Crn as a dietary component may provide protective benefits against Crt-induced depression-like behavior and memory impairment.

[Efficacy of octreotide LAR and lanreotide autogel in acromegaly assessed by SAGIT].

Rev Med Inst Mex Seguro Soc

Francisco Javier Núñez-Martínez, Alejandro de Jesús Chávez-Lárraga, Enrique Hernández-Salazar +2 more

Biochemical control has been the main objective in the treatment of acromegaly; however, GH and IGF-1 levels do not necessarily translate into clinical response, as they fail to account for the complexity of symptoms and patients' perceptions. The SAGIT instrument was developed to assist in assessing the status and evolution of the disease in patients with acromegaly and facilitate decision-making.

Evidence Gap and Challenges in the Management of Mild Pulmonary Hypertension.

JACC Asia

Jian'an Lin, Xinjian Gu, Zongye Cai

Curcumin Alleviates Bone Cancer Pain by Inhibiting Satellite Glial Cell Activity via Janus Kinase 1/Signal Transducer and Transcription 3 Pathway Activator.

Phytother Res

Xinchao Jiang, Yi Song, Mei Fang +4 more

Curcumin is the main active component of Curcuma longa L and has anti-inflammatory, antitumor, and neuroprotective properties, making it a potential candidate for bone cancer pain management. Network pharmacology, molecular docking, and molecular dynamics simulations were used to screen and validate core therapeutic targets of curcumin in bone cancer pain. An in vivo mouse model of bone cancer pain was established via intrafemoral injection of Lewis lung cancer cells. A series of in vivo assays was conducted to evaluate pain sensitivity, bone microstructure, inflammatory cytokines, pain-related neuropeptides, and protein expression levels. In silico analysis verified that curcumin has a strong binding affinity for JAK1 and STAT3. In vivo results demonstrated that curcumin dose-dependently elevated the paw withdrawal threshold and latency, as well as ameliorated bone mineral density and bone destruction. Curcumin also suppressed pro-inflammatory cytokines, substance P, calcitonin gene-related peptides, and inhibited satellite glial cell activation by blocking the JAK1/STAT3 pathway. Notably, JAK1 agonist (RO8191) co-administration markedly reversed the analgesic effects of curcumin. Curcumin targets the JAK1/STAT3 signaling pathway, inhibits satellite glial cell activation, downregulates pro-inflammatory cytokine release, and pain-related neuropeptide expression. Therefore, curcumin exerted a significant analgesic effect against bone cancer pain. Elucidating the analgesic mechanism revealed the core therapeutic targets of curcumin in treating bone cancer pain. This study provides experimental evidence for further research on bone cancer pain.

Computational phenotyping of effort-based decision-making in type-2 diabetes on and off semaglutide.

Neuropsychopharmacology

Sara Z Mehrhof, Hugo Fleming, Camilla L Nord

Motivation plays a fundamental role in human behaviour. Dopaminergic pathways have long been implicated in individual differences in motivation. Emerging evidence suggests such neural mechanisms interact with metabolic processes to coordinate energy expenditure with energy resources, thereby linking motivation with metabolic health. We ask whether a cognitive-computational index of motivation-reliably linked to neuropsychiatric symptoms-is altered in the context of type-2 diabetes and treatment with a GLP-1 agonist (semaglutide). In a pre-registered experiment, we quantified computational effort-based decision-making parameters in participants with diabetes on (N = 58) or off (N = 54) semaglutide treatment, compared to two groups of matched controls without diabetes (N = 58 each). Subjects with type-2 diabetes showed a blunted acceptance bias, a computational parameter describing the bias to accept effort for reward. This effect was not driven by neuropsychiatric comorbidity or antidepressant use. Across all participants, we found that increasing diabetes risk linearly predicted reduced acceptance bias. Participants with diabetes treated with semaglutide did not show restored motivation. Metabolic ill-health is associated with reduced acceptance bias during motivational decision-making. This blunting mirrors-but is largely independent of-neuropsychiatric motivational deficits. This suggests metabolic ill-health is accompanied by a cognitive shift towards energy conservation, potentially contributing to comorbidity between metabolic ill-health and mental illness.

Clinical Characteristics of Users of Weight Loss Drugs: Population-Based Case-Control Study.

Diabetes Obes Metab

Inger Johanne Bakken, Paz Lopez-Doriga Ruiz, Kari Furu +6 more

To investigate the clinical characteristics of weight loss drugs (WLDs) users in Norway.

Ultraviolet irradiation-induced enhancement of inflammatory potential of polystyrene nano- and microplastics and effects of dispersion on lung clearance.

Part Fibre Toxicol

Yeonjeong Ha, Jun Hui Jeon, Eunsol Bae +7 more

Microplastics are pervasive environmental pollutants that pose potential risks to human health, particularly through inhalation. Despite growing concerns, limited data exist on how environmental aging, such as ultraviolet (UV) irradiation, affects the pulmonary toxicity of inhaled nano- and microplastics. This study evaluated the influence of UV-driven surface oxidation on the inflammatory potential and lung clearance kinetics of polystyrene (PS) particles. Spherical PS particles (50, 200, and 400 nm) were synthesized, selectively oxidized by UV irradiation, and thoroughly characterized for surface chemistry and intrinsic reactive oxygen species (ROS) generation.

Endocrine Regulation of Appetite: Interactions between Gut Microbiota, Microbial Metabolites, and Appetite-related Hormones.

Horm Metab Res

Seval Arvas, Oguz Ozcelik, Yunus E Beyhan +1 more

The gut microbiota has emerged as a key endocrine modulator that shapes host appetite regulation through its metabolites and their interactions with enteroendocrine and central neuroendocrine pathways. Microbial metabolites-including short-chain fatty acids, bile acid derivatives, indole compounds, and tryptophan-derived serotonin-activate receptors such as G-protein-coupled receptor 41/43, Takeda G protein-coupled receptor 5, and Toll-like receptor 4 on enteroendocrine cells, influence the secretion of appetite-related hormones including ghrelin, leptin, glucagon-like peptide-1, peptide YY, nesfatin-1, and cholecystokinin. These hormones subsequently modulate hypothalamic circuits, particularly the NPY/AgRP and POMC/CART pathways, establishing a mechanistic link between microbial signaling and central appetite control. Ghrelin serves as the primary orexigenic hormone, whereas leptin, glucagon-like peptide-1, peptide YY, nesfatin-1, and cholecystokinin collectively exert anorexigenic effects that promote satiety and energy homeostasis. Dysbiosis disrupts receptor-mediated endocrine signaling, alters hormonal secretion, and contributes to leptin resistance, impaired glucagon-like peptide-1 responsiveness, and dysregulated appetite-key features in obesity, insulin resistance, and metabolic syndrome. This review synthesizes current mechanistic insights into the microbiota-hormone axis and highlights how microbial modulation influences endocrine appetite regulation. Understanding these interactions provides a translational framework for developing microbiota-targeted endocrine therapies aimed at restoring metabolic balance and preventing obesity and related metabolic disorders.

The GHK-Cu delays aging in Caenorhabditis elegans via coordinated regulation of mitochondrial function and activation of DAF-16/SKN-1 pathways.

Biogerontology

Huijun Wen, Keshu Zhao, Xiangjian Luo +7 more

Aging is a complex biological process characterized by progressive functional decline across tissues and increased susceptibility to age-related diseases, with oxidative stress being a key contributing factor. Glycine-Histidine-Lysine (GHK), a naturally occurring tripeptide present in human plasma and urine, possesses potent antioxidant properties; however, its broader anti-aging potential remains inadequately explored. In this study, we employed the model organism Caenorhabditis elegans to systematically investigate the anti-aging effects of GHK-Cu (GHK complexed with copper) and elucidate its underlying molecular mechanisms. Our results demonstrated that GHK-Cu significantly extended lifespan of C. elegans and ameliorated mutiple aging-related phenotypes, including enhanced resistance to oxidative and thermal stress, improved motility, pharyngeal pumping, defecation rhythm, and reduced lipofuscin/lipid accumulation. Mechanistically, GHK-Cu preserved mitochondrial function by increasing mitochondrial membrane potential, alleviating age-related mitochondrial network fragmentation, shifting mitochondrial dynamics toward fusion via regulating drp-1 and fzo-1 expression, and promoting ATP biosynthesis. Meanwhile, GHK-Cu activating DAF-16 and SKN-1 pathway, and upregulating sod-3, gst-4, gcs-1, lys-7 and lys-8. This study provides the first mechanistic evidence that GHK-Cu delays aging through coordinated regulation of mitochondrial function and activation of both DAF-16 and SKN-1 pathways. Our findings identify novel molecular targets for developing anti-aging interventions and underscore the potential of GHK-Cu's as a multifaceted geroprotective compound.

[Current and future medical treatments for metabolic dysfunction-associated steatohepatitis].

Rev Prat

Rodolphe Anty, Marwin A Farrugia

Drug treatment of metabolic dysfunction-associated steatotic liver disease (MASLD) is undergoing a revolution. The fight against cardiovascular risk factors, the optimization of the treatment of type 2 diabetes, the screening of common extra-hepatic cancers, personalized dietary measures, therapeutic physical exercise programs and the fight against a sedentary lifestyle remain fundamental to propose to all patients. For patients with metabolic dysfunction-associated steatohepatitis (MASH) and liver fibrosis (F2-F3), resmetirom is the first effective and well-tolerated drug marketed in the USA and Europe. Semaglutide or double or triple incretin receptor/glucagon receptor agonists could constitute the future cornerstone of drug management for patients with MASLD, due to the achievement of very significant weight loss (from 10 to more than 24% of the initial weight). Semaglutide has been shown to reduce cardiovascular and renal events, and has been approved for marketing in the USA, for MASH without cirrhosis. The choice of the best drug combination, the optimal prescription duration and the best drug option in the case of MASH-related cirrhosis remain to be determined.

Research Hotspots and Emerging Frontiers in Ovarian Aging: A Bibliometric Analysis (2006-2025).

Endocr Metab Immune Disord Drug Targets

Qingquan Gong, Wenhong Ma, Chao Yang +4 more

Ovarian aging has a critical impact on women's fertility and overall health. This study uses bibliometric methods to analyze the current state of research in the field of natural ovarian aging and to identify emerging trends.

Translational nanomedicine strategies for selective senescent cell clearance in aging and age-related diseases: a critical review.

Ther Deliv

Dilpreet Singh, Sankha Bhattacharya

Aging is driven by progressive cellular damage, dysfunction, and senescence, a therapeutically actionable contributor to chronic inflammation, tissue degeneration, and age-related disease. However, senolytic and senomorphic translation remains constrained by senescent-cell heterogeneity, narrow therapeutic windows, inconsistent exposure, limited tissue penetration, uncertain nanoparticle accumulation in poorly perfused aged organs, and the absence of definitive clinical efficacy. Nanomedicine should therefore be viewed not as generic drug packaging, but as a strategy to improve the senolytic index through controlled exposure, multi-step selectivity, intracellular delivery, and context-responsive release. This review critically evaluates lipid-based, polymeric, hybrid, and biomimetic nanoplatforms by asking whether they improve target engagement, functional recovery, and safety over free drugs, rather than merely increasing encapsulation efficiency or in vitro cytotoxicity. Emphasis is placed on assay-aware interpretation of quantitative claims, limitations of single-marker targeting, variability of EPR-like behavior in aging tissues, manufacturability, and regulatory readiness. Overall, nanomedicine-based senotherapy is highly promising but not yet clinically de-risked; meaningful progress will require disciplined biology-to-design integration, human-tissue validation, and rigorous benchmarking against clinically relevant outcomes.

Targeting senescence mitigates the deleterious effects of midlife obesity on neurovascular function by partially restoring blood-brain barrier integrity and neurovascular coupling.

J Cereb Blood Flow Metab

Sharon Negri, Madison Milan, Rakesh Rudraboina +17 more

Midlife obesity is a major risk factor for vascular cognitive impairment (VCI) and dementia, but the cellular mechanisms linking obesity to brain microvascular dysfunction remain unclear. Here, we show that high-fat diet (HFD)-induced obesity accelerates cellular senescence within the neurovascular unit (NVU), resulting in structural and functional microcirculatory deficits. Combining multimodal in vivo longitudinal imaging with single-cell RNA sequencing, we identify a senescence-associated transcriptional program in endothelial cells and neurons, coinciding with reduced brain microvascular density, impaired neurovascular coupling (NVC), and disruption of blood-brain barrier (BBB) integrity. These vascular abnormalities associate with cognitive decline in behavioral assays. Transcriptomic profiling further revealed cell-type-specific senescence signatures, including dysregulation of angiogenic, mitochondrial, and inflammatory pathways, which were alleviated by senescent-cell clearance. Notably, clearing p16+ senescent cells partially restored BBB integrity, improved NVC responses, and reduced neuroinflammation. Together, these findings identify cellular senescence as a mechanistic driver of midlife obesity-induced cerebrovascular and cognitive dysfunction and provide proof-of-concept that senescence-targeted therapies may preserve brain health in individuals with midlife obesity who are at risk for dementia.

High-amylose maize starch as a functional carbohydrate: Long-term regulation of glucose homeostasis following early-life intervention.

Food Res Int

Zhiqiang Xu, Lingjin Li, Li Cheng +2 more

Carbohydrate intake in early life drives long-term host metabolic homeostasis. Maternal obesity is recognized as a risk factor for metabolic disorders in offspring. High-amylose maize starch (HAMS) is a functional carbohydrate with metabolic regulatory capabilities. However, its mechanisms and potential effects in improving glucose metabolism disorders in offspring with maternal obesity during early life remain unexplored. Here, we characterized the structural properties of HAMS and assessed its structural stability during gastrointestinal digestion. Subsequently, using a high-fat diet-induced maternal obesity model, we evaluated the long-term effects of early-life HAMS supplementation (3-8 weeks) on glucose metabolism in offspring and explored the potential mechanisms, focusing on hormone secretion, pancreatic islet function, and hepatic metabolomics. HAMS supplementation significantly improved glucose metabolism disorders in offspring with maternal obesity. Mechanistically, in vitro digestion experiments demonstrated that HAMS partially escaped gastrointestinal digestion and delivered increased amounts of fermentable carbohydrates to the colon. HAMS digestion products activated intestinal L-cells, restoring maternal obesity-induced reductions in serum glucagon-like peptide-1 (GLP-1) levels. HAMS also significantly increased GLP-1R, Ngn3, and Pdx1 gene expression, promoting pancreatic β-cell neogenesis and enhancing insulin secretion. Furthermore, hepatic metabolomics revealed that HAMS intake activated insulin signaling and energy metabolism-related pathways, including the AMPK, PI3K-Akt, and FoxO signaling pathways, and modulated amino acid metabolic networks in offspring with maternal obesity. This study provides new insights for investigating the regulatory role of HAMS in glucose metabolism and indicates that HAMS may serve as an effective dietary strategy in early life to improve glucose homeostasis in offspring with maternal obesity.

Shifts in waist-to-height ratio categories within tirzepatide groups: a post-hoc analysis of SURMOUNT-1.

J Endocrinol Invest

Naveed Sattar, Beverly G Tchang, Royce P Vincent +5 more

To evaluate shifts in waist-to-height ratio (WHtR) categories among adults with obesity or overweight, with or without prediabetes, treated with tirzepatide in the SURMOUNT-1 study.

Reduced Left Atrial Reservoir Strain is Associated with Histopathologically Confirmed ANP-Amyloid Deposition.

J Am Soc Echocardiogr

Shun Nishino, Yujiro Asada, Chiharu Nishino +6 more

Isolated atrial amyloidosis is characterized by atrial natriuretic peptide (ANP)-amyloid deposition confined to the atria and has been primarily linked to atrial fibrillation. However, its relationship with atrial mechanical function remains unclear. We investigated the association between left atrial reservoir strain (LASr) and histopathologically confirmed ANP-amyloid deposition. We also explored the potential clinical implications.

Severe Short Stature and rhGH Resistance in a Child Born SGA: The Role of a Novel IGF1R Mutation, Case Report and Narrative Review.

Children (Basel)

Giovanni Luppino, Eleonora Ini', Letteria Anna Morabito +5 more

Background: Genetic causes of growth failure should be suspected in patients born small for gestational age (SGA) who fail to show postnatal catch-up growth, present with severe short stature (SS), and exhibit a poor or absent response to growth hormone (rhGH) therapy. Mutations in the insulin-like growth factor 1 receptor (IGF1R) gene are associated with impaired growth, intrauterine growth restriction (IUGR), low birth weight and/or length, and postnatal SS. Case Description: A 9-year-old boy, born SGA for birth length, was evaluated for severe SS. Common causes of SS were excluded. At 9 years and 7 months of age, his height was 112.6 cm (-3.99 SDS), weight 18 kg (-3.79 SDS), and BMI 14.2 kg/m2 (-1.8 SDS); pubertal development was Tanner stage 1. The target height was 158 cm (-2.62 SDS). Bone age was delayed by approximately one year compared with chronological age. Serum IGF-1 levels were within the upper-normal range for age. GH therapy (0.035 mg/kg/day) was initiated due to the lack of catch-up growth in an SGA subject. After three years of treatment, the height gain was only 0.5 SDS. IGF-1 levels showed a transient treatment-related increase, followed by persistent normalization during ongoing therapy. Next-generation sequencing (NGS) analysis identified novel heterozygous paternal nonsense variant in the IGF1R gene: c.3498C>G (p.Tyr1166Ter). At 12 years of age, impaired fasting glucose and reduced glucose tolerance were detected; consequently, it was decided to discontinue rhGH therapy, also in light of the IGF1R mutation and the lack of height recovery. Conclusions: This case underlines the critical role of genetic testing in the evaluation of patients born SGA. The coexistence of SGA status and an IGF1R gene mutation may provide a clear explanation for both the poor response to rhGH therapy and the increased risk of alterations in glucose metabolism. An extensive narrative review of the literature on growth outcomes and glucose metabolism abnormalities during GH treatment in SGA patients carrying IGF1R variants was also performed.

Ageing-Associated Dysregulation of Myogenic Differentiation in Inclusion Body Myositis.

J Cachexia Sarcopenia Muscle

Geert M de Vries, Willem De Ridder, Jonathan Baets

Skeletal muscle is a postmitotic tissue dependent on a complex and tightly regulated regeneration process involving numerous intracellular and extracellular factors, including myogenic regulatory factors (MRFs), cytokines and myokines. Quiescent satellite cells are activated by physiological stimuli, injury or other traumatic insults for the repair of injuries or growth of the tissue. Activation of satellite cells induces proliferation and expression of MRFs, which in turn activate myogenic differentiation transcription programmes. Transitioning into and committing to terminal differentiation are regulated by myogenin and cell cycle exit markers, notably Rb1 and p21. Differentiation is then complete with the formation of new muscle fibres which incorporate into existing fibres. Upon ageing, the efficiency of differentiation is reduced as a consequence of a loss in the physiological balance between pathways regulating satellite cell quiescence and activation, notably the Notch and Wnt pathways, and increased senescence of the satellite cell pool. Extracellular factors involved in the dysregulation of differentiation upon ageing include low-grade chronic inflammation and remodelling of the extracellular matrix by fibro-adipogenic progenitor cells, thereby negatively affecting the differentiation capacity of satellite cells, resulting in either premature differentiation or senescence. These ageing-associated alterations in muscle homeostasis appear to be amplified in inclusion body myositis (IBM), an idiopathic inflammatory myopathy that almost exclusively manifests in individuals over 45 years of age, making it a prototypical age-related muscle disease. IBM is characterised by chronic inflammation, progressive muscle degeneration and premature ageing of both muscle tissue and the satellite cell niche. Studied with immunohistochemical techniques and multi-omics, muscle biopsy tissue demonstrated increased expression of MRFs as well as increased expression of senescence and genomic stress markers. IBM primary myoblasts demonstrated premature ageing and senescence and increased activity of the Wnt pathway, though differentiation into multinucleated myotubes did not show notable aberrations in signalling pathways or differentiation efficiency. In conclusion, ageing and chronic inflammation lead to dysregulation of key pathways that, in turn, alter the capacity of satellite cells to activate and proliferate, leading to prematurely aged satellite cells that still retain their capacity to differentiate into myofibres. Though in IBM there is an increased abundance of active differentiation markers, reflecting a regenerative response to the massive, sustained muscle atrophy, senescence of the satellite cell niche may impair effective regeneration of the lost muscle tissue.