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Primary culture and characterization of human upper limb muscle satellite cells: an experimental study.
J Yeungnam Med Sci
Young-Ju Lim, Min-Jung Ma, Wansuk Son +5 more
Human muscle satellite (stem) cells (MuSCs) are essential for investigating muscle physiology, regeneration, and disease mechanisms. Primary cultures derived directly from human tissues offer a more physiologically relevant model than immortalized cell lines. However, the isolation and characterization of MuSCs from human upper limb tissues are limited. Therefore, this study aimed to establish and characterize a primary culture system for MuSCs obtained from human upper limb muscle tissue.
Regenerative Medicine: Advanced Therapy for Muscle Tissue Restoration.
Int J Mol Sci
Roman Deev, Evgeniy Kopylov, Iurii Slepov +3 more
Skeletal muscle loss resulting from traumatic injury, sarcopenia, and myopathies remains a major clinical challenge due to the limited regenerative capacity of adult muscle tissue. This review systematically examines advanced biomedical therapeutic approaches to restoring muscle mass and function, including gene therapy, microRNA, cell-based strategies, and tissue engineering. Key mechanisms of muscle histogenesis and regeneration are discussed, with emphasis on the roles of satellite cells, growth factors (IGF-1, VEGF), and transcriptional regulators. Preclinical studies demonstrate that viral and non-viral delivery of myogenic factors can enhance muscle repair, reduce fibrosis, and improve functional outcomes. However, translation to clinical practice is hindered by challenges such as immune responses, inadequate reinnervation, and the complexity of replicating native tissue architecture. Emerging strategies combining gene delivery with rehabilitation, immunomodulation, or exosome therapy show synergistic effects. Although clinical trials targeting sarcopenia and muscle defects using anti-myostatin antibodies, stem cell-derived products, and acellular scaffolds have reported modest gains in strength and lean mass, no definitive regenerative therapy has been approved. While significant progress has been made, achieving full structural and functional muscle regeneration will require combinatorial approaches that address vascularization, innervation, and the inflammatory microenvironment.
Fibro-Adipogenic Progenitor Cell Alterations in Skeletal Muscle: Pathological Dysfunction or Adaptive Reprogramming?
Int J Mol Sci
Margarita Y Sorokina, Oksana A Ivanova, Anna A Kostareva +1 more
In skeletal muscle, there are two main progenitor populations crucial for growth, maintenance, and repair: satellite cells (SCs) and interstitial cells, of which fibro-adipogenic progenitor cells (FAPs) are the best characterized fraction. However, data on how specific diseases or physiological conditions affect the biological properties of FAPs are limited. In this review we analyze data obtained with FAPs purified from skeletal muscle tissue from Duchenne muscular dystrophy (both human patients and mdx mice models), hindlimb functional unloading (rats), and type 2 diabetes (T2DM, human patients). Here we discuss how disuse/disease affect FAP's properties: the adaptive metabolic remodeling; the alterations in adipogenic differentiation in vitro; the possible role of particular subpopulations of FAPs in disease development; the role of FAPs in cell-to-cell interactions during skeletal muscle degeneration and regeneration. Current research has outlined how different physiological and pathological conditions alter FAPs' behavior, highlighting FAPs as a potential target for clinical protocols aimed at treating or mitigating skeletal muscle disorders. Future studies should clarify how FAPs govern cell-to-cell interactions during skeletal muscle degeneration and regeneration, offering critical insights for therapies targeting diverse neuromuscular diseases.
n-3 Polyunsaturated Fatty Acids and Sarcopenia: Recent Advances and Mechanistic Research.
Nutrients
Haoran Li, Wenlong Xu, Yingjia Hu +3 more
Sarcopenia is an age-related syndrome characterized by the progressive loss of skeletal muscle mass, strength, and function, significantly impairing older adults' independence and quality of life. Given their anti-inflammatory, antioxidant, and metabolic regulatory properties, n-3 polyunsaturated fatty acids (n-3 PUFAs) have emerged as a promising nutritional strategy to mitigate this muscle degeneration. This review systematically synthesizes existing evidence regarding the association between n-3 PUFAs and sarcopenia. To capture the relevant literature, we searched PubMed, Web of Science, CNKI, and Wanfang Data using a combination of subject headings and free-text terms. We supplemented primary search terms-such as "n-3 polyunsaturated fatty acids," "omega-3 fatty acids," "sarcopenia," and "muscle mass"-with mechanism-related keywords like "inflammation," "muscle satellite cells," and "oxidative stress." We also manually screened the reference lists of the included literature. Our inclusion criteria encompassed interventional studies, observational studies, and high-quality reviews, while excluding conference abstracts, duplicate publications, and studies with incomplete data. This review first outlines the established biological mechanisms linking n-3 PUFAs to the pathological progression of sarcopenia, specifically detailing how these fatty acids improve muscle satellite cell function, suppress inflammation and oxidative stress, and ameliorate metabolic disorders. Next, we critically evaluate recent clinical studies and reviews, analyzing sources of study heterogeneity such as variations in sample size, intervention dose and duration, outcome measures, and baseline participant characteristics. We also highlight current research hotspots-including specialized pro-resolving mediators (SPMs), the gut-organ axis, combined interventions, and precision nutrition strategies-while emphasizing the functional differences between EPA and DHA to guide future intervention designs. Current evidence indicates that while n-3 PUFA supplementation can improve muscle strength and physical performance in older adults, its effects on muscle mass remain inconsistent. Addressing key research gaps, particularly the lack of standardized core outcome measures and unclear dose-response relationships, is critical. Ultimately, future research must prioritize developing high-bioavailability formulations, conducting personalized trials based on baseline n-3 PUFA status, and deepening investigations into inter-organ networks to translate these nutritional insights into effective sarcopenia prevention and management strategies.
Retrospective Comparative Study of Oral Versus Subcutaneous Semaglutide in Patients with Type 2 Diabetes Mellitus.
Int J Mol Sci
Barbara Toffoli, Matteo Michieletto, Stella Bernardi +1 more
Semaglutide represents a unique therapeutic option for patients with type 2 diabetes mellitus (T2DM), being the first and currently only glucagon-like peptide-1 receptor agonist (GLP-1RA) available in both subcutaneous and oral formulations. This study aimed to compare the effectiveness of oral versus subcutaneous (sc) semaglutide on metabolic parameters and cardiovascular risk factors in T2DM patients. This is a retrospective real-world study including adult patients with T2DM taking oral or sc semaglutide followed at the ASUGI Diabetes Center. We analyzed data from 434 patients (median age 70 years, diabetes duration 13 years), treated with oral (n = 232) or sc (n = 202) semaglutide. The oral formulation had a higher discontinuation rate. Among these patients, 130 patients in the oral group and 145 in the sc group had an 18-month follow-up. When comparing these groups, patients taking sc semaglutide had a significantly higher baseline BMI. However, multivariate linear regression models suggested that both formulations were comparably effective in reducing HbA1c and BMI, with baseline values being the primary predictors of response. To address BMI imbalances, propensity score matching was performed, identifying 55 matched pairs. Both oral and sc semaglutide reduced HbA1c and BMI and there were no significant differences in the median change in HbA1c and BMI between groups. Interestingly, oral semaglutide was associated with a significantly greater reduction in diastolic blood pressure compared to the sc formulation. Furthermore, concomitant therapy with SGLT2 inhibitors significantly enhanced the reduction in total and LDL cholesterol. Oral and subcutaneous semaglutide show comparable effectiveness in lowering HbA1c and BMI in a real-world setting.
Evaluation of the Efficacy of Semaglutide Dose Escalation in Reducing HbA1c Levels and Insulin Dose in Type 2 Diabetes Patients: Real-World Semaglutide Data from Türkiye, SEMA-TR Study.
J Clin Med
Hilmi Erdem Sumbul, Bektas Isik, Ahmet Gazi Mustan +16 more
Background: Several studies have demonstrated that adding semaglutide to the treatment of patients with type 2 diabetes mellitus (T2DM) reduces insulin requirements and glycated hemoglobin (HbA1c) levels. This study aimed to investigate real-world evidence for the effects of semaglutide dose escalation on HbA1c, body weight, dyslipidemia, and insulin dose reduction in patients with T2DM in the Cukurova region of Türkiye. Methods: This retrospective cohort study enrolled 500 patients (255 male, 245 female; mean age 56.1 ± 10.8 years) who initiated semaglutide therapy for T2DM between 2024 and 2025. Patients were grouped according to their maximum semaglutide dose: 0.25 mg (Group I), 0.50 mg (Group II), and 1.00 mg (Group III). The primary endpoint was the change in HbA1c from baseline to end of study (30 weeks) across semaglutide dose escalation groups. Secondary endpoints included changes in body weight, frequency of insulin dose reduction, and effects on lipid parameters. Results: A total of 117 patients (23.4%) discontinued semaglutide therapy, while 383 patients (76.6%) completed the study. The primary endpoint revealed a mean HbA1c reduction of -1.03 ± 0.35% from baseline to end of study (95% CI 0.99-1.07; t = 58.644; p < 0.001). Reductions in HbA1c increased progressively from Group I to Group III (HbA1c: -0.72 ± 0.28, -1.02 ± 0.26, -1.27 ± 0.34%). Insulin dose reduction frequency increased significantly from Group I to Group III (40%, 41%, and 51%, respectively; p = 0.010), with a statistically significant difference only between Group I and Group III. At the end of follow-up, rates of hypoglycemic episodes and gastrointestinal (GI) adverse events were similar across groups. Conclusions: In a real-world population from the Cukurova region of Türkiye, semaglutide dose escalation in T2DM patients achieved clinically meaningful glycemic control, body weight reduction, LDL-cholesterol lowering, and a significant increase in insulin dose reduction frequency, without a significant increase in GI adverse events.
Nutrition-First Support for GLP-1 and Dual Incretin Therapy in Obesity: A Practical Framework for Dietary Management, Symptom Tolerability, and Long-Term Weight Maintenance.
Nutrients
Raynier Zambrano-Villacres, Martín Campuzano-Donoso, Claudia Reytor-González +6 more
Glucagon-like peptide-1 receptor agonists (GLP-1RAs) and dual glucose-dependent insulinotropic polypeptide (GIP)/GLP-1 receptor agonists have transformed obesity treatment, producing substantial weight loss during active therapy. However, real-world effectiveness may be limited by gastrointestinal adverse events, reduced dietary intake, fat-free mass loss as part of total weight reduction, and weight regain after discontinuation.
GLP-1RA- and Incretin-Based Therapies Within Lifestyle Interventions for Adults with Overweight or Obesity: A Systematic Review and Meta-Analysis.
Nutrients
Alejandro Bruna-Mejias, Juan José Valenzuela-Fuenzalida, Gustavo Oyanedel +5 more
Glucagon-like peptide-1 receptor agonist (GLP-1RA)- and incretin-based therapies are now central to obesity management. Their clinical value, however, should be interpreted beyond total weight loss, because changes in fat mass, lean mass, physical function, and cardiometabolic risk may depend on the accompanying dietary, behavioral, and exercise co-interventions. This systematic review and meta-analysis evaluated GLP-1RA- and incretin-based therapies delivered within lifestyle interventions in adults with overweight or obesity.
GLP-1 Receptor Agonists and Dual GIP/GLP-1 Receptor Agonists in Children and Adolescents with Obesity: Clinical Outcomes and the Impact of Nutritional and Behavioral Co-Interventions-A Systematic Review.
Nutrients
Dominika Myśliwczyk, Krzysztof Ksawery Gofron, Andrzej Wasilewski +2 more
Introduction: Glucagon-like peptide-1 receptor agonists (GLP-1 RAs), originally developed for the treatment of type 2 diabetes (T2D), are increasingly used for the management of overweight and obesity in children and adolescents. However, the impact of concomitant lifestyle interventions, which vary in scope, structure, and intensity, remains unclear. Methods: A systematic search of PubMed, Scopus, and ClinicalTrials.gov was conducted from April to December 2025 (last update: 12 December 2025), in accordance with the PRISMA 2020 statement. Randomized and observational studies including patients aged 6-19 years with overweight or obesity, with or without T2D, treated with GLP-1 RAs or dual GIP/GLP-1 agonists, were included. Anthropometric outcomes, metabolic parameters, and the scope and structure of concomitant nutritional and behavioral interventions were assessed. Results: Fifteen studies (12 interventional [RCT/non-RCT] and 3 observational), including 1448 participants, were analyzed: liraglutide (n = 6), exenatide (n = 5), semaglutide (n = 1), dulaglutide (n = 1), tirzepatide (n = 1), and lixisenatide (n = 1). Intervention duration ranged from 6 to 68 weeks. Reported BMI reductions varied across studies and pharmacological agents, with semaglutide trials reporting reductions of up to -16.1%. Lifestyle interventions were heterogeneously reported, ranging from general dietary advice to structured, multidisciplinary programs including nutritional counseling, physical activity, and behavioral or family support. Due to heterogeneity in study design and reporting, the independent contribution of lifestyle interventions could not be determined. Conclusions: Available evidence suggests that GLP-1 RAs may represent an effective therapeutic option for children and adolescents with obesity and metabolic disorders. However, available evidence is largely derived from studies incorporating inconsistently reported lifestyle interventions, limiting the ability to disentangle pharmacological and lifestyle effects. Standardized reporting and studies specifically designed to assess their independent and combined effects are needed. Future research should standardize the reporting of lifestyle protocols (e.g., using TIDieR), incorporate validated measures of eating behavior, food preferences, and dietary intake, and use designs (e.g., factorial or stratified randomization of lifestyle intensity) that allow for the pharmacological and behavioral contributions to be quantified separately. This review highlights a critical and previously underexplored methodological gap regarding the structure and reporting of lifestyle co-interventions in pediatric GLP-1 trials.
Intrinsic and extrinsic regulators of cancer dormancy and awakening.
J Natl Cancer Cent
Jingwei Zhang, Md Imtiaz Khalil, Ranjan Mishra +3 more
Metastatic relapse is frequently driven by dormant disseminated tumor cells (DTCs) that previously evaded initial therapy, disseminated to distant tissues, entered into a non-proliferative state termed dormancy, and later reawakened to reinitiate active proliferation and the outgrowth of macroscopic metastases. Cancer dormancy manifests itself in two principal forms: cellular dormancy, characterized by the reversible, proliferative quiescence of individual cells, and tumor mass dormancy, defined by a balance between proliferation and compensating cell death. Dormant cells are notably resistant to conventional therapies and immune-mediated clearance, yet retain viability and the potential to re-enter the active cell cycle. The present review focuses on dormancy of DTCs residing in distant tissues and highlights recent advances in our understanding of both cell-intrinsic and -extrinsic regulators of cancer dormancy. Key cell-autonomous mechanisms include ERK/p38 signaling ratios, epithelial-mesenchymal plasticity, and Wnt signaling. At the same time, signals received by dormant DTCs from the adjacent tissue microenvironment-such as TGF-β family cytokines, immune surveillance, and other stromal interactions-induce and sustain dormancy. Importantly, emerging evidence suggests that microenvironmental conditions, including inflammation and aging, can trigger the awakening of dormant DTCs, leading to metastatic outgrowth. We review these evolving insights into the molecular and environmental control of cancer dormancy and awakening, underscoring their clinical relevance and therapeutic potential in preventing metastatic recurrence.
Glymphatic system impairment in neurological disorders: potential mechanisms and therapeutic targets.
Mol Biomed
Nan-Nan Wang, Zhi-Jun Liu, Yong Wang +2 more
The glymphatic system is a brain-wide metabolic clearance pathway, orchestrating the removal of neurotoxic wastes via glial-dependent perivascular networks. Mediated by polarized aquaporin-4 (AQP4) channels on astrocytic end-feet, this macroscopic system drives the convective exchange of cerebrospinal fluid (CSF) and interstitial fluid (ISF), establishing a functional coupling between the central nervous system (CNS) and the adaptive immune system. Emerging evidence highlights that glymphatic dysfunction act as both a consequence and a driver of numerous neurological disorders. Neurological pathologies, including neuroinflammation and gliovascular remodeling, compromise the structural and functional integrity of glymphatic architectures. Conversely, glymphatic dysfunction exacerbates neurotoxic wastes accumulation, accelerates disease progression, and perpetuates a pathological positive-feedback loop. Despite growing recognition of this bidirectional relationship, the precise mechanisms remain incompletely understood, and targeted therapeutic strategies are still lacking. In this review, we map the functional architecture of this pathway, from periarteriolar CSF influx to perivenous efflux, and dissect its dependence on critical modulators including sleep-wake rhythms, arterial pulsatility, and aging. Furthermore, we explore novel therapeutic interventions, ranging from AQP4-targeted pharmacological modulation to non-invasive physical approaches, and evaluate their potential to shift clinical paradigms from symptomatic management to disease modification.
Aging Slows Maximum Shortening Velocity and Reduces Peak Power Output of Rat Diaphragm Muscle.
J Appl Physiol (1985)
Genesis Hernandez-Vizcarrondo, Matthew J Fogarty, Humzah Abdulkader +3 more
Sarcopenia is the age-related atrophy and weakening (decrease in force per cross-sectional area) of muscle fibers. In rat diaphragm muscle (DIAm), sarcopenia primarily affects type IIx/IIb fibers that generate greater specific force, have the fastest maximum shortening velocities (Vmax), but display greater fatigue with repeated activation. We hypothesized that because of the selective effect of sarcopenia on type IIx/IIb DIAm fibers, Vmax and peak power output of the DIAm decreases in old age, while endurance during repetitive isovelocity shortening is unaffected. Mid-costal DIAm strips were excised from 6-month (n=8; 4 female and 4 male) and 24-month (n=8; 4 female and 4 male) Fischer 344 rats. The DIAm was supramaximally stimulated using platinum plate electrodes to measure mechanical and endurance properties at 26oC. In 24- compared to 6-month old rats, maximum specific force of the DIAm decreased by ~35%, Vmax slowed by ~20%, and peak power output was reduced by ~35%. During repetitive isovelocity (~30% Vmax; approximating peak power output) contractions, endurance (the period during which power output was sustained) of the DIAm was not different between 6- and 24-month rats. The changes in DIAm mechanical properties corresponded to an age-related decline in the cross-sectional area of type IIx/IIb muscle fibers (~35%). We conclude that age-related atrophy of type IIx/IIb DIAm fibers underlies the changes in mechanical properties of the DIAm, which would only impact more forceful expulsive airway clearance and voiding behaviors of the DIAm. The resilience of type I and IIa DIAm fibers with aging ensures that force generation and endurance required for breathing is sustained in old age.
Comparative effects of sacubitril/valsartan versus enalapril on QRS duration and cardiac function in heart failure patients undergoing left bundle branch area pacing.
Pak J Pharm Sci
Rui Wang, Cuijun Hao, Zhiqin Fang +2 more
Left bundle branch area pacing (LBBaP) has emerged as a physiological pacing strategy for cardiac resynchronization therapy in patients with heart failure (HF) and left bundle branch block (LBBB). However, evidence comparing different pharmacological regimens following LBBaP implantation remains limited.
Complex CTO Revascularization in Patients with Ischemic Heart Failure and Reduced Ejection Fraction: An Illustrative Case Series.
J Clin Med
Ioana Paula Blaj-Tunduc, Mihnea-Traian Nichita-Brendea, Vlad-Victor Babes +2 more
Background/Objectives: Revascularization of chronic total occlusions (CTO) in patients with heart failure and reduced ejection fraction (HFrEF) remains controversial, as randomized trials have not demonstrated a clear prognostic benefit. Methods: We present an imaging-guided case series of patients with ischemic HFrEF who underwent CTO percutaneous coronary intervention (PCI) following myocardial viability assessment using single-photon emission computed tomography (SPECT). Contemporary antegrade and retrograde techniques were employed. Results: At 6- and 12-month follow-ups, all patients demonstrated marked improvement in NYHA (New York Heart Association) functional class, significant reductions in NT-proBNP (N-terminal pro-brain natriuretic peptide) levels, and substantial improvement in quality of life assessed by the Minnesota Living with Heart Failure Questionnaire (MLHFQ). These benefits occurred despite only modest improvement in left ventricular (LV) ejection fraction (EF) and limited reverse remodeling. SPECT enabled identification of viable but ischemic myocardium, supporting individualized revascularization decisions. Conclusions: In selected high-risk patients with ischemic HFrEF, CTO-PCI was associated with meaningful clinical and biomarker improvement independent of substantial EF recovery. Careful patient selection, incorporating myocardial viability assessment, may refine individualized clinical decision-making in selected patients. These findings support an imaging-guided approach and warrant further prospective evaluation.
Sacubitril/Valsartan Improves Functional Capacity and Reverses LV Remodeling in Obese Patients with Hypertrophic HFpEF: A Randomized Open-Label Study.
J Clin Med
Artem Ovchinnikov, Alexandra Potekhina, Anastasiya Shchendrygina +5 more
Background: Heart failure with preserved ejection fraction (HFpEF) has multiple phenotypic manifestations with heterogeneous treatment responses. Objective: To evaluate the effect of sacubitril/valsartan (Sac/Val) on functional capacity and cardiac remodeling in overweight/obese HFpEF patients with concentric left ventricular hypertrophy (LVH). Methods: Sixty-one overweight/obese HFpEF patients (body mass index ≥ 25 kg/m2) with hypertensive LVH (LV mass index ≥ 115 g/m2 for men or ≥94 g/m2 for women) were randomized to Sac/Val (100-400 mg a day; n = 30) versus the usual care group (n = 31) for 6 months. Changes in six-minute walk test distance (6MWTD) were the primary outcomes. Secondary outcomes included changes in echocardiographic parameters of cardiac structure and function, and N-terminal pro-brain natriuretic peptide (NT-proBNP). Results: After 6 months of Sac/Val therapy, 6MWTD increased, and E/e' ratio, LV mass index, LA volume index, and NT-proBNP levels decreased compared with the usual care group (p < 0.05 for all). Conclusions: In overweight/obese patients with HFpEF and LVH, Sac/Val significantly improved functional capacity and reduced LV mass and filling pressure compared with standard medical therapy.
Expression and Correlation Analysis of Neuropeptide Family Members in the Peripheral Blood of Patients with COVID-19.
Curr Pediatr Rev
Hong Wei Li, Shang Zhi Wu, Si Xiang Tang +5 more
The purpose of this article is to investigate the expression of neuropeptide family members and their correlation with inflammatory indicators in the peripheral blood of children infected with COVID-19.
Lentiviral GLP-1 gene therapy elicits developmental stage-dependent β-cell regeneration in diabetic rats.
J Mol Med (Berl)
Ezgi Erbasan, Melike Aliciaslan, Fulya Erendor +4 more
Pancreatic β-cell differentiation and regenerative capacity differ markedly between developmental stages, with the neonatal pancreas exhibiting high plasticity that enables ongoing progenitor- and ductal-derived β-cell formation, whereas the adult pancreas demonstrates limited neogenic potential. Glucagon-like peptide-1 (GLP-1) promotes β-cell survival, proliferation, and differentiation; however, its developmental stage-specific effects on β-cell regeneration are not fully understood. To investigate this, we generated a third-generation HIV-based lentiviral vector encoding native GLP-1 (LentiGLP-1) under the control of cytomegalovirus (CMV) promoter using the Multisite Gateway® recombination cloning system. The vector's ability to modulate β-cell differentiation and proliferation was subsequently assessed in neonatal and adult diabetic rat models. Type 2 Diabetes (T2DM) was induced in neonatal rats by administering low-dose streptozotocin (STZ), exploiting the intrinsic plasticity of the developing pancreas, whereas in adult rats, a high-fat diet combined with low-dose STZ was used. LentiGLP-1 administration markedly promoted differentiation of ductal and progenitor cells into insulin-producing β-cells in neonatal rats, accompanied by enhanced β-cell proliferation, demonstrating effective engagement of developmental plasticity. In adults, LentiGLP-1 partially restored β-cell populations through activation of residual progenitors and stimulation of replication in existing β-cells, improving glycemic control and insulin sensitivity. Notably, acinar cells did not contribute to β-cell generation in either neonatal or adult models. These results indicate that GLP-1 exerts developmentally regulated effects on β-cell differentiation, facilitating neogenesis in neonates and partially restoring regenerative capacity in adults. Long term GLP-1 expression, thus represents a promising strategy to restore β-cell mass by proliferation and differentiation, providing insight into its therapeutic potential for diabetes.
Benefits of Incretin Therapy on Ovarian Function: A Scientific Literature Review.
Int J Mol Sci
Sandro La Vignera, Rosita A Condorelli
Incretin-based therapies, particularly glucagon-like peptide-1 receptor agonists (GLP-1 RAs), have emerged as potentially promising therapeutic agents for improving ovarian function, especially in women with polycystic ovary syndrome (PCOS) and obesity-related reproductive dysfunction. This comprehensive review synthesizes evidence from 30 highly relevant studies examining the mechanisms of action, clinical outcomes, and safety profile of incretin therapies on ovarian function. The evidence suggests that GLP-1 RAs may exert beneficial effects through multiple molecular pathways, including FOXO1 signaling, modulation of steroidogenesis, and enhancement of insulin sensitivity, although most mechanistic data derive from animal models and in vitro studies without validation in human ovarian tissue. Clinical outcomes from randomized controlled trials and meta-analyses show improvements in menstrual regularity, hormonal profiles, and spontaneous conception rates, though evidence certainty is limited by small sample sizes, short duration, high heterogeneity, and restriction to overweight/obese populations. While preliminary safety data regarding inadvertent early pregnancy exposure are reassuring, animal studies suggest potential dose-dependent risks that warrant careful consideration. Importantly, GLP-1 RAs are not currently approved or guideline-recommended for fertility restoration, and substantial uncertainty remains regarding long-term reproductive safety, optimal patient selection, and clinical guidelines. This review provides a balanced synthesis of current evidence and identifies critical gaps requiring further investigation before routine clinical use can be recommended.
Differential Modulation of Postprandial Glycemic, Incretin, and Satiety Responses by Low-Digestible Carbohydrates in Humans: An Exploratory Investigation.
Nutrients
Jinsoo Noh, Hye Rim Kim, Jungsook Han +6 more
Effective postprandial glycemic regulation is essential for preventing metabolic disorders such as type 2 diabetes. While pharmacological interventions like GLP-1 (Glucagon-Like Peptide-1) receptor agonists are effective, dietary strategies using low-digestible carbohydrates (LDCs) may offer a sustainable and complementary approach.
Impact of the Cosecretion of Cortisol on Surgical Outcomes and in the Urinary Steroid Profile in Primary Aldosteronism.
Endocr Pract
Marta Araujo-Castro, Gregori Casals, Jessica Goi +9 more
To analyze if there are differences in the urinary steroid profile before and after cosyntropin stimulation and in the surgical outcomes between patients with primary aldosteronism (PA) with associated mild autonomous secretion of cortisol (MACS) (MACS-PA) and those without it (only PA).