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Clinical effect of uterine artery embolization combined with curettage in the treatment of cesarean scar pregnancy.
Pak J Med Sci
Tao Zhang, Jihong Zhu, Miao Li +3 more
To observe the clinical effect of uterine artery embolization combined with curettage in the treatment of cesarean scar pregnancy(CSP).
Real-World Evidence of the Effectiveness and Safety of Biosynthetic Semaglutide in Type 2 Diabetes: A Multicentre Study From Pakistan.
Diabetes Obes Metab
Arshad Hussain, Muhammad Umar Wahab, Saleem Qureshi +7 more
To evaluate the real-world effectiveness, safety and patient-reported outcomes of biosynthetic semaglutide in adults with type 2 diabetes mellitus (T2DM) receiving routine outpatient care in a cost-constrained setting.
GLP-1 Receptor Agonists and the Ocular Surface: A Narrative Review of Restoration, Remodeling, and Clinical Implications.
Ophthalmol Ther
Henry Bair, Molly Orlick, Zeba A Syed
Glucagon-like peptide 1 receptor agonists (GLP-1RAs) have become a recurring topic in ophthalmology, yet most reviews emphasize posterior segment and neuro-ophthalmic disease while giving comparatively little attention to the ocular surface. In this review, we frame the relevant target not as isolated anterior structures but as a proposed metabolic surface unit composed of the lacrimal gland, tear film, conjunctiva, meibomian glands, corneal epithelium, corneal nerves, and the periocular tissues that support lid-globe function, and we argue that current evidence is best understood as restoration versus remodeling. Preclinical work provides the clearest biologic rationale: liraglutide studies have reported reduced lacrimal gland inflammation and fibrosis, and improved tear secretion, corneal epithelial migration, and nerve regeneration, while a semaglutide study in aged mice suggests lacrimal structural rescue through attenuation of senescence-associated inflammatory, oxidative, and fibrotic programs. Human evidence remains limited and largely observational, with retrospective diabetic cohorts showing lower rates of dry eye disease and superficial keratitis and a small clinical study showing better Schirmer testing and tear breakup time in GLP-1RA users. At the same time, emerging oculoplastic and imaging studies, particularly from obesity and weight loss populations, suggest periocular volume loss, brow descent, and dermatochalasis which may alter lid support, blink mechanics, and tear distribution. For anterior segment clinicians, the practical implication is that GLP-1RA exposure should prompt phenotype-based assessment of both ocular surface status and periocular geometry, although these recommendations remain expert extrapolations rather than guideline-level evidence. Current data are therefore consistent with a dual thesis: GLP-1RAs may be associated with biologic restoration at the lacrimal-corneal-neural axis and with structural remodeling of the periocular scaffold, although direct mechanistic support is presently stronger for the former than for the latter.
GLP-1 receptor agonists in pediatric obesity and diabetes: a systematic review of efficacy, metabolic effects, and safety.
Diabetes Res Clin Pract
Ashraf T Soliman, Fawzia Alyafei, Ahmed Khalil +4 more
Childhood obesity and youth-onset type 2 diabetes mellitus (T2DM) are increasing, highlighting the need for effective treatments beyond lifestyle intervention and metformin. This review systematically evaluated the efficacy and safety of glucagon-like peptide-1 receptor agonists (GLP-1 RAs) in children and adolescents with obesity or T2DM. PubMed-indexed studies published from 2000 to 2025 were reviewed, including seven pivotal randomized controlled trials and six meta-analyses involving 901 participants aged 6 to < 18 years. Semaglutide 2.4 mg/week produced the greatest BMI reduction in adolescents with obesity, followed by liraglutide 3.0 mg/day, which also improved BMI SDS in adolescents and younger children. In youth-onset T2DM, liraglutide 1.8 mg/day and dulaglutide significantly improved HbA1c compared with placebo. Weight-reducing agents also improved insulin resistance and modestly reduced triglycerides, while LDL-cholesterol changes were minimal. Gastrointestinal adverse events, mainly nausea and vomiting, were the most frequent and were generally transient and dose dependent. No significant adverse effects on linear growth or pubertal progression were reported. GLP-1 RAs are effective adjuncts for pediatric obesity and T2DM, but longer-term studies are needed to assess cardiovascular safety, bone health, and growth outcomes.
Plasma cyclophilin a as a novel predictor of major adverse cardiac events in patients with acute myocardial injury cohort study.
BMC Cardiovasc Disord
Chaopu Zhang, Wei Zhong, Xiang Tang +1 more
Cyclophilin A (CypA) is a multifaceted immunophilin implicated in cardiovascular disease; however, its predictive value for Major Adverse Cardiac Events (MACEs) after acute myocardial injury remains poorly defined.
A Case of Transient ACTH and Cortisol Suppression Caused by Dexamethasone Mouthwash during Immune Checkpoint Inhibitor Treatment.
Intern Med
Yosuke Aoyama, Yurie Haruyama, Yukinori Ozaki +2 more
Immune checkpoint inhibitors (ICIs) can cause endocrine adverse events, including isolated adrenocorticotropic hormone deficiency (IAD). We report a case of transient ACTH and cortisol suppression mimicking ICI-induced IAD during pembrolizumab therapy for metastatic triple-negative breast cancer. A 59-year-old woman developed low ACTH and cortisol levels while receiving pembrolizumab in combination with nab-paclitaxel. ICI-related IAD was initially suspected. However, her hormone levels normalized after the discontinuation of dexamethasone mouthwash used for oral mucositis. These findings suggest the transient suppression of the hypothalamic-pituitary-adrenal axis due to exogenous steroid exposure. Clinicians should consider steroid-containing mouthwashes as a potential cause of adrenal axis suppression during ICI therapy.
Associations of stress hormones, autonomic function, and endothelial function in patients with diabetes.
Endocr J
Takanobu Saheki, Keisuke Takahashi, Eri Harada +5 more
Endothelial dysfunction is an early feature of diabetic vascular injury. Stress-induced activation of the hypothalamic-pituitary-adrenal (HPA) axis, together with autonomic imbalance, may contribute to endothelial dysfunction. However, its clinical relevance in diabetes remains to be fully elucidated. We retrospectively analyzed 60 patients with diabetes who underwent both flow-mediated dilation (FMD) of the brachial artery and the coefficient of variation of the R-R interval (CVRR) measurements. The primary objective was to examine the association between FMD and stress-related hormones, including adrenocorticotropic hormone (ACTH) and cortisol. The secondary objective was to evaluate the association with autonomic function (CVRR) and other clinical variables. Mean FMD was 5.10 ± 2.32%. FMD correlated inversely with ACTH (r = -0.41, p = 0.0015) and cortisol (r = -0.39, p = 0.0024), and positively with CVRR (r = 0.49, p < 0.001). These relationships were stronger in patients with BMI ≥27 kg/m2, among whom the correlation between FMD and ACTH was particularly pronounced (r = -0.68, p = 0.0007). No significant associations were found between FMD and hemoglobin A1c or other lipid parameters. Given the cross-sectional design, these findings indicated associations rather than causality. Our results suggest that the HPA axis activity and autonomic function may be associated with endothelial dysfunction in diabetes, particularly in individuals with a higher BMI. This study was registered in the UMIN Clinical Trials Registry (UMIN-CTR; UMIN000060540).
Activation of the nucleus nuclear factor erythroid 2-related factor 2ghrelin/growth hormone secretagogue receptor 1a signaling by Yueju pill confers cardioprotective and antidepressant effects.
J Tradit Chin Med
Jing Yunjia, Y E Zhaoyi, Zhu Yan +6 more
To investigate the efficacy and mechanistic foundations of the Traditional Chinese Medicine Yueju pill (YJP, ) for treating the complex comorbidity of heart failure and depression.
Neurotherapeutic roles of the protective arm of the renin-angiotensin system: from inflammation to cognitive rescue.
Mol Biol Rep
Amirali Ebrahimbabaei, Ava Soltani Hekmat, Kazem Javanmardi
The renin-angiotensin system (RAS), traditionally recognized for its role in regulating blood pressure and fluid homeostasis, is increasingly understood to exert important effects across multiple organ systems, including the central nervous system (CNS). A local brain RAS contributes to neurovascular regulation, inflammation, oxidative stress, synaptic plasticity, and cognitive function. This review critically summarizes the neurotherapeutic relevance of the protective RAS arm, particularly the angiotensin-converting enzyme 2 (ACE2)-angiotensin-(1-7)-Mas receptor axis, the angiotensin II type 2 receptor (AT2R), and the alamandine/Mas-related G protein-coupled receptor D (MrgD) pathway. Experimental evidence suggests that these pathways may counterbalance angiotensin II type 1 receptor signaling by reducing neuroinflammation, oxidative injury, vascular dysfunction, and neuronal loss in models of ischemic stroke, Alzheimer's disease, Parkinson's disease, and multiple sclerosis. The strongest evidence remains preclinical, with most data derived from cell culture and animal models, whereas human evidence is still indirect and largely based on observational or early translational studies of RAS-modifying drugs. Important uncertainties remain regarding blood-brain barrier penetration, receptor-specific signaling, disease-stage dependency, systemic vascular effects, and reproducibility across models. Therefore, protective RAS signaling should be considered a promising but still exploratory therapeutic framework rather than an established treatment strategy for neurological disease. Future work should prioritize selective brain-penetrant agonists, validated biomarkers of central RAS activity, and rigorously designed clinical trials to determine whether modulation of ACE2-angiotensin-(1-7)-Mas, AT2R, or alamandine/MrgD signaling can produce clinically meaningful neuroprotection.
[The role of obesity and weight reduction in obstructive sleep apnea].
Orv Hetil
Gellért Horváth, Sophia Christine Berner, Anna Boglárka Bardóczi +3 more
Obesity plays a central role in the pathomechanism of obstructive sleep apnea and is strongly associated with the severity of sleep-disordered breathing. Weight reduction in obese patients has been shown to decrease the apnea-hypopnea index (AHI), improve sleep architecture, and reduce cardiometabolic risk. However, traditional, specialty-specific models of care do not address sleep and metabolic disorders in an integrated manner, and weight management often receives less emphasis in obstructive sleep apnea care compared with positive airway pressure (PAP) therapy. Incretin-based therapies - particularly glucagon-like peptide-1 (GLP1) receptor agonists and dual GLP1/glucose-dependent insulinotropic polypeptide (GIP) receptor agonists - have demonstrated promising results in the treatment of obesity, thereby generating growing interest in their potential role in obstructive sleep apnea management. Based on an analysis of randomized clinical trials, our review indicates that GLP1/GIP receptor agonist therapy not only promotes weight loss but also alleviates sleep-disordered breathing in obstructive sleep apnea, as reflected by reductions in AHI. An additional benefit of weight loss is the concurrent reduction in cardiometabolic risk among obese patients, alongside the improvement in obstructive sleep apnea severity. Collectively, the combined application of GLP1/GIP receptor agonist pharmacotherapy and PAP therapy may represent a novel, comprehensive, and effective therapeutic approach for the management of obstructive sleep apnea. As the management of obesity requires consideration of multiple somatic, psychological, and lifestyle-related factors, the success of a multidisciplinary sleep-metabolic program depends on the coordinated involvement of relevant specialists (pulmonologists, internists, dietitians, psychologists, and physiotherapists) with clearly defined roles and responsibilities. Further studies are needed to evaluate the effectiveness of integrated sleep-metabolic programs and to determine their potential clinical benefits. Orv Hetill. 2026; 167(26): 1011-1017.
Early life adversity influences brain development through neuroendocrine, immune, and microbiota-related mechanisms: A review.
Endocr Regul
Peter Vargovic, Jana Osacka, Lubica Horvathova +7 more
The early life experiences have an important impact on the development of the brain and behavior and early life adversities (ELA) may affect several biological systems including the hypothalamic-pituitary-adrenal (HPA) axis, neurotransmitter and immune signaling systems, and microbiota composition. Dysregulation of these systems may result in an altered stress reactivity in both early life and the adulthood periods leading to maladaptive responses to the environmental stimuli. The activation of certain neuropeptides, including oxytocin, stimulation of the HPA axis, and increased glucocorticoid levels, may also play an important role in the early adaptive processes. In terms of brain maturation, ELA can directly or indirectly elicit structural changes in neurite growth, neurogenesis, neuronal connectivities, and signaling processes, which may contribute to the production of the long-term behavioral changes associated with an increased risk of the neuropsychiatric disorders' development in later periods of the life. In this review, we summarize the effect of ELA on the HPA axis function, stress-related hormonal balance, immune responses, and the gut microbiome indicating how these changes may affect the brain function and behavior in the early stages of the life and adulthood. We also provide insight into animal studies revealing the responses of corticotropin-releasing hormone, urocortins, and corticosterone in various neural circuits in response to ELA evoked by maternal separation and limited bedding paradigms.
Cortical Thickness and Appetite Hormones in Adolescent Obesity and Binge Eating Disorder: A Comparative Study.
Int J Eat Disord
Serkan Turan, İbrahim Mert Erbaş, Fatma Ceren Sarıoğlu +8 more
This study examined cortical thickness and appetite-regulating hormones-neuropeptide Y (NPY) and ghrelin-to better understand the neurobiological mechanisms underlying binge eating disorder (BED) and obesity in adolescence. We compared adolescents with BED and obesity, adolescents with obesity without BED, and healthy controls (HCs), and explored the relationships among these measures, BMI, and psychological symptoms.
Yiqi Huoxue formula relieves heart failure with reduced ejection fraction in calcium/calmodulin-dependent protein kinase Ⅱ delta B isoform and calcium/calmodulin-dependent protein kinase Ⅱ delta C isoform transgenic mice by inhibiting myocardial remodeling and enhancing calcium homeostasis.
J Tradit Chin Med
X U Jianglin, Shi Xiaolu, L I Yan +11 more
To confirm the efficacy of Yiqi Huoxue formula (, YQHX) on heart failure with reduced ejection fraction (HFrEF), and elucidate its potential effect on calcium homeostasis.
Chronic semaglutide alters ingestive behavior without impairing taste function in mice.
Mol Metab
Alisha A Acosta, Hillary Ellis, Fang-Yu Hsu +3 more
Glucagon-like peptide-1 receptor (GLP-1R) agonists such as semaglutide are highly effective treatments for obesity, yet the mechanisms by which they reduce food intake remain incompletely understood. Because taste plays a critical role in guiding food intake, several clinical studies have investigated whether GLP-1R agonists alter taste function, but these reports have yielded conflicting results. Here, we systematically tested the effects of chronic semaglutide treatment on taste responsivity in diet-induced obese mice. Mice were evaluated using brief-access gustometer tests to assess responses to sweet, bitter, sour, salty, and fatty tastants. Chronic semaglutide treatment produced robust weight loss but did not alter lick rates for any tastant, indicating intact taste-driven orosensory evaluation across modalities. Psychophysical analysis using a broad range of sucrose concentrations revealed similar concentration-response functions and comparable EC50 values between vehicle- and semaglutide-treated mice, demonstrating unchanged sweet taste sensitivity. However, semaglutide modestly increased total licking and trial initiation for sucrose, suggesting enhanced behavioral engagement rather than altered taste perception. Consistent with the behavioral findings on taste, semaglutide did not affect the abundance of taste receptor cell subtypes in the circumvallate papilla or the expression of genes involved in taste receptor signaling and neurotransmission. Together, these results indicate that chronic semaglutide does not detectably impair peripheral taste function in mice under our experimental conditions. Instead, GLP-1R agonists likely influence ingestive behavior through mechanisms independent of taste signaling, potentially involving alterations in motivational processes.
GLP-1 Receptor Agonists in Adolescents: Emerging Endocrine, Reproductive, and Psychosocial Concerns.
J Pediatr Adolesc Gynecol
Muhammad Ali Haider, Haseeba Javed
Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are increasingly prescribed to adolescents for obesity and type 2 diabetes mellitus (T2DM), with growing interest in extending their use to conditions such as polyendocrine metabolic ovarian syndrome (PMOS, formerly known as polycystic ovary syndrome or PCOS). However, adolescence represents the critical window for peak bone mass acquisition, and the implications of pharmacologic weight loss during this developmental period have received limited attention. Furthermore, this commentary addresses potential concerns related to eating disorder risk and future reproductive outcomes in this population.
Kisspeptin-10/basal LH ratio improves differentiation of central precocious puberty and premature thelarche.
Clin Chim Acta
Antara A Banerjee, Shital R Bhanarkar, Swati Kashikar +14 more
Distinguishing idiopathic central precocious puberty (ICPP) from premature thelarche (PT) remains a clinical challenge and often necessitates GnRH stimulation testing. Kisspeptin-10 (Kp-10), Neurokinin B (NKB), and Neuropeptide Y (NPY) are key regulators of GnRH secretion and may serve as surrogate biomarkers. We evaluated whether these neuropeptides, alone or in combination with basal gonadotropins, could provide clinically useful discrimination of ICPP and PT.
Integrating metabolic rehabilitation with incretin-based anti-obesity therapy: a narrative review of a multimodal strategy for sustainable weight loss.
Int J Obes (Lond)
Emmanuel Olumuyide, Katz Ariel, Ehimen Aneni
Obesity is a chronic condition associated with substantial cardiometabolic morbidity and mortality. Incretin-based anti-obesity therapies, including glucagon-like peptide-1 receptor agonists (GLP-1 RAs) and dual glucose-dependent insulinotropic polypeptide/glucagon-like peptide-1 receptor agonists, have transformed obesity management by producing clinically meaningful weight loss and improvements in glycemic and cardiometabolic risk profiles. However, weight loss achieved with these agents includes reductions in lean tissue in many studies, and the clinical significance of these body-composition changes remains incompletely defined. Importantly, reductions in DXA-derived lean mass should not be assumed to represent impaired muscle quality, strength, or function, as no published clinical trial has demonstrated that incretin-based therapy impairs muscle function. Metabolic rehabilitation encompasses structured exercise training, nutrition optimization, and behavioral support that have independently demonstrated benefits in preserving lean mass, improving insulin sensitivity, and enhancing cardiopulmonary fitness. Emerging evidence suggests that combining incretin-based therapy with metabolic rehabilitation may provide additive and complementary benefits, promote sustainable fat loss, while mitigating adverse metabolic adaptations. Metabolic rehabilitation also addresses skeletal muscle quality, bone health, and functional capacity, domains not directly targeted by pharmacologic appetite suppression. This narrative review synthesizes current evidence on the physiological effects of incretin-based obesity pharmacotherapy and metabolic rehabilitation, explores the mechanistic rationale for their combined use, reviews available clinical data, and proposes a practical framework for integrated obesity care. Key knowledge gaps and future research priorities are highlighted.
Therapeutic Opportunities Targeting the ACE2/Ang-(1-7)/MasR Pathway in Cardiometabolic Disease.
Curr Hypertens Rep
Thilina U Jayawardena, Dineth P Nagahawatta, Maria B Grant +2 more
PURPOSE OF REVIEW: This review examines the protective angiotensin-converting enzyme 2/angiotensin-(1–7)/Mas receptor axis of the renin–angiotensin system. We sought to integrate evidence from preclinical and early human studies on how activation of this pathway influences vascular, cardiac, renal, hepatic and metabolic health, and to identify methodological lessons for developing future therapies. RECENT FINDINGS: Animal models show that augmenting this axis improves endothelial function, limits cardiac remodelling, enhances insulin sensitivity, reduces renal injury and mitigates hepatic steatosis associate with MASH/NAFLD. Early-phase trials of recombinant angiotensin-converting enzyme 2 and angiotensin-(1–7) analogues demonstrate favourable safety profiles and clear pharmacodynamic target engagement but inconsistent immediate clinical effects. Emerging work highlights the value of biomarker ratios, gene and lifestyle based modulation and patient stratification strategies. Activation of the angiotensin-converting enzyme 2/angiotensin-(1–7)/Mas receptor axis offers a promising route to address cardiometabolic disease. Filling gaps in long-term outcomes, receptor-specific mechanisms and precision patient selection could transform this counter-regulatory pathway into a cornerstone of next-generation therapies.
Adverse hepato-biliary-pancreatic events in acromegaly patients treated with first generation somatostatin receptor ligands.
Pituitary
Francesco Ferraù, Elena Sofia Blanca, Marta Ragonese +16 more
First-generation somatostatin receptor ligands (SRLs) are first-line medical therapy for acromegaly. During long-term treatment, hepato-biliary-pancreatic adverse events can occur. This study aimed to evaluate the prevalence and predictors of hepato-biliary-pancreatic adverse events during SRL-treatment.In this multicenter study, data of 371 acromegaly patients (223 females) were retrospectively collected at the start of SRL therapy (T0), and at the last follow-up visit (120 ± 97.31 months). The occurrence of hepato-biliary-pancreatic adverse events and their relationship with features at T0 were investigated.Sixty-one patients (16.4%) underwent cholecystectomy (CH-Tx), cholecystitis (CH) occurred in 3.8%, severe or mild hyperlipasemia/hyperamylasemia in 2.2% and in 5.1%, severe or mild hypertransaminasemia in 1.1% and in 6.4%,respectively. No significant differences emerged after patient stratification by gender or age (≤/>50yrs). BMI, GH and IGF1 values were not associated with a higher risk of biliary complications. Patients undergoing CH-Tx or CH had a higher prevalence of cholelithiasis at T0 (p = 0.002 and p = 0.005). Cholelithiasis (p = 0.040) and biliary sludge (p = 0.014) at T0 were independent predictors of cholecystectomy. Cholelithiasis also strongly predicted cholecystitis in both univariable (p = 0.012) and multivariable (p = 0.025) analyses. Ursodeoxycholic acid (UDCA) treatment was associated with cholecystitis (p = 0.007) and mild-hypertransaminasemia (p = 0.035). When considering overall hepato-biliary-pancreatic adverse events, cholelithiasis, biliary sludge and age at T0 were significant predictors in both univariate (p = 0.006,p = 0.010,p = 0.013) and multivariable analysis (p = 0.029,p = 0.028,p = 0.044).Hepato-biliary-pancreatic adverse events are not infrequent during long-term SRLs therapy and are influenced overall by older age, cholelithiasis and biliary sludge.
Efficacy and safety of once-weekly somatrogon in adults with growth hormone deficiency: a randomized phase 3 study.
Pituitary
Maria Fleseriu, Beverly M K Biller, Susan M Webb +15 more
PURPOSE: This study assessed the efficacy and safety of once-weekly somatrogon, a long-acting growth hormone, in adults with growth hormone deficiency (aGHD). METHODS: A phase 3 randomized, double-blind, placebo-controlled study consisted of a 26-week double-blind period (Period 1), a 26-week open-label extension (OLE; Period 2), and a multi-year OLE (Period 3). Patients were randomized 2:1 to somatrogon or placebo in Period 1, with dosing adjusted for gender, age, and estrogen therapy. All patients received somatrogon in Periods 2 and 3. Primary endpoint was change in trunk fat mass (FM; baseline-Week 26). Secondary endpoints included changes in total FM, lean body mass (LBM), percentage change in trunk FM, and trunk FM. Changes in percent trunk FM relative to total trunk mass (FM + LBM), trunk LBM, and appendicular skeletal muscle mass were also evaluated in a post-hoc supplemental analysis. Safety assessments included adverse events (AEs) and laboratory evaluations. RESULTS: Of 389 patients screened, 202 were randomized, and 198 received treatment (somatrogon:133; placebo:65). Mean IGF-I SDS normalized following somatrogon initiation. There was no significant difference between somatrogon and placebo in change in trunk FM from baseline to Week 26 (-0.37 vs 0.03 kg; p=0.0821; primary endpoint) or in total FM. However, somatrogon significantly improved LBM, trunk FM as a percentage of total FM and the three supplemental endpoints. AE incidence was similar between groups, with most being mild to moderate in severity. CONCLUSION: Somatrogon significantly improved several body composition parameters and was well tolerated overall in adults with GHD. CLINICALTRIALS.GOV: NCT01909479; registration date: 25/07/2013