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Pilot Trial of Vachellia farnesiana Pod Polyphenol Extract: Feasibility, Acute Postprandial Glycemic Response, and Incretin Hormone Modulation in Healthy Adults.

Curr Dev Nutr

Yonatan Y Cariño-Cervantes, Martha Guevara-Cruz, Omar Noel Medina-Campos +9 more

Medicinal plants contain bioactive compounds with potential benefits for metabolic regulation, including glucose homeostasis. Vachellia farnesiana (VF) pods are rich in polyphenols, including quercetin, catechins, methyl gallate, prutin, and hydroxycinnamic acids; however, their clinical effects in humans remain underexplored.

Adrenal Biomarkers of Stress in Transgender and Gender-Diverse Adolescents.

Dev Psychobiol

Simone Coslovich, Stefania Tonetto, Giulia Bragato +7 more

Transgender and gender diverse (TGD) adolescents are frequently exposed to minority stress, which may influence the hypothalamic-pituitary-adrenal (HPA) axis during critical developmental windows. Altered cortisol dynamics have been described in populations facing chronic stress, yet evidence in TGD youth is limited. Understanding adrenal function in this context is essential for clarifying potential biological pathways linking social stressors to developmental and health outcomes. In the present study, identifying as TGD serves as an indirect proxy of exposure to minority stressors, which were not directly measured. We conducted a retrospective, case-control study at a tertiary pediatric center, including 48 TGD adolescents and 298 controls referred for evaluation of premature pubarche with nonclassical congenital adrenal hyperplasia excluded. All participants underwent a standard dose synacthen test (SDST; 250 µg tetracosactide iv, sampling at baseline and 60 min, 8:00 a.m.), which assesses adrenal responsiveness to pharmacological ACTH stimulation. Serum cortisol, DHEAS, ACTH, and 17-hydroxyprogesterone were assayed. Statistical analyses included nonparametric group comparisons, correlations, and multivariable regression adjusting for age and sex assigned at birth. TGD individuals demonstrated significantly higher baseline cortisol levels (293 vs. 214 nmol/L; p < 0.001) and a reduced cortisol response to SDST (Δcortisol: 354 vs. 446 nmol/L; p < 0.001). In the full sample, basal DHEAS levels were higher in TGD youth (231 vs. 142 nmol/L; p = 0.362), whereas the DHEAS-to-cortisol ratio did not differ significantly between groups. In an age-matched subsample (1:2 matching), the DHEAS-to-cortisol ratio was significantly lower in TGD adolescents (0.72 vs. 1.03; p = 0.004). Multivariate analysis confirmed an independent association between TGD status and higher basal cortisol, lower Δcortisol, and a reduced DHEAS-to-cortisol ratio after adjustment for covariates (all p < 0.001). Our findings provide preliminary evidence of altered adrenal responsiveness in TGD adolescents, potentially reflecting the biological embedding of minority stress during development. Although exploratory, these results highlight the need for prospective, longitudinal studies integrating psychosocial and neuroendocrine measures to clarify mechanisms linking stress, HPA axis function, and developmental outcomes in gender-diverse youth.

The mechanism of Longdan Xiegan pills in chronic stress-induced hypertension:a study based on network pharmacology and experimentalvalidation.

In Silico Pharmacol

Huizhuo Jia, Mingyao Lv, Ying Yang +7 more

This study integrated network pharmacology and experimental validation to elucidate the mechanism of Longdan Xiegan Pills (LDXG) in treating chronic stress-induced hypertension. Active components of LDXG were retrieved from the TCMSP database and screened based on oral bioavailability (OB) and drug-likeness (DL). Potential targets were predicted using SwissTargetPrediction. Disease targets related to hypertension were collected from OMIM and GeneCards. A compound-target network was constructed using Cytoscape, and protein-protein interaction (PPI) analysis was performed via the STRING database. Functional enrichment analysis (GO and KEGG) was conducted using DAVID. Molecular docking was performed with LeDock. In vivo, systolic and diastolic blood pressures were measured non-invasively, myocardial histopathology was evaluated by HE staining, the content of target protein in pvn and adrenal gland was measured by western blot, and serum inflammatory markers were quantified via ELISA. A total of 178 active components of LDXG were screened, Gentiana scabra Bunge (Gentian), Gardenia jasminoides Ellis (Gardeniae fructus), Scutellaria baicalensis Georgi (Huangcen), Bupleurum chinense DC (Bupleurum), and Glycyrrhiza uralensis Fisch (Licorice) were identified as the core components.The core targets included SRC, MAPK3, MAPK1, PIK3R1, RELA and STAT3. GO functional enrichment and KEGG pathway enrichment analyses indicated that LDXG primarily modulated protein kinase activity, ATP binding, protein serine/threonine kinase activity and protein kinase binding.These processes involved the PI3K-Akt, HIF-1, VEGF, ErbB and FoXO. Animal experiments demonstrated LDXG can significantly lowered blood pressure level in chronic stress-induced hypertension rats,reduced the contents of src and STAT3 in the PVN and MAPK1 in the adrenal gland and reduced serum levels of angiotensin II (Ang II), cortisol and adrenocorticotropic hormone(ACTH). LDXG can attenuate chronic stress hypertension by regulating JAK/STAT, Src/MAPK and other signaling pathways and reducing the expression of Ang II through a variety of active compounds.

Yttrium-90 Radioembolization Versus Transarterial Embolization for Lung Carcinoid Hepatic Metastasis.

JTO Clin Res Rep

Gavin Yuan, Marios Platon Dimopoulos, Elena N Petre +8 more

To compare the safety and efficacy of transarterial embolization (TAE) and transarterial radioembolization (TARE) in the treatment of lung carcinoid liver metastasis.

GHRH and insulin hypersecretion from a pancreatic neuroendocrine tumor in multiple endocrine neoplasia type 1.

JCEM Case Rep

Elisa Lamback, Daniel Alves Bulzico, Delmar Muniz Lourenço +3 more

Acromegaly caused by ectopic growth hormone-releasing hormone (GHRH)-secreting neuroendocrine tumor (NET) is extremely rare, with cosecreting NETs even more seldom. We report a case of a female patient who presented with primary hyperparathyroidism (pHPT) and a GHRH- and insulin cosecreting pancreatic NET (pNET) and genetically confirmed multiple endocrine neoplasia type 1 (MEN1), within an undiagnosed family with various MEN1-related NETs. Due to the diagnosis of MEN1, screening for pituitary tumor was performed with biochemical evidence of acromegaly. Sellar magnetic resonance imaging revealed a sellar lesion, which was excised and compatible with somatotroph hyperplasia. Postoperatively, the patient developed severe hypoglycemia requiring hospitalization and the pNET was removed. Histopathology confirmed GHRH and insulin secreting pNET. Ectopic acromegaly in MEN1 is exceedingly rare. Patients with MEN1 often present with multiple pNETs, which may exhibit multihormonal secretion and frequently cosecrete GHRH and insulin in MEN1, while hypoglycemia may not be manifested possibly due to GH and insulin's counteractive effects on glucose metabolism.

Leucine supplementation modulates body composition and early weight rebound during GLP-1 receptor agonist therapy in diet-induced obese mice.

J Endocrinol Invest

Ze-Wei Zhao

GLP-1 receptor agonists (GLP-1RAs) like semaglutide are effective for obesity treatment but may cause lean mass loss and post-discontinuation weight rebound. This study aimed to explore whether leucine supplementation alone or combined with semaglutide optimizes body composition in diet-induced obese (DIO) mice.

Reversion to normoglycemia with tirzepatide vs semaglutide in participants with obesity and prediabetes: a post hoc analysis of SURMOUNT-5.

J Endocrinol Invest

Rodolfo J Galindo, Louis J Aronne, Deborah B Horn +8 more

Depressed mood and suicidal thoughts reporting with GLP-1 receptor agonists in type 2 diabetes: A WHO VigiBase study.

J Affect Disord

Mohammed Aboukaoud, Bosmat Hoch, Mark Weiser +1 more

Evidence regarding depression and suicidality with glucagon-like peptide-1 receptor agonists (GLP-1RAs) remains inconsistent, particularly in patients with type 2 diabetes mellitus (T2DM) and underlying affective vulnerability.

Impact of GLP-1 RA plus progestin therapy on fertility-sparing management of endometrial intraepithelial neoplasia and endometrial cancer.

Gynecol Oncol

Tina Yi Jin Hsieh, Ting-Tai Yen, Michele R Hacker +2 more

We examined whether the addition of GLP-1RA to progestin therapy reduced the risk of hysterectomy in patients with endometrial intraepithelial neoplasia (EIN) and endometrial cancer (EC) in the U.S. managed with fertility-sparing management.

Tirzepatide therapy reduces subclinical leaflet thrombosis and paravalvular leak after transcatheter aortic valve replacement in obese patients: The TAVR-MET trial.

Cardiovasc Revasc Med

A M Thirugnanam, Chandrakanth, Pruthvi

Obesity is increasingly recognized as a critical modifier of outcomes following transcatheter aortic valve replacement (TAVR), predisposing patients to subclinical leaflet thrombosis (SLT), hypo-attenuated leaflet thickening (HALT), and paravalvular leak (PVL). Metabolic inflammation, endothelial dysfunction, and pro-thrombotic states associated with obesity contribute to impaired bioprosthetic valve healing. Tirzepatide, a dual glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) receptor agonist, has demonstrated robust metabolic, anti-inflammatory, and vascular protective effects. However, its impact on post-TAVR valve performance has not been previously evaluated.

GLP-1 receptor agonists in stroke prevention: a narrative review on emerging therapeutic frontiers.

Ann Med

Rahul Chikatimalla, Ashka Shah, Twinkle Shah +4 more

To evaluate the current evidence supporting the cerebrovascular protective effects of glucagon-like peptide-1 receptor agonists (GLP-1RAs) in individuals with type 2 diabetes mellitus (T2DM), and to outline their mechanisms of action in stroke prevention.

GLP-1 therapies and hair loss: A systematic review of current evidence and implications for counseling.

Sci Prog

Aditya K Gupta, Elizabeth M Teasell, Vasiliki Economopoulos +1 more

ObjectiveTo evaluate glucagon-like peptide-1 receptor agonist (GLP-1 RA)-specific associations with hair loss, characterize reported alopecia subtypes and discuss potential underlying mechanisms.MethodsA systematic literature search was conducted across four databases (PubMed, Embase, Scopus, and Web of Science) according to PRISMA guidelines and registered in PROSPERO (CRD420261297384). Studies were included if they were primary articles assessing hair loss related to GLP-1 RA use.ResultsOf 133 studies identified, 24 met inclusion criteria. Among GLP-1 RAs, semaglutide and tirzepatide demonstrated the highest incidence rates of hair loss and more frequent signal detection in pharmacovigilance studies. Although infrequently classified overall, androgenetic alopecia and telogen effluvium were the predominant subtypes of hair loss reported. Tirzepatide, associated with the greatest magnitude of weight loss, was most frequently linked to telogen effluvium. Hair loss associated with semaglutide appeared to be dose-dependent, with doses < 2mg weekly rarely implicated while higher obesity-treatment doses were more commonly associated with hair loss. Females appeared to be disproportionately affected. Rapid weight loss emerged as a potential contributor, particularly for telogen effluvium. In contrast, fewer studies assessed hair loss with liraglutide, dulaglutide, lixisenatide and exenatide, and they typically exhibited lower reported risk when compared to semaglutide and tirzepatide.ConclusionsAccumulating evidence from pharmacovigilance databases and clinical cohorts suggests an increased risk of hair loss with certain GLP-1 RAs, particularly semaglutide and tirzepatide. Further studies are needed to clarify the etiology of drug-induced weight loss, identify vulnerable populations, and establish causality and temporal relationship through large, prospective randomized trials.

Efficacy of GLP-1 receptor agonists in Parkinson's disease: a systematic review and exploratory network meta-analysis of randomized controlled trials.

Neurol Sci

Muaz Ali, Arkansh Sharma, Amith Paruchuri +7 more

Current therapies for Parkinson’s disease lack proven disease-modifying effects. Glucagon-like peptide-1 receptor agonists (GLP-1RAs), developed for type 2 diabetes, have shown potential neuroprotective properties. Their comparative efficacy in Parkinson’s disease remains unclear.

GIPR:GCGR co-agonism restores normal weight in obese rodents.

Mol Metab

Diego Perez-Tilve, Fa Zhang, Yujin Zhang +6 more

Functional co- and tri-agonists at the receptors for GLP-1, GIP and glucagon effectively decrease body weight and hyperglycemia but are associated with adverse gastrointestinal effects related to GLP-1R agonism. Here we report the discovery that obesity can be reversed in the absence of a functional GLP-1R. It propelled the identification of a unimolecular GIPR:GCGR co-agonist lacking GLP-1 activity that corrects obesity in obese mice and rats.

From mechanisms to therapeutics: The expanding role of cell-based strategies in Alzheimer's disease.

Eur J Pharmacol

Xuan Sun, Wenwen Deng, Jiangnan Yu +1 more

Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterized by cognitive decline. Its core pathologies include the deposition of amyloid-β plaques, the formation of neurofibrillary tangles composed of hyperphosphorylated tau protein, chronic neuroinflammation, and neuronal loss. With the rapidly aging global population, the prevalence of AD continues to rise. Current pharmacological treatments offer only limited symptomatic relief and cannot modify the underlying disease trajectory, leaving a significant unmet clinical need. In this context, cell-based therapy has emerged as a promising therapeutic strategy, leveraging its unique multi-targeted and regenerative capacities. This review systematically examines the therapeutic potential of various cell types, including mesenchymal stem cells, neural stem cells, immune cells, and engineered cells. We elaborate on their mechanisms of action, which encompass neurotrophic support, immunomodulation, and clearance of pathological proteins. These concerted actions contribute to remodeling the hostile brain microenvironment and promoting neuroregeneration in AD. Although preclinical evidence is robust, the clinical translation of cellular therapies faces considerable challenges. These hurdles include selecting the optimal cell source, developing efficient delivery strategies, determining the ideal intervention timing, and establishing standardized manufacturing protocols. Looking forward, we discuss how the development of precise disease models, the integration of gene editing and engineering strategies, advances in combination therapies, and the establishment of personalized treatment regimens are poised to position cell therapy at the forefront of comprehensive AD management. These innovations hold new promise for achieving true disease modification.

Simulated aquatic aging exacerbates pulmonary toxicity of graphite nanoplatelets by mechanically and chemically induced surface oxidation, enhancing oxidative potential.

Part Fibre Toxicol

Karthika Viswanathan, Youn-Joo Jung, Maruthupandy Muthuchamy +3 more

Graphite nanoplatelets (GNPs) are increasingly used in advanced materials, yet their environmental transformation and resulting health impacts remain poorly understood. This study investigated how long-term aquatic aging alters the physicochemical properties and pulmonary toxicity of GNPs.

Restrictive filling pattern of transmitral inflow in acute decompensated heart failure with preserved ejection fraction: insights from the KCHF registry.

Open Heart

Yutaro Miyoshi, Takao Kato, Takeshi Morimoto +17 more

The restrictive filling pattern of transmitral inflow has been shown to be associated with a poor prognosis in patients with heart failure (HF) with reduced ejection fraction or myocardial infarction. We aimed to investigate the significance of restrictive filling pattern in patients with HF with preserved ejection fraction (HFpEF).

N-terminal proBNP adds prognostic value to high-sensitivity cardiac troponin I in elective thoracic surgery: an observational cohort study.

BMJ Open

María Alonso, Ekaterine Popova, Marcos De Miguel +13 more

Perioperative myocardial injury (PMI) is a common complication following non-cardiac, particularly thoracic, surgery and is associated with increased cardiovascular risk. Although guidelines recommend cardiac biomarker monitoring to detect PMI, its implementation in routine clinical practice remains limited.

Therapeutic targets for fibro-inflammation in Graves' orbitopathy.

Taiwan J Ophthalmol

Young Jae Kang, Jin Sook Yoon

Graves' orbitopathy (GO), a complex autoimmune disorder, remains the most common extrathyroidal manifestation of Graves' disease. Its pathogenesis is characterized by a progressive transition from inflammation to fibrosis, leading to debilitating ocular complications. While high-dose intravenous glucocorticoids have been the standard treatment for active moderate-to-severe GO, their lack of specificity to GO pathogenesis and limited efficacy in the fibrotic phase underscore the need for targeted therapies. This review explores emerging therapeutic targets in GO, focusing on pathways implicated in both inflammatory and fibrotic mechanisms. Teprotumumab, an insulin-like growth factor 1 receptor (IGF-1R) inhibitor, has revolutionized GO treatment, demonstrating clinical efficacy in reducing proptosis and inflammation. Interleukin-6 (IL-6) inhibitors including satralizumab are undergoing clinical trials. New studies on molecular pathways have been conducted regarding inflammation and fibrosis of GO, including platelet-derived growth factor/fibroblast growth factor signaling, yes-associated protein 1/transcriptional coactivator with PDZ-binding motif mechanotransduction, sphingosine-1-phosphate (S1P)/S1P receptor axis, bone morphogenic protein 7, IL-11, IL-17 and microRNAs as well as, IGF-1R/thyroid-stimulating hormone receptor crosstalk, and IL-6 trans-signaling. Most studies focus on exploring the potential of therapeutic agents through preclinical investigations but represent promising therapeutic avenues. Therapies targeting these pathways may offer a promising potential efficacy across the entire disease spectrum, from inflammation to fibrosis, thus overcome the limitations of conventional glucocorticoid therapy and expand therapeutic options in GO. Advances in in vivo GO models may bring forward a new era of GO treatment.

STAT3 isoform dynamics reveal robust splice ratio maintenance across cytokine-activated human immune cells.

Front Immunol

Nils Ott, Bodo Grimbacher, Virginia Andreani

Alternative splicing of STAT3 produces two principal isoforms, STAT3α and STAT3β, that differ in transactivation capacity and DNA-binding behavior. Whereas STAT3α is thought to be a transcriptional activator, STAT3β - due to the lack of the transactivation domain - is thought to be a transcriptional repressor. Therefore, the relative abundance of STAT3α and STAT3β molecules within a leukocyte will be critical for immune homeostasis and for gene-therapeutic strategies targeting STAT3. This study investigates whether short-term exposure to IFN-α, IL-6/sIL-6Rα, or IL-10 alters STAT3α/STAT3β stoichiometry in purified human CD4+, CD8+, CD14+ and CD19+ cells. We evaluated in healthy donors PBMCs the STAT3α and STAT3β mRNA and protein levels after stimulation with IFN-α, IL-6/sIL-6Rα or IL-10. For mRNA analysis, twelve candidate reference genes were assessed for stability across subsets and stimuli, with UBE2D2 identified as the most stable reference gene. We demonstrate that at mRNA level, cytokine treatment induced STAT3α and STAT3β mRNA in a subset-dependent manner. STAT3β mRNA largely paralleled STAT3α, and crucially, the STAT3α/STAT3β mRNA ratio remained constrained within a narrow range. At protein level, STAT3α predominated markedly, yielding a pronounced transcript-protein decoupling. Together, these data indicate that ex vivo short-term cytokine signaling with IFN-α, IL-6/sIL-6Rα, and IL-10 co-induces STAT3 isoforms without broadly reprogramming their splice balance in primary human leukocytes and underscore the importance of preserving physiological isoform ratios in gene-therapeutic strategies targeting STAT3. These findings suggest that short-term inflammatory signals alone are insufficient to shift STAT3 isoform production, supporting the idea that additional or more prolonged regulatory inputs are required to modulate STAT3 splicing in vivo and that physiologically, the STAT3α/STAT3β ratio may be modulated at protein level.