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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.

Editorial: Lifetime achievements in avian physiology.

Front Physiol

Colin G Scanes, Sandra G Velleman

Renalase knockdown inhibits proliferation of mouse satellite cells.

Mol Biol Rep

Yuri Kato, Katsuyuki Tokinoya, Kai Aoki +1 more

Cy3-Conjugated Biocompatible Polymer Nanoparticles for Long-Term Mitochondrial Imaging.

Chembiochem

Souma Kawashima, Mitsuo Inui, Izumi Takaba +2 more

The cyanine dye Cy3 has recently gained attention as a membrane potential-responsive, small-molecule mitochondrial imaging probe. However, the efficiency of Cy3 for mitochondrial imaging is relatively low, as diffusion of Cy3 leads to staining of the entire cell over time. This problem could be due to the passive diffusion-based, concentration-dependent uptake into cells and molecular diffusion inherent to small-molecule compounds. Therefore, we hypothesized that polymer chemistry approach could be applied to overcome these limitations. In this study, we designed modified dye in which biocompatible polymers were covalently attached to Cy3. This enabled control of intracellular dynamics that could not be achieved using Cy3 alone. Toward this objective, we synthesized a Cy3-modified amphiphilic dextran with phenylalanine ethyl ether side chains. The amphiphilic polymers self-assembled into nanoparticles. We then characterized the synthesized polymer in terms of intracellular uptake and the mitochondria translocation capacity of the nanoparticles using human skeletal muscle satellite cells. Our approach changed the cellular internalization process, resulting in increased cellular uptake efficiency, enhanced mitochondrial imaging capability, and improved mitochondrial retention over the long term. These nanoparticles, which can stain mitochondria regardless of cell type, have the potential to become a new type of mitochondrial imaging reagent.

Thymalfasin combined with immune checkpoint inhibitors in the treatment of non-small cell lung cancer: A retrospective study on efficacy, safety, and immunological function.

Pak J Med Sci

Peipei Wang, Xiaojing Zhang, Cheng Xiang +2 more

To evaluate the efficacy, safety, and immunomodulatory effects of thymalfasin in combination with different immune checkpoint inhibitor (ICI)-based regimens in patients with advanced driver gene-negative non-small cell lung cancer(NSCLC).

From Maternal Exposure to Fetal Risk: Unraveling the PFAS Exposure Pathway and Its Placental Toxicity Mechanism.

Environ Sci Technol

Yurou Gao, Zichen Kuang, Qian S Liu +2 more

Per- and polyfluoroalkyl substances (PFAS) have triggered a global crisis due to their severe toxicities and widespread occurrence in human populations. Notably, PFAS is frequently detected in maternal blood, placental tissue, and umbilical cord blood, indicating direct fetal exposure to PFAS through the maternal-fetal interface. As the central organ regulating nutrient exchange, endocrine signaling, and immune balance, the placenta is particularly vulnerable to PFAS exposure, and its dysfunction is linked with various adverse pregnancy outcomes, including fetal growth restriction, low birth weight, preterm birth, preeclampsia, etc. However, existing knowledge on PFAS-induced placental dysfunction remains fragmented, typically addressing their occurrence, transplacental transfer, specific mechanistic targets, or epidemiological evidence in isolation. This review synthesizes evidence tracing the entire trajectory of PFAS exposure─from maternal uptake and distribution in the bloodstream to placental accumulation, transplacental passage, and fetal exposure. It further highlights how PFAS may interfere with key processes of placental development, including angiogenesis and vascular remodeling, trophoblast migration and invasion, lipid metabolism, hormone production, and establishment of the maternal-fetal immune microenvironment, which provides mechanistic explanations linking PFAS exposure to adverse pregnancy outcomes. By integrating transplacental behaviors, mechanistic insights, epidemiological findings, and methodological advances, this review offers a comprehensive perspective on PFAS-induced placental toxicity and presents new directions for assessing maternal-fetal health risks.

Semaglutide Treatment in Young Adults Living With Type 2 Diabetes: A Post Hoc Analysis From the SUSTAIN and PIONEER Clinical Trials.

Diabetes Obes Metab

Francesco Zaccardi, Vanita R Aroda, Ecenur Guder Arslan +6 more

Young adults (aged ≤ 40 years) are underrepresented in clinical trials that investigate interventions for those living with Type 2 diabetes (T2D). This study evaluated the efficacy of semaglutide treatment in young adults with T2D by examining the effects on HbA1c and body weight (BW) during the SUSTAIN and PIONEER programmes compared to placebo and active comparators, according to age at study enrolment. This study also assessed aggregated safety data across age subgroups.

Insights from changes in NDEV biomarkers of metabolism: Effects of PPARγ and GLP1 receptor agonists on brain metabolism.

J Clin Endocrinol Metab

Audrey Evers, Kathleen Watson, Fahim Abbasi +4 more

Insulin resistance (IR) is implicated in central nervous system disorders, including depression and Alzheimer's disease (AD).

Effect of Incretin-Based and Nonpharmacologic Weight Loss on Body Composition : A Systematic Review.

Ann Intern Med

John A Batsis, Alessandro Gavras, Danae C Gross +12 more

Incretin-based therapies induce substantial weight loss and are widely prescribed; disproportionate losses in fat-free mass (FFM) and skeletal muscle are a concern.

Use of Glucagon-Like Peptide-1 Receptor Agonists and Risk of Parkinson's Disease: Scandinavian Cohort Study.

Diabetes Obes Metab

Arvid Engström, Henrik Svanström, Anders Hviid +8 more

To investigate the association between use of GLP-1 receptor agonists and incident Parkinson's disease.