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Validation of NT-proBNP cutoff points for heart failure diagnosis in adults with CHD in the outpatient clinic and emergency department.
Int J Cardiol Congenit Heart Dis
Ahmed E Ali, Zeyad Kholeif, Marwan Ahmed +2 more
Empirical data support the use of N-terminal pro-B-type brain natriuretic peptide (NT-proBNP) for heart failure (HF) rule-in and rule-out in patients with acquired heart disease, but similar data are lacking in adults with congenital heart disease (CHD). The purpose of this study was to assess diagnostic performance of conventional NT-proBNP cutoff points for HF diagnosis (rule-in and rule-out) in adults with CHD.
Clearance of multiple antibiotic-resistant coagulase-negative staphylococci is selectively associated with higher circulating α-melanocyte stimulating hormone in patients evaluated for chronic inflammatory response syndrome.
Front Endocrinol (Lausanne)
Margaret DiTulio, Christian A Navarro-Torres
Neuroimmune regulatory peptides play central roles in coordinating inflammatory, metabolic, and mucosal immune processes in humans. Among these, α-melanocyte stimulating hormone (α-MSH), a proopiomelanocortin-derived peptide, has been implicated in modulation of cytokine signaling, epithelial barrier function, and pain processing. However, determinants of circulating α-MSH levels in chronic inflammatory states remain incompletely characterized in human clinical populations. Persistent sinonasal colonization with multiple antibiotic-resistant coagulase-negative staphylococci (MARCoNS) has been reported in some cohorts presenting with environmentally associated multisystem illness, described in some clinical settings as Chronic Inflammatory Response Syndrome (CIRS). Yet its relationship to systemic neuroendocrine biomarkers has not been quantitatively examined.
Da-yuan-yin decoction ameliorates inflammatory injury in severe pancreatitis by protecting intestinal mucosal barrier and immune function and preventing intestinal dysbiosis.
Ann Med Surg (Lond)
Yi-Hong Zhang, Lei Wang, Li Li +1 more
Acute pancreatitis (AP) is a common gastrointestinal condition characterized by inflammation of the pancreas. AP treatment is highly challenging due to the long hospital stays, higher medical expenses, and multiple complications. Traditional Chinese medicine has been used in China for thousands of years and is clinically proven to be a safe and effective treatment strategy for pancreatitis.
Injectable thermosensitive hydrogel-based sustained delivery system for anti-diabetic peptides in type 2 diabetes mellitus therapy: A review.
Biomed Pharmacother
Lam Quoc Vu, I-Hui Chiu, Cuong Thai Hoa Hoang +3 more
Injectable thermosensitive hydrogels have emerged as a promising class of biomaterials for the sustained delivery of drug. These smart systems undergo a sol-gel phase transition in response to physiological temperature, enabling minimally invasive injection and the formation of an in situ drug depot capable of controlled and sustained drug release. In recent years, thermosensitive hydrogels have drawn increasing attention in type 2 diabetes mellitus (T2DM) therapy, offering enhanced patient adherence, stable glycemic control, and reduced injection frequency compared with conventional formulations. Importantly, beyond glucose lowering, several hydrogel-based incretin therapies-particularly GLP-1 receptor agonists and dual GIP/GLP-1 agonists-have demonstrated clinically significant body-weight reduction and improved metabolic outcomes, addressing both hyperglycemia and obesity, two core components of T2DM pathophysiology. This review summarizes the classification, polymer composition, and drug release mechanisms of thermosensitive hydrogels. Special emphasis is placed on their use in the sustained delivery of insulin, GLP-1 receptor agonists and dual GIP/GLP-1 agonists. These hydrogel-based depots have demonstrated prolonged pharmacological efficacy, while preserving drug bioactivity, minimizing burst release, and achieving superior improvements in glycemic control and providing superior body-weight management with GLP-1 receptor agonists-loaded thermosensitive hydrogels, as compared with conventional injectable regimens. Finally, the challenges and future prospects of thermosensitive hydrogel systems are discussed, including the need for improved formulation stability, scalable manufacturing, and regulatory translation. With continued interdisciplinary advancements, injectable thermosensitive hydrogels hold strong potential as next-generation, long-acting, and patient-friendly delivery platforms for comprehensive diabetes management, encompassing both glycemic control and body-weight reduction in T2DM patients.
A role for vagal activity in preventing the suppression of glucagon secretion by GLP-1 during hypoglycemia.
Am J Physiol Endocrinol Metab
Carolina B Lobato, Amalie B E Nielsen, Jens J Holst
Glucagon-like peptide 1 (GLP-1) is generally safe against hypoglycemia, although it stimulates insulin and inhibits glucagon secretion. One explanation is that glucagon secretion is not inhibited by GLP-1 during hypoglycemia. We aimed at understanding the lack of suppression of glucagon secretion by GLP-1 by exploring the paracrine and neural regulation of pancreatic hormone secretion during hypoglycemia. Isolated rat pancreas (A) and an organ block comprising pancreas and stomach (B) were perfused. We performed 1) dose-response studies with GLP-1 (7-36) at hypoglycemia; 2) studies with GLP-1 (7-36) with and without blockage of somatostatin (SST) activity (with SST receptor antagonists); 3) and 4) dose-response experiments with acetylcholine at euglycemia and studies under hypoglycemia; and 5) finally, we studied the role of cholinergic signaling for modulation of GLP-1 activity under hypoglycemia. We measured glucagon, SST, and insulin levels. The secretion of SST was dependent on surgical preparation (A or B, P = 0.0006) and on cholinergic stimulation (P < 0.0001), rather than on glucose levels (P > 0.05). The infusion of SSTR antagonists in the isolated perfused rat pancreas blocked the paracrine effects of SST (P = 0.0041) and stimulated glucagon secretion (P = 0.0023). Cholinergic activity stimulated glucagon secretion during hypoglycemia through suppression of SST secretion. Cholinergic signaling delivered through the gastric intramural autonomic ganglia and/or vagus nerve efferents to the pancreas appears to be crucial for preventing GLP-1-induced inhibition of glucagon secretion during hypoglycemia.NEW & NOTEWORTHY Autonomic signaling suppresses somatostatin secretion, crucial for paracrine stimulation of glucagon secretion. SST mediates GLP-1-induced inhibition of glucagon secretion, but autonomic signaling may interfere with this mechanism. Activation of cholinergic pathways in a preparation with prepancreatic parasympathetic structures suppresses SST secretion in response to GLP-1 and potentiates glucagon secretion during hypoglycemia. These findings support the clinical importance of autonomic signaling in regulating pancreatic hormone secretion and hypoglycemia risk in some patients on GLP-1 receptor agonists.
Glucagon-like Peptide-1 and Dual GIP/GLP-1 Receptor Agonists in Brain: Exploring the Expanding Role and Safety in Neuropsychiatry.
Int J Mol Sci
Ana Cristina Tudosie, Loredana-Maria Marin, Simona Georgiana Popa +1 more
Glucagon-like peptide-1 (GLP-1) and dual GIP/GLP-1 receptor agonists, originally introduced for the management of type 2 diabetes mellitus and obesity, are increasingly recognized for their broader actions within the central nervous system, with emerging implications in neuropsychiatry and neurodegeneration. This review integrates current preclinical and clinical evidence, emphasizing their pharmacodynamic profile, central receptor distribution, and the molecular pathways linking metabolic signaling to neural function. Evidence suggests that GLP-1 receptor activation across key brain regions involved in energy balance and reward modulates multiple neurotransmitter systems, including dopamine and serotonin, as well as glutamatergic and GABAergic transmission, thereby influencing behavior, affective processes, and cognitive function. In parallel, these agents exhibit neuroprotective properties through improved neuronal insulin sensitivity, attenuation of neuroinflammatory pathways, and support of neuroplasticity, alongside effects on limiting pathological protein aggregation. Dual GIP/GLP-1 agonism may further potentiate these central actions through complementary metabolic and synaptic mechanisms. Although pharmacovigilance data have identified isolated neuropsychiatric adverse events, current clinical evidence does not support a consistent causal association. Collectively, incretin-based therapies represent a promising translational approach at the interface of metabolic and neuropsychiatric disorders, warranting further investigation into their long-term central safety, therapeutic efficacy, and clinical relevance.
A Systematic Review Identifying Critical Evidence Gaps in Reporting Dietary Change in Randomized Controlled Trials Prescribing Liraglutide, Semaglutide, or Tirzepatide.
Obes Rev
Anna K Jansson, María Gómez-Martín, Linnea Hedin +14 more
With the growing use of GLP-1/GIP receptor agonist medications, their impact on dietary intake and quality remains unclear. This systematic review examined how randomized controlled trials (RCT) prescribing liraglutide, semaglutide, or tirzepatide assessed and reported dietary intake and quality as outcome measures, alongside weight loss and/or glycemic control, and identified gaps in the use and methodological quality of dietary assessment methods.
Molecular Mechanisms of Dysregulated LH and FSH Secretion in Human Reproductive Failure.
Biomedicines
Athanasios Zikopoulos, Efthalia Moustakli, Anastasios Potiris +7 more
Several reproductive issues in both men and women are caused by changes in the pulsatile secretion of luteinizing hormone (LH) and follicle-stimulating hormone (FSH). For males to sustain spermatogenesis and Leydig cell function, and for females to ensure orderly folliculogenesis, ovulation, and ovarian steroidogenesis, precise coordination of LH and FSH secretion is necessary. Pituitary responsiveness, the frequency or amplitude of gonadotropin-releasing hormone pulses, or the dysregulation of feedback signals mediated by sex steroids and inhibins all disrupt the balance between LH and FSH secretion. Oligozoospermia, luteal-phase abnormalities, anovulation, or complete spermatogenic failure are possible clinical signs of these alterations. In addition to functional neuroendocrine disturbances, emerging genetic and epigenetic evidence, including pathogenic variants in genes such as gonadotropin-releasing hormone receptor, kisspeptin, kisspeptin receptor, luteinizing hormone beta subunit, follicle-stimulating hormone beta subunit, follicle-stimulating hormone receptor, and luteinizing hormone/choriogonadotropin receptor, has highlighted the role of inherited and acquired molecular defects in disrupting gonadotropin regulation. This narrative review synthesizes contemporary mechanistic, clinical, translational, and genetic evidence elucidating how dysregulated secretion of LH and FSH contributes to reproductive dysfunction. The molecular processes that regulate gonadotropin synthesis and release, as well as neuroendocrine regulation, gene-level determinants of hypothalamic-pituitary-gonadal (HPG) axis dysfunction, and the clinical phenotypes that result from their disruption, are all given special attention. We conclude with a discussion of new treatment strategies that target local intragonadal regulators to enhance gametogenic capacity, modulate gonadotropin signaling, or restore physiological gonadotropin-releasing hormone (GnRH) pulsatility, with consideration of how genetic insights may inform personalized therapeutic approaches.
The Skin-Brain-Exposome Axis in Stress-Sensitive Dermatoses: A Narrative Review.
J Clin Med
Anna Kubrak, Siddarth Agrawal, Mateusz Dróżdż +2 more
Background: Dermatological conditions represent a leading cause of global nonfatal disease burden, accounting for approximately 42.9 million disability-adjusted life years annually. Their complex pathogenesis is increasingly understood through the skin-brain-exposome axis, a bidirectional neuroimmunological and environmental communication network. The study aims to synthesize the neurobiological mechanisms of the skin-brain-exposome axis with macroscopic sociodemographic modifiers, clinical manifestations, and evidence-based psychodermatological interventions. Methods: A narrative review was conducted, following a structured search of PubMed, Scopus, and Web of Science (from inception to February 2026), yielding 54 sources. Mechanistic and interventional data (including randomized controlled trials and meta-analyses) were integrated with large-scale population-based epidemiological findings, anchored by a recent cross-sectional Polish cohort of 27,000 adults. Results: Psychological distress is associated with hyperactivation of the hypothalamic-pituitary-adrenal (HPA) axis and peripheral neurogenic inflammation (e.g., Substance P, corticotropin-releasing hormone), exacerbating stress-sensitive conditions such as atopic dermatitis, psoriasis, acne, and chronic pruritus. External exposome factors (urbanization, pollution) and sociodemographic variables (education, gender) may modify biological risk and diagnostic capture rates, frequently generating an epidemiological diagnostic paradox. Randomized trials support that psychotherapeutic interventions, particularly Cognitive Behavioral Therapy (CBT) and Mindfulness-Based Stress Reduction (MBSR), effectively disrupt the physical itch-scratch-stress cycle and improve disease-specific quality of life, serving as evidence-based adjunctive strategies in comprehensive care. Conclusions: Effective dermatological management requires targeting both the cutaneous barrier and the psychological exposome. Integrating routine psychosocial screening and stratified behavioral interventions into standard clinical care is essential for addressing the neuroimmune chronicity of inflammatory skin diseases.
Alterations of Growth Performance, Blood Parameters, and Antioxidant Function of Brown Adipose Tissue in Mice Exposed to Cold.
Antioxidants (Basel)
Xuekai Zhang, Xiao Jin, Zhipeng Han +2 more
Cold exposure is an unavoidable stressor in cold regions, leading to growth retardation, oxidative damage, and endocrine disruption. This study investigated changes in blood parameters and antioxidant function in the brown adipose tissue (BAT) of mice exposed to cold. Sixteen naturally mated female mice (aged 70 days) were selected and divided into a control group (CON, n = 8, 25 ± 1 °C) and a cold exposure group (CE, n = 8, 4 ± 1 °C). Each pregnant female gave birth to approximately 12 pups, and the litter (dams and pups co-housed) served as the independent experimental unit, with both euthanized for sampling when the pups reached 20 days of age. Results showed that cold exposure increased ADFI and ADG but decreased the feed conversion rate (FCR) in lactating mice. It also decreased platelet count (PLT) and mean corpuscular hemoglobin concentration (MCHC), elevated lactate dehydrogenase (LDH) activity, and decreased TG and non-esterified fatty acid (NEFA) levels. Hormonal changes included increased adrenocorticotropic hormone (ACTH), apelin 12 (AP12), INS, NE, decreased cortisol (COR), LEP, and thyroid-stimulating hormone (TSH). In pups, cold exposure inhibited growth, reduced PLT, plateletcrit (PCT), red blood cells (RBC), and hemoglobin (HGB), altered lipid profiles, and induced hormonal shifts. Notably, cold exposure enhanced the BAT antioxidant capacity in pups, increasing the total antioxidant capacity (T-AOC) and antioxidant enzyme activities, as supported by gene expression. These findings suggest that, despite growth suppression, mice maintain homeostasis by modulating blood parameters and enhancing BAT antioxidant function to mitigate cold-induced damage.
The NeuroImmunoEndocrine Circuit of Umami Peptides: A Systems Biology Approach.
Nutrients
Shiva Hemmati, Abdolali Mohagheghzadeh
Background/Objectives: Umami peptides enhance flavor and contribute to appetite regulation (satiety) and metabolic health. By signaling to the orbitofrontal cortex, umami has been shown to improve cognitive function in Alzheimer's disease dementia. This taste boosts the immune system and induces saliva secretion. However, the molecular mechanisms linking umami peptides to systemic physiology remain poorly understood. This study provides the first integrated analysis of neurological, immunological, and endocrinological pathways activated by umami peptides. Methods: Novel umami peptides were identified using machine-learning and deep-learning analyses from a library of marine-derived bioactive peptides. T1R1-T1R3 heterodimer is the dominant receptor for umami taste transmission in humans, expressed on taste cells, intestinal cells, and hypothalamic tanycytes. Molecular docking confirmed the binding of novel ligands to the T1R1-T1R3 receptor complex. New candidates and experimentally validated umami peptides, identified by sensomics approaches from tauco, chicken soup, pufferfish, and dry-cured ham, were analyzed using gene ontology. Results: The functional enrichment analysis revealed crosstalk among key signaling processes, including glutamatergic and opioidergic pathways. In addition to the role of µ1 opioid receptor (OPRM1), hub gene intersections highlight cholecystokinin (CCK), glucagon-like peptide 1 (GLP-1), and the anorexigenic pro-opiomelanocortin (POMC) neurons as potential regulators of the gut-brain axis in satiety signaling. Chemokine-encoding genes, melanin-concentrating hormone (MCH), oxytocin (OXT), and neurotensin (NTS) were other key target genes. Conclusions: The identified targets reveal the coordinated crosstalk between peripheral and central umami signaling that may contribute to the regulation of feeding behavior, satiety, cognition, memory, learning, and immune function. These network-based insights generate hypotheses and guide the design of nutritional and drug-like effectors for metabolic and cognitive health.
Angiopoietin-2 and Growth Differentiation Factor-15 as Predictors of Device-Detected Atrial Fibrillation Burden.
Biomedicines
Valentin Bilgeri, Philipp Spitaler, Jasmina Gavranovic-Novakovic +13 more
Background: Pacemakers enable continuous long-term surveillance of atrial fibrillation detected by implanted devices. Circulating biomarkers reflecting endothelial dysfunction, inflammation, and myocardial stress may help identify patients at risk for atrial fibrillation (AF) progression and higher arrhythmic burden. Methods: This analysis included patients from the prospective ACaSA study (NCT05127720) with a dual chamber pacemaker (Microport® BOREA DR or TEO DR) and monitored weekly via remote monitoring technology (SMARTVIEW®). Individuals with permanent AF or single-chamber systems were excluded. Baseline plasma concentrations of angiopoietin-2 (ANGPT2), growth differentiation factor-15 (GDF-15), fibroblast growth factor-23 (FGF-23), bone morphogenetic protein-10 (BMP10), and tumor necrosis factor-related apoptosis-inducing ligand receptor-2 (TRAIL-R2) were quantified using enzyme-linked immunosorbent assays. N-terminal pro-B-type natriuretic peptide (NT-proBNP) was measured using electrochemiluminescence immunoassay. Biomarkers were log2-transformed, with values below assay detection limits imputed at half the lower limit of detection. Two endpoints were assessed following a 30-day blanking period: (1) progression to persistent AF, defined as ≥7 consecutive days with >99% daily AF burden, analyzed using Cox regression; and (2) AF burden, calculated as total AF time normalized to monitored days and categorized as <25%, 25-75%, or >75%, analyzed using multinomial logistic regression. Multivariable models were adjusted for age, sex, heart failure, diabetes, and prior myocardial infarction; Cox models were limited to age, sex, and heart failure due to fewer events. Results: A total of 223 patients were included (median age 75 years; 37.2% women). During follow-up, 28 patients (13.3%) progressed to persistent AF. Higher baseline ANGPT2 was the strongest predictor of progression (HR per doubling 1.83, 95% CI 1.27-2.66, p = 0.001), followed by GDF-15 (HR 1.52, 95% CI 1.03-2.24, p = 0.036). In the burden analysis, ANGPT2 demonstrated a pronounced graded relationship with arrhythmic load, with markedly increased odds of high (>75%) AF burden (OR 8.31, 95% CI 2.63-26.26, p < 0.001). GDF-15 independently predicted both medium (OR 2.05, p = 0.025) and high burden (OR 2.32, p = 0.037). NT-proBNP displayed a borderline association with high burden (OR 2.02, p = 0.061). No significant associations were observed for FGF-23, BMP10, or TRAIL-R2. Conclusions: In continuously monitored pacemaker patients, ANGPT2 and GDF-15 emerged as key biomarkers associated with AF disease severity. ANGPT2 was strongly linked to both progression to persistent AF and high AF burden, whereas GDF-15 consistently predicted higher AF burden and also contributed to risk of progression. These findings highlight endothelial and inflammatory pathways as potential markers of atrial disease progression.
H2S Donor Therapy Reverses Established Pulmonary Arterial Hypertension and Pulmonary Vascular Structural Remodeling in Rats.
Biomedicines
Jie Zheng, Yanan Zhang, Boyang Lv +5 more
Objectives: Downregulation of the endogenous gasotransmitter hydrogen sulfide (H2S) contributes to the pathogenesis of pulmonary arterial hypertension (PAH). While prophylactic H2S supplementation prevents PAH initiation in different rat models, its ability to reverse fully established PAH and pulmonary vascular structural remodeling is unknown. In this study, we aimed to test whether H2S donor therapy can reverse the existing PAH in a chronic-hypoxia rat model. Methods: After 3 weeks of hypoxia exposure, rats with established hypoxia-induced pulmonary hypertension (HPH) were randomized to receive either continued hypoxia alone or hypoxia plus the H2S donor NaHS (56 μmol/kg·d, ip) for an additional 6 weeks. Pulmonary artery pressure, pulmonary artery muscularization, and right ventricular hypertrophy were assessed. Furthermore, the cell proliferation (Ki-67 and PCNA), ERK1/2 phosphorylation, and persulfidation of the endothelin type A receptor (ETAR) were examined and detected in rat lung tissues and pulmonary artery smooth muscle cells (PASMCs). Results: H2S therapy effectively reversed established HPH and pulmonary artery structural remodeling, reducing RVSP, mPAP, and the proportion of fully muscularized small pulmonary arteries by 13.8%, 12.0%, and 62.7%, respectively. Moreover, the PAT/PET ratio was normalized to normoxic levels. The right ventricular hypertrophy index decreased by 29.2%. Mechanistically, H2S therapy suppressed PASMC proliferation, reduced ERK1/2 phosphorylation, and enhanced ETAR persulfidation. Furthermore, dithiothreitol-mediated reduction of ETAR persulfidation abrogated these antiproliferative effects of H2S therapy, establishing persulfidation as an obligatory mechanism. Conclusions: H2S donor therapy effectively reverses established HPH and pulmonary vascular structural remodeling by inhibiting PASMC proliferation, which is linked to enhanced ETAR persulfidation. These data provide preclinical proof-of-concept for H2S-based interventions in patients with manifest PAH.
Cadmium-induced stress memory regulates Bacillus subtilis transport in porous media: Evidence from multi-scale analysis.
J Hazard Mater
Yijun Mo, Jialin Huang, Zihan Xiao +8 more
Accurately predicting microbial transport under environmental stress in subsurface and aquatic environments is essential for assessing microbial risks, from modeling pathogen spread to optimizing in-situ bioremediation. While the biological foundations of microbial heavy metal tolerance are established, the effects of toxic heavy metals like cadmium (Cd) on microbial-mineral interactions and subsequent transport mechanisms remain poorly understood. To address these challenges, we explored how Cd stress reconfigures the deposition behavior of Bacillus subtilis in porous media. We report, for the first time, that Cd pre-exposure induces a "stress memory" that attenuates the acute escape response from toxic surfaces, thereby enhancing deposition. We employed a multi-scale approach, integrating column experiments, quartz crystal microbalance with dissipation (QCM-D), whole-genome resequencing, and proteomics. This integrated analysis determined that the history-dependent shift from active avoidance to tolerant colonization may be driven by enhanced EPS secretion (Increased by 100.0-139.0%) and a reprogrammed signal transduction pathway (increased from 0 to 5). Consequently, B. subtilis subjected to higher prior Cd stress exhibited more attenuated migration responses, resulting in greater deposition and colonization while encountering Cd on the contact surface, with maximum deposited mass being 49.1-91.2% higher than that of the unstressed cells. These findings highlight the necessity of incorporating microbial active behavior and stress adaptation strategies into existing transport theory and provide insights for the prevention and control of pathogenic bacteria in polluted environments.
Comparative molecular characterisation of myeloid cathelicidins reveals subspecies-level diversification in indigenous livestock.
Dev Comp Immunol
Jini Roy, Varuna P Panicker, Vrindha Madhavan +7 more
Innate immune-related genes are shaped by strong selection pressures due to host-pathogen co-evolution, yet the evolutionary trajectory of cathelicidin antimicrobial (AMP) gene is poorly understood. Despite their central role in innate immunity, the extent of sequence diversification of myeloid cathelicidins across livestock subspecies remains unclear. Present study investigated inter-breed and inter-species level sequence variations of myeloid cathelicidin gene in Vechur cattle (Bos taurus indicus), Ankamali pig (Sus scrofa domesticus), Naked neck chicken (Gallus gallus domesticus) and compared them with their counterparts Bos taurus taurus, Large White Yorkshire (Sus scrofa domesticus), and White leghorn (Gallus gallus domesticus). Sequence and phylogenetic analysis revealed limited divergence and variations confined only to the subspecies level. Two Vechur-derived peptides vBMAP-27 (Vechur cattle Bovine Myeloid Antimicrobial Peptide) and vBMAP-28 displayed single amino acid substitutions at its active motif, whereas vBMAP-34, Ankamali pig and Naked neck chicken sequences were highly conserved. Single amino-acid substitutions altered predicted physicochemical properties, suggesting potential functional modulation. Cathelicidin gene evolution demonstrated by purifying selection, highlighting subtle genetic variation within immune-related gene could contribute to adaptive resilience in locally evolved local livestock breeds.
Combination of Ophiopogonin D, Ginsenoside Rg1, and Ginsenoside Rg3 ameliorates idiopathic pulmonary fibrosis via inhibiting type 2 alveolar epithelial cell senescence and epithelial-mesenchymal transition.
Naunyn Schmiedebergs Arch Pharmacol
Jiang Zhu, Kai Gong, Mengzhen Xu +7 more
Idiopathic pulmonary fibrosis (IPF) represents a chronic, non-reversible, and irreversible interstitial lung disease with the lack of curative interventions and a poor prognosis; identifying safe and effective therapeutic agents is of paramount importance. The Ophiopogon-Ginseng herb pair, a classical traditional Chinese medicine (TCM), exerts Qi-replenishing and Yin-nourishing effects. Its active constituents Ophiopogonin D (OP-D), Ginsenoside Rg1 (Rg1), and Ginsenoside Rg3 (Rg3) have individual anti-fibrotic potential, while their synergistic effects in IPF remain to be elucidated. This study aimed to explore how OP-D-Rg1-Rg3 attenuates IPF and to clarify its possible molecular mechanisms. Bleomycin (BLM)-induced cellular senescence and transforming growth factor-β1 (TGF-β1) induce epithelial-mesenchymal transition (EMT) in A549 cells. MTT assay and RSM determined the optimal combination ratio. Cellular senescence and EMT were assessed by SA-β-Gal staining, RT-qPCR, WB, and ELISA. An IPF mouse model was established by intratracheal BLM administration, followed by treatment with the optimized OP-D-Rg1-Rg3 combination, pirfenidone (PFD), or saline for 21 days. Pulmonary structural alterations and molecular changes were then evaluated by micro-CT, HE, Masson, and molecular analyses. The results showed that the synergistic OP-D-Rg1-Rg3 combination markedly attenuated A549 cell senescence, as evidenced by reduced SA-β-Gal activity and decreased expression of p53, p21, p16, and TGF-β1-induced EMT (upregulated E-cadherin, downregulated vimentin, fibronectin, Col-I). In vivo, the combination alleviated AEC2s senescence and pulmonary EMT, improved mouse body weight and lung morphology, reduced histopathological damage, and attenuated IPF. In conclusion, the OP-D-Rg1-Rg3 combination ameliorates IPF by inhibiting AEC2s senescence and EMT, highlighting promising clinical application prospects for IPF treatment.
Association between epilepsy duration and glymphatic dysfunction assessed by DTI-ALPS: A systematic review and meta-analysis.
Seizure
Su Ji Lee, Soomi Cho, Hui Jin Shin +2 more
To systematically evaluate whether epilepsy duration is associated with glymphatic dysfunction as measured by diffusion tensor image analysis along the perivascular space (DTI-ALPS).
Glycyl-L-histidyl-L-lysine-Cu2+ (GHK-Cu) Attenuates CuSO4 or LPS induced-inflammation in Zebrafish larvae model.
Eur J Pharmacol
Jing Hu, Chao Zhang, Feifei Wang
Inflammation serves as a basic defense mechanism against both internal and external threats, while the unresolved or excessive inflammation can lead to irreversible tissue damage. Glycyl-L-histidyl-L-lysine-Cu2+ (GHK-Cu), a bioactive tripeptide complex known for its anti-aging and tissue repair properties, is extensively utilized in dermatological and hair care formulations. However, the role of GHK-Cu in regulating inflammation is less known. In this study, we explored the anti-inflammatory effects of GHK-Cu against the acute inflammation induced by copper sulfate (CuSO4) and lipopolysaccharide (LPS) in zebrafish larvae. GHK-Cu notably decreased the migration of neutrophils and macrophages, suppressed the expression of pro-inflammatory cytokines (tnf-a, il-1β, il6) and increased the expression of the anti-inflammatory cytokine il-10. Moreover, GHK-Cu mitigated oxidative stress by reducing levels of nitric oxide (NO) and reactive oxygen species (ROS), and improved superoxide dismutase (SOD) activity. Furthermore, pathway analysis revealed that GHK-Cu administration downregulated the JAK1 pathway. In summary, this study highlights the dual role of GHK-Cu in both anti-inflammatory and anti-oxidant properties, which provides the theoretical evidences supporting its addition as a functional cosmetic ingredient.
iPSC-derived skeletal muscle spheroids for Duchenne Muscular Dystrophy modeling.
Skelet Muscle
Joyce Esposito, Felipe de Souza Leite, Igor Neves Barbosa +10 more
The progressive skeletal muscle degeneration observed in Duchenne Muscular Dystrophy (DMD) patients requires multiple cycles of satellite cells (SCs) activation to promote tissue regeneration. Dystrophic SCs present intrinsic defects, and the disrupting fibrotic niche hinders appropriate muscle recovery. Traditional 2D culture systems face challenges in modeling the DMD muscle niche and SCs behavior. Our aim was to validate a 3D culture of skeletal muscle spheroids (iSMS) for DMD modeling, as compared to the traditional 2D culture, while investigating the pathophysiological mechanisms of dystrophin deficiency in vitro.
Meeting report: Translating exercise research in dystrophinopathy to the clinic.
J Neuromuscul Dis
Donovan J Lott, Tina Duong, Rachel Schrader +2 more
To integrate current evidence and expert consensus on safe, effective exercise prescription in Duchenne and Becker muscular dystrophy (DMD/BMD), translating key pathophysiological principles into practical clinical guidance.