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[Bioimpedance analysis parameters and metabolic profile in children with non- alcoholic fatty liver disease].
Vopr Pitan
A M Yakubovich, E V Pavlovskaya, M E Bagaeva +4 more
Non-alcoholic fatty liver disease (NAFLD) in children is considered a manifestation of metabolic disturbances, that is a complex of interrelated alterations in carbohydrate and lipid metabolism associated with insulin resistance and an increased proportion of visceral fat. In this context, a comprehensive assessment of metabolic parameters combined with body composition analysis in children with NAFLD and without it is relevant for clarifying the role of visceral obesity in the development and progression of the disease, as well as for improving the accuracy of clinical assessment. The aim of the research was to assess the characteristics of the metabolic profile and bioimpedance analysis (BIA) parameters and to determine their associations with clinical and biochemical features of NAFLD in children.
Noninvasive Biomarkers for Graves' Orbitopathy: Clinical Relevance of Circulating PAI-1, TGF-β and IGF-1R.
Clin Ther
Diana Leszczyńska, Bartosz Pomichter, Małgorzata Szelachowska +8 more
Graves' orbitopathy (GO) involves fibrotic and inflammatory processes. Plasminogen activator inhibitor-1 (PAI-1), transforming growth factor-β (TGF-β), and soluble insulin-like growth factor-1 receptor (IGF-1R) have been identified as key mediators. This study primarily focused on the diagnostic value of circulating PAI-1, TGF-β, and IGF-1R, with their prognostic and treatment-monitoring significance assessed as exploratory endpoints.
Therapeutic potential of Amentoflavone against myostatin for skeletal muscle atrophy treatment: An in silico, in vitro, and in vivo study.
Phytomedicine
Jeong Ho Lim, Syed Sayeed Ahmad, Eun Ju Lee +2 more
Myostatin (MSTN) negatively regulates skeletal muscle (SM) growth, and its over activity suppresses myogenic differentiation, promoting muscle atrophy and aging. Amentoflavone (AMF), a biflavonoid from Ginkgo biloba, possesses anti-atrophy effects. AMF has anti-inflammatory, antioxidant, antitumor, and anti-viral properties. The effect of AMF on SM atrophy and myoblast differentiation has not been explained.
Liraglutide ameliorates diabetic lung injury and muscle damage via modulation of TLR4/NF-κB and Atrogin-1/AMPK signaling pathways.
Mol Biol Rep
Marwa Abdeltawab Mohammed, Mai Abdou Yousef, Alshimaa Mohamed Abdelmohymen +4 more
Diabetic complications extend beyond metabolic disturbances to include end-organ damage, with emerging evidence including lung and skeletal muscle dysfunction as under recognized manifestations. This study investigated the protective effects of liraglutide against pulmonary and muscular impairments in a rat model of type 2 diabetes.
GLP-1 receptor agonist therapy before bariatric surgery: Effects on weight loss and body composition in clinical practice.
Obes Res Clin Pract
Sonsoles Gutiérrez-Medina, Isabel Higuera, Gloria Velasco +7 more
The use of anti-obesity medications, particularly including glucagon-like peptide-1 receptor agonists (GLP1-RA), is expanding and increasingly combined with bariatric surgery (BS). However, evidence on their use preoperative and impact on body composition remains limited.
A randomised, double-blind, placebo-controlled trial to assess the postprandial dose-dependent effects of wild blueberries on metabolic and cognitive outcomes following a high-carbohydrate breakfast.
Eur J Nutr
Lucy R Ellis, Dominic O'Connor, Haseena Khan +2 more
Despite equivocal human study data, anthocyanin-rich blueberries are associated with positive glycaemic effects which could benefit satiety and other cardiometabolic outcomes. The objective of this study was to examine the dose-dependent effects of freeze-dried wild blueberries on postprandial glucose response simultaneously with changes in satiety, blood pressure and cognitive function.
AnvRV virus in the parasitoid wasp Anagyrus vladimiri: localization, effect on gene expression, and prevalence.
Microbiol Spectr
Gal Wodowski, Yehuda Izraeli, Netta Mozes-Daube +3 more
Insect-virus associations have been studied extensively in the context of pathogenic viruses transmitted by insects, whereas research on nonpathogenic viruses remains relatively scarce. Recently, we discovered three nonpathogenic RNA viruses in the parasitoid wasp Anagyrus vladimiri: AnvRV, AnvDV, and AnvIfV. Here, using transmission electron microscopy, we detected AnvRV in the wasp oocytes and in a distinct group of cells in the ovaries, which we termed "satellite cells," but not in the venom gland or venom reservoir, indicating that AnvRV is transmitted transovarially. Next, we analyzed gene expression in AnvRV-infected and uninfected wasps and found that AnvRV modulates the immune response and alters venom composition. Notably, the NF-κB inhibitor gene was upregulated in the wasp ovaries, where AnvRV is localized, suggesting that AnvRV locally suppresses the immune response of A. vladimiri to facilitate its transmission. Next, we studied the prevalence of the three viruses in field populations of A. vladimiri and its hosts, Planococcus citri and Planococcus ficus. AnvRV was absent from both mealybug species and detected at low prevalence in A. vladimiri, whereas AnvDV and AnvIfV were consistently present in P. citri. Lastly, by datamining of public RNAseq data sets, we investigated the prevalence of these viruses in other parasitoid species and revealed only a few related viruses. Taken together, we postulate that AnvRV is an active symbiont of A. vladimiri, influencing host gene regulation. These findings provide new insights into the diversity of insect-virus interactions and their potential roles in shaping parasitoid biology.
Real-World Effectiveness and 12-Month Persistence of a Semaglutide-Supported Digital Weight-Loss Service: A Retrospective Cohort Study in Germany.
Diabetes Obes Metab
Louis Talay, Jason Hom, Marilyn Tan +1 more
To evaluate the 12-month effectiveness and patient persistence of a semaglutide-supported digital weight-loss service (DWLS) in a real-world German cohort.
Association of Glucagon-like Peptide-1 Receptor Agonist Use with Stroke and Mortality Outcomes in Asymptomatic Intracranial Atherosclerotic Disease: Propensity Score-Matched Real-World Analysis.
Neurol Int
Pranjal Rai, Daniel Mandel, Girish Bathla +18 more
Asymptomatic intracranial atherosclerotic arterial stenosis (ICAS) is an underrecognized entity for which vascular risk-factor optimization is the primary management strategy, with no current indication for routine antiplatelet therapy or endovascular intervention for primary stroke prevention. Glucagon-like peptide-1 receptor agonists (GLP-1RAs) reduce major adverse cardiovascular events, including stroke, in high-risk cardiometabolic populations, but their association with outcomes in asymptomatic ICAS is yet to be evaluated. The present study aims to evaluate the association between GLP-1RA use and cerebrovascular outcomes in adults with asymptomatic ICAS.
Beyond biochemical cascades: novel bio-mechanical and epigenetic paradigms of glial SASP in brain aging.
Metab Brain Dis
Emad Manni, Hayder M Al-Kuraishy, Mustafa M Shokr +1 more
One of the most pressing scientific challenges of the current century is the mounting loss of cognitive function and vulnerability to neurodegenerative disorders associated with brain aging. This requires a paradigm shift beyond traditional neuron-focused models to address the central importance of non-neuronal glial cells, most notably astrocytes, in promoting age-related neuroinflammation. While the pro-inflammatory secretome of senescent cells, known as the senescence-associated secretory phenotype (SASP), is well-characterized in peripheral tissues, its specific role in the central nervous system remains a critical knowledge gap. This narrative review synthesizes current evidence to propose that the SASP of glial and vascular cells acts as a contributor mechanism, where it interacts with other aging hallmarks to amplify the pathological environment rather than acting as the sole link. Moving beyond standard biochemical signaling cascades, we propose conceptually transformative frameworks to explain central SASP aggression. The glymphatic-SASP traffic jam, establishing a bio-mechanical feedback loop where waste clearance failure traps secretomes in localized hotspots; and the metabolic energy vampire paradigm, demonstrating the active competition for resources between hyper-secretory glia and energy-starved neurons, were explored. Also, the innate immune mimicry triggered by retrotransposon awakening, explaining how unleashed genetic elements actively fuel self-propagating inflammation, and the loss of glial identity dictated by epigenomic state drift and SASP mosaicism were demonstrated. Furthermore, we evaluate the classic regulatory cross-talk between the SASP and nutrient-sensing pathways like AMPK and mTOR, and discuss the therapeutic potential of selectively targeting the SASP through senomorphics and metabolic resetters. Elucidating these complex, brain-specific SASP dynamics is paramount for translating these concepts into effective interventions against age-related neurological diseases.
Sensory Neuroimmunology: Bidirectional Neuro-Immune Circuits Governing Pain, Itch, Inflammation, and Host Defense at Barrier Surfaces.
Biology (Basel)
Reza Mosaddeghi-Heris, Nasrin Forghani, Negin Safari Dehnavi +5 more
Sensory neurons at barrier tissues were once seen as passive detectors of environmental stimuli. However, in the last five years, increasing evidence has challenged this view, redefining these cells as active immune sentinels that directly affect tissue immunity in the skin, lungs, and gastrointestinal tract. Nociceptors and pruriceptors express various immune-sensing receptors, including Toll-like receptors, cytokine receptors, and alarmin sensors, which allow them to directly detect pathogens, allergens, and tissue damage. When activated, sensory neurons quickly release neuropeptides such as calcitonin gene-related peptide (CGRP), substance P, vasoactive intestinal peptide (VIP), and PACAP (pituitary adenylate cyclase-activating polypeptide), which guide immune cell recruitment, activation, and resolution. Reciprocally, immune-derived mediators, including IL-33, IL-31, thymic stromal lymphopoietin (TSLP), IL-4/IL-13, and TNF-α, modulate neuronal excitability and plasticity, forming bidirectional neuroimmune circuits that control inflammation, host defense, pain, and itch. Landmark studies published in 2024-2025, including neuronal control of gut Treg function and the identification of sensory nerve immune niches, have further refined this framework and revealed tissue-specific circuit specialization. This review synthesizes recent insights from molecular, cellular, and systems levels into the sensory neuroimmune axis, emphasizes its protective versus pathogenic roles, and critically evaluates emerging therapeutic strategies and safety concerns, positioning sensory neuroimmunology as a unifying framework for tissue barrier homeostasis and disease.
Biological and neurocognitive correlates of comorbid post-traumatic stress disorder and alcohol use disorder: a systematic review.
Eur J Psychotraumatol
Ellen E Towers, Joel Hoffman, Eva E Louie +4 more
Background: Post-traumatic stress disorder (PTSD) and alcohol use disorder (AUD) frequently co-occur, leading to greater clinical burden than either disorder alone. Despite this, little is known about the biological pathways linking these two disorders.Objective: We conducted a systematic review to synthesize evidence on molecular, genetic, neural, and cognitive mechanisms contributing to comorbid PTSD & AUD.Method: Following PRISMA guidelines, we performed a comprehensive search of five databases using PTSD-related, AUD-related, biological, and neurocognitive terms. Participants had to meet diagnostic criteria for both PTSD and AUD, and studies were required to have a comparator including controls, PTSD only, or AUD only. A critical appraisal was completed for all studies.Results: From 3904 identified papers, 14 met the inclusion criteria. Four studies examined the same molecular marker, with three papers derived from the same cohort, investigating baseline and stress-induced cortisol and adrenocorticotropic hormone, and found no differences unique to PTSD & AUD. One study linked low brain-derived neurotrophic factor and hazardous drinking to PTSD onset over 2 years following hospital admission. Genetic studies showed considerable overlap (72%) between PTSD and AUD in female twins, whereby the DRD2 A1 allele and the absence of the APOE ϵ2 allele were strongly associated with PTSD and drinking. Studies also reported lower neurometabolites, white matter integrity, and hippocampal volume in PTSD & AUD. Critical appraisal of these studies highlighted prominent selection bias (predominantly male and veterans) and limited justification of sample size.Conclusions: These findings suggest that PTSD & AUD may be characterized by distinct neurobiological alterations and genetic vulnerabilities relative to comparator groups. However, as there are currently insufficient data to support or refute these findings, this highlights the need for further research.
Ferroptosis bridges early-life oxidative stress and lifetime meat quality defects in broilers.
Poult Sci
Xuyang Gao, Caiwei Luo, Bo Wang +1 more
This study investigated whether oxidized oil impairs broiler meat quality by triggering ferroptosis and evaluated the synergistic protective effect of composite antioxidants compared with individual antioxidants. The study integrated in vivo broiler trials with in vitro cell models. First, the effects of normal oil and oxidized oil on meat quality were compared through a broiler feeding trial, and the relief effects of BHT (54 g/ton), EQ (90 g/ton), and their complexes BHT+EQ (BE; 18 and 15 g/ton) and BHT+EQ+citric acid blend (BEC; 18, 15, and 9 g/ton) were evaluated using the oxidized oil group as a positive control. Subsequently, an oxidative damage model was constructed using in ovo injection technology, and its muscle satellite cells were isolated to evaluate their potential for proliferation and differentiation, finally focusing on the Nrf2-GPX4 axis to reveal the molecular mechanism by which composite antioxidants alleviate the meat quality deterioration caused by oxidized oil. The results found that, compared with normal oil, oxidized oil significantly impaired the meat quality of broilers, manifested as a decrease pH24h and redness (a*), while drip loss and cooking loss increased, antioxidant defense capacity was damaged, and myoglobin was unstable (P < 0.05). Antioxidant intervention can significantly alleviate the above negative effects (P < 0.05), among which the protective effect of the BEC group was the most outstanding, superior to the BE group and individual antioxidant treatments. At the cellular level, compared with normal oil, oxidized oil inhibited the abundance of Pax7 and MyHC and induced mitochondrial dysfunction (P < 0.05). The synergized BE and BEC groups effectively cleared reactive oxygen species and inhibited GPX4-mediated ferroptosis by activating the Nrf2-GPX4 signaling axis and upregulating cytoprotective genes such as NQO1 and HO-1, thereby maintaining cellular redox homeostasis. In summary, oxidized oils cause meat quality deterioration by triggering Nrf2-GPX4-mediated ferroptosis, the BEC composite strategy confirmed in this study provides an important theoretical basis for the precise regulation of meat quality and the optimization of antioxidant programs in poultry production.
Phenome-wide analysis of downstream health outcomes following second-line antidiabetic agent prescriptions in All of Us.
Nat Commun
Maxwell Salvatore, Bingyu Zhang, Huilin Tang +7 more
Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are increasingly prescribed for type 2 diabetes (T2D) and weight management, yet their real-world health impacts remain understudied. Using a retrospective cohort design with electronic health record data from 17,267 adults with type 2 diabetes in the All of Us Research Program, we conduct propensity score-matched phenome-wide association studies comparing diagnoses following GLP-1 RA prescription (including semaglutide-specific analyses) to those following sodium-glucose cotransporter-2 inhibitor (SGLT2i) and dipeptidyl peptidase-4 inhibitor (DPP4i) prescriptions between January 2018 and October 2023. We employ both intention-to-treat and per-protocol Cox proportional hazards models alongside restricted mean survival time analyses evaluating up to 974 phenotypes. We identify multiple phenome-wide significant and suggestive associations, including for cardiovascular, genitourinary, dental, and metabolic outcomes. Compared to SGLT2i, semaglutide demonstrates reduced risk for genitourinary infections in women (e.g., candidiasis of vulva and vagina (per-protocol hazard ratio 0.31, 95% confidence interval (0.17-0.55)). Compared to DPP4i, GLP-1 RAs are associated with reduced risk of diseases of hard tissues of teeth (0.45 (0.33-0.61)). Time-to-event analyses reveal modest delays for key diagnoses. These findings underscore differences in downstream diagnostic associations across second-line T2D therapies and highlight semaglutide's distinct profile, with implications for clinical decision-making and personalized prescribing.
Saikosaponins aggravate mitochondrial damage and senescence of cholangiocyte in cholestatic liver diseases by inhibiting protective autophagy.
Phytomedicine
Guifang Fan, Xiao Chen, Yufei Li +6 more
Cholestasis is a common pathological feature in multiple liver diseases which is characterized by toxic bile acid accumulation and liver injury. Emerging evidence indicated that total saikosaponins (TSS) from Radix Bupleuri (RB) could disrupt autophagic flux, probably exacerbating cholestatic liver injuries and warranting further investigation.
[Electroacupuncture improves hypothalamic-pituitary-gonadal axis function and testosterone synthesis in high-fat diet-induced obese male rats].
Zhen Ci Yan Jiu
Jing-Yi Zhang, Yi-Feng Shen, Ke-Qiang Yu +8 more
To observe the effect of electroacupuncture (EA) on hypothalamic-pituitary-gonadal (HPG) axis function and the expression of key enzymes for testosterone synthesis in high-fat diet-induced obese male rats, so as to explore its mechanism in improving obesity-related reproductive dysfunction.
Mirtazapine alleviates depressive-like behaviors through the paraventricular SIK1-CRTC1 signaling pathway.
J Affect Disord
Haibo Zhang, Hongli Dong, Zhengrong Xi +3 more
The paraventricular nucleus (PVN) plays a pivotal role in integrating neuroendocrine responses to stress, with the salt-inducible kinase 1 (SIK1)-CREB-regulated transcription co-activator 1 (CRTC1) pathway critically regulating corticotropin-releasing hormone expression and hypothalamic-pituitary-adrenal (HPA) axis activity. Mirtazapine is a clinically effective antidepressant with a unique noradrenergic and specific serotonergic mechanism, yet whether its therapeutic actions involve modulation of this PVN pathway remains unexplored.
Renal-diabetic overlap in pulmonary arterial hypertension.
Heart
Matteo Toma, Suela Vani, Giulio Savonitto +15 more
Comorbidities add complexity to pulmonary arterial hypertension (PAH), but also open opportunities to use therapies with benefits beyond the cardiovascular (CV) system, particularly preserving renal function and maintaining glucose homeostasis.
SLD5/GINS4 controls dynein-dependent centrosome maturation and exposes a candidate mitotic vulnerability in cancer.
bioRxiv
Vipin Kumar, Vivek Singh, Raksha Singh +2 more
Faithful proliferation requires coordinated DNA replication with centrosome maturation and spindle-pole integrity. SLD5, encoded by GINS4, is a core component of the GINS replication complex and is frequently elevated in tumors, but whether it links replication-associated cancer states to centrosome control has remained unclear. Here, we show that GINS4/SLD5 is recurrently upregulated across human cancers at transcript and protein levels and marks tumor programs enriched for DNA replication, chromosome segregation, and mitotic control. In cancer cells, Sld5 depletion dispersed PCM1, AZI1, and CEP290-positive centriolar satellites without eliminating these satellite proteins, reduced dynein heavy chain expression, and destabilized dynein-dynactin localization at spindle poles. Direct depletion of dynein heavy chain, co-depletion analyses, and pharmacological inhibition of dynein motor activity with ciliobrevin D phenocopied Sld5 loss, causing satellite dispersion, defective recruitment of PLK1, Aurora A, CEP192, and CEP215 to centrosomes, and multipolar spindle formation. These defects occurred without detectable DNA damage or checkpoint activation, indicating a non-canonical Sld5 function beyond its role in the replisome. Cancer dependency and kinase network analyses further nominate SLD5-associated mitotic and checkpoint pathways as therapeutic targets. Our findings identify SLD5/GINS4 as a regulator of dynein-dependent centrosome maturation and a candidate vulnerability in replication-driven cancers, with potential value for biomarker-guided therapeutic stratification.
Satellite microglia-like cells in human dorsal root ganglia and changes with diabetic neuropathy.
bioRxiv
Khadijah Mazhar, Jayden A O'Brien, Michael A Wilde +9 more
Phagocytic and immune-like cells have been observed in the satellite envelope of neuronal somata in peripheral sensory ganglia of many species for several decades. These cells likely play an important role in normal function of sensory neurons and they may also play an important role in neuronal dysfunction and neurodegeneration seen with neuropathy. Recent findings have described a satellite macrophage population transcriptomically similar to microglia in peripheral ganglia of some mammalian species. The function of these cells, and the mechanisms by which they may influence neurons in neuropathy are unclear. We sought to understand the phenotype and localization of these cells in the human dorsal root ganglion (hDRG) using large-scale single nucleus and spatial transcriptomic datasets from individuals with and without a history of peripheral diabetic neuropathy. We observed a large population of macrophages that express classical microglia makers such as TMEM119 and P2RY12 in the hDRG, as previously described. Our findings confirm that these microglia-like cells (MLCs) localize to the satellite envelope around neuronal somata, yet are transcriptomically distinct from all glial cell types characterized in the hDRG. These MLCs exhibit changes in abundance and localization with diabetic painful neuropathy (DPN) in both the hDRG and sural nerves suggesting that they are not exclusively localized to the DRG. We conclude that microglia-like cells are likely the resident tissue macrophage (RTM) of the hDRG, and perhaps the peripheral nervous system (PNS) given their localization to the sural nerve and other ganglia, where they are predicted to regulate homeostatic neuronal functions and response to injury.