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Bergamot Essential Oil Beverage: Preparation, Formulation Optimization, and Preliminary Evaluation of Antidepressant-like Effects in Mice Induced by Chronic Corticosterone Treatment.
Foods
Qingqing Yang, Zhirenyong Zhang, Yan Li
Bergamot essential oil (BEO) has demonstrated antidepressant potential, but its oral application is limited by poor water solubility and undesirable organoleptic properties. In this study, a BEO-loaded beverage was developed based on a whey protein-stabilized oil-in-water emulsion system. The optimal formulation, determined via single-factor experiments combined with orthogonal optimization, consisted of inulin (0.5 g/50 g), milk powder (2.0 g/50 g), sucralose (0.008 g/50 g), and sodium carboxymethyl cellulose (0.04 g/50 g). The resulting beverage remained stable without visible phase separation during 4 months of storage at 4 °C. In a chronic corticosterone treatment (CCT)-induced mouse model of depression, oral administration of the BEO beverage increased activity in the central area of the open field test and exploratory behavior in the elevated plus maze, while reducing repetitive stereotyped behaviors in the marble burying test. At the molecular level, the BEO beverage was associated with reduced levels of interleukin-1β (IL-1β), tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), and corticosteroid (CORT), and increased levels of corticotropin-releasing hormone (CRH), adrenocorticotropic hormone (ACTH), serotonin (5-HT), dopamine (DA), and norepinephrine (NE). Additionally, the BEO beverage was associated with observed alleviation of neuronal damage in the hippocampal CA3 region, upregulation of brain-derived neurotrophic factor (BDNF), improved gut microbial diversity, and altered host metabolic profiles. Collectively, these findings suggest that the BEO emulsion beverage is a feasible intervention for alleviating depression-like behaviors in the mouse model, and provide initial associative evidence supporting its potential as a functional food for mood management.
Utility of the post-cosyntropin urinary metabolomic profile for the subtype diagnosis of primary aldosteronism.
J Hypertens
Marta Araujo-Castro, Felicia A Hanzu, Jessica Goi +8 more
To analyze if differences between patients with unilateral (UPA) and bilateral primary aldosteronism (BPA) in baseline and cosyntropin-stimulated urinary steroid metabolomic profile (USMP), might serve to identify patients in whom adrenal venous sampling (AVS) could be avoided because of a low probability of UPA.
[Growth differentiation factor 11 attenuates hypoxia/reoxygenation injury in rat H9C2 cardiomyocytes in vitro by inhibiting thioredoxin-1 nitrative inactivation].
Nan Fang Yi Ke Da Xue Xue Bao
Jia Wei, Wei Jiang, Linying Xia +2 more
To verify the hypothesis that growth differentiation factor 11 (GDF11) attenuates myocardial ischemia/reperfusion (MI/R) injury and explore the underlying mechanism.
Association between upper airway obstruction and pulmonary hypertension in children with Down syndrome.
Curr Opin Pulm Med
Kevin Guy, Amal Isaiah
Down syndrome (DS) is the most common nonlethal chromosomal aneuploidy, affecting 1 in 700 live births. Pulmonary hypertension (PH) occurs in approximately 25% of children with DS and contributes to a 10% mortality rate within 3  years of diagnosis. Despite obstructive sleep apnea (OSA) affecting up to 80% of children with DS, the specific contribution of upper airway obstruction to PH in this population remains poorly characterized. This review synthesizes current evidence to address that gap.
Somatostatin in Aging: Correlations with Selected Central Nervous System and Gastrointestinal Tract Diseases.
Int J Mol Sci
Aldona Kasprzak
The hypothalamic-pituitary-somatotropic (HPS) axis, which includes growth hormone (GH) and insulin-like growth factor 1 (IGF-1), is one of three endocrine systems that show a decline in hormone concentration with age. Among the hypothalamic hormones involved in the aging process, GH-releasing hormone (GHRH) and somatostatin (SST) are most affected, resulting in several age-related changes. The pathophysiology of GH decline in the aging process is unclear, specifically, whether it results from decreased GHRH or increased SST levels. Similarly, it is not known whether quantitative changes in hypothalamic peptides (including SST) precede or follow age-related pathological behavioral changes. SST is produced mainly by cells of the central nervous system (CNS) and the gastrointestinal (GI) tract, which are functionally interconnected systems that undergo significant changes during aging. The physical changes in the aging organism are considered physiological, and experimental evidence indicates that a large proportion of these changes are the result of declining hormonal activity (including the SST system). It is particularly important to understand the role of SST in diseases of old age, which affect both cognitive processes and memory (e.g., Alzheimer's and Parkinson's diseases) and the proper functioning of the GI tract and pancreas (e.g., obesity, type 2 diabetes mellitus, and colorectal cancer). This narrative review discusses systemic and peripheral changes in SST production and secretion observed in aging individuals and their potential association with selected diseases of old age, especially CNS and GI tract diseases. Understanding the role of SST expression with age will enable the better application of this neuropeptide in the diagnosis and treatment of diseases of old age (including cancers).
[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.