Castration Model Illuminates Sex Differences in Healthy Aging: Insights from Metabolome and Transcriptome Analyses DOI Creative Commons
Jianjun Jiang, Na Ge, Yuzhi Wang

и другие.

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2023, Номер unknown

Опубликована: Дек. 28, 2023

ABSTRACT Background Sex, as a critical biological variable, has historically been underappreciated, despite the pervasive influence of sexual dimorphism across physiological and pathological processes. A significant obstacle to advancing sex-biased research is absence an effective animal model. In recent years, castration emerged potential model for elucidating sex-based differences in context healthy aging, where it shown equalize lifespan growth trajectories genetically diverse mice. However, molecular shifts induced by common laboratory models, such C57BL/6 mice, broader applicability this other sex-related contexts remain largely unexplored. Methods We employed multi-omics observational analyses investigate changes associated with sex hormones following castration. analyzed serum, kidney, liver samples from 12-week-old 18-month-old castrated male alongside intact female counterparts. The was further applied assess cisplatin-induced toxicity age-related cognitive decline comparison unaltered controls. Results LC-MS/MS metabolomics revealed that males exhibited substantial alterations steroid hormone levels increased concentrations antioxidant compounds, taurine, identical diets. Integrated metabolome-transcriptome analysis confirmed distinct patterns lipid peroxidation oxidative stress sham-operated female, male, Histopathological evaluations cisplatin treatment aging-related behavioral tests demonstrated model’s utility investigating sex-dependent drug decline. These findings underscored role modulating both defense mechanisms performance. Conclusion This study provides systematic spectrum on demonstrates its capacity feminize metabolic transcriptomic profiles, establishing valuable tool exploring hormone-driven differences. Our lay groundwork mechanistic studies broaden applications biomedical domains.

Язык: Английский

Resolvin D2/GPR18 signaling enhances monocytic myeloid‐derived suppressor cell function to mitigate abdominal aortic aneurysm formation DOI
Paolo Bellotti, Zachary Ladd, Victoria Leroy

и другие.

The FASEB Journal, Год журнала: 2024, Номер 38(18)

Опубликована: Сен. 25, 2024

Abstract Abdominal aortic aneurysm (AAA) formation is a chronic vascular pathology characterized by inflammation, leukocyte infiltration, and remodeling. The aim of this study was to delineate the protective role Resolvin D2 (RvD2), bioactive isoform specialized pro‐resolving lipid mediators, via G‐protein‐coupled receptor 18 (GPR18) signaling in attenuating AAAs. Importantly, RvD2 GPR18 levels were significantly decreased tissue AAA patients compared with controls. Furthermore, using an established murine model C57BL/6 (WT) mice, we observed that treatment attenuated diameter, pro‐inflammatory cytokine production, immune cell infiltration (neutrophils macrophages), elastic fiber disruption, increased smooth muscle α‐actin expression as well TGF‐β2 IL‐10 expressions untreated mice. Moreover, RvD2‐mediated protection from remodeling blocked when mice previously treated siRNA for signifying importance RvD2/GPR18 inflammation. Mechanistically, enhanced activation monocytic myeloid‐derived suppressor cells (M‐MDSCs) increasing secretions GPR18‐dependent manner attenuate inflammation Collectively, demonstrates induces expansion myeloid‐lineage committed progenitors, such M‐MDSCs, activates enhance secretion, mitigates SMC contributes resolution during formation.

Язык: Английский

Процитировано

1

RVD2 emerges as a serological marker in relation to severity and six-month clinical outcome following acute intracerebral hemorrhage: A prospective cohort study from a single academic institution DOI

Wenjie Yang,

Tiancheng Lu,

Hao Shan

и другие.

Clinica Chimica Acta, Год журнала: 2024, Номер unknown, С. 119988 - 119988

Опубликована: Окт. 1, 2024

Язык: Английский

Процитировано

1

Study on potential differentially expressed genes in idiopathic pulmonary fibrosis by bioinformatics and next generation sequencing data analysis DOI Open Access
Basavaraj Vastrad, Chanabasayya Vastrad

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2023, Номер unknown

Опубликована: Сен. 20, 2023

Abstract Idiopathic pulmonary fibrosis (IPF) is a chronic progressive lung disease with reduced quality of life and earlier mortality, but its pathogenesis key genes are still unclear. In this investigation, bioinformatics was used to deeply analyze the IPF related genes, so as investigate potential molecular provide guidance for clinical treatment. Next generation sequencing dataset GSE213001 obtained from Gene Expression Omnibus (GEO), differentially expressed (DEGs) were identified between normal control group. The DEGs group screened DESeq2 package R language. Ontology (GO) REACTOME pathway enrichment analyses performed.. Using g:Profiler, function analysis performed. Then, protein–protein interaction (PPI) network constructed via Integrated Interactions Database (IID) database. Cytoscape Network Analyzer identify hub genes. miRNet NetworkAnalyst database construct targeted microRNAs (miRNAs) transcription factors (TFs) Finally receiver operating characteristic (ROC) curve validates A total 958 out in study, including 479 up regulated down Most significantly enriched response stimulus, GPCR ligand binding, microtubule-based process defective GALNT3 causes HFTC. combination results PPI network, miRNA-hub gene regulatory TF-hub LRRK2, BMI1, EBP, MNDA, KBTBD7, KRT15, OTX1, TEKT4, SPAG8 EFHC2 selected. Our findings will contribute identification biomarkers novel strategies treatment IPF, strategy therapy.

Язык: Английский

Процитировано

2

Naringin dihydrochalcone alleviates sepsis-induced acute lung injury via improving gut microbial homeostasis and activating GPR18 receptor DOI
Siqi He,

Yuzhen Zhuo,

Lingzhi Cui

и другие.

International Immunopharmacology, Год журнала: 2024, Номер 137, С. 112418 - 112418

Опубликована: Июнь 19, 2024

Язык: Английский

Процитировано

0

Profiling Molecular Changes of Host Response to Predict Outcome in Children with Septic Shock DOI Open Access
A. V. Lalitha, Anil Vasudevan, M. Moorthy

и другие.

Indian Journal of Critical Care Medicine, Год журнала: 2024, Номер 28(9), С. 879 - 886

Опубликована: Авг. 29, 2024

Septic shock is associated with high mortality and there significant heterogeneity in the host response. The aim of this study was to understand genome-wide expression transcriptomic signatures children septic correlate them outcomes.

Язык: Английский

Процитировано

0

Research progress in the mechanisms and functions of specialized pro-resolving mediators in neurological diseases DOI Creative Commons

Yu Deng,

Fei Wang, Tianle Wang

и другие.

Prostaglandins & Other Lipid Mediators, Год журнала: 2024, Номер 175, С. 106905 - 106905

Опубликована: Сен. 10, 2024

Язык: Английский

Процитировано

0

Visual exposure to green light therapy reduces knee joint pain and alters the lipidome in osteoarthritic rats DOI Creative Commons
Melissa O’Brien,

Emily Richter,

Taylor J. Woodward

и другие.

Pain, Год журнала: 2024, Номер unknown

Опубликована: Окт. 18, 2024

Abstract Visual exposure to dim, green, light has been found reduce pain levels in patients living with migraine, low back pain, and fibromyalgia. Preclinical studies discovered that the analgesic effect of green was due central release endogenous opioids a reduction inflammatory cytokines cerebrospinal fluid. The present study assessed therapy (GLT) on joint rat model osteoarthritis (OA) investigated role endolipids. Male female Wistar rats (207-318 g) received an intra-articular injection sodium monoiodoacetate (3 mg 50 μL saline) into knee induce OA. On day 9, animals were placed room illuminated by either white (neutral-white 4000K; 20 lux) or (wavelength: 525 nm; luminance: for 5 days (8 hours per day). Joint nociception von Frey hair algesiometry, dynamic weight bearing, vivo single unit extracellular recordings from mechanonociceptors. Compared light, GLT significantly reduced secondary mechanical hypersensitivity both sexes improved hindlimb bearing females only. There no nociceptor activity sex. Serum lipidomics indicated increase circulating endolipids response GLT, particularly N -acyl-glycines. Partial blockade endocannabinoid system G protein receptor-18/cannabinoid-1 receptor antagonist AM281 (500 μg/kg i.p.) attenuated GLT-induced analgesia. These data show first time acts OA upregulating endolipids, which then engage system.

Язык: Английский

Процитировано

0

Resolvin D2/GPR 18 axis ameliorates pressure overload-induced heart failure by inhibiting pro-inflammatory macrophage polarization DOI Creative Commons
Zihui Zheng,

Mengmeng Zhao,

Yao Xu

и другие.

Journal of Lipid Research, Год журнала: 2024, Номер unknown, С. 100679 - 100679

Опубликована: Окт. 1, 2024

Язык: Английский

Процитировано

0

Castration Model Illuminates Sex Differences in Healthy Aging: Insights from Metabolome and Transcriptome Analyses DOI Creative Commons
Jianjun Jiang, Na Ge, Yuzhi Wang

и другие.

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2023, Номер unknown

Опубликована: Дек. 28, 2023

ABSTRACT Background Sex, as a critical biological variable, has historically been underappreciated, despite the pervasive influence of sexual dimorphism across physiological and pathological processes. A significant obstacle to advancing sex-biased research is absence an effective animal model. In recent years, castration emerged potential model for elucidating sex-based differences in context healthy aging, where it shown equalize lifespan growth trajectories genetically diverse mice. However, molecular shifts induced by common laboratory models, such C57BL/6 mice, broader applicability this other sex-related contexts remain largely unexplored. Methods We employed multi-omics observational analyses investigate changes associated with sex hormones following castration. analyzed serum, kidney, liver samples from 12-week-old 18-month-old castrated male alongside intact female counterparts. The was further applied assess cisplatin-induced toxicity age-related cognitive decline comparison unaltered controls. Results LC-MS/MS metabolomics revealed that males exhibited substantial alterations steroid hormone levels increased concentrations antioxidant compounds, taurine, identical diets. Integrated metabolome-transcriptome analysis confirmed distinct patterns lipid peroxidation oxidative stress sham-operated female, male, Histopathological evaluations cisplatin treatment aging-related behavioral tests demonstrated model’s utility investigating sex-dependent drug decline. These findings underscored role modulating both defense mechanisms performance. Conclusion This study provides systematic spectrum on demonstrates its capacity feminize metabolic transcriptomic profiles, establishing valuable tool exploring hormone-driven differences. Our lay groundwork mechanistic studies broaden applications biomedical domains.

Язык: Английский

Процитировано

0