Exosomes derived from 3D-cultured hUCMSCs exhibit superior hepatoprotection against ALF
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PROVIDER: PRJNA1304384 | ENA |
REPOSITORIES: ENA
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Project description:Researching exosomes derived from human umbilical cord mesenchymal stem cells (hUCMSCs) cultured in 2D and 3D environments, it was discovered that exosomes from 3D-cultured hUCMSCs exhibit superior hepatoprotective effects on acute liver failure by upregulating YAP/TAZ and autophagy signaling
2025-08-15 | GSE305065 | GEO
Project description:Superbugs such as drug-resistant Mycobacterium tuberculosis (DR-M.tb) poses a serious global health threat. Upon infection, M.tb reaches the alveolar space and comes in close contact with soluble components of the human alveolar lining fluid (ALF) for an uncertain period of time prior to and following its encounter with alveolar compartment cells. Homeostatic ALF hydrolases, which main function is maintaining lung health, modify the M.tb cell envelope, driving M.tb-host cell interactions. Still, the contribution of human ALF to M.tb adaptation to the host during infection is poorly understood. Here, we exposed 4 M.tb strains (H37Rv, HN878, CDC1551, W-7642) with different levels of virulence, transmissibility, and drug resistance to human ALF for shorter (15 min) and longer (12 h) periods of time. RNA sequencing was performed to determine the strains’ transcriptional profiles in response to ALF exposure. Gene expression analysis showed a clear temporal and strain-specific adaptation to human ALF. When comparing ALF-exposed vs. unexposed bacteria for each M.tb strain, differential expression (DE) analysis revealed a total of 397 DE genes associated with lipid metabolism, cell envelope and processes, intermediary metabolism and respiration, and regulatory proteins, among others. Most DE was detected at 12 h post-ALF exposure, with DR-M.tb strain W-7642 having the highest number of DE genes. Interestingly, genes from the KstR2 regulon, which controls the degradation of cholesterol C and D rings, were significantly upregulated early in all strains post-ALF exposure. These results indicate that M.tb-ALF contact (15 min to 12 h prior to M.tb recognition by host cells in the alveolar space) drives global metabolic and physiologic changes in M.tb during the initial stages of the infection, with potential implications in infection outcome.
2024-02-20 | GSE228998 | GEO
Project description:Fifty percent of all acute liver failure (ALF) cases in the United States are due to acetaminophen (APAP) overdose. Assessment of canonical features of liver injury, such as plasma alanine aminotransferase activities are poor predictors of acute liver failure (ALF), suggesting the involvement of additional mechanisms independent of hepatocyte death. Previous work demonstrated a severe overdose of APAP results in impaired regeneration, the induction of senescence by p21, and increased mortality. We hypothesized that a discrete population of p21+ hepatocytes acquired a secretory phenotype that directly impedes liver recovery after a severe APAP overdose. Leveraging in-house human APAP explant liver and publicly available singlenuclei RNAseq data, we identified a subpopulation of p21+ hepatocytes enriched in a unique secretome of factors, such as Cxcl14. Spatial transcriptomics in the mouse model of APAP overdose confirmed the presence of a p21+ hepatocyte population that directly surrounded the necrotic areas. In both male and female mice, we found a dose-dependent induction of p21 and persistent circulating levels of the p21-specific constituent, Cxcl14, in the plasma after a severe APAP overdose. In parallel experiments, we targeted either the putative senescent hepatocytes with the senolytic drugs, dasatinib and quercetin, or Cxcl14 with a neutralizing antibody. We found that targeting Cxcl14 greatly enhanced liver recovery after APAP-induced liver injury, while targeting the senescent hepatocyte had no effect. This data supports that the sustained induction of p21 in hepatocytes with persistent Cxcl14 secretion are critical mechanistic events leading to ALF in mice and human patients.
2024-04-15 | GSE255777 | GEO
Project description:Acute liver failure (ALF) has an extremely high mortality rate and lacks effective treatment. Previous studies have shown that targeting macrophage pyruvate kinase isoenzyme type M2 (PKM2) may be a new approach for ALF treatment, but the exact mechanism remains to be elucidated. In this project, based on Single-cell RNA-sequencing (scRNA-seq), Pkm myeloid selective knockout (PL) mice and wild-type (WT) mice were used to establish ALF model, analyze the single-cell transcriptomic features of liver tissues of WT mice during ALF pathology, and screen for the differentially expressed genes in liver tissues of PL mice. Potential molecular pathways of PKM2 regulation of ALF in macrophages were explored by bioinformatics analysis and validated by molecular biology methods. Result shows that, up-regulated genes in macrophages and neutrophils in mouse liver tissues during ALF were mainly enriched in multiple programmed death, such as pyroptosis, apoptosis and necroptosis, and immune-inflammation pathways. The down-regulated genes in PL mouse liver macrophages and neutrophils were mostly enriched in the above pathways. Among them, Pkm knockdown significantly down-regulated the expression of key genes of NOD-like signaling pathway, such as NLRP3, IL-1β and IL-18, inhibited hepatic macrophage pyroptosis and attenuated ALF. This study will help to elucidate the molecular mechanism of PKM2 regulating macrophage inflammatory response involved in ALF, suggesting that PKM2 may be a potential therapeutic target for ALF, and providing a theoretical basis for further research on new methods of targeting PKM2 in the treatment of ALF.
2024-10-28 | GSE254497 | GEO
Project description:Evaluation of early transcriptional changes in blood brain barrier genes involved in the patogenesis of brain edema associated with ALF. Two different well stablished rat models were analyzed: Portacaval anastomosis plus hepatic artery ligation and portacaval anastomosis plus total hepatectomy. ALF was induced by portocaval anastomosis (PCA) and 24 hours after the surgery animals underwent hepatic artery ligation (HAL) or total hepatectomy (HEP). Sham rats were subjected to a fictitious two-step surgery. Between 8 and 12 hours after the last surgery rats were euthanized by decapitation, to avoid anesthetic effects, and cortical microvessels isolated.
2016-04-05 | E-GEOD-79906 | biostudies-arrayexpress
Project description:Mesenchymal stem cell (MSC)-derived exosomes had been reported to be a prospective candidate in accelerating diabetic wound healing. Hence, this study intended to explore whether exosomes originating from the human umbilical cord MSC (hucMSC) could display a superior proangiogenic effect on diabetic wound repair and its underlying molecular mechanism.
2022-03-04 | GSE197900 | GEO
Project description:Candidatus Nasuia deltocephalinicola str. NAS-ALF Genome sequencing
| PRJNA206993 | ENA
Project description:Candidatus Karelsulcia muelleri str. Sulcia-ALF Genome sequencing
| PRJNA206992 | ENA
Project description:microRNA profiles of Exosomes from Pooled NPC Patients serum comparing Control Exosomes from Healthy donors serum Two-condition experiment, Exosomes from Pooled Healthy donors serum vs. Exosomes from Pooled NPC Patients serum. Biological replicates: 1 Exosomes from Pooled Healthy donors serum, 1 Exosomes from Pooled NPC Patients serum,
2014-05-06 | E-GEOD-57319 | biostudies-arrayexpress