Frontiers in bioscience (Landmark edition)最新文献

{"title":"Therapeutic Efficacy of Extracellular Vesicles Derived from Stem Cell for Alzheimer's Disease: A Meta-Analysis Study.","authors":"Huiyin Deng, Jing Zhao, Jiuyi Li, Chunli Chen, Zhiping Hu, Xiaomei Wu, Lite Ge","doi":"10.31083/j.fbl2909340","DOIUrl":"10.31083/j.fbl2909340","url":null,"abstract":"<p><strong>Background: </strong>Alzheimer's disease (AD) poses a significant public health challenge, increasingly affecting patients' finances, mental health, and functional abilities as the global population ages. Stem cell-derived extracellular vesicles (SC-EVs) have emerged as a promising cell-free therapeutic approach for AD, although their precise mechanisms remain unclear. This meta-analysis aims to evaluate the effectiveness of SC-EVs in treating AD.</p><p><strong>Methods: </strong>We systematically searched PubMed, EMBASE, and Web of Science databases up to December 31, 2023, identifying studies investigating SC-EVs therapy in AD rodent models. Outcome measures included Morris water maze and Y maze tests, β-amyloid pathology, and inflammatory markers. Statistical analyses utilized Stata 15.1 and R software.</p><p><strong>Results: </strong>This meta-analysis of 16 studies (2017-2023, 314 animals) demonstrates significant efficacy of SC-EVs therapy in AD models. Pooled analyses demonstrated that SC-EVs therapy significantly increased the learning function as measured by Morris water maze tests (MWM) by -1.83 (95% CI = -2.51 to -1.15, <i>p</i> < 0.0001), Y maze test by 1.66 (95% CI = 1.03 to 2.28, <i>p</i> < 0.0001), decreased Aβ plaques in the hippocampal by -2.10 (95% CI = -2.96 to -1.23, <i>p</i> < 0.0001), and proinflammatory cytokines Tumor necrosis factor alpha (TNFα) by -2.61 (95% CI = -4.87 to -0.35, <i>p</i> < 0.05), Interleukin-1 beta (IL-1β) by -2.37 (95% CI = -3.68 to -1.05, <i>p</i> < 0.001).</p><p><strong>Conclusions: </strong>SC-EVs therapy shows promise in enhancing cognitive function and mitigating AD progression in preclinical models. Future research should focus on standardizing methodologies and comparing SC-EVs isolation techniques and dosing strategies to facilitate clinical translation.</p>","PeriodicalId":73069,"journal":{"name":"Frontiers in bioscience (Landmark edition)","volume":"29 9","pages":"340"},"PeriodicalIF":3.3,"publicationDate":"2024-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142333790","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"ACE2 Alleviates Endoplasmic Reticulum Stress and Protects against Pyroptosis by Regulating Ang1-7/Mas in Ventilator-Induced Lung Injury.","authors":"Xingsheng Lin, Yingfeng Zhuang, Fengying Gao","doi":"10.31083/j.fbl2909334","DOIUrl":"https://doi.org/10.31083/j.fbl2909334","url":null,"abstract":"<p><strong>Background: </strong>Ventilator-induced lung injury (VILI) is a consequence of inflammation and increased alveolar-capillary membrane permeability due to alveolar hyperdistention or elevated intrapulmonary pressure, but the precise mechanisms remain unclear. The aim of the study was to analyze the mechanism by which angiotensin converting enzyme 2 (ACE2) alleviates endoplasmic reticulum stress (ERS) and protects alveolar cells from pyroptosis in VILI by regulating angiotensin (Ang)1-7/Mas.</p><p><strong>Methods: </strong>VILI was induced in mice by mechanical ventilation by regulating the tidal volume. The alveolar cell line, A549, mimics VILI <i>in vitro</i> by cyclic stretch (CS). Ang (1-7) (100 nmol/L) was added to the medium. ERS was induced in cells by stimulating with tunicamycin (TM, 2 μg/mL). ERS was inhibited by tracheal instillation of 4-phenylbutyric acid (4-PBA) (1 mg/kg). ACE2's enzymatic function was activated or inhibited by subcutaneous injection of resorcinolnaphthalein (RES, 20 μg/kg) or MLN-4760 (20 μg/kg). pGLV-EF1a-GFP-ACE2 was instilled into the trachea to increase the protein expression of ACE2. The Ang (1-7) receptor, Mas, was antagonized by injecting A779 subcutaneously (80 μg/kg).</p><p><strong>Results: </strong>ACE2 protein levels decreased after modeling. Ang (1-7) level was decreased and Ang II was accumulated. ERS was significantly induced in VILI mice, and pyroptosis was observed in cells. When ERS was inhibited, pyroptosis under the VILI condition was significantly inhibited. Ang (1-7) alleviated ERS and pyroptosis under CS. When ERS was continuously activated, the function of Ang (1-7) in inhibiting pyroptosis was blocked. Resorcinolnaphthalein (RES) effectively promoted Ang II conversion, alleviated the Ang (1-7) level in VILI, ameliorated lung injury, and inhibited ERS and cell pyroptosis. Inhibiting ACE2's function in VILI hindered the production of Ang (1-7), promoted the accumulation of Ang II, and exacerbated ERS and pyroptosis, along with lung injury. The Mas antagonist significantly blocked the inhibitory effects of ACE2 on ERS and pyroptosis in VILI.</p><p><strong>Conclusions: </strong>Reduced ACE2 expression in VILI is involved in ERS and pyroptosis-related injury. ACE2 can alleviate ERS in alveolar cells by catalyzing the production of Ang (1-7), thus inhibiting pyroptosis in VILI.</p>","PeriodicalId":73069,"journal":{"name":"Frontiers in bioscience (Landmark edition)","volume":"29 9","pages":"334"},"PeriodicalIF":3.3,"publicationDate":"2024-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142333766","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"ZNF429 Participates in the Progression of Coronary Heart Disease through Regulating Inflammatory and Adhesive Factors.","authors":"Hao Wang, Bo Wu, Xueqin He, Wei Li, Wenqi Guan","doi":"10.31083/j.fbl2909335","DOIUrl":"https://doi.org/10.31083/j.fbl2909335","url":null,"abstract":"<p><strong>Background: </strong>Coronary heart disease (CHD) is an intricate and multifaceted cardiovascular disorder that contributes significantly to global morbidity and mortality. Early and accurate identification and diagnosis of CHD are paramount to ensuring patients receive optimal therapeutic interventions and satisfactory outcomes.</p><p><strong>Methods: </strong>Data on CHD gene expression were obtained from the Gene Expression Omnibus (GEO) repository and potential hub genes were screened through gene ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), weighted gene co-expression network analysis (WGCNA), and least absolute shrinkage and selection operator (LASSO) analyses. Functional validation of these hub genes was conducted by interfering with them in human umbilical vein endothelial cells (HUVECs). Cell proliferation and apoptosis were assessed through cell counting kit-8 (CCK-8) and flow cytometry assays, respectively, while enzyme-linked immunosorbent assay (ELISA), quantitative polymerase chain reaction (qPCR), Western blot, and immunofluorescence were used to measure the expression of key indicators.</p><p><strong>Results: </strong>We identified 700 upregulated differentially expressed genes (DEGs) and 638 downregulated DEGs in CHD, and utilized LASSO analyses to screen disease potential biomarkers, such as zinc finger protein 429 (ZNF429). Interference with ZNF429 in HUVECs mitigated the CHD-induced decrease in cell proliferation and increase in apoptosis. Moreover, the expression of interleukin-1β (IL-1β), interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), vascular cell adhesion molecule-1 (VCAM-1), intercellular adhesion molecule-1 (ICAM-1), cluster of differentiation 62E (CD62E), and cluster of differentiation 62P (CD62P) was reduced, leading to decreased cellular inflammation and adhesion.</p><p><strong>Conclusions: </strong>CHD-associated biomarker ZNF429 was identified through bioinformatics analysis to potentially regulate the expression of inflammatory factors <i>IL-6</i>, <i>IL-1β</i>, and <i>TNF-α</i>, along with adhesion molecules <i>ICAM-1</i>, <i>VCAM-1</i>, <i>CD62E</i>, and <i>CD62P</i>. This modulation influence was subsequently found to impact the progression of CHD. These findings offered valuable insights into potential targets for further investigation and therapeutic interventions for CHD management.</p>","PeriodicalId":73069,"journal":{"name":"Frontiers in bioscience (Landmark edition)","volume":"29 9","pages":"335"},"PeriodicalIF":3.3,"publicationDate":"2024-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142333793","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Toll-Like Receptor 2 Deficiency Exacerbates Dextran Sodium Sulfate-Induced Intestinal Injury through <i>Marinifilaceae-</i>Dependent Attenuation of Cell Cycle Signaling.","authors":"Yun-Jie Shi, Kai-Wen Sheng, Hai-Nan Zhao, Cong Liu, Hao Wang","doi":"10.31083/j.fbl2909338","DOIUrl":"https://doi.org/10.31083/j.fbl2909338","url":null,"abstract":"<p><strong>Background: </strong>Ulcerative colitis (UC) is an intestinal disorder marked by chronic, recurring inflammation, yet its underlying mechanisms have not been fully elucidated.</p><p><strong>Methods: </strong>The current research dealt with examining the biological impacts of toll-like receptor 2 (TLR2) on dextran sulfate sodium (DSS)-triggered inflammation in the intestines of wild-type (WT) and TLR2-knockout (TLR2-KO) colitis mouse models. To elucidate the protective function of TLR2 in DSS-triggered colitis, RNA-sequencing (RNA-Seq) was carried out to compare the global gene expression data in the gut of WT and TLR2-KO mice. Further, 16S rRNA gene sequencing revealed notable variations in gut microbiota composition between WT and TLR2-KO colitis mice.</p><p><strong>Results: </strong>It was revealed that TLR2-KO mice exhibited increased susceptibility to DSS-triggered colitis. RNA-Seq results demonstrated that cell cycle pathway-related genes were notably downregulated in TLR2-KO colitis mice (enrichment score = 30, <i>p</i> < 0.001). 16S rRNA gene sequencing revealed that in comparison to the WT colitis mice, the relative abundance of <i>Marinifilacea</i> (<i>p</i> = 0.006), <i>Rikenellacea</i> (<i>p</i> = 0.005), <i>Desulfovibrionaceae</i> (<i>p</i> = 0.045), <i>Tannerellaceae</i> (<i>p</i> = 0.038), <i>Ruminococcaceae</i> (<i>p</i> = 0.003), <i>Clostridia</i> (<i>p</i> = 0.027), and <i>Mycoplasmataceae</i> (<i>p</i> = 0.0009) was significantly increased at the family level in the gut of TLR2-KO colitis mice. In addition, microbiome diversity-transcriptome collaboration analysis highlighted that the relative abundance of <i>Marinifilaceae</i> was negatively linked to the expression of cell cycle signaling-related genes (<i>p</i> values were all less than 0.001).</p><p><strong>Conclusion: </strong>Based on these findings, we concluded that TLR2-KO exacerbates DSS-triggered intestinal injury by mitigating cell cycle signaling in a <i>Marinifilaceae</i>-dependent manner.</p>","PeriodicalId":73069,"journal":{"name":"Frontiers in bioscience (Landmark edition)","volume":"29 9","pages":"338"},"PeriodicalIF":3.3,"publicationDate":"2024-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142333791","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Functions of Coenzyme A and Acyl-CoA in Post-Translational Modification and Human Disease.","authors":"Jumin Xie, Zhang Yu, Ying Zhu, Mei Zheng, Yanfang Zhu","doi":"10.31083/j.fbl2909331","DOIUrl":"https://doi.org/10.31083/j.fbl2909331","url":null,"abstract":"<p><p>Coenzyme A (CoA) is synthesized from pantothenate, L-cysteine and adenosine triphosphate (ATP), and plays a vital role in diverse physiological processes. Protein acylation is a common post-translational modification (PTM) that modifies protein structure, function and interactions. It occurs via the transfer of acyl groups from acyl-CoAs to various amino acids by acyltransferase. The characteristics and effects of acylation vary according to the origin, structure, and location of the acyl group. Acetyl-CoA, formyl-CoA, lactoyl-CoA, and malonyl-CoA are typical acyl group donors. The major acyl donor, acyl-CoA, enables modifications that impart distinct biological functions to both histone and non-histone proteins. These modifications are crucial for regulating gene expression, organizing chromatin, managing metabolism, and modulating the immune response. Moreover, CoA and acyl-CoA play significant roles in the development and progression of neurodegenerative diseases, cancer, cardiovascular diseases, and other health conditions. The goal of this review was to systematically describe the types of commonly utilized acyl-CoAs, their functions in protein PTM, and their roles in the progression of human diseases.</p>","PeriodicalId":73069,"journal":{"name":"Frontiers in bioscience (Landmark edition)","volume":"29 9","pages":"331"},"PeriodicalIF":3.3,"publicationDate":"2024-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142333774","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"GRN Activates TNFR2 to Promote Macrophage M2 Polarization Aggravating Mycobacterium Tuberculosis Infection.","authors":"Bingling Zhang, Lan Xiang, Jun Chen, Jun Zhang, Renliu Dong, Guolun Mo, Feng Wu","doi":"10.31083/j.fbl2909332","DOIUrl":"https://doi.org/10.31083/j.fbl2909332","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;The polarization of macrophages plays a critical role in the immune response to infectious diseases, with M2 polarization shown to be particularly important in various pathological processes. However, the specific mechanisms of M2 macrophage polarization in Mycobacterium tuberculosis (Mtb) infection remain unclear. In particular, the roles of Granulin (&lt;i&gt;GRN&lt;/i&gt;) and tumor necrosis factor receptor 2 (&lt;i&gt;TNFR2&lt;/i&gt;) in the M2 polarization process have not been thoroughly studied.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Objective: &lt;/strong&gt;To investigate the effect of macrophage M2 polarization on Mtb infection and the mechanism of &lt;i&gt;GRN&lt;/i&gt; and &lt;i&gt;TNFR2&lt;/i&gt; in M2 polarization.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;Forty patients with pulmonary tuberculosis (PTB) and 40 healthy volunteers were enrolled in this study, and peripheral blood samples were taken to detect the levels of &lt;i&gt;TNFR2&lt;/i&gt; and &lt;i&gt;GRN&lt;/i&gt; mRNA by Quantitative Reverse Transcription Polymerase Chain Reaction (RT-qPCR); monocytes were isolated and then assessed by Flow Cytometry (FC) for M1 and M2 macrophage levels. To further validate the function of &lt;i&gt;TNFR2&lt;/i&gt; in macrophage polarization, we used interleukin 4 (IL-4) to induce mouse monocyte macrophages RAW264.7 to M2 polarized state. The expression of &lt;i&gt;TNFR2&lt;/i&gt; was detected by Western Blot and RT-qPCR. Next, we constructed a &lt;i&gt;GRN&lt;/i&gt; knockdown plasmid and transfected it into IL-4-induced mouse monocyte macrophage RAW264.7, and detected the expression of &lt;i&gt;TNFR2&lt;/i&gt;, M1 macrophage-associated factors tumor necrosis factor-α (TNF-α), inducible nitric oxide synthase (iNOS), and interleukin 6 (IL-6), and the M2 macrophage-associated factors CD206, IL-10, and Arginase 1 (Arg1); Immunofluorescence staining was used to monitor the expression of CD86&lt;sup&gt;+&lt;/sup&gt; and CD206&lt;sup&gt;+&lt;/sup&gt;, and FC was used to analyze the macrophage phenotype. Subsequently, immunoprecipitation was used to detect the binding role of &lt;i&gt;GRN&lt;/i&gt; and &lt;i&gt;TNFR2&lt;/i&gt;. Finally, the effects of &lt;i&gt;GRN&lt;/i&gt; and &lt;i&gt;TNFR2&lt;/i&gt; in macrophage polarization were further explored by knocking down &lt;i&gt;GRN&lt;/i&gt; and simultaneously overexpressing &lt;i&gt;TNFR2&lt;/i&gt; and observing the macrophage polarization status.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;The results of the study showed elevated expression of &lt;i&gt;TNFR2&lt;/i&gt; and &lt;i&gt;GRN&lt;/i&gt; and predominance of M2 type in macrophages in PTB patients compared to healthy volunteers (&lt;i&gt;p&lt;/i&gt; &lt; 0.05). Moreover, &lt;i&gt;TNFR2&lt;/i&gt; was highly expressed in M2 macrophages (&lt;i&gt;p&lt;/i&gt; &lt; 0.05). Additionally, &lt;i&gt;GRN&lt;/i&gt; knockdown was followed by elevated expression of M1 polarization markers TNF-α, iNOS and IL-6 (&lt;i&gt;p&lt;/i&gt; &lt; 0.05), decreased levels of M2 polarization-associated factors CD206, IL-10 and Arg1 (&lt;i&gt;p&lt;/i&gt; &lt; 0.05), and macrophage polarization towards M1. Subsequently, we found that &lt;i&gt;GRN&lt;/i&gt; binds to &lt;i&gt;TNFR2&lt;/i&gt; and that &lt;i&gt;GRN&lt;/i&gt; upregulates TNFR2 expression (&lt;i&gt;p&lt;/i&gt; &lt; 0.05). In addition, knockdown of GRN elevated M1 polarization marker expression, decre","PeriodicalId":73069,"journal":{"name":"Frontiers in bioscience (Landmark edition)","volume":"29 9","pages":"332"},"PeriodicalIF":3.3,"publicationDate":"2024-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142333776","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Molecular Insights into the Interaction of Tryptophan Metabolites with the Human Aryl Hydrocarbon Receptor <i>in Silico</i>: Tryptophan as Antagonist and no Direct Involvement of Kynurenine.","authors":"Abdulla A-B Badawy, Shazia Dawood","doi":"10.31083/j.fbl2909333","DOIUrl":"https://doi.org/10.31083/j.fbl2909333","url":null,"abstract":"<p><strong>Background: </strong>A direct link between the tryptophan (Trp) metabolite kynurenine (Kyn) and the aryl hydrocarbon receptor (AhR) is not supported by metabolic considerations and by studies demonstrating the failure of Kyn concentrations of up to 100 μM to activate the receptor in cell culture systems using the proxy system of cytochrome <i>P-</i>450-dependent metabolism. The Kyn metabolite kynurenic acid (KA) activates the AhR and may mediate the Kyn link. Recent studies demonstrated down regulation and antagonism of activation of the AhR by Trp. We have addressed the link between Kyn and the AhR by looking at their direct molecular interaction <i>in silico</i>.</p><p><strong>Methods: </strong>Molecular docking of Kyn, KA, Trp and a range of Trp metabolites to the crystal structure of the human AhR was performed under appropriate docking conditions.</p><p><strong>Results: </strong>Trp and 30 of its metabolites docked to the AhR to various degrees, whereas Kyn and 3-hydroxykynurenine did not. The strongest docking was observed with the Trp metabolite and photooxidation product 6-Formylindolo[3,2-b]carbazole (FICZ), cinnabarinic acid, 5-hydroxytryptophan, N-acetyl serotonin and indol-3-yllactic acid. Strong docking was also observed with other 5-hydroxyindoles.</p><p><strong>Conclusions: </strong>We propose that the Kyn-AhR link is mediated by KA. The strong docking of Trp and its recently reported down regulation of the receptor suggest that Trp is an AhR antagonist and may thus play important roles in body homeostasis beyond known properties or simply being the precursor of biologically active metabolites. Differences in AhR activation reported in the literature are discussed.</p>","PeriodicalId":73069,"journal":{"name":"Frontiers in bioscience (Landmark edition)","volume":"29 9","pages":"333"},"PeriodicalIF":3.3,"publicationDate":"2024-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142333781","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Retinal Biology in Health and Disease.","authors":"Adrian Gericke","doi":"10.31083/j.fbl2909337","DOIUrl":"https://doi.org/10.31083/j.fbl2909337","url":null,"abstract":"","PeriodicalId":73069,"journal":{"name":"Frontiers in bioscience (Landmark edition)","volume":"29 9","pages":"337"},"PeriodicalIF":3.3,"publicationDate":"2024-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142333785","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"CTRP9: An Anti-Atherosclerotic Factor in ApoE Knockout Mice through Oxidative Stress Inhibition.","authors":"Hua Guan, Hao Xu, Bin Yan, Aoqi Xiang, Xiaochang Chen, Qi Yu, Lixian Xu","doi":"10.31083/j.fbl2909339","DOIUrl":"https://doi.org/10.31083/j.fbl2909339","url":null,"abstract":"<p><strong>Background: </strong>C1q/tumor necrosis factor-related protein-9 (CTRP9) is critically involved in the pathophysiology of metabolic and cardiovascular disorders. This investigation aimed to clarify the mechanism underlying the role of CTRP9 in atherosclerosis in apolipoprotein E (ApoE) knockout (KO) mice.</p><p><strong>Methods: </strong>ApoE KO mice were fed a Western diet and injected with a virus which resulted in CTRP9 overexpression or knockdown for 12 weeks. The plasma lipid levels and atherosclerotic plaque areas were measured after the mice were euthanized. Aortas were isolated, and RNA sequencing was performed to identify the differentially expressed genes and related signaling pathways. Finally, plasma oxidative stress factors were measured to demonstrate the reliability of the RNA sequencing results.</p><p><strong>Results: </strong>The plasma lipid levels in the CTRP9 overexpression group did not significantly differ from those in the green fluorescence protein (GFP) group. Markablely, CTRP9 overexpression inhibited atherosclerotic plaque formation in ApoE KO mice, whereas CTRP9 knockdown promoted plaque formation. RNA sequencing analysis identified 3485 differentially expressed genes that were prominently enriched across 55 signaling pathways. Additionally, plasma oxidative stress factors were significantly reduced after CTRP9 overexpression, whereas these factors were increased after CTRP9 knockdown, which was consistent with the results of the RNA sequencing analysis.</p><p><strong>Conclusions: </strong>These findings demonstrated that CTRP9 alleviated inflammation and cholesterol metabolism, which reduced oxidative stress in an atherosclerotic animal model. These beneficial effects may mediate the suppression of lesion development in the aorta.</p>","PeriodicalId":73069,"journal":{"name":"Frontiers in bioscience (Landmark edition)","volume":"29 9","pages":"339"},"PeriodicalIF":3.3,"publicationDate":"2024-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142333771","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"β-Adrenoceptor Signaling Activation Improves Bladder Fibrosis by Inhibiting Extracellular Matrix Deposition of Bladder Outlet Obstruction.","authors":"Junyu Lai, Guo Chen, Hongwei Su, Qing He, Kaiwen Xiao, Banghua Liao, Jianzhong Ai","doi":"10.31083/j.fbl2909336","DOIUrl":"https://doi.org/10.31083/j.fbl2909336","url":null,"abstract":"<p><strong>Background: </strong>Partial bladder outlet obstruction (pBOO) causes deposition of extracellular matrix (ECM), promotes bladder fibrosis, and decreases bladder compliance.</p><p><strong>Methods: </strong>To investigate the effect of β-adrenoceptor (ADRB) on the ECM deposition of pBOO rat model and explore its underlying mechanism, human bladder smooth muscle cells (hBSMCs) were exposed to the pathological hydrostatic pressure (100 cm H₂O) for 6 h, reverse transcription-polymerase chain reaction (RT-PCR) and western blotting were employed. Then the rats of sham operation and pBOO model were treated with vehicle or ADRB agonists for 3 weeks, and the alterations of the bladder were observed via Masson staining and immunohistochemical analysis.</p><p><strong>Results: </strong>100 cm H₂O hydrostatic pressure significantly upregulated the expression of collagen I (COL1), collagen III (COL3) and fibronectin (FN), and downregulated the expression of ADRB2 and ADRB3 of hBSMCs at 6 h. The agonists of ADRB2 and ADRB3, Formoterol and BRL 37344, decreased COL1 and FN expression of hBSMCs under 100 cm H₂O for 6 h compared with the cells exposed to hydrostatic pressure only. As the classic downstream pathways of ADRB, the EPAC pathway inhibited COL1 and FN expression of hBSMCs via regulating SMAD3 and SMAD2 activities, respectively. In pBOO rats, Procaterol (ADRB2 agonist), and Mirabegron (ADRB3 agonist) inhibited the formation of collagen and decreased the expression of FN and COL1 in the bladders of pBOO rats.</p><p><strong>Conclusions: </strong>The bladder fibrosis of pBOO and deposition of hBSMCs ECM under hydrostatic pressure were regulated by ADRB2, and ADRB3 via EPAC/SMAD2/FN and EPAC/SMAD3/COL1 pathways, these findings pave an avenue for effective treatment of pBOO.</p>","PeriodicalId":73069,"journal":{"name":"Frontiers in bioscience (Landmark edition)","volume":"29 9","pages":"336"},"PeriodicalIF":3.3,"publicationDate":"2024-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142333805","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}