Discovery medicine最新文献

{"title":"Circ-100290 Regulates Autophagy-Mediated Angiogenesis of Human Umbilical Vein Endothelial Cells Induced by Conditioned Medium of Human Amniotic Mesenchymal Stem Cells.","authors":"Leiting Yang,&nbsp;Han Yan,&nbsp;Yi Liang,&nbsp;Dian Sun,&nbsp;Shijun Lu,&nbsp;Zichun Tang,&nbsp;Ming Ma,&nbsp;Ming Shen","doi":"10.24976/Discov.Med.202335176.39","DOIUrl":"https://doi.org/10.24976/Discov.Med.202335176.39","url":null,"abstract":"<p><strong>Background: </strong>Conditioned medium (CM) from human amnion-derived mesenchymal stem cells (hAMSCs) exhibits excellent pro-angiogenic capacity, and circ-100290 participates in this process. Autophagy is involved in the relevant mechanisms of angiogenesis, but it is unclear whether autophagy is related to the pro-angiogenesis effect of hAMSCs. This research sought to determine whether autophagy involved in the process of pro-angiogenesis induced by hAMSCs might be regulated by circ-100290.</p><p><strong>Methods: </strong>Upon treatment with CM from hAMSC or 3-methyladenine (3-MA), autophagosomes in human umbilical vein endothelial cells (HUVECs) were observed by transmission electron microscopy. HUVECs' angiogenic ability was evaluated by <i>in vitro</i> assays (transwell, wound healing, tube formation) and an <i>in vivo</i> Matrigel plug assay. Specific small interfering RNAs (siRNA) or inhibitors were used to regulate circ-100290 expression. Additionally, western blot and quantitative reverse transcription-polymerase chain reaction (RT-qPCR) were used to evaluate expression of the following indicators: Beclin-1, LC3-II, matrix metalloproteinase 2 (MMP2), MMP9, vascular endothelial growth factor (VEGF)-A, and endothelial nitric oxide synthase (eNOS).</p><p><strong>Results: </strong>Incubation with hAMSC-CM increased autophagy, angiogenesis and the expressions of VEGF-A and eNOS in HUVECs, all of which were inhibited by 3-MA. Knocking down circ-100290 in hAMSC-CM-treated HUVECs reduced Beclin-1 expression and inhibited autophagy. This resulted in lower angiogenesis in the Matrigel plug assay showing that reduced angiogenesis occurred after circ-100290 silencing in hAMSC-CM-treated HUVECs.</p><p><strong>Conclusions: </strong>Circ-100290 promotes autophagy-mediated angiogenesis in hAMSC-CM-treated HUVECs.</p>","PeriodicalId":11379,"journal":{"name":"Discovery medicine","volume":"35 176","pages":"383-393"},"PeriodicalIF":1.4,"publicationDate":"2023-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9980805","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"PTIP Deficiency in B Lymphocytes Ameliorates Dextran Sulfate Sodium-Induced Ulcerative Colitis in Mice.","authors":"Jiaxuan Liu, Yaqin Xu, Yong Q Chen, Dan Su","doi":"10.24976/Discov.Med.202335176.35","DOIUrl":"10.24976/Discov.Med.202335176.35","url":null,"abstract":"<p><strong>Background: </strong>Immune dysregulation contributes to the development of ulcerative colitis (UC). The research on the inflammatory response of UC is mainly focused on T cells, with less understanding of the role of B cells. Pax transactivation domain-interacting protein (PTIP) is essential for the development of B cell subpopulations and humoral immunity. The purpose of this study was to elucidate the role of PTIP in B cells of mice with dextran sodium sulfate (DSS)-induced colitis.</p><p><strong>Methods: </strong>The B-cell-specific PTIP knockout (PTIP^-/-) mice were established by crossbreeding cluster of differentiation (CD)19^cre/cre mice with PTIP^flox/flox mice. The UC mice were induced by drinking water supplemented with 3.8% Dextran Sulfate Sodium (DSS) (PTIP^-/- + DSS). The histological analysis was performed using hematoxylin and eosin staining. The immune cells were isolated using a fluorescence-activated cell sorter. The serum antibodies (immunoglobulin M (IgM) or immunoglobulin G (IgG)) and tumor necrosis factor (TNF)-α were determined by Enzyme linked immunosorbent assay (ELISA).</p><p><strong>Results: </strong>Interestingly, our findings demonstrate that PTIP deficiency in B cells significantly ameliorates UC. In contrast to PTIP^-/- + DSS, the wild type (WT) + DSS group showed a more robust increase in disease activity index (DAI) scores (<i>p</i> < 0.05), a substantially shortened colon (<i>p</i> < 0.001) and a decrease of mucous-producing goblet cells and the complete destruction of crypts. Moreover, PTIP-deficient mice manifested markedly altered neutrophil and T-cell distribution in UC (<i>p</i> < 0.05). Although anti-commensal IgG exacerbates UC, we demonstrated, for the first time, that serum natural IgG does not aggravate the pathology of UC. Furthermore, PTIP regulates UC by controlling B-2 cells independently from T cells.</p><p><strong>Conclusions: </strong>Transplantation of splenic B-2 cells from PTIP-deficient mice protected recipient NOD/ShiltJGpt-Prkdcem26Cd52Il2rgem26Cd22/Gpt (NCG) mice from severe UC.</p>","PeriodicalId":11379,"journal":{"name":"Discovery medicine","volume":"35 176","pages":"343-352"},"PeriodicalIF":2.1,"publicationDate":"2023-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9980802","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Safety and Tolerability of Omalizumab in Children with Allergic (<i>IgE</i>-Mediated) Asthma: A Systematic Review and Meta-Analysis.","authors":"Dandan Lang,&nbsp;Zhengmin Liu,&nbsp;Dejun Li","doi":"10.24976/Discov.Med.202335176.24","DOIUrl":"https://doi.org/10.24976/Discov.Med.202335176.24","url":null,"abstract":"<p><strong>Background: </strong>Omalizumab is a recombinant humanized monoclonal antibody against immunoglobulin E., which can specifically bind to <i>IgE</i> in blood and inhibit the release of inflammatory mediators to improve the symptoms of <i>IgE</i>-mediated asthma effectively. This meta-analysis was used to retrieve the studies in recent years to provide a clinical reference for the omalizumab in treating allergic asthma (AA).</p><p><strong>Methods: </strong>The databases Ovid, Embase, Pubmed, the Cochrane Library of clinical trials, CNKI (China National Knowledge Infrastructure) (China), and Wangfang Data (China) were searched for all studies on omalizumab involvement in treating allergic childhood asthma up to January 2022. Effectiveness, rate of exacerbation within 24 weeks (and 52 weeks), and the incidence of adverse reactions and serious adverse reactions were used as the primary data analysis indicators.</p><p><strong>Results: </strong>Seven eligible pieces of literature were included. Meta-analysis indicated that omalizumab could significantly improve the treatment efficacy in children with asthma [<i>RR</i> (Risk Ratio) = 1.24, 95% CI (Confidential Interval) (1.09, 1.41), <i>Z</i> = 3.30, <i>p</i> = 0.001], reduced the incidence of significant clinical exacerbation in children with asthma within 24 weeks [<i>RR</i> = 0.55, 95% CI (0.35, 0.85), <i>Z</i> = -2.67, <i>p</i> = 0.001], reduced the incidence of significant clinical exacerbation in children with asthma within 52 weeks [<i>RR</i> = 0.52, 95% CI (0.39, 0.71), <i>Z</i> = -4.2, <i>p</i> < 0.0001], and the incidence of total serious adverse reactions was not statistically different from placebo [<i>RR</i> = 1.00, 95% CI (0.98, 1.03), <i>Z</i> = 0.71, <i>p</i> = 0.479], the incidence of serious adverse reactions was significantly decreased [<i>RR</i> = 0.53, 95% CI (0.36, 0.77), <i>Z</i> = -3.35, <i>p</i> = 0.001].</p><p><strong>Conclusions: </strong>In treating <i>IgE</i> (immunoglobulin E)-mediated asthma in children, adding oral (or subcutaneous) omalizumab to a glucocorticoid regimen can enhance the effectiveness of treatment, reduce the probability of significant exacerbation during treatment, and reduce the incidence of serious adverse reactions.</p>","PeriodicalId":11379,"journal":{"name":"Discovery medicine","volume":"35 176","pages":"233-241"},"PeriodicalIF":1.4,"publicationDate":"2023-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9599842","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Risk Factors for Sarcopenia in Thai Patients with Rheumatoid Arthritis.","authors":"Wanruchada Katchamart,&nbsp;Suppavich Kieattisaksopon,&nbsp;Pongthorn Narongroeknawin,&nbsp;Weerasak Muangpaisan,&nbsp;Narittaya Varothai","doi":"10.24976/Discov.Med.202335176.44","DOIUrl":"https://doi.org/10.24976/Discov.Med.202335176.44","url":null,"abstract":"<p><strong>Background: </strong>Sarcopenia is a common condition that can occur in people with chronic inflammatory diseases, including rheumatoid arthritis (RA). The aim of this study was to determine the prevalence and factors associated with this condition in patients with RA.</p><p><strong>Methods: </strong>This prospective cross-sectional study was conducted on 182 adult patients with RA. They were diagnosed with sarcopenia using the Asian Working Group's 2019 update on sarcopenia diagnosis. The body composition was estimated using a body impedance analyzer. Physical performance and muscle strength were evaluated with six-meter walk test and hand grip dynamometer, respectively. The Disease Activity Score (DAS) 28 and the Health Assessment Questionnaire (HAQ) were used to assess disease activity and functional status, respectively.</p><p><strong>Results: </strong>The majority (87.4%) were female with a mean age (SD) of 59.2 (10.2) years. They had been suffering from RA for a long time (median disease duration [Interquartile range (IQR)] 11 [6-16] years) and had mildly active disease [mean DAS28 (SD) 2.61 (0.83)] with slightly functional disability [median HAQ (IQR) 0.34 (0-0.65)]. Of these, 26.4% had sarcopenia. Advanced age [relative risk (RR) 1.07 (95% confidence interval (CI) 1.02-1.11), <i>p</i> = 0.002], low body mass index (BMI) [RR (95% CI) 0.81 (0.72-0.90), <i>p</i> < 0.001], high disease activity [RR (95% CI) 1.64 (1.22-2.12), <i>p</i> = 0.045], and depression [RR (95% CI) 1.18 (1.01-1.37), <i>p</i> = 0.04] were independently associated with sarcopenia.</p><p><strong>Conclusions: </strong>Sarcopenia was found to be common in Thai RA, and its independent risk factors are age, disease activity, BMI, and depression. Well-controlled disease activity may be beneficial for preventing or minimizing sarcopenia and improving patient outcomes.</p>","PeriodicalId":11379,"journal":{"name":"Discovery medicine","volume":"35 176","pages":"436-443"},"PeriodicalIF":1.4,"publicationDate":"2023-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9599854","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Antifatigue Effect of Asiaticoside in Mice by Attenuating Oxidative Stress.","authors":"Xinghai Liu, Tong Liu, Kunli Yang, Hong Liu","doi":"10.24976/Discov.Med.202335176.28","DOIUrl":"10.24976/Discov.Med.202335176.28","url":null,"abstract":"<p><strong>Background: </strong>Asiaticoside is one of the main components of triterpenoid saponins extracted from <i>Centella asiatica</i>. Asiaticoside has shown the effects of wound healing, osteoclastogenesis, anti-inflammatory, anti-cancer, and improving cognition in multiple human disease models. However, studies on the antifatigue effects of asiaticoside have not been explored. Therefore, the aim of this study was to investigate the potential antifatigue effect and underlying mechanism of asiaticoside administration on exhaustive exercise performance.</p><p><strong>Methods: </strong>Male Kunming mice were divided into four groups randomly (n = 20/group). Saline (10 mL/kg) was administered to the model control group and the other three experimental groups were fed with low (10 mg/kg), medium (20 mg/kg) and high (40 mg/kg) asiaticoside once/daily for 14 days. The antifatigue effect of asiaticoside on mice was estimated by analyzing changes in body weight, weight-loaded swimming time, rotating time, lactic acid, urea nitrogen, liver/muscle glycogen, serumal superoxide dismutase, superoxide dismutase and the liver tissues of hematoxylin and eosin (H&E) staining.</p><p><strong>Results: </strong>The results indicated that no significant differences were observed in the body weight of each group (<i>p</i> > 0.05). Compared with the model control group, supplementation of asiaticoside significantly prolonged the weight-loaded swimming time and rotating time; Decreased the blood lactic acid (LA), blood urea nitrogen (BUN), and serumal malonaldehyde (MDA); And increased the content of liver/muscle glycogen and serumal superoxide dismutase levels (SOD) (<i>p</i> < 0.05). Furthermore, the pathological results of the liver were improved greatly. The maximal effect was observed in the medium group of 20 mg/kg.</p><p><strong>Conclusions: </strong>Asiaticoside is capable of reducing the fatigue effect by regulating energy consumption, energy metabolism and improving antioxidant activity after exercise. While there are still some shortcomings in this study, our findings provide a scientific basis for developing an asiaticoside-based antifatigue supplement.</p>","PeriodicalId":11379,"journal":{"name":"Discovery medicine","volume":"35 176","pages":"275-282"},"PeriodicalIF":2.1,"publicationDate":"2023-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9607575","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Development of FAP-Targeted Chimeric Antigen Receptor NK-92 Cells for Non-Small Cell Lung Cancer.","authors":"Yang Fang,&nbsp;Yan-Jing Wang,&nbsp;Hong-Li Zhao,&nbsp;Xin Huang,&nbsp;Yi-Nan Fang,&nbsp;Wen-Yi Chen,&nbsp;Ruo-Zhen Han,&nbsp;Ai Zhao,&nbsp;Ji-Min Gao","doi":"10.24976/Discov.Med.202335176.41","DOIUrl":"https://doi.org/10.24976/Discov.Med.202335176.41","url":null,"abstract":"<p><strong>Objectives: </strong>Over the past two decades, great progress has been made in advancing the early detection and multimodal treatment of non-small cell lung cancer (NSCLC). However, overall cure rates and survival rates of NSCLC are still not satisfactory, and research into new therapies is needed. This study attempted to construct human Fibroblast Activation Protein-Chimeric Antigen Receptor Natural killer (NK)-92 cells (hFAP-CAR-NK-92 cells) and explore their potential therapeutic effects in NSCLC.</p><p><strong>Methods: </strong>Immunohistochemistry analysis was carried out to examine fibroblast activation protein (FAP) and Gasdermin E (GSDME) expression in clinical specimens of lung adenocarcinoma and squamous cell carcinoma tissue. Then the engineered hFAP-CAR-NK-92 cells efficiency was determined <i>in vitro</i> with lactate dehydrogenase (LDH) cytotoxicity assay and the cell morphology of A549, H226, and cancer-related fibroblast (CAF) was observed by electron microscopy. After the co-culture of target cells and effect cells, flow cytometry was employed for examining the CD107a expression in the effect cells, and western blotting was conducted for the cleavage levels of Caspase 3 and GSDME proteins in the target cells. The safety and efficacy of hFAP-CAR-NK-92 cells adoptive transfer immunotherapy in a tumor-bearing mouse were evaluated.</p><p><strong>Results: </strong>Clinical studies have shown FAP positivity in patients with NSCLC. Compared with A549 or H226 cells alone, FAP expression was notably raised in A549+CAF cells or H226+CAF cells in nude mice, respectively (<i>p</i> < 0.05). The killing efficiency of K562 cells was not significantly different between hFAP-CAR-NK-92 and NK-92 cells (<i>p</i> > 0.05). The hFAP-CAR-NK-92 cells presented a higher killing efficiency against the hFAP-target (A549-hFAP, H226-hFAP and CAF-hFAP) cells than the NK-92 cells (<i>p</i> < 0.05). The degranulation of CD107a and cleavage levels of GSDME and Caspase 3 protein in the hFAP-CAR-NK-92 group were higher than those in the NK-92 group (<i>p</i> < 0.05). The 300 nM Granzyme B also induced pyroptosis in hFAP- or GSDME-positive cells (<i>p</i> < 0.05). <i>In vivo</i> experiments revealed that hFAP-CAR-NK-92 cells inhibited tumor progression of hFAP-positive NSCLC (<i>p</i> < 0.05).</p><p><strong>Conclusions: </strong>In this study, we successfully constructed hFAP-CAR-NK-92 cells and confirmed that hFAP-CAR-NK-92 cells could target hFAP-positive NSCLC to inhibit the progression of NSCLC by activating the Caspase-3/GSDME pyroptosis pathway.</p>","PeriodicalId":11379,"journal":{"name":"Discovery medicine","volume":"35 176","pages":"405-417"},"PeriodicalIF":1.4,"publicationDate":"2023-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9980799","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comparison of Third-Generation Sequencing Technology and Traditional Microbiological Detection in Pathogen Diagnosis of Lower Respiratory Tract Infection.","authors":"Wang Luo,&nbsp;Yanbin He,&nbsp;Jianhui Xu,&nbsp;Shuhua Zhang,&nbsp;Chunxi Li,&nbsp;Jiangfeng Lv,&nbsp;Youfeng Shen,&nbsp;Zhao Ou,&nbsp;Hangming Dong","doi":"10.24976/Discov.Med.202335176.34","DOIUrl":"https://doi.org/10.24976/Discov.Med.202335176.34","url":null,"abstract":"<p><strong>Background: </strong>It is common to obtain a low detection rate and unsatisfactory detection results in complex infection or rare pathogen detection. This retrospective study aimed to illustrate the application value and prospect of the third-generation sequencing technology in lower respiratory tract infection disease.</p><p><strong>Methods: </strong>This study recruited 70 patients with lower respiratory tract infection (LRTI). Pathogen detection of bronchoalveolar lavage fluid (BALF) from all patients was performed using nanopore metagenomic sequencing technology and traditional culture. BALF culture combined with quantitiative PCR (qPCR) was used as a reference standard to analyze the sensitivity and specificity of nanopore sequencing technology. The current study also collected the examination results of enrolled samples using technical methods sputum culture, tuberculosis DNA (TB-DNA), and Xpert MTB/RIF and analyzed the detection efficiency of nanopore sequencing for <i>Mycobacterium tuberculosis</i>.</p><p><strong>Results: </strong>The positive rates of pathogens in 70 BALF samples detected by conventional culture and nanopore sequencing were 25.71% and 84.29%, respectively. Among the 59 positive BALF cases using nanopore sequencing, a total of 31 pathogens were identified, of which the proportions of bacteria, fungi, viruses, and other pathogens were 50%, 17%, 32%, and 1%, respectively. Using the results combined with culture and qPCR detection methods as the standard, the pathogen detection of BALF using nanopore sequencing had a sensitivity of 70% and a specificity of 91.7%. Additionally, the positive rate of the detection of <i>M. tuberculosis</i> using nanopore sequencing was 33.3% (6/18). The clinical medication plans of 74.3% (52/70) of the patients were referred to the nanopore sequencing results, of which 31 cases changed their treatment strategy, 21 supported the previous treatment plans, and 90% (47/52) of the patients finally had clinical improvement.</p><p><strong>Conclusions: </strong>BALF detection using nanopore sequencing technology improves the process of detecting pathogens in patients with LRTI, especially for <i>M. tuberculosis</i>, fungi, and viruses, by reducing the report time from three days to six hours. The clinical application prospect of nanopore sequencing technology is promising in the pathogen diagnosis of LRTI.</p>","PeriodicalId":11379,"journal":{"name":"Discovery medicine","volume":"35 176","pages":"332-342"},"PeriodicalIF":1.4,"publicationDate":"2023-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9599848","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Baicalin Reduces Renal Inflammation in Mesangial Proliferative Glomerulonephritis through Activation of Nrf2/ARE and PI3K/AKT Pathways.","authors":"Xiaoyuan Ning,&nbsp;Dongping Luo,&nbsp;Yong Chen,&nbsp;Yeqing Shao,&nbsp;Jiayun Xu","doi":"10.24976/Discov.Med.202335176.38","DOIUrl":"https://doi.org/10.24976/Discov.Med.202335176.38","url":null,"abstract":"<p><strong>Objective: </strong>Mesangial proliferative glomerulonephritis (MPGN) is a prevalent form of primary glomerulonephritis, distinguished by the proliferation of mesangial cells and the accompanying inflammatory response. Baicalin, the active ingredient in the Scutellaria baicalensis Georgi plant, has been observed to have a protective effect on the kidneys. However, its specific impact on MPGN has yet to be studied widely. Hence, this study aimed to investigate the effect on MPGN and the underlying mechanisms of Baicalin.</p><p><strong>Methods: </strong>Thirty-six Sprague-Dawley (SD) rats, aged 6 to 8 weeks, were randomly allocated into different subgroups: control, model, benazepril, and three baicalin subgroups (low, medium, and high dose), each consisting of six rats. The concentrations of 24-hour urinary protein, blood urea nitrogen (BUN), serum creatinine (SCr), triglycerides (TG), total cholesterol (TC), interleukins (IL-1α, IL-2, IL-10), and interferon-γ (IFN-γ) were measured with biochemistry. The pathological alterations in the renal tissue were examined using Hematoxylin and Eosin (HE) along with Periodic Acid-Schiff (PAS) staining. Concurrently, the extent of apoptosis was evaluated using TdT-mediated dUTP nick end labeling (TUNEL) staining. <i>In vitro</i>, mesangial cells were exposed to 30 μg/mL lipopolysaccharide for 24 h, with or without varying concentrations of baicalin (10, 20, 40 μM). MTT assay was applied to estimate cell activity, flow cytometry to evaluate the cell cycle, and 5-ethynyl-2-deoxyuridine (EdU) detection to measure cell proliferation. IL-1α, IL-2, IL-10, and IFN-γ concentrations in the cell supernatant were assayed with biochemistry. Furthermore, the expression of apoptosis-related proteins, concluding BCL2-Associated X (Bax), Bcl-2, NOD-like receptor thermal protein domain associated protein 3 (NLRP3), and caspase-1, NF-E2-related factor 2/antioxidant response element (Nrf2/ARE) pathway-related proteins (Nrf2 and HO-1), and phosphatidylinositol 3 kinase/protein kinase B (PI3K/AKT) pathway-related proteins (p-PI3K, PI3K, p-AKT, and AKT) in both the renal tissue and cell supernatant were measured.</p><p><strong>Results: </strong>Baicalin treatment significantly reduced the 24-hour urinary protein, serum levels of BUN, SCr, TG, TC, IL-1α, IL-2, IL-10, and IFN-γ <i>in vivo</i> experiments. Baicalin treatment also improved the pathological condition of renal tissue and decreased the occurrence of apoptosis. <i>In vitro</i>, findings confirmed that baicalin inhabits the proliferation of mesangial cells triggered by Lipopolysaccharide (LPS), induces a G1 phase cell cycle arrest, and reduces the concentrations of IL-1α, IL-2, IL-10, and IFN-γ. Baicalin also decreased the ratios of p-PI3K/PI3K and p-AKT/AKT while enhancing the levels of Nrf2 and HO-1 in both renal tissue and cell supernatant.</p><p><strong>Conclusions: </strong>Baicalin can mitigate MPGN by impeding the proliferation and inflammation of mesangi","PeriodicalId":11379,"journal":{"name":"Discovery medicine","volume":"35 176","pages":"372-382"},"PeriodicalIF":1.4,"publicationDate":"2023-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9599851","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Curcumin Induces Ferroptosis in A549 CD133⁺ Cells through the GSH-GPX4 and FSP1-CoQ10-NAPH Pathways.","authors":"Jiajing Zhou, Lanyue Zhang, Jifeng Yan, Aihua Hou, Wenchao Sui, Meiling Sun","doi":"10.24976/Discov.Med.202335176.26","DOIUrl":"10.24976/Discov.Med.202335176.26","url":null,"abstract":"<p><strong>Background: </strong>Cancer stem cells (CSCs) are characterized by an ability for unlimited proliferation and efficiency of self-renewal. The targeting of lung CSCs (LCSCs)-related signaling pathways represent a promising therapeutic strategy for treatment of lung cancer. Ferroptosis a potential strategy for LCSCs treatment, and curcumin cloud induce ferroptosis. In this study, we aimed to observe the effects of curcumin on LCSCs via ferroptosis-related pathways.</p><p><strong>Methods: </strong>In this study, A549 cluster of differentiation (CD)133⁺ and A549 CD133^- cells were isolated using magnetic bead-based separation. Colony formation and sphere formation assays, as well as cells injection in non-obese diabetes/severe combined immune deficiency (NOD/SCID) mice, were used to analyze the tumorigenic ability of cells differentially expressing CD133. A549 CD133⁺ cells were treated with different doses of curcumin (0, 10, 20, 40, 80 μM). Cell viability, glutathione peroxidase 4 (GPX4) and ferroptosis suppressor protein 1 (FSP1) expressions were measured. The 50% inhibitory concentration (IC₅₀) of curcumin, two ferroptosis inducers, inhibitor of GPX4 (RSL3) and inhibitor of FSP1 (iFSP1), and a ferroptosis inhibitor, ferrostatin-1 (Fer-1), were used to investigate the mechanism underlying the effect of curcumin on ferroptosis in A549 CD133⁺ cells.</p><p><strong>Results: </strong>A549 CD133⁺ cells had greater tumorigenic ability than A549 cells. Curcumin treatment suppressed the expressions of GPX4 (glutathione peroxidase 4) and FSP1 in A549 CD133⁺ cells, thereby inducing ferroptosis. RSL3 and iFSP1 respectively suppressed the GSH (glutathione)-GPX4 and FSP1 (ferroptosis suppressor protein 1)-CoQ10 (coenzyme Q10)-nicotinamide adenine dinucleotide (NADH) pathways in A549 CD133⁺ cells. However, the roles of curcumin were blocked by Fer-1 treatment.</p><p><strong>Conclusions: </strong>In this study, curcumin induced ferroptosis through inhibiting the GSH-GPX4 and FSP1-CoQ10-NADH pathways in A549 CD133⁺ cells, resulting in the inhibition of their self-renewal potential.</p>","PeriodicalId":11379,"journal":{"name":"Discovery medicine","volume":"35 176","pages":"251-263"},"PeriodicalIF":2.1,"publicationDate":"2023-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9607571","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effects of Combined Live <i>Bifidobacterium</i>, <i>Lactobacillus, Enterococcus</i> and <i>Bacillus Cereus</i> Tablets on Post-Stroke Depression and Serum Inflammatory Factorse.","authors":"Yuanwei Wang,&nbsp;Xian Zhang,&nbsp;Ying Wang,&nbsp;Liwu Lu,&nbsp;Rui Wei,&nbsp;Benchi Xu,&nbsp;Xiaojie Hu,&nbsp;Xi Jiang,&nbsp;Li Du","doi":"10.24976/Discov.Med.202335176.32","DOIUrl":"https://doi.org/10.24976/Discov.Med.202335176.32","url":null,"abstract":"<p><strong>Objectives: </strong>Although probiotics have been shown to improve several mental-related diseases, their association with post-stroke depression (PSD) remains unclear. This research aimed to investigate the effect of combined live <i>Bifidobacterium</i>, <i>Lactobacillus, Enterococcus</i> and <i>Bacillus cereus</i> tablets on PSD and serum inflammatory factors.</p><p><strong>Methods: </strong>A total of 400 stroke patients treated from January 2020 to March 2022 in Shuyang Hospital were included and randomly divided into two groups: The observation group (n = 200) and the control group (n = 200). The control group was treated with conventional therapy, while the observation group was given combined live <i>Bifidobacterium</i>, <i>Lactobacillus, Enterococcus</i> and <i>Bacillus cereus</i> tablets on the basis of conventional therapy. The Hamilton Depression Scale score was used to assess the degree and incidence of depression in the two groups. Recurrence and complications of PSD in stroke patients after treatment were followed up. In addition, ELISA (enzyme-linked immunosorbent assay) was employed for the detection of serum levels of nuclear factor kappa light chain enhancer of activated B cells (NF-κB), interleukin (IL)-1β and tumor necrosis factor (TNF)-α, and logistics regression analysis was also performed for the correlation between the occurrence of PSD and NF-κB, IL-1β, and TNF-α levels.</p><p><strong>Results: </strong>The analysis of clinical baseline data showed that the two groups of patients were comparable. After treatment, the Hamilton Depression Scale score in the observation group was significantly lower than in the control group (<i>p</i> < 0.05), and the observation group had a lower incidence rate of PSD, follow-up recurrence rate and complications (<i>p</i> < 0.05). In addition, the observation group showed a significant decrease in the serum levels of NF-κB, IL-1β and TNF-α compared with the control group (<i>p</i> < 0.05). Further logistics regression analysis indicated that the levels of NF-κB (OR (odds ratio) = 3.337, <i>p</i> < 0.001), IL-1β (OR = 2.411, <i>p</i> < 0.001) and TNF-α (OR = 1.557, <i>p</i> < 0.001) were risk factors for the development of PSD.</p><p><strong>Conclusions: </strong>Combined live <i>Bifidobacterium</i>, <i>Lactobacillus, Enterococcus</i> and <i>Bacillus cereus</i> tablets can promote neurological recovery and remission of depression in stroke patients. Such effects may be achieved by regulating the levels of NF-κB, IL-1β and TNF-α.</p>","PeriodicalId":11379,"journal":{"name":"Discovery medicine","volume":"35 176","pages":"312-320"},"PeriodicalIF":1.4,"publicationDate":"2023-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9980797","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}