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Identification of small molecule glucokinase activators for the treatment of diabetes based on plants from the traditional Chinese medicine: In silico analysis 基于中药植物鉴定治疗糖尿病的小分子葡萄糖激酶激活剂:硅学分析。
IF 3.3 3区 医学 Q3 IMMUNOLOGY Pub Date : 2024-08-26 DOI: 10.1016/j.micpath.2024.106851

Mutations in glucokinase (GCK) can either enhance or inhibit insulin secretion, leading to different forms of diabetes, including gestational diabetes. While many glucokinase activators (GKAs) have been explored as treatments, their long-term effectiveness has often been unsatisfactory. However, recent interest has surged with the introduction of dorzagliatin and TTP399. This study investigates the efficacy of four previously studied compounds (Swertiamarin, Apigenin, Mangiferin, and Tatanan A) in activating GCK using computational methods.

Initial molecular docking revealed binding affinities ranging from −6.7 to −8.6 kcal/mol. The compounds were then evaluated for drug-likeness and pharmacokinetic properties. Re-docking studies were performed for validation. Based on their favorable binding affinities and compliance with Lipinski's rule and ADMET criteria, three compounds (Swertiamarin, Apigenin, and Tatanan A) were selected for molecular dynamics (MD) simulations.

MD simulations demonstrated that Swertiamarin showed excellent stability, as indicated by analyses of RMSD, RMSF, radius of gyration (Rg), hydrogen bonding, and principal component analysis (PCA). These results suggest that Swertiamarin holds promise for further investigation in in vivo and clinical settings to evaluate its potential in enhancing GCK activity and treating diabetes.

This study assessed the potential of four compounds as GCK activators using molecular docking, pharmacokinetic profiling, and MD simulations. Swertiamarin, in particular, showed significant stability and adherence to drug-likeness criteria, making it a promising candidate for further research in combating diabetes.

葡萄糖激酶(GCK)的突变可以增强或抑制胰岛素分泌,从而导致不同形式的糖尿病,包括妊娠糖尿病。虽然许多葡萄糖激酶激活剂(GKA)已被用作治疗手段,但其长期疗效往往不尽如人意。不过,最近随着多扎格雷丁和 TTP399 的问世,人们对它们的兴趣大增。本研究利用计算方法研究了以前研究过的四种化合物(獐牙菜素、芹菜素、芒果素和 Tatanan A)激活 GCK 的功效。最初的分子对接显示了-6.7至-8.6 kcal/mol的结合亲和力。然后对这些化合物的药物相似性和药代动力学特性进行了评估。进行了重新对接研究以进行验证。由于这些化合物具有良好的结合亲和力,并且符合利宾斯基规则和 ADMET 标准,因此选择了三个化合物(獐牙菜素、芹菜素和 Tatanan A)进行分子动力学(MD)模拟。MD 模拟结果表明,獐牙菜苷表现出极佳的稳定性,RMSD、RMSF、回旋半径 (Rg)、氢键和主成分分析 (PCA) 等分析结果均表明了这一点。这些结果表明,獐牙菜苷有望在体内和临床环境中进行进一步研究,以评估其在增强 GCK 活性和治疗糖尿病方面的潜力。本研究利用分子对接、药代动力学分析和 MD 模拟评估了四种化合物作为 GCK 激活剂的潜力。特别是獐牙菜苷,它表现出了显著的稳定性,并符合药物相似性标准,因此有望成为进一步研究抗击糖尿病的候选药物。
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引用次数: 0
Gut microbiota alterations in colorectal adenoma-carcinoma sequence based on 16S rRNA gene sequencing: A systematic review and meta-analysis 基于 16S rRNA 基因测序的结直肠腺瘤-癌序列中的肠道微生物群改变:系统回顾和荟萃分析
IF 3.3 3区 医学 Q3 IMMUNOLOGY Pub Date : 2024-08-26 DOI: 10.1016/j.micpath.2024.106889

Background

Most sporadic colorectal cancers (CRC) develop through the adenoma-carcinoma sequence. While dysbiosis of the intestinal flora contributes to CRC's pathogenesis, precise microbial taxa closely associated with the colorectal adenoma-carcinoma sequence remain elusive. This meta-analysis aimed to summarize the features of intestinal flora in patients with AD and CRC.

Methods

PubMed, Embase, Cochrane Library, and Web of Science were searched for case-control studies comparing the relative abundance of gut microbiota in the feces of patients with AD, CRC, and healthy controls (HC) from inception to January 2024. The weighted mean difference (WMD) with a 95 % confidence interval (CI) was used to display the results. The Newcastle-Ottawa Scale (NOS) was used to assess the quality of the entailed literature. Publication bias was evaluated with the Egger's and Begg's tests.

Results

Eleven studies were included, involving 477 CRC patients, 628 AD patients, and 864 healthy controls. Compared with HC, the patients with AD had a significantly lower Chao 1 index (WMD = −30.17, 95 % CI [-41.10, −19.23], P < 0.001) and Shannon index (WMD = −0.11 95 % CI [-0.18, −0.04], P = 0.002). Compared with AD, the CRC patients had a significantly higher Chao1 index (WMD = 22.09, 95 % CI [7.59, 36.00], P = 0.003) and Shannon index (WMD = 0.08, 95 % CI [0.00, 0.15], P = 0.037). Enterobacteriaceae (WMD = 0.03 95 % CI [0.00,0.05], P = 0.047; WMD = 0.02 95 % CI [0.00,0.04], P = 0.027) significantly increased in the order of Control-AD-CRC, while that of Blautia (WMD = −0.00 95 % CI [-0.01, −0.00], P = 0.001; WMD = −0.00 95 % CI [-0.00, −0.00], P = 0.002) was reduced. Compared with HC, the relative abundance of Proteobacteria (WMD = 0.05 95 % CI [0.03,0.07], P < 0.001), Fusobacteria (WMD = 0.02 95 % CI [0.00,0.03], P = 0.042), Streptococcaceae (WMD = 0.03 95 % CI [0.01,0.05], P = 0.017), Prevotellaceae (WMD = 0.02 95 % CI [0.00,0.04], P = 0.040), and Escherichia-Shigella (WMD = 0.06 95 % CI [0.01, 0.11], P = 0.021) was enriched in the CRC group. The relative abundance of Alistipes (WMD = 0.00 95 % CI [0.00,0.01], P = 0.032) and Streptococcus (WMD = 0.00 95 % CI [0.00,0.00], P = 0.001) was increased in the AD vs HC. The relative abundance of Firmicutes (WMD = −0.07 95 % CI [-0.12, −0.03], P = 0.003), Bifidobacteria (WMD = −0.03 95 % CI [-0.05, −0.01], P = 0.016), and Klebsiella (WMD = −0.01 95 % CI [-0.01, −0.00], P = 0.001) was decreased in the CRC vs HC. Compared with AD, the relative abundance of Firmicutes (WMD = −0.04 95 % CI [-0.07, −0.02], P = 0.002), Peptostreptococcaceae (WMD = −0.03 95 % CI [-0.05, −0.00], P = 0.021), Lachnospiraceae (WMD = −0.04 95 % CI [-0.08,-0.00], P = 0.037), Ruminococcaceae (WMD = −0.06 95 % CI [-0.09,-0.03], P < 0.001), Faecalibacterium (WMD = −0.01 95 % CI [-0.02, −0.01], P = 0.001), and Lachnoclostridium (WMD = −0.02 95 % CI [-0.03, −0.00], P = 0.040) was decre

背景大多数散发性结直肠癌(CRC)是通过腺瘤-癌序列发展而来的。虽然肠道菌群失调是导致 CRC 发病的原因之一,但与结直肠腺瘤-癌序列密切相关的确切微生物类群仍然难以确定。本荟萃分析旨在总结 AD 患者和 CRC 患者肠道菌群的特征。方法在 PubMed、Embase、Cochrane Library 和 Web of Science 上搜索了从开始到 2024 年 1 月期间比较 AD 患者、CRC 患者和健康对照组(HC)粪便中肠道微生物群相对丰度的病例对照研究。研究采用加权平均差 (WMD) 和 95% 置信区间 (CI) 来显示结果。采用纽卡斯尔-渥太华量表(NOS)评估相关文献的质量。结果共纳入 7 项研究,涉及 477 名 CRC 患者、628 名 AD 患者和 864 名健康对照者。与 HC 相比,AD 患者的 Chao 1 指数(WMD = -30.17,95 % CI [-41.10, -19.23],P < 0.001)和 Shannon 指数(WMD = -0.11 95 % CI [-0.18, -0.04],P = 0.002)明显较低。与 AD 相比,CRC 患者的 Chao1 指数(WMD = 22.09,95 % CI [7.59,36.00],P = 0.003)和香农指数(WMD = 0.08,95 % CI [0.00,0.15],P = 0.037)明显更高。肠杆菌科细菌(WMD = 0.03 95 % CI [0.00,0.05],P = 0.047;WMD = 0.02 95 % CI [0.00,0.04],P = 0.027)在对照组-AD-CRC 的顺序中显著增加,而布洛陀菌(WMD = -0.00 95 % CI [-0.01, -0.00], P = 0.001; WMD = -0.00 95 % CI [-0.00, -0.00], P = 0.002)则有所降低。与 HC 相比,蛋白质细菌(WMD = 0.05 95 % CI [0.03,0.07],P < 0.001)、镰刀菌(WMD = 0.02 95 % CI [0.00,0.03],P = 0.042)、链球菌(WMD = 0.CRC 组富集了链球菌科(WMD = 0.02 95 % CI [0.00,0.03],P = 0.042)、链球菌属(WMD = 0.03 95 % CI [0.01,0.05],P = 0.017)、前鞭毛菌科(WMD = 0.02 95 % CI [0.00,0.04],P = 0.040)和志贺氏菌属(WMD = 0.06 95 % CI [0.01,0.11],P = 0.021)。AD组与HC组相比,Alistipes(WMD = 0.00 95 % CI [0.00,0.01],P = 0.032)和Streptococcus(WMD = 0.00 95 % CI [0.00,0.00],P = 0.001)的相对丰度有所增加。CRC与HC相比,固缩菌(WMD = -0.07 95 % CI [-0.12,-0.03],P = 0.003)、双歧杆菌(WMD = -0.03 95 % CI [-0.05,-0.01],P = 0.016)和克雷伯菌(WMD = -0.01 95 % CI [-0.01,-0.00],P = 0.001)的相对丰度降低。与 AD 相比,CRC 中固球菌属(WMD = -0.04 95 % CI [-0.07,-0.02],P = 0.002)、肽球菌属(WMD = -0.03 95 % CI [-0.05,-0.00],P = 0.021)、漆树菌属(WMD = -0.04 95 % CI [-0.08,-0.00],P = 0.001)的相对丰度下降。08,-0.00],P = 0.037)、反刍球菌科(WMD = -0.06 95 % CI [-0.09,-0.03],P < 0.001)、粪杆菌科(WMD = -0.01 95 % CI [-0.02,-0.01],P = 0.001)和腔肠动物科(WMD = -0.02 95 % CI [-0.03,-0.00],P = 0.结论以产生短链脂肪酸(SCFA)的细菌水平降低、抗炎细菌减少、促炎细菌增加以及具有损伤 DNA 的细胞毒性作用的细菌增多为特征的菌群失调可能代表了结直肠腺瘤/癌的特定微生物特征。要阐明肠道菌群失调导致从 AD 发展为 CRC 的机制,并探索特定微生物群标记在临床治疗和非侵入性筛查中的潜力,还需要进一步的研究。
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引用次数: 0
Impact of wheat processing on growth, serum biochemistry, and ruminal microbiota in sheep (Ovis aries) 小麦加工对绵羊(Ovis aries)生长、血清生化和瘤胃微生物群的影响。
IF 3.3 3区 医学 Q3 IMMUNOLOGY Pub Date : 2024-08-24 DOI: 10.1016/j.micpath.2024.106887

This study investigated the impact of wheat processing methods (wheat flour vs wheat pellets) on the growth performance, serum biochemical parameters, and rumen microbiome composition in sheep. Results indicated that feeding of wheat flour resulted in significantly higher terminal weight and average daily gain (P < 0.05) and lower cholesterol and ALP04 levels (P < 0.05) in sheep compared to those fed wheat pellets. Analysis of 16s rDNA high-throughput sequencing data revealed significantly higher microbial richness (Chao1 index) in the rumen of sheep fed wheat flour (P < 0.05), even though the phylum-level composition dominated by Firmicutes, Bacteroidetes, and Proteobacteria was similar in both groups of sheep. Notably, sheep fed wheat flour were found to have a significantly higher relative abundance of Bacteroidetes (P < 0.05). At the genus level, Succinivibrionaceae_UCG-001 and Prevotella_1 were significantly more abundant in the rumen of sheep fed wheat flour (P < 0.05). Correlation analysis identified that both terminal weight and average daily gain were positively correlated with ruminal abundance of Bacteroidetes and Prevotella_1, while ALP04 was negatively correlated with the abundance of these taxa. Functional prediction using PICRUSt2 indicated enrichment of pathways related to the ABC-type glycerol-3-phosphate transport system, and periplasmic components in both wheat flour and pellet fed sheep. Overall, these findings suggest that dietary wheat flour modulates rumen microbiota composition, and improves growth performance in sheep.

本研究调查了小麦加工方法(小麦粉与小麦颗粒)对绵羊生长性能、血清生化指标和瘤胃微生物组组成的影响。结果表明,饲喂小麦粉可显著提高绵羊的终重和平均日增重(P
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引用次数: 0
Development of a triplex RT-RAA-LFA assay for the rapid differential diagnosis of porcine epidemic diarrhea virus, porcine deltacoronavirus and transmissible gastroenteritis virus 开发用于快速鉴别诊断猪流行性腹泻病毒、猪三角锥病毒和传染性胃肠炎病毒的三重 RT-RAA-LFA 检测法。
IF 3.3 3区 医学 Q3 IMMUNOLOGY Pub Date : 2024-08-24 DOI: 10.1016/j.micpath.2024.106885

Porcine epidemic diarrhea virus (PEDV), porcine deltacoronavirus (PDCoV) and transmissible gastroenteritis virus (TGEV) are three clinically common coronaviruses causing diarrhea in pigs, with indistinguishable clinical signs and pathological changes. Rapid, portable and reliable differential diagnosis of these three pathogens is crucial for the prompt implementation of appropriate control measures. In this study, we developed a triplex nucleic acid assay that combines reverse transcription recombinase-aided amplification (RT-RAA) with lateral flow assay (LFA) by targeting the most conserved genomic region in the ORF1b genes of PEDV, PDCoV and TGEV. The entire detection process of the triplex RT-RAA-LFA assay included 10-min nucleic acid amplification at 42 °C and 5-min visual LFA readout at room temperature. The assay could specifically differentiate PEDV, PDCoV and TGEV without cross-reaction with any other major swine pathogens. Sensitivity analysis showed that the triplex RT-RAA-LFA assay was able to detect the viral RNA extracted from the spiked fecal samples with the minimum of 1 × 100 TCID50 PEDV, 1 × 104 TCID50 PDCoV, and 1 × 102 TCID50 TGEV per reaction, respectively. Further analysis showed that the 95 % detection limit (LOD) of triplex RT-RAA-LFA for PEDV, PDCoV, and TGEV were 22, 478, and 205 copies of recombinant plasmids per reaction, respectively. The diagnostic performance of triplex RT-RAA-LFA was compared with that of PEDV, PDCoV and TGEV respective commercial real-time RT-PCR kits by testing 114 clinical rectal swab samples in parallel. The total diagnostic coincidence rates of triplex RT-RAA-LFA with real-time RT-PCR kits of PEDV, PDCoV and TGEV were 100 %, 99.1 % and 99.1 %, respectively, and their Kappa values were 1.00, 0.958 and 0.936, respectively. Collectively, the RT-RAA-LFA assay is a powerful tool for the rapid, portable, visual, and synchronous differential diagnosis of PEDV, PDCoV, and TGEV.

猪流行性腹泻病毒(PEDV)、猪三角冠状病毒(PDCoV)和传染性胃肠炎病毒(TGEV)是临床上常见的三种引起猪腹泻的冠状病毒,其临床症状和病理变化难以区分。对这三种病原体进行快速、便携和可靠的鉴别诊断对于迅速实施适当的控制措施至关重要。在本研究中,我们针对 PEDV、PDCoV 和 TGEV ORF1b 基因中最保守的基因组区域,开发了一种三重核酸检测方法,该方法结合了反转录重组酶辅助扩增(RT-RAA)和侧流检测(LFA)。三重 RT-RAA-LFA 检测法的整个检测过程包括在 42 °C 下进行 10 分钟的核酸扩增和在室温下进行 5 分钟的视觉 LFA 读数。该检测方法可特异性区分 PEDV、PDCoV 和 TGEV,不会与任何其他主要猪病原体产生交叉反应。灵敏度分析表明,三重 RT-RAA-LFA 检测法能够检测从粪便样本中提取的病毒 RNA,每个反应的最低检测量分别为 1×100 TCID50 PEDV、1×104 TCID50 PDCoV 和 1×102 TCID50 TGEV。进一步分析表明,三重 RT-RAA-LFA 对 PEDV、PDCoV 和 TGEV 的 95% 检测限(LOD)分别为每反应 22、478 和 205 个 ORF1b 重组质粒拷贝。通过平行检测114份临床直肠拭子样本,比较了三重RT-RAA-LFA与PEDV、PDCoV和TGEV各自的商用实时RT-PCR试剂盒的诊断性能。三重 RT-RAA-LFA 与 PEDV、PDCoV 和 TGEV 的实时 RT-PCR 试剂盒的总诊断吻合率分别为 100%、99.1% 和 99.1%,其 Kappa 值分别为 1.00、0.958 和 0.936。总之,RT-RAA-LFA 检测法是快速、便携、直观和同步鉴别诊断 PEDV、PDCoV 和 TGEV 的有力工具。
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引用次数: 0
Prevalence of Blastocystis infection in humans in Türkiye: A systematic review and meta-analysis 图尔基耶人感染布拉氏囊虫的流行情况:系统回顾和荟萃分析。
IF 3.3 3区 医学 Q3 IMMUNOLOGY Pub Date : 2024-08-23 DOI: 10.1016/j.micpath.2024.106876

Although Blastocystis, a protozoan, is commonly found in all species of animals and in humans, there remains a lack of clear information about its epidemiology and routes of transmission. The aim of this meta-analysis study was to determine the changes in Blastocystis prevalence and subtype distribution in humans in Türkiye according to geographical regions. Databases were searched using the Web of Science, PubMed, Scopus, EBSCO, and TRDizin to identify studies on the prevalence of Blastocystis in humans in Türkiye published from 2009 to 2023. As a result of this systematic search, 117 of 730 articles were included in the meta-analysis. The pooled prevalence of human Blastocystis infection in Türkiye was 13.08 %. The prevalence of the pool was higher in the Black Sea region, which is the most humid region in Türkiye, than in other regions. Blastocystis subtypes were identified in a total of 885 positive samples. The most common subtypes (ST) in Türkiye were ST3, ST1 and ST2, respectively. In addition to these ST4, ST5, ST6 and ST7 were also detected in humans in Türkiye. In conclusion, the prevalence of Blastocystis in humans is high in Türkiye, especially in the Black Sea region.

虽然布氏囊虫是一种原生动物,常见于各种动物和人类,但目前仍缺乏有关其流行病学和传播途径的明确信息。这项荟萃分析研究的目的是根据地理区域确定图尔基耶人体内布拉氏囊虫流行率和亚型分布的变化情况。研究人员使用 Web of Science、PubMed、Scopus、EBSCO 和 TRDizin 对数据库进行了检索,以确定 2009 年至 2023 年期间发表的有关土耳其人体中布氏杆菌流行率的研究。经过系统搜索,730 篇文章中的 117 篇被纳入荟萃分析。图尔基耶人感染布氏囊虫的总体流行率为 13.08%。黑海地区是土耳其最潮湿的地区,该地区的感染率高于其他地区。在总共 885 份阳性样本中发现了大疱菌亚型。图尔基耶最常见的亚型(ST)分别为 ST3、ST1 和 ST2。除此之外,土耳其人体内还检测到 ST4、ST5、ST6 和 ST7。总之,在土耳其,尤其是在黑海地区,人体内的布氏囊虫感染率很高。
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引用次数: 0
Toxoplasma gondii infection is associated with schizophrenia from the perspectives of seroepidemiology and serum metabolomics in Hunan Province, China 从血清流行病学和血清代谢组学角度看弓形虫感染与中国湖南省精神分裂症的关系
IF 3.3 3区 医学 Q3 IMMUNOLOGY Pub Date : 2024-08-22 DOI: 10.1016/j.micpath.2024.106880

Toxoplasma gondii (T.gondii) can influence the host's neurotransmission, central immune responses, and brain structure, potentially impacting the onset and development of various psychiatric disorders such as schizophrenia. We employed Electrochemiluminescence Immunoassay (ECLIA) to measure anti-Toxoplasma antibodies in 451 schizophrenic patients and 478 individuals from the general population in Hunan, China. The incidence rate of T.gondii infection in schizophrenic patients (8.87 %) was higher than that in the general population (3.77 %). A significant difference was observed among females, but not in males. Age-stratified analysis revealed significant differences in the 21–40 and 41–60 age groups. The two populations had no significant difference in the antibody titer for T. gondii infection. Additionally, the profile of circulating metabolites in the serum of schizophrenic patients with or without T. gondii infection was examined using non-targeted metabolomics assay. A total of 68 metabolites were differentially expressed between Toxoplasma-positive and Toxoplasma-negative groups, potentially mediating the connection between T. gondii infection and schizophrenia. Our research suggests that schizophrenic patients are susceptible to T. gondii infection with distinct metabolic program.

弓形虫(Toxoplasma gondii,T.gondii)会影响宿主的神经传递、中枢免疫反应和大脑结构,可能会影响精神分裂症等各种精神疾病的发病和发展。我们采用电化学发光免疫分析法(ECLIA)检测了中国湖南451名精神分裂症患者和478名普通人群的抗弓形虫抗体。精神分裂症患者的弓形虫感染率(8.87%)高于普通人群(3.77%)。女性与男性之间存在明显差异。年龄分层分析显示,21-40 岁年龄组和 41-60 岁年龄组之间存在显著差异。这两个人群的淋球菌感染抗体滴度没有明显差异。此外,研究人员还使用非靶向代谢组学分析方法对感染或未感染淋病的精神分裂症患者血清中的循环代谢物进行了检测。弓形虫阳性组和弓形虫阴性组之间共有68种代谢物的表达存在差异,这可能是弓形虫感染与精神分裂症之间联系的介导因素。我们的研究表明,精神分裂症患者易受弓形虫感染,并具有独特的代谢程序。
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引用次数: 0
Mycoplasma genitalium membrane lipoprotein induces GAPDH malonylation in urethral epithelial cells to regulate cytokine response 生殖支原体膜脂蛋白诱导尿道上皮细胞中的 GAPDH 丙二酰化以调节细胞因子反应
IF 3.3 3区 医学 Q3 IMMUNOLOGY Pub Date : 2024-08-22 DOI: 10.1016/j.micpath.2024.106872

Membrane lipoproteins serve as primary pro-inflammatory virulence factors in Mycoplasma genitalium. Membrane lipoproteins primarily induce inflammatory responses by activating Toll-like Receptor 2 (TLR2); however, the role of the metabolic status of urethral epithelial cells in inflammatory response remains unclear. In this study, we found that treatment of uroepithelial cell lines with M. genitalium membrane lipoprotein induced metabolic reprogramming, characterized by increased aerobic glycolysis, decreased oxidative phosphorylation, and increased production of the metabolic intermediates acetyl-CoA and malonyl-CoA. The metabolic shift induced by membrane lipoproteins is reversible upon blocking MyD88 and TRAM. Malonyl-CoA induces malonylation of glyceraldehyde 3-phosphate dehydrogenase (GAPDH), and malonylated GAPDH could dissociate from the 3′ untranslated region of TNF-α and IFN-γ mRNA. This dissociation greatly reduces the inhibitory effect on the translation of TNF-α and IFN-γ mRNA, thus achieving fine-tuning control over cytokine secretion. These findings suggest that GAPDH malonylation following M. genitalium infection is an important inflammatory signal that plays a crucial role in urogenital inflammatory diseases.

膜脂蛋白是生殖支原体的主要促炎毒力因子。膜脂蛋白主要通过激活Toll样受体2(TLR2)诱导炎症反应;然而,尿道上皮细胞的代谢状态在炎症反应中的作用仍不清楚。在这项研究中,我们发现用生殖器畸形膜脂蛋白处理尿道上皮细胞系会诱导代谢重编程,其特点是有氧糖酵解增加、氧化磷酸化减少以及代谢中间产物乙酰-CoA 和丙二酰-CoA 生成增加。膜脂蛋白诱导的代谢转变在阻断 MyD88 和 TRAM 后是可逆的。丙二酰-CoA诱导甘油醛-3-磷酸脱氢酶(GAPDH)发生丙二酰化,丙二酰化的 GAPDH 可与 TNF-α 和 IFN-γ mRNA 的 3' 非翻译区分离。这种解离大大降低了对 TNF-α 和 IFN-γ mRNA 翻译的抑制作用,从而实现了对细胞因子分泌的微调控制。这些研究结果表明,M. genitalium 感染后的 GAPDH 丙二酰化是一种重要的炎症信号,在泌尿生殖系统炎症疾病中起着至关重要的作用。
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引用次数: 0
Combating bacterial biofilms and related drug resistance: Role of phyto-derived adjuvant and nanomaterials 抗击细菌生物膜及相关耐药性:植物源佐剂和纳米材料的作用。
IF 3.3 3区 医学 Q3 IMMUNOLOGY Pub Date : 2024-08-22 DOI: 10.1016/j.micpath.2024.106874

The emergence of antimicrobial resistance (AMR) in clinical microbes has led to a search for novel antibiotics for combating bacterial infections. The treatment of bacterial infections becomes more challenging with the onset of biofilm formation. AMR is further accelerated by biofilm physiology and differential gene expression in bacteria with an inherent resistance to conventional antibiotics. In the search for innovative strategies to control the spread of AMR in clinical isolates, plant-derived therapeutic metabolites can be repurposed to control biofilm-associated drug resistance. Unlike antibiotics, designed to act on a single cellular process, phytochemicals can simultaneously target multiple cellular components. Furthermore, they can disrupt biofilm formation and inhibit quorum sensing, offering a comprehensive approach to combat bacterial infections. In bacterial biofilms, the first line of AMR is due to biofilms associated with the extracellular matrix, diffusion barriers, quorum sensing, and persister cells. These extracellular barriers can be overcome using phytochemical-based antibiotic adjuvants to increase the efficacy of antibiotic treatment and restrict the spread of AMR. Furthermore, phytochemicals can be used to target bacterial intracellular machinery such as DNA replication, protein synthesis, efflux pumps, and degrading enzymes. In parallel with pristine phytochemicals, phyto-derived nanomaterials have emerged as an effective means of fighting bacterial biofilms. These nanomaterials can be formulated to cross the biofilm barriers and function on cellular targets. This review focuses on the synergistic effects of phytochemicals and phyto-derived nanomaterials in controlling the progression of biofilm-related AMR. IT provides comprehensive insights into recent advancements and the underlying mechanisms of the use of phyto-derived adjuvants and nanomaterials.

临床微生物中出现的抗菌药耐药性(AMR)促使人们寻找新型抗生素来对抗细菌感染。随着生物膜的形成,细菌感染的治疗变得更具挑战性。生物膜生理学和细菌基因表达的差异进一步加速了 AMR 的产生,而这些细菌本身就对传统抗生素具有抗药性。在寻找创新战略以控制 AMR 在临床分离物中扩散的过程中,植物提取的治疗性代谢物可被重新用于控制生物膜相关的耐药性。抗生素只能作用于单一的细胞过程,而植物化学物质则不同,可以同时作用于多种细胞成分。此外,它们还能破坏生物膜的形成并抑制法定人数感应,从而提供了一种全面的抗击细菌感染的方法。在细菌生物膜中,AMR 的第一线是与细胞外基质、扩散屏障、法定量感应和持久细胞相关的生物膜。使用植物化学抗生素佐剂可以克服这些细胞外基质障碍,从而提高抗生素的疗效并限制 AMR 的扩散。此外,植物化学物质还可用于靶向细菌细胞内机制,如 DNA 复制、蛋白质合成、外排泵和降解酶。在使用纯植物化学物质的同时,植物提取的纳米材料也已成为抗击细菌生物膜的有效手段。这些纳米材料可以穿过生物膜屏障,在细胞靶标上发挥作用。本综述重点介绍植物化学物质和植物衍生纳米材料在控制生物膜相关 AMR 进展方面的协同作用。它全面介绍了植物源佐剂和纳米材料的最新进展和使用机制。
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引用次数: 0
Porcine epidemic diarrhea virus: A review of detection, inhibition of host gene expression and evasion of host innate immune 猪流行性腹泻病毒:关于检测、抑制宿主基因表达和逃避宿主先天免疫的综述。
IF 3.3 3区 医学 Q3 IMMUNOLOGY Pub Date : 2024-08-21 DOI: 10.1016/j.micpath.2024.106873

As one of the most important swine enteropathogenic coronavirus, porcine epidemic diarrhea virus (PEDV) is the causative agent of an acute and devastating enteric disease that causes lethal watery diarrhea in suckling piglets. Recent progress in studying PEDV has revealed many intriguing findings on its prevalence and genetic evolution, rapid diagnosis, suppression of host gene expression, and suppression of the host innate immune system. Due to the continuous mutation of the PEDV genome, viral evasions from innate immune defenses and mixed infection with other coronaviruses, the spread of the virus is becoming wider and faster, making it even more necessary to prevent the infections caused by wild-type PEDV variants. It has also been reported that PEDV nsp1 is an essential virulence determinant and is critical for inhibiting host gene expression by structural and biochemical analyses. The inhibition of host protein synthesis employed by PEDV nsp1 may contribute to the regulation of host cell proliferation and immune evasion-related biological functions. In this review, we critically evaluate the recent studies on these aspects of PEDV and assess prospects in understanding the function of PEDV proteins in regulating host innate immune response and viral virulence.

作为最重要的猪肠道致病性冠状病毒之一,猪流行性腹泻病毒(PEDV)是一种急性、破坏性肠道疾病的病原体,可引起哺乳仔猪致命性水样腹泻。最近在研究 PEDV 方面取得的进展揭示了它在流行和遗传进化、快速诊断、抑制宿主基因表达和抑制宿主先天免疫系统等方面的许多耐人寻味的发现。由于 PEDV 基因组的不断变异、病毒对先天性免疫防御系统的逃避以及与其他冠状病毒的混合感染,病毒的传播范围越来越广,速度越来越快,因此更有必要预防野生型 PEDV 变体引起的感染。另据报道,通过结构和生化分析,PEDV nsp1 是一个重要的毒力决定因子,对抑制宿主基因表达至关重要。PEDV nsp1 对宿主蛋白质合成的抑制可能有助于调控宿主细胞增殖和与免疫逃避相关的生物功能。在这篇综述中,我们对最近有关 PEDV 这些方面的研究进行了严格的评估,并对了解 PEDV 蛋白在调节宿主先天性免疫反应和病毒毒力方面的功能的前景进行了评估。
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引用次数: 0
VmSom1 is essential for growth, development, maintenance of cell wall integrity and virulence in Valsa mali VmSom1 对麦芽藻的生长、发育、细胞壁完整性的维持和病毒性至关重要。
IF 3.3 3区 医学 Q3 IMMUNOLOGY Pub Date : 2024-08-21 DOI: 10.1016/j.micpath.2024.106878

Apple Valsa canker disease, caused by Valsa mali Miyabe et Yamada, severely endangers the healthy growth of apple trees. The Som1, located downstream of the cyclic AMP-dependent protein kinase A (cAMP-PKA) pathway, plays crucial roles in the growth, development, morphological differentiation, and virulence of filamentous fungi. In this study, we identify and functionally characterize VmSom1, a homolog of Som1, in Valsa mali. The VmSom1 gene is located on chromosome 12, encoding an 824 amino acid protein. Phylogenetic analysis reveals VmSom1 as a fungal Som1 homolog. The VmSom1 deletion mutants exhibit slower growth rates and fail to produce pycnidia. Additionally, their hyphal growth is significantly inhibited on media containing Calcofluor White, Congo Red, NaCl, and sorbitol. The growth rate of VmSom1 deletion mutants is reduced on maltose, lactose, sucrose and fructose media but increases on glucose medium. Moreover, the mycelial growth rate of the VmSom1 deletion mutant is significantly lower than that of the wild-type strain in peptone, NH4SO4, NaNO3, and no nitrogen. Notably, the distances between the septa increase, and chitin concentration shifts to the hyphal tip in the VmSom1 deletion mutant. Furthermore, compared with the wild-type strain, the VmSom1 deletion mutant exhibits fewer diseased spots on apple fruit and branches. Overall, our findings demonstrate that VmSom1 is involved in regulating the growth and development, colony surface hydrophobicity, osmotic stress, cell wall integrity maintenance, carbon and nitrogen source utilization, septa formation, and virulence of V. mali.

由 Valsa mali Miyabe et Yamada 引起的苹果瓦尔萨腐烂病严重危害苹果树的健康生长。位于环磷酸腺苷依赖性蛋白激酶 A(cAMP-PKA)通路下游的 Som1 在丝状真菌的生长、发育、形态分化和毒力方面起着至关重要的作用。在这项研究中,我们鉴定并从功能上描述了 VmSom1 的同源基因 VmSom1。VmSom1 基因位于第 12 号染色体上,编码 824 个氨基酸的蛋白质。系统进化分析表明,VmSom1 是真菌 Som1 的同源物。VmSom1 基因缺失突变体的生长速度较慢,不能产生菌丝。此外,在含有钙氟白、刚果红、氯化钠和山梨醇的培养基上,它们的头状花序生长会受到明显抑制。VmSom1 基因缺失突变体在麦芽糖、乳糖、蔗糖和果糖培养基上的生长速度降低,但在葡萄糖培养基上的生长速度提高。此外,在蛋白胨、NH4SO4、NaNO3 和无氮培养基中,VmSom1 基因缺失突变体的菌丝生长速度明显低于野生型菌株。值得注意的是,在 VmSom1 基因缺失突变体中,隔膜之间的距离增加,几丁质的浓度向顶端转移。此外,与野生型菌株相比,VmSom1 缺失突变体在苹果果实和枝条上表现出的病斑更少。总之,我们的研究结果表明,VmSom1 参与调控苹果蠹蛾的生长发育、菌落表面疏水性、渗透胁迫、细胞壁完整性维持、碳源和氮源利用、隔膜形成和毒力。
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引用次数: 0
期刊
Microbial pathogenesis
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