Pub Date : 2024-08-26DOI: 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.
{"title":"Identification of small molecule glucokinase activators for the treatment of diabetes based on plants from the traditional Chinese medicine: In silico analysis","authors":"","doi":"10.1016/j.micpath.2024.106851","DOIUrl":"10.1016/j.micpath.2024.106851","url":null,"abstract":"<div><p>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.</p><p>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.</p><p>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.</p><p>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.</p></div>","PeriodicalId":18599,"journal":{"name":"Microbial pathogenesis","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2024-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142093537","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-08-26DOI: 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。
{"title":"Gut microbiota alterations in colorectal adenoma-carcinoma sequence based on 16S rRNA gene sequencing: A systematic review and meta-analysis","authors":"","doi":"10.1016/j.micpath.2024.106889","DOIUrl":"10.1016/j.micpath.2024.106889","url":null,"abstract":"<div><h3>Background</h3><p>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.</p></div><div><h3>Methods</h3><p>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.</p></div><div><h3>Results</h3><p>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","PeriodicalId":18599,"journal":{"name":"Microbial pathogenesis","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2024-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142088605","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-08-24DOI: 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.
{"title":"Impact of wheat processing on growth, serum biochemistry, and ruminal microbiota in sheep (Ovis aries)","authors":"","doi":"10.1016/j.micpath.2024.106887","DOIUrl":"10.1016/j.micpath.2024.106887","url":null,"abstract":"<div><p>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 <em>Firmicutes, Bacteroidetes,</em> and <em>Proteobacteria</em> was similar in both groups of sheep. Notably, sheep fed wheat flour were found to have a significantly higher relative abundance of <em>Bacteroidetes</em> (P < 0.05). At the genus level, <em>Succinivibrionaceae_UCG-001</em> and <em>Prevotella_1</em> 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 <em>Bacteroidetes</em> and <em>Prevotella_1,</em> 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.</p></div>","PeriodicalId":18599,"journal":{"name":"Microbial pathogenesis","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2024-08-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142073252","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-08-24DOI: 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.
{"title":"Development of a triplex RT-RAA-LFA assay for the rapid differential diagnosis of porcine epidemic diarrhea virus, porcine deltacoronavirus and transmissible gastroenteritis virus","authors":"","doi":"10.1016/j.micpath.2024.106885","DOIUrl":"10.1016/j.micpath.2024.106885","url":null,"abstract":"<div><p>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 × 10<sup>0</sup> TCID<sub>50</sub> PEDV, 1 × 10<sup>4</sup> TCID<sub>50</sub> PDCoV, and 1 × 10<sup>2</sup> TCID<sub>50</sub> 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.</p></div>","PeriodicalId":18599,"journal":{"name":"Microbial pathogenesis","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2024-08-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142056030","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-08-23DOI: 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.
{"title":"Prevalence of Blastocystis infection in humans in Türkiye: A systematic review and meta-analysis","authors":"","doi":"10.1016/j.micpath.2024.106876","DOIUrl":"10.1016/j.micpath.2024.106876","url":null,"abstract":"<div><p>Although <em>Blastocystis</em>, 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 <em>Blastocystis</em> 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 <em>Blastocystis</em> 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 <em>Blastocystis</em> 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. <em>Blastocystis</em> 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 <em>Blastocystis</em> in humans is high in Türkiye, especially in the Black Sea region.</p></div>","PeriodicalId":18599,"journal":{"name":"Microbial pathogenesis","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2024-08-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142056033","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-08-22DOI: 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.
{"title":"Toxoplasma gondii infection is associated with schizophrenia from the perspectives of seroepidemiology and serum metabolomics in Hunan Province, China","authors":"","doi":"10.1016/j.micpath.2024.106880","DOIUrl":"10.1016/j.micpath.2024.106880","url":null,"abstract":"<div><p><em>Toxoplasma gondii</em> (<em>T</em>.<em>gondii</em>) 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-<em>Toxoplasma</em> antibodies in 451 schizophrenic patients and 478 individuals from the general population in Hunan, China. The incidence rate of <em>T</em>.<em>gondii</em> 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 <em>T. gondii</em> infection. Additionally, the profile of circulating metabolites in the serum of schizophrenic patients with or without <em>T. gondii</em> infection was examined using non-targeted metabolomics assay. A total of 68 metabolites were differentially expressed between <em>Toxoplasma</em>-positive and <em>Toxoplasma</em>-negative groups, potentially mediating the connection between <em>T. gondii</em> infection and schizophrenia. Our research suggests that schizophrenic patients are susceptible to <em>T. gondii</em> infection with distinct metabolic program.</p></div>","PeriodicalId":18599,"journal":{"name":"Microbial pathogenesis","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2024-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142056034","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-08-22DOI: 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.
{"title":"Mycoplasma genitalium membrane lipoprotein induces GAPDH malonylation in urethral epithelial cells to regulate cytokine response","authors":"","doi":"10.1016/j.micpath.2024.106872","DOIUrl":"10.1016/j.micpath.2024.106872","url":null,"abstract":"<div><p>Membrane lipoproteins serve as primary pro-inflammatory virulence factors in <em>Mycoplasma genitalium</em>. 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 <em>M. genitalium</em> 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 <em>M. genitalium</em> infection is an important inflammatory signal that plays a crucial role in urogenital inflammatory diseases.</p></div>","PeriodicalId":18599,"journal":{"name":"Microbial pathogenesis","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2024-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142036344","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-08-22DOI: 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。
{"title":"Combating bacterial biofilms and related drug resistance: Role of phyto-derived adjuvant and nanomaterials","authors":"","doi":"10.1016/j.micpath.2024.106874","DOIUrl":"10.1016/j.micpath.2024.106874","url":null,"abstract":"<div><p>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.</p></div>","PeriodicalId":18599,"journal":{"name":"Microbial pathogenesis","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2024-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142056118","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-08-21DOI: 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.
{"title":"Porcine epidemic diarrhea virus: A review of detection, inhibition of host gene expression and evasion of host innate immune","authors":"","doi":"10.1016/j.micpath.2024.106873","DOIUrl":"10.1016/j.micpath.2024.106873","url":null,"abstract":"<div><p>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.</p></div>","PeriodicalId":18599,"journal":{"name":"Microbial pathogenesis","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2024-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142036345","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-08-21DOI: 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.
{"title":"VmSom1 is essential for growth, development, maintenance of cell wall integrity and virulence in Valsa mali","authors":"","doi":"10.1016/j.micpath.2024.106878","DOIUrl":"10.1016/j.micpath.2024.106878","url":null,"abstract":"<div><p>Apple <em>Valsa</em> canker disease<em>,</em> caused by <em>Valsa mali</em> Miyabe et Yamada, severely endangers the healthy growth of apple trees. The <em>Som1,</em> 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 <em>VmSom1</em>, a homolog of Som1, in <em>Valsa mali</em>. The <em>VmSom1</em> gene is located on chromosome 12, encoding an 824 amino acid protein. Phylogenetic analysis reveals VmSom1 as a fungal Som1 homolog. The <em>VmSom1</em> 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 <em>VmSom1</em> deletion mutants is reduced on maltose, lactose, sucrose and fructose media but increases on glucose medium. Moreover, the mycelial growth rate of the <em>VmSom1</em> deletion mutant is significantly lower than that of the wild-type strain in peptone, NH<sub>4</sub>SO<sub>4</sub>, NaNO<sub>3</sub>, and no nitrogen. Notably, the distances between the septa increase, and chitin concentration shifts to the hyphal tip in the <em>VmSom1</em> deletion mutant. Furthermore, compared with the wild-type strain, the <em>VmSom1</em> deletion mutant exhibits fewer diseased spots on apple fruit and branches. Overall, our findings demonstrate that <em>VmSom1</em> 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 <em>V. mali</em>.</p></div>","PeriodicalId":18599,"journal":{"name":"Microbial pathogenesis","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2024-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142036346","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}