Precision Clinical Medicine最新文献

{"title":"Computational insights into CRISP3 downregulation in cervical cancer and its cervical lineages pattern","authors":"Ricardo Cesar Cintra, Andrés Galindo Céspedes, Mércia Patrícia Ferreira Conceição, Maiza Vitoria Aguiar Silva Oliveira, Alessandro Buron, Deisiane Rodrigues das Neves, Fabio Alves Moraes, Olinda Maria Gamarra, Daniel Rodrigues de Bastos","doi":"10.1093/pcmedi/pbae016","DOIUrl":"https://doi.org/10.1093/pcmedi/pbae016","url":null,"abstract":"\u0000 \u0000 \u0000 Cysteine-Rich Secretory Protein 3 (CRISP3) emerges as a potential biomarker in the study of many cancers, including cervical cancer.\u0000 \u0000 \u0000 \u0000 To analyze the expression pattern of CRISP3 in cervical cancer patients and cervical cancer cell lineages, following treatment with the epigenetic drugs: trichostatin A (TSA) and 5-aza-2'-deoxycytidine (5-aza).\u0000 \u0000 \u0000 \u0000 The differentially expressed genes identified in GSE63514 were used to construct a protein-protein interaction network. CRISP3 was selected for subsequent analyses. We utilized data from the TCGA and GENT2 projects to evaluate the expression profile and clinical behavior of CRISP3. Additionally, we conducted cell culture experiments to analyze the expression profile of CRISP3 in cells.\u0000 \u0000 \u0000 \u0000 Low levels of CRISP3 were observed in squamous cell carcinoma (SCC) and HPV16+, along with being associated with worse overall survival (OS). MIR-1229-3p was analyzed, and its high expression was associated with worse prognostic outcomes. In cervical cancer-derived cell lines, we observed low levels of CRISP3 in SiHa, followed by SW756, C33A, HeLa, and higher levels in CaSki. All cells were treated with TSA, 5-aza, or both. In all cell lines, treatment with TSA resulted in increased transcription of CRISP3.\u0000 \u0000 \u0000 \u0000 we identified a significant downregulation of CRISP3 in cervical cancer, particularly in cases with HPV16 infection and SCC, which was associated with poorer OS. Preliminary findings suggest that epigenetic treatments with TSA and 5-aza may modulate CRISP3 expression, warranting further research to elucidate its regulatory mechanisms and potential as a prognostic biomarker.\u0000","PeriodicalId":510407,"journal":{"name":"Precision Clinical Medicine","volume":"44 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141808455","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"COVID-19: from immune response to clinical intervention","authors":"Zheng-Yang Guo, Yan-Qing Tang, Zi- Bo Zhang, Juan Liu, Yu-Xin Zhuang, Tingxin Li","doi":"10.1093/pcmedi/pbae015","DOIUrl":"https://doi.org/10.1093/pcmedi/pbae015","url":null,"abstract":"\u0000 The coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has highlighted the pivotal role of the immune response in determining the progression and severity of viral infections. In this paper, we review the most recent studies on the complicated dynamics between SARS-CoV-2 and the host immune system, highlight the importance of understanding these dynamics in developing effective treatments and formulate potent management strategies for COVID-19. We describe the activation of the host's innate immunity and the subsequent adaptive immune response following infection with SARS-CoV-2. In addition, the review emphasizes the immune evasion strategies of the SARS-CoV-2, including inhibition of interferon production and induction of cytokine storms, along with the resulting clinical outcomes. Finally, we assess the efficacy of current treatment strategies, including antiviral drugs, monoclonal antibodies, and anti-inflammatory treatments, and discuss their role in providing immunity and preventing severe disease.","PeriodicalId":510407,"journal":{"name":"Precision Clinical Medicine","volume":" 15","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141826098","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Suppression of MyD88 disturbs gut microbiota and activates NLRs pathway hence fails to ameliorate DSS-induced colitis","authors":"Jun-hua Li, Yu Chen, Zheng-hao Ye, Li-ping Chen, Jia-xin Xu, Jian Han, Lin Xie, Shuai Xing, De-an Tian, Ursula Seidler, JiaFu Liao, Fang Xiao","doi":"10.1093/pcmedi/pbae013","DOIUrl":"https://doi.org/10.1093/pcmedi/pbae013","url":null,"abstract":"\u0000 \u0000 \u0000 Myeloid differentiation factor 88 (MyD88) is the core adaptor for TLRs defending against microbial invasion and initiating downstream immune response during microbiota-host interaction. However, the role of MyD88 in the pathogenesis of IBD is controversial. This study aims to investigate the impact of MyD88 on intestinal inflammation and the underlying mechanism.\u0000 \u0000 \u0000 \u0000 MyD88 knockout (MyD88−/−) mice and the MyD88 inhibitor (TJ-M2010-5) were used to investigate the impact of MyD88 on acute dextran sodium sulfate (DSS)-induced colitis. Disease activity index, colon length, histological score, and inflammatory cytokines were examined to evaluate the severity of colitis. The RNA transcriptome analysis and 16S rDNA sequencing were used to detect the potential mechanism.\u0000 \u0000 \u0000 \u0000 In the acute DSS-colitis model, the severity of colitis was not alleviated in MyD88−/− mice and TJ5-treated mice, despite significantly lower levels of NF-κB activation exhibited compared to control mice. Meanwhile, the 16S rDNA sequencing and RNA transcriptome analysis revealed a higher abundance of intestinal Proteobacteria and an up-regulation of the NOD-like receptors (NLRs) signaling pathway in colitis mice following MyD88 suppression. Further blockade of the NLR signaling pathway or elimination of gut microbiota with broad-spectrum antibiotics in DSS-induced colitis mice treated with TJ5 ameliorated the disease severity, which was not improved solely by MyD88 inhibition. After treatment with broad-spectrum antibiotics, the downregulation of the NLR signaling pathway was observed.\u0000 \u0000 \u0000 \u0000 Our study suggests that the suppression of MyD88 might be associated with unfavorable changes in the composition of gut microbiota, leading to NLR-mediated immune activation and intestinal inflammation.\u0000","PeriodicalId":510407,"journal":{"name":"Precision Clinical Medicine","volume":"98 9","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-06-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141378061","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Double-blinded, Randomized Clinical Trial of Gegen Qinlian Decoction Pinpoints Faecalibacterium as Key Gut Bacteria in Alleviating Hyperglycemia","authors":"Zezheng Gao, Wenhui Zhang, Lisha He, Han Wang, Yufei Li, Xiaotian Jiang, Sha Di, Xinmiao Wang, Xuan Zhang, Lin Han, Yanwen Liu, C. Gu, Mengyi Wu, Xinhui He, Lei Cheng, Jun Wang, Xiaolin Tong, Linhua Zhao","doi":"10.1093/pcmedi/pbae003","DOIUrl":"https://doi.org/10.1093/pcmedi/pbae003","url":null,"abstract":"\u0000 \u0000 \u0000 Accumulating evidence suggests that metabolic disorders, including type 2 diabetes mellitus, can be treated with traditional Chinese medicine formulas, such as the Gegen Qinlian Decoction (GQD). This study elucidated the mechanisms by which gut microbes mediate the anti-diabetic effects of GQD.\u0000 \u0000 \u0000 \u0000 We conducted a double-blind randomized clinical trial involving 110 untreated participants with type 2 diabetes. During the 12-week intervention, anthropometric measurements and diabetic traits were recorded every four weeks. Fecal microbiota and serum metabolites were measured before and after the intervention using 16S rDNA sequencing, liquid chromatography-mass spectrometry, and Bio-Plex panels. The diabetes-alleviating effect of Faecalibacterium was confirmed by oral administration of Faecalibacterium prausnitzii in a type 2 diabetes mouse model.\u0000 \u0000 \u0000 \u0000 Anti-diabetic effects were observed in the GQD group in the human trial. Specifically, the glycated hemoglobin (HbA1c), fasting plasma glucose (FPG), and two-hour postprandial blood glucose levels were significantly lower in the GQD group than in the placebo group. Additionally, Faecalibacterium was significantly enriched in the GQD group, and the short-chain fatty acid levels were higher and the serum inflammation-associated marker levels were lower in the GQD group compared to the placebo group. Moreover, the Faecalibacterium abundance positively correlated with the levels of serum HbA1c, FPG, and pro-inflammatory cytokines. Finally, administering Faecalibacterium prausnitzii (DSMZ 17677) mirrored the findings of the human trial.\u0000 \u0000 \u0000 \u0000 GQD improved type 2 diabetes primarily by modulating the abundance of Faecalibacterium in the gut microbiota, alleviating metabolic disorders and the inflammatory state.\u0000 Trial registration: Registry No. ChiCTR-IOR-15006626.\u0000","PeriodicalId":510407,"journal":{"name":"Precision Clinical Medicine","volume":"102 11","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-02-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139963675","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}