Discovery medicine最新文献

{"title":"Hypomethylation and the Resultant Overexpressed PARM1: a Biomarker for Poor Prognosis of Diffuse Large B-cell Lymphoma.","authors":"Baoping Cao,&nbsp;Xiaochuan Guo,&nbsp;Bin Wang,&nbsp;Weixia Wang,&nbsp;Dong Han,&nbsp;Weijing Zhang,&nbsp;Kaili Zhong","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Prostate androgen-regulated mucin-like protein (PARM1) is known to promote cell survival via protecting the cell surface, thus being involved in cancer development. The Gene Expression Profiling Interactive Analysis (GEPIA), MEXPRESS database, LinkedOmics database, GeneMANIA database, and the Tumor Immune Estimation Resource (TIMER) database were accessed to explore the epigenetic regulation, prognostic value, biological functions and mechanisms of PARM1 in diffuse large B-cell lymphoma (DLBCL). Hypomethylation and resultant overexpression of PARM1 was found in DLBCL. The high-level expression of PARM1 was related to the poor outcome of DLBCL patients. PARM1 participated in DNA repair, cell cycle, and cellular response to stress. PARM1 was also associated with autophagy, apoptosis, Ras pathway, and MAPK cascade. Significant kinase targets of PARM1 included ATM, CDK1, and CDK2. Significant transcription factor targets of PARM1 involved ELK1, MYC and so on. Significant miRNA targets of PARM1 included miR21, miR202, miR323, and miR345. Further analysis suggested that the PARM1 regulated autophagy through the PI3K-Akt signaling. PARM1 was found to be correlated with immune cell infiltration, which indicated the important roles of PARM1 in microenvironment of DLBCL. Our study lays a foundation for further research on the impact of PARM1 in DLBCL tumorigenesis and precision therapy.</p>","PeriodicalId":11379,"journal":{"name":"Discovery medicine","volume":"33 168","pages":"27-40"},"PeriodicalIF":1.4,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10341465","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":"Serum CHI3L1 as a Biomarker for Non-invasive Diagnosis of Liver Fibrosis.","authors":"Jianfeng Bao,&nbsp;Yuan Ouyang,&nbsp;Liang Qiao,&nbsp;Jiahui He,&nbsp;Fang Liu,&nbsp;Yi Wang,&nbsp;Liangbin Miao,&nbsp;Ai Fu,&nbsp;Zhonghan Lou,&nbsp;Qian Zang,&nbsp;Weiqiang Huang,&nbsp;Jinsong Huang,&nbsp;Zhaoyi Li","doi":"","DOIUrl":"","url":null,"abstract":"<p><strong>Background: </strong>Liver fibrosis is the early pathological manifestation of various chronic liver diseases (including schistosomiasis, alcoholic, viral, nonalcoholic, fatty liver, etc.), which can progress to cirrhosis and even liver cancer. Out of the 7.7 billion world population, approximately 2 billion individuals have evidence of hepatitis B virus (HBV) infection; of these, 350 to 400 million suffer from chronic HBV infection, accounting for about 5% of the global population. The global prevalence of hepatitis C is 3%. These figures indicate that liver fibrosis is quite common.</p><p><strong>Methods: </strong>98 patients with liver fibrosis were included in this study. The serum chitinase-3 Like Protein-1 (CHI3L1) level was measured by the double antibody Sandwich ELISA method.</p><p><strong>Results: </strong>Serum levels of CHI3L1 were significantly different between no-fibrosis and fibrosis groups (P < 0.01). There was a strong correlation between the levels of CHI3L1, elastometry, hyaluronan, CIV (P < 0.01) and age and sex, TBIL, DBIL, ALB, AST, ALT, GGT, ALP, PLT, LN, PIINP, FIB-4, and APRI (P < 0.05). The expression of CHI3L1 was different from fibrosis grades S1, S3, and S4 (P < 0.05, P < 0.001). The expression of CHI3L1 was significantly different between F1 and F4 (P < 0.05). Serum CHI3L1 expression level can be a valuable metric for diagnosing liver fibrosis, with an AUC value of 0.812. Out of the 98 patients who had undergone liver puncture, 79 patients (30.38%) had ALT ≤ 2ULN.</p><p><strong>Conclusions: </strong>The expression level of serum CHI3L1 was significantly higher in patients with liver fibrosis than that in patients without liver fibrosis. The expression levels of serum CHI3L1 were different in different grades of liver fibrosis and increased with the severity of liver fibrosis. Serum CHI3L1 can distinguish early stage (S1) of liver fibrosis from late stage (S3-4) of liver fibrosis. Serum CHI3L1 combined with HA is even more effective in the diagnosis of S2-4 hepatic fibrosis. The diagnostic efficacy of serum CHI3L1 in patients with ALT ≤ 2ULN was better than that of the other non-invasive diagnostic models.</p>","PeriodicalId":11379,"journal":{"name":"Discovery medicine","volume":" ","pages":"41-49"},"PeriodicalIF":1.4,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40580430","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":"circRNA-miRNA Complex Participates in the Apoptosis of Myocardial Cells in Myocardial Ischemia/Reperfusion Injury.","authors":"Yu Sun,&nbsp;Yuanmei Zhang,&nbsp;Zebing Ye,&nbsp;Yan Wang,&nbsp;Yu Lao,&nbsp;Juhong Zhang,&nbsp;Ming Fang,&nbsp;Jie He,&nbsp;Hao Yin,&nbsp;Wen Yan,&nbsp;Wen Jin","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Myocardial ischemia/reperfusion (I/R) injury is a common condition. This study aimed to investigate the potential mechanisms of circ_Ddx60 in the mouse model of I/R injury. Cardiac tissues were used to extract RNA for subsequent RNA sequencing analysis. Bioinformatic analysis was performed and circ_Ddx60 and Bcl2a1a (B cell leukemia/lymphoma 2 related protein A1a) were selected for further validation. Quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) was used to detect the gene expression level. The effect of circ_Ddx60 on cardiac cell apoptosis was examined. The function of miR-302a-3p in cell apoptosis was further explored in circ_Ddx60-overexpressed HL-1 cells under hypoxia/reoxygenation (H/R) treatment. We have revealed a number of differentially expressed circRNAs and mRNAs between the I/R group and sham groups, with circ_Ddx60 being among them. Treatment of HL-1 cells with hypoxia/reoxygenation (H/R) led to an overexpression of circ_Ddx60, which then inhibited apoptosis and promoted the Bcl2a1a expression. Furthermore, circ_Ddx60 directly binds with miR-302a-3p, which could reverse the effect of circ_Ddx60 overexpression on cellular apoptosis and Bcl2a1a expression. Our study revealed that circ_Ddx60 inhibits apoptosis in myocardial cells by regulating the miR-302a-3p/Bcl2a1a axis, which provides novel insights into the prevention of myocardial I/R injury.</p>","PeriodicalId":11379,"journal":{"name":"Discovery medicine","volume":" ","pages":"13-26"},"PeriodicalIF":1.4,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40540625","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":"Using Next-generation Sequencing to Identify Novel Exosomal miRNAs as Biomarkers for Significant Hepatic Fibrosis.","authors":"Qianqian Wang,&nbsp;Qiankun Hu,&nbsp;Yue Ying,&nbsp;Chuan Lu,&nbsp;Weixia Li,&nbsp;Chenlu Huang,&nbsp;Wei Xu,&nbsp;Qiang Li,&nbsp;Xun Qi,&nbsp;Xueyun Zhang,&nbsp;Xiaoqin Liu,&nbsp;Zunguo Du,&nbsp;Yanling Feng,&nbsp;Yi Zhang,&nbsp;Xinyan Li,&nbsp;Yuanyuan Ji,&nbsp;Jiming Zhang,&nbsp;Jin Wang,&nbsp;Liang Chen,&nbsp;Yuxian Huang","doi":"","DOIUrl":"","url":null,"abstract":"<p><strong>Objective: </strong>The aim of this study is to determine the role of serum exosomal miRNAs as potential non-invasive biomarkers for distinguishing no-or-mild fibrosis from significant fibrosis in patients with chronic hepatitis B (CHB).</p><p><strong>Methods: </strong>Next-generation sequencing was used to identify fibrosis-related serum exosomal miRNAs in 9 CHB patients. The candidate exosomal miRNAs were further validated by qRT-PCR in 282 CHB patients. Receiver operating characteristic curves were generated to assess the diagnostic performance of exosomal miRNAs and other non-invasive models.</p><p><strong>Results: </strong>Seventy-two miRNAs were differentially expressed in serum exosomes between patients with no-or-mild fibrosis and significant fibrosis. The expression of serum exosomal miR-92a-3p and miR-146a-5p progressively increased with the aggravation of liver fibrosis in the validation cohort. Multivariate analysis identified miR-92a-3p (P<0.001), miR-146a-5p (P<0.001), and liver stiffness measurement (LSM) (P=0.012) as independent predictors for significant fibrosis. The area under the receiver operating characteristic curve (AUROC) of exosomal miR-92a-3p (AUROC=0.88) was significantly higher than that of APRI (aspartate aminotransferase-to-platelet ratio index) (AUROC=0.72, P<0.001), FIB-4 (AUROC=0.71, P<0.001), and LSM (AUROC=0.80, P=0.022) for identifying significant fibrosis. Similarly, the AUROC of exosomal miR-146a-5p (AUROC=0.82) was also significantly better than that of APRI (AUROC=0.72, P=0.009), FIB-4 (AUROC=0.71, P=0.002), and comparable to LSM (AUROC=0.80, P=0.551) for discriminating significant fibrosis.</p><p><strong>Conclusion: </strong>Serum exosomal miR-92a-3p and miR-146a-5p are superior to APRI, FIB-4, and LSM for diagnosing significant fibrosis in CHB patients and offer a promising non-invasive alternative to liver biopsy.</p>","PeriodicalId":11379,"journal":{"name":"Discovery medicine","volume":"31 164","pages":"147-159"},"PeriodicalIF":1.4,"publicationDate":"2021-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39942329","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 of Fatal Outcome of Hospitalized Patients with COVID-19.","authors":"Weihua Wu,&nbsp;Xulei Zhang,&nbsp;Yuxin Chen,&nbsp;Baofeng Wang,&nbsp;Jing Wu,&nbsp;Yali Xiong,&nbsp;Bei Jia,&nbsp;Jian Wang,&nbsp;Juan Xia,&nbsp;Yangjuan Pu,&nbsp;Wensan Zhou,&nbsp;Zhong Chen,&nbsp;Zhaoping Zhang,&nbsp;Xiaomin Yan,&nbsp;Rui Huang,&nbsp;Chao Wu","doi":"","DOIUrl":"","url":null,"abstract":"<p><strong>Background: </strong>Few studies reported the risk factors of fatal outcome of hospitalized patients with coronavirus disease 2019 (COVID-19). We aimed to identify the independent risk factors associated with fatal outcome of hospitalized COVID-19 patients.</p><p><strong>Methods: </strong>The clinical data of 109 consecutive COVID-19 patients including 40 (36.7%) common cases and 69 (63.3%) severe cases were included and analyzed.</p><p><strong>Results: </strong>Multivariate regression analysis indicated that platelets (PLT, OR, 0.988; 95% CI, 0.978-0.998; P=0.017) and C-reactive protein (CRP) (OR, 1.047; 95% CI, 1.026-1.068; P<0.001) levels were the independent risk factors of fatal outcome in COVID-19 patients. The optimal cut-off value of PLT counts for predicting fatal outcome was 161x109/L with the area under receiver operating characteristic curve (AUROC) of 0.824 (95% CI, 0.739-0.890). The optimal cut-off value of CRP for the prediction of fatal outcome was 46.2 mg/L with the AUROC of 0.954 (95% CI, 0.896-0.985). The CRP levels had higher predictive values for fatal outcome than PLT (P=0.016). The cumulative survival rate was significantly higher in patients with PLT>161x109/L compared with patients with PLT≤161x109/L (89.4% vs. 12.5%, log-rank test X2=72.17; P<0.001). Survival rate of COVID-19 patients was prominently higher in CRP≤46.2 mg/L patients compared with patients with CRP>46.2 mg/L (95.9% vs. 22.9%, log-rank test X2=77.85; P<0.001).</p><p><strong>Conclusions: </strong>PLT counts and CRP levels could predict fatal outcome of hospitalized COVID-19 patients with relatively high accuracy.</p>","PeriodicalId":11379,"journal":{"name":"Discovery medicine","volume":"31 164","pages":"121-127"},"PeriodicalIF":1.4,"publicationDate":"2021-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39941429","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":"Metabolic Reprogramming of Myeloid-derived Suppressor Cells in the Tumor Microenvironment.","authors":"Liang Liu,&nbsp;Shuping Huo,&nbsp;Jianghui Liu,&nbsp;Qiaomin Li,&nbsp;Jing Wang","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>A large number of studies on the metabolism of immune cells in anti-tumor response have been carried out in recent years. It is proved that metabolic reprogramming can determine the differentiation and functions of immune cells. Myeloid-derived suppressor cells (MDSCs) are a heterogeneous population of immunosuppressive cells in the tumor microenvironment (TME). They can significantly inhibit the anti-tumor response of T cells and play an important role in promoting tumor growth, metastasis, and invasion. This review summarizes the energy metabolic pathways of MDSCs in the TME, such as fatty acid oxidation (FAO), glycolysis, and amino acids (AAs) metabolism, and highlights the importance of metabolic reprogramming of MDSCs for its immunosuppressive functions.</p>","PeriodicalId":11379,"journal":{"name":"Discovery medicine","volume":"31 164","pages":"141-146"},"PeriodicalIF":1.4,"publicationDate":"2021-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39941431","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":"Gene Signatures and Prognostic Value of m6A RNA Methylation Regulators in Uterine Corpus Endometrial Carcinoma.","authors":"Yuanling Feng,&nbsp;Chunfang Yao,&nbsp;Jiayu Shen,&nbsp;Jianwei Zhou","doi":"","DOIUrl":"","url":null,"abstract":"<p><strong>Background: </strong>Uterine corpus endometrial carcinoma (UCEC) is the second most common malignancy of female reproductive system. Though most UCEC are diagnosed at an early age, the mortality has increased. It is important to develop new targets for prognosis evaluation and treatment.</p><p><strong>Methods: </strong>Expression profiles of 19 m6A regulators and UCEC samples' epidemiologic information were obtained from GTEx and TCGA datasets. Nonnegative matrix factorization (NMF) was used to cluster UCEC samples into three groups and overall survival (OS) was compared among them. Multivariate cox proportional hazard model was used to select targets for the construction of m6A-related prognosis prediction signature. A nomogram consisting of m6A-related signature, stage, and histology was provided for clinical application.</p><p><strong>Results: </strong>Eighteen m6A regulators were found to be differentially expressed between normal sample and UCEC samples. There was a significant difference in the OS probability among three clusters with different expression levels of m6A. VIRMA, YTHDF3, and IGF2BP1 were picked as UCEC prognosis prediction signatures and the prognostic value was confirmed. Risk score estimated by this signature was demonstrated to be the independent prognostic factor for UCEC.</p><p><strong>Conclusion: </strong>Aberrant expression of m6A RNA methylation regulators was significantly associated with the development and prognosis of UCEC. A three-gene signature consisting of VIRMA, YTHDF3, and IGF2BP1 may effectively predict the prognosis of UCEC patients.</p>","PeriodicalId":11379,"journal":{"name":"Discovery medicine","volume":"31 164","pages":"111-120"},"PeriodicalIF":1.4,"publicationDate":"2021-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39651017","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":"mTOR in the Mechanisms of Atherosclerosis and Cardiovascular Disease.","authors":"Zhe Liu,&nbsp;Yuxin Fan,&nbsp;Zhongliang Zhang,&nbsp;Yudong Fang,&nbsp;Xin Cheng,&nbsp;Qintong Yang,&nbsp;Jingwen Liu,&nbsp;Jun Xie","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>mTOR (the mammalian target of rapamycin) is a serine/threonine kinase that can regulate a variety of signaling pathways, including cell growth, proliferation, and apoptosis. mTOR can regulate the proliferation and migration of endothelial cells and smooth muscle cells during the occurrence and progression of atherosclerosis. By inhibiting or activating mTOR at different time points, atherosclerotic vulnerable plaques can be stabilized and the occurrence and progression of atherosclerosis can be impeded. The mTOR signaling pathway plays a multifaceted role in the progression of atherosclerosis. mTOR and its interactions with molecular targets in the mechanisms of atherosclerosis and cardiovascular diseases are reviewed in this article, taking into consideration their potential of opening up novel therapeutic avenues.</p>","PeriodicalId":11379,"journal":{"name":"Discovery medicine","volume":"31 164","pages":"129-140"},"PeriodicalIF":1.4,"publicationDate":"2021-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39941434","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":"Efficacy of Remdesivir for COVID-19.","authors":"Hongming Zhang,&nbsp;Jibei Chen,&nbsp;Xiyong Wang,&nbsp;Baoan Chen","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Remdesivir is a broad-spectrum antiviral agent. With the rapid spread of Coronavirus disease 2019 (COVID-19) globally, remdesivir is taking the spotlight for COVID-19 treatment. Despite the promising signs of anti-CoV activity in several preclinical and clinical studies, more data of remdesivir in the treatment of COVID-19 is still needed for evaluating its efficacy.</p>","PeriodicalId":11379,"journal":{"name":"Discovery medicine","volume":"31 163","pages":"57-60"},"PeriodicalIF":1.4,"publicationDate":"2021-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39772766","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":"Advanced Techniques in Predicting Breast Tumor Response to Neoadjuvant Chemotherapy.","authors":"Mohamed Abbas","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Neoadjuvant therapy is used to treat breast cancer through preventive agents. This new type of chemotherapy is prescribed according to the size of the tumor, so as to reduce the tumor mass and give more surgical options. Neoadjuvant hormone treatment is also helping to shrink breast cancer in lymph nodes or elsewhere in the breast before surgery. A significant aspect of the treatment is to predict breast tumor response to neoadjuvant chemotherapy. Here, the latest advanced breast tumor response techniques have been presented for this type of therapy. These techniques are classified into three categories: deep and machine learning, quantitative ultrasound spectroscopy, and magnetic resonance imaging. These methods were important for the prediction of a tumor's chemical response to the neoadjuvant chemotherapy. Tumor response assessment leads to effective chemical treatment, which decreases the size of the breast tumor and allows surgery to remove the tumor effectively.</p>","PeriodicalId":11379,"journal":{"name":"Discovery medicine","volume":"31 163","pages":"69-77"},"PeriodicalIF":1.4,"publicationDate":"2021-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39772768","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}