Pharmacogenomics & Personalized Medicine最新文献

{"title":"Discovery of Drug-Responsive Phenomic Alteration-Related Driver Genes in the Treatment of Coronary Heart Disease.","authors":"Shuang Guan,&nbsp;Ya-Nan Yu,&nbsp;Bing Li,&nbsp;Hao Gu,&nbsp;Lin Chen,&nbsp;Nian Wang,&nbsp;Bo Wang,&nbsp;Xi Liu,&nbsp;Jun Liu,&nbsp;Zhong Wang","doi":"10.2147/PGPM.S398522","DOIUrl":"https://doi.org/10.2147/PGPM.S398522","url":null,"abstract":"Background The Xueyu Zheng (XYZ) phenome is central to coronary heart disease (CHD), but efforts to detect genetic associations in the XYZ phenome have been disappointing. Methods The phenomic alteration-related genes (PARGs) for the XYZ phenome were screened using |ρ| > 0.4 and p < 0.05 after treatment with Danhong injection at day 14 and day 30. Then, the driver genes for the Protein-Protein Interaction (PPI) networks of the PARGs established using STRING 11.0 were detected using a personalized network control algorithm (PNC). Finally, the molecular correlations of the driver genes with the XYZ phenome were analyzed with the Gene Ontology (GO) biological processes and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways from a holistic viewpoint. Results A total of 525 and 309 PARGs in the XYZ phenome at day 14 and day 30 were identified. These genes were separately enriched in 48 and 35 pathways. Furthermore, five driver genes were detected. These genes were mainly correlated with endoplasmic reticulum stress-mediated apoptosis and autophagy regulation, which could suppress atherosclerosis progression. Conclusion Our study detected the drug-responsive PARGs of the XYZ phenome in CHD and provides an exemplary strategy to investigate the genetic associations among this common phenome and its component symptoms in patients with CHD. Trial Registration ClinicalTrials.gov, NCT01681316; registered on September 7, 2012.","PeriodicalId":56015,"journal":{"name":"Pharmacogenomics & Personalized Medicine","volume":"16 ","pages":"201-217"},"PeriodicalIF":1.9,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/98/18/pgpm-16-201.PMC10024908.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9513447","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Influence of Cytochrome P450 Polymorphisms on Pharmacokinetic Profiles and Treatment Outcomes Among Malaria Patients in Sub-Saharan Africa: A Systematic Review.","authors":"Karol J Marwa,&nbsp;Anthony Kapesa,&nbsp;Erasmus Kamugisha,&nbsp;Göte Swedberg","doi":"10.2147/PGPM.S379945","DOIUrl":"https://doi.org/10.2147/PGPM.S379945","url":null,"abstract":"<p><strong>Background: </strong>Sub-Saharan Africa (SSA) population is genetically diverse and heterogenous thus variability in drug response among individuals is predicted to be high. Cytochrome P450 (CYP450) polymorphisms is a major source of variability in drug response. This systematic review presents the influence of CYP450 single nucleotide polymorphisms (SNPs), particularly CYP3A4*1B, CYP2B6*6 and CYP3A5*3 on antimalarial drug plasma concentrations, efficacy and safety in SSA populations.</p><p><strong>Methods: </strong>Searching for relevant studies was done through Google Scholar, Cochrane Central Register of controlled trials (CENTRAL), PubMed, Medline, LILACS, and EMBASE online data bases. The Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines were used. Two independent reviewers extracted data from the studies.</p><p><strong>Results: </strong>Thirteen studies reporting the influence of CYP450 SNPs on plasma concentrations, efficacy and safety were included in the final data synthesis. CYP3A4*1B, CYP3A5*5, CYP2B6*6 and CYP2C8*2 did not affect antimalarial drug plasma concentration significantly. There was no difference in treatment outcomes between malaria patients with variant alleles and those with wild type alleles.</p><p><strong>Conclusion: </strong>This review reports lack of influence of CYP3A4*1B, CYP3A5*3, CYP2C8*3 and CYP2B6*6 SNPs on PK profiles, efficacy and safety in SSA among <i>P. falciparum</i> malaria patients.</p>","PeriodicalId":56015,"journal":{"name":"Pharmacogenomics & Personalized Medicine","volume":"16 ","pages":"449-461"},"PeriodicalIF":1.9,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/fd/bc/pgpm-16-449.PMC10202199.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9518986","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mental Health Prescribers' Perceptions on the Use of Pharmacogenetic Testing in the Management of Depression in the Middle East and North Africa Region.","authors":"Shimaa Aboelbaha,&nbsp;Monica Zolezzi,&nbsp;Oraib Abdallah,&nbsp;Yassin Eltorki","doi":"10.2147/PGPM.S410240","DOIUrl":"https://doi.org/10.2147/PGPM.S410240","url":null,"abstract":"<p><strong>Objective: </strong>A wide variety of commercial pharmacogenetic (PGx) tools are available worldwide to guide treatment selection for depression based on individuals' genetic profiles. However, the use of genetic testing to inform psychiatric care has faced challenges due to the limited training and education for mental health clinicians. The aim of this study was to explore the knowledge, level of engagement, and perspectives on the use of PGx testing when making depression management decisions among practicing psychiatrists within the Middle East and North Africa (MENA) region.</p><p><strong>Methods: </strong>This is a qualitative study using semi-structured interviews. Consenting psychiatrists were interviewed through an online platform (Skype^TM or Microsoft Teams^TM). Interviews were audio recorded, transcribed, and thematically analyzed with the assistance of NVivo^® software.</p><p><strong>Results: </strong>Eighteen interviews from 12 countries have been conducted. Analysis of the current interviews produced five major themes including: (1) Overall perceptions and attitudes; (2) Knowledge and awareness; (3) Education, training, and professional experience; (4) Facilitators and barriers; and (5) Ethical dilemmas. These themes support the notion that there is limited, mostly basic, education, knowledge, and training regarding genetic testing in the management of depression, although there is significant interest and willingness in the part of prescribers to adopt this strategy in their practice.</p><p><strong>Conclusion: </strong>The findings of the study suggest that psychiatrists practicing in the MENA region appear to be interested in implementing PGx testing when managing people with depression. However, it is also important to recognize that this cannot be achieved unless more supporting strategies are implemented within their current health system environment.</p>","PeriodicalId":56015,"journal":{"name":"Pharmacogenomics & Personalized Medicine","volume":"16 ","pages":"503-518"},"PeriodicalIF":1.9,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10239256/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9934982","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Allelic Expression of RNA Editing Gene <i>ADARB1</i> in Hepatocellular Carcinoma Treated with Transarterial Chemoembolization.","authors":"Jiajia Zeng,&nbsp;Linyu Han,&nbsp;Teng Wang,&nbsp;Linying Huang,&nbsp;Yanxiu Zheng,&nbsp;Nasha Zhang,&nbsp;Ziqiang Li,&nbsp;Ming Yang","doi":"10.2147/PGPM.S402115","DOIUrl":"https://doi.org/10.2147/PGPM.S402115","url":null,"abstract":"<p><strong>Introduction: </strong>Transarterial chemoembolization (TACE) is the commonly used therapy of unresectable hepatocellular carcinoma (HCC), though the prognosis of different TACE-treated HCC patients varies, which may be due to the heterogeneity of HCC tumors caused by genetic variants and epigenetic changes such as RNA editing. There is dysregulated RNA adenosine-to-inosine (A-to-I) editing in HCC and RNA-edited genes are involved in the epigenetic process. It remains unclear how genetic variants of RNA editing genes affect the prognosis of HCC cases treated by TACE.</p><p><strong>Methods: </strong>In this study, we examined 28 potentially functional single-nucleotide polymorphisms (SNPs) of four RNA editing genes (<i>ADARB1, ADAR, ADARB2</i> and <i>AIMP2</i>) in two independent TACE patient cohorts.</p><p><strong>Results: </strong>We found that <i>ADARB1</i> rs1051367 and rs2253763 polymorphisms were markedly associated with the prognosis of HCC cases who received TACE in both cohorts. In HCC cells, the rs2253763 C-to-T change in <i>ADARB1</i> 3'-untranslated region attenuated its binding with miR-542-3p and allele-specifically elevated <i>ADARB1</i> levels. Consistent with this, patients carrying the rs2253763 C allele showed reduced <i>ADARB1</i> expression in cancer tissues and notably shorter survival after TACE therapy in comparison with individuals with the T allele. Ectopic <i>ADARB1</i> profoundly enhanced the efficacy of oxaliplatin, one of the common TACE chemotherapeutic drugs.</p><p><strong>Discussion: </strong>Our findings highlighted the value of <i>ADARB1</i> polymorphisms as prognostic markers in TACE therapy for HCC patients. Notably, our findings revealed that targeting the ADARB1 enzyme may be a promising therapeutic strategy in combination with TACE for HCC cases.</p>","PeriodicalId":56015,"journal":{"name":"Pharmacogenomics & Personalized Medicine","volume":"16 ","pages":"229-238"},"PeriodicalIF":1.9,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/c4/e7/pgpm-16-229.PMC10032144.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9194066","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Plasma Homocysteine (Hcy) Concentration Functions as a Predictive Biomarker of SPECT-Evaluated Post-Ischemic Hyperperfusion in Acute Ischemic Stroke.","authors":"Yingqiu Wang,&nbsp;Renhua Hou,&nbsp;Yan Liu","doi":"10.2147/PGPM.S400767","DOIUrl":"https://doi.org/10.2147/PGPM.S400767","url":null,"abstract":"<p><strong>Introduction: </strong>Homocysteine (Hcy) concentration has been reported to be associated with ischemic stroke. In this study, we aimed to investigate the potential of plasma Hcy in the prediction of post-ischemic hyperperfusion in AIS patients, which was diagnosed with the single-photon emission computed tomography (SPECT) method.</p><p><strong>Methods: </strong>A total of 112 ischemic stroke patients were recruited in this study. According to whether the patients were subjected to post-ischemic hyperperfusion, all recruited subjects were divided into a post-ischemic hyperperfusion (+) group (N=48) and post-ischemic hyperperfusion (-) group (N=64). The basic demographical data, clinicopathological data and laboratory biochemical data were collected and compared. Level of homocysteine (Hcy) and cystatin-C (Cys-C) and their potential as predictive biomarker are also investigated.</p><p><strong>Results: </strong>No significant differences were spotted between the post-ischemic hyperperfusion group (+) and post-ischemic hyperperfusion (-) group in respect to the basic demographical and clinicopathological data. And the serum Hcy levels were lower in the post-ischemic hyperperfusion (+) group. Moreover, ROC analysis indicated significant relationships between Hcy levels and the onset of post-ischemic hyperperfusion.</p><p><strong>Conclusion: </strong>In conclusion, we validated that the plasma Hcy concentration can be used as a predictive biomarker of SPECT-evaluated post-ischemic hyperperfusion in patients suffering from acute ischemic stroke.</p>","PeriodicalId":56015,"journal":{"name":"Pharmacogenomics & Personalized Medicine","volume":"16 ","pages":"481-489"},"PeriodicalIF":1.9,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/2a/e1/pgpm-16-481.PMC10226540.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9924329","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Integrated Bioinformatics Analysis and Experimental Verification of Immune Cell Infiltration and the Related Core Genes in Ulcerative Colitis.","authors":"Danya Zhao,&nbsp;Danping Qin,&nbsp;Liming Yin,&nbsp;Qiang Yang","doi":"10.2147/PGPM.S406644","DOIUrl":"https://doi.org/10.2147/PGPM.S406644","url":null,"abstract":"<p><strong>Background: </strong>Ulcerative colitis is a recurrent autoimmune disease. At present, the pathogenesis of UC is not completely clear. Hence, the etiology and underlying molecular mechanism need to be further investigated.</p><p><strong>Methods: </strong>Three sets of microarray datasets were included from the Gene Expression Omnibus database. The differentially expressed genes in two sets of datasets were analyzed using the R software, and the core genes of UC were screened using machine learning. The sensitivity and specificity of the core genes were evaluated with the receiver operating characteristic curve in another microarray dataset. Subsequently, the CIBERSORT tool was used to analyze the relationship between UC and its core genes and immune cell infiltration. To verify the relationship between UC and core genes and the relationship between core genes and immune cell infiltration in vivo.</p><p><strong>Results: </strong>A total of 36 DEGs were identified. <i>AQP8, HMGCS2</i>, and <i>VNN1</i> were determined to be the core genes of UC. These genes had high sensitivity and specificity in receiver operating characteristic curve analysis. According to the analysis of immune cell infiltration, neutrophils, monocytes, and macrophages were positively correlated with UC. <i>AQP8, HMGCS2</i>, and <i>VNN1</i> were also correlated with immune cell infiltration to varying degrees. In vivo experiments verified that the expressions of neutrophils, monocytes, and macrophages increased in the UC colon. Furthermore, the expressions of <i>AQP8</i> and <i>HMGCS2</i> decreased, whereas that of <i>VNN1</i> increased. Azathioprine treatment improved all the indicators to different degrees.</p><p><strong>Conclusion: </strong><i>AQP8, HMGCS2</i>, and <i>VNN1</i> are the core genes of UC and exhibit different degrees of correlation with immune cells. These genes are expected to become new therapeutic targets for UC. Moreover, the occurrence and development of UC are influenced by immune cell infiltration.</p>","PeriodicalId":56015,"journal":{"name":"Pharmacogenomics & Personalized Medicine","volume":"16 ","pages":"629-643"},"PeriodicalIF":1.9,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/b1/f7/pgpm-16-629.PMC10296601.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10113420","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Expression and Correlation of MIF and ERK1/2 in Liver Cirrhosis and Hepatocellular Carcinoma Induced by Hepatitis B.","authors":"Dong Jia,&nbsp;Bin Li,&nbsp;Jun-Ke Wang,&nbsp;Pan Wang,&nbsp;Chu-Yi Li,&nbsp;Li-Xia Lu,&nbsp;Wen-Yan Tian,&nbsp;Xiao-Hui Yu,&nbsp;Jiu-Cong Zhang,&nbsp;Ying Zheng","doi":"10.2147/PGPM.S398976","DOIUrl":"https://doi.org/10.2147/PGPM.S398976","url":null,"abstract":"<p><strong>Objective: </strong>To detect expression and phosphorylation level of macrophage migration inhibitor (MIF) and extracellular-regulated kinases 1 and 2 (ERK1/2) in hepatitis B-induced liver cirrhosis (HBILC) and hepatocellular carcinoma (HCC) with a background of HBILC and analyze the correlation of MIF and ERK1/2 with HBILC and HCC.</p><p><strong>Methods: </strong>Twenty cases of normal liver tissues were collected as a control group, and 48 specimens of HBILC tissues and 48 specimens of HCC tissues were collected as the experimental group, which were assigned as the HBILC group and HCC group, respectively. All tissue specimens were processed into tissue chips. The expressions of MIF, ERK1/2, and their phosphorylated proteins were detected via immunohistochemistry, and MIF and ERK1/2 nucleic acid expressions were detected by in situ hybridization. The results were statistically analyzed using the chi-square test.</p><p><strong>Results: </strong>Proteins and nucleic acids of MIF and ERK1/2 presented low expression in the control group and high expression in the HBILC group and HCC group. MIF expression in the three groups was 25.0%, 75.0%, and 79.17%, respectively, while that of the nucleic acids was 25.0%, 70.83%, and 68.75%, respectively. Expression of ERK1/2 in the three groups was 40.0%, 60.42%, and 81.25%, respectively, and that of nucleic acids was 40.0%, 79.17%, and 77.08%. Expression of pERK1/2 was low in the control and HBILC group and high in the HCC group. Expression of pERK1/2 in the three groups was 20%, 45.83%, and 75%, respectively. Expression of pERK1/2 in the HCC group was significantly different from that in the HBILC and control group (<i>P</i><0.05), but the difference between the HBILC group and control group was not statistically significant (<i>P</i>>0.05).</p><p><strong>Conclusion: </strong>Occurrence and development of HBILC and HCC are not only related to the high expression of MIF but also closely related to the activation of the ERK1/2 signaling pathway.</p>","PeriodicalId":56015,"journal":{"name":"Pharmacogenomics & Personalized Medicine","volume":"16 ","pages":"381-388"},"PeriodicalIF":1.9,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/c5/c9/pgpm-16-381.PMC10145491.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9392985","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"<i>NOTCH2, ATIC, MRI1, SLC6A13, ATP13A2</i> Genetic Variations are Associated with Ventricular Septal Defect in the Chinese Tibetan Population Through Whole-Exome Sequencing.","authors":"Xiaohui Zhang,&nbsp;Da Zhen,&nbsp;Xuemei Li,&nbsp;Faling Yi,&nbsp;Zhanhao Zhang,&nbsp;Wei Yang,&nbsp;Xuguang Li,&nbsp;Yemeng Sheng,&nbsp;Xiaoli Liu,&nbsp;Tianbo Jin,&nbsp;Yongjun He","doi":"10.2147/PGPM.S404438","DOIUrl":"https://doi.org/10.2147/PGPM.S404438","url":null,"abstract":"<p><strong>Background: </strong>Ventricular septal defect (VSD) is the most common congenital cardiac abnormality in children and the second most common in adults. This study aimed to explore the potentially causative genes in VSD patients in the Chinese Tibetan population, and to provide a theoretical basis for the genetic mechanism of VSD.</p><p><strong>Methods: </strong>Peripheral venous blood was collected from 20 VSD subjects, and whole-genome DNA was extracted. High-throughput sequencing was performed on qualified DNA samples using whole-exome sequencing (WES) technology. After filtering, detecting, and annotating qualified data, single nucleotide variations (SNVs) and insertion-deletion (InDel) markers were analyzed, and data processing software such as GATK, SIFT, Polyphen, and MutationTaster were used for comparative evaluation and prediction of pathogenic deleterious variants associated with VSD.</p><p><strong>Results: </strong>A total of 4793 variant loci, including 4168 SNVs, 557 InDels and 68 unknown loci and 2566 variant genes were obtained from 20 VSD subjects through bioinformatics analysis. According to the screening of the prediction software and database, the occurrence of VSD was predicted to be associated with five inherited pathogenic gene mutations, all of which were missense mutations, including <i>NOTCH2</i> (c.1396C >A:p.Gln466Lys), <i>ATIC</i> (c.235C >T:p.Arg79Cys), <i>MRI1</i> (c.629G >A:p.Arg210Gln), <i>SLC6A13</i> (c.1138G >A:p.Gly380Arg), <i>ATP13A2</i> (c.1363C >T:p.Arg455Trp).</p><p><strong>Conclusion: </strong>This study demonstrated that <i>NOTCH2, ATIC, MRI1, SLC6A13, ATP13A2</i> gene variants were potentially associated with VSD in Chinese Tibetan population.</p>","PeriodicalId":56015,"journal":{"name":"Pharmacogenomics & Personalized Medicine","volume":"16 ","pages":"389-400"},"PeriodicalIF":1.9,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/48/91/pgpm-16-389.PMC10150769.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9411903","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Dysregulation of circRNA-0076906 and circRNA-0134944 is Correlated with Susceptibility to Osteoporosis and Osteoporotic Fracture in Postmenopausal Females from the Chinese Han Population.","authors":"Weijie Yang,&nbsp;Wei Zhang,&nbsp;Fengqian Li,&nbsp;Ning Xu,&nbsp;Ping Sun","doi":"10.2147/PGPM.S394757","DOIUrl":"https://doi.org/10.2147/PGPM.S394757","url":null,"abstract":"<p><strong>Introduction: </strong>Many circRNAs, such as circRNA-0076906 and circRNA-0134944, have been reported to participate in the pathogenesis of osteoporosis via sponging miRNAs in postmenopausal female patients. In this study, we aimed to study potential signaling pathways underlying the role of certain circRNAs, miRNAs and their target genes in the pathogenesis of osteoporotic fracture in postmenopausal females.</p><p><strong>Methods: </strong>Quantitative real-time PCR was performed to analyze the expression of circRNAs, miRNAs and their targets genes. Luciferase assays were carried out to explore the regulatory relationship between circ_0076906/miR-548i/OGN and circ_0134944/miR-630/TLR4.</p><p><strong>Results: </strong>Osteoporosis and fracture were positively correlated to the expression of circ_0134944, miR-548i and TLR4, but negatively correlated to the expression of circ_0076906, miR-630 and OGN in the peripheral blood and bone tissue samples of postmenopausal women. Luciferase activities of wild-type circ_0076906 and OGN were inhibited by miR-548i, and the luciferase activities of wild-type circ_0134944 and TLR4 were suppressed by miR-630 in MG-63 and U-2 OS cells. Inhibition of circ_0076906 expression in MG-63 and U-2 OS cells activated the expression of miR-548i and inhibited the expression of OGN. Moreover, the overexpression of circ_0134944 in MG-63 and U-2 OS cells suppressed the expression of miR-630 and enhanced the expression of TLR4.</p><p><strong>Conclusion: </strong>This study implied that the dysregulation of circRNA-0076906 and circRNA-0134944 modulated their specific signaling and thus contributed to the severity of osteoporosis, increasing the risk of osteoporotic fracture.</p>","PeriodicalId":56015,"journal":{"name":"Pharmacogenomics & Personalized Medicine","volume":"16 ","pages":"183-194"},"PeriodicalIF":1.9,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/df/94/pgpm-16-183.PMC10013579.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9484704","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"<i>PUS1</i> May Be a Potential Prognostic Biomarker and Therapeutic Target for Hepatocellular Carcinoma.","authors":"Chenlu Lan,&nbsp;Xinlei Huang,&nbsp;Xiwen Liao,&nbsp;Xin Zhou,&nbsp;Kai Peng,&nbsp;Yongguang Wei,&nbsp;Chuangye Han,&nbsp;Tao Peng,&nbsp;Jianyao Wang,&nbsp;Guangzhi Zhu","doi":"10.2147/PGPM.S405621","DOIUrl":"https://doi.org/10.2147/PGPM.S405621","url":null,"abstract":"<p><strong>Objective: </strong>The mechanisms of pseudouridine synthase (PUS) are not definite in hepatocellular carcinoma (HCC), the objective of this study is to investigate the effect of PUS genes in HCC.</p><p><strong>Materials and methods: </strong>Differentially expressed and prognostic gene of PUS enzymes was identified based on The Cancer Genome Atlas (TCGA), International Cancer Genome Consortium (ICGC) and Gene Expression Profiling Interactive Analysis (GEPIA) databases. For the identified gene, pseudouridine synthase 1 (<i>PUS1</i>), was used for further research. The clinicopathological feature of <i>PUS1</i> was analyzed by Student's <i>t</i>-test. Prognostic significance was explored by Kaplan-Meier (KM) analysis and Cox proportional hazards regression model. Receiver operating characteristic (ROC) curve was applied to appraise diagnostic and prognostic value. The Database for Annotation, Visualization, and Integrated Discovery (DAVID) and Gene Set Enrichment Analysis (GSEA) were implemented to explore mechanism of <i>PUS1</i>. A Guangxi cohort was applied to verify differential expression. In vitro cell experiments were implemented to investigate the influence for proliferation, reactive oxygen species (ROS) level, migration, and invasion of HCC cells after a knockdown of <i>PUS1</i>.</p><p><strong>Results: </strong><i>PUS1</i> was significantly overexpressed in HCC tissues, and patients with high <i>PUS1</i> were related to unpromising clinicopathological features. Survival analysis revealed high <i>PUS1</i> expression was associated with a poor overall survival (OS) and 1 year-recurrence free survival (RFS), was an independent risk factor. Meanwhile, ROC curve showed that <i>PUS1</i> had a diagnostic and prognostic significance to HCC. Functional enrichment analysis implied that <i>PUS1</i> may be involved in metabolic pathways, mitochondrial function, non-alcoholic fatty liver disease (NAFLD), and some important carcinogenic pathways. Cell assays revealed that knockdown of <i>PUS1</i> significantly constrained the migration, proliferation, invasion and improved the ROS level of HCC cells.</p><p><strong>Conclusion: </strong><i>PUS1</i> may be a prognostic biomarker and a underlying treatment target for HCC.</p>","PeriodicalId":56015,"journal":{"name":"Pharmacogenomics & Personalized Medicine","volume":"16 ","pages":"337-355"},"PeriodicalIF":1.9,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/3d/65/pgpm-16-337.PMC10115212.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9758052","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}