Noor Ghaffar Said Al Habooby, N. Yousif, N. Hadi, J. J. Al-Baghdadi
{"title":"Vitamin D Attenuates Myocardial Injury by Reduces ERK Phosphorylation Induced by I/R in Mice Model","authors":"Noor Ghaffar Said Al Habooby, N. Yousif, N. Hadi, J. J. Al-Baghdadi","doi":"10.2174/2213988501812010027","DOIUrl":"https://doi.org/10.2174/2213988501812010027","url":null,"abstract":"Received: August 24, 2018 Revised: October 4, 2018 Accepted: October 10, 2018 Abstract: Objectives: Myocardial injury caused by ischemia followed by reperfusion mediates a complex series of inflammatory response that reduces the benefit of medical interventions, such as percutaneous coronary intervention, thrombolytic therapy, and coronary bypass surgery. Therefore, suppression of Ischemia/Reperfusion (I/R) -mediated myocardial injury is important in clinical practice. The objective of this study was to investigate whether vitamin has some protective effect on heart after myocardial I/R, and the mechanistic pathway of this effect.","PeriodicalId":10755,"journal":{"name":"Current Chemical Genomics and Translational Medicine","volume":"36 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2018-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"74925329","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}
Azam Roohi, Mina Tabrizi, Mehdi Yaseri, Fereshteh Mir Mohammadrezaei, Behrouz Nikbin
{"title":"Healthy Adult LDL-C Bears Reverse Association with Serum IL-17A Levels.","authors":"Azam Roohi, Mina Tabrizi, Mehdi Yaseri, Fereshteh Mir Mohammadrezaei, Behrouz Nikbin","doi":"10.2174/2213988501812010001","DOIUrl":"https://doi.org/10.2174/2213988501812010001","url":null,"abstract":"<p><strong>Background: </strong>Hypercholesterolemia is a modifiable risk factor in atherosclerosis with a complex association with inflammation.</p><p><strong>Objective: </strong>In the present study, the association between low-density lipoprotein cholesterol (LDL-C) and interleukin 17A (IL-17A), as an inflammatory cytokine, was investigated. In addition to IL-17A, serum levels of interleukin 23 (IL-23) and transforming growth factor β (TGF-β), as effective cytokines in T helper 17 cell (Th17) development, were also determined.</p><p><strong>Method: </strong>Cytokine levels were measured using enzyme-linked immunosorbent assay (ELISA) in healthy subjects with LDL-C<130 versus LDL-C=>130 mg/dL.</p><p><strong>Results: </strong>Although IL-17A is an inflammatory cytokine and a positive association between its levels and LDL-C is expected, the data obtained in this study provide support for a reverse association (<i>p</i><0.05).</p><p><strong>Conclusion: </strong>Inflammation plays a major role in atherosclerosis development; however, various inflammatory components involved in atherosclerosis assert their own unique association with hypercholesterolemia.</p>","PeriodicalId":10755,"journal":{"name":"Current Chemical Genomics and Translational Medicine","volume":"12 ","pages":"1-8"},"PeriodicalIF":0.0,"publicationDate":"2018-06-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6047196/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"36362948","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Hepatocellular Carcinoma: Causes, Mechanism of Progression and Biomarkers.","authors":"Amit Kumar Singh, Ramesh Kumar, Abhay K Pandey","doi":"10.2174/2213988501812010009","DOIUrl":"10.2174/2213988501812010009","url":null,"abstract":"<p><p>Hepatocellular Carcinoma (HCC) is one of the most common malignant tumours in the world. It is a heterogeneous group of a tumour that vary in risk factor and genetic and epigenetic alteration event. Mortality due to HCC in last fifteen years has increased. Multiple factors including viruses, chemicals, and inborn and acquired metabolic diseases are responsible for its development. HCC is closely associated with hepatitis B virus, and at least in some regions of the world with hepatitis C virus. Liver injury caused by viral factor affects many cellular processes such as cell signalling, apoptosis, transcription, DNA repair which in turn induce important effects on cell survival, growth, transformation and maintenance. Molecular mechanisms of hepatocellular carcinogenesis may vary depending on different factors and this is probably why a large set of mechanisms have been associated with these tumours. Various biomarkers including α-fetoprotein, des-γ-carboxyprothrombin, glypican-3, golgi protein-73, squamous cell carcinoma antigen, circulating miRNAs and altered DNA methylation pattern have shown diagnostic significance. This review article covers up key molecular pathway alterations, biomarkers for diagnosis of HCC, anti-HCC drugs and relevance of key molecule/pathway/receptor as a drug target.</p>","PeriodicalId":10755,"journal":{"name":"Current Chemical Genomics and Translational Medicine","volume":"12 ","pages":"9-26"},"PeriodicalIF":0.0,"publicationDate":"2018-06-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2174/2213988501812010009","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"36362951","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Duodenal-Jejunal Bypass Surgery Reverses Diabetic Phenotype and Reduces Obesity in <i>db/db</i> Mice.","authors":"Yongjun Liang, Yueqian Wang, Zhengdong Qiao, Ting Cao, Ying Feng, Lin Zhang, Peng Zhang","doi":"10.2174/2213988501711010041","DOIUrl":"https://doi.org/10.2174/2213988501711010041","url":null,"abstract":"<p><p>Type 2 diabetes mellitus (T2DM), a complex metabolic disorder typically accompanying weight gain, is associated with progressive β-cell failure and insulin resistance. Bariatric surgery ameliorates glucose tolerance and provides a near-perfect treatment. Duodenal-jejunal bypass (DJB) is an experimental procedure and has been studied in several rat models, but its influence in <i>db/db</i> mice, a transgenic model of T2DM, remains unclear. To investigate the effectiveness of DJB in <i>db/db</i> mice, we performed the surgery and evaluated metabolism improvement. Results showed that mice in DJB group weighed remarkably less than sham group two weeks after surgery. Compared to the preoperative level, postoperative fasting blood glucose (FBG) was dramatically reduced. Statistical analysis revealed that changes in body weight and FBG were significantly correlated. Besides, DJB surgery altered plasma insulin level with approximate 40% reduction. Thus, for the first time we proved that DJB can achieve rapid therapeutic effect in transgenic <i>db/db</i> mice with severe T2DM as well as obesity. In addition, decreased insulin level reflected better insulin sensitivity induced by DJB. In conclusion, our study demonstrates that DJB surgery may be a potentially effective way to treat obesity-associated T2DM.</p>","PeriodicalId":10755,"journal":{"name":"Current Chemical Genomics and Translational Medicine","volume":"11 ","pages":"41-49"},"PeriodicalIF":0.0,"publicationDate":"2017-10-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2174/2213988501711010041","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"35654498","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"MiR-9 Promotes Apoptosis <i>Via</i> Suppressing SMC1A Expression in GBM Cell Lines.","authors":"Yong Zu, Zhichuan Zhu, Min Lin, Dafeng Xu, Yongjun Liang, Yueqian Wang, Zhengdong Qiao, Ting Cao, Dan Yang, Lili Gao, Pengpeng Jin, Peng Zhang, Jianjun Fu, Jing Zheng","doi":"10.2174/2213988501711010031","DOIUrl":"https://doi.org/10.2174/2213988501711010031","url":null,"abstract":"<p><strong>Objective: </strong>Glioblastomas multiforme (GBM) is the most malignant brain cancer, which presented vast genomic variation with complicated pathologic mechanism.</p><p><strong>Method: </strong>MicroRNA is a delicate post-transcriptional tuner of gene expression in the organisms by targeting and regulating protein coding genes. MiR-9 was reported as a significant biomarker for GBM patient prognosis and a key factor in regulation of GBM cancer stem cells. To explore the effect of miR-9 on GBM cell growth, we over expressed miR-9 in U87 and U251 cells. The cell viability decreased and apoptosis increased after miR-9 overexpression in these cells. To identify the target of miR-9, we scanned miR-9 binding site in the 3'UTRs region of expression SMC1A (structural maintenance of chromosomes 1A) genes and designed a fluorescent reporter assay to measure miR-9 binding to this region. Our results revealed that miR-9 binds to the 3'sUTR region of SMC1A and down-regulated SMC1A expression.</p><p><strong>Result: </strong>Our results indicated that miR-9 was a potential therapeutic target for GBM through triggering apoptosis of cancer cells.</p>","PeriodicalId":10755,"journal":{"name":"Current Chemical Genomics and Translational Medicine","volume":"11 ","pages":"31-40"},"PeriodicalIF":0.0,"publicationDate":"2017-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5564015/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"35373539","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Shuaizhang Li, Jinghua Zhao, Ruili Huang, Toni Steiner, Maureen Bourner, Michael Mitchell, David C Thompson, Bin Zhao, Menghang Xia
{"title":"Development and Application of Human Renal Proximal Tubule Epithelial Cells for Assessment of Compound Toxicity.","authors":"Shuaizhang Li, Jinghua Zhao, Ruili Huang, Toni Steiner, Maureen Bourner, Michael Mitchell, David C Thompson, Bin Zhao, Menghang Xia","doi":"10.2174/2213988501711010019","DOIUrl":"10.2174/2213988501711010019","url":null,"abstract":"<p><p>Kidney toxicity is a major problem both in drug development and clinical settings. It is difficult to predict nephrotoxicity in part because of the lack of appropriate <i>in vitro</i> cell models, limited endpoints, and the observation that the activity of membrane transporters which plays important roles in nephrotoxicity by affecting the pharmacokinetic profile of drugs is often not taken into account. We developed a new cell model using pseudo-immortalized human primary renal proximal tubule epithelial cells. This cell line (SA7K) was characterized by the presence of proximal tubule cell markers as well as several functional properties, including transporter activity and response to a few well-characterized nephrotoxicants. We subsequently evaluated a group of potential nephrotoxic compounds in SA7K cells and compared them to a commonly used human immortalized kidney cell line (HK-2). Cells were treated with test compounds and three endpoints were analyzed, including cell viability, apoptosis and mitochondrial membrane potential. The results showed that most of the known nephrotoxic compounds could be detected in one or more of these endpoints. There were sensitivity differences in response to several of the chemicals between HK-2 and SA7K cells, which may relate to differences in expressions of key transporters or other components of nephrotoxicity pathways. Our data suggest that SA7K cells appear as promising for the early detection of renal toxicants.</p>","PeriodicalId":10755,"journal":{"name":"Current Chemical Genomics and Translational Medicine","volume":"11 ","pages":"19-30"},"PeriodicalIF":0.0,"publicationDate":"2017-02-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5362976/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"34906540","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Targeting Wolman Disease and Cholesteryl Ester Storage Disease: Disease Pathogenesis and Therapeutic Development.","authors":"Francis Aguisanda, Natasha Thorne, Wei Zheng","doi":"10.2174/2213988501711010001","DOIUrl":"https://doi.org/10.2174/2213988501711010001","url":null,"abstract":"<p><p>Wolman disease (WD) and cholesteryl ester storage disease (CESD) are lysosomal storage diseases (LSDs) caused by a deficiency in lysosomal acid lipase (LAL) due to mutations in the <i>LIPA</i> gene. This enzyme is critical to the proper degradation of cholesterol in the lysosome. LAL function is completely lost in WD while some residual activity remains in CESD. Both are rare diseases with an incidence rate of less than 1/100,000 births for WD and approximate 2.5/100,000 births for CESD. Clinical manifestation of WD includes hepatosplenomegaly, calcified adrenal glands, severe malabsorption and a failure to thrive. As in CESD, histological analysis of WD tissues reveals the accumulation of triglycerides (TGs) and esterified cholesterol (EC) in cellular lysosomes. However, the clinical presentation of CESD is less severe and more variable than WD. This review is to provide an overview of the disease pathophysiology and the current state of therapeutic development for both of WD and CESD. The review will also discuss the application of patient derived iPSCs for further drug discovery.</p>","PeriodicalId":10755,"journal":{"name":"Current Chemical Genomics and Translational Medicine","volume":"11 ","pages":"1-18"},"PeriodicalIF":0.0,"publicationDate":"2017-01-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2174/2213988501711010001","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"34906541","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Michael K Hancock, Leisha Kopp, Navjot Kaur, Bonnie J Hanson
{"title":"A facile method for simultaneously measuring neuronal cell viability and neurite outgrowth.","authors":"Michael K Hancock, Leisha Kopp, Navjot Kaur, Bonnie J Hanson","doi":"10.2174/2213988501509010006","DOIUrl":"https://doi.org/10.2174/2213988501509010006","url":null,"abstract":"<p><p>Neurite outgrowth is an important morphological phenotype of neuronal cells that correlates with their function and cell health, yet there are limited methods available for measuring this phenomenon. Current approaches to measuring neurite outgrowth are laborious and time-consuming, relying largely upon immunocytochemical staining of neuronal markers (e.g., beta-III tubulin or MAP2) followed by manual or automated microscopy for image acquisition and analysis. Here we report the development of a quick and simple dual-color fluorescent dye-based staining method that allows for the simultaneous measurement of neuronal cell health and relative neurite outgrowth from the same sample. An orangered fluorescent dye that stains cell membrane surfaces is used as an indirect reporter of changes in relative neurite outgrowth due to alterations in the number or length of membrane projections emanating from neuronal cell bodies. Cell viability is assessed simultaneously via the use of a cell-permeant dye that is converted by intracellular esterase activity from a non-fluorescent substrate to a green-fluorescent product. Using Neuroscreen-1 cells (a PC-12 subclone), primary rat cortex neurons, and human induced pluripotent stem cell (iPSC)-derived neurons, we demonstrate that this multiplex assay allows for rapid visualization and unbiased, quantitative plate reader analysis of neuronal cell health and neurite outgrowth. </p>","PeriodicalId":10755,"journal":{"name":"Current Chemical Genomics and Translational Medicine","volume":"9 ","pages":"6-16"},"PeriodicalIF":0.0,"publicationDate":"2015-02-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/50/71/CCGTM-9-6.PMC4382562.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"33198947","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Evidence for Natural Selection in Nucleotide Content Relationships Based on Complete Mitochondrial Genomes: Strong Effect of Guanine Content on Separation between Terrestrial and Aquatic Vertebrates.","authors":"Kenji Sorimachi, Teiji Okayasu","doi":"10.2174/2213988501509010001","DOIUrl":"10.2174/2213988501509010001","url":null,"abstract":"<p><p>The complete vertebrate mitochondrial genome consists of 13 coding genes. We used this genome to investigate the existence of natural selection in vertebrate evolution. From the complete mitochondrial genomes, we predicted nucleotide contents and then separated these values into coding and non-coding regions. When nucleotide contents of a coding or non-coding region were plotted against the nucleotide content of the complete mitochondrial genomes, we obtained linear regression lines only between homonucleotides and their analogs. On every plot using G or A content purine, G content in aquatic vertebrates was higher than that in terrestrial vertebrates, while A content in aquatic vertebrates was lower than that in terrestrial vertebrates. Based on these relationships, vertebrates were separated into two groups, terrestrial and aquatic. However, using C or T content pyrimidine, clear separation between these two groups was not obtained. The hagfish (Eptatretus burgeri) was further separated from both terrestrial and aquatic vertebrates. Based on these results, nucleotide content relationships predicted from the complete vertebrate mitochondrial genomes reveal the existence of natural selection based on evolutionary separation between terrestrial and aquatic vertebrate groups. In addition, we propose that separation of the two groups might be linked to ammonia detoxification based on high G and low A contents, which encode Glu rich and Lys poor proteins. </p>","PeriodicalId":10755,"journal":{"name":"Current Chemical Genomics and Translational Medicine","volume":"9 ","pages":"1-5"},"PeriodicalIF":0.0,"publicationDate":"2015-02-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/ec/9c/CCGTM-9-1.PMC4382559.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"33198946","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Jaime Freitas, Nicole Miller, Brenda J Mengeling, Menghang Xia, Ruili Huang, Keith Houck, Ivonne M C M Rietjens, J David Furlow, Albertinka J Murk
{"title":"Identification of thyroid hormone receptor active compounds using a quantitative high-throughput screening platform.","authors":"Jaime Freitas, Nicole Miller, Brenda J Mengeling, Menghang Xia, Ruili Huang, Keith Houck, Ivonne M C M Rietjens, J David Furlow, Albertinka J Murk","doi":"10.2174/2213988501408010036","DOIUrl":"https://doi.org/10.2174/2213988501408010036","url":null,"abstract":"<p><p>To adapt the use of GH3.TRE-Luc reporter gene cell line for a quantitative high-throughput screening (qHTS) platform, we miniaturized the reporter gene assay to a 1536-well plate format. 1280 chemicals from the Library of Pharmacologically Active Compounds (LOPAC) and the National Toxicology Program (NTP) 1408 compound collection were analyzed to identify potential thyroid hormone receptor (TR) agonists and antagonists. Of the 2688 compounds tested, eight scored as potential TR agonists when the positive hit cut-off was defined at ≥10% efficacy, relative to maximal triiodothyronine (T3) induction, and with only one of those compounds reaching ≥20% efficacy. One common class of compounds positive in the agonist assays were retinoids such as all-trans retinoic acid, which are likely acting via the retinoid-X receptor, the heterodimer partner with the TR. Five potential TR antagonists were identified, including the antiallergy drug tranilast and the anxiolytic drug SB 205384 but also some cytotoxic compounds like 5-fluorouracil. None of the inactive compounds were structurally related to T3, nor had been reported elsewhere to be thyroid hormone disruptors, so false negatives were not detected. None of the low potency (>100µM) TR agonists resembled T3 or T4, thus these may not bind directly in the ligand-binding pocket of the receptor. For TR agonists, in the qHTS, a hit cut-off of ≥20% efficacy at 100 µM may avoid identification of positives with low or no physiological relevance. The miniaturized GH3.TRE-Luc assay offers a promising addition to the in vitro test battery for endocrine disruption, and given the low percentage of compounds testing positive, its high-throughput nature is an important advantage for future toxicological screening. </p>","PeriodicalId":10755,"journal":{"name":"Current Chemical Genomics and Translational Medicine","volume":"8 ","pages":"36-46"},"PeriodicalIF":0.0,"publicationDate":"2014-03-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/9f/9f/CCGTM-8-36.PMC3999704.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"32296623","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}