Yan Dou, Martin Darvas, Kavita Sharma, Julie Mathieu, John Morton, Heidi Tan, Carolina Soto-Palma, Luise A Angelini, Sara J McGowan, Laura J Niedernhofer, Yousin Suh, Paul D Robbins, Nir Barzilai, Warren C Ladiges
{"title":"Development of an IGF1R longevity variant mouse line using CRISPR/Cas9 genome editing.","authors":"Yan Dou, Martin Darvas, Kavita Sharma, Julie Mathieu, John Morton, Heidi Tan, Carolina Soto-Palma, Luise A Angelini, Sara J McGowan, Laura J Niedernhofer, Yousin Suh, Paul D Robbins, Nir Barzilai, Warren C Ladiges","doi":"10.15761/jtbr.1000121","DOIUrl":"10.15761/jtbr.1000121","url":null,"abstract":"<p><p>An insulin-like growth factor-1 receptor (IGF1R) variant in exon 6 (Arg-407-His) in Ashkenazi Jewish centenarians was previously found to be associated with reduced IGF1R activity. To further study this longevity associated IGF1R variant, we generated a novel mouse line carrying the R407H variant in exon 6 of the <i>Igf1r</i> gene by employing CRISPR/Cas9 genome editing technology. Here, we show that the <i>Igf1r</i> gene can be edited in mouse embryos by zygotic electroporation of Cas9 protein and a single-guide RNAs together with a single stranded oligonucleotide donor containing the desired key nucleotide changes at the <i>Igf1r</i> locus. Sequence analysis of F0 and F1 mice following targeted editing demonstrated the robustness of this approach in mice using CRISPR/Cas9 directed homologous recombination (HDR). Western blot analysis indicates that mice heterozygous for the variant have a significant decrease in IGF1R phosphorylation in various tissues, including skeletal muscle, compared to wildtype. In addition, depletion of IGF1R signaling specifically in skeletal muscle of progeroid <i>Ercc1</i> <sup>-/Δ</sup> mice resulted in extended health span and median lifespan providing the rationale for long term lifespan studies in <i>Igf1r</i> hR407H variant mice. This mouse line will be a valuable genetic tool to help determine the impact of IGF1R signaling on aging and longevity. The CRISPR editing approach represents a prototype for generating additional longevity associated gene variant mouse lines to study relevance to human exceptional longevity.</p>","PeriodicalId":75256,"journal":{"name":"Trends in biomedical research","volume":"3 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2020-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10131096/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9744675","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}
K. Marek-Bukowiec, A. Konieczny, K. Ratajczyk, K. Macur, P. Czaplewska, A. Czyżewska-Buczyńska, P. Kowal, W. Witkiewicz
{"title":"The Value of Urinary RBP4 in The Diagnosis of FSGS and other Renal Diseases.","authors":"K. Marek-Bukowiec, A. Konieczny, K. Ratajczyk, K. Macur, P. Czaplewska, A. Czyżewska-Buczyńska, P. Kowal, W. Witkiewicz","doi":"10.21203/rs.3.rs-35997/v1","DOIUrl":"https://doi.org/10.21203/rs.3.rs-35997/v1","url":null,"abstract":"\u0000 BackgroundUnequivocal diagnosis of FSGS can only be made with a renal biopsy, which is an invasive, risk-associated medical procedure. The discovery of non-invasive molecular biomarkers for the diagnosis of FSGS remains an important scientific goal. This study examines the urinary proteome of FSGS patients and reference groups, in order to identify urinary protein expression alterations indicative of FSGS. Methods Urine samples were collected from subjects representing FSGS, IgA nephropathy (IgAN), clear cell renal cell carcinoma (ccRCC), chromophobe renal cell carcinoma (chRCC), and healthy control group, respectively. The samples were subjected to SWATH-MS proteomics analysis. ELISA was utilized to validate the expression level of Retinol-binding protein 4 (uRBP4) in FSGS and reference samples (IgAN, ccRCC, chRCC, prostate cancer and healthy subjects).ResultsThe MS study identified 194 (FSGS), 179 (IgAN), 271 (ccRCC), 255 (chRCC), and 275 (healthy controls) urinary proteins. The comparative proteomic analysis revealed that urinary Retinol-binding protein 4 (uRBP4) clearly discriminates FSGS from the rest of the groups. Increased levels of uRBP4 in FSGS urine specimens were also evidenced by ELISA. Significantly elevated levels of uRBP4 were also observed for IgAN, ccRCC and chRCC versus healthy individuals. ConclusionsDetermining FSGS diagnosis based on uRBP4 expression alone is not possible. Specific uRBP4 concentration cut-off can be applied to accurately distinguish individuals with renal disorder (in general) from healthy subjects. Possibly, urinary RBP4 could serve as a screening biomarker identifying people at risk of renal disorders, who should undergo more detailed diagnostics.","PeriodicalId":75256,"journal":{"name":"Trends in biomedical research","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2020-06-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"42718267","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}
Bouchoucha Mongia, Bouchoucha Rim, Bellali Hédia, Akrout Mouna, K. Amani, J. Riadh, F. Moncef, S. Hédia, B. Abderraouf
{"title":"Therapeutic effectiveness of moderate energy restriction in obese Tunisian women","authors":"Bouchoucha Mongia, Bouchoucha Rim, Bellali Hédia, Akrout Mouna, K. Amani, J. Riadh, F. Moncef, S. Hédia, B. Abderraouf","doi":"10.15761/JTBR.1000115","DOIUrl":"https://doi.org/10.15761/JTBR.1000115","url":null,"abstract":"Objective: To assess the effectiveness of moderate energy restriction for 6 months with reinforcement of household activities, in Tunisian obese women. Design: We conducted a nutritional intervention for 6 months. Participants: We included consecutively 75 volunteer obese women in the “Obesity Unit”, Endocrinology Service, La Rabta Hospital, Tunisia; in January 2013. Intervention(s): We prescribed a diet of 1600 Kcal/day; providing 57% of energy as carbohydrate, 30% as fat, and 13% as protein. We advised the reinforcement of the domestic housework activities. Main outcome measure(s): Demographics, lifestyle behaviors, anthropometrics, biologic parameters and dietary intake were assessed at baseline and at 6 months. Analysis: All quantitative variables were reported as the mean ± standard deviation. We used paired-samples t test for comparison of two means and Pearson correlation coefficient (n > 30) to check for correlations. Significance level was set at 0.05. Results: Sixty (80%) women were reviewed at 6 months. There was a significant decrease in body mass index and fat mass and a significant increase of the percentage of lean mass. The total cholesterol, low-density lipoprotein cholesterol, C-reactive protein and leptin levels were reduced at 6 months. Conclusion and implication: The prevention of the cardiovascular complications of the obesity for women of a modest socioeconomic level is achievable through readily accessible means.","PeriodicalId":75256,"journal":{"name":"Trends in biomedical research","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2020-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"67486743","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":"Estimating human glioblastoma xenograft DCE-MRI response to Bevacizumab treatment","authors":"J. Carl, K. Nielsen, Soeren Ravn","doi":"10.15761/JTBR.1000117","DOIUrl":"https://doi.org/10.15761/JTBR.1000117","url":null,"abstract":"Background and purpose: It has been suggested that consecutive DCE-MRI in the early phase of treatment with bevacizumab could provide a better estimate of treatment response. Materials and methods: The xenograft study was performed using adult (8-12 weeks of age) male type NMRINUM Mice (Taconic, Denmark). A human glioblastoma xenograft was inoculated subcutaneously in the posterior flank of the mouse. DCE MRI and compartment analysis was performed extended Toft´s model. Pathology immunohistochemistry of Glial fibrillary acidic protein (GFAP) of excised tumors slides were analyzed using an ImageJ threshold watershed technique to determine tissue fraction of glial tumor cells. Results: A total of 15 intervention tumors and two C16MG control tumors were subjected to DCE MRI. A significant correlation between Ktrans and GFAP was observed. Furthermore a significant reduction in Ktrans following Bevacizumab was observed. Conclusion: To conclude this study successfully established a technique, which allowed small animals with Xenograft heterotopic implanted GBM tumors to be scanned with a DCE-MRI technique using a clinical 3T MR scanner setting. Furthermore the Ktrans parameters derived was demonstrated to be a potential imaging biomarker of GBM GFAP activity and treatment response to Bevacizumab.","PeriodicalId":75256,"journal":{"name":"Trends in biomedical research","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2020-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"67486856","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":"The role of wild dreams in living objects","authors":"M. Vlček","doi":"10.15761/JTBR.1000113","DOIUrl":"https://doi.org/10.15761/JTBR.1000113","url":null,"abstract":"Based on economic modeling in living systems, described e.g. in 3) till 5), the potential role of dreams in living objects is examined. It appears that their role is irreplaceable and serves as a screening mechanism. Everything takes place in the context of increasing the object’s existence – see also 1) and 2). In light of the findings, the question is whether dreams can be used for objective diagnosis. The article concludes that this is possible, but after further studies.","PeriodicalId":75256,"journal":{"name":"Trends in biomedical research","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2020-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"67486238","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":"Understanding of “-omics” of Parkinson’s disease","authors":"Shan Zheng, Xue Wen, Jian Feng, Fangfang Liu, Greg Mirt, Fan Xu","doi":"10.15761/JTBR.1000114","DOIUrl":"https://doi.org/10.15761/JTBR.1000114","url":null,"abstract":"Parkinson’s Disease (PD), as one neurodegenerative disease, reduce the life quality of our patients extensively. Since the identification and validation of role of alpha-synuclein in PD, several impactful hypotheses pointed out the direction of our research, while the bioinformatic studies initialized to focus on the generation, formation, transportation and aberrant clearance of alpha-synuclein. The pioneer studies of Braak provided a comprehensive classification between alpha-synuclein and the severity of PD. Currently our understanding of bioinformatic on PD are increasing sharply as well from genomic, proteomic and metabolomic. To our best knowledge, here we provide a comprehensive picture of this disease from genomic to metabolomic.","PeriodicalId":75256,"journal":{"name":"Trends in biomedical research","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2020-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"67486384","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}
M. Pokorski, A. Barik, N. Chakravorty, Sunil Munakomi, D. Poudel
{"title":"Trends in Biomedical Research","authors":"M. Pokorski, A. Barik, N. Chakravorty, Sunil Munakomi, D. Poudel","doi":"10.1007/978-3-030-41219-7","DOIUrl":"https://doi.org/10.1007/978-3-030-41219-7","url":null,"abstract":"","PeriodicalId":75256,"journal":{"name":"Trends in biomedical research","volume":"41 2","pages":""},"PeriodicalIF":0.0,"publicationDate":"2020-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1007/978-3-030-41219-7","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"50964257","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":"Investigation of susceptible gas station workers to neurological disorders based on evidence of catechol -O- methyltransferase (COMT) gene expression alters","authors":"Rezaei Tpm, Mohamadi F, R. Y., A. G","doi":"10.15761/jtbr.1000108","DOIUrl":"https://doi.org/10.15761/jtbr.1000108","url":null,"abstract":"","PeriodicalId":75256,"journal":{"name":"Trends in biomedical research","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"67486343","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":"Identification of ANXA1 as a diagnostic and lymphatic metastasis factor in colorectal cancer","authors":"Qing-hua Liu, M. Ding, Jinmin Sun, Zu’an Zhu","doi":"10.15761/jtbr.1000107","DOIUrl":"https://doi.org/10.15761/jtbr.1000107","url":null,"abstract":"Objective: To determine whether ANXA1 can be served as biomarker for diagnosis in colorectal cancer (CRC) and analyse the correlation of ANXA1 and clinicopathological parameters of CRC patients. Methods: Tissue array (n=95) CRC specimens were utilised in this study. ANXA1 in cancer and non-cancerous tissues were detected immunohistochemically. The correlations between ANXA1 and clinicopathological parameters of CRC were evaluated. Concentrations of ANXA1 in peripheral blood were detected by enzymelinked immunosorbent assay (ELISA). Results: ANXA1 was upregulated in CRC tissues than that in non-cancerous tissues (P <0.05). The mean value for ANXA1 level in peripheral blood of CRC patients was significantly higher than that of healthy individuals (P <0.05). Increased ANXA1 was observed in deeper tumor invasion, lymphatic metastasis and late TNM stage of CRC patients. Conclusions: ANXA1 increased in CRC tissues and in peripheral blood of CRC patients. In addition, increased ANXA1 was correlated with deeper tumor invasion, lymph node metastasis and late TNM stage of CRC patients. Our findings would provide new insights into significant of ANXA1 in diagnosis and lymphatic metastasis of CRC. The underlying mechanism of ANXA1 in CRC progress will be further explored. *Correspondence to: Zu-An Zhu, Department of Gastroenterology, Affiliated Hospital of Xuzhou Medical University, 84 Huai-Hai Western Road, Xuzhou, 221000, Jiangsu Province, China, Tel: +86 15852162813; E-mail: zhuzuanliu@126.com","PeriodicalId":75256,"journal":{"name":"Trends in biomedical research","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"67486177","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}