{"title":"Oral feeding with Arachidonic Acid (AA) and Docosahexanoic Acid (DHA) help in better recovery of haematopoiesis in sub-lethally irradiated mice","authors":"Kedar Limbkar, V. Kale, L. Limaye","doi":"10.4103/2349-3666.240611","DOIUrl":"https://doi.org/10.4103/2349-3666.240611","url":null,"abstract":"Haematopoiesis is severely hampered after exposure to ionizing radiations. Role of polyunsaturated fatty acids (PUFAs) during embryonic development as well as during various physiological processes is well established. However, few studies on their effect on haematopoiesis are reported. Hence, we studied the effect of oral administration of PUFAs-AA/DHA on haematopoiesis of sub-lethally irradiated mice. To determine the optimal dose for haematopoiesis, non-irradiated healthy mice were orally fed with different doses of AA/DHA daily for ten days. Additionally, mice were sub lethally irradiated and kept for ten days on normal diet. Further, sub-lethally irradiated mice were orally fed with optimal dose of AA/DHA for ten days. Mice from the experiments were sacrificed after ten days and their bone marrow cells were harvested and analyzed for their total nucleated cell (TNC) count, side population (SP) and lin-Sca-1+c-kit+(LSK) phenotype. Peripheral blood collected from this set of mice was subjected to hemogram analysis. Daily dose of 8 mg AA/DHA for ten days was assessed as optimal for enhancing BM-MNCs and primitive HSCs in non-irradiated mice. Significant depletion in BM-MNCs, SP and LSK cells was observed in sub lethally irradiated mice compared to un-irradiated control mice. Feeding with DHA or AA in sub lethally irradiated mice showed significantly higher number of BM-MNCs and increased percentage of SP and LSK cells, suggesting that DHA and AA resulted in better recovery of hematopoietically compromised mice. The data indicated that DHA or AA may serve as useful dietary supplements in patients exposed to irradiation.","PeriodicalId":34293,"journal":{"name":"Biomedical Research Journal","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2016-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"73302729","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":"Physiology of embryo-endometrial cross talk","authors":"Deepak Modi, Pradeep Bhartiya","doi":"10.4103/2349-3666.240622","DOIUrl":"https://doi.org/10.4103/2349-3666.240622","url":null,"abstract":"Implantation of the blastocyst stage embryo into the maternal endometrium is a critical determinant and a rate-limiting process for successful pregnancy. Embryo implantation requires synchronized changes in the endometrium before and after arrival of blastocyst into the uterine cavity. Extensive cross talks occur between the fetal and maternal compartments around the time of implantation which are reflected by morphologic, biochemical and molecular changes in the endometrial cells and the differentiating trophoblast cells. The embryo induced morphologic changes include occurrence of epithelial plaque reaction, stromal compaction and decidualization. Embryonic signals also alter the expression of a large number of transcription factors, growth factors and their receptors and integrins. Thus the embryo superimposes a unique signature on the receptive endometrium for successful implantation. Functionally, the embryo-endometrial cross talk is essential for endowing a “selector activity” to the receptive endometrium to ensure implantation of only a developmentally competent embryo. On selection, the decidua creates a conducive microenvironment for trophoblast invasion leading to placentation. Clinical evidences suggest that along with receptivity, a defective “selector” activity of the receptive uterus may be a cause of infertility and recurrent miscarriages. Defects in trophoblast invasion are associated with pregnancy complications like preeclampsia and intra-uterine growth retardation. It is envisaged that understanding of the embryo-endometrial dialogue leading to the “selector” activity, aids in development of appropriate therapeutic modalities for infertility related disorders and miscarriages. Conversely, it might also benefit the development of anti-implantation drugs for contraception.","PeriodicalId":34293,"journal":{"name":"Biomedical Research Journal","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2015-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"82164615","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}
C. Schlaff, W. Arscott, I. Gordon, K. Camphausen, A. Tandle
{"title":"Human EGFR-2, EGFR and HDAC triple-inhibitor CUDC-101 enhances radiosensitivity of GBM cells","authors":"C. Schlaff, W. Arscott, I. Gordon, K. Camphausen, A. Tandle","doi":"10.4103/2349-3666.240616","DOIUrl":"https://doi.org/10.4103/2349-3666.240616","url":null,"abstract":"Radiotherapy remains the standard treatment for glioblastoma multiforme (GBM) following surgical resection. Given the aberrant expression of human epidermal growth factor receptor 2 (HER2) and epidermal growth factor receptor (EGFR) which may play a role in therapeutic resistance to receptor tyrosine kinase inhibitors, and the emerging use of histone deacetylase (HDAC) inhibitors as radiosensitizers, we defined the effects of CUDC-101, a triple inhibitor of HER2, EGFR and HDAC on the radiosensitivity of GBM cells. Clonogenic survival was used to determine the in vitro radiosensitizing potential of CUDC-101 on GBM, breast cancer, and normal fibroblast cell lines. Inhibitory activity was defined using immunoblots and DNA double strand breaks were evaluated using yH2AX foci. Effects of CUDC-101 on cell cycle and radiation-induced cell kill were determined using flow cytometry and fluorescent microscopy. CUDC-101 inhibited HER2, EGFR and HDAC and enhanced in vitro radiosensitivity of both GBM and breast cancer cell lines, with no effect on normal fibroblasts. Retention of yH2AX foci was increased by CUDC-101 alone and in combination with irradiation for 24 h. Treatment with CUDC-101 increased the number of cells in G2 and M phase, with only increase in M phase statistically significant. An increase in mitotic catastrophe was seen in a time-dependent fashion with combination treatment. The results indicate the tumor specific CUDC-101 enhanced radiosensitization in GBM, and suggest that the effect involves inhibition of DNA repair.","PeriodicalId":34293,"journal":{"name":"Biomedical Research Journal","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2015-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"81192205","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}
Shweta Singh, Suprita S. Ghode, M. Devi, L. Limaye, V. Kale
{"title":"Phenotypic and functional characterization of a marrow-derived stromal cell line, M210B4 and its comparison with primary marrow stromal cells","authors":"Shweta Singh, Suprita S. Ghode, M. Devi, L. Limaye, V. Kale","doi":"10.4103/2349-3666.240617","DOIUrl":"https://doi.org/10.4103/2349-3666.240617","url":null,"abstract":"In vitro co-culture system consisting of bone marrow stromal cells (BMSCs) or mesenchymal stromal cell lines of marrow origin has provided important clues about the regulation of hematopoietic stem cells (HSCs) by their microenvironment or niche. In the current studies, we have compared phenotypic and functional characters of a marrow-derived mesenchymal stem cell line, M210B4, with BMSCs. We demonstrate that M210B4 resembles BMSCs in terms of phenotypic characters. Unlike the BMSCs, M210B4 differentiated only towards adipogenic lineage, and was refractory towards osteogenic differentiation. However, M210B4 cells exhibited a higher HSC-supportive ability as assessed by flow cytometry analyses of the output cells from co-cultures. We observed that M210B4 cells show a constitutively higher activation of p44/42 and p38 MAPK pathways compared to BMSCs, contributing to their higher HSC-support in vitro. Overall, the results show that M210B4 forms a suitable in vitro system to study HSC regulation in vitro.","PeriodicalId":34293,"journal":{"name":"Biomedical Research Journal","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2015-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"72471077","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":"Genetic markers and evolution of targeted therapy in cancer","authors":"P. Kadam Amare","doi":"10.4103/2349-3666.240654","DOIUrl":"https://doi.org/10.4103/2349-3666.240654","url":null,"abstract":"The advances in biotechnology including high throughput platforms, and bioinformatics has resulted in detailing molecular pathology of various cancers, identifying targets such as fusion genes, chimeric RNA, fusion proteins, amplified gene, genes with point mutation, overexpression or down regulation of RNA, microRNA (miRNA) and aberrant DNA methylation. The genetic markers provide diagnostic, prognostic and therapeutic markers, and may also provide predictive markers. Several targeted molecules have been identified as cell surface antigens and tyrosine kinases e. g. FLT3, NPM1, CEBPA and PRAM1 in acute myeloid leukemia (AML); BCR-ABL1 in chronic myeloid leukemia; JAK2 in chronic myeloproliferative disorders; ALK, EGFR, K-RAS and BRAF in lung cancer; BRAF, KIT in melanoma; HER2 in breast cancer. The driver molecules and their mechanism of actions revealed various oncogenic pathways in the development of effective inhibitor molecules/proteins as targeted therapy, and novel mutations in the genes associated with the inhibitor protein. Targeted cancer therapy aimed to antagonize the deregulated molecule/s, commonly comprises therapeutic monoclonal antibodies and small molecule inhibitors. In vitro studies and clinical trials of the inhibitory molecules showed promising results as single drug therapy or in combination with conventional chemotherapy. Further, multiple mutations associated with resistance to targeted therapy were identified, leading to treatment with second line drugs and consequent better prognosis. Further advancements of biotechnology with identification of genetic variation, multiple resistant mutations which help discovery of a cascade of genetic markers with deeper understanding of biology of disease that offers hopes towards identification of development of more efficient targeted therapy with reduced toxicity and resistance.","PeriodicalId":34293,"journal":{"name":"Biomedical Research Journal","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2015-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"77213922","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":"Right patient, right diagnosis, right treatment!","authors":"D. Saranath, A. Khanna","doi":"10.4103/2349-3666.240651","DOIUrl":"https://doi.org/10.4103/2349-3666.240651","url":null,"abstract":"The 2015 Nobel Prize in Medicine for drugs to fight malaria and other tropical diseases, and in Chemistry for fundamental contributions towards understanding DNA repair and maintaining of genomic integrity in cells, highlights the interdisciplinary approach for maximizing benefits of contemporary science to mankind. The Nobel Prize in Medicine was awarded to William Campbell Ph.D., born in Ireland and migrated to US; Satoshi Omura, Ph.D., from Japan, and Youyou Tu, the first Chinese Nobel laureate. The Nobel laureates – Dr. Campbell and Dr. Omura were cited for their discovery of Avermecitin, derivatives of the drug responsible for decreasing incidence of river blindness and lymphatic filariasis affecting millions in Asia and Africa. Ms. Tu's intensive efforts led to the active compound from the herbal Chinese sweet wormwood plant, giving us the antimalarial drug artemisinin, currently the first line drug for malaria affecting 50% of global population. The Chemistry Nobel acknowledged three scientists for their research in DNA repair, for their intensive work on mapping the process at a molecular level and providing insights into cell functioning and maintenance of genomic stability. The Nobel laureates were Dr. Thomas Lindahl, Ph.D., Francis Crick Institute, London, for his discoveries in base excision repair; Dr. Paul Modrich, Ph.D., Howard Hughes Medical Institute, and Duke University School of Medicine, North Carolina, USA, for the mismatch repair pathway; and Dr. Aziz Sancar, M.D., Ph.D., at the University of North Carolina, USA, for nucleotide excision pathway. The understanding of DNA repair mechanisms in the cells is a breakthrough in understanding how cancer develops and furthers treatment of cancer and also several diseases, much needed for better health management. Despite the tremendous advances in technology, particularly biotechnology, information technology and imaging technology, cancer development, Dhananjaya Saranath and Aparna Khanna","PeriodicalId":34293,"journal":{"name":"Biomedical Research Journal","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2015-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"79457812","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}
U. Maachani, U. Shankavaram, K. Camphausen, A. Tandle
{"title":"Advances in Omics Technologies in GBM","authors":"U. Maachani, U. Shankavaram, K. Camphausen, A. Tandle","doi":"10.4103/2349-3666.240621","DOIUrl":"https://doi.org/10.4103/2349-3666.240621","url":null,"abstract":"Glioblastoma multiforme (GBM) is one of the most lethal human cancers and poses a great challenge in the therapeutic interventions of GBM patients worldwide. Despite prominent recent advances in oncology, on an average GBM patients survive 12–15 months with conventional standard of care treatment. To understand the pathophysiology of this disease, recently the research focus has been on omics-based approaches. Advances in high-throughput assay development and bioinformatic techniques have provided new opportunities in the molecular analysis of cancer omics technologies including genomics, transcriptomics, epigenomics, proteomics, and metabolomics. Further, the enormous addition and accessibility of public databases with associated clinical demographic information including tumor histology, patient response and outcome, have profoundly improved our knowledge of the molecular mechanisms driving cancer. In GBM, omics have significantly aided in defining the molecular architecture of tumorigenesis, uncovering relevant subsets of patients whose disease may require different treatments. In this review, we focus on the unique advantages of multifaceted omics technologies and discuss the implications on translational GBM research.","PeriodicalId":34293,"journal":{"name":"Biomedical Research Journal","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2015-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"77861099","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":"Microbiota in immune pathogenesis and the prospects for pre and probiotic dietetics in psoriasis","authors":"A. Pandey, G. Pandey, S. Pandey, B. Pandey","doi":"10.4103/2349-3666.240656","DOIUrl":"https://doi.org/10.4103/2349-3666.240656","url":null,"abstract":"Psoriasis is a common autoimmune inflammatory disease wherein pathogenesis is advanced by fundamental genetic predisposition/s in concert with environmental triggers. Inflammation in psoriasis may represent efforts of innate immune system to target pathogens for restoring immune homeostasis. Aberrant microbiota may resist elimination efforts by shear advantage of several fold gene pool as compared to the host. The microbes deregulate gene expression by the molecular insults targeting host immune system. Role of microbiota in autoimmunity dictates establishment of microbiome homeostasis and suppress host immune response; as a treatment approach. Dietary prebiotics and probiotics are of particular interest for prevention and amelioration of autoimmune inflammatory diseases, due to their potential to foster healthy host-microbiome relationship. The rational dietetics aims towards balancing friendly versus enemical microbes via manipulation of gut environment and modulation of immune system to improve regulation of inflammatory and autoimmune mechanisms.","PeriodicalId":34293,"journal":{"name":"Biomedical Research Journal","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2015-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"91140083","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":"Precision/Personalized medicine in cancer","authors":"D. Saranath, A. Khanna","doi":"10.4103/2349-3666.240615","DOIUrl":"https://doi.org/10.4103/2349-3666.240615","url":null,"abstract":"In precision medicine, doctors use information from certain lab tests to put together a plan of care that usually includes specific recommendations. In some cases, it can help make a more accurate diagnosis and improve treatment. In other cases, it can help people make decisions about healthy habits, earlier screening tests, and other steps they can take that might help lower their risk for a particular cancer.","PeriodicalId":34293,"journal":{"name":"Biomedical Research Journal","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2015-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"82708507","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":"Developmental signalling in maintenance and regulation of cancer stem cells","authors":"Sweta Dash, R. Sunkara, S. Waghmare","doi":"10.4103/2349-3666.240619","DOIUrl":"https://doi.org/10.4103/2349-3666.240619","url":null,"abstract":"Tissue stem cells self-renew throughout the life of an organism thereby maintaining tissue homeostasis and prevent cancer. The major signalling pathways such as Wnt, Notch and Sonic hedgehog control the stem cell regulation and their deregulation leads to cancer. Recent evidences showed that there exists a subset of cells within tumour termed as cancer stem cells (CSCs). These CSCs escape the conventional chemo-radiotherapy and further lead to tumour relapse followed by metastasis. This review focuses on the developmental signalling pathways that are involved in the regulation and maintenance of normal stem cells and CSCs. Understanding the molecular mechanism may be useful to specifically target the CSCs while sparing the normal stem cells to reduce tumorigenecity.","PeriodicalId":34293,"journal":{"name":"Biomedical Research Journal","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2015-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"82559140","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}