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931.
932.
Rui Zhang Shaoyun Chen Peng Han Fangfang Chen Shan Kuang Zhuo Meng Junnian Liu Ruliang Sun Zhiwei Wang Xiaohong He Yong Li Yuanning Guan Zhengfang Yue Chen Li Subrata Kumar Dey Yuanfang Zhu Santasree Banerjee 《Journal of cellular and molecular medicine》2020,24(2):1906-1916
Meckel syndrome (MKS) is a pre‐ or perinatal multisystemic ciliopathic lethal disorder with an autosomal recessive mode of inheritance. Meckel syndrome is usually manifested with meningo‐occipital encephalocele, polycystic kidney dysplasia, postaxial polydactyly and hepatobiliary ductal plate malformation. Germline variants in CEP290 cause MKS4. In this study, we investigated a 35‐years‐old Chinese female who was 17+1 weeks pregnant. She had a history of adverse pregnancy of having foetus with multiple malformations. We performed ultrasonography and identified the foetus with occipital meningoencephalocele and enlarged cystic dysplastic kidneys. So, she decided to terminate her pregnancy and further genetic molecular analysis was performed. We identified the aborted foetus without postaxial polydactyly. Histological examination of foetal kidney showed cysts in kidney and thinning of the renal cortex with glomerular atrophy. Whole exome sequencing identified a novel homozygous variant (c.2144T>G; p.L715*) in exon 21 of the CEP290 in the foetus. Sanger sequencing confirmed that both the parents of the foetus were carrying this variant in a heterozygous state. This variant was not identified in two elder sisters of the foetus as well as in the 100 healthy individuals. Western blot analysis showed that this variant leads to the formation of truncated CEP290 protein with the molecular weight of 84 KD compared with the wild‐type CEP290 protein of 290 KD. Hence, it is a loss‐of‐function variant. We also found that the mutant cilium appears longer in length than the wild‐type cilium. Our present study reported the first variant of CEP290 associated with MKS4 in Chinese population. 相似文献
933.
Embryonic stem cells (ESCs) have emerged as potential cell sources for tissue engineering and regeneration owing to its virtually unlimited replicative capacity and the potential to differentiate into a variety of cell types. Current differentiation strategies primarily involve various growth factor/inducer/repressor concoctions with less emphasis on the substrate. Developing biomaterials to promote stem cell proliferation and differentiation could aid in the realization of this goal. Extracellular matrix (ECM) components are important physiological regulators, and can provide cues to direct ESC expansion and differentiation. ECM undergoes constant remodeling with surrounding cells to accommodate specific developmental event. In this study, using ESC derived aggregates called embryoid bodies (EB) as a model, we characterized the biological nature of ECM in EB after exposure to different treatments: spontaneously differentiated and retinoic acid treated (denoted as SPT and RA, respectively). Next, we extracted this treatment-specific ECM by detergent decellularization methods (Triton X-100, DOC and SDS are compared). The resulting EB ECM scaffolds were seeded with undifferentiated ESCs using a novel cell seeding strategy, and the behavior of ESCs was studied. Our results showed that the optimized protocol efficiently removes cells while retaining crucial ECM and biochemical components. Decellularized ECM from SPT EB gave rise to a more favorable microenvironment for promoting ESC attachment, proliferation, and early differentiation, compared to native EB and decellularized ECM from RA EB. These findings suggest that various treatment conditions allow the formulation of unique ESC-ECM derived scaffolds to enhance ESC bioactivities, including proliferation and differentiation for tissue regeneration applications. 相似文献
934.
Muthulakshmi Muthuswami Vignesh Ramesh Saikat Banerjee Soundara Viveka Thangaraj Jayaprakash Periasamy Divya Bhaskar Rao Georgina D. Barnabas Swetha Raghavan Kumaresan Ganesan 《PloS one》2013,8(10)
Genomic aberrations are common in cancers and the long arm of chromosome 1 is known for its frequent amplifications in breast cancer. However, the key candidate genes of 1q, and their contribution in breast cancer pathogenesis remain unexplored. We have analyzed the gene expression profiles of 1635 breast tumor samples using meta-analysis based approach and identified clinically significant candidates from chromosome 1q. Seven candidate genes including exonuclease 1 (EXO1) are consistently over expressed in breast tumors, specifically in high grade and aggressive breast tumors with poor clinical outcome. We derived a EXO1 co-expression module from the mRNA profiles of breast tumors which comprises 1q candidate genes and their co-expressed genes. By integrative functional genomics investigation, we identified the involvement of EGFR, RAS, PI3K / AKT, MYC, E2F signaling in the regulation of these selected 1q genes in breast tumors and breast cancer cell lines. Expression of EXO1 module was found as indicative of elevated cell proliferation, genomic instability, activated RAS/AKT/MYC/E2F1 signaling pathways and loss of p53 activity in breast tumors. mRNA–drug connectivity analysis indicates inhibition of RAS/PI3K as a possible targeted therapeutic approach for the patients with activated EXO1 module in breast tumors. Thus, we identified seven 1q candidate genes strongly associated with the poor survival of breast cancer patients and identified the possibility of targeting them with EGFR/RAS/PI3K inhibitors. 相似文献
935.
Tusha Sharma Basu Dev Banerjee Md Mustafa Kiran Guleria Rafat S Ahmed Ashok K Tripathi 《International Journal of Biochemistry and Molecular Biology》2013,4(4):209-214
Objectives: To assess the Gene-Environmental interaction between maternal organochlorine pesticides (OCPs) level and CYP17 gene polymorphism with the risk of preterm delivery (PTD). Materials and methods: Maternal blood samples of hundred cases (n = 100) of PTD and of equal number of healthy controls were collected at the time of delivery. OCPs levels were estimated by Gas chromatography system equipped with electron capture detector and PCR-RFLP was used for polymorphic analysis of CYP17 gene. Results: Significantly (p < 0.05) higher levels of α-HCH, β-HCH, and γ-HCH were found in maternal blood samples of PTD cases as compared to controls. We did not found any significant difference in the frequency genotype distribution CYP17 gene in PTD cases as compared to controls. When gene environmental interaction between the CYP17 gene polymorphism and OCPs level was considered, a significant interaction was observed between ≥ 50th percentile of γ-HCH and CYP17 A1A1 (wild type) genotype. Conclusions: Higher levels of OCPs along with wild type state of CYP17 gene (A1A1) in women may be considered as an important etiological factor in ‘idiopathic’ PTD. The present study provides evidence that genetic variation and its interaction with the environmental exposure may increase the risk of PTD. 相似文献
936.
During vertebrate development, trunk neural crest cells delaminate along the entire length of the dorsal neural tube and initially migrate as a non-segmented sheet. As they enter the somites, neural crest cells rearrange into spatially restricted segmental streams. Extracellular matrix components are likely to play critical roles in this transition from a sheet-like to a stream-like mode of migration, yet the extracellular matrix components and their modifying enzymes critical for this transition are largely unknown. Here, we identified the glycosyltransferase Lh3, known to modify extracellular matrix components, and its presumptive substrate Collagen18A1, to provide extrinsic signals critical for neural crest cells to transition from a sheet-like migration behavior to migrating as a segmental stream. Using live cell imaging we show that in lh3 null mutants, neural crest cells fail to transition from a sheet to a stream, and that they consequently enter the somites as multiple streams, or stall shortly after entering the somites. Moreover, we demonstrate that transgenic expression of lh3 in a small subset of somitic cells adjacent to where neural crest cells switch from sheet to stream migration restores segmental neural crest cell migration. Finally, we show that knockdown of the presumptive Lh3 substrate Collagen18A1 recapitulates the neural crest cell migration defects observed in lh3 mutants, consistent with the notion that Lh3 exerts its effect on neural crest cell migration by regulating post-translational modifications of Collagen18A1. Together these data suggest that Lh3–Collagen18A1 dependent ECM modifications regulate the transition of trunk neural crest cells from a non-segmental sheet like migration mode to a segmental stream migration mode. 相似文献
937.
Subhasis Barik Saptak Banerjee Atanu Mallick Kuntal Kanti Goswami Soumyabrata Roy Anamika Bose Rathindranath Baral 《PloS one》2013,8(6)
We have observed restriction of the murine sarcoma growth by therapeutic intervention of neem leaf glycoprotein (NLGP). In order to evaluate the mechanism of tumor growth restriction, here, we have analyzed tumor microenvironment (TME) from sarcoma bearing mice with NLGP therapy (NLGP-TME, in comparison to PBS-TME). Analysis of cytokine milieu within TME revealed IL-10, TGFβ, IL-6 rich type 2 characters was switched to type 1 microenvironment with dominance of IFNγ secretion within NLGP-TME. Proportion of CD8+ T cells was increased within NLGP-TME and these T cells were protected from TME-induced anergy by NLGP, as indicated by higher expression of pNFAT and inhibit related downstream signaling. Moreover, low expression of FasR+ cells within CD8+ T cell population denotes prevention from activation induced cell death. Using CFSE as a probe, better migration of T cells was noted within TME from NLGP treated mice than PBS cohort. CD8+ T cells isolated from NLGP-TME exhibited greater cytotoxicity to sarcoma cells in vitro and these cells show higher expression of cytotoxicity related molecules, perforin and granzyme B. Adoptive transfer of NLGP-TME exposed T cells, but not PBS-TME exposed cells in mice, is able to significantly inhibit the growth of sarcoma in vivo. Such tumor growth inhibition by NLGP-TME exposed T cells was not observed when mice were depleted for CD8+ T cells. Accumulated evidences strongly suggest NLGP mediated normalization of TME allows T cells to perform optimally to inhibit the tumor growth. 相似文献
938.
939.
Jamila H. Siamwala Paul M. Dias Syamantak Majumder Manoj K. Joshi Vilas P. Sinkar Gautam Banerjee Suvro Chatterjee 《The Journal of nutritional biochemistry》2013,24(3):595-605
Consumption of tea (Camellia sinensis) improves vascular function and is linked to lowering the risk of cardiovascular disease. Endothelial nitric oxide is the key regulator of vascular functions in endothelium. In this study, we establish that l-theanine, a non-protein amino-acid found in tea, promotes nitric oxide (NO) production in endothelial cells. l-theanine potentiated NO production in endothelial cells was evaluated using Griess reaction, NO sensitive electrode and a NO specific fluorescent probe (4-amino-5-methylamino-2',7'-difluororescein diacetate). l-Theanine induced NO production was partially attenuated in presence of l-NAME or l-NIO and completely abolished using eNOS siRNA. eNOS activation was Ca2 + and Akt independent, as assessed by fluo-4AM and immunoblotting experiments, respectively and was associated with phosphorylation of eNOS Ser 1177. eNOS phosphorylation was inhibited in the presence of ERK1/2 inhibitor, PD-98059 and partially inhibited by PI3K inhibitor, LY-294002 and Wortmanin suggesting PI3K-ERK1/2 dependent pathway. Increased NO production was associated with vasodilation in ex ovo (chorioallantoic membrane) model. These results demonstrated that l-theanine administration in vitro activated ERK/eNOS resulting in enhanced NO production and thereby vasodilation in the artery. The results of our experiments are suggestive of l-theanine mediated vascular health benefits of tea. 相似文献
940.
Ashutosh Banerjee Simone Maschauer Harald Hübner Peter Gmeiner Olaf Prante 《Bioorganic & medicinal chemistry letters》2013,23(22):6079-6082
Taking advantage of click chemistry, a library of N-arylpiperazinylmethyl triazoles bearing fluoro substituted appendages was synthesized and the target compounds were investigated for dopamine and serotonin receptor binding. With the aim to bias their hydrophilicity and to optimize their D4 receptor affinity and selectivity, a concise series of triazoles containing fluoroalkyl, fluoroalkoxy, fluoroalkoxyphenyl, and deoxyfluoroglucosyl substituents was studied. The D4 receptor affinity and selectivity could be tuned by altering the chemical moiety attached to the triazole unit. Among the test compounds, the fluoroethoxyphenyl derivative 15b showed weak partial agonism at D4 and a Ki value of 14 nM, while its fluoropropoxyphenyl homologue 16a turned out to act as a neutral D4 antagonist (Ki = 5.1 nM). Both, 15b and 16a revealed an excellent balance between D4 receptor affinity and subtype selectivity, providing lead candidates for the development of 18F-labeled radioligands for D4 receptor imaging studies by positron emission tomography (PET). 相似文献