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      • KCI등재

        Understanding the molecular evolution of tiger diversity through DNA barcoding marker ND4 and NADH dehydrogenase complex using computational biology

        Chiranjib Chakraborty,Ashish Ranjan Sharma,Sharma Garima,Manojit Bhattacharya,Bidhan C. Patra,Bimal Kumar Sarkar,Saptarshi Banerjee,Kankana Banerjee,Sang‑Soo Lee 한국유전학회 2021 Genes & Genomics Vol.43 No.7

        Background Currently, Tigers (the top predator of an ecosystem) are on the list of endangered species. Thus the need is to understand the tiger’s population genomics to design their conservation strategies. Objective We analyzed the molecular evolution of tiger diversity using NADH dehydrogenase subunit 4 (ND4), a signifcant electron transport chain component. Methods We have analyzed nucleotide composition and distribution pattern of ND genes, molecular evolution, evolutionary conservation pattern and conserved blocks of NADH, phylogenomics of ND4, and estimating species divergence, etc., using diferent bioinformatics tools and software, and MATLAB programming and computing environment. Results The nucleotide composition and distribution pattern of ND genes in the tiger genome demonstrated an increase in the number of adenine (A) and a lower trend of A+T content in some place of the distribution analysis. However, the observed distributions were not signifcant (P > 0.05). Evolutionary conservation analysis showed three highly align blocks (186 to 198, 406 to 416, and 527 to 545). On mapping the molecular evolution of ND4 among model species (n = 30), we observed its presence in a broader range of species. ND4 based molecular evolution of tiger diversity and time divergence for a tiger (20 diferent other species) shows that genus Panthera originated more or less at a similar time. Conclusions The nucleotide composition and nucleotide distribution pattern of tiger ND genes showed the evolutionary pattern and origin of tiger and Panthera lineage concerning the molecular clock, which will help to understand their adaptive evolution.

      • Micro-Environmental Signature of The Interactions between Druggable Target Protein, Dipeptidyl Peptidase-IV, and Anti-Diabetic Drugs

        Chakraborty, Chiranjib,Mallick, Bidyut,Sharma, Ashish Ranjan,Sharma, Garima,Jagga, Supriya,Doss, C George Priya,Nam, Ju-Suk,Lee, Sang-Soo Royan Institute 2017 Cell journal (Yakhteh) Vol.19 No.1

        <P><B>Objective</B></P><P> Druggability of a target protein depends on the interacting micro-environment between the target protein and drugs. Therefore, a precise knowledge of the interacting micro-environment between the target protein and drugs is requisite for drug discovery process. To understand such micro-environment, we performed in silico interaction analysis between a human target protein, Dipeptidyl Peptidase-IV (DPP-4), and three anti-diabetic drugs (saxagliptin, linagliptin and vildagliptin). </P><P><B>Materials and Methods</B></P><P> During the theoretical and bioinformatics analysis of micro-environmental properties, we performed drug-likeness study, protein active site predictions, docking analysis and residual interactions with the protein-drug interface. Micro-environmental landscape properties were evaluated through various parameters such as binding energy, intermolecular energy, electrostatic energy, van der Waals’+H-bond+desolvo energy (E<SUB>VHD</SUB>) and ligand efficiency (LE) using different in silico methods. For this study, we have used several servers and software, such as Molsoft prediction server, CASTp server, AutoDock software and LIGPLOT server. </P><P><B>Results</B></P><P> Through micro-environmental study, highest log P value was observed for linagliptin (1.07). Lowest binding energy was also observed for linagliptin with DPP-4 in the binding plot. We also identified the number of H-bonds and residues involved in the hydrophobic interactions between the DPP-4 and the anti-diabetic drugs. During interaction, two H-bonds and nine residues, two H-bonds and eleven residues as well as four H-bonds and nine residues were found between the saxagliptin, linagliptin as well as vildagliptin cases and DPP-4, respectively. </P><P><B>Conclusion</B></P><P>Our in silico data obtained for drug-target interactions and micro-environmental signature demonstrates linagliptin as the most stable interacting drug among the tested anti-diabetic medicines.</P>

      • KCI우수등재

        Ongoing Clinical Trials of Vaccines to Fight against COVID-19 Pandemic

        Chakraborty Chiranjib,SHARMA ASHISH RANJAN,Bhattacharya Manojit,Sharma Garima,Saha Rudra P.,이상수 대한면역학회 2021 Immune Network Vol.21 No.1

        Coronavirus disease 2019 (COVID-19) has developed as a pandemic, and it created an outrageous effect on the current healthcare and economic system throughout the globe. To date, there is no appropriate therapeutics or vaccines against the disease. The entire human race is eagerly waiting for the development of new therapeutics or vaccines against severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). Efforts are being taken to develop vaccines at a rapid rate for fighting against the ongoing pandemic situation. Amongst the various vaccines under consideration, some are either in the preclinical stage or in the clinical stages of development (phase-I, -II, and -III). Even, phase-III trials are being conducted for some repurposed vaccines like Bacillus Calmette–Guérin, polio vaccine, and measles-mumps-rubella. We have highlighted the ongoing clinical trial landscape of the COVID-19 as well as repurposed vaccines. An insight into the current status of the available antigenic epitopes for SARS-CoV-2 and different types of vaccine platforms of COVID-19 vaccines has been discussed. These vaccines are highlighted throughout the world by different news agencies. Moreover, ongoing clinical trials for repurposed vaccines for COVID-19 and critical factors associated with the development of COVID-19 vaccines have also been described.

      • Effect of Wnt3a on Keratinocytes Utilizing <i>in Vitro</i> and Bioinformatics Analysis

        Nam, Ju-Suk,Chakraborty, Chiranjib,Sharma, Ashish Ranjan,Her, Young,Bae, Kee-Jeong,Sharma, Garima,Doss, George Priya,Lee, Sang-Soo,Hong, Myung-Sun,Song, Dong-Keun Molecular Diversity Preservation International (MD 2014 INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES Vol.15 No.4

        <P>Wingless-type (Wnt) signaling proteins participate in various cell developmental processes. A suppressive role of Wnt5a on keratinocyte growth has already been observed. However, the role of other Wnt proteins in proliferation and differentiation of keratinocytes remains unknown. Here, we investigated the effects of the Wnt ligand, Wnt3a, on proliferation and differentiation of keratinocytes. Keratinocytes from normal human skin were cultured and treated with recombinant Wnt3a alone or in combination with the inflammatory cytokine, tumor necrosis factor α (TNFα). Furthermore, using bioinformatics, we analyzed the biochemical parameters, molecular evolution, and protein–protein interaction network for the Wnt family. Application of recombinant Wnt3a showed an anti-proliferative effect on keratinocytes in a dose-dependent manner. After treatment with TNFα, Wnt3a still demonstrated an anti-proliferative effect on human keratinocytes. Exogenous treatment of Wnt3a was unable to alter mRNA expression of differentiation markers of keratinocytes, whereas an altered expression was observed in TNFα-stimulated keratinocytes. <I>In silico</I> phylogenetic, biochemical, and protein–protein interaction analysis showed several close relationships among the family members of the Wnt family. Moreover, a close phylogenetic and biochemical similarity was observed between Wnt3a and Wnt5a. Finally, we proposed a hypothetical mechanism to illustrate how the Wnt3a protein may inhibit the process of proliferation in keratinocytes, which would be useful for future researchers.</P>

      • Computational Biophysical, Biochemical, and Evolutionary Signature of Human R-Spondin Family Proteins, the Member of Canonical Wnt/ <i>β</i> -Catenin Signaling Pathway

        Sharma, Ashish Ranjan,Chakraborty, Chiranjib,Lee, Sang-Soo,Sharma, Garima,Yoon, Jeong Kyo,George Priya Doss, C.,Song, Dong-Keun,Nam, Ju-Suk Hindawi Publishing Corporation 2014 BioMed research international Vol.2014 No.-

        <P>In human, Wnt/<I>β</I>-catenin signaling pathway plays a significant role in cell growth, cell development, and disease pathogenesis. Four human (Rspo)s are known to activate canonical Wnt/<I>β</I>-catenin signaling pathway. Presently, (Rspo)s serve as therapeutic target for several human diseases. Henceforth, basic understanding about the molecular properties of (Rspo)s is essential. We approached this issue by interpreting the biochemical and biophysical properties along with molecular evolution of (Rspo)s thorough computational algorithm methods. Our analysis shows that signal peptide length is roughly similar in (Rspo)s family along with similarity in aa distribution pattern. In Rspo3, four N-glycosylation sites were noted. All members are hydrophilic in nature and showed alike GRAVY values, approximately. Conversely, Rspo3 contains the maximum positively charged residues while Rspo4 includes the lowest. Four highly aligned blocks were recorded through Gblocks. Phylogenetic analysis shows Rspo4 is being rooted with Rspo2 and similarly Rspo3 and Rspo1 have the common point of origin. Through phylogenomics study, we developed a phylogenetic tree of sixty proteins (<I>n</I> = 60) with the orthologs and paralogs seed sequences. Protein-protein network was also illustrated. Results demonstrated in our study may help the future researchers to unfold significant physiological and therapeutic properties of (Rspo)s in various disease models.</P>

      • KCI등재

        Influence of single nucleotide polymorphisms (SNPs) in genetic susceptibility towards periprosthetic osteolysis

        Supriya Jagga,SHARMA ASHISH RANJAN,Manojit Bhattacharya,Chiranjib Chakraborty,이상수 한국유전학회 2019 Genes & Genomics Vol.41 No.10

        Wear debris-induced inflammatory osteolysis remains a significant limiting factor for implant replacement surgeries. Hence, a comprehensive understanding of the complex network of cellular and molecular signals leading to these inflammatory responses is required. Both macrophages and monocytes have a critical role in the instigation of the inflammatory reaction to wear debris but differ in the extent to which they induce cytokine expression in patients. Lately, single nucleotide polymorphisms (SNPs) have been associated with genetic susceptibility among individual patients with implant failure. Studies have shown that SNPs in key pro-inflammatory cytokines and their receptors are associated with osteolytic susceptibility. Likewise, SNPs within several genes involved in the regulation of bone turnover have also been found to be associated with wear debris induced osteolysis. It is presumed that SNP variance might play a decisive role in the activation and signaling of macrophages, osteoblasts, chondrocytes, fibroblasts and other cells involved in inflammatory bone loss. Understanding the extent to which SNPs exist among genes that are responsible for inflammatory bone loss may provide potential targets for developing future therapeutic interventions. Herein, we attempt to summarize the various susceptible genes with possible SNP variance that could contribute to the severity of periprosthetic osteolysis in patients with implants.

      • Review of Prospects of Biological Fluid Biomarkers in Osteoarthritis

        Nguyen, Lich Thi,Sharma, Ashish Ranjan,Chakraborty, Chiranjib,Saibaba, Balaji,Ahn, Moo-Eob,Lee, Sang-Soo MDPI 2017 INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES Vol.18 No.3

        <P>Osteoarthritis (OA) is a degenerative disease of the joints and is one of the leading causes of disability in adults. However, there are no key therapeutics for OA and medical treatment is based on managing the symptoms and slowing down progression of the disease. Diagnostics based on clinical examination and radiography have provided little information about metabolic changes in joint tissues, disease onset and progression. Due to lack of effective methods for early detection and evaluation of treatment outcome, the measurement of biochemical markers (biomarkers) shows promise as a prospective method aiding in disease monitoring. OA biomarkers that are present in biological fluids such as blood, urine and synovial fluid, sources that are easily isolated from body, are of particular interest. Moreover, there are increasingly more studies identifying and developing new biomarkers for OA. In this review, efforts have been made to summarize the biomarkers that have been reported in recent studies on patients. We also tried to classify biomarkers according to tissue metabolism (bone, cartilage and synovial metabolism markers), pathological pathways (inflammatory and genetic markers) and biological function (chemokines, growth factors, acute phase proteins, etc.).</P>

      • SCISCIESCOPUS

        Methoxy poly(ethylene glycol)-poly(lactide) nanoparticles encapsulating quercetin act as an effective anticancer agent by inducing apoptosis in breast cancer.

        Sharma, Garima,Park, Jongbong,Sharma, Ashish Ranjan,Jung, Jun-Sub,Kim, Haesung,Chakraborty, Chiranjib,Song, Dong-Keun,Lee, Sang-Soo,Nam, Ju-Suk Kluwer Academic/Plenum Publishers 2015 Pharmaceutical research Vol.32 No.2

        <P>Purpose To overcome the therapeutic restrictions offered by hydrophobic quercetin (Qu), this study aims to synthesize MPEG-PLA encapsulated Qu nanoparticle and to evaluate their anticancer efficacy. Materials and Methods In vitro anticancer potential and apoptotic studies were done by cell cytotoxicity assay and flow cytometry, respectively. MPEG-PLA-Qu nanoparticles were evaluated for anticancer efficacy in vivo using xenograft mice model. TUNEL assay was performed to observe the frequency of apoptotic cells in vivo. Results The hydrodynamic particle size, polydispersity index, zeta potential and drug loading % of MPEG-PLA-Qu nanoparticle was 155.3 +/- 3.2 nm, 0.2 +/- 0.05, -3.14 mV and 5.3 +/- 1.1%, respectively. Also, MPEG-PLA-Qu showed sustained drug release for 10 days. In vitro results showed that MPEG-PLA-Qu could efficiently induce apoptosis in triple negative breast cancer cell line (MDA-MB-231) with higher amount of quercetin in cell lysate treated with MPEG-PLA-Qu in comparison to free quercetin. In xenograft model for breast cancer, peritumorally injected MPEG-PLA-Qu significantly inhibited the tumor growth. Moreover, TUNEL assay showed more occurrence of apoptotic cells in MPEG-PLA-Qu treated tumors compared to free quercetin at similar dose. Conclusion Our data suggest that MPEG-PLA-Qu nanoparticle can have a promising clinical potential for the treatment of breast cancer.</P>

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