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        Modulatory effect of Tinospora cordifolia extract on Cd-induced oxidative stress in Wistar rats

        Viswanadha Vijaya Padma,Rathinasamy Baskaran,Subramani Divya,Lohanathan Bharathi Priya,Sithuraj Saranya 한국한의학연구원 2016 Integrative Medicine Research Vol.5 No.1

        Background Cadmium (Cd), a nonessential heavy metal, is a major environmental and public health concern. Oxidative stress plays an important role in Cd-induced kidney dysfunction. Tinospora cordifolia, a medicinal plant rich in phytochemicals, possesses antioxidant activity. The objective of the present study was to assess the protective effect of Tinospora cordifolia-stem methanolic extract (TCE) on Cd-induced nephrotoxicity in Wistar rats. Methods Male Wistar rats were administered ∼5 mg/kg body weight Cd orally and 100 mg/kg body weight TCE for 28 days. At the end of Cd and TCE treatment, biochemical assays were performed in serum and tissue homogenate. Results Cd-induced oxidative stress in the kidney resulted in increased levels of lipid peroxidation and protein carbonyl content with a significant decrease in cellular antioxidants, such as reduced GSH, SOD, CAT, GPX, and GST. Cd-induced nephrotoxicity was further confirmed by marked changes in the histology of the kidney and increased levels of kidney markers. Additionally, Cd-treated rats showed alterations in membrane-bound ATPase activity and decreased levels of tissue glycoproteins. Cotreatment with TCE considerably reduced the biochemical alterations in serum and renal tissue induced by Cd, and also restored ATPase activity and glycoproteins to near normal levels. Conclusion Our results suggested that TCE with its antioxidant effect offered cytoprotection against Cd-induced toxicity in kidneys by restoring the altered cellular antioxidants and renal markers. TCE treatment for 28 days reversed ATPase activity and tissue glycoprotein levels. These results revealed the protective effect of TCE on Cd-induced toxicity in kidneys and oxidative stress.

      • KCI등재후보

        Neferine, a bisbenzylisoquinoline alkaloid, offers protection against cobalt chloride-mediated hypoxia-induced oxidative stress in muscle cells

        Rathinasamy Baskaran,Palanisamy Kalaiselvi,Chih-Yang Huang,Viswanadha Vijaya Padma 한국한의학연구원 2015 Integrative Medicine Research Vol.4 No.4

        Background Neferine, a bisbenzylisoquinoline alkaloid, isolated from Nelumbo nucifera has a wide range of biological activities. Cobalt chloride (CoCl2) was known to mimic hypoxic condition. In the present study, we assessed the cytoprotective effect of neferine against CoCl2-induced oxidative stress in muscle cells. Methods Rhabdomyosarcoma cells were exposed to different concentrations of CoCl2, and the IC50 value was determined using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. Lactate dehydrogenase and NO assays were performed in order to determine the cytotoxic effect of CoCl2. Reactive oxygen species generation and cellular antioxidant status were determined for evaluating oxidative stress. For analyzing the effect of neferine on CoCl2-induced apoptosis, propidium iodide staining was performed. Results The results of the present study indicate that CoCl2 induces cell death in a dose-dependent manner. Neferine pretreatment at 700 nM concentration offers better cytoprotection in the cells exposed to CoCl2. Lactate dehydrogenase and NO release in the culture medium were restored after neferine pretreatment. CoCl2 triggers time-dependent reactive oxygen species generation in muscle cells. Further, results of propidium iodide staining, mitochondrial membrane potential, and intracellular calcium accumulation confirm that neferine offers protection against CoCl2-induced hypoxic injury. Depleted activities of antioxidants such as superoxide dismutase, catalase, glutathione peroxidase, and glutathione S-transferase due to CoCl2 exposure were also reinstated in the group that received neferine pretreatment. Conclusion Our study suggests that neferine from N. nucifera offers protection to muscle cells by counteracting the oxidative stress induced by CoCl2.

      • KCI등재

        What Should an Ideal Adult Spinal Deformity Classification System Consist of?: Review of the Factors Affecting Outcomes of Adult Spinal Deformity Management

        J. Naresh-Babu,Arun-Kumar Viswanadha,Manabu Ito,박종범 대한척추외과학회 2019 Asian Spine Journal Vol.13 No.4

        This literature review aims to determine potential clinical factors or comorbidities besides radiological parameters that affect the outcome of adult spinal deformity (ASD) management and review existing classifications associated with ASD. ASD is a multifactorial disease that comprises pathologies like radiological spine deformity, coexistence of spinal canal stenosis, radiculopathy, and multiple comorbidities. The available classification systems of ASD are predominantly based on radiological parameters and do not consider related clinical conditions. ASD patients with different combinations of these parameters behave differently and need different management strategies. We conducted a narrative literature review with search limited to English language of PubMed/MEDLINE using Medical Subject Heading (MeSH) terms. The terms specific to the review were ASD and several other related terminologies. We analyzed the information of the selected papers including factors affecting surgical outcomes for degenerative scoliosis. We reviewed 614 citations. Based on the inclusion criteria, 39 citations were selected for full-text retrieval; of these, 28 were excluded because of not fulfilling the inclusion criteria. Thus, 11 studies were selected and included for the final analysis. The presence of leg pain, spinal stenosis, obesity, osteoporosis, smoking, and age of patients were major influencing factors. Furthermore, the factors included in the available classifications, such as the Scoliosis Research Society–Schwab classifications, were reviewed and results were tabulated. This review highlights the significance of neurological symptoms, spinal stenosis, osteoporosis, obesity, age, and smoking, which markedly affect the management of ASD. With increasing number of patients being diagnosed and treated with ASD, there has been a growing need to comprehensively classify these patients into clinicoradiological subgroups.

      • KCI등재

        A Novel, Potent, Small Molecule AKT Inhibitor Exhibits Efficacy against Lung Cancer Cells In Vitro

        Saketh S. Dinavahi,Rajagopalan Prasanna,Sriram Dharmarajan,Yogeeswari Perumal,Srikant Viswanadha 대한암학회 2015 Cancer Research and Treatment Vol.47 No.4

        Purpose Anomalies of Akt regulation, including overexpression in lung cancer, impart resistance toconventional chemotherapy and radiation, thereby implicating this kinase as a therapeuticintervention point. A novel scaffold of Akt inhibitors was developed through virtual screeningof chemical databases available at Birla Institute of Technology and Science, Pilani, Hyderabad,based on docking studies using Maestro. A benzothienopyrimidine derivative (BIA-6)was identified as a potential lead molecule that inhibited Akt1 enzyme activity with an IC50of 256 nM. Materials and MethodsBIA-6 was tested for in vitro Akt1 inhibition using a fluorescence resonance energy transferkit. Anti-proliferative activity was tested in NCI-H460, A549, NCI-H1975, and NCI-H2170cell lines. The effect of the compound on p-Akt (S473) was estimated. ResultsBIA-6 allosterically caused a dose dependent reduction of growth of cell lines with a halfmaximal growth inhibition (GI50) range of 0.49 !M to 6.6 !M. Cell cycle analysis indicatedthat BIA-6 caused a G1 phase arrest at < 100 nM but led to apoptosis at higher doses. BIA-6 also exhibited synergism with standard chemotherapeutic agents. ConclusionBIA-6 is a novel, allosteric Akt inhibitor with potent anti-cancer activity in lung cancer celllines, that effectively blocks the phosphoinositide-3 kinase/Akt pathway with a high marginselectivity towards normal cells.

      • KCI등재

        Alpinate Oxyphyllae Fructus Inhibits IGFII-Related Signaling Pathway to Attenuate Ang II-Induced Pathological Hypertrophy in H9c2 Cardiomyoblasts

        Chuan-Te Tsai,Yung-Ming Chang,Shu-Luan Lin,Yueh-Sheng Chen,Yu-Lan Yeh,Viswanadha Vijaya Padma,Chin-Chuan Tsai,Ray-Jade Chen,Tsung-Jung Ho,Chih-Yang Huang 한국식품영양과학회 2016 Journal of medicinal food Vol.19 No.3

        Angiotensin II (Ang II) is a very important cardiovascular disease inducer and may cause cardiac pathological hypertrophy and remodeling. We evaluated a Chinese traditional medicine, alpinate oxyphyllae fructus (AOF), for therapeutic efficacy for treating Ang II-induced cardiac hypertrophy. AOF has been used to treat patients with various symptoms accompanying hypertension and cerebrovascular disorders in Korea. We investigated its protective effect against Ang II-induced cytoskeletal change and hypertrophy in H9c2 cells. The results showed that treating cells with Ang II resulted in pathological hypertrophy, such as increased expression of transcription factors NFAT-3/p-NFAT-3, hypertrophic response genes (atrial natriuretic peptide [ANP] and b-type natriuretic peptide [BNP]), and Gαq down-stream effectors (PLCβ3 and calcineurin). Pretreatment with AOF (60–100 μg/mL) led to significantly reduced hypertrophy. We also found that AOF pretreatment significantly suppressed the cardiac remodeling proteins, metalloproteinase (MMP9 and MMP2), and plasminogen activator, induced by Ang II challenge. In conclusion, we provide evidence that AOF protects against Ang II-induced pathological hypertrophy by specifically inhibiting the insulin-like growth factor (IGF) II/IIR-related signaling pathway in H9c2 cells. AOF might be a candidate for cardiac hypertrophy and ventricular remodeling prevention in chronic cardiovascular diseases.

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