Endoplasmic Reticulum Stress and Cancer

Raj Kumar Yadav,채수완,김형룡,채한정 대한암예방학회 2014 Journal of cancer prevention Vol.19 No.2

The endoplasmic reticulum (ER) is the principal organelle responsible for multiple cellular functions including protein folding and maturation and the maintenance of cellular homeostasis. ER stress is activated by a variety of factors and triggers the unfolded protein response (UPR), which restores homeostasis or activates cell death. Multiple studies have clarified the link between ER stress and cancer, and particularly the involvement of the UPR. The UPR seems to adjust the paradoxical microenvironment of cancer and, as such, is one of resistance mechanisms against cancer therapy. This review describes the activity of different UPRs involved in tumorigenesis and resistanceto cancer therapy.

TMBIM6 (transmembrane BAX inhibitor motif containing 6) enhances autophagy and reduces renal dysfunction in a cyclosporine A-induced nephrotoxicity model

Yadav, Raj Kumar,Lee, Geum-Hwa,Lee, Hwa-Young,Li, Bo,Jung, Han-Eul,Rashid, Harun-Or,Choi, Min Kyung,Yadav, Binod Kumar,Kim, Woo-Ho,Kim, Kyung-Woon,Park, Byung-Hyun,Kim, Won,Lee, Yong-Chul,Kim, Hyung-R Informa UK (TaylorFrancis) 2015 AUTOPHAGY Vol.11 No.10

<P>Cyclosporine A (CsA) is widely used as an immunosuppressor in transplantation. Previous studies reported that CsA induces autophagy and that chronic treatment with CsA results in accumulation of autophagosomes and reduced autophagic clearance. Autophagy is a prosurvival process that promotes recovery from acute kidney injury by degrading misfolded proteins produced in the kidney. In the present study, we used TMBIM6-expressing HK-2, human kidney tubular cells (TMBIM6 cells) and Tmbim6 knockout (tmbim6(-/-)) mice. When exposed to CsA, the TMBIM6 cells maintained autophagy activity by preventing autophagosome accumulation. With regard to signaling, PRKKA/AMPK phosphorylation and mechanistic target of rapamycin (serine/threonine kinase) complex 1 (MTORC1) expression and its downstream target TFEB (transcription factor EB), a lysosome biogenesis factor, were regulated in the TMBIM6 cells. Lysosomal activity was highly increased or stably maintained in the presence of TMBIM6. In addition, treatment of tmbim6(-/-) mice with CsA resulted in increased autophagosome formation and decreased lysosome formation and activity. We also found that tmbim6(-/-) mice were susceptible to CsA-induced kidney injury. Taken together, these results indicate that TMBIM6 protects against CsA-induced nephrotoxicity both in vitro and in vivo by inducing autophagy and activating lysosomes.</P>

Comparative Performance of Line Probe Assay (Version 2) and Xpert MTB/RIF Assay for Early Diagnosis of Rifampicin-Resistant Pulmonary Tuberculosis

( Raj Narayan Yadav ),( Binit Kumar Singh ),( Rohini Sharma ),( Jigyasa Chaubey ),( Sanjeev Sinha ),( Pankaj Jorwal ) 대한결핵 및 호흡기학회 2021 Tuberculosis and Respiratory Diseases Vol.84 No.3

Background: The emergence of drug-resistant tuberculosis (TB), is a major menace to cast off TB worldwide. Line probe assay (LPA; GenoType MTBDRplus ver. 2) and Xpert MTB/RIF assays are two rapid molecular TB detection/diagnostic tests. To compare the performance of LPA and Xpert MTB/RIF assay for early diagnosis of rifampicin-resistant (RR) TB in acid-fast bacillus (AFB) smear-positive and negative sputum samples. Methods: A total 576 presumptive AFB patients were selected and subjected to AFB microscopy, Xpert MTB/RIF assay and recent version of LPA (GenoType MTBDRplus assay version 2) tests directly on sputum samples. Results were compared with phenotypic culture and drug susceptibility testing (DST). DNA sequencing was performed with rpoB gene for samples with discordant rifampicin susceptibility results. Results: Among culture-positive samples, Xpert MTB/RIF assay detected Mycobacterium tuberculosis (Mtb) in 97.3% (364/374) of AFB smear-positive samples and 76.5% (13/17) among smear-negative samples, and the corresponding values for LPA test (valid results with Mtb control band) were 97.9% (366/374) and 58.8% (10/17), respectively. For detection of RR among Mtb positive molecular results, the sensitivity of Xpert MTB/RIF assay and LPA (after resolving discordant phenotypic DST results with DNA sequencing) were found to be 96% and 99%, respectively. Whereas, specificity of both test for detecting RR were found to be 99%. Conclusion: We conclude that although Xpert MTB/RIF assay is comparatively superior to LPA in detecting Mtb among AFB smear-negative pulmonary TB. However, both tests are equally efficient in early diagnosis of AFB smear-positive presumptive RR-TB patients.

Tobacco Use Increases Oxidative DNA Damage in Sperm - Possible Etiology of Childhood Cancer

Kumar, Shiv Basant,Chawla, Bhavna,Bisht, Shilpa,Yadav, Raj Kumar,Dada, Rima Asian Pacific Journal of Cancer Prevention 2015 Asian Pacific journal of cancer prevention Vol.16 No.16

Background: Cigarette smoking and tobacco chewing are common modes of consuming tobacco all over the world. Parents need to be aware that germ cell integrity is vital for birth of healthy offspring as biological parenting begins much before birth of a child and even before conception. The present study was conducted to determine the etiology of non-familial sporadic heritable retinoblastoma (NFSHRb), by evaluating oxidative sperm DNA damage in fathers due to use of tobacco (smoking and chewing). Materials and Methods: We recruited 145 fathers of NFSHRb children and 53 fathers of healthy children (controls) in the study. Tobacco history was obtained by personal interview. Seminal reactive oxygen species (ROS) in semen, sperm DNA fragmentation index (DFI) and 8 hydroxy 2' deoxyguanosine (8-OHdG) levels in sperm were evaluated. The RB1 gene was screened in genomic blood DNA of parents of children with NFSHRb and controls. Odds ratios (ORs) derived from conditional logistic regression models. Results: There was significant difference in the levels of ROS (p<0.05), DFI (p<0.05) and 8-OHdG (p<0.05) between tobacco users and non-users. The OR of NFSHRb for smokers was 7.29 (95%CI 2.9-34.5, p<0.01), for tobacco chewers 4.75 (2.07-10.9, p<0.05) and for both 9.11 (3.79-39.2; p<0.01). Conclusions: This study emphasizes the adverse effect of tobacco on the paternal genome and how accumulation of oxidative damage in sperm DNA may contribute to the etiology of NFSHRb. In an ongoing parallel study in our laboratory, 11 of fathers who smoked underwent. Meditation and yoga interventions, showed significant decline in levels of highly mutagenic oxidised DNA adducts after 6 months. Thus our lifestyle and social habits impact sperm DNA integrity and simple interventions like yoga and meditation are therapeutic for oxidative damage to sperm DNA.

DOES SOCIAL MEDIA PROMOTES NON-DECEPTIVE COUNTERFEITING? EMPIRICAL EVIDENCES FROM INDIA

Ritu Raj,Saurabh Verma,Sunil Kumar Yadav 글로벌지식마케팅경영학회 2023 Global Marketing Conference Vol.2023 No.07

Social media has become popular in both business and research as many studies have explored the impact of this medium on the purchase behavior of consumers but surprisingly not in the domain of counterfeiting. Social media has become a significant part of today's lifestyle and it has created new channels for brand manufacturers and consumers to communicate. The present study tries to assess the impact of social media determinants on counterfeit purchase intention. The study explored three factors of social media namely social media platform, user-generated content, and social media word of mouth. Further, the study checks for the mediation effect of consumer attitude between social media determinants and purchase intention. The data for the present study were collected from three metropolitan cities of India namely Delhi, Kolkata, and Mumbai. The PLS-SEM was used on 406 respondents for further analysis and validation. The results revealed that there is a significant relationship between social media platforms, user-generated content, and purchase intention. However, an insignificant relationship was found between social media word of mouth and purchase intention. Further, the study suggested that attitude mediates the relationship between social media determinants and the purchase intention of consumers towards the purchase of counterfeit products in India.

On-Farm Diversity Assessment and Participatory Varietal Evaluation of Cold-Tolerant Rice in Mid-Hills of Nepal

Ritesh Kumar Yadav,Rita Gurung,Rajeev Dhakal,Achyut Raj Adhikari,Subash Gautam,크리슈나 하리 기미르,Bhuwon Ratna Sthapit 한국작물학회 2019 Journal of crop science and biotechnology Vol.22 No.5

Drawing upon consequentially growing food insecurity in mid-hills attributed to poor adoption levels inter alia inflicted by narrow range of locally adaptive farmer’s preferred cold tolerant rice varietal options in national agricultural system, the present study was undertaken. We conducted on farm diversity assessment of 60 high altitude rice genotypes from ex-situ and on farm employing un-replicated diversity block in 2015. Subsequently, we identified eight promising locally adaptive genotypes as candidate genotypes based on the inferences of diversity block trial and evaluated them through participatory variety selection (PVS) using randomized block design in 2016 under on-farm conditions. Our studies revealed marked diversity among the Nepalese cold-tolerant rice genotypes. The UPGMA cluster analysis categorized the 60 genotypes into six distinct clusters. Strong positive correlation between grain yield and plant height; panicle length; straw yield and strong negative correlation between grain yield and 1000-grain weight was detected. PCA suggested traits viz., plant height, panicle length, days to 50% heading, and grain yield to be principal discriminatory characteristics of the cold-tolerant rice. Seto Kattike, Naulo Dhan, and Borang were most promising and adaptive genotypes whose eminence were justifiably corroborated and validated by farmer’s overall evaluation. The most valued farmer’s selection criteria were grain and straw yield, earliness, disease resistance, and stem borer tolerance. The findings bolster employment of novel and proven participatory plant breeding approach using diversity kits and IRD kits to expand and promote varietal choice options for immediate benefits to the farmers and facilitate rapid varietal release and registration.

Transmembrane BAX Inhibitor Motif-6 (TMBIM6) protects against cisplatin-induced testicular toxicity

Kim, Hyun-Kyoung,Yadav, Raj Kumar,Bhattarai, Kashi Raj,Jung, Han-Wool,Kim, Hyung-Ryong,Chae, Han-Jung Oxford University Press 2018 Human reproduction Vol.33 No.3

Metabolic Changes Enhance the Cardiovascular Risk with Differentiated Thyroid Carcinoma - A Case Control Study from Manipal Teaching Hospital of Nepal

Mittal, Ankush,Poudel, Bibek,Pandeya, Dipendra Raj,Gupta, Satrudhan Pd,Sathian, Brijesh,Yadav, Shambhu Kumar Asian Pacific Journal of Cancer Prevention 2012 Asian Pacific journal of cancer prevention Vol.13 No.5

Objective: To evaluate several metabolic changes in patients with differentiated thyroid carcinoma (DTC ) which enhance cardiovascular risk in the western region of Nepal. Materials and Methods: This hospital based case control study was carried out using data retrieved from the register maintained in the Department of Biochemistry of the Manipal Teaching Hospital, Pokhara, Nepal between $1^{st}$ January, 2009 and $31^{st}$ December, 2011. The variables collected were age, gender, BMI, glucose, insulin, HbA1C, CRP, fibrinogen, total cholesterol, triglycerides, HDL, LDL, VLDL, f-T3, f-T4, TSH. One way ANOVA was used to examine statistical significance of differences between groups, along with the Post Hoc test LSD for comparison of means. Results: fT3 values were markedly raised in DTC cases ($5.7{\pm}SD1.4$) when compared to controls ($2.2{\pm}SD0.9$). Similarly, fT4 values were also moderately raised in cases of DTC ($4.9{\pm}SD1.3$ and $1.7{\pm}SD0.9$). In contrast, TSH values were lowered in DTC cases ($0.39{\pm}SD0.4$) when compared to controls ($4.2{\pm}SD1.4$). Mean blood glucose levels were decreased while insulin was increased and HDL reduced ($39.5{\pm}SD4.7$ as compared to the control $43.1{\pm}SD2.2$). Conclusion: Cardiovascular risk may be aggravated by insulin resistance, a hypercoagulable state, and an atherogenic lipid profile in patients with differentiated thyroid cancer.

Sulforaphane prevents doxorubicin-induced oxidative stress and cell death in rat H9c2 cells

LI, BO,KIM, DO SUNG,YADAV, RAJ KUMAR,KIM, HYUNG RYONG,CHAE, HAN JUNG UNKNOWN 2015 INTERNATIONAL JOURNAL OF MOLECULAR MEDICINE Vol.36 No.1

<P>Sulforaphane, a natural isothiocyanate compound found in cruciferous vegetables, has been shown to exert cardioprotective effects during ischemic heart injury. However, the effects of sulforaphane on cardiotoxicity induced by doxorubicin are unknown. Thus, in the present study, H9c2 rat myoblasts were pre-treated with sulforaphane and its effects on cardiotoxicity were then examined. The results revealed that the pre-treatment of H9c2 rat myoblasts with sulforaphane decreased the apoptotic cell number (as shown by trypan blue exclusion assay) and the expression of pro-apoptotic proteins (Bax, caspase-3 and cytochrome <I>c</I>; as shown by western blot analysis and immunostaining), as well as the doxorubicin-induced increase in mitochondrial membrane potential (measured by JC-1 assay). Furthermore, sulforaphane increased the mRNA and protein expression of heme oxygenase-1 (HO-1, measured by RT-qPCR), which consequently reduced the levels of reactive oxygen species (ROS, measured using MitoSOX Red reagent) in the mitochondria which were induced by doxorubicin. The cardioprotective effects of sulforaphane were found to be mediated by the activation of the Kelch-like ECH-associated protein 1 (Keap1)/NF-E2-related factor-2 (Nrf2)/antioxidant-responsive element (ARE) pathway, which in turn mediates the induction of HO-1. Taken together, the findings of this study demonstrate that sulforaphane prevents doxorubicin-induced oxidative stress and cell death in H9c2 cells through the induction of HO-1 expression.</P>

A Comparative Analysis of the Metabolic and Coagulative Profiles in Patients with Idiopathic Scoliosis, Congenital Scoliosis and Healthy Controls: A Case–Control Study

Kaustubh Ahuja,Bhavuk Garg,Buddhadev Chowdhuri,Raj Kumar Yadav,Pradeep Kumar Chaturvedi 대한척추외과학회 2018 Asian Spine Journal Vol.12 No.6

Study Design: Single-center, observational, case–control study. Purpose: Comparison and analysis of the metabolic and coagulative profiles in patients with idiopathic scoliosis, patients with congenital scoliosis, and healthy controls. Overview of Literature: Serum melatonin deficiency has been a controversial topic in the etiopathogenesis of scoliosis. Low bone mineral density, low vitamin D3 levels, and high parathyroid hormone levels are common metabolic abnormalities associated with scoliosis that may be responsible for its pathogenesis. In addition to metabolic defects, several studies have shown coagulation defects that either persist from the preoperative period or occur during surgery and usually lead to more than the expected amount of blood loss in patients undergoing deformity correction for scoliosis. Methods: The study population (n=73) was classified into those having congenital scoliosis (n=31), those with idiopathic scoliosis (n=30), and healthy controls (n=12). After detailed clinicoradiological evaluation of all the subjects, 10-mL blood samples were collected, measured, and analyzed for various metabolic and coagulation parameters. Results: The mean serum melatonin levels in patients with idiopathic scoliosis were significantly lower than those in the healthy controls. Although the mean serum melatonin level in the congenital group was also low, the difference was not statistically significant. Serum alkaline phosphatase and parathyroid hormone levels were higher in the scoliosis groups, whereas the vitamin D level was lower. No differences were observed in the coagulation profiles of the different groups. Conclusions: Low serum melatonin levels associated with scoliosis can be a cause or an effect of scoliosis. Moreover, low bone mineral density, high bone turn over, and negative calcium balance appear to play an important role in the progression, if not the onset, of the deformity.