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>

Interleukin-1B (IL-1B-31 and IL-1B-511) and interleukin-1 receptor antagonist (IL-1Ra) gene polymorphisms in primary immune thrombocytopenia

Deependra Kumar Yadav,Anil Kumar Tripathi,Divya Gupta,Saurabh Shukla,Aloukick Kumar Singh,Ashutosh Kumar,Jyotsna Agarwal,K. N. Prasad 대한혈액학회 2017 Blood Research Vol.51 No.4

Background: Immune thrombocytopenia (ITP) is an immune-mediated disease caused by autoanti-bodies against platelets membrane glycoproteins GPIIb/IIIa and GPIb/IX. The etiology of ITP remains unclear. This study evaluated the association of polymorphisms in interleukin (IL)-1B-31, IL-1B-511, and IL-1Ra with ITP. Methods: Genotyping of IL-1B-31, IL-1B-511, and IL-1Ra was performed in 118 ITP patients and 100 controls by polymerase chain reaction restriction fragment length polymorphism and detection of variable number tandem repeats. Results: Genotype differences in IL-1B-31 and IL-1Ra were significantly associated with ITP. Patients showed a higher frequency of the IL-1B-31 variant allele (T) and a 1.52-fold greater risk of susceptibility to ITP (odds ratio [OR]=1.52, 95% confidence interval [CI]=1.04‒2.22, P=0.034). The frequencies of both homozygous and heterozygous variant geno-types of IL-1B-31 were higher (OR=2.33, 95% CI=1.069‒5.09, P=0.033 and OR=2.044, 95% CI=1.068‒39, P=0.034) among patients and were significantly associated with ITP susceptibility. Both homozygous and heterozygous variant genotypes of IL-1Ra were also more frequent (OR=4.48, 95% CI=1.17‒17.05, P=0.0230 and OR=1.80, 95% CI=1.03‒3.14, P=0.0494) among patients and were associated with ITP risk. IL-1B-31 and IL-1Ra also showed significant association with severe ITP. However, IL-1B-511 was not asso-ciated with ITP. Conclusion: IL-1B-31 and IL-1Ra polymorphisms may significantly impact ITP risk, and they could be associated with disease severity, which may contribute to the pathogenesis of ITP.

Vibration upshot of operating mechanical sewing machine

Prakash Kumar Yadav,Ram Lochan Yadav,Deepak Sharma,Dev Kumar Shah,Niraj Khatri Sapkota,Dilip Thakur,Nirmala Limbu,Md Nazrul Islam 대한직업환경의학회 2017 대한직업환경의학회지 Vol.29 No.-

Background: Most of the people associated with tailoring occupation in Nepal are still using mechanical sewing machine as an alternative of new technology for tailoring. Common peroneal nerves of both right and left legs are exposed to strenuous and chronic stress exerted by vibration and paddling of mechanical sewing machine. Methods: The study included 30 healthy male tailors and 30 healthy male individuals. Anthropometric variables as well as cardio respiratory variables were determined for each subject. Standard Nerve Conduction Techniques using constant measured distances were applied to evaluate common peroneal nerve (motor) in both legs of each individual. Data were analyzed and compared between study and control groups using Man Whitney U test setting the significance level p ≤ 0.05. Results: Anthropometric and cardio respiratory variables were not significantly altered between the study and control groups. The Compound muscle action potential (CMAP) latency of common peroneal nerves of both right [(11.29 ± 1.25 vs. 10.03 ± 1.37), P < 0.001] and left [(11.28 ± 1.38 vs. 10.05 ± 1.37), P < 0.01] legs was found to be significantly prolonged in study group as compared to control group. The Amp-CMAP of common peroneal nerves of both right [(4.57 ± 1.21 vs. 6.22 ± 1.72), P < 0.001] and left [(4.31 ± 1.55 vs. 6.25 ± 1.70), P < 0.001] legs was found significantly reduced in study group as compared to control group. Similarly, the motor nerve conduction velocity (MNCV) of common peroneal nerves of both right [(43.72 ± 3.25 vs. 47.49 ± 4.17), P < 0.001] and left [(42.51 ± 3.82 vs. 46.76 ± 4.51), P < 0.001] legs was also found to be significantly reduced in study group in comparison to control group. Conclusion: Operating mechanical sewing machine by paddling chronically and arduously could have attributed to abnormal nerve conduction study parameters due to vibration effect of the machine on right and left common peroneal nerves. The results of present study follow the trend towards presymptomatic or asymptomatic neuropathy similar to subclinical neuropathy.

Interleukin-1B (IL-1B-31 and IL-1B-511) and interleukin-1 receptor antagonist (IL-1Ra) gene polymorphisms in primary immune thrombocytopenia

Deependra Kumar Yadav,Anil Kumar Tripathi,Divya Gupta,Saurabh Shukla,Aloukick Kumar Singh,Ashutosh Kumar,Jyotsna Agarwal,K. N. Prasad 대한혈액학회 2017 Blood Research Vol.52 No.4

Background: Immune thrombocytopenia (ITP) is an immune-mediated disease caused by autoanti-bodies against platelets membrane glycoproteins GPIIb/IIIa and GPIb/IX. The etiology of ITP remains unclear. This study evaluated the association of polymorphisms in interleukin (IL)-1B-31, IL-1B-511, and IL-1Ra with ITP. Methods: Genotyping of IL-1B-31, IL-1B-511, and IL-1Ra was performed in 118 ITP patients and 100 controls by polymerase chain reaction restriction fragment length polymorphism and detection of variable number tandem repeats. Results: Genotype differences in IL-1B-31 and IL-1Ra were significantly associated with ITP. Patients showed a higher frequency of the IL-1B-31 variant allele (T) and a 1.52-fold greater risk of susceptibility to ITP (odds ratio [OR]=1.52, 95% confidence interval [CI]=1.04‒2.22, P=0.034). The frequencies of both homozygous and heterozygous variant geno-types of IL-1B-31 were higher (OR=2.33, 95% CI=1.069‒5.09, P=0.033 and OR=2.044, 95% CI=1.068‒39, P=0.034) among patients and were significantly associated with ITP susceptibility. Both homozygous and heterozygous variant genotypes of IL-1Ra were also more frequent (OR=4.48, 95% CI=1.17‒17.05, P=0.0230 and OR=1.80, 95% CI=1.03‒3.14, P=0.0494) among patients and were associated with ITP risk. IL-1B-31 and IL-1Ra also showed significant association with severe ITP. However, IL-1B-511 was not asso-ciated with ITP. Conclusion: IL-1B-31 and IL-1Ra polymorphisms may significantly impact ITP risk, and they could be associated with disease severity, which may contribute to the pathogenesis of ITP.

Oxidative Stress and Antioxidants in Disease and Cancer: A Review

Gupta, Rakesh Kumar,Patel, Amit Kumar,Shah, Niranjan,Choudhary, Arun Kumar,Jha, Uday Kant,Yadav, Uday Chandra,Gupta, Pavan Kumar,Pakuwal, Uttam Asian Pacific Journal of Cancer Prevention 2014 Asian Pacific journal of cancer prevention Vol.15 No.11

Reactive oxygen species (ROS), highly reactive molecules, are produced by living organisms as a result of normal cellular metabolism and environmental factors, and can damage nucleic acids and proteins, thereby altering their functions. The human body has several mechanisms to counteract oxidative stress by producing antioxidants. A shift in the balance between oxidants and antioxidants in favor of oxidants is termed as "oxidative stress". Paradoxically, there is a large body of research demonstrating the general effect of oxidative stress on signaling pathways, less is known about the initial and direct regulation of signaling molecules by ROS, or what we term the "oxidative interface." This review focuses on the molecular mechanisms through which ROS directly interact with critical signaling molecules to initiate signaling in a broad variety of cellular processes, such as proliferation and survival (MAP kinases and PI3 kinase), ROS homeostasis, and antioxidant gene regulation (Ref-1 and Nrf-2). This review also deals with classification as well as mechanisms of formation of free radicals, examining their beneficial and deleterious effects on cellular activities and focusing on the potential role of antioxidants in preventing and repairing damage caused by oxidative stress. A discussion of the role of phytochemical antioxidants in oxidative stress, disease and the epigenome is included.

Composition of Artificial Tear Solution Affects <i>In Vitro Pseudomonas aeruginosa</i> Biofilm Formation on Silicone Hydrogel Lens

Yadav, Mukesh Kumar,Chuck, Roy S.,Park, Choul Yong Mary Ann Liebert 2013 Journal of ocular pharmacology and therapeutics Vol.29 No.6

<P>To investigate Pseudomonas aeruginosa biofilm formation on silicone hydrogel contact lens in various artificial tears.</P>

Understanding cross-tolerance mechanism and effect of drought priming on individual heat stress and combinatorial heat and drought stress in chickpea

Yadav Renu,Juneja Sumandeep,Kumar Rashpal,Saini Rashmi,Kumar Sanjeev 한국작물학회 2022 Journal of crop science and biotechnology Vol.25 No.5

In northern India, chickpea experiences abrupt heat and drought stress during the late developmental stage and entails significant production loss. In the present study, the effect of heat stress and combined stress (heat and drought) was assessed in five varieties of chickpea along with the underlying mechanism of cross-tolerance by priming. Healthy seedlings (24 days old) were primed with mild drought stress and exposed to three different temperatures, i.e., 38 °C, 35 °C, and 32 °C for 12, 24, and 36 h respectively, and also in combination with drought. The damage and tolerance were evaluated based on biochemical and physiological indicators. Results indicate that significant response was observed at 35 °C as compared to 32 and 38 °C in terms of decrease in leaf water content, increased electrolyte leakage and lipid peroxidation, decreased chlorophyll content, increased accumulation of proline and total sugars, and increased antioxidative activity of superoxide dismutase, catalase, guaiacol peroxidase, ascorbate peroxidase, and glutathione reductase. The consequence of combined stress was more distinct than the individual heat stress and cannot be extrapolated from the synergistic effect of the two stresses. In addition, priming induced cross-tolerance at 35 °C by improving the membrane damage, photorespiration, photosynthetic pigment, osmolyte accumulation, and some antioxidative enzymes. On the basis of all the above parameters, PDG4 was identified as the best performing variety and tolerant to heat stress while GPF2 was the worst performing and sensitive to heat stress. It can be inferred that both severity and duration of stress are important and priming can be considered as an important tool to induce cross-tolerance in crop plants.

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.

Creating Backup Management Resources for Spine Care during the Coronavirus Disease 2019 Pandemic

Yadav Sandeep Kumar,Kar Bikram Keshri,Banta Aditya,Kumar Awkash 대한척추외과학회 2020 Asian Spine Journal Vol.14 No.3

During this unprecedented time of the coronavirus disease 2019 (COVID 19) pandemic, most countries are struggling to optimize their healthcare resources. Although the prevention and treatment of COVID 19 has become the priority for the majority of the population, most medical professionals are facing the challenge of balancing the management of this pandemic and treating patients with other diseases. Healthcare professionals from all specialties are facing this situation and designing guidelines and recommendations that are contributing to the literature that is crucial for disease management at the current time. We share our experience with two ends of the spectra that we currently observe in spine patients. One group of patients included the non-operative cases that presented with back pain. Further, we discuss our experience with operative precautions and digitally assisted discharge.

Extensive Extra-laryngeal Branching and Sympathetic Anastomosis of Recurrent Laryngeal Nerve: Nerve Wracking Trap

Yadav Sanjay Kumar,Silodia Ashutosh,Anand Aaryan,B Rajesh,Rai Roshni 대한내분비외과학회 2021 The Koreran journal of Endocrine Surgery Vol.21 No.2

Damage to the recurrent laryngeal nerves (RLNs) is one of the dreaded complications of thyroid and parathyroid surgery (1). In case of anatomical variations this risk is further increased. Terminal branching of RLN occurs anywhere from several centimeters from the cricothyroid muscle to within the larynx itself (2). Prevalence of extra-laryngeal branching (ELB) is reported to be around 60% (3). Another anatomical variation is anastomosis between RLN, and the cervical sympathetic chain known as sympathetic inferior laryngeal anastomotic branch (SILAB) which is rare (1%–2%) (4). We recently operated upon a patient of papillary thyroid carcinoma and encountered both these anatomic variations.