Various Forms of Silicon Electronic Waste and Predisposition to Cancer

Nilesh Kumar Sharma,Sachin Chakradhar Sarode 대한암예방학회 2023 Journal of cancer prevention Vol.28 No.1

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Optical dating of late Quaternary carbonate sequences of Saurashtra, western India

Sharma, Komal,Bhatt, Nilesh,Shukla, Anil Dutt,Cheong, Dae-Kyo,Singhvi, Ashok Kumar Cambridge University Press 2017 Quaternary research Vol.87 No.1

<B>Abstract</B><P>Bioclastic carbonate deposits that formed because of a combination of nearshore marine, fluvial, and aeolian processes, occur along the Saurashtra coast and in the adjacent interior regions of western India. Whether these carbonates formed by marine or aeolian processes has been debated for many decades. The presence of these deposits inland poses questions as to whether they are climate controlled or attributable to postdepositional tectonic uplift. In particular, the debate centres on chronologic issues including (1) appropriate sampling strategies and (2) the use of <SUP>230</SUP>Th/<SUP>234</SUP>U and <SUP>14</SUP>C ages on the bulk carbonates. Using traces (<1%) of quartz grains trapped in carbonate matrices, optically stimulated luminescence (OSL) dating of quartz grains, deposited along with the carbonate grains, provides ages for the most recent deposition events. The OSL ages range from >165 to 44 ka for the shell limestones, 75-17 ka for the fluvially reworked sheet deposits, and 80-11 ka for miliolites deposited by aeolian processes. These are younger than the <SUP>230</SUP>Th/<SUP>234</SUP>U and <SUP>14</SUP>C ages and suggest that the inland carbonate deposits were reworked from older carbonate sediments that were transported during more arid phases.</P>

Non-homologous End Joining Inhibitor SCR-7 to Exacerbate Low-dose Doxorubicin Cytotoxicity in HeLa Cells

Ajay Kumar,Devyani Bhatkar,Devashree Jahagirdar,Nilesh Kumar Sharma 대한암예방학회 2017 Journal of cancer prevention Vol.22 No.1

Among the genotoxic drug regimens, doxorubicin (DOX) is known for its high-dose side effects in several carcinomas, including cervical cancer. This study reports on testing the combined use of a DOX genotoxic drug and SCR-7 non-homologous end joining (NHEJ) inhibitor for HeLa cells. An in vitro DNA damaging assay of DOX was performed on plasmid and genomic DNA substrate. In vitro cytotoxicity was investigated using trypan blue dye exclusion, DNA metabolizing, and propidium iodide-based flow cytometric assays. DOX (between 20-100 M) displayed clear DNA binding and interaction, such as the shearing and smearing of plasmid and genomic DNA. DNA metabolizing assay data indicate that HeLa lysate with DOX and SCR-7 treatment exhibited better in vitro plasmid DNA stability compared with DOX treatment alone. SCR-7 augmented the effects of low-dose DOX by demonstrating enhanced cell death from 15% to 50%. The flow cytometric data also supported that the combination of SCR-7 with DOX lead to a 23% increase in propidium iodide-based HeLa staining, thus indicating enhanced death. In summary, the inhibition of NHEJ DNA repair pathway can potentiate low-dose DOX to produce appreciable cytotoxicity in HeLa cells.

Elevated N1-Acetylspermidine Levels in Doxorubicintreated MCF-7 Cancer Cells: Histone Deacetylase 10 Inhibition with an N1-Acetylspermidine Mimetic

Ajay Kumar Raj,Kiran Bharat Lokhande,Kratika Khunteta,Sachin Chakradhar Sarode,Nilesh Kumar Sharma 대한암예방학회 2024 Journal of cancer prevention Vol.29 No.2

Cancer drug resistance is associated with metabolic adaptation. Cancer cells have been shown to implicate acetylated polyamines in adaptations during cell death. However, exploring the mimetic of acetylated polyamines as a potential anticancer drug is lacking. We performed intracellular metabolite profiling of human breast cancer MCF-7 cells treated with doxorubicin (DOX), a well known anticancer drug. A novel and in-house vertical tube gel electrophoresis assisted procedure followed by LC-HRMS analysis was employed to detect acetylated polyamines such as N1-acetylspermidine. We designed a mimetic N1-acetylspermidine (MINAS) which is a known substrate of histone deacetylase 10 (HDAC10). Molecular docking and molecular dynamics (MDs) simulations were used to evaluate the inhibitory potential of MINAS against HDAC10. The inhibitory potential and the ADMET profile of MINAS were compared to a known HDAC10 inhibitor Tubastatin A. N1-acetylspermidine, an acetylated form of polyamine, was detected intracellularly in MCF-7 cells treated with DOX over DMSO-treated MCF-7 cells. We designed and curated MINAS (PubChem CID 162679241). Molecular docking and MD simulations suggested the strong and comparable inhibitory potential of MINAS (–8.2 kcal/ mol) to Tubastatin A (–8.4 kcal/mol). MINAS and Tubastatin A share similar binding sites on HDAC10, including Ser138, Ser140, Tyr183, and Cys184. Additionally, MINAS has a better ADMET profile compared to Tubastatin A, with a high MRTD value and lower toxicity. In conclusion, the data show that N1-acetylspermidine levels rise during DOX-induced breast cancer cell death. Additionally, MINAS, an N1-acetylspermidine mimetic compound, could be investigated as a potential anticancer drug when combined with chemotherapy like DOX.

Aberrant DNA Double-strand Break Repair Threads in Breast Carcinoma: Orchestrating Genomic Insult Survival

Azad Kumar,Shruti Purohit,Nilesh Kumar Sharma 대한암예방학회 2016 Journal of cancer prevention Vol.21 No.4

Breast carcinoma is a heterogeneous disease that has exhibited rapid resistance to treatment in the last decade. Depending genotype and phenotype of breast cancer, there are discernible differences in DNA repair protein responses including DNA double strand break repair. It is a fact that different molecular sub-types of breast carcinoma activate these dedicated protein pathways in a distinct manner. The DNA double-strand damage repair machinery is manipulated by breast carcinoma to selectively repair the damage or insults inflicted by the genotoxic effects of chemotherapy or radiation therapy. The two DNA double-strand break repair pathways employed by breast carcinoma are homologous recombination and non-homologous end joining. In recent decades, therapeutic interventions targeting one or more factors involved in repairing DNA double-strand breaks inflicted by chemo/radiation therapy have been widely studied. Herein, this review paper summarizes the recent evidence and ongoing clinical trials citing potential therapeutic combinatorial interventions targeting DNA double-strand break repair pathways in breast carcinoma.

Understanding Heavy Metal Stress in a Rice Crop: Toxicity, Tolerance Mechanisms, and Amelioration Strategies

Namira Arif,Nilesh C. Sharma,Vaishali Yadav,Naleeni Ramawat,Nawal Kishore Dubey,Durgesh Kumar Tripathi,Devendra Kumar Chauhan,Shivendra Sahi 한국식물학회 2019 Journal of Plant Biology Vol.62 No.4

Heavy metal (HMs) pollution is regarded as oneof the major concerns for soil and water, causing varieties oftoxic and stress effects on plants and ecosystems. It hasbecome one of the important limiting factors to cropproductivity and quality. Due to an ever-increasing populationgrowth and food demands, this situation has further worsened. Rice, a leading staple food crop that feeds more than 50%populations of the world, is constantly affected by abioticstressors including HMs. In most of the countries, a majorsource of HM intake by humans is the rice grain producedthrough the paddy soils contaminated with HMs such as As,Al, Cu, Cr, Cd, Pb, Hg, Mn, Se, and Zn. Thus, gradualagglomeration of HMs in rice grains and their subsequenttransfer to the food chain is a major menace to agricultureand human health. In recent years, several studies examinedthe impact of HMs toxicity on rice at multiple levels:molecular, biochemical, physiological, cellular and tissue,and demonstrated a correlation between HMs toxicity andthe decreasing trend in rice productivity. Therefore, it isnecessary to understand the interaction of HMs with ricecrop spanning from the cell to whole plant level and deviseappropriate effective means to alleviate these stress responses. This review focuses on tracing the pathways involved instress responses and stress tolerance mechanisms displayedby different varieties of rice. However, it is essential touncover the mechanisms related to stress responses in ricefor designing improved investigations to develop novelvarieties with high attributes. Therefore, this communication summarizes various defense strategies induced against HMstress and includes the function of metabolites (metabolomics),trace elements (ionomics), transcription factors (transcriptomics),and various stress-inducible proteins (proteomics) includingthe role of plant hormones.

Epigenomic Hard Drive Imprinting: A Hidden Code Beyond the Biological Death of Cancer Patients

Pritish Nilendu,Nilesh Kumar Sharma 대한암예방학회 2017 Journal of cancer prevention Vol.22 No.4

Several genetic and epigenetic theories have been suggested to explain the intricacies of life and death. However, several questions remain unsettled regarding cellular death events, particularly of living tissue in the case of cancer patients, such as the fate and adaptation of cancer cells after biological death. It is possible that cancer cells can display the intent to communicate with the external environment after biological death by means of molecular, genetic, and epigenetic pathways. Whether these cancer cells contain special information in the form of coding that may help them survive beyond the biological death of cancer patients is unknown. To understand these queries in the cancer field, we hypothesize the epigenomic hard drive (EHD) as a cellular component to record and store global epigenetic events in cancerous and non-cancerous tissues of cancer patients. This mini-review presents the novel concept of EHD that is reinforced with the existing knowledge of genetic and epigenetic events in cancer. Further, we summarize the EHD understanding that may impart much potential and interest for basic and clinical scientists to unravel mechanisms of carcinogenesis, therapeutic markers, and differential drug responses.

Evaluating the Pathway for Co-fermentation of Glucose and Xylose for Enhanced Bioethanol Production Using Flux Balance Analysis

Richa Arora,Shuvashish Behera,Nilesh Kumar Sharma,Sachin Kumar 한국생물공학회 2019 Biotechnology and Bioprocess Engineering Vol.24 No.6

Two novel thermotolerant yeasts, Kluyveromyces marxianus NIRE-K1.1 and Kluyveromyces marxianus NIRE-K3.1, evolutionarily adapted for fermentation of glucose and xylose were analyzed for their metabolic fluxes with an objective of maximum ethanol production. Metabolic fluxes were analyzed for these thermotolerant yeasts by co-fermenting glucose/xylose mixture in two different ratios (1:1 and 4:1). Flux balance analysis revealed the active role of pentose phosphate pathway for effective xylose utilization in both yeasts. A comparison between co-fermentation of glucose/xylose mixtures in the ratio of 1:1 and 4:1 (g/L) reveals that the flux from glucose-6- phosphate to ribulose-5-phosphate was approximately 2.56-fold and 3.75-fold higher in 1:1 mixture in K. marxianus NIRE-K1.1 and K. marxianus NIRE-K3.1, respectively. Overall, flux towards pyruvate (for ethanol production) was found to be higher in both glucose/xylose mixtures 1:1 (1.87%) and 4:1 (0.89%) for K. marxianus NIRE-K3.1 than K. marxianus NIRE-K1.1. Tricarboxylic Acid (TCA) cycle was also found to be incomplete for both the isolates which signify that most of the available substrates were utilized for ethanol production rather than biomass formation. Moreover, it was also observed that in both, the ethanol yields were found to be higher in case of K. marxianus NIRE-K3.1 than K. marxianus NIRE-K1.1, however, xylose uptake rates were higher in the later as compared to the former. Thus, this study concludes with the capable potential of both the yeasts for the production of bioethanol from glucose/xylose mixtures with higher yield and is highly correlated to the relative concentration of both xylose and glucose in a mixture.

Investigation of transport of radionuclide in a thermal stratification test facility using radiotracer technique

Harish Jagat Pant,Sunil Goswami,Sunil B. Chafle,Vijay Kumar Sharma,Vimal Kotak,Vikram Shukla,Amitanshu Mishra,Nilesh C. Gohel,Sujay Bhattacharya 한국원자력학회 2022 Nuclear Engineering and Technology Vol.54 No.4

A radiotracer investigation was carried out in a Thermal Stratification Test Facility (TSTF) with objectivesof investigating the dispersion and diffusion of radionuclide and effectiveness of the thermocline tominimize the radionuclide content in the hot water layer. Technetium-99m (99mTc) as sodium pertechnetate was used as a radiotracer in the investigation. Qualitative analysis showed that a thermoclineis formed within the TSTF and is effective in preventing the transport of radionuclide from bottomsection to the top section of the facility. It was found that the radiotracer injected at the bottom of thepool took about 17.4 h to disperse from bottom to the top of the facility. The results of the investigationhelped in understanding the effectiveness of hot water layer and thus to minimize the pool top radiationlevels.

Organic Acids Derived from Saliva-amalgamated Betel Quid Filtrate Are Predicted as a Ten-eleven Translocation-2 Inhibitor

Bhatkar Devyani,Ananda Nistha,Lokhande Kiran Bharat,Khunteta Kratika,Jain Priyadarshini,Hebale Ameya,Sarode Sachin C.,Sharma Nilesh Kumar 대한암예방학회 2023 Journal of cancer prevention Vol.28 No.3

There is a lack of evidence regarding the use of betel quid (BQ) and its potential contribution to oral cancer. Limited attention has been directed towards investigating the involvement of BQ-derived organic acids in the modulation of metabolic-epigenomic pathways associated with oral cancer initiation and progression. We employed novel protocol for preparing saliva-amalgamated BQ filtrate (SABFI) that mimics the oral cavity environment. SABFI and saliva control were further purified by an in-house developed vertical tube gel electrophoresis tool. The purified SABFI was then subjected to liquid chromatography-high resolution mass spectrometry analysis to identify the presence of organic acids. Profiling of SABFI showed a pool of prominent organic acids such as citric acid. malic acid, fumaric acid, 2-methylcitric acid, 2-hydroxyglutarate, cis-aconitic acid, succinic acid, 2-hydroxyglutaric acid lactone, tartaric acid and β-ketoglutaric acid. SABFI showed anti-proliferative and early apoptosis effects in oral cancer cells. Molecular docking and molecular dynamics simulations predicted that SABFI-derived organic acids as potential inhibitors of the epigenetic demethylase enzyme, Ten-Eleven Translocation-2 (TET2). By binding to the active site of α-ketoglutarate, a known substrate of TET2, these organic acids are likely to act as competitive inhibitors. This study reports a novel approach to study SABFI-derived organic acids that could mimic the chemical composition of BQ in the oral cavity. These SABFI-derived organic acids projected as inhibitors of TET2 and could be explored for their role oral cancer