School Of Basic And Applied Sciences
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Item Regulation of thymidylate synthase: an approach to overcome 5-FU resistance in colorectal cancer(Springer, 2022-10-29T00:00:00) Kumar, Adarsh; Singh, Ankit Kumar; Singh, Harshwardhan; Thareja, Suresh; Kumar, PradeepThymidylate synthase is the rate-limiting enzyme required for DNA synthesis and overexpression of this enzyme causes resistance to cancer cells. Long treatments with 5-FU cause resistance to Thymidylate synthase targeting drugs. We have also compiled different mechanisms of drug resistance including autophagy and apoptosis, drug detoxification and ABC transporters, drug efflux, signaling pathways (AKT/PI3K, RAS-MAPK, WNT/? catenin, mTOR, NFKB, and Notch1 and FOXM1) and different genes associated with resistance in colorectal cancer. We can overcome 5-FU resistance in cancer cells by regulating thymidylate synthase by natural products (Coptidis rhizoma), HDAC inhibitors, mTOR inhibitors, Folate antagonists, and several other drugs which have been used in combination with TS inhibitors. This review is a compilation of different approaches reported for the regulation of thymidylate synthase to overcome resistance in colorectal cancer cells. Graphical abstract: [Figure not available: see fulltext.] � 2022, The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.Item Thiazole and Related Heterocyclic Systems as Anticancer Agents: A Review on Synthetic Strategies, Mechanisms of Action and SAR Studies(Bentham Science Publishers, 2022-03-21T00:00:00) Sahil; Kaur, Kamalpreet; Jaitak, VikasBackground: Cancer is the second leading cause of death worldwide. Many anticancer drugs are commercially available, but lack of selectivity, target specificity, cytotoxicity, and development of resistance lead to serious side effects. Several experiments have been going on to develop compounds with minor or no side effects. Objective: This review mainly emphasizes synthetic strategies, SAR studies, and mechanism of action if thiazole, benzothiazole, and imidazothiazole-containing compounds as anticancer agents. Methods: Recent literature related to thiazole and thiazole-related derivatives endowed with encouraging anticancer potential is reviewed. This review emphasizes contemporary strategies used for the synthesis of thiazole and related derivatives, mechanistic targets, and comprehensive structural activity relationship studies to provide perspective into the rational design of high-efficiency thiazole-based anticancer drug candidates. Results: Exhaustive literature survey indicated that thiazole derivatives are associated with properties of inducing apoptosis and disturbing tubulin assembly. Thiazoles are also associated with the inhibition of NFkB/mTOR/PI3K/AkT and regulation of estrogenmediated activity. Furthermore, thiazole derivatives have been found to modulate critical targets, such as topoisomerase and HDAC. Conclusion: Thiazole derivatives seem to be quite competent and act through various mechanisms. Some of the thiazole derivatives, such as compounds 29, 40, 62, and 74a with IC50 values of 0.05 ?M, 0.00042 ?M, 0.18 ?M, and 0.67 ?M, respectively, not only exhibit anticancer activity, but they also have lower toxicity and better absorption. Therefore, some other similar compounds could be investigated to aid in the development of anticancer pharmacophores. � 2022 Bentham Science Publishers.Item Genome recoding: a review of basic concepts, current research and future prospects of virus attenuation for controlling plant viral diseases(Springer, 2020-08-10T00:00:00) Kumar, Vinay; Singh, TanyaPlants are very susceptible to pathogens and every year, 25% of crop loss is caused by various types of pathogens including viruses. Many different strategies are being used for developing resistance against virus infection, including RNA silencing, and the genome editing including CRISPR-Cas-9 but these may produce variants/recombinants and could cause the problems for future crops. Another promising approach named as genome recoding or rewriting would be a better potential tool for controlling viral infections in plants. It relies on the concepts of replacement of synonymous codons, change in codon bias, codon pair bias and dinucleotide content. Recoding of the genome does not alter the amino acid sequences but it affects the expression level and translation efficiency. In the present report, the concept of synonymous codons, the basics of genome recoding and the possible strategies to generate genome recoded organisms are provided in details. Viral attenuation has been achieved by consideration of dinucleotide bias and codon pair bias manipulations and used in the synthesis of vaccines against various types of pathogenic bacteria and viruses. The idea of the future scope of genome recoding for developing virus-resistant plants and their challenges for the same are also comprehensively discussed. Although genome recoding is not yet tested on plants, however it could be very helpful in controlling plant viral diseases. So, it is a novel emerging area of research for developing viral resistant plants and thus would help in minimizing the agricultural losses in the near future. � 2020, Society for Plant Biochemistry and Biotechnology.Item Genome recoding: a review of basic concepts, current research and future prospects of virus attenuation for controlling plant viral diseases(Springer, 2020-08-10T00:00:00) Kumar, Vinay; Singh, TanyaPlants are very susceptible to pathogens and every year, 25% of crop loss is caused by various types of pathogens including viruses. Many different strategies are being used for developing resistance against virus infection, including RNA silencing, and the genome editing including CRISPR-Cas-9 but these may produce variants/recombinants and could cause the problems for future crops. Another promising approach named as genome recoding or rewriting would be a better potential tool for controlling viral infections in plants. It relies on the concepts of replacement of synonymous codons, change in codon bias, codon pair bias and dinucleotide content. Recoding of the genome does not alter the amino acid sequences but it affects the expression level and translation efficiency. In the present report, the concept of synonymous codons, the basics of genome recoding and the possible strategies to generate genome recoded organisms are provided in details. Viral attenuation has been achieved by consideration of dinucleotide bias and codon pair bias manipulations and used in the synthesis of vaccines against various types of pathogenic bacteria and viruses. The idea of the future scope of genome recoding for developing virus-resistant plants and their challenges for the same are also comprehensively discussed. Although genome recoding is not yet tested on plants, however it could be very helpful in controlling plant viral diseases. So, it is a novel emerging area of research for developing viral resistant plants and thus would help in minimizing the agricultural losses in the near future. � 2020, Society for Plant Biochemistry and Biotechnology.Item MicroRNAs Involved in Nutritional Regulation During Plant�Microbe Symbiotic and Pathogenic Interactions with Rice as a Model(Springer, 2023-07-19T00:00:00) Yadav, Radheshyam; Ramakrishna, WusirikaPlants are constantly challenged with numerous adverse environmental conditions, including biotic and abiotic stresses. Coordinated regulation of plant responses requires crosstalk between regulatory pathways initiated by different external cues. Stress induced by excessiveness or deficiency of nutrients has been shown to positively or negatively interact with pathogen-induced immune responses. Also, colonization by arbuscular mycorrhizal (AM) fungi can improve plant nutrition, mainly phosphorus and resistance to pathogen infection. The proposed review addresses these issues about a new question that integrates adaptation to nutrient stress and disease resistance. The main goal of the current review is to provide insights into the interconnected regulation between nutrient signaling and immune signaling pathways in rice, focusing on phosphate, potassium and iron signaling. The underpinnings of plant/pathogen/AM fungus interaction concerning rice/M. oryzae/R. irregularis is highlighted. The role of microRNAs (miRNAs) involved in Pi (miR399, miR827) and Fe (miR7695) homeostasis in pathogenic/symbiotic interactions in rice is discussed. The intracellular dynamics of membrane proteins that function in nutrient transport transgenic rice lines expressing fluorescent protein fusion genes are outlined. Integrating functional genomic, nutritional and metal content, molecular and cell biology approaches to understand how disease resistance is regulated by nutrient status leading to novel concepts in fundamental processes underlying plant disease resistance will help to devise novel strategies for crop protection with less input of pesticides and fertilizers. � 2023, The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.Item Drug Targeting Strategies in Breast Cancer Treatment(Bentham Science, 2014) Mayank; Jaitak, VikasBreast cancer (BC) is the leading cause of death among women all over the world. Estrogen receptor (ER) based therapy is one of the major approaches to target BC and is associated with various problems such as primary as well as secondary resistance. ER signaling is a complex pathway as many factors are involved; including several types of ERs and their associated co-regulators. Increasing understanding of ER signals results in new approaches targeting towards BCs. In this context, ER co-regulators have been explored and many modulators of ER co-regulators have been found out. EGFR and mTOR pathways also have significant impact on BC endocrine therapy because of the complex crosstalk mechanism which is responsible for primary and secondary resistance. Triple negative breast cancer (TNBC) is majorly associated with BRCA mutations. Currently there is no approved targeted therapy available in such form of cancer. Although PARP inhibitors seem to be suitable candidates for it. The present review is focused on the current scenario of ER, EGFR, as well as mTOR signaling target therapy. We have also discussed the current status of PARP inhibitors in BC chemotherapy.