Department Of Biochemistry And Microbial Sciences
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Item Polydopamine films change their physicochemical and antimicrobial properties with a change in reaction conditions(Royal Society of Chemistry, 2018) Patel, Khushbu; Singh, Nimisha; Yadav, Jyoti; Nayak, Jyotsna M.; Sahoo, Suban K; Lata, Jeevan; Chand, Duni; Kumar, Shashank; Kumar, RajenderThe morphology and physicochemical properties of polydopamine are not totally inherent and undergo changes with differing reaction conditions like the choice of solvent used for polymerization. The polymerisation of dopamine to polydopamine carried out in different solvents like sodium hydroxide, sodium bicarbonate, PBS and Tris leads to polydopamine with exceptionally different morphological and physicochemical features with each solvent. Additionally, the different physicochemical characteristics and morphologies bestow the polymer films with different extents of antimicrobial activity. Moreover, the findings supported by chemical evidence from X-ray photoelectron spectroscopy reveal that higher antibacterial activities were obtained against E. coli and S. aureus with polydopamine films prepared by Tris and NaOH solvent induced polymerization. The antibacterial activity observed in saline was found to be higher than that in PBS medium for both E. coli and S. aureus. The higher antibacterial activity of polydopamine films prepared in Tris and NaOH solvents was attributed to the covalent incorporation of -OH groups on the surface provided by nucleophilic Tris and NaOH solvents during the polymerisation process. The distinct physicochemical and morphological changes were supported by the results from contact angle measurements, FE-SEM, EDAX, AFM, and XPS analysis. The present finding provides insight into the different chemistry, morphologies and properties of the designed polydopamine films with controlled antibacterial/antifouling properties. Additionally, new insights into the mechanism of formation, physicochemical changes in morphology and properties of polydopamine coatings were revealed. ? the Owner Societies.Item Oxidative stress-related microRNAs as diagnostic markers: A newer insight in diagnostics(Springer Singapore, 2017) Kumar, Shashank; Pandey, Abhay K.[No abstract available]Item Geminin a multi task protein involved in cancer pathophysiology and developmental process: A review(Elsevier B.V., 2016) Kushwaha, Prem Prakash; Rapalli, Krishna Chaitanya; Kumar, ShashankDNA replicates in a timely manner with each cell division. Multiple proteins and factors are involved in the initiation of DNA replication including a dynamic interaction between Cdc10-dependent transcript (Cdt1) and Geminin (GMNN). A conformational change between GMNN-Cdt1 heterotrimer and heterohexamer complex is responsible for licensing or inhibition of the DNA replication. This molecular switch ensures a faithful DNA replication during each S phase of cell cycle. GMNN inhibits Cdt1-mediated minichromosome maintenance helicases (MCM) loading onto the chromatin-bound origin recognition complex (ORC) which results in the inhibition of pre-replication complex assembly. GMNN modulates DNA replication by direct binding to Cdt1, and thereby alters its stability and activity. GMNN is involved in various stages of development such as pre-implantation, germ layer formation, cell commitment and specification, maintenance of genome integrity at mid blastula transition, epithelial to mesenchymal transition during gastrulation, neural development, organogenesis and axis patterning. GMNN interacts with different proteins resulting in enhanced hematopoietic stem cell activity thereby activating the development-associated genes' transcription. GMNN expression is also associated with cancer pathophysiology and development. In this review we discussed the structure and function of GMNN in detail. Inhibitors of GMNN and their role in DNA replication, repair, cell cycle and apoptosis are reviewed. Further, we also discussed the role of GMNN in virus infected host cells. ? 2016 Elsevier B.V. and Soci?t? Fran?aise de Biochimie et Biologie Mol?culaire (SFBBM)Item Natural Compounds Are Smart Players in Context to Anticancer Potential of Receptor Tyrosine Kinases: An In Silico and In Vitro Advancement(Springer, 2017) Singh, Pushpendra; Kumar, Shashank; Bast, FelixCancer is the ruling cause of mortality worldwide. Chemotherapeutic toxicity and drug resistance have provided impulsion for the formulation of new anticancer agents. Receptor tyrosine kinases (RTKs) are the most activated cell surface receptors for copious polypeptide growth factors, cytokines, and hormones that play a considerable role in cancer initiation, promotion, and progression. Natural products are a prime source of new anticancer drugs and their leads. The objective of computer-aided drug design (CADD) is to enhance the set of compounds with prudent active drug-like properties and eliminate inactive, toxic, poor absorption, distribution, metabolism, and excretion toxicity (ADME/T) compounds. In the present chapter, in silico advancement of anticancer natural compounds and molecular mechanisms of action of flavonoids, viz., genistein, myricetin, quercetin, luteolin, morin, kaempferol, catechin, and epigallocatechin gallate (EGCG), on RTK and PI3K signaling pathway attributing to their potential anticancer activity have been discussed.Item Oxidative Stress-Related MicroRNAs 6 as Diagnostic Markers: A Newer Insight in Diagnostics(Springer, 2017) Kumar, Shashank; Pandey, Abhay K.Despite rapid strides in the medical and technological fields during the last four decades including the development of nucleic acid and protein-based biomarkers, the mortality still remains a burning problem because of the delayed diagnosis of many diseases. This is particularly ascribed to the lower specificity and sensitivity of the methods used for diagnosis. The compelling situation has shifted the focus of expression biology toward identification and development of sensitive and specific markers for diagnosis and prognosis of different diseases by using microRNAs (miRNAs). miRNAs are short noncoding RNAs of 18–25 nucleotides. In mammals and multicellular organisms, they play significant role in nearly all biological pathways. Next-generation sequencing techniques have played role in discovery of noncoding RNA molecules. As compared to total protein coding sequences, large numbers of noncoding RNAs exist which are key to many new discoveries related to biological phenomena and pathologies. Noncoding RNA family in humans consists of about 1400 miRNAs. Their functional significance has been shown in developmental and pathological processes. miRNAs can be easily detected in tissue samples and body fluid of the patients. Hence, miRNAs could act as potential biomarker candidates. miRNA molecules have already made their way to clinical medicine as biomarkers for diagnosis and prognosis of diseases as well as therapeutic targets for treatment. Redox imbalance leads to oxidative stress which is associated with various diseases. Accumulated evidence suggests that oxidative stress stimulates production of several miRNAs which area known as oxidative stress-responsive miRNAs. They further play a role in connecting the dysregulated antioxidant defense system with imbalanced redox state. The present chapter summarizes recent findings on diagnostic and prognostic ability of oxidative stress-responsive miRNAs. In addition, the role of miRNAs in cancer has also been discussed. Studies on functional and regulatory aspects of oxidative stress-associated miRNAs will provide new direction to discovery of novel diagnostic and prognostic biomarkers.Item Recent advancement to target Breast Cancer and Cancer Stem Cells(Open Access, 2017) Kushwaha, Prem Prakash; Kumar, ShashankBreast cancer is the second most prominent reason of cancer death in women after lung cancer, and it accounts for 25.2% of all cancer in women [1]. In the US, approximately about one in eight women (12%) develop invasive breast cancer [2]. In 2015, approximately 40,290 US women were expected to die from breast cancer. There was an estimation of 231,840 new cases of invasive breast cancer among US women in 2015 [3]. The chance of breast cancer causes woman’s death is about 3%. Various kinds of therapies such as hormonal, immunotherapeutic agents, surgery and cytotoxic currently are being used to target the breast cancer. The response rate from these treatments comprises 60% to 80% for primary breast cancers and about 50% for metastases [4,5]. However, 20%-70% of patients showed reversion of cancer within five year of time [6]. Recurrence development allied with resistance to therapy and augmented death risk. In patients with primary breast cancer, combining cytotoxic and radiation therapy with anastrozole attained four-year survival rate of 91.6 % [7]. Gene mutations and dysregulation has been identified in breast cancers like the enhanced expression of the heparan sulfate interacting protein, p53 mutations (connecting with high histological grade) and mitochondrial D-loop mutation (allied with lymph node-positive breast carcinoma)Item Biological/Biosimilar Drugs: A New Hope for Better and Low Cost Treatment(Juniper Publishers, 2016) Kumar, ShashankBiological and biosimilar drugs Medicines that are derived from living cells/organisms are known as biological medicines. They consist of of highly complex molecular entities difficult to characterize. Certain degree of variations might found among biological medicines due to variation of the biological system and manufacturing process. A medicine that is very similar and clinically equivalent to a biological medicine is known as biosimilar medicine. Reference or originator medicine is an already approved biological medicine from which a biosimilar active medicine is derived. The biological product is highly similar to the reference product not withstanding minor differences in clinically inactive components; and there are no clinically meaningful differences between the biological product and the reference product in terms of the safety, purity, and potency of the product. Biosimilar medicines are not the same as generic medicines, which contain simpler chemical structures and are identical, in terms of molecular structure, to their reference drugs [1].Item Novel Wnt and Notch Signaling Natural Inhibitors as Double Edged Sword Against Cancer War: An approach Towards Computer Based Drug Design(Juniper Publishers, 2016) Kumar, ShashankCancer is a group of disease characterized by the uncontrolled growth and spread of abnormal cells which may lead to death. According to a report by GLOBOCAN the number of new cancer cases would increase to 19.3 million by 2025 worldwide. Thus globally cancer has become a big threat to human beings, among various diseases. Carcinogen induced deregulation in cellular signaling pathway, may leads to the cancer development. Chemotherapy is an important mode of cancer treatment that used to cure and improve the patient’s quality of life [1]. At the same time chemotherapy is known to induce drug resistance and toxicity that hurdles the improvement of overall response and survival of cancer patients. Many cancers contain a sub-population of self-renewing and expanding stem cells known as cancer stem cells (CSCs). These are associated with chemotherapeutic resistant leading to tumor recurrence and poor patient prognosis. Acquired drug resistance renders subsequent anticancer therapy effectiveness leading to tumor recurrence and progression. Hence it is urgency of time to identify effective and safer anticancer agents, which can be found in natural agents. The use of natural products is promising because they target multiple signaling pathways and have minimal toxicity compared to conventional chemotherapeutics. Malignancy transformation and progression are multistage progress involved gene alterations and multi signaling pathways. In this regard herbal products may do a lot. Several natural compounds viz., vinblastine, etoposide, paclitaxel, camptothecin, bleomycin, and doxorubicin are known to prevent the occurrence and/or spread of various cancers by targeting numerous key elements in intracellular signaling network involved in carcinogenesis and is being investigated in clinical trials.Item Inter Conversion of Somatic and Cancer Stem Cell: From Discovery to New Paradigm in Cancer Therapy(OMICS International, 2017) Kumar, ShashankOrgan is composed of special type of tissue and cells. Deficits in functionality and number of particular cells lead to the development of various type of human disease such as diabetes, neurological disease, cardiovascular, hepatic disorder and cancer etc. In the world of chronic disease there is a need of new branch of medicine that might help in the regeneration of tired and failing organ system. Present scientific community is giving emphasis and hope that regeneration of tired and failing organ system which results into various disease and disorders, might be cured/mitigated by special type of cells known as stem cellsItem Association of MTHFR (C677T) Gene Polymorphism With Breast Cancer in North India(Sage, 2016) Waseem, Mohammad; Hussain, Syed Rizwan; Kumar, Shashank; Serajuddin, Mohammad; Mahdi, Farzana; Sonkar, Satyendra Kumar; Bansal, Chery; Ahmad, Mohammad KaleemBackground Breast cancer is one of the most common malignancies in women and is associated with a variety of risk factors. The functional single-nucleotide polymorphism (SNP) C677T in the gene encoding 5,10-methylenetetrahydrofolate reductase (MTHFR) may lead to decreased enzyme activity and affect the chemosensitivity of tumor cells. This study was designed to investigate the association of MTHFR gene polymorphism (SNP) in the pathogenesis of breast cancer among the North Indian women population. Materials and Methods Genotyping was performed by polymerase chain reaction (PCR) using genomic DNA, extracted from the peripheral blood of subjects with (275 cases) or without (275 controls) breast cancer. Restriction fragment length polymorphism was used to study C677T polymorphism in the study groups. Results The distribution of MTHFR (C677T) genotype frequencies, ie, CC, TT, and CT, among the patients was 64.7%, 2.18%, and 33.09%, respectively. In the healthy control group, the CC, TT, and CT frequencies were 78.91%, 1.09%, and 20.1%, respectively. The frequencies of C and T alleles were 81.2% and 18.7%, respectively, in the patient subjects, while they were 88.9% and 11.09%, respectively, among the healthy control group. Frequencies of the CT genotype and the T allele were significantly different (P= 0.007 and P = 0.005, respectively) between the control and the case subjects. Conclusion This study shows an association of the CT genotype and the T allele of the MTHFR (C667T) gene with increased genetic risk for breast cancer among Indian women.