School Of Health Sciences
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Item Evolution of Zebrafish as a Novel Pharmacological Model in Endocrine Research(Springer Nature, 2022-05-30T00:00:00) Navik, Umashanker; Rawat, Pushkar Singh; Allawadhi, Prince; Khurana, Amit; Banothu, Anil Kumar; Bharani, Kala KumarZebrafish is a powerful platform in the modern era of phenotype-based drug discovery and eminent vertebrate model to study disease progression and its pathophysiology. Zebrafish possess several advantages over rodent model including low cost, females that lay up to 300 eggs per week, the optical clarity of embryo, external fertilization, and highly amenable to transgenic modifications using various genetic toolkits. Zebrafish have almost 70% genetic homology with humans, and 82% of disease-causing human proteins are orthologue to zebrafish. The bottleneck in drug discovery is high cost, laborious, and time taking processes to generate hits. Zebrafish provide a novel option to overcome this bottleneck and have enabled rapid drug discovery in the area of cancer, cardiovascular diseases, endocrine diseases, and many more. However, zebrafish cannot completely replace the mammalian model in drug discovery, but it can form a bridge between cell-based assays and mammalian models, thus reducing the overall cost and time in lead generation. Therefore, in this chapter, we have discussed the role of zebrafish as an emerging vertebrate model in the area of endocrinology disorders. � The Editor(s) (if applicable) and The Author(s), under exclusive license to Springer Nature Singapore Pte Ltd. 2022.Item Obesity-Induced Chronic Low-Level Inflammation and Cancers(Springer Singapore, 2021-07-18T00:00:00) Bhattacharya, Neetu; Maurya, Shashank Kumar; Bhattacharya, Amit; Senapati, SabyasachiThe World Health Organization (WHO) has highlighted �overweight and obesity� as a public health concern and a significant risk factor for several chronic diseases, including diabetes, cardiovascular diseases, and cancers. The association between the different factors that can lead to the chronic inflammatory condition in the obese persons and their effect in tumorigenesis and several cancers (esophageal, liver, colon, postmenopausal breast, and endometrial cancers) have been partially unraveled. The functional association between inflammation and cancer is not new. Existing hypotheses of obesity-associated cancer underline direct effects of dietary ingredients or metabolic imbalance in the body. The recent evidences suggest a significant connection between chronic inflammation and cancer risk, possibly involving dietary and metabolic components. In the nineteenth century, Virchow first addressed the involvement of immune cells in tumorigenesis (Balkwill and Mantovani, The Lancet 357:539�545, 2001). The mediators and cellular effectors of inflammation are essential components of the tumor microenvironment and are more likely to contribute to tumor growth, its development and immunosuppression (Coussens and Werb, Nature 420:860�867, 2002). A strong relationship of chronic inflammation with malignant diseases can be traced in several individuals with inflammatory bowel diseases, such as Ulcerative colitis and Crohn�s disease, also developing colon carcinogenesis. Further, hepatitis C infection in the hepatic cells has been predisposed to liver carcinoma. Understanding these molecular pathways of cancer-related inflammation could lead to identification of new target molecules for improved diagnosis and treatment regimes. In this chapter, we will critically discuss the roles of cytokines, chemokines, growth factors, and inflammatory signaling pathways related to obesity and cancer risk. � The Editor(s) (if applicable) and The Author(s), under exclusive license to Taylor and Francis Pte Ltd. 2021.Item mTOR and AMP-Activated Protein Kinase in Obesity and Cancer(Springer Singapore, 2021-07-18T00:00:00) Biswas, Indranil; Maurya, Shashank Kumar; Senapati, SabyasachiThe mTOR (mechanistic target of rapamycin) is the main regulator of important cellular processes, including cellular growth, proliferation, protein synthesis, protein remodeling, autophagy, and cell metabolism in response to nutrition status, growth factor, and stress signals. Previous studies demonstrated that mTOR signaling plays a crucial role in the function of adipose tissue such as adipogenesis, lipid metabolism, thermogenesis, and adipokine biosynthesis and release. Nutritional status in adipose tissues is different than its surrounding microenvironment, which receive altered metabolic ques. from the adipose tissues. In regard to its critical role in cellular processes, it is expected that obesity and related metabolic disorders will have direct role in dysregulation of mTOR signaling. Aberrant mTOR signaling is commonly observed in different types of cancer. Hyperactivation of mTORC1 pathway activates cell proliferation and decreased autophagy, which leads to initiation of tumor growth, progression, and angiogenesis. Another regulator of metabolic activity, adenosine monophosphate (AMP)-activated protein kinase (AMPK), maintains the energy homeostasis in response to metabolic alteration. Previous research demonstrated that AMPK is a key cellular energy sensor responsible for regulating the metabolic activity of brown and beige adipose tissues. AMPK has also been demonstrated to negatively regulate diabetes, cardiovascular disease, and other metabolic syndromes. Apart from metabolic syndrome and diabetes, the AMPK signaling has shown therapeutic potential due to its unique potential in regulating of cancer cell proliferation via cell metabolism reprogramming.. Previous reports suggest the tumor suppressive role of AMPK that sense the energy deficiency in solid tumors, thereby inhibit the cellular proliferation. However, recent data proposes that tumor cells gain growth advantage in oxygen and nutrient deprived condition via exploiting AMPK activation. In light of adipose tissue associated tumors, it is well known that adipose tissues activate inflammation in response oxygen deprivation. However, the role of altered metabolism, specifically interaction between adipose tissues and tumor microenvironment, in terms of mTOR and AMPK signaling is not well known. � The Editor(s) (if applicable) and The Author(s), under exclusive license to Taylor and Francis Pte Ltd. 2021.Item Apolipoprotein C3 gene polymorphisms in Southern Indian patients with nonalcoholic fatty liver disease(Springer, 2014) Munshi, AnjanaAim Nonalcoholic fatty liver disease (NAFLD) is the most common liver disease in the world today. A previous study has suggested an association of apolipoprotein C3 (APOC3) gene variants with the risk of NAFLD in Asian Indian men living in the Western regions. The present study was carried out with an aim to evaluate the association of demographic features, serum lipid profile and APOC3 gene variants (C-482T and T-455C) NAFLD. Methods One hundred and fifty NAFLD patients and 150 age and gender-matched controls were included in the study. Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) was performed to detect the genotypes of APOC3. Serum lipid profile was analyzed. Results In the present study, body mass index was not a predictive demographic marker for NAFLD. Serum triglycerides were higher in patients (mean 155.95 ± 59.0) with NAFLD compared to the control group (mean 133.75 ± 44.71) (p = 0.016). APOC3 gene polymorphism T-455C (rs2854116) was significantly associated with NAFLD (p = 0.001). However, we did not find a significant association of C-482T polymorphism (rs2854117) of APOC3 gene with NAFLD. Genotype -455C/C of the SNP, rs2854116 associated significantly with the elevated serum triglycerides in patients. Conclusions The polymorphism T-455C in APOC3 gene and elevated serum triglycerides were associated with NAFLD.Item A low frequency variant within the GWAS locus of MTNR1B affects fasting glucose concentrations: Genetic risk is modulated by obesity(2012) Been, L.F.; Hatfield, J.L.; Shankar, A.; Aston, C.E.; Ralhan, S.; Wander, G.S.; Mehra, N.K.; Singh, J.R.; Mulvihill, J.J.; Sanghera, D.K.Two common variants (rs1387153, rs10830963) in MTNR1B have been reported to have independent effects on fasting blood glucose (FBG) levels with increased risk to type 2 diabetes (T2D) in recent genome-wide association studies (GWAS). In this investigation, we report the association of these two variants, and an additional variant (rs1374645) within the GWAS locus of MTNR1B with FBG, 2h glucose, insulin resistance (HOMA IR), ?-cell function (HOMA B), and T2D in our sample of Asian Sikhs from India. Our cohort comprised 2222 subjects [1201 T2D, 1021 controls]. None of these SNPs was associated with T2D in this cohort. Our data also could not confirm association of rs1387153 and rs10830963 with FBG phenotype. However, upon stratifying data according to body mass index (BMI) (low ? 25 kg/m2 and high > 25 kg/m2) in normoglycemic subjects (n = 1021), the rs1374645 revealed a strong association with low FBG levels in low BMI group (? = -0.073, p = 0.002, Bonferroni p = 0.01) compared to the high BMI group (? = 0.015, p = 0.50). We also detected a strong evidence of interaction between rs1374645 and BMI with respect to FBG levels (p = 0.002). Our data provide new information about the significant impact of another MTNR1B variant on FBG levels that appears to be modulated by BMI. Future confirmation on independent datasets and functional studies will be required to define the role of this variant in fasting glucose variation. ? 2011.