Examining the role of perceived stress on learning satisfaction under the influence of academic burnout in the post-COVID world.

BACKGROUND: In the last two years, due to the impact of COVID-19, students were forced to continue their education online because the government imposed restrictions to limit the spread of the virus. However, with the resumption of offline classes, the students seem to be suffering more from stress and isolation as they must face the challenges of the real world, which are quite different from the virtual one to which they have become accustomed. In this study, the effect of stress on students leading to their academic burnout and the influence of burnout on their learning satisfaction was studied. MATERIALS AND METHODS: The data were collected from 343 students of final year postgraduation courses in business management studies in India. The collected data were subject to analysis using PLS-SEM through SmartPLS 4.0 software. RESULT: The results of the study state that the perceived stress significantly increases cynicism, and exhaustion with a coefficient value of 0.481 each and decreases self-efficacy with - 0.03. Additionally, exhaustion acts as a mediator that decreases the effect of perceived stress over learning satisfaction with a positive indirect effect of 0.176. CONCLUSION: The study concludes that not all types of stress are bad for students; hence, increasing perceived stress leads to increased learning satisfaction. Whereas, in the presence of burnout factors, such as exhaustion and cynicism, learning satisfaction decrease. However, self-inefficacy, one of the factors under burnout, doesn't show any effect on learning satisfaction. The present study is widely applicable to industry and academia to deal with burnout to improve students learning satisfaction.

Antidiabetic Effect of Tamarindus indica and Momordica charantia and Downregulation of TET-1 Gene Expression by Saroglitazar in Glucose Feed Adipocytes and Their Involvement in the Type 2 Diabetes-Associated Inflammation In Vitro.

To date, there is no satisfactory and effective therapy available to cure type 2 diabetes mellitus (T2DM). This present work is focused on plant extracts and the effect of saroglitazar and TET genes on oxidative stress and inflammation in vitro adipocytes. Aqueous extracts of Tamarindus indica and Momordica charantia seed have shown potent antidiabetic activity that decreases glucose levels in diabetic adipocytes. After seven and fourteen days, the sugar level in the blood was significantly reduced when plant extracts were supplemented. Lipid profiles including total cholesterol (TC), triglyceride (TGL), high-density lipoprotein (HDL), low-density lipoprotein (LDL), and very low-density lipoprotein (VLDL) showed a highly significant change as expected in adipocytes treated with glucose compared with controlled adipocytes (P < 0.001). Gene expression of catalase, superoxide dismutase (SOD1, SOD2), and glutathione peroxidase (GPx) are changed twice, thrice, and quadruplet, respectively. The level of interleukin-1 (IL1) and tumor necrosis factor-α (TNF-α) was restored but the interleukin-6 (IL6) and ten-eleven-translocation-1 (TET1) were completely knocked down by the use of saroglitazar. In comparison with the diabetic group, this supplementation significantly increased glycogen content and glucose-6-phosphate dehydrogenase activity. In the extract supplemented group, glucose-6-phosphatase, glucose-oxidizing enzyme, and glucose-phosphorylating enzyme activities were significantly reduced. After seven days of extract supplementation, these parameters were not resettled to a controlled level; however, after 14 days of supplementation, all parameters were restored to the control level. In addition to altering gene expression, TET enzymes may contribute to altered adiposity and its metabolic consequences. The purpose of this study is to examine new ideas and approaches for treating obesity, T2DM, and other associated metabolic disorders.

Association of TNF-α Gene Expression and Release in Response to Anti-Diabetic Drugs from Human Adipocytes in vitro.

INTRODUCTION: TNF-α, a proinflammatory cytokine secreted by activated immune cells, and overexpression of it in adipocytes, has an important role in insulin resistance progression and diabetes development. AIM AND OBJECTIVE: Subcutaneous adipocytes derived from mesenchymal stem cells were used for in vitro analysis to find the role of antidiabetic drugs on TNF-α in high glucose-fed adipocytes. METHODS: In vitro adipocytes were used along with variable concentration of anti-diabetic drugs. The level of TNF-α was measured by ELISA and the mRNA level was quantified using SYBR-Green real-time PCR. All data were statistically analyzed. RESULTS: The level of TNF-α and the mRNA expression were observed and analyzed with normal adipocytes. TNF-α level and expression of it showed agonistic behavior, ie no change at low concentration while enhances with the increase of glucose. The level was decreased significantly when the adipocytes were treated with metformin (p=0.015) and pioglitazone (p=0.020). A combination of drugs showed that the expression of TNF-α was almost the same as for metformin alone. However, insulin increases the TNF-α expression as for pioglitazone. DISCUSSION: Such a report on adipocytes may be helpful for clinical benefits to understand the additional mechanism of adipocytes on the release and expression of TNF-α. However, anti-diabetic drugs including insulin up-regulate the TNF-α gene expression in mild or severe glucose load.

1H NMR based serum metabolic profiling reveals differentiating biomarkers in patients with diabetes and diabetes-related complication.

BACKGROUND: Diabetes is among the most prevalent diseases worldwide, of all the affected individuals a significant proportion of the population remains undiagnosed due to lack of specific symptoms early in this disorder and inadequate diagnostics. Diabetes and its associated sequela, i.e., comorbidity are associated with microvascular and macrovascular complications. As diabetes is characterized by an altered metabolism of key metabolites and regulatory pathways. Metabolic phenotyping can provide us with a better understanding of the unique set of regulatory perturbations that predispose to diabetes and its associated complication/comorbidities. METHODOLOGY: The present study utilizes the analytical platform NMR spectroscopy coupled with Random Forest statistical analysis to identify the discriminatory metabolites in diabetes (DB = 38) vs. diabetes-related complication (DC = 35) along with the healthy control (HC = 50) subjects. A combined and pairwise analysis was performed to identify the discriminatory metabolites responsible for class separation. The perturbed metabolites were further rigorously validated using t-test, AUROC analysis to examine the statistical significance of the identified metabolites. RESULTS: The DB and DC patients were well discriminated from HC. However, 15 metabolites were found to be significantly perturbed in DC patients compared to DB, the identified panel of metabolites are TCA cycle (succinate, citrate), methylamine metabolism (trimethylamine, methylamine, betaine), -intermediates; energy metabolites (glucose, lactate, pyruvate); and amino acids (valine, arginine, glutamate, methionine, proline, and threonine). CONCLUSION: The 1H NMR metabolomics may prove a promising technique to differentiate and predict diabetes and its complication on their onset or progression by determining the altered levels of the metabolites in serum.

Cytokine Gene Variants as Predictors of Type 2 Diabetes Mellitus.

BACKGROUND: Diabetes is the third widespread after heart disease and cancer. We have investigated genetic polymorphisms in cytokine genes viz. IL-4, IL-1Ra, IL-1ß, IL-18, IL-6, TNF-α, IL-10 and ADIPOQ. The aim of study was to investigate the haplotypes, gene-gene interactions and their role in determining individual susceptibility to T2DM of family members with diabetic history. METHODS: Haplotype analysis of 2 SNPs each in IL-6 and adiponectin genes showing Pairwise Linkage disequilibrium (LD) was done by SHEsis software. Logistic regression was used to study various combinations of gene-gene interactions. RESULTS: The TCGT* set of allele combination appeared to increase the disease risk upto 2 times while TATG* upto 51.4 times when four SNPs are taken together viz. IL-1ß-511 C/T, IL-18-607 A/C, ADIPOQ1 +45 G/T and ADIPOQ2 +10211 T/G. Interaction of SNPs in eight genes showed one highly significant combination of alleles, TCGAGCTT* which increased the risk of T2DM upto 7.4 times while CAGAGCGT* allele combination increased the risk upto 4 times. CONCLUSION: During pedigree analysis in six families with four SNPs, it was interesting to note that susceptible 'AC' genotype of IL-18-607 A/C was frequent in diabetic individuals in almost all families. Moreover, when checked for the presence of risk haplotypes it was observed that TCGT* and TATG* sets of allele combinations were present in most of the diabetic individuals. Individuals with certain abnormal biochemical parameters but not yet diagnosed for T2DM carried the risk genotype or haplotype. This suggested that individuals carrying risk genotypes/haplotypes might be susceptible to T2DM and develop the disease in the future.

Interleukin-6 (IL-6)-597 A/G (rs1800797) & -174 G/C (rs1800795) gene polymorphisms in type 2 diabetes.

BACKGROUND & OBJECTIVES: Diabetes is a metabolic pro-inflammatory disorder characterized by chronic hyperglycaemia and increased levels of circulating cytokines suggesting a causal role for inflammation in its aetiology. In order to decipher the role of interleukin-6 (IL-6) in type 2 diabetes mellitus (T2DM) we analyzed two promoter polymorphisms -597 A/G (rs1800797) and -174 G/C (rs1800795) in T2DM cases from north India, and in healthy controls. METHODS: DNA was isolated from venous blood samples of T2DM patients (n=213) and normal healthy controls (n=145). Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) was performed after biochemical analysis. The genotypic and allelic frequency distributions were analyzed. RESULTS: The clinical/biochemical parameters of T2DM cases when compared to controls showed a significant difference. No significant association was observed with -597A/G polymorphism while, -174 G/C showed a highly significant association (P<0.001). In haplotypic analysis, combination of -597GFNx01/-174CFNx01 showed significant association (P=0.010). INTERPRETATION & CONCLUSIONS: Our data suggest that IL-6 gene polymorphisms play a prominent role in T2DM disease susceptibility in population from north India.

Genetic polymorphisms of cytokine genes in type 2 diabetes mellitus.

Diabetes mellitus is a combined metabolic disorder which includes hyperglycemia, dyslipidemia, stroke and several other complications. Various groups all over the world are relentlessly working out the possible role of a vast number of genes associated with type 2 diabetes (T2DM). Inflammation is an important outcome of any kind of imbalance in the body and is therefore an indicator of several diseases, including T2DM. Various ethnic populations around the world show different levels of variations in single nucleotide polymorphisms (SNPs). The present review was undertaken to explore the association of cytokine gene polymorphisms with T2DM in populations of different ethnicities. This will lead to the understanding of the role of cytokine genes in T2DM risk and development. Association studies of genotypes of SNPs present in cytokine genes will help to identify risk haplotype(s) for disease susceptibility by developing prognostic markers and alter treatment strategies for T2DM and related complications. This will enable individuals at risk to take prior precautionary measures and avoid or delay the onset of the disease. Future challenges will be to understand the genotypic interactions between SNPs in one cytokine gene or several genes at different loci and study their association with T2DM.

Association of IL-6, TNF-α and IL-10 gene polymorphisms with type 2 diabetes mellitus.

Type 2 diabetes mellitus (T2DM) is a metabolic pro-inflammatory disorder characterized by chronic hyperglycemia and increased levels of circulating cytokines suggesting a causal role of inflammation in its etiology. Polymorphism of cytokine genes including interleukin-6 (IL-6), tumour necrosis factor-α (TNF-α) and interleukin-10 (IL-10) were studied in T2DM patients as well as in normal healthy controls. Genomic DNA was isolated from both T2DM patients and controls followed by quantification and genotyping by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) using suitable primers. The genotypic, allelic and carriage rate frequency distribution in patients and controls were analyzed by SPSS (version 15.0). Odd ratios with 95 % confidence interval was determined to describe the strength of association by logistic regression model. Double and triple combinations of genotypes were analyzed by χ(2) test. Gene-gene interaction and linkage disequilibrium tests were performed using SHEsis software. Individually, IL-6, TNF-α and IL-10 did not show any association. In double combination, IL-6 -597 GA and TNF-α -308 GG genotypes increased the risk up to 21 times and in triple combination IL-6 -597 AA, TNF-α -308 GG and IL-10 -592 CA increased the risk of T2DM up to 314 times. In gene-gene interaction allele 'A' of all studied polymorphisms increased the risk of T2DM up to 1.41 times. Our results suggest that individuals having a haplotype combination of AA, GG and CA for IL-6, TNF-α and IL-10 gene polymorphisms will have higher susceptibility and be at greater risk of developing T2DM.

Genome-wide association study for type 2 diabetes in Indians identifies a new susceptibility locus at 2q21.

Indians undergoing socioeconomic and lifestyle transitions will be maximally affected by epidemic of type 2 diabetes (T2D). We conducted a two-stage genome-wide association study of T2D in 12,535 Indians, a less explored but high-risk group. We identified a new type 2 diabetes-associated locus at 2q21, with the lead signal being rs6723108 (odds ratio 1.31; P = 3.32 × 10⁻9). Imputation analysis refined the signal to rs998451 (odds ratio 1.56; P = 6.3 × 10⁻¹²) within TMEM163 that encodes a probable vesicular transporter in nerve terminals. TMEM163 variants also showed association with decreased fasting plasma insulin and homeostatic model assessment of insulin resistance, indicating a plausible effect through impaired insulin secretion. The 2q21 region also harbors RAB3GAP1 and ACMSD; those are involved in neurologic disorders. Forty-nine of 56 previously reported signals showed consistency in direction with similar effect sizes in Indians and previous studies, and 25 of them were also associated (P < 0.05). Known loci and the newly identified 2q21 locus altogether explained 7.65% variance in the risk of T2D in Indians. Our study suggests that common susceptibility variants for T2D are largely the same across populations, but also reveals a population-specific locus and provides further insights into genetic architecture and etiology of T2D.

Genetic association of adiponectin gene polymorphisms (+45T/G and +10211T/G) with type 2 diabetes in North Indians.

Adiponectin (ADIPOQ) is an abundant protein hormone which belongs to a family of so-called adipokines. It is expressed mostly by adipocytes and is an important regulator of lipid and glucose metabolism. It was shown that decreased serum adiponectin concentration indicated insulin resistance and type 2 diabetes (T2DM) with the risk of cardiovascular complications. The fact that adiponectin is an insulin-sensitizing hormone with anti-diabetic, anti-inflammatory and anti-atherogenic properties, we proposed to study the association of ADIPOQ gene polymorphisms in subjects with T2DM. DNA was isolated from venous blood samples, quantified and subjected to Polymerase Chain Reaction-Restriction Fragment Length Polymorphism (PCR-RFLP) using suitable primers and restriction endonucleases. Adiponectin levels were measured in serum using ELISA. The genotypic, allelic and carriage rate frequencies distribution in patients and controls were analyzed by PSAW software (ver. 17.0). Odd ratios (OR) with 95% confidence interval (CI) were determined to describe the strength of association by logistic regression model. Out of the two polymorphisms studied, +10211T/G showed significant association (P=0.042), the 'G' allele association being highly significant (P=0.022). Further analysis showed that individuals with 'GG' haplotype were at increased risk of T2DM up to 15.5 times [P=0.015, OR (95% CI); 15.558 (1.690-143.174)]. The present study showed that the 'G' allele of ADIPOQ gene (+10211T/G) plays a prominent role with respect to T2DM susceptibility in North-Indian population.

Interleukin-1 (IL-1) family of cytokines: role in type 2 diabetes.

Cytokines are small cell signaling protein molecules which encompass a large and diverse family. They consist of immunomodulating agents such as interleukins and inteferons. Virtually all nucleated cells, especially endo/epithelial cells and macrophages are potent producers of IL-1, IL-6 and TNF-α. IL-1 family is a group of cytokines which play a central role in the regulation of immune and inflammatory responses. Type 2 diabetes (T2D) has been recognized as an immune mediated disease leading to impaired insulin signaling and selective destruction of insulin producing ß-cells in which cytokines play an important role. Disturbance of anti-inflammatory response could be a critical component of the chronic inflammation resulting in T2D. IL-1 family of cytokines has important roles in endocrinology and in the regulation of responses associated with inflammatory stress. The IL-1 family consists of two pro-inflammatory cytokines, IL-1α and IL-1ß, and a naturally occurring anti-inflammatory agent, the IL-1 receptor antagonist (IL-1Ra or IL-1RN). This review is an insight into the different types of cytokines belonging to IL-1 family, their modes of action and association with Type 2 diabetes.

An interleukin-10 gene promoter polymorphism (-592A/C) associated with type 2 diabetes: a North Indian study.

In this first report on the association of an IL-10 promoter polymorphism with type 2 diabetes mellitus in a North Indian population, the -592A/C SNP (rs1800872) was genotyped by PCR-RFLP and the IL-10 level measured using ELISA. Although no significant difference was observed in the genotypic frequencies (P = 0.657), diabetes patients carried a significantly higher number of A alleles at the -592 position, 25.6% (P < 0.001, odds ratio 0.887, 95% CI 0.670-1.184). Significant correlations were detected in postprandial glucose levels of CC-genotype patients and controls (P = 0.025), age and waist-hip ratio of CA patients and controls (P ≤ 0.001), and fasting glucose (P = 0.045) and low-density lipoprotein (P = 0.049) in all patients and controls. The serum IL-10 level was significantly higher in patients than in controls (P = 0.033). The polymorphism was significantly associated with disease incidence and its biochemical manifestations.

Vitamin D receptor (FokI, BsmI and TaqI) gene polymorphisms and type 2 diabetes mellitus: a North Indian study.

BACKGROUND: The vitamin D receptor (VDR) gene is a candidate gene for susceptibility to several diseases. Studies on association between VDR polymorphisms and risk of type 2 diabetes (T2DM) in different ethnic populations are yet inconclusive. AIMS: This study was conducted to evaluate association between VDR polymorphisms and genetic susceptibility to T2DM in the north Indian population. SETTINGS AND DESIGN: One hundred clinically diagnosed T2DM patients and 160 healthy controls from the north Indian population were recruited for genetic association study. MATERIALS AND METHODS: Genomic DNA was extracted from blood and genotyped for the single nucleotide polymorphism SNPs of FokI (T/C) [rs2228570], BsmI (A/G) [rs1544410] and TaqI (C/T) [rs731236] by polymerase chain reaction and restriction fragment length polymorphism (PCR-RFLP) analysis. STATISTICAL ANALYSIS USED: Genotype distribution and allelic frequencies were compared between patients and controls. Mean values and odds ratios (ORs) with 95% confidence interval (CI) were calculated using SPSS software (version 15.0). RESULTS: The genotype distribution, allele and haplotype frequencies of VDR polymorphism did not differ significantly between patients and controls. Mean age and waist-hip ratio of patients were found to be associated with VDR polymorphism. Combination studies showed FFBbtt increased the risk of T2DM in north Indians. CONCLUSIONS: Our data suggest that VDR gene polymorphism in combination of genotypes is associated with the risk of T2DM and thus requires further studies as a probable genetic risk marker for T2DM.