Manoj Kumar Sethi’s scientific contributions

In normal human microbiome, the polymorphic fungus Candida albicans is a crucial member. C. albicans resides mostly in individual as harmless commensal life. In specific situations, however, C. albicans can cause diseases that cause contaminations of the skin to life-threatening fundamental contaminations. Pathogenesis of Candida species is contributed by multiple factors. Some of the major contributors are enlisted here. These include host pathogen interaction, receptors molecule like TLR recognition, TLR signaling, C type lectin receptors, Dectin 1,2 and 3, mannose receptor, mincle, DC sign, Nod-Like Receptors (NLRs) and inflammasomes, soluble molecules in candida recognition, cellular responses to candida such as neutrophils, macrophages. This chapter enlightens all the components of candida pathogenicity by the assessment of Candida species pathogenic determinants. All together these will explain the current knowledge about how these determinant factors and receptors modulate virulence as well as consequent infection. Better understanding of candida pathogenicity mechanism can be the resultant of better treatment guidelines along with development of novel antifungal agents. Overall, in this review we present an update in the current understanding of the insight of pathogenicity mechanisms in this important human pathogen.

Allergic asthma is mainly characterized by allergen-induced IAR (immediate airway response) and LAR (late airway response). In regards to the results of lung tissue histology and bronchoalveolar lavage fluid analysis, it was confirmed that there is the existence of a casual relationship of eosinophil and other inflammatory cell infiltration in bronchial sub-mucosa in the mechanism of LAR. This investigation aimed to examine the anti-asthmatic effect of novel adjuvant therapeutic regimens using a low dose of potent glucocorticoid receptor agonist i.e., Dexamethasone, along with iNOS inhibitor i.e., Aminoguanidine in a both acute and chronic murine model of asthma. Female BALB/c mice of 8 weeks of age were taken and divided into 6 experimental groups i.e. normal control, OVA control, aminoguanidine (200mg/kg), combination of aminoguanidine (200mg/kg) along with dexamethasone (0.03mg/kg), low dose dexamethasone (0.03mg/kg) and Dexamethasone (0.1mg/kg) treated group. After sensitization and introduction of drugs, mice were sacrificed by cervical dislocation and bronchoalveolar lavage (BAL) fluid analyzed. The result of this study stated that there is a significant reduction in the levels of inflammatory cytokines in combination-treated animals with respect to alone dexamethasone, which may be due to the synergistic effect of aminoguanidine and dexamethasone. From histopathological evidence, it can be concluded that combination treatment having a better lung adaptation mechanism and can improve the condition aggressively. The findings of the study throw some light on an additive therapeutic regimen of aminoguanidine can have a better impact with glucocorticoids.

Objective: Atherosclerotic cardiovascular diseases were the major culprit in diabetic patients with high mortality rate in non-communicable disease worldwide. Present study was conducted to assess cardiovascular risk among type-2 diabetic patients without the history of cardiovascular disease. Methods: The present study was conducted on type-2 diabetes patients without history of cardiovascular disease (CVD) and the number of samples was 118 (65 male and 53 female) aged between 36 and 74 years in a teaching hospital of southern part of India. The individual patient risk factors were determined. Framingham cardiovascular risk prediction model was used to calculate the 10-year risk for CVD. The relationship between Framingham cardiovascular risk score and individual risk factors was determined using chi-square test. Key findings: Framingham risk score for cardiovascular disease (FRS-CVD) risk assessment model shows 11.01% were at high risk, 33.05% were at intermediate risk, and 55.93% were at low risk for developing CVD in the next 10 years. Visceral adiposity index (VAI), waist circumference, waist height ratio, smoking, systolic blood pressure, diastolic blood pressure contributed significantly to high degree of cardiovascular risk. Conclusion: The results of our study concluded that, in this population of patient with type-2 diabetes mellitus, the estimated cardiovascular risk in relationship with the central obesity, but not with glycemic control parameters. The use of CVD assessment tools like Framingham risk score, VAI, and ankle braquial index can prevent the diabetic patient from CVD.

Objective: The current investigation for antidiabetic activity of the plant Vernonia divergens (DC.) Edgew. has not been reported till date. However, to enlighten the folkloric claim of the plant, the study was carried out on various animal models such as albino mice, albino rabbits, Wistar rats, rabbits, hamsters, dogs, and monkeys. Methods: The whole plant of V. divergens was studied on various animal models. Screening methods generally have been carried out on rodents and non-rodents, respectively. Various biochemical and hematological parameters such as serum glucose, plasma insulin, lipid profile and activities of liver enzymes, red blood cells, white blood cells, hemoglobin, and differential counts were measured to assess the antihyperglycemic and antihyperlipidemic activities as well as safety profile of the extract. Results: Among all experimental extracts of V. divergens, it was found that the aqueous and methanolic extracts had maximum control of blood glucose in diabetic Wistar rats. While comparing with normoglycemic animals, it was observed that reduction of blood sugar level and increase in plasma insulin level are maximum with test extract. Among the study, the effects of the methanolic extract of V. divergens (MEVD) and aqueous extract of V. divergens (AEVD) were done through oral route in both the models, i.e., normoglycemic and hyperglycemic animal models. The safety profile was evaluated by toxicological evaluation and observed that, even at a higher dose level of 3000 mg/kg body weight, the MEVD and AEVD were safe and retain normal physiological and behavioral effect. The whole protein, whole cholesterol, aspartate aminotransferase, alanine aminotransferase, and alkaline phosphatase enzyme activity of streptozotocin-administered rats showed significantly higher than normal rats, and the test extract-treated rats significantly reduced the elevated levels. Conclusion: It is concluded that the MEVD and AEVD (DC.) Edgew. might be beneficial in effectively reducing the blood glucose concentration and managing the various complications of diabetes. However, in comparison between both the extracts, the methanol extract was found to be significantly more potent than that of the A.E. in all aspects.