Triglyceride-Fasting Glucose Index and Homeostatic Model Assessment for Insulin Resistance as Predictors of Type 2 Diabetes Mellitus in South Indians With Normal Body Mass Index.

INTRODUCTION:  Early detection of type 2 diabetes mellitus (T2DM) is imperative to prevent the complications associated with the disease. Current guidelines for diagnosis rely on the assessment of serum glucose (fasting and post-prandial) and glycosylated hemoglobin (HbA1c) levels. Insulin resistance, a phenomenon associated with T2DM, has been observed before the changes in these metrics. The homeostatic model assessment for insulin resistance (HOMA-IR) has been widely used to assess the degree of insulin resistance. The triglyceride-fasting glucose (TyG) index is a newer marker of insulin resistance that merits further study.  Aim: The study aimed to assess the validity of the TyG index and HOMA-IR as markers for the development of T2DM in non-obese individuals.  Materials and methods: One hundred eight non-obese patients without T2DM were included in this prospective cohort study and followed up for eight years. Anthropometric and biochemical parameters, including fasting glucose levels, HbA1c, fasting serum insulin, low-density lipoprotein (LDL), high-density lipoprotein (HDL), and triglycerides (TG), were measured at enrolment and eight years follow-up, and HOMA-IR and TyG index were calculated.  Results: Twenty participants out of 108 (18.5%) developed T2DM over eight years. On performing the area under the curve (AUC)-receiver operating characteristic curve analysis, TyG of >8.61 and HOMA-IR of >1.5 had the highest validity (ability) to predict new-onset T2DM in the study population (TyG: AUC: 0.612 (95% CI: 0.514-0.705); HOMA-IR: AUC: 0.529 (95% CI: 0.431-0.626)); however, this was not statistically significant.  Conclusion: At an eight-year follow-up, TyG and HOMA-IR were unreliable predictors of the development of T2DM in non-obese individuals.

Antimicrobial, antioxidant, anticancer, and antithrombotic, competency of saponins from the root of Decalepis hamiltonii.

The goal of this study was to extract saponins from the tuberous root of Decalepis hamiltonii and assess their potential clinical applications, which included antioxidant, antibacterial, antithrombotic, and anticancer properties. Surprisingly, the results of this study revealed that the extracted saponins have excellent antioxidant activities, as demonstrated by 2,2-diphenylpicrylhydrazyl (DPPH), 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS), Hydrogen peroxide (H2O2), and Nitric oxide (NO) scavenging assays. Nonetheless, at a concentration of 100 g/mL, crude saponin had excellent antibacterial activity, particularly against gramme positive bacteria (Staphylococcus aureus, Bacillus subtilis, Staphylococcus epidermidis, and Micrococcus luteus), followed by gramme negative bacteria (Escherichia coli, Salmonella typhi, Proteus mirabilis, and Klebsiella pneumonia). Despite this, the crude saponin had no effect on Aspergillus niger and Candida albicans. The crude saponin also possesses outstanding in vitro antithrombotic activity on blood clot. Interestingly, the crude saponins have an outstanding anticancer activity of 89.26%, with an IC50 value of 58.41 µg/mL. Overall, the findings conclude that crude saponin derived from D. hamiltonii tuberous root could be used in pharmaceutical formulations.

Single crystal XRD, DFT investigations and molecular docking study of 2- ((1,5-dimethyl-3-oxo-2-phenyl-2,3-dihydro-1H-pyrazol-4-yl)amino)naphthalene-1,4-dione as a potential anti- cancer lead molecule.

A derivative of naphthaquinone, 2-((1,5-dimethyl-3-oxo-2-phenyl-2,3-dihydro-1H-pyrazol-4-yl)amino)naphthalene-1,4-dione (DPDHN) was synthesized from lawsone by ultrasound accelerated technique. The compound was characterized by elemental analysis, IR, UV-vis, NMR and mass spectral studies. Single crystal X-ray diffraction studies revealed that the compound crystallized in monoclinic space group P21/c. Density functional calculations of DPDHN was performed using DFT (B3LYP) method with 6-311G (5D, 7F) basis set, geometrical optimization best fit to single crystal XRD values. The charge delocalization has been analyzed using natural orbital (NBO) analysis. Effects of halogenations at ortho, meta and para positions in the title compound is discussed for frontier molecular orbital analysis, molecular electrostatic potential plots and nonlinear optical properties. It exhibited significant antioxidant property. To predict the anticancer activity of the compound, molecular docking studies were done using Schrödinger software. Molecular docking studies for DPDHN was performed on the active site of protein kinase CK2 (PDB ID: 2OXX, 1M2R and 1M2P) and to explore the estrogen receptor binding ability, the target protein with PDB ID: 3ERT and 2YLY were selected. Docking scores of the designed compound was compared with FDA approved drugs, Tamoxifen, Daunorubicin and Doxorubicin. The compound DPDHN exhibited good Glide scores for all the proteins. Glide score of DPDHN (PDB ID: 2YLY) was -9.67 kcal/mol which was as good as the currently used breast cancer drug, Tamoxifen (-10.37 kcal/mol) and found better than the drug Doxorubicin (-7.3 kcal/mol). Lead compound that satisfies predefined minimum criteria further structure and activity optimization. In the present work, hence it was further subjected to in vitro studies towards human breast cancer (MCF-7) and colon cancer (HCT-15) cell lines. The IC50 value of compound DPDHN in MCF-7 cells was 15.21 µM and that of HCT-15 was 39.21 µM which was a lower value and better than that of lawsone. Therefore DPDHN exhibited much higher toxicity towards MCF-7 cell lines. Thus, the results indicate that DPDHN is a potential anti cancer lead molecule especially for breast cancer studies.

Synthesis, spectral characterization, crystal structure, cytotoxicity and apoptosis-Inducing activity of two derivatives of 2-hydroxy-1,4-naphthaquinone.

A phenaxazone compound [5H-Benzo[a]phenoxazin-5-one (BP)] along with an aminoquinone[2-[(o-hydroxyphenyl)amino]-1,4-naphthaquinone (HAN)] derivatives were synthesized from lawsone using ultrasound irradiation technique. The structure of the compounds were characterized by elemental analysis and various spectral studies. Optoelectronic properties were studied using Schrodinger material science suit (2015). The compounds exhibit fluorescence emission in longer wave length it may find applications in photodynamic therapy. Single crystal X-ray diffraction studies reveals that the compound BP crystallizes in monoclinic space group. The antioxidant activity of HAN and BP were determined using DPPH radical scavenging assay and the results indicate that both the compounds have good antioxidant capacity, HAN having more scavenging activity than BP. Lead molecules were identified using in silico molecular docking studies as a green chemistry approach. iGEMDOCK, GOLD and Schrödinger softwares were used for these studies. The docking studies reveal that the structural modification of the parent compound gave more active compounds making them promising lead molecules. The lead molecules were subjected to in vitro studies. The cytotoxicity of BP and HAN was studied using human breast cancer (SKBR3) cell lines. The IC50 value of HAN was found to be 19.8µM while BP was found to have cell viability, less than 10% even at 25µM concentration. The chemotherapeutic agents kill the cancer cells mainly through apoptosis. HAN and BP were subjected to apoptosis studies. BP was found to more active than HAN. Thus it can be suggested that the mechanism of cell death may be through apoptosis.

Skin and Soft Tissue Infections due to Shewanella algae - An Emerging Pathogen.

INTRODUCTION: Shewanella spp. are emerging human pathogens, the predominant species being Shewanella algae. Shewanella skin and soft tissue infections are more commonly seen in immunocompromised patients with a pre-existing cutaneous ulcer and most often associated with exposure to marine environments. AIM: The study was conducted to investigate the epidemiological and clinical characteristics of Shewanella skin and soft tissue infections (SSTIs) for a period of five years. MATERIALS AND METHODS: All Gram-negative non-fermenting motile isolates which produced pigmented colonies and positive for oxidase and H2S were further identified with Vitek 2 system. RESULTS: A total of 16 patients with SSTIs due to Shewanella species were identified during the period from 2010 to 2014. Majority of patients were urban, elderly and fisher men. Shewanella algae (n=12, 75%) was the predominant isolate. Skin or mucosal portal of entry was found in all patients and seawater contact was recorded in 56.25% of the patients. 81% of infections were polymicrobial, common concomitant pathogens being gut and marine flora. Peripheral vascular diseases were the predominant risk factors with comorbidities like diabetes, hypertension and hepatobiliary diseases. Third generation cephalosporins, meropenem and gentamicin were the most effective antibiotics while two of the isolates were multidrug resistant. 75% of the infected patients recovered completely and three patients died of complications. CONCLUSION: Shewanella algae should be considered as an emerging pathogen of SSTIs mainly in patients with chronic ulcers and at times be multidrug resistant. These infections have a good clinical outcome if prompt medical, surgical and supportive treatment is offered.