Repression of resistance mechanisms of Pseudomonas aeruginosa: implications of the combination of antibiotics and phytoconstituents.

Antimicrobial resistance is a prevalent problem witnessed globally and creating an alarming situation for the treatment of infections caused by resistant pathogens. Available armaments such as antibiotics often fail to exhibit the intended action against resistant pathogens, leading to failure in the treatments that are causing mortality. New antibiotics or a new treatment approach is necessary to combat this situation. P. aeruginosa is an opportunistic drug resistant pathogen and is the sixth most common cause of nosocomial infections. P. aeruginosa due to its genome organization and other factors are exhibiting resistance against drugs. Bacterial biofilm formation, low permeability of outer membrane, the production of the beta-lactamase, and the production of several efflux systems limits the antibacterial potential of several classes of antibiotics. Combination of phytoconstituents with antibiotics is a promising strategy to combat multidrug resistant P. aeruginosa. Phytoconstituents such as flavonoids, terpenoids, alkaloids, polypeptides, phenolics, and essential oils are well known antibacterial agents. In this review, the activity of combination of the phytoconstituents and antibiotics, and their corresponding mechanism of action was discussed elaborately. The combination of antibiotics and plant-derived compounds exhibited better efficacy compared to antibiotics alone against the antibiotic resistance P. aeruginosa infections.

Developmental Toxicity Assessment of Drymaria Cordata (Linn.) Willd using Zebrafish Embryo.

INTRODUCTION: Drymaria cordata (Linn.) Willd is a creeping herb belonging to the Caryophyllaceae family, widely used as a traditional medicine in Africa and North-east India for various ailments. Many therapeutic applications of D. cordata have been reported in various scientific studies, but the teratogenicity study of this herb has not been documented till now. METHODS: The present study aimed to assess the developmental toxic effect and median lethal concentration (LC50) of methanol extract of Drymaria cordata leaf (DCME) using zebrafish embryos. After spawning of male and female zebrafish, healthy zebrafish embryos were selected by microscopic screening and transferred into 96-well plate for the study. Embryos were exposed to DCME at concentrations ranging from 50-400 µg/ml in 2% DMSO from 24 hpf to 72 hpf. RESULTS: Developmental and morphological abnormalities were microscopically evaluated. Fifty percent lethal concentration (LC50) of DCME was determined by observation from 24 hpf to 72 hpf. The concentration-dependent toxic effects of DCME on developing embryos of zebrafish were found in the study in a time-dependent manner. CONCLUSION: At 72 hpf, the median lethal concentration (LC50) of DCME was found with visible developmental defects, such as heartbeat rate, less pigmentation, oedema, spinal curvature, immature yolk sac as well as reduced hatching rate and a slow growth. The median lethal dose was found to be 448 µg/ml at 72 hpf for zebra fish embryos, meriting further studies on toxicological profiling of the plants.

Role of Glycogen Synthase Kinase-3 in the Etiology of Type 2 Diabetes Mellitus: A Review.

The risk of type 2 diabetes mellitus (T2DM) is increasing abundantly due to lifestyle-related obesity and associated cardiovascular problems. Presently, Glycogen synthase kinase-3 (GSK-3) has gained considerable attention from biomedical scientists to treat diabetes. Phosphorylation of GSK-3 permits a number of cellular activities like regulation of cell signaling, cellular metabolism, cell proliferation and cellular transport. Inhibiting GSK-3 activity by pharmacological intervention has become an important strategy for the management of T2DM. This review focuses on the schematic representation of fundamental GSK-3 enzymology and encompasses the GSK-3 inhibitors as a future therapeutic lead target for the management of T2DM that may significantly regulate insulin sensitivity to insulin receptor, glycogen synthesis and glucose metabolism. The various signaling mechanisms of inhibiting the GSK-3 by describing insulin signaling through Insulin Receptor Substrate (IRS-1), Phosphatidylinositol-3 Kinase (PI3K) and Protein Kinase B (PKB/ AKT) pathways that may hopefully facilitate the pharmacologist to design for antidiabetic drug evaluation model in near future have also been highlighted.

Antidiabetic effect of Drymaria cordata leaf against streptozotocin-nicotinamide-induced diabetic albino rats.

Drymaria cordata (Caryophyllaceae), commonly known as Abhijalo in Sikkimese-Tibetan, is a creeping herb grown in tropical and subtropical regions of the world. It is used by ethnic groups of Sikkim, North-East India, for the treatment of various diseases including diabetes. This study aimed to investigate the antidiabetic effect of methanol extract from D. cordata leaf (DCME) in streptozotocin (STZ) and nicotinamide (NA)-induced type 2 diabetes in rats. Diabetic Wistar albino rats were treated with DCME at 200 mg/kg and 400 mg/kg orally for 28 days. Metformin (150 mg/kg b.w.) was used as a reference drug. Fasting blood glucose (FBG) level; serum biochemical parameters; and liver, kidney, and antioxidant parameters were estimated, and pancreatic histopathology was performed after 28 days of treatment. Administration of DCME to STZ-NA-induced diabetic rats at 200 mg/kg and 400 mg/kg orally for 28 days exhibited statistically significant (P < 0.05) and dose-dependent reduction of FBG, glycosylated hemoglobin, serum lipid, and hepatorenal antioxidative parameters in DCME-treated groups when compared to those of diabetic controls. Histopathological studies of pancreas in DCME-treated rats showed improvement in ß-cell density compared to diabetic group. The results demonstrate the significant antidiabetic potential of D. cordata leaf in albino rats plausibly by reducing oxidative stress and serum lipids levels, justifying the folkloric use of this plant in the treatment of diabetes.

Expressions of CK-19, NF-kappaB, E-cadherin, beta-catenin and EGFR as diagnostic and prognostic markers by immunohistochemical analysis in thyroid carcinoma.

Immunohistochemical markers have been proposed for thyroid cancer diagnosis and prognostic studies. Immunohistochemical analysis of CK-19, NF-kappaB, beta-catenin, E-cadherin and EGFR were done to evaluate their diagnostic and prognostic efficiencies in eighty eight cancer specimen (PTC-52, FTC-16, benign nodule-12 and MNG-8). CK-19 was positive in 91% (62/68) DTC, 98% (51/52) PTC, 69% (11/16) FTC and 15% (3/20) benign thyroid nodules. NF-kappaB was expressed 93% (63/68) DTC, in 96% (50/52) PTC, 81% (11/16) FTC and 15% (3/20) benign thyroid nodules. Both CK-19 and NF-kappaB were significantly differentiated DTC, PTC and FTC from benign thyroid nodule (p < 0.0001) with diagnostic accuracy of 89.74%, 94.4% and 77.4% for CK-19 and 91.0%, 90.5% and 83.5% respectively for NF-kappaB. Though CK-19 and NF-kappaB were equally sensitive but CK-19 was most specific in the diagnosis of DTC and PTC. The diagnostic accuracy of beta-catenin was 96% and 94% and accuracy of E-cadherin was 90.1% and 93.9% for the diagnosis of metastatic PTC and FTC respectively. EGFR showed 90% (18/20) of metastatic PTC (p < 0.0001) and sensitivity, specificity and accuracy were 90%, 71.8% and 78.85% respectively. CK-19 and NF-kappaB were accurately diagnosed in DTC, PTC and FTC whereas, NF-kappaB, E-cadherin, beta-catenin and EGFR were strongly expressed in invasive papillary thyroid cancers and FTC, thus can be important diagnostic and prognostic marker for FTC and metastatic PTC. This may be concluded that immunohistochemical expression of panel of markers CK-19, NF-kappaB, E-cadherin, beta-catenin and EGFR can be useful in diagnosis and prognosis of DTC.