Bashir A. Ganai

Type 2 diabetes mellitus: From a metabolic disorder to an inflammatory condition

Diabetes mellitus is increasing at an alarming rate and has become a global challenge. Insulin resistance in target tissues and a relative deficiency of insulin secretion from pancreatic β-cells are the major features of type 2 diabetes (T2D). Chronic low-grade inflammation in T2D has given an impetus to the field of immuno-metabolism linking inflammation to insulin resistance and β-cell dysfunction. Many factors advocate a causal link between metabolic stress and inflammation. Numerous cellular factors trigger inflammatory signalling cascades, and as a result T2D is at the moment considered an inflammatory disorder triggered by disordered metabolism. Cellular mechanisms like activation of Toll-like receptors, Endoplasmic Reticulum stress, and inflammasome activation are related to the nutrient excess linking pathogenesis and progression of T2D with inflammation. This paper aims to systematically review the metabolic profile and role of various inflammatory pathways in T2D by capturing relevant evidence from various sources. The perspectives include suggestions for the development of therapies involving the shift from metabolic stress to homeostasis that would favour insulin sensitivity and survival of pancreatic β-cells in T2D.

Chemical composition, antioxidant and antibacterial activities of the leaf essential oil of Juglans regia L. and its constituents

The essential oil from the leaves of Juglans regia L. (Juglandaceae) growing wild in Kashmir (India) was obtained by hydrodistillation and analysed by a combination of capillary GC-FID and GC-MS. A total of 38 compounds, representing 92.7% of the oil, were identified and the major components were found to be α-pinene (15.1%), β-pinene (30.5%), β-caryophyllene (15.5%) germacrene D (14.4%) and limonene (3.6%). The essential oil and the main individual constituents were screened for antibacterial activity and the essential oil evaluated for antioxidant activity. Antibacterial activity was evaluated using the disc diffusion and microdilution methods against a group of clinically significant Gram-positive (Staphylococcus epidermidis MTCC-435, Bacillus subtilis MTCC-441, Staphylococcus aureus) and Gram-negative bacteria (Proteus vulgaris MTCC-321, Pseudomonas aeruginosa MTCC-1688, Salmonella typhi, Shigella dyssenteriae, Klebsiella pneumonia and Escherichia coli). The essential oil and its major components exhibited broad spectrum inhibition against all the bacterial strains with Gram-positive being more susceptible to the oil than Gram-negative bacteria. Antioxidant activity of the oil was evaluated by the scavenging effect on DPPH (2,2-diphenyl-1-picrylhydrazyl) and hydroxyl radicals. In general, the essential oil exhibited high antioxidant activity which was comparable to the reference standards at the same dose (ascorbic acid and butylated hydroxyl toluene, BHT) with IC(50) values of 34.5 and 56.4μg/ml calculated by DPPH and hydroxyl radical scavenging assays respectively.

Polymorphic Variation in Glutathione-S-transferase Genes and Risk of Chronic Myeloid Leukaemia in the Kashmiri Population

Cancer is a complex disease and the genetic susceptibility to it could be an outcome of the inherited difference in the capacity of xenobiotic metabolizing enzymes. Glutathione-S-transferases (GSTs) are phase II metabolizing enzymes whose various genotypes have been associated with increased risk of different types of cancer. Null mutations caused by the deletion of the entire gene result in the absence of the enzymatic activity and increase in the risk of developing cancer including chronic myeloid leukaemia (CML). In the present case-control study we evaluated the effect of null mutations in GSTM1 and GSTT1 genes on the risk of developing CML. The study included 75 CML patients (43 males and 32 females; age (mean ± S.D) 42.3 ± 13.4 years) and unrelated non-malignant controls (76 male and 48 females; age (mean ± S.D) 41.5 ± 12.9). The distribution of GSTM1 and GSTT1 genotypes in CML patients and controls was assessed by multiplex-PCR method. Logistic regression was used to assess the relationship between GSTM1 and GSTT1 genotypes and risk of CML. Chi-square test was used to evaluate the trend in modulating the risk to CML by one or more potential high risk genotype. Although GSTM1 null genotype frequency was higher in CML patients (41%) than in the controls (35%), it did not reached a statistical significance (OD = 1.32, 95% CI: 0.73-2.40; P value = 0.4295). The frequency of GSTT1 null genotypes was higher in the CML patients (36%) than in the controls (21%) and the difference was found to be statistically significant (OD = 2.12, 95% CI: 1.12-4.02; P value = 0.0308). This suggests that the presence of GSTT1 genotype may have protective role against the CML. We found a statistically significant (OD = 3.09, 95% CI: 1.122-8.528; P value = 0.0472) interaction between the GSTM1 and GSTT1 null genotypes and thus individuals carrying null genotypes of both GSTM1 and GSTT1 genes are at elevated risk of CML.

Brick kiln emissions and its environmental impact: A Review

Brick manufacturing is the fastest-growing industrial sector in many countries (like china, India, Bangladesh and Pakistan) and among the top three sectors, along with vehicle exhaust and resuspended road dust, contributing to the air pollution and health problems in Dhaka (Bangladesh). The total emissions from the brick manufacturing in the Greater Dhaka region, to produce 3.5 billion bricks per year has been estimated about 23,300 tons of particulate matter having aerodynamic diameter < 2.5 μm (PM2.5), 15,500 tons of sulfur dioxide (SO2), 302,000 tons of carbon monoxide (CO), 6,000 tons of black carbon (BC) and 1.8 million tons of carbon dioxide (CO2). Emission of individual air pollutant from brick kilns varied significantly during a firing batch (seven days) and between kilns. Average emission factors per 1,000 bricks were 6.35 to 12.3 kg of CO, 0.52 to 5.9 kg of SO2 and 0.64 to 1.4 kg of particulate matter (PM). Presently sulphur dioxide (SO2), oxides of nitrogen (NOx) and suspended particulate matter (SPM) are the main issue pertaining to air pollution problems in developing countries, where it contributes both to urban pollution and to regional acid depositions. Among man-made sources, coal combustion in stationary sources accounts for 74%, industries 22% and transportation 2% of the total oxides of sulphur (SOx). and it is considered that SO2 is the chief emission in brick production. On an international basis, 75 to 85% of SO2 emissions are the result of fossil fuel burning. It is predictable that just about 93% of the global SO2 emissions are emitted in the northern hemisphere. It has been revealed that biomass is responsible for the emission of both trace and non trace gases such as carbon dioxide (CO2), methane (CH4) and oxides of nitrogen (NOx) from traditional brick industries and lots of toxic fumes containing suspended particulate matters rich in carbon particles and high concentration of CO and SOx get produced. Studies have shown the average value of particulate matter of size less than ten microns and total suspend particles for the pre-operation time of brick kilns was 0.029 and 0.033 mg/m³, respectively whereas, it reached 0.050 and 0.056 mg/m³, respectively during the brick kiln operation time. Similarly, recent studies on brick kilns in District Budgam of Kashmir valley (India) have shown some major negative impacts on the environment in respect of air quality, human health and vegetation in particular. Key words: Pollution, emissions, environment, industrialization, transportation, brick kiln, human health, vegetation.

Antimicrobial studies of unsymmetrical bis-1,2,3- triazoles

Aryl azides were treated with allenylmagnesium bromide to generate 1,5-disubstituted butynyl 1,2,3-triazoles in a domino fashion, which upon Cu(I) catalyzed 1,3-dipolar cycloaddition with aryl azides afforded novel bis-1,2,3-triazoles in quantitative yields. The final products were analyzed for their antimicrobial activities against a panel of bacterial and fungal strains which revealed the products to be potent antimicrobials.

A Potent Inhibitor of Phosphoinositide 3-Kinase (PI3K) and Mitogen Activated Protein (MAP) Kinase Signalling, Quercetin (3, 3', 4', 5, 7-Pentahydroxyflavone) Promotes Cell Death in Ultraviolet (UV)-B-Irradiated B16F10 Melanoma Cells.

Ultraviolet (UV) radiation–induced skin damage contributes strongly to the formation of melanoma, a highly lethal form of skin cancer. Quercetin (Qu), the most widely consumed dietary bioflavonoid and well known inhibitor of phosphoinositide 3-kinase (PI3K) and mitogen activated protein (MAP) kinase signalling, has been reported to be chemopreventive in several forms of non-melanoma skin cancers. Here, we report that the treatment of ultraviolet (UV)-B-irradiated B16F10 melanoma cells with quercetin resulted in a dose dependent reduction in cell viability and increased apoptosis. The present study has brought out that the pro-apoptotic effects of quercetin in UVB-irradiated B16F10 cells are mediated through the elevation of intracellular reactive oxygen species (ROS) formation, calcium homeostasis imbalance, modulation of anti-oxidant defence response and depolarization of mitochondrial membrane potential (ΔΨM). Promotion of UVB-induced cell death by quercetin was further revealed by cleavage of chromosomal DNA, caspase activation, poly (ADP) ribose polymerase (PARP) cleavage, and an increase in sub-G1 cells. Quercetin markedly attenuated MEK-ERK signalling, influenced PI3K/Akt pathway, and potentially enhanced the UVB-induced NF-κB nuclear translocation. Furthermore, combined UVB and quercetin treatment decreased the ratio of Bcl-2 to that of Bax, and upregulated the expression of Bim and apoptosis inducing factor (AIF). Overall, these results suggest the possibility of using quercetin in combination with UVB as a possible treatment option for melanoma in future.

Antidiabetic Activity of Artemisia amygdalina Decne in Streptozotocin Induced Diabetic Rats

Artemisia species have been extensively used for the management of diabetes in folklore medicine. The current study was designed to investigate the antidiabetic and antihyperlipidemic effects of Artemisia amygdalina. Petroleum ether, ethyl acetate, methanol, and hydroethanolic extracts of Artemisia amygdalina were tested for their antidiabetic potentials in diabetic rats. The effect of extracts was observed by checking the biochemical, physiological, and histopathological parameters in diabetic rats. The hydroethanolic and methanolic extracts each at doses of 250 and 500 mg/kg b. w significantly reduced glucose levels in diabetic rats. The other biochemical parameters like cholesterol, triglycerides, low density lipoproteins (LDL), serum creatinine, serum glutamate pyruvate transaminase (SGPT), serum glutamate oxaloacetate transaminase (SGOT), and alkaline phosphatise (ALP), were found to be reduced by the hydroethanolic and methanolic extracts. The extracts also showed reduction in the feed and water consumption of diabetic rats when compared with the diabetic control. The histopathological results of treated groups showed the regenerative/protective effect on β-cells of pancreas in diabetic rats. The current study revealed the antidiabetic potential of Artemisia amygdalina being effective in hyperglycemia and that it can effectively protect against other metabolic aberrations caused by diabetes in rats, which seems to validate its therapeutic traditional use.

Isolation and antiproliferative activity of Lotus corniculatus lectin towards human tumour cell lines.

The objective of the study was to investigate the anti cancer activity of a lectin isolated from Lotus corniculatus seeds. A tetrameric 70kDa galactose specific lectin was purified using two step simple purification protocol which involved affinity chromatography on AF-BlueHC650M and gel filtration on Sephadex G-100. The lectin was adsorbed on AF-BlueHC650M and desorbed using 1M NaCl in the starting buffer. Gel filtration on Sephadex G-100 yielded a major peak absorbance that gave two bands of 15kDa and 20kDa in SDS PAGE. Hemagglutination activity was completely preserved, when the temperature was in the range of 20-60°C. However, drastic reduction in activity occurred at temperatures above 60°C. Full hemagglutination activity was retained at ambient pH 4-12. Thereafter no activity was observed above pH 13. Hemaglutination of the lectin was inhibited by d-galactose. The lectin showed a strong antiproliferative activity towards human leukemic (THP-1) cancer cells followed by lung cancer (HOP62) cells and HCT116 with an IC50 of 39μg/ml and 50μg/ml and 60μg/ml respectively. Flow cytometry analysis showed an increase in the percentage of cells in sub G0G1 phase confirming that Lotus corniculatus lectin induced apoptosis. Morphological observations showed that Lotus corniculatus lectin (LCL) treated THP-1 cells displayed apparent apoptosis characteristics such as nuclear fragmentation, appearance of membrane enclosed apoptotic bodies and DNA fragmentation. Lotus corniculatus lectin (LCL) effectively inhibits the cell migration in a dose dependent manner as indicated by the wound healing assay.

Association of a VDR Gene Polymorphism with Risk of Colorectal Cancer in Kashmir

Roles of the vitamin D receptor in etiology of cancers, including colorectal cancer, have been repeatedly stressed in different parts of the world. A case control study aimed to evaluate the relationship between the two was therefore initiated in Kashmir, known both for its increasing incidence of gastrointestinal cancers and deficiency of micro-nutrients especially vitamin D. The study included a total of 617 subjects (312 colorectal cancer cases and 305 controls), with sampling carried out over a period of 5 years. DNA samples from the blood of the subjects were analyzed for start codon Fok I VDR polymorphism. We obtained a 1.3 fold increased risk among individuals homozygous for f variants as compared to subjects homozygous for F allele (odds ratio OR 1.3, 95%CI, 0.861-1.65). Our study also showed statistically significant results when dwelling and tumor location characteristics were stratified with Fok I polymorphism, all of which suggests a possible role of Fok I polymorphism in the etiology of CRC in Kashmir.

Polymorphisms in the 3′UTR of the human leptin gene and their role in hypertension

Leptin is a protein hormone, mainly synthesized in adipocytes, that regulates the food intake and energy expenditure of the body. Rare mutations in the leptin gene cause obesity. Common polymorphisms of the leptin gene have been associated with obesity, however their association with arterial blood pressure has not been fully elucidated. The aim of the present study was to examine the effect of variants in the 3′ flanking region of the leptin gene on blood pressure in hypertensive subjects with high (35.2±5.12) and low (20.13±1.3) body mass index (BMI). Microsatellite polymorphisms and the C538T SNP in the 3′UTR of the leptin gene were screened in 362 subjects, and different biochemical and anthropometric parameters were measured. The levels of serum urea, creatinine, glucose, cholesterol, triglyceride, leptin and angiotensin II were determined in all subjects. A strong association of microsatellite polymorphisms with essential hypertension was found in subjects with a high BMI, but this association was only slight in subjects with a normal BMI. The C538T variant was not found in this population. The frequency of the Class I/Class I and Class I/Class II genotype for tetranucleotide polymorphisms was also significantly higher in the hypertensive compared to the normotensive group (p≤0.0001). In addition, a significant correlation was found between serum leptin and Class I/I and Class I/II genotypes. Linear regression analysis showed an independent correlation of leptinemia with BMI (p=0.019), while a notable correlation was found between serum leptin concentration and angiotensin II. The study confirmed that shorter alleles of microsatellites in the 3′ flanking region of leptin are significantly associated with hypertension, however, the underlying mechanism remains unknown.