Superior antibacterial activity of ZnO-CuO nanocomposite synthesized by a chemical Co-precipitation approach.

Synthesis of highly efficient antibacterial agents has become highly important due to emergence of antibiotic resistance. Herein, Pristine ZnO and ZnO-CuO nanocomposite has been synthesized by simple chemical co-precipitation method and characterized by X-ray diffraction (XRD), microscopic and spectroscopic techniques. The prepared ZnO-CuO nanocomposite is composed of two dimensional nanosheets consisting of hexagonal ZnO and monoclinic CuO crystal phases present in coexistence. Moreover, a minute presence of Cu5Zn8 cubic phase has been evident in the XRD pattern of ZnO-CuO nanocomposite. Fourier Transform Infrared Spectroscopy (FTIR) spectrum of the prepared nanocomposite has revealed the presence of vibrational modes related to both Zn-O and Cu-O. Photoluminescence (PL) investigations depicted the formation of huge amounts of surface defects in ZnO-CuO nanocomposite as compared to pristine ZnO nanostructures. The prepared ZnO-CuO nanocomposite has efficiently killed Methicillin resistant Staphylococus aureus (s. aureus) bacterium by producing 24 mm of zone of inhibition (ZOI) comparing to 8 mm ZOI produced by pristine ZnO. The superior antibacterial activity of ZnO-CuO nanocomposite has been attributed to oxidative stress generated by electron transfer pathway and reactive oxygen species (ROS) generation.

SERPINA1 Hepatocyte-Specific Promoter Polymorphism Associate with Chronic Obstructive Pulmonary Disease in a Study of Kashmiri Ancestry Individuals.

PURPOSE: Different mutations in coding and non-coding sequences of the SERPINA1 gene have been implicated in the pathogenesis of COPD. However, - 10T/C mutation in the hepatocyte-directed promoter region has not been associated with COPD pathogenesis so far. Here, we report an increased frequency of - 10C genotype that is associated with decreased levels of serum alpha1-antitrypsin (α1AT) in COPD patients. METHODS: The quantification of serum α1AT was done by ELISA, the phenol-chloroform method was used for DNA extraction, PCR products were directly sequenced. The IBM SPSS Statistics v21 software was used for statistical analyses of the data. RESULTS: The mean serum α1AT level was found to be 1.203+0.239 and 3.162+0.160 g/L in COPD cases and in control, respectively. The - 10C allele is associated with an increased risk of COPD [OR, 3.50 (95%CI, 1.86-6.58); p < 0.001]. The combined variant genotype (TT+CC) was significantly found associated with an increased risk of COPD [OR, 3.20 (95% CI, 1.47-6.96); p = 0.003]. A significant association of the family history with COPD (overall p value= 0.0331) suggests that genetics may play an important role in the pathogenesis of COPD. CONCLUSION: The polymorphism associated with hepatocyte-specific promoter region (- 10T/C) is likely to be associated with the pathogenesis of COPD. It is quite possible that the change of the base in the hepatocyte-specific promoter of the SERPINA1 gene can modulate its strength, thereby driving the reduced expression of α1AT.

Enhanced production of α-amylase by Penicillium chrysogenum in liquid culture by modifying the process parameters.

In this paper, we have assessed the role of changing physicochemical parameters and substrate types on the production of α-amylase enzyme from Penicillium chrysogenum, with a view to determining the optimal conditions required for its maximum production. The findings of this research revealed that, at pH 6 using linseed oil cake as substratum, α-amylase enzyme production was maximum (550.0 U/mL), when the fungi was incubated for 6 days at 30 °C in 0.1 M acetate buffer. Further, reasonably good production of the α-amylase enzyme was also observed at pH 9 with all the experimented carbon sources as substrates. Moreover, statistical analysis, using analysis of variance (ANOVA) carried out to study the impact of different studied parameters on the α-amylase enzyme production revealed that incubation period of 6-18 days is highly significant (p = 0.01) factor in amylotic activity of the P. chrysogenum. Under the researched out optimal conditions, P. chrysogenum is an economically viable option for the industrial and biotechnological production of α-amylase enzyme.

Clinical relevance of genetic polymorphism in CYP2C9 gene to pharmacodynamics and pharmacokinetics of phenytoin in epileptic patients: validatory pharmacogenomic approach to pharmacovigilance.

AIMS AND OBJECTIVES: Variations in drug metabolizing genes are known to have a clinical impact on AED therapy. We genotyped normal and epileptic patient cohorts of monoethnic population of Kashmir valley for CYP2C9 gene and allelic polymorphism and investigated the effect of CYP2C9*2 and *3 polymorphism on the Pharmacokinetic and therapeutic and/or adverse pharmacodynamic responses to Phenytoin in the idiopathic epilepsy patients. METHODS: PCR-RFLP methods were used for genotyping of 121 normal controls and 92 idiopathic epilepsy patients for CYP2C9*2 and *3 polymorphism, the results were validated by direct sequencing. Phenytoin pharmacokinetic (PK) analysis in idiopathic epilepsy patients was done using a validated EMIT assay technique. Pharmacodynamic analysis was done by evaluating clinical response to phenytoin therapy and ADR monitoring. RESULTS: The respective frequencies of CYP2C9 *1, *2, and *3 alleles were 64%, 6.6%, 29.3%, and 58%, 9.8%, 32.6% in controls and idiopathic epilepsy patients from Kashmir valley. PK analysis revealed that AUC0–4 was a better surrogate biomarker of CYP2C9 metabolizer status compared to C4 and C0 concentrations alone. A comparison of “phenytoin response categories” among CYP2C9 Wild and Heterozygous groups did not reveal any significant difference between the groups (p=0.3800). CONCLUSION: CYP2C9* 3 was the most frequent mutant allele found in healthy controls and idiopathic epilepsy patients of ethnic Kashmiri population. CYP2C9 genotype based phenytoin therapy is highly relevant in Kashmiri population due to a high incidence of genetic variations associated with therapeutic and adverse responses to phenytoin. Phenytoin AUC0–4 tends to correlate better with genetic polymorphism of CYP2C9.

Contribution of TGFß1 codon 10 polymorphism to high myopia in an ethnic Kashmiri population from India.

This study looks at novel variants of the TGFß1 gene and their potential association with high myopia in an ethnic population from Kashmir, India. Allele frequencies of 247 Kashmiri subjects (from India) with high myopia and 176 ethnically matched healthy controls were tested for Hardy-Weinberg disequilibrium. The genotype and allele frequencies were evaluated using chi-square or Fisher's exact tests. One of the three SNPs in codon 10 showed a significant difference between patients and control subjects (rs1982073: p genotype = 0.003, p allele = 0.001). There were no statistically significant differences between patients and control subjects for the other two SNPs, rs1800471 at codon 25 and a novel variant at codon 52. SNP rs1982073, substituting proline with leucine, appeared to be significantly associated with high myopia (p < 0.05). In silico predictions show that substitutions are likely to have an impact on the structure and functional properties of the protein, making it imperative to understand their functional consequences in relation to high myopia.

MYP2 locus genes: Sequence variations, genetic association studies and haplotypic association in patients with High Myopia.

High Myopia (HM) is a common complex-trait eye disorder. There is essential evidence that genetic factors play a significant role in the development of nonsyndromic high myopia. Identification of susceptibility genes of high myopia will shed light on the pathophysiological mechanism underlying their genesis. This was a case control study examining the prospect of association of DLGAP1, EMILIN2 & MYOM1 genes on MYP2 locus in purely ethnic (Kashmiri) population representing a homogeneous cohort. Genomic DNA was extracted using phenol chloroform and salting out method. Extracted DNA was genotyped for polymorphic variations in MYOM1, EMILIN2 and DLGAP1 genes involving Sanger di-deoxy method. Allele frequencies were tested for Hardy-Weinberg disequilibrium in 224 cases and compared with 220 emmetropic controls. In DLGAP1, documented single nucleotide polymorphism (SNP); Pro517Pro was observed. A previously reported Asn451Asn SNP was observed in EMILIN2. MYOM1 showed five polymorphic variations; two in coding region (Gly333Gly & Gly341Ala) and three intronic (c.1022+23, G>A; c.3418+44 G>T & c.3418+65; C>G). All of the elucidated SNPs were having statistical significant role in increasing or decreasing the risk of disease. Although not statistically significant, a novel Glu507Lys SNP was observed in DLGAP1 (P>0.05). In silico predictions showed MYOM1 Gly341Ala to be benign & tolerated substitution while as DLGAP1 Glu507Lys to be possibly damaging substitution. The studied SNPs followed Over-Dominant, Recessive and Co-Dominant mode of inheritance with specific haplotypes associated with the disease. Our study reveals the involvement of MYP2 locus candidate gene polymorphism in the pathogenesis of HM.

A novel G26A variation in 5' half of TGIF1 gene associates with high myopia in ethnic Kashmiri population from India.

This study aims to look at novel variations in TGIF1 gene and explores their potential association with high myopia in an ethnic population from Kashmir (India). Genomic DNA was genotyped for polymorphic variations, and allele frequencies were tested for the Hardy-Weinberg disequilibrium in 240 ethnic Kashmiri cases with high myopia with a spherical equivalent of >-6 diopters (D) and compared with emmetropic controls with spherical equivalent within -0.5D in one or both eyes represented by a sample size of 228. In this study, we found a novel sequence variation G26A (GAT to AAT) in 5' half of TGIF1 gene (p. aspartic acid >asparagine) at a frequency of 62% (148/240, P ≤ 0.0001). Variation appears to associate with high myopia significantly (P ≤ 0.001) as it happens to be present only in high myopia affected individuals. Further, it shows statistical significance for its association with gender and the degree of myopia (P ≤ 0.05). In addition, in silico predictions show that variation likely has an impact on the structure and functional properties of the protein. The assessment of the I-TASSER protein structure showed higher energy for a wild-type protein (-5820.186 kJ/mol) as compared to mutant protein (-6595.593 kJ/mol).

Calibration-Free Laser-Induced Plasma Analysis of Nanoparticle-Doped Material Using Self-Absorption Correction Methodologies.

The qualitative and quantitative analysis of doped nanomaterial containing iron (Fe) and tin (Sn) nanoparticles was investigated using laser-induced breakdown spectroscopy (LIBS). Doped nanoparticles were prepared via co-precipitation and hydrothermal processes. The emission spectra of ablated plasma of doped material revealed the existence of different species in the doped nanomaterial. Simple calibration-free LIBS (CF-LIBS) and internal reference self-absorption correction (IRSAC) CF-LIBS approaches were applied to emission spectra of nanomaterial for quantitative analysis. For both approaches, different spectroscopic parameters such as plasma temperature and electron number density were also determined. Plasma temperature was estimated using a Boltzmann plot and Saha-Boltzmann plot while electron number density was estimated by Stark broadening methods and Saha-Boltzmann equations. Results of both calibration-free approaches were compared with a weight percentage method and other recognized techniques such as laser ablation time of flight (LA-TOF) spectroscopy and energy dispersive X-ray (EDX). We concluded that our results provide good agreement with experimental data obtained using LA-TOF spectroscopy and a small deviation from data obtained using the EDX technique. The current work confirms LIBS as a valid analytical approach for quantitative analysis of nanomaterials.

Polymorphic Analysis of Leptin Promoter in Obese/diabetic Subjects in Kashmiri Population.

BACKGROUND: The role of common variants in leptin promoter has already been established to play a major role in obesity and diabetes in humans. The study was accordingly focused on leptin promoter variants and their potential association with diabetes and obesity in ethnic population from Kashmir, India. METHODS: Allele frequencies of 620 Kashmiri subjects with diabetes (200), obese subjects (200), and ethnically matched healthy controls (200) were tested for the Hardy-Weinberg disequilibrium. Among 200 obese subjects, a total of 50 persons were with diabetes. The genotype and allele frequencies were evaluated using the Chi-square or Fisher's exact tests. RESULTS: Sequence analysis revealed two reported variations i.e., rs72563764C>T and rs7799039G>A in promoter region. Both variants show homozygous as well as heterozygous genotypes. These variations indicated significant difference with respect to allelic and genotypic frequencies in all groups i.e., persons with diabetes, obese, and obese persons with diabetes (P < 0.05). We also analyzed the association of these variations with biochemical characteristics and found significant association of rs72563764C>T with triglycerides (TG) in obese patients and fasting plasma glucose (FPG) and random blood sugar (RBS) in obese/persons with diabetes. Also rs7799039G>A showed association with postprandial plasma sugar (PPPS) in obese patients and FPG and resting plasma glucose (RPG) in obese persons with diabetes. CONCLUSIONS: Our results are suggestive of the association of leptin promoter gene variations i.e., rs72563764C>T and rs7799039G>A with both diabetes and obesity.

Optimised synthesis of ZnO-nano-fertiliser through green chemistry: boosted growth dynamics of economically important L. esculentum.

Mounting-up economic losses to annual crops yield due to micronutrient deficiency, fertiliser inefficiency and increasing microbial invasions (e.g. Xanthomonas cempestri attack on tomatoes) are needed to be solved via nano-biotechnology. So keeping this in view, the authors' current study presents the new horizon in the field of nano-fertiliser with highly nutritive and preservative effect of green fabricated zinc oxide-nanostructures (ZnO-NSs) during Lycopersicum esculentum (tomato) growth dynamics. ZnO-NS prepared via green chemistry possesses highly homogenous crystalline structures well-characterised through ultraviolet and visible spectroscopy, Fourier transform infrared spectroscopy, X-ray diffraction and scanning electron microscope. The ZnO-NS average size was found as small as 18 nm having a crystallite size of 5 nm. L. esculentum were grown in different concentrations of ZnO-NS to examine the different morphological parameters includes time of seed germination, germination percentage, the number of plant leaves, the height of the plant, average number of branches, days count for flowering and fruiting time period along with fruit quantity. Promising results clearly predict that bio-fabricated ZnO-NS at optimum concentration resulted as growth booster and dramatically triggered the plant yield.

Antimicrobial potential of green synthesized CeO2 nanoparticles from Olea europaea leaf extract.

This article reports the green fabrication of cerium oxide nanoparticles (CeO2 NPs) using Olea europaea leaf extract and their applications as effective antimicrobial agents. O. europaea leaf extract functions as a chelating agent for reduction of cerium nitrate. The resulting CeO2 NPs exhibit pure single-face cubic structure, which is examined by X-ray diffraction, with a uniform spherical shape and a mean size 24 nm observed through scanning electron microscopy and transmission electron microscopy. Ultraviolet-visible spectroscopy confirms the characteristic absorption peak of CeO2 NPs at 315 nm. Fourier transform infrared spectroscopy reflects stretching frequencies at 459 cm-1, showing utilization of natural components for the production of NPs. Thermal gravimetric analysis predicts the successful capping of CeO2 NPs by bioactive molecules present in the plant extract. The antimicrobial studies show significant zone of inhibition against bacterial and fungal strains. The higher activities shown by the green synthesized NPs than the plant extract lead to the conclusion that they can be effectively used in biomedical application. Furthermore, reduction of cerium salt by plant extract will reduce environmental impact over chemical synthesis.

TGIF1 is a potential candidate gene for high myopia in ethnic Kashmiri population.

PURPOSE: High myopia is a complex disorder that imposes serious consequences on ocular health. Linkage analysis has identified several genetic loci with a series of potential candidate genes that reveal an ambiguous pattern of association with high myopia due to population heterogeneity. We have accordingly chosen to examine the prospect of association of one such gene [transforming growth ß-induced factor 1 (TGIF1)] in population that is purely ethnic (Kashmiri) and represents a homogeneous cohort from Northern India. METHODS: Cases with high myopia with a spherical equivalent of ≥-6 diopters (D) and emmetropic controls with spherical equivalent within ±0.5 D in one or both eyes represented by a sample size of 212 ethnic Kashmiri subjects and 239 matched controls. Genomic DNA was genotyped for sequence variations in TGIF1 gene and allele frequencies tested for Hardy-Weinberg disequilibrium. Potential association was evaluated using χ(2) or Fisher's exact test. RESULTS: Two previously reported missense variations C > T, rs4468717 (first base of codon 143) changing proline to serine and rs2229333 (second base of codon 143) changing proline to leucine were identified in exon 10 of TGIF1. Both variations exhibited possibly significant (p < 0.05) association with the disease phenotype. Since the variant allele frequency of both the single-nucleotide polymorphisms in cases is higher than controls with odds ratio greater than 1.Therefore, variant allele of both the single-nucleotide polymorphisms represents the possible risk factor for myopia in the Kashmiri population. In silico predictions show that substitutions are likely to have an impact on the structure and functional properties of the protein, making it imperative to understand their functional consequences in relation to high myopia. CONCLUSIONS: TGIF1 is a relevant candidate gene with potential to contribute in the genesis of high myopia.

Sn doping induced enhancement in the activity of ZnO nanostructures against antibiotic resistant S. aureus bacteria.

Highly ionic metal oxide nanostructures are attractive, not only for their physiochemical properties but also for antibacterial activity. Zinc oxide (ZnO) nanostructures are known to have inhibitory activity against many pathogens but very little is known about doping effects on it. The antibacterial activity of undoped ZnO and tin (Sn) doped ZnO nanostructures synthesized by a simple, versatile, and wet chemical technique have been investigated against Escherichia coli, methicillin-resistant Staphylococcus aureus, and Pseudomonas aeruginosa bacterial strains. It has been interestingly observed that Sn doping enhanced the inhibitory activity of ZnO against S. aureus more efficiently than the other two bacterial strains. From cytotoxicity and reactive oxygen species (ROS) production studies it is found that Sn doping concentration in ZnO does not alter the cytotoxicity and ROS production very much. It has also been observed that undoped and Sn doped ZnO nanostructures are biosafe and biocompatible materials towards SH-SY5Y Cells. The observed behavior of ZnO nanostructures with Sn doping is a new way to prevent bacterial infections of S. aureus, especially on skin, when using these nanostructures in creams or lotions in addition to their sunscreen property as an ultraviolet filter. Structural investigations have confirmed the formation of a single phase wurtzite structure of ZnO. The morphology of ZnO nanostructures is found to vary from spherical to rod shaped as a function of Sn doping. The excitation absorption peak of ZnO is observed to have a blue shift, with Sn doping leading toward a significant tuning in band gap.