Concomitant Effect of Quercetin and Its Copper Complex in the Development of Sustained-Release Nanoparticles of Polycaprolactone, Used for the Treatment of Skin Infection.

The study aimed to improve the treatment of impetigo with naturally occurring quercetin and its copper-quercetin (Cu-Q) complex by preparing sustained-release (SR) nanoparticles of polycaprolactone (PCL). The solvent evaporation method was used for the copper-quercetin (Cu-Q) complex formation, and their PCL nanoparticles (PCL-NPs, Q-PCL-NPs, and Cu-Q-PCL-NPs) were prepared by the high-pressure homogenization method. Synthesis of nanoparticles was confirmed by their physicochemical and antibacterial properties of quercetin against Gram-positive as well as Gram-negative bacteria. The percentage loading efficiency of quercetin and release in 100 mM of phosphate buffer pH 7.4 and 5.5 at 37 °C was found to be more than 90% after 24 h with the zero-order release pattern. Minimum inhibitory concentration of nanoparticles was found to increase threefold in the case of Cu-Q-PCL-NPs may be due to the synergistic antibacterial behavior. Scanning electron microscopy showed spherical nanoparticles, and surface roughness was confirmed by atomic force microscopy analysis. Fortunately, no sign of irritation on rat skin even at 3%, was seen. In vitro antioxidant assay by 2,2-diphenyl-1-picrylhydrazyl reduction was found to be ≤80 ± 0.02% which confirmed their scavenging activity. Interestingly, for the ex vivo study, the tape-stripping model was applied against Staphylococcus aureus containing rats and showed the formation of the epidermal layer within 4-5 days. Confirmation of antibacterial activity of pure quercetin, from Cu-Q complex, and their SR release from Q-PCL-NPs and Cu-Q-PCL-NPs was considered an effective tool for the treatment of skin diseases and can be used as an alternative of already resistant ciprofloxacin in impetigo.

Methyl Jasmonate Alleviated the Adverse Effects of Cadmium Stress in Pea (Pisum sativum L.): A Nexus of Photosystem II Activity and Dynamics of Redox Balance.

The accumulation of cadmium (Cd) in leaves reduces photosynthetic capacity by degrading photosynthetic pigments, reducing photosystem II activity, and producing reactive oxygen species (ROS). Though it was demonstrated that the application of Methyl Jasmonate (MeJA) induces heavy metal (HM) stress tolerance in plants, its role in adjusting redox balance and photosynthetic machinery is unclear. In this study, the role of MeJA in modulating photosystem II (PSII) activity and antioxidant defense system was investigated to reduce the toxic effects of Cd on the growth of pea (Pisum sativum L.) cultivars. One-week-old seedlings of three pea varieties were subjected to Cd stress (0, 50, 100 µm), and MeJA (0, 1, 5, 10 µm) was applied as a foliar spray for 2 weeks. Cadmium stress reduced the growth of all three pea varieties. Cadmium stress decreased photosynthetic pigments [Chl a (58.15%), Chl b (48.97%), total Chl (51.9%) and carotenoids (44.01%)] and efficiency of photosystem II [Fv/Fm (19.52%) and Y(II; 67.67%)], while it substantially increased Cd accumulation along with an increase in ROS (79.09%) and lipid peroxidation (129.28%). However, such adverse effects of Cd stress varied in different pea varieties. Exogenous application of MeJA increased the activity of a battery of antioxidant enzymes [superoxide dismutase (33.68%), peroxidase (29.75%), and catalase (38.86%)], improved photosynthetic pigments and PSII efficiency. This led to improved growth of pea varieties under Cd stress, such as increased fresh and dry weights of shoots and roots. In addition, improvement in root biomass by MeJA was more significant than that of shoot biomass. Thus, the mitigating effect of MeJA was attributed to its role in cellular redox balance and photosynthetic machinery of pea plants when exposed to Cd stress.

Antibiograms of Gut Flora of Poultry Farms Workers Reveal Higher Resistance Levels as Compared to Non-Workers.

Introduction: Antibiotics are being used in humans and animals for treatment and control of bacterial infections. Excessive use of antibiotics in the production of poultry is a popular practice, but it poses serious health issues by transferring resistance from farm to humans via food or direct exposure. Study Objective: The objective of this study was to carry out a comparison of the resistance and sensitivity profile of isolated isolates from sewage of toilets that were in use of workers inside the farm and from sewage of household toilets. Methodology: In this study, a total of 320 sewage samples were collected. The antibiotic susceptibility profile was checked by Kirby-Bauer disc diffusion method, and the statistical analysis was carried out by MS excel. Chi-square test was performed to determine whether the antibiograms from two sample types were statistically different from each other or not. Results: From 320 sewage samples, a total of 296 bacterial isolates were isolated among which the leading bacterium was E. coli. The proportion of resistance, ESBL production and MDR was significantly higher in bacteria isolated from sewage of toilets under use of poultry farm workers as compared to the sewage from domestic use toilets. Conclusion: Resistance significantly increased in the bacteria isolated from toilets under use of poultry farm workers as compared to the ones isolated from control sewage samples.

Two-Component System Genes in Sorghum bicolor: Genome-Wide Identification and Expression Profiling in Response to Environmental Stresses.

The two-component signal transduction system (TCS) acts in a variety of physiological processes in lower organisms and has emerged as a key signaling system in both prokaryotes and eukaryotes, including plants. TCS genes assist plants in processes such as stress resistance, cell division, nutrition signaling, leaf senescence, and chloroplast division. In plants, this system is composed of three types of proteins: response regulators (RRs), histidine kinases (HKs), and histidine phosphotransfer proteins (HPs). We aimed to study the Sorghum bicolor genome and identified 37 SbTCS genes consisting of 13 HKs, 5 HPs, and 19 RRs (3 type-A RRs, 7 type-B RRs, 2 type-C RRs, and 7 pseudo-RRs). The structural and phylogenetic comparison of the SbTCS members with their counterparts in Arabidopsis thaliana, Oryza sativa, Cicer arietinum, and Glycine max showed group-specific conservations and variations. Expansion of the gene family members is mostly a result of gene duplication, of both the tandem and segmental types. HKs and RRs were observed to be originated from segmental duplication, while some HPs originated from tandem duplication. The nuclear genome of S. bicolor contain 10 chromosomes and these SbTCS genes are randomly distributed on all the chromosomes. The promoter sequences of the SbTCS genes contain several abiotic stress-related cis-elements. RNA-seq and qRT-PCR-based expression analysis demonstrated most of the TCS genes were responsive to drought and salt stresses in leaves, which suggest their role in leaf development. This study lays a foundation for further functional study of TCS genes for stress tolerance and developmental improvement in S. bicolor.

Artificial Neural Network (ANN) Approach to Predict an Optimized pH-Dependent Mesalamine Matrix Tablet.

BACKGROUND: Severe bleeding and perforation of the colon and rectum are complications of ulcerative colitis which can be treated by a targeted drug delivery system. PURPOSE: Development of colon-targeted delivery usually involves a complex formulation process and coating steps of pH-sensitive methacrylic acid based Eudragit®. The current work was purposefully designed to develop dicalcium phosphate (DCP) facilitated with Eudragit-S100-based pH-dependent, uncoated mesalamine matrix tablets. MATERIALS AND METHODS: Mesalamine formulations were compressed using wet granulation technique with varying compositions of dicalcium phosphate (DCP) and Eudragit-S100. The developed formulations were characterized for physicochemical and drug release profiles. Infrared studies were carried out to ensure that there was no interaction between active ingredients and excipients. Artificial neural network (ANN) was used for the optimization of final DCP-Eudragit-S100 complex and the experimental data were employed to train a multi-layer perception (MLP) using quick propagation (QP) training algorithm until a satisfactory root mean square error (RMSE) was reached. The ANN-aided optimized formulation was compared with commercially available Masacol®. RESULTS: Compressed tablets met the desirability criteria in terms of thickness, hardness, weight variation, friability, and content uniformity, ie, 5.34 mm, 7.7 kg/cm2, 585±5 mg (%), 0.44%, and 103%, respectively. In-vitro dissolution study of commercially available mesalamine and optimized formulation was carried out and the former showed 100% release at 6 h while the latter released only 12.09% after 2 h and 72.96% after 12 h which was fitted to Weibull release model with b value of 1.3, indicating a complex release mechanism. CONCLUSION: DCP-Eudragit-S100 blend was found explicative for mesalamine release without coating in gastric and colonic regions. This combination may provide a better control of ulcerative colitis.

Antibacterial activity and characterization of zinc oxide nanoparticles synthesized by microalgae.

Biosynthesis of zinc oxide nanoparticles (ZnO-NPs) using microalgae is novel and cost-effective approach. We studied production, molecular characterization, and antibacterial activity. Filtrates of isolated microalgae strain ZAA1 (MF140241), ZAA2 (MF114592) and ZAA3 (MF114594) were used. Incubation of these strains in 5mM solution of zinc nitrate was resulted in the synthesis of ZnO-NPs. Fourier-transform infrared, UV-visible spectroscopy and scanning electron microscopy were used to characterize the nanoparticles. Significant antibacterial activity of ZnO-NPs was measured against Escherichia coli, Staphylococcus aureus, Micrococcus luteus, Klebsiella pneumoniae and Citrobacter freundii. The microalgae mediated ZnO-NPs production is a successful procedure that can be used in a wide range of biomedical applications.

RNA therapeutics: Identification of novel targets leading to drug discovery.

The established concept that RNA works only for protein synthesis has been changed over the past few decades and shifted towards therapeutic purposes. Almost 98% of mammalian genome is transcribed into nonprotein coding RNA termed as noncoding RNA (ncRNA) which plays regulatory role in molecular and cellular functions as controlling gene expression. These ncRNAs are classified as long noncoding RNA (lncRNA), short noncoding RNA (sncRNA), and translational/structural RNA which possess diverse functions. These ncRNAs regulate expression of normal gene and modulate disease development and progression. The characterization of ncRNA genes and their mechanisms can aid in disease diagnosis, examining its development and direct specific therapies in different disease treatments. Due to their unique modes of action, they are designated as novel class of targets leading to drug discovery. The modulation in these ncRNAs can enhance therapeutic treatments against different diseases by targeting mRNA for its cleavage via antisense olionucleotides (ASOs)/DNA duplex, RNA alternative splicing/editing, chromatin modification, transcriptional/translational interference, RNA masking, small interfering RNA/microRNA-based gene silencing and by inducing immunity via RNA-based vaccination. Here in this review, we tried to summarize the emerging fields of ncRNA, their role in different diseases, their modes of action, and their potential in target identification and therapeutic drug development.

Influence of single-nucleotide polymorphisms in the IFNG towards susceptibility to tuberculosis in a Pakistani population.

Tuberculosis (TB) is a global issue as one-third of the population worldwide is considered to be infected. TB has become a critical public health problem as a result of increasing drug resistance, which poses a challenge to current control strategies. Similar to environmental factors, genetic makeup of the host equally contributes to disease onset. We performed genotypic analysis to examine the relationship between IFNG and TB onset and drug resistance in a Pakistani population comprising 689 subjects. Notable differences were observed in the IFNG polymorphism (+874T/A) between the case and control groups. The frequency of the wild-type genotype (TT) in the controls (43.2%) was significantly higher than in the cases (25.3%) (odds ratio [OR] = 0.77, p < 0.0001), while the mutant genotype frequency (AA) (38.57%) in the cases was significantly higher than in the controls (22.6%) (OR = 1.46, p < 0.0001). The heterozygous genotype frequency (TA) did not significantly differ between the control and case groups. Compared with the controls, the variant allele (A) was approximately twice as frequent in the cases. Females and older people have a higher chance of disease development. Finally, the IFNG (+874T/A) polymorphism was not associated with drug sensitivity or resistance. However, a genotypic polymorphism of IFNG (+874T/A) was significantly associated with susceptibility to TB, and the T allele conferred protection against TB. Additional studies involving larger cohorts are needed to further explore this relationship between genetics and disease vulnerability.

Genetic polymorphism in association with susceptibility to tuberculosis: a study in a Pakistani population.

Tuberculosis is becoming a global issue with raising occurrences; particularly in developing countries, the situation is alarming. Besides environmental factors, host genetic factors are vital in disease development. A demographical and genotypic analysis in relation to tuberculosis commencement is conducted in a Pakistani population, and genotypic frequency of EBI3 (rs4740) was analyzed. Allelic frequencies of EBI3 (rs4740) were significantly associated with disease susceptibility in the reviewed population. Analysis for EBI3 (rs4740) genotyping showed a significant association of "GG" with reduced risk for disease. Moreover, females and older age found to be more perilous to develop TB while smoking and a family history of TB are additional risk factors for disease development. Further work with a larger population is necessary to identify the true causative variants of tuberculosis.

An Overview of the Genetics of Plant Response to Salt Stress: Present Status and the Way Forward.

Salinity is one of the major threats faced by the modern agriculture today. It causes multidimensional effects on plants. These effects depend upon the plant growth stage, intensity, and duration of the stress. All these lead to stunted growth and reduced yield, ultimately inducing economic loss to the farming community in particular and to the country in general. The soil conditions of agricultural land are deteriorating at an alarming rate. Plants assess the stress conditions, transmit the specific stress signals, and then initiate the response against that stress. A more complete understanding of plant response mechanisms and their practical incorporation in crop improvement is an essential step towards achieving the goal of sustainable agricultural development. Literature survey shows that investigations of plant stresses response mechanism are the focus area of research for plant scientists. Although these efforts lead to reveal different plant response mechanisms against salt stress, yet many questions still need to be answered to get a clear picture of plant strategy to cope with salt stress. Moreover, these studies have indicated the presence of a complicated network of different integrated pathways. In order to work in a progressive way, a review of current knowledge is critical. Therefore, this review aims to provide an overview of our understanding of plant response to salt stress and to indicate some important yet unexplored dynamics to improve our knowledge that could ultimately lead towards crop improvement.

Influence of sub-lethal crude oil concentration on growth, water relations and photosynthetic capacity of maize (Zea mays L.) plants.

Maize tolerance potential to oil pollution was assessed by growing Zea mays in soil contaminated with varying levels of crude oil (0, 2.5 and 5.0 % v/w basis). Crude oil contamination reduced soil microflora which may be beneficial to plant growth. It was observed that oil pollution caused a remarkable decrease in biomass, leaf water potential, turgor potential, photosynthetic pigments, quantum yield of photosystem II (PSII) (Fv/Fm), net CO2 assimilation rate, leaf nitrogen and total free amino acids. Gas exchange characteristics suggested that reduction in photosynthetic rate was mainly due to metabolic limitations. Fast chlorophyll a kinetic analysis suggested that crude oil damaged PSII donor and acceptor sides and downregulated electron transport as well as PSI end electron acceptors thereby resulting in lower PSII efficiency in converting harvested light energy into biochemical energy. However, maize plants tried to acclimate to moderate level of oil pollution by increasing root diameter and root length relative to its shoot biomass, to uptake more water and mineral nutrients.

There's more to the picture than meets the eye: nitric oxide cross talk with Ca2+ signaling.

Calcium and nitric oxide (NO) are two important biological messengers. Increasing evidence indicates that Ca(2+) and NO work together in mediating responses to pathogenic microorganisms and microbe-associated molecular patterns. Ca(2+) fluxes were recognized to account for NO production, whereas evidence gathered from a number of studies highlights that NO is one of the key messengers mediating Ca(2+) signaling. Here, we present a concise description of the current understanding of the molecular mechanisms underlying the cross talk between Ca(2+) and NO in plant cells exposed to biotic stress. Particular attention will be given to the involvement of cyclic nucleotide-gated ion channels and Ca(2+) sensors. Notably, we provide new evidence that calmodulin might be regulated at the posttranslational level by NO through S-nitrosylation. Furthermore, we report original transcriptomic data showing that NO produced in response to oligogalacturonide regulates the expression of genes related to Ca(2+) signaling. Deeper insight into the molecules involved in the interplay between Ca(2+) and NO not only permits a better characterization of the Ca(2+) signaling system but also allows us to further understand how plants respond to pathogen attack.

Study of oligogalacturonides-triggered nitric oxide (NO) production provokes new questioning about the origin of NO biosynthesis in plants.

We investigated the production and function of nitric oxide (NO) in Arabidopsis thaliana leaf discs as well as whole plants elicited by oligogalacturonides (OGs). Using genetic, biochemical and pharmacological approaches, we provided evidence that OGs induced a Nitrate Reductase (NR)-dependent NO production together with an increased NR activity and NR transcripts accumulation. In addition, NO production was sensitive to the mammalian NOS inhibitor L-NAME. Intriguingly, L-NAME impaired OG-induced NR activity and did not further affect the remaining OG-induced NO production in the nia1nia2 mutant. These data suggest that the L-arginine and NR pathways, co-involved in NO production, do not work independently. Taking account these new data, we propose scenarios to explain NO production in response to biotic stress.

S-nitrosylation: an emerging post-translational protein modification in plants.

Increasing evidences support the assumption that nitric oxide (NO) acts as a physiological mediator in plants. Understanding its pleiotropic effects requires a deep analysis of the molecular mechanisms underlying its mode of action. In the recent years, efforts have been made in the identification of plant proteins modified by NO at the post-translational level, notably by S-nitrosylation. This reversible process involves the formation of a covalent bond between NO and reactive cysteine residues. This research has now born fruits and numerous proteins regulated by S-nitrosylation have been identified and characterized. This review describes the basic principle of S-nitrosylation as well as the Biotin Switch Technique and its recent adaptations allowing the identification of S-nitrosylated proteins in physiological contexts. The impact of S-nitrosylation on the structure/function of selected proteins is further discussed.