Leprosy Reactions Show Increased Th17 Cell Activity and Reduced FOXP3+ Tregs with Concomitant Decrease in TGF-β and Increase in IL-6

Background

50% of leprosy patients suffer from episodes of Type 1/ reversal reactions (RR) and Type 2/ Erythema Nodosum Leprosum (ENL) reactions which lead to morbidity and nerve damage. CD4⁺ subsets of Th17 cells and CD25⁺FOXP3⁺ regulatory T cells (Tregs) have been shown to play a major role in disease associated immunopathology and in stable leprosy as reported by us and others. The aim of our study was to analyze their role in leprosy reactions.

Methodology and Principle Findings

Quantitative reverse transcribed PCR (qPCR), flowcytometry and ELISA were used to respectively investigate gene expression, cell phenotypes and supernatant levels of cytokines in antigen stimulated PBMC cultures in patients with stable disease and those undergoing leprosy reactions. Both types of reactions are associated with significant increase of Th17 cells and associated cytokines IL-17A, IL-17F, IL-21, IL-23 and chemokines CCL20, CCL22 as compared to matching stable forms of leprosy. Concurrently patients in reactions show reduction in FOXP3⁺ Treg cells as well as reduction in TGF-β and increase in IL-6. Moreover, expression of many T cell markers, cytokines, chemokines and signaling factors were observed to be increased in RR as compared to ENL reaction patients.

Conclusions

Patients with leprosy reactions show an imbalance in Th17 and Treg populations. The reduction in Treg suppressor activity is associated withhigherTh17cell activity. The combined effect of reduced TGF-β and enhanced IL-6, IL-21 cytokines influence the balance between Th17 or Treg cells in leprosy reactions as reported in the murine models and autoimmune diseases. The increase in Th17 cell associated cytokines may contribute to lesional inflammation.     

Ultrasonic synthesis of tyramine derivatives as novel inhibitors of α-glucosidase in vitro

Tyramine derivatives 3–27 were synthesized by using conventional and environmental friendly ultrasonic techniques. These derivatives were then evaluated for the first time for their α-glucosidase (Sources: Saccharomyces cerevisiae and mammalian rat-intestinal acetone powder) inhibitory activity by using in vitro mechanism-based biochemical assays. Compounds 7, 14, 20, 21 and 26 were found to be more active (IC₅₀?=?49.7?±?0.4, 318.8?±?3.7, 23.5?±?0.9, 302.0?±?7.3 and 230.7?±?4.0?μM, respectively) than the standard drug, acarbose (IC₅₀?=?840.0?±?1.73?μM (observed) and 780?±?0.028?μM (reported)) against α-glucosidase obtained from Saccharomyces cerevisiae. Kinetic studies were carried out on the most active members of the series in order to determine their mode of inhibition and dissociation constants. Compounds 7, 20 and 26 were found to be the competitive inhibitors of α-glucosidase. These compounds were also screened for their protein antiglycation, and dipeptidyl peptidase-IV (DPP-IV) inhibitory activities. Only compounds 20, 22 and 27 showed weak antiglycation activity with IC₅₀ values 505.27?±?5.95, 581.87?±?5.50 and 440.58?±?2.74?μM, respectively. All the compounds were found to be inactive against DDP-IV enzyme. Inhibition of α-glucosidase, DPP-IV enzymes and glycation of proteins are valid targets for the discovery of antidiabetic drugs. Cytotoxicity of compounds 3–27 was also evaluated by using mouse fibroblast 3T3 cell lines. All the compounds were found to be noncytotoxic. The current study describes the synthesis α-glucosidase inhibitory activity of derivatives, based on a natural product tyramine template. The compounds reported here may serve as the starting point for the design and development of novel α-glucosidase inhibitors as antidiabetic agents.     

Heavy metal uptake capacity of fresh water algae (Oedogonium westti) from aqueous solution: A mesocosm research

The green macroalgae present in freshwater ecosystems have attracted a great attention of the world scientists for removal of heavy metals from wastewater. In this mesocosm study, the uptake rates of heavy metals such as cadmium (Cd), nickel (Ni), chromium (Cr), and lead (Pb) by Oedogonium westi (O. westti) were measured. The equilibrium adsorption capabilities of O. westti were different for Cd, Ni, Cr, and Pb (0.974, 0.418, 0.620, and 0.261 mgg^–1, respectively) at 18°C and pH 5.0. Furthermore, the removal efficiencies for Cd, Cr, Ni and Pb were observed from 55–95%, 61–93%, 59–89%, and 61–96%, respectively. The highest removal efficiency was observed for Cd and Cr from aqueous solution at acidic pH and low initial metal concentrations. However, the removal efficiencies of Ni and Pb were higher at high pH and high concentrations of metals in aqueous solution. The results summarized that O. westti is a suitable candidate for removal of selected toxic heavy metals from the aqueous solutions.     

Non-pathogenic Staphylococcus strains augmented the maize growth through oxidative stress management and nutrient supply under induced salt stress

The present study was conducted to elucidate the role of phytobeneficial bacteria to control the cellular oxidative damage in maize (Zea mays L.) plants caused by salinity. Bacteria were isolated from the rhizosphere of kallar grass (Leptochloa fusca L.) through serial dilution method and taxonomically identified on the basis of their 16S ribosomal RNA gene sequencing. In vitro phosphate solubilization, indole-3-acetic acid (IAA) synthesis, and 1-aminocyclopropane-1-carboxylic acid (ACC) deaminase activity were evaluated by solubilization index measurement, colorimetric method, and turbidity assay, respectively. In the pot experiment, the impact of single and mixed inoculation of these strains at four levels (0, 50, 100, and 200 mM) of salt stress was evaluated in terms of growth and physiological response of maize plants to salinity. The bacterial strains (STN-1, STN-5, and STN-14) were taxonomically classified as Staphylococcus spp. At 5% NaCl level, the strains demonstrated substantial potential for phosphate solubilization, ACC deaminase activity, and IAA production both with and without tryptophan. The inoculation of strains STN-1, STN-5, and mixed inoculation resulted in substantial growth improvement of maize plants along with increased antioxidant enzyme activity and decreased levels of reactive oxygen species. In addition, single inoculation of STN-1 and STN-5 along with mixed inoculation augmented the uptake of N, P, K, and Ca+2 and reduced Na+ uptake. Current results demonstrated that the strains STN-1 and STN-5 modulated stress-responsive mechanisms and regulated ion balance in induced salinity to promote maize growth.     

Assessments of 226Ra and 222Rn concentration in well and tap water from Sik,Malaysia, and consequent dose estimates

Abstract

The ingestion of ²²⁶Ra, inhalation, and ingestion of ²²²Rn in water is considered the primary health risk for lungs and stomach. This study presents the concentrations of ²²⁶Ra and ²²²Rn in well and tap water collected from Sik, Malaysia, using HPGe and RAD7 detectors. Maximum average concentrations of ²²⁶Ra and ²²²Rn were found 47.6?±?3.6 mBq/l and 9.3?±?1.4?Bq/l in well water, respectively, and minimum were found 17.1?±?3.6 mBq/l and 1.6?±?1.0?Bq/l in tap water, respectively. A positive correlation (R=.88) was found between ²²⁶Ra and ²²²Rn determined by HPGe and RAD7 detectors, respectively. Infants in the age group of 0–1 y appeared to be at risk with respect to the annual effective doses from ²²⁶Ra and ²²²Rn as compared to the other age groups. However, annual effective doses for all three age groups from intake of ²²⁶Ra and ²²²Rn in well and tap drinking water were found below the World Health Organization (WHO) recommended level of .1 mSv/y_.     

Blockchain based secure,efficient and coordinated energy trading and data sharing between electric vehicles

Cluster Computing - In this study, a secure and coordinated blockchain based energy trading system for Electric Vehicles (EVs) is presented. The major goals of this study are to provide secure and...     

N-(2-hydroxyphenyl)acetamide and its gold nanoparticle conjugation prevent glycerol-induced acute kidney injury by attenuating inflammation and oxidative injury in mice

Molecular and Cellular Biochemistry - The protective activity of N-(2-hydroxyphenyl)acetamide (NA-2) and NA-2-coated gold nanoparticles (NA-2-AuNPs) in glycerol-treated model of acute kidney injury...     

Predicting subcellular localization of multi-label proteins by incorporating the sequence features into Chou's PseAAC

The emergence of numerous genome projects has made the experimental classification of the protein localization almost impossible due to the exponential increase in the number of protein samples. However, most of the applications are merely developed for single-plex and completely ignored the presence of one protein at two or more locations in a cell. In this regard, few attempts were carried out to target Multi-label protein localizations; consequently, undesirable accuracies are achieved. This paper presents a novel approach, in which a discrete feature extraction method is fused with physicochemical properties of amino acids by using Chou's general form of Pseudo Amino Acid Composition. The technique is tested on two benchmark datasets namely: Gpos-mploc and Virus-mPLoc. The empirical results demonstrated that the proposed method yields better results via two examined classifiers i.e. ML-KNN and Rank-SVM. It is established that the proposed model has improved values in all performance measures considered for the comparison.