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Background: Tuberculosis (TB), a global infectious threat, has seen a concerning rise in aminoglycoside‑resistant Mycobacterium tuberculosis(M.tb) strains. The potential role of capsule proteins remains largely unexplored. This layer acts as the primary barrier for tubercle bacilli, attempting to infiltrate host cells and subsequent disease development. Methods: The study aims to bridge this gap by investigating the differentially expressed capsule proteins in aminoglycoside‑resistant M.tb clinical isolates compared with drug‑sensitive isolates employing two‑dimensional gel electrophoresis, mass spectrometry, and bioinformatic approaches. Results: We identified eight proteins that exhibited significant upregulation in aminoglycoside-resistant isolates. Protein Rv3029c and Rv2110c were associated with intermediary metabolism and respiration; Rv2462c with cell wall and cell processes; Rv3804c with lipid metabolism; Rv2416c and Rv2623 with virulence and detoxification/adaptation; Rv0020c with regulatory functions; and Rv0639 with information pathways. Notably, the Group-based Prediction System for Prokaryotic Ubiquitin-like Protein (GPS-PUP) algorithm identified potential pupylation sites within all proteins except Rv3804c. Interactome analysis using the STRING 12.0 database revealed potential interactive partners for these proteins, suggesting their involvement in aminoglycoside resistance. Molecular docking studies revealed suitable binding between amikacin and kanamycin drugs with Rv2462c, Rv3804c, and Rv2623 proteins. Conclusion: As a result, our findings illustrate the multifaceted nature of aminoglycoside resistance in M.tb and the importance of understanding how capsule proteins play a role in counteracting drug efficacy. Identifying the role of these proteins in drug resistance is crucial for developing more effective treatments and diagnostics for TB. [ABSTRACT FROM AUTHOR]

Diabetes mellitus has become a global epidemic as its prevalence is steadily increasing everywhere at an alarming rate, most markedly in the India. Traditional Indian system of medicine based on herbal therapies is being practiced since ancient times and has been proved very effective against number of diseases. Trigonella foenum-graecum (Tfg) and Cinnamomum zeylanicum (Cz), the two spices, possess multiple medicinal properties. Hence present study is aimed to evaluate the protective effects of these plants on the oxidative DNA damage in diabetic rats. The presence of DNA base oxidation was investigated by modified comet assay which uses bacterial repair enzymes, formamidopyrimidine glycosylase and Endonuclease III which can measure oxidatively damaged purines and pyrimidines, respectively. Diabetes induced alteration in total antioxidant capacity (TAC), generation of superoxide anion and the levels of GSH, GSSG, NADH, NAD+, NADPH and NADP+ were monitored. Diabetes was induced by intravenous injection of alloxan, followed by oral administration of aqueous suspension of Tfg seeds and bark of Cz. Treatment of Tfg and Cz significantly restored the altered level of superoxide anion, TAC, ratios of GSH/GSSG, NAD(P)H/NAD(P)+ and NADH/NAD+ in the diabetic group. Furthermore, both the treatment effectively decreased the level of oxidatively damaged purine and pyrimidine bases. [ABSTRACT FROM AUTHOR]

Sarin is an organophosphorus (OP) chemical warfare agent which irreversibly inhibits acetylcholinesterase. Acute toxicity after sarin exposure is because of hyper activation of the nicotinic and muscarinic receptor. Survivors of sarin exposure often develop long-term neuropathology referred as OP ester-induced chronic neurotoxicity. However, the exact mechanism of chronic neurotoxicity is yet unknown. We studied proteomic changes in rat brain regions after 0.5 LD50 dose of sarin and investigated some milestone changes associated with long-term CNS injury.We used two-dimensional gel electrophoresis/mass spectrometry approach to identify early proteomic changes and traced expression of selected proteins for longer time points. This study shows changes in chaperone function, endoplasmic reticulumstress, and defect in cytoskeleton functions at earlier stages. Predictive interaction analysis demonstrated putative role of Parkinson's disease-related proteins after sarin exposure. Our results clearly indicated neurodegenerative changes which started after 2.5h and showed prominence after 3-month postexposure. The study also unmasks changes in proteins related to movement and cognitive function. The markers for astrocytosis (GFAP) and neurodegenerative changes (alpha-synuclein and amyloid precursor protein) exhibited altered expression in brain. This is the first proteomic study among survivors of sarin exposure in animal model. Some of the early changes, including those involved in neurodegeneration, movement, and cognitive function, defects in chaperone function and cytoskeleton, were shown to persist for a longer period. The study provides a preliminary framework for further validation of major mechanisms of sarin toxicity is suggested here and opens new avenues for elucidation of therapeutic intervention. [ABSTRACT FROM AUTHOR]

Background: Justicia gendarussa Burm f. of family Acanthaceae is medicinally important herb used in the treatment of inflammatory disorders, asthma, hepatic injuries, pathogenic infection and also shows antiproliferative activity against various cancer cell lines. Materials and Methods: Pharmacognostical evaluation (macro-microscopy, physicochemical analysis and preliminary phytochemical analysis), high-performance thin layer chromatography (HPTLC) fingerprinting and chemical profiling by gas chromatography-mass spectrometry (GCMS) of dried roots of J. gendarussa were done according to quality standard procedures. Results: Microscopic analysis revealed the compact arrangement of cells in cork region and thin-walled cortex beneath epidermis. Parenchymatous cells with xylem vessel were observed in the roots of J. gendarussa. Physicochemical studies revealed loss on drying (10.474%), total ash (2.990%), acid-insoluble ash (0.099%), water-soluble ash (1.528%), alcohol-soluble extractive value (0.564%) and water-soluble extractive value (4.11%) of the raw drug. Preliminary phytochemical analysis of ethanolic extract of J. gendarussa showed the presence of alkaloid, steroid, flavonoid, phenol, carbohydrate, saponin and quinone. Rf, color of the spots and densitometric scan were recorded by HPTLC fingerprinting using toluene: ethyl acetate: formic acid (5.0:4.0:1.0). On photodocumentation, six spots were visualized under 254 nm, nine spots under 360 nm and six spots at 620 nm. Identification of components in ethanolic extract of J. gendarussa was done by GC-MS. GC-MS results in the presence of oleic acid, 9,12-octadecadienoic acid, 6,9,12-octadecatrienoic acid and estra-1, 3,5 (10)-trein-17-β-ol in ethanolic extract of J. gendarussa. Conclusion: These specific identities will be useful in identification and authentication of the raw drug in dried form. [ABSTRACT FROM AUTHOR]

ABSTACT Organophosphates (OPs) pesticides are among the most toxic synthetic chemicals purposefully added in the environment. The common use of OP insecticides in public health and agriculture results in an environmental pollution and a number of acute and chronic poisoning events. Present study was aimed to evaluate the potential of monocrotophos and quinalphos to effect the redox status and glutathione (GSH) homeostasis in rat tissues and find out whether antioxidant vitamins have some protection on the pesticide-induced alterations. The results showed that these pesticides alone or in combination, caused decrease in the levels of GSH and the corresponding increase in the levels of GSSG, decreasing the GSH/GSSG ratio. The results also showed that NADPH/NADP+ and NADH/NAD+ ratios were decreased in the liver and brain of rats on exposure with mococrotophos, quinalphos, and their mixture. These pesticides, alone or in combination, caused alterations in the activities of GSH reductase and glucose-6-phosphate dehydrogenase in the rat tissues. However, the expression of the GSH recycling enzymes did not show significant alterations as compared to control. From the results, it can be concluded that these pesticides generate oxidative stress but their effects were not synergistic when given together and prior feeding of antioxidant vitamins tend to reduce the toxicities of these pesticides. © 2013 Wiley Periodicals, Inc. Environ Toxicol 30: 472-482, 2015. [ABSTRACT FROM AUTHOR]

Organophosphate pesticides are among the most widely used synthetic chemicals for controlling a wide variety of pests. Chlorpyrifos (CPF), methyl parathion (MPT), and malathion (MLT) are among the most extensively used organophosphate (OP) pesticides. The main target of action of OP compounds is the central and peripheral nervous system, although it has also been postulated that these compounds in both acute and chronic intoxication, disturb the redox processes and thus induce oxidative stress. The excessive generation of reactive oxygen species (ROS) causes damage to all vital macromolecules including lipids, proteins, and DNA. This study was aimed to investigate the genotoxicity and cytotoxicity of CPF, MPT, and MLT when given singly or in combination. The DNA damage was measured by alkaline single-cell gel electrophoresis or comet assay and expressed as DNA damage index. The results showed that both acute and chronic exposure with CPF, MPT, and MLT, caused significantly marked DNA damage in rat tissues namely, liver, brain, kidney, and spleen, when measured 24 hour posttreatment. It was also observed that MPT caused highest level of DNA damage and brain was maximally affected by these OP compounds. When these pesticides were given in mixture, the damage was not the sum of damage caused by individual pesticide, confirming that these pesticides do not potentiate the toxicity of each other. When the DNA damage was measured 48 and 72 hour posttreatment, the damage was partially repaired. Pesticide exposure also caused histopathological changes in rat tissues. © 2011 Wiley Periodicals, Inc. Environ Toxicol 28: 543-552, 2013. [ABSTRACT FROM AUTHOR]

The human malaria parasite Plasmodium vivax is globally widespread, causing high malaria morbidity. As P. vivax is highly endemic to India, and previous reports indicate genetic homogeneity in population samples, we tested the hypothesis of no genetic structuring in Indian P. vivax. Further, based on the reports of increasing incidence of Plasmodium falciparum infection in comparison with P. vivax in recent years in India, it was important to understand whether reduction in population size has resulted in decrease in P. vivax infection rate in India. For this, we utilized recently developed putatively neutral markers from chromosome 13 of P. vivax to score single nucleotide polymorphisms in 126 P. vivax isolates collected from 10 different places in India. The overall results indicated that Indian P. vivax bears high nucleotide diversity within population samples but moderate amount of genetic differentiation between population samples. STRUCTURE analysis grouped 10 population samples into three clusters based on the proportion of the genetic ancestries in each population. However, the pattern of clustering does not correlate with sampling locations in India. Furthermore, analyses of past demographic events indicated reduction in population size in majority of population samples, but when isolates from all the 10 samples were considered as a single population, the data fit to the demographic equilibrium model. All these observations clearly indicate that Indian P. vivax presents complex evolutionary history but possesses several features of being a part of ancestral distribution range of this species. [ABSTRACT FROM AUTHOR]

Calcium/calmodulin-dependent protein kinase II (CaMKII) and c-Jun N-terminal kinases (JNKs) exert numerous and diverse functions in the brain. However, their role in nerve agent poisoning is poorly understood. In the present study, rats were exposed to soman (80 µg/kg) subcutaneously to study the changes in the protein levels of calcium/calmodulin-dependent protein kinase II alpha subunit (CaMKIIα) and JNK3 and activities of acetylcholinestarase (AChE) and CaMKII in the rat brain. Western blot analysis revealed that significant changes were found in both the protein kinases expression. Immunoreactivity levels of neural specific JNK3 isoform increased from 2.5 hours to 30 days after soman exposure in cerebral cortex, hippocampus, striatum and thalamus regions and decreased in the case of cerebellum. CaMKIIα expression levels were also increased from 2.5 hours to 30 days after soman exposure in cerebral cortex, hippocampus, thalamus and down regulated in cerebellum. AChE activity remained inhibited in plasma and brain up to 3 days post exposure. CaMKII activity was increased in cerebrum and decreased in cerebellum. Results suggest that altered expression of both the protein kinases play a role in nerve agent-induced long-term neurotoxic effects. [ABSTRACT FROM PUBLISHER]