Neuro-protective potential of quercetin during chlorpyrifos induced neurotoxicity in rats

Chlorpyrifos (CPF) has been considered as one of the most potent organophosphates and is linked to several neurological disorders. On the other hand, Quercetin is a vital plant flavanoid and has been reported to regulate a number of physiological processes in the central nervous system. The present study was conducted to investigate the protective potential of quercetin during chlorpyrifos induced neurotoxicity. Female Wistar rats weighing 150–200?g were divided into four different groups viz: Normal control, CPF treated (13.5?mg/kg.b.wt. every alternate day), Quercetin treated (50?mg/kg.b.wt./day) and combined CPF and quercetin-treated. All the treatments were carried out for a total duration of eight weeks. Chlorpyrifos treatment showed significant alterations in the cognitive behavior and motor activities of rats, which were appreciably improved upon simultaneous supplementation with quercetin. Further, CPF treatment caused a significant inhibition in the enzyme activities of acetylcholinesterase and choline acetyltransferase, but caused an increase in the levels of acetylcholine in the brain. Further, chlorpyrifos exposure significantly elevated the levels of lipid peroxidation and protein carbonyl contents as well as the activities of catalase, superoxide dismutase, which were interestingly found to be decreased following co-treatment with quercetin. In contrast, CPF treatment decreased the activities of glutathione reductase, transferase, as well as levels of reduced and total glutathione in both the cerebrum and cerebellum but co-administration of quercetin, increased these levels. Chlorpyrifos treatment altered the neuro-histoarchitecture, which showed improvement upon quercetin supplementation. Hence, this study suggests that quercetin can be used as a prophylactic intervention to prevent CPF induced neurotoxicity.     

Novel analogs of sulfasalazine as system xc− antiporter inhibitors: Insights from the molecular modeling studies

System x_c⁻ (Sx_c⁻), a cystine-glutamate antiporter, is established as an interesting target for the treatment of several pathologies including epileptic seizures, glioma, neurodegenerative diseases, and multiple sclerosis. Erastin, sorafenib, and sulfasalazine (SSZ) are a few of the established inhibitors of Sx_c⁻. However, its pharmacological inhibition with novel and potent agents is still very much required due to potential issues, for example, potency, bioavailability, and blood–brain barrier (BBB) permeability, with the current lead molecules such as SSZ. Therefore, in this study, we report the synthesis and structure–activity relationships (SAR) of SSZ derivatives along with molecular docking and dynamics simulations using the developed homology model of xCT chain of Sx_c⁻ antiporter. The generated homology model attempted to address the limitations of previously reported comparative protein models, thereby increasing the confidence in the computational modeling studies. The main objective of the present study was to derive a suitable lead structure from SSZ eliminating its potential issues for the treatment of glioblastoma multiforme (GBM), a deadly and malignant grade IV astrocytoma. The designed compounds with favorable Sx_c⁻ inhibitory activity following in vitro Sx_c⁻ inhibition studies, showed moderately potent cytotoxicity in patient-derived human glioblastoma cells, thereby generating potential interest in these compounds. The xCT-ligand model can be further optimized in search of potent lead molecules for novel drug discovery and development studies.     

Group psychoeducative cognitive-behaviour therapy for mixed anxiety and depression with older adults

Objectives: There is a dearth of older adult evidence regarding the group treatment for co-morbid anxiety and depression. This research evaluated the effectiveness of a low-intensity group psychoeducational approach.

Method: Patients attended six sessions of a manualised cognitive-behavioural group. Validated measures of anxiety, depression and psychological well-being were taken at assessment, termination and six-week follow-up from patients, who also rated the alliance and their anxiety/depression at each group session. Staff rated patients regarding their functioning at assessment, termination and six-week follow-up. Outcomes were categorised according to whether patients had recovered, improved, deteriorated or been harmed. Effect sizes were compared to extant group interventions for anxiety and depression.

Results: Eight groups were completed with 34 patients, with a drop-out rate of 17%. Staff and patient rated outcome measures showed significant improvements (with small effect sizes) in assessment to termination and assessment to follow-up comparisons. Over one quarter (26.47%) of patients met the recovery criteria at follow-up and no patients were harmed. Outcomes for anxiety were better than for depression with the alliance in groups stable over time.

Conclusion: The intervention evaluated shows clinical and organisational promise. The group approach needs to be further developed and tested in research with greater methodological control.     

A potent enzybiotic against methicillin-resistant Staphylococcus aureus

Virus Genes - Staphylococcus aureus is one of the most dreadful infectious agents, responsible for high mortality and morbidity in both humans and animals. The increased prevalence of...     

Interaction of pretilachlor with PS-II activity of the cyanobacterium Desmonostoc muscorum PUPCCC 405.10

Interaction of pretilachlor with photosystem (PS)-II of the cyanobacterium Desmonostoc muscorum PUPCCC 405.10 has been studied in this paper. Pretilachlor negatively affected growth, chlorophyll a (Chl a), photosynthesis, and carbon dissimilation in a dose-dependent manner. Effects were also observed in PSs, especially PS-II (an 11–35% decrease), as well as the whole photosynthetic electron transport activity. The fluorescence emission spectrum of Chl a revealed a dose-dependent effect of pretilachlor on both the antenna and the core complex of PSs, with more severe effect on the former. Data of O-J-I-P fluorescence transient of Chl a revealed that pretilachlor interfered with electron flow between Q_A and Q_B sites of PS-II. It was further observed that pretilachlor decreased maximum fluorescence, variable and relative variable fluorescence, maximum quantum yield, quantum yield of electron transport, the rate of trapped exciton movement, quantum yield of electron transfer, and performance index of primary photochemistry; however, there was a progressive increase in the net rate of PS-II closure, quantum yield of energy dissipation, and effective antenna size per active reaction center. A decrease in photosynthetic activity leads to a decrease in carbon dissimilation, as evidenced by low activity of glucose-6-phosphate dehydrogenase and pyruvate kinase. Thus, pretilachlor, which is otherwise known to kill weeds by interfering with cell division, affected the growth of the cyanobacteria by interacting with PS-II.     

Radical pathways for the formation of non-canonical nucleobases in prebiotic environments

Due to the inability of canonical nucleobases (adenine, uracil, guanine and cytosine) to spontaneously form ribonucleosides and base pairs in free form in solution, RNA is believed to be preceded by a primitive information polymer (preRNA). The preRNA is proposed to contain non-canonical, heterocyclic bases that possess the above-mentioned capabilities. An extensive search for such candidate heterocycles has recently revealed that barbituric acid (BA), melamine (MM) and 2,4,6-triaminopyrimidine (TAP) have the capability to spontaneously form ribonucleosides and supramolecular assemblies that are held by Watson–Crick type hydrogen-bonded base pairs involving BA, MM, TAP and cyanuric acid (CA) heterocycles. However, despite this evidence, the prebiotic formation pathways of these heterocycles have not been fully explored. Further, for these heterocycles to interact and assemble into informational polymers under prebiotic conditions, it is expected that they should have formed in the proximity of each other. In this context, the present work employs density functional theory to propose the associated radical based formation pathways starting from cyanamide. Our pathways suggest that cyanamide, its derivatives (malonic acid and urea) and malononitrile can form BA, MM, CA and TAP in the presence of ammonia and hydroxyl radicals. In addition to originating from a common precursor, similarities in the highest reaction barriers (13 to 20 kcal mol⁻¹) obtained for these pathways suggest that these heterocycles may likely form under similar conditions. Specifically, these pathways are relevant to high energy events such as meteoritic impact during the late heavy bombardment period on the early earth, which would have created conditions where radicals might have formed in reasonable concentrations. Overall, the present study emphasizes the importance of cyanamide in prebiotic heterocycle formation.

The study explores radical-assisted formations of the nucleobase components of primitive genetics from cyanamide and related precursors in impact events.