Identification of potential phytochemicals and their inhibitory effect on the PERK receptor mediated UPR pathway for neuronal disease regulation: an in silico insight.

The endoplasmic reticulum (ER) has been considered as the key site of protein biosynthesis and maturation in the eukaryotic cell. In recent years, the sequence at the N-terminal region of translated protein has shown a particular emphasis as a signal responsible for site-specific translocation mediated by post-translational modification. Once the native conformation is not achieved, the degradation pathway is activated, and therefore the restoration of the homeostasis of ER function in UPR pathway is initiated. One of the transmembrane proteins, PKR-like ER kinase (PERK) plays a key role in the activation of UPR through the inhibition of the translation process, thus preventing the cells from apoptosis due to chronic ER stress. Dysregulation of the neuronal proteostasis often results in neuronal dysfunction and its crucially associated neurodegenerative diseases or its manifestation of neuropathic pain. The correlation between ER stress and its associated signaling cascade, namely UPR, is well established in context of neuropathological modifications. This furthermore suggests that the proteins of the signaling cascade such as PERK can serve as a potential target during the onset of neuronal damage. The aim of this study was to identify the potential phytocompounds by evaluating the physicochemical properties, Lipinski screening, ADMET and toxicity properties of the selected phytocompounds by using SwissADME, MolInspiration and pKCSM webservers, which could establish a comparatively better affinity and binding energy than the control drug as GSK2606414 in set up the treatment of the neuronal diseases through molecular docking via PyRx and validating their structural stability through simulation using the Sybyl software for over100ns.Communicated by Ramaswamy H. Sarma.

Cellular and Molecular Machinery of Neuropathic Pain: an Emerging Insight.

Purpose of Review: Neuropathic pain (NP) has been ubiquitously characterized by lesion and its linked somatosensory system either the central nervous system (CNS) or peripheral nervous system (PNS) This PNS episode is the most prevalent site of NP origin and is found to be associated with afferent nerve fibers carrying pain signals from injured/trauma site to the CNS including the brain. Several kinds of pharmacotherapeutic drugs shuch as analgesics, anti-convulsants, and anti-depressants are being employed for the its possible interventions. The NP has been a great interest to follow different pathophysiological mechanisms which are often considered to correlate with the metabolic pathways and its mediated disease. There is paucity of knowledge to make such mechanism via NP. Recent Finding: Most notably, recent pandemic outbreak of COVID-19 has also been reported in chronic pain mediated diabetes, inflammatory disorders, and cancers. There is an increasing incidence of NP and its complex mechanism has now led to identify the possible investigations of responsible genes and proteins via bioinformatics tools. The analysis might be more instrumental as collecting the genes from pain genetic database, analyzing the variants through differential gene expression (DEG) and constructing the protein-protein interaction (PPI) networks and thereby determining their upregulating and downregulating pathways. Summary: This review sheds a bright light towards several mechanisms at both cellular and molecular level, correlation of NP-mediated disease mechanism and possible cell surface biomarkers (receptors), and identified genes could be more promising for their pharmacological targets.

Statistical optimization for the efficacious degradation of reactive azo dyes using Acinetobacter baumannii JC359.

The aim of this study is to biodegrade the reactive azo dyes- Reactive black 5 (B-GDN), Reactive red 120 (RP) and Reactive blue 19 (RNB) using bacteria Acinetobacter baumannii JC359. Optimization of the process variables such as pH, temperature, dye concentration, incubation time, inoculum volume and dynamic incubating conditions for dye decolorization were performed using One Factor At a Time (OFAT) approach. Box- Behnken Design (BBD) of Response Surface Methodology (RSM) was further used to optimize the process variables. Decolorization rates of 98.8% for B-GDN, 96% for RP and 96.2% for RNB were observed after treating with A. baumannii for 48 h using the obtained design value. UV-Visible spectrophotometry and FT-IR spectral scan of dye and degraded metabolites confirmed that biodegradation had taken place. Further, the phytotoxicity evaluation was performed with Vigna radiata seeds and the degraded metabolites proved to be non-toxic. Docking studies were performed and it was found that there was significant binding affinity between the dyes and azoreductase enzyme of A. baumannii. Thus, the biodegradation of these reactive azo dyes was found to be a suitable alternative for the effective treatment of textile dyes.

Emerging Role of Mitophagy in Inflammatory Diseases: Cellular and Molecular Episodes.

Mitochondria are the crucial regulators for the major source of ATP for different cellular events. Due to damage episodes, mitochondria have been established for a plethora ofalarming signals of stress that lead to cellular deterioration, thereby causing programmed cell death. Defects in mitochondria play a key role in arbitrating pathophysiological machinery with recent evince delineating a constructive role in mitophagy mediated mitochondrial injury. Mitophagy has been known for the eradication of damaged mitochondria via the autophagy process. Mitophagy has been investigated as an evolutionarily conserved mechanism for mitochondrial quality control and homeostasis. Impaired mitophagy has been critically linked with the pathogenesis of inflammatory diseases. Nevertheless, the exact mechanism is not quite revealed, and it is still debatable. The purpose of this review was to investigate the possible role of mitophagy and its associated mechanism in inflammation-mediated diseases at both the cellular and molecular levels.