ZERUMBONE, A NATURAL PLANT DIETARY COMPOUND INDUCES EXPRESSION OF INTERLEUKIN-12P70 CYTOKINE IN HUMAN PERIPHERAL BLOOD MONONUCLEAR CELLS

ABSTRACTObjective: Despite possessing many biological activities as antiproliferative, antioxidant, anti-inflammatory, and anticancerous, and zerumbone lacksany evidence for its immunomodulatory activity. This naturally occurring dietary compound needs to be developed as drug to support therapeuticclaims in various infections and diseases.Methods: Hence, in this study, the immunomodulatory effects of zerumbone were investigated by evaluating the effect of this compound toward thelymphocytes proliferation in human peripheral blood mononuclear cells.Results: Lymphocyte proliferation assay showed that zerumbone was able to activate human lymphocytes at dosage-dependent manner at the highestconcentration 40 μl/mL. The production of human interleukin-12p70 cytokine in culture supernatant from activated lymphocytes was upregulatedby zerumbone at 24 hrs and gradually decreased at 48 hrs. Hence, the study confirms the immunomodulatory activity of zerumbone which play animportant role in boosting up the immune system through cytokine production in dosage dependent manner.Conclusion: The study concludes that zerumbone could be used as a lead molecule in herbal therapeutic world as an immunomodulatory drug in thetreatment of chronic infections and various autoimmune disorders.Keywords: Zerumbone, Peripheral blood mononuclear cells, Immunomodulation, Cytokine, Lymphocyte proliferation

Novel indole derivatives as hepatitis C virus NS5B polymerase inhibitors: Pharmacophore modeling and 3D QSAR studies

Hepatitis C Virus (HCV) encodes its own RNA dependent RNA polymerase (NS5b) in order to replicate its genome. An efficient pharmacophore was identified, by executing structural analysis of a set of 49 indole-based inhibitors of the HCV NS5B polymerase. Identified pharmacophoric features, two hydrophobic regions, and 4 aromatic rings i.e. HHRRRR.649. Ligand based 3D-QSAR was performed, partial least square regression analysis was employed which gave a regression coefficient R2 of 0.98 and Q2 of 0.88, and Pearson-R of 0.96

A novel ionic liquid/polyoxomolybdate based sensor for ultra-high sensitive monitoring of Al(III): Optimization by Taguchi statistical design

A novel ionic liquid electrostatically supported Nano-Cs-polyoxomolybdate modified carbon paste electrode (Nano-IL-PMo12-CPE) has been developed by using 1-n-butyl-3-methylimidazolium tetrafluoroborate (Bmim.BF4) as a superconductive hydrophobic binder. The supramolecular gel (IL-PMo12) exhibits an ordered structure, various physicochemical properties, and specifically as a result of its substantial reversible self-assembly, it can be used as an intelligent ion-exchange smart platform in the carbon paste bulk of the electrode. The provided materials were characterized by XRD, FT-IR, UV–vis, and elemental analyses. As expected, a significant linear correspondence was found between the sensor output signal (emf/mV) and logarithm of Al(III) ion activity with a Nernstian slope of 19.9 (±0.2) mV decade−1 over a wide concentration range of 1.0 × 10−9 to 2.2 × 10−1 mol L−1 (R2 = 0.9997). The sensor considered, exploits an astounding lower limit of detection and short response time of 7.94 × 10−10 mol L−1 and 8 s respectively within the working pH range of 2.0 to 5.0. A statistical design of experimental (Taguchi method with Qualitek-4 software and L16 orthogonal array robust design) was implemented in this work to optimize the process to achieve the least number of experimental runs as much as possible. Ultimately, practical capability of the sensor was investigated successfully by assessment of Al(III) ion quantity in some aqueous samples namely mineral water, Al-Mg syrup, black tea extract, and ore samples (Basalt and Andesite), in perfect agreement with flame atomic absorption spectroscopy (FAAS).Peer reviewe

Drug Targets for Cardiovascular-Safe Anti-Inflammatory: In Silico Rational Drug Studies.

Cyclooxygenase-2 (COX-2) plays an important role in memory consolidation and synaptic activity, the most fundamental functions of the brain. It converts arachidonic acid to prostaglandin endoperoxide H2. In contrast, if over-expressed, it causes inflammation in response to cytokine, pro-inflammatory molecule, and growth factor. Anti-inflammatory agents, by allosteric or competitive inhibition of COX-2, alleviate the symptoms of inflammation. Coxib family drugs, particularly celecoxib, are the most famous anti-inflammatory agents available in the market showing significant inhibitory effect on COX-2 activity. Due to high cardiovascular risk of this drug group, recent researches are focused on the investigation of new safer drugs for anti-inflammatory diseases. Natural compounds, particularly, phytochemicals are found to be good candidates for drug designing and discovery. In the present study, we performed in silico studies to quantitatively scrutinize the molecular interaction of curcumin and its structural analogs with COX-2, COX-1, FXa and integrin αIIbβIII to investigate their therapeutic potential as a cardiovascular-safe anti-inflammatory medicine (CVSAIM). The results of both ADMET and docking study indicated that out of all the 39 compounds studied, caffeic acid had remarkable interaction with proteins involved in inflammatory response. It was also found to inhibit the proteins that are involved in thrombosis, thereby, having the potential to be developed as therapeutic agent

STAT3 and NTRK2 Genes Predicted by the Bioinformatics Approach May Play Important Roles in the Pathogenesis of Multiple Sclerosis and Obsessive–Compulsive Disorder

Background: There are no data available on the levels of genetic networks between obsessive–compulsive disorder (OCD) and multiple sclerosis (MS). To this point, we aimed to investigate common mechanisms and pathways using bioinformatics approaches to find novel genes that may be involved in the pathogenesis of OCD in MS. Methods: To obtain gene–gene interactions for MS and OCD, the STRING database was used. Cytoscape was then used to reconstruct and visualize graphs. Then, ToppGene and Enrichr were used to identify the main pathological processes and pathways involved in MS-OCD novel genes. Additionally, to predict transcription factors and microRNAs (miRNAs), the Enrichr database and miRDB database were used, respectively. Results: Our bioinformatics analysis showed that the signal transducer and the activator of transcription 3 (STAT3) and neurotrophic receptor tyrosine kinase 2 (NTRK2) genes had connections with 32 shared genes between MS and OCD. Furthermore, STAT3 and NTRK2 had the greatest enrichment parameters (i.e., molecular function, cellular components, and signaling pathways) among ten hub genes. Conclusions: To summarize, data from our bioinformatics analysis showed that there was a significant overlap in the genetic components of MS and OCD. The findings from this study make two contributions to future studies. First, predicted mechanisms related to STAT3 and NTRK2 in the context of MS and OCD can be investigated for pharmacological interventions. Second, predicted miRNAs related to STAT3 and NTRK2 can be tested as biomarkers in MS with OCD comorbidity. However, our study involved bioinformatics research; therefore, considerable experimental work (e.g., postmortem studies, case–control studies, and cohort studies) will need to be conducted to determine the etiology of OCD in MS from a mechanistic view

The Glymphatic System May Play a Vital Role in the Pathogenesis of Hepatic Encephalopathy: A Narrative Review

Hepatic encephalopathy (HE) is a neurological complication of liver disease resulting in cognitive, psychiatric, and motor symptoms. Although hyperammonemia is a key factor in the pathogenesis of HE, several other factors have recently been discovered. Among these, the impairment of a highly organized perivascular network known as the glymphatic pathway seems to be involved in the progression of some neurological complications due to the accumulation of misfolded proteins and waste substances in the brain interstitial fluids (ISF). The glymphatic system plays an important role in the clearance of brain metabolic derivatives and prevents aggregation of neurotoxic agents in the brain ISF. Impairment of it will result in aggravated accumulation of neurotoxic agents in the brain ISF. This could also be the case in patients with liver failure complicated by HE. Indeed, accumulation of some metabolic by-products and agents such as ammonia, glutamine, glutamate, and aromatic amino acids has been reported in the human brain ISF using microdialysis technique is attributed to worsening of HE and correlates with brain edema. Furthermore, it has been reported that the glymphatic system is impaired in the olfactory bulb, prefrontal cortex, and hippocampus in an experimental model of HE. In this review, we discuss different factors that may affect the function of the glymphatic pathways and how these changes may be involved in HE