Epilepsy, a common multifactorial neurological disease, affects about 69 million people worldwide constituting nearly 1% of the world population. Despite decades of extensive research on understanding its underlying mechanism and developing the pharmacological treatment, very little is known about the biological alterations leading to epileptogenesis. Due to this gap, the currently available antiepileptic drug therapy is symptomatic in nature and is ineffective in 30% of the cases. Mounting evidences revealed the pathophysiological role of neuroinflammation in epilepsy which has shifted the focus of epilepsy researchers towards the development of neuroinflammation-targeted therapeutics for epilepsy management. Markedly increased expression of key inflammatory mediators in the brain and blood-brain barrier may affect neuronal function and excitability and thus may increase seizure susceptibility in preclinical and clinical settings. Cyclooxygenase-2 (COX-2), an enzyme synthesizing the proinflammatory mediators, prostaglandins, has widely been reported to be induced during seizures and is considered to be a potential neurotherapeutic target for epilepsy management. However, the efficacy of such therapy involving COX-2 inhibition depends on various factors viz., therapeutic dose, time of administration, treatment duration, and selectivity of COX-2 inhibitors. This article reviews the preclinical and clinical evidences supporting the role of COX-2 in seizure-associated neuroinflammation in epilepsy and the potential clinical use of COX-2 inhibitors as a future strategy for epilepsy treatment.

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Antiepileptic drug therapy has significant inter-patient variability in response towards it. The current study aims to understand this variability at the molecular level using microarray-based analysis of peripheral blood gene expression profiles of patients receiving valproate (VA) monotherapy. Only 10 unique genes were found to be differentially expressed in VA responders (n = 15) and 6 genes in the nonresponders (n = 8) (fold-change >2, p < 0.05). PTGS2 which encodes cyclooxygenase-2, COX-2, showed downregulation in the responders compared to the non-responders. PTGS2/COX-2 mRNA profiles in the two groups corresponded to their plasma profiles of the COX-2 product, prostaglandin E 2 (PGE 2). Since COX-2 is believed to regulate P-glycoprotein (P-gp), a multidrug efflux transporter over-expressed at the blood-brain barrier (BBB) in drug-resistant epilepsy, the pathway connecting COX-2 and P-gp was further explored in vitro. Investigation of the effect of VA upon the brain endothelial cells (hCMEC/D3) in hyperexcitatory conditions confirmed suppression of COX-2-dependent P-gp upregulation by VA. Our findings suggest that COX-2 downregulation by VA may suppress seizure-mediated P-gp upregulation at the BBB leading to enhanced drug delivery to the brain in the responders. Our work provides insight into the association of peripheral PTGS2/COX-2 expression with VA efficacy and the role of COX-2 as a potential therapeutic target for developing efficacious antiepileptic treatment. Epilepsy, a multifactorial neurological disease, affects about 69 million people worldwide constituting nearly 1% of the world population 1. The treatment is primarily based on symptomatic pharmacological interventions i.e. antiepileptic drug (AED) therapy which controls the frequency of seizures in the patients. Despite the availability of appropriate therapy, there is significant inter-individual variability in AED response. Nearly 40-50% of the patients with epilepsy (PWE) fail to respond to their first AED monotherapy 2,3 with 30% cases showing refractoriness 4. This non-responsiveness to AEDs encouraged researchers to identify the predictors of poor response in PWE. Clinical factors such as early age at onset, higher pretreatment seizure frequency, cryptogenic epilepsy, brain neuroanatomic abnormality, etc. have previously been observed to be potential predictors of poor response to prescribed AEDs 3,5. Several studies also investigated the pharmacogenetics of AEDs and suggested the involvement of various drug-metabolizing enzymes (CYPs), drug transporters (ABC transporters), and drug target genes (ion-channels in brain) in deciding treatment outcome, however, remained inconclusive due to the inconsistency in their findings and failure of replication in different populations 6. One reason behind this failure could be the multifactorial nature of the disease which involves genome-environment interactions and therefore limits the independent use of genetics in studying AED response 6-8. Since any change in genetic or environmental factors

Recent advances in woundcare is targeted towards developing active-dressings, where multiple components are combined to provide a suitable environment for rapid healing. The aim of the present research is to study the preparation of biomimic composite wound dressings by the grafting of hydrogel on silk fibroin fabric. The swelling ability of hydrogel grafted silk fibroin fabric was optimized by changing the initiator concentration. In order to impart antimicrobial properties, these dressing are further coated sono-chemically with zinc oxide nanoparticles. The water vapor transmission rate of the prepared samples was measured. The conformation of silk fibroin proteins after grafting with hydrogel was also confirmed using Fourier Transform Infrared Spectroscopy (FTIR). The morphology of the zinc oxide-coated silk fibroin fabric and hydrogel-coated silk fibroin was studied using Scanning Electron Microscope (SEM). The antimicrobial activity of the zinc oxide-coated samples was studied against E coli. The cytocompatibility of the prepared dressing materials were evaluated using L929 fibroblast cells. MTT assay and phase contrast microscopic studies showed that the adherence, growth, and proliferation of the L929 fibroblast cells that were seeded on zinc oxide nanoparticles on the functionalized hydrogel-coated silk fibroin dressing was significantly higher than that of pure silk fibroin due to the highly porous, bio-mimic structure that allowed ease of passage of nutrients, growth factors, metabolites, and the exchange of gases which is beneficial for successful regeneration of damaged tissues. The expression of TNF-α and IL-2 were not significantly higher than that of control. The proposed composite dressing would be a promising material for wound dressing and regenerative medicine but in order to prove the efficacy of these materials, more in vivo experiments and clinical tests are required to be conducted in future.

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The alcohol oxidase (AOx) cDNA from Aspergillus terreus MTCC6324 with an open reading frame (ORF) of 2001 bp was constructed from n-hexadecane induced cells and expressed in Escherichia coli with a yield of ∼4.2 mg protein g−1 wet cell. The deduced amino acid sequences of recombinant rAOx showed maximum structural homology with the chain B of aryl AOx from Pleurotus eryngii. A functionally active AOx was achieved by incubating the apo-AOx with flavin adenine dinucleotide (FAD) for ∼80 h at 16°C and pH 9.0. The isoelectric point and mass of the apo-AOx were found to be 6.5±0.1 and ∼74 kDa, respectively. Circular dichroism data of the rAOx confirmed its ordered structure. Docking studies with an ab-initio protein model demonstrated the presence of a conserved FAD binding domain with an active substrate binding site. The rAOx was specific for aryl alcohols and the order of its substrate preference was 4-methoxybenzyl alcohol >3-methoxybenzyl alcohol>3, 4-dimethoxybenzyl alcohol > benzyl alcohol. A significantly high aggregation to ∼1000 nm (diameter) and catalytic efficiency (kcat/Km) of 7829.5 min−1 mM−1 for 4-methoxybenzyl alcohol was also demonstrated for rAOx. The results infer the novelty of the AOx and its potential biocatalytic application.

Loop-mediated isothermal amplification (LAMP) is a sensitive, efficient, and rapid nucleic acid amplification technique resulting in a large number of amplicons; however, it suffers from a high incidence of false positives due to carry-over and aerosol. Herein, we report a 10 min nano-capture system that is used in conjunction with a modified reverse transcriptase-LAMP (RT-LAMP) assay for the accurate detection of SARS CoV-2 virus. The nano-capture system employs in-house-designed probe-functionalized magnetic nanoparticles Co 2 FeAl (cobalt-based Heusler alloy) for efficient capture of contaminating amplicons from the reaction mixture preceding RT-LAMP. The nano-cleaned RT-LAMP assay along with engineered primers successfully detected the presence of 10 copies of SARS CoV-2 virus while completely eliminating the incidence of false positives. The presented contaminant-capture method has been compared with other approaches for elimination of contaminants and was found to be more effective. The insight brought in this work is the design of a rapid nano-capture system that hybridizes with contaminating amplicons (carry-over) with high specificity to enable easy removal from the assay for elimination of false positives. The method has been proven to be successful for RT-LAMP assays in the rapid and highly specific detection of SARS CoV-2, which is currently a major challenge for global health. To the best of our knowledge, this is the first work involving a nano-based cleaning strategy for reliable and rapid diagnosis using isothermal amplification approaches.

Background and Aims:Effect of serum 25-hydroxy vitamin D (25[OH] D) levels on the recovery of critically ill mechanically ventilated patients is unclear. Hence, this study assessed 25(OH)D levels of critically ill patients on mechanical ventilation at the time of admission to the Intensive Care Unit (ICU) and its relationship with clinical outcome.Methods:In this prospective observational pilot study, forty adult patients receiving mechanical ventilation in the ICU were included. Serum 25(OH)D was assessed within 24 h of admission. Primary outcome was 30-day mortality and secondary outcomes were days on mechanical ventilation, ICU-length of stay (ICU-LOS), days to reach spontaneous breathing trial (SBT), requirement of advanced care modality and complications.Results:Seventy-five percent patients had low serum 25(OH)D (65% deficient and 10% insufficient). Between patients with low and normal vitamin D, there was no significant difference in 30-day mortality (10% vs. 16.7%; P = 0.81), days on mechanical ventilation (16.2 ± 8.9 vs. 19.9 ± 8.4; P = 0.23), ICU-length of stay (18.7 ± 8.5 vs. 23.3 ± 11.4; P = 0.28), days to reach SBT (11.5 (0–20) vs. 21 (8–30); P = 0.78), complications developed during ICU stay (P = 0.60) and need for advanced care modalities (P = 0.72).Conclusion:Low Vitamin D level at admission did not affect 30-day mortality of critically ill patients on mechanical ventilation.