Protein S-palmitoylation is a reversible post-translational lipid modification that plays a critical role in neuronal development and plasticity, while dysregulated S-palmitoylation underlies a number of severe neurological disorders. Dynamic S-palmitoylation is regulated by a large family of ZDHHC palmitoylating enzymes, their accessory proteins, and a small number of known de-palmitoylating enzymes. Here, we curated and analyzed expression data for the proteins that regulate S-palmitoylation from publicly available RNAseq datasets, providing a comprehensive overview of their distribution in the mouse nervous system. We developed a web-tool that enables interactive visualization of the expression patterns for these proteins in the nervous system (http://brainpalmseq.med.ubc.ca/), and explored this resource to find region and cell-type specific expression patterns that give insight into the function of palmitoylating and de-palmitoylating enzymes in the brain and neurological disorders. We found coordinated expression of ZDHHC enzymes with their accessory proteins, de-palmitoylating enzymes and other brain-expressed genes that included an enrichment of S-palmitoylation substrates. Finally, we utilized ZDHHC expression patterns to predict and validate palmitoylating enzyme-substrate interactions.

Ebola virus is a member of Filoviridae and cause severe human disease with 90 percent mortality. The life cycle of Ebola contains an assembly stage which is mediated by VP40 proteins. VP40 subunits oligomerize and form ring-structures which are either octamers or hexamers. Prevention of VP40 matrix protein assembly prevents virus particle formation as well as virus budding. In the present study we simulated the biological condition for a single VP40 subunit. Then a library containing 120.000 drugs like chemicals was used as the virtual screening database. Top 10 successive hits were then analyzed regarding absorption, distribution, metabolism, and excretion properties. Moreover probable accessorial human protein targets and toxicity properties of successive hits were analyzed by in silico tools. We found 4 chemicals that could bind VP40 subunits in a manner that by making an interfering steric condense prevents matrix protein oligomerization. The pharmacokinetic and toxicity studies also validated the potential of 4 finlay successive hits to be considered as a new anti-Ebola drugs.

Application of wound-healing/dressing biomaterials is amongst the most promising approaches for wound repair through protection from pathogen invasion/contamination, maintaining moisture, absorbing exudates, modulating inflammation, and facilitating the healing process. A wide range of materials are used to fabricate wound-healing/dressing biomaterials. Active wound-healing/dressings are next-generation alternatives for passive biomaterials, which provide a physical barrier and induce different biological activities, such as antibacterial, antioxidant, and proliferative effects. Cellulose-based biomaterials are particularly promising due to their tunable physical, chemical, mechanical, and biological properties, accessibility, low cost, and biocompatibility. A thorough description and analysis of wound-healing/dressing structures fabricated from cellulose-based biomaterials is discussed in this review. We emphasize and highlight the fabrication methods, applied bioactive molecules, and discuss the obtained results from in vitro and in vivo models of cellulose-based wound-healing biomaterials. This review paper revealed that cellulose-based biomaterials have promising potential as the wound-dressing/healing materials and can be integrated with various bioactive agents. Overall, cellulose-based biomaterials are shown to be effective and sophisticated structures for delivery applications, safe and multi-customizable dressings, or grafts for wound-healing applications.

Objectives: Post-dural Puncture Headache (PDPH) is prevalent among individuals undergoing lumbar punctures. The non-invasive effect of some drugs, such as aminophylline on PDPH has been investigated in several clinical studies. As there is no comprehensive systematic review and meta-analysis about the preventive and therapeutic effects of aminophylline on PDPH in the literature, the clinical effectiveness of this drug on the prevention and/or treatment of PDPH will be assessed in this study. Methods: PubMed/MEDLINE, Embase, WoS (Clarivate Analytics), the Cochrane Central Register of Controlled Trials (CENTRAL), CINAHL Complete, Scopus, and Google Scholar as electronic databases will be precisely searched for clinical studies that assessed the effect of aminophylline on PDPH. Studies between 01-01-1980 and 30-06-2020 will be evaluated in this study, and there will not be any language restrictions. Contradictions between the reviewers within any phase of the study (screening, selecting, quality assessment, and data extraction) will be resolved by consensus; in case of unsolved disagreements, a third reviewer will eventually decide. The combination method will be applied according to the methodological resemblance in the selected articles using the Random Effect Model or the Fixed Effect Model. Also, for the included articles, forest plots will be drawn. For assessing statistical heterogeneity, the I2 statistic and the Q-statistic test will be applied. In addition, funnel plots will be used for assessing non-significant study effects and potential reporting bias. Furthermore, Egger’s and Begg’s tests will be done, and publication bias will be indicated by significant findings (P < 0.05). Conclusions: It is expected that the results of this study will be of benefit to researchers and clinicians for managing PDPH, and will be reported in conferences and publications.

It is well documented that use of Cisplatin, Lead acetate and Cyclosporine in the chemotherapy and medical interventions is highly associated with nephrotoxicity and interrelated comorbidities. Here, we proposed the possible molecular mechanisms responsible for nephrotoxicity of these compounds. We utilized the microarray dataset GSE59913 consisting of approximately 600 different compounds profiled in up to 8 different tissues. After analysis with GEO2R, gene expression profiles of three aforementioned compounds were integrated with protein-protein interactions (PPI) networks and topological properties of the networks were measured using Cytoscape software. We found several key genes and signaling pathways that seem to be involved in nephrotoxicity of the examined compounds. Myc and Smad4 were identified as principal players of three compounds' nephrotoxicity through various pathways. Our results revealed the critical functions of Il2, Jak-Stat, Mapk-Pi3k, TGFβ and Ca 2+ signaling pathways as well as novel biomarkers that may mediate the nephrotoxicity of Cisplatin, Lead acetate and Cyclosporine. The significantly altered genes in the compound-treated samples were substantially correlated with regulation of cell proliferation, apoptosis, inflammatory responses and homeostatic processes. This study reveals the important hub genes, biological networks and key pathways as well as novel biomarkers involved in nephrotoxicity of Cisplatin, Lead acetate and Cyclosporine.