Neuroprotective Effect of Hyperbaric Oxygen Therapy on Anterior Ischemic Optic Neuropathy

The study investigated the therapeutic effect of hyperbaric oxygen (HBO) on anterior ischemic optic neuropathy in a rodent model (rAION). rAION was laser-induced in one eye of 63 mice. The fellow (uninjured) eye served as an internal control. Thirty-three mice underwent two 90-min sessions of 100% oxygen (2 atm) treatment immediately following injury and one session daily thereafter for up to 14 days. The remaining mice were untreated. Retinas were harvested at different time points, and mRNA levels of various genes were analyzed by real-time polymerase chain reaction and histologic study. Untreated mice: day 1 post-rAION – SOD-1 (oxidative-stress-related) decreased to 82% of control (uninjured eye) levels (P < 0.05), Caspase-3 (proapoptotic) decreased to 89%, Bcl-xL mildly increased (117%; all NS); day 3 – HO-1 and endothelial nitric oxide synthase (eNOS; ischaemia-related) decreased to 74%, and Bcl-2-associated X protein, Caspase-3, and B-cell lymphoma 2 (Bcl-2; apoptotic) increased by 170, 120, and 111%, respectively (all NS); day 21 – HO-1 increased to 222% (NS) and eNOS decreased to 48% (P < 0.05). Treated mice: day 1 – SOD-1 and Caspase-3 remained unchanged, Bcl-2 and Bcl-xL mildly increased (112 and 126% respectively); day 3 – HO-1 and eNOS increased, apoptosis-related gene decreased; day 21 – SOD-1 decreased whereas eNOS increased (P < 0.05), and HO-1 increased to a lesser degree than without treatment. None of the oxygen-treated animals had retinal ganglion cell loss or a decrease in Thy-1 expression. In conclusion, HBO treatment after rAION induction influences the expression of apoptosis-related genes as well as oxidative-stress-induced and ischaemia-related genes and may exert a neuroprotective effect

Novel Cyclic Peptides for Targeting EGFR and EGRvIII Mutation for Drug Delivery

The epidermal growth factor&ndash;epidermal growth factor receptor (EGF-EGFR) pathway has become the main focus of selective chemotherapeutic intervention. As a result, two classes of EGFR inhibitors have been clinically approved, namely monoclonal antibodies and small molecule kinase inhibitors. Despite an initial good response rate to these drugs, most patients develop drug resistance. Therefore, new treatment approaches are needed. In this work, we aimed to find a new EGFR-specific, short cyclic peptide, which could be used for targeted drug delivery. Phage display peptide technology and biopanning were applied to three EGFR expressing cells, including cells expressing the EGFRvIII mutation. DNA from the internalized phage was extracted and the peptide inserts were sequenced using next-generation sequencing (NGS). Eleven peptides were selected for further investigation using binding, internalization, and competition assays, and the results were confirmed by confocal microscopy and peptide docking. Among these eleven peptides, seven showed specific and selective binding and internalization into EGFR positive (EGFR+ve) cells, with two of them&mdash;P6 and P9&mdash;also demonstrating high specificity for non-small cell lung cancer (NSCLC) and glioblastoma cells, respectively. These peptides were chemically conjugated to camptothecin (CPT). The conjugates were more cytotoxic to EGFR+ve cells than free CPT. Our results describe a novel cyclic peptide, which can be used for targeted drug delivery to cells overexpressing the EGFR and EGFRvIII mutation

Ecogeographic Conditions Dramatically Affect <i>Trans</i>-Resveratrol and Other Major Phenolics’ Levels in Wine at a Semi-Arid Area

Grapevines are susceptible and responsive to their surrounding environment. Factors such as climate region and terroir are known to affect polyphenolic compounds in wine and therefore, its quality. The uniqueness of the terroir in Israel is the variety of soil types and the climatic conditions, ranging from Mediterranean to arid climates. Thus, understanding the effects of climate on grapevine performance in Israel may be a test case for the effect of climate change on grapevine at other areas in the future. First, we present a preliminary survey (2012–2014) in different climate zones and terroirs, which showed that trans-resveratrol concentrations in Merlot and Shiraz were high, while those of Cabernet Sauvignon were significantly lower. A further comprehensive countrywide survey (2016) of Merlot wines from 62 vineyards (53 wineries) compared several phenolic compounds’ concentrations between five areas of different climate and terroir. Results show a connection between trans-resveratrol concentrations, variety, and terroir properties. Furthermore, we show that trans-resveratrol concentrations are strongly correlated to humidity levels at springtime, precipitation, and soil permeability. This work can be considered a glimpse into the possible alterations of wine composition in currently moderate-climate wine-growing areas

Integration of the Connectivity Map and Pathway Analysis to Predict Plant Extract&rsquo;s Medicinal Properties&mdash;The Study Case of Sarcopoterium spinosum L.

Medicinal properties of plants are usually identified based on knowledge of traditional medicine or using low-throughput screens for specific pharmacological activities. The former is very biased since it requires prior knowledge of plants&rsquo; properties, while the latter depends on a specific screening system and will miss medicinal activities not covered by the screen. We sought to enrich our understanding of the biological activities of Sarcopoterium spinosum L. root extract based on transcriptome changes to uncover a plurality of possible pharmacological effects without the need for prior knowledge or functional screening. We integrated Gene Set Enrichment Analysis of the RNAseq data to identify pathways affected by the treatment of cells with the extract and perturbational signatures in the CMAP database to enhance the validity of the results. Activities of signaling pathways were measured using immunoblotting with phospho-specific antibodies. Mitochondrial membrane potential was assessed using JC-1 staining. SARS-CoV-2-induced cell killing was assessed in Vero E6 and A549 cells using an MTT assay. Here, we identified transcriptome changes following exposure of cultured cells to the medicinal plant Sarcopoterium spinosum L. root extract. By integrating algorithms of GSEA and CMAP, we confirmed known anti-cancer activities of the extract and predicted novel biological effects on oxidative phosphorylation and interferon pathways. Experimental validation of these pathways uncovered strong activation of autophagy, including mitophagy, and excellent protection from SARS-CoV-2 infection. Our study shows that gene expression analysis alone is insufficient for predicting biological effects since some of the changes reflect compensatory effects, and additional biochemical tests provide necessary corrections. This study defines the advantages and limitations of transcriptome analysis in predicting the biological and medicinal effects of the Sarcopoterium spinosum L. extract. Such analysis could be used as a general approach for predicting the medicinal properties of plants