Anticancer Effects of New Ceramides Isolated from the Red Sea Red Algae Hypnea musciformis in a Model of Ehrlich Ascites Carcinoma: LC-HRMS Analysis Profile and Molecular Modeling

Different classes of phytochemicals were previously isolated from the Red Sea algae Hypnea musciformis as sterols, ketosteroids, fatty acids, and terpenoids. Herein, we report the isolation of three fatty acids—docosanoic acid 4, hexadecenoic acid 5, and alpha hydroxy octadecanoic acid 6—as well as three ceramides—A (1), B (2), and C (3)—with 9-methyl-sphinga-4,8-dienes and phytosphingosine bases. Additionally, different phytochemicals were determined using the liquid chromatography coupled with electrospray ionization high-resolution mass spectrometry (LC-ESI-HRMS) technique. Ceramides A (1) and B (2) exhibited promising in vitro cytotoxic activity against the human breast adenocarcinoma (MCF-7) cell line when compared with doxorubicin as a positive control. Further in vivo study and biochemical estimation in a mouse model of Ehrlich ascites carcinoma (EAC) revealed that both ceramides A (1) and B (2) at doses of 1 and 2 mg/kg, respectively, significantly decreased the tumor size in mice inoculated with EAC cells. The higher dose (2 mg/kg) of ceramide B (2) particularly expressed the most pronounced decrease in serum levels of vascular endothelial growth factor -B (VEGF-B) and tumor necrosis factor-α (TNF-α) markers, as well as the expression levels of the growth factor midkine in tumor tissue relative to the EAC control group. The highest expression of apoptotic factors, p53, Bax, and caspase 3 was observed in the same group that received 2 mg/kg of ceramide B (2). Molecular docking simulations suggested that ceramides A (1) and B (2) could bind in the deep grove between the H2 helix and the Ser240-P250 loop of p53, preventing its interaction with MDM2 and leading to its accumulation. In conclusion, this study reports the cytotoxic, apoptotic, and antiangiogenic effects of ceramides isolated from the Red Sea algae Hypnea musciformis in an experimental model of EAC.

Low-level laser therapy for treatment of tinnitus in Red Sea scuba divers: a randomized clinical study

Background Scuba diving has become a popular hobby. However, diving puts the auditory system at the risk of a wide variety of complaints including tinnitus. Low-level laser therapy is a new modality in treatment of tinnitus. This study evaluates effect of laser therapy on tinnitus of scuba divers in Red Sea. This randomized study included 200 scuba diving patients with tinnitus without any other audiological symptoms. They were randomly divided into two groups: GI (n=100) patients were subjected to 60 sessions of laser therapy, and in the other group GII (n=100), the machine was off while doing the procedure. The Tinnitus Questionnaire (TQ) was done every 20 days to evaluate the severity of the tinnitus for both groups. Results Both groups were matched regarding age and sex distribution. GI group experienced significantly decreased tinnitus severity compared to GII after laser therapy. There was no relation between duration of diving and laser therapy effect in GI. Conclusion Laser therapy is effective in treatment of tinnitus of scuba divers and its effect is increased by number of laser sessions.

Profiling Signal Transduction in Global Marine Biofilms

Microbes use signal transduction systems in the processes of swarming motility, antibiotic resistance, virulence, conjugal plasmid transfer, and biofilm formation. However, the signal transduction systems in natural marine biofilms have hardly been profiled. Here we analyzed signal transduction genes in 101 marine biofilm and 91 seawater microbial metagenomes. The abundance of almost all signal transduction-related genes in biofilm microbial communities was significantly higher than that in seawater microbial communities, regardless of substrate types, locations, and durations for biofilm development. In addition, the dominant source microbes of signal transduction genes in marine biofilms were different from those in seawater samples. Co-occurrence network analysis on signal communication between microbes in marine biofilms and seawater microbial communities revealed potential inter-phyla interactions between microorganisms from marine biofilms and seawater. Moreover, phylogenetic tree construction and protein identity comparison displayed that proteins related to signal transductions from Red Sea biofilms were highly similar to those from Red Sea seawater microbial communities, revealing a possible biological basis of interspecies interactions between surface-associated and free-living microbial communities in a local marine environment. Our study revealed the special profile and enrichment of signal transduction systems in marine biofilms and suggested that marine biofilms participate in intercellular interactions of the local ecosystem where they were seeded.

Characterization of a novel peptide mined from the Red Sea brine pools and modified to enhance its anticancer activity

Peptide-based drugs have emerged as highly selective and potent cancer therapy. Cancer is one of the leading causes of death worldwide. Multiple approaches have been developed towards cancer treatment, including chemotherapy, radiation, and hormonal therapy; however, such procedures' non-specificity, toxicity, and inefficiency present a hurdle. In this study, we developed a support vector machine (SVM) model to detect the potential anticancer properties of novel peptides through scanning the American University in Cairo Red Sea metagenomics library. Further, we performed in silico studies on a novel 37-mer antimicrobial peptide mined from SVM pipeline analysis. This peptide was further modified to enhance its anticancer activity, analyzed for gene oncology, and subsequently synthesized. The anticancer properties of this 37-mer peptide were evaluated via cellular viability and cell morphology of SNU449, HepG2, SKOV3, and HeLa cells, using MTT assay. Furthermore, we assessed the migration capability of SNU449 and SKOV3 via scratch wound healing assay. Moreover, the targeted selectivity of the peptide for cancerous cells was assessed by testing its hemolytic activity on human erythrocytes. The peptide caused a significant reduction in cellular viability and critically affected the morphology of hepatocellular carcinoma (SNU449 and HepG2), ovarian cancer (SKOV3), and to a limited extent, cervical cancer cell lines (HeLa), in addition to decreasing viability of human fibroblast cell line (1Br-hTERT). Peptide treatment significantly affected the proliferation and migration ability of SNU449 and SKOV3 cells. Annexin V assay was used to evaluate induced cell death upon peptide treatment, attributing programmed cell death (Apoptosis) as the main cause of cell death in SNU449 cells. Finally, we established broad-spectrum antimicrobial properties of the peptide on both gram-positive and gram-negative bacterial strains. Thus, these findings infer the novelty of the peptide as a potential anticancer and antimicrobial agent.

Daily Atmospheric Circulation Patterns and Their Influence on Dry/Wet Events in Iran

Analyzing atmospheric circulation patterns characterize prevailing weather in a region. The method of principal component analysis and clustering was used to classify daily atmospheric circulation patterns. The average daily geopotential height of 500 hPa with 0.5° resolution of the ECMWF (1990–2019) were extracted from the Middle East. The S array was used to identify air types, and k-means clustering was used to classify daily air types. All days were divided into eighteen groups. Then, the surface maps and moisture flux divergence at the 850-hPa level of each pattern were studied. The, the connection between circulation patterns and precipitation occurrence is investigated by the PI index. The existence of a variety of precipitation and temperature regimes and consequent dry/wet periods is related to the type and frequency of the circulation patterns. In patterns with south to southwesterly currents, the low-pressure surface center extends from the south of the Red Sea to southern Turkey and is associated with the mid-level trough, where the moisture fluxes converge in the south of the Red Sea, southwest/south of Iran, and east of the Mediterranean Sea. Therefore, according to the intensity of the patterns, the most precipitation falls in the country’s western half, and the Zagros Mountain’s wind side. With the eastward movement of the Cyclonic patterns, the rainfall area extends to the eastern half of the country. With the pattern that the thermal low surface pressure extends to 35 °N latitude and is associated with the mid-level subtropical high, almost no rain occurs in the country.

Regime Shifts in Future Shoreline Dynamics of Saudi Arabia

The Saudi Arabian tourism sector is growing, and its economy has flourished over the last decades. This has resulted in numerous coastal developments close to large economic centers, while many more are proposed or planned. The coastal developments have influenced the behavior of the shoreline in the past. Here we undertake a national assessment on the state of the coast of Saudi Arabia based on recent data sets on historic and future shoreline positions. While at national scale the shoreline is found to be stable over the last three decades, the Red Sea coast shows a regional-mean retreat rate while the Gulf coast shows a regional-mean prograding behavior. Detailed analysis of the temporal evolution of shoreline position at selected locations show that human interventions may have accelerated shoreline retreat along adjacent shorelines, some of which are Marine Protected Areas. Furthermore, reef-fronted coastal sections have a mean accretive shoreline change rate, while the open coast shows a mean retreat rate. Future shoreline projections under RCP 4.5 and RCP 8.5 show that large parts of the shoreline may experience an accelerated retreat or a change in its regime from either stable or sprograding to retreating. Under the high emission RCP 8.5 scenario, the length of coastline projected to retreat more than doubles along the Red Sea coast, and approximately triples along the Gulf coast in 2100. At national scale, the Saudi Arabian coastline is projected to experience regional-mean retreats of ~30 m and of ~130 m by 2050 and 2100 under both RCPs considered in this study. These results indicate that effective adaptation strategies will be required to protect areas of ecological and economic value, and that climate resilience should be a key consideration in planned or proposed coastal interventions.