The Status of Natural Radioactivity and Heavy Metals Pollution on Marine Sediments Red Sea Coast, At Safaga, Egypt

Natural 226Ra, 232Th and 40K radio nuclides concentration in beach Sediments along Safaga coast of Red sea, Egypt has been carried out using a NaI (Tl) gamma ray spectrometric technique. The total average concentrations of radionuclides ± uncertainty of 226Ra, 232Th and 40K were 22.2 ± 1.7, 19.2 ± 2.5, and 477.6 ± 27.6 Bqkg-1, respectively. The total average absorbed dose rate is found to be 41.4 nGyh-1, whereas the annual effective dose rate has an average value of 54 μSvy-1. The total organic matter (TOC), carbonates (CaCo3) and Heavy metals distribution have been measured at some locations, the concentration for the investigated heavy metals overtake the allowable limits recommended by the Canadian Environmental Quality Guidelines, this assigned to the ratio of metals pollution is caused by anthropogenic activities (phosphate shipment as in Abu Tartour harbor and navigation as in Touristic harbor) and or by natural impacts such in mangrove interment. Statistical analyses were carried out between the parameters obtained from the radioactivity to know the existing relations and to study the spatial distribution of radionuclide

AM-1241 CB2 Receptor Agonist Attenuates Inflammation, Apoptosis and Stimulate Progenitor Cells in Bile Duct Ligated Rats

BACKGROUND: The cannabinoid receptor 2 (CB2) plays a pleiotropic role in the innate immunity and is considered a crucial mediator of liver disease. Cannabinoid CB2 receptor activation has been reported to attenuate liver fibrosis in CCl4 exposed mice and also plays a potential role in liver regeneration in a mouse model of I/R and protection against alcohol-induced liver injury. AIM: In this study, we investigated the impact of CB2 receptors on the antifibrotic and regenerative process associated with cholestatic liver injury. METHODS: Twenty-six rats had bile duct ligation co-treated with silymarin and AM1241 for 3 consecutive weeks. Serum hepatotoxicity markers were determined, and histopathological evaluation was performed. RESULTS: Following bile duct ligation (BDL) for 3 weeks, there was increased aminotransferase levels, marked inflammatory infiltration and hepatocyte apoptosis with induced oxidative stress, as reflected by increased lipid peroxidation. Conversely, following treatment with the CB2 agonist, AM-1241, BDL rats displayed a reduction in liver injury and attenuation of fibrosis as reflected by expression of hydroxyproline and α-smooth muscle actin. AM1241 treatment also significantly attenuated lipid peroxidation end-products, p53-dependent apoptosis and also attenuated inflammatory process by stimulating IL-10 production. Moreover, AM1241 treated rats were associated with significant expression of hepatic progenitor/oval cell markers. CONCLUSION: In conclusion, this study points out that CB2 receptors reduce liver injury and promote liver regeneration via distinct mechanisms including IL-10 dependent inhibition of inflammation, reduction of p53-reliant apoptosis and through stimulation of oval/progenitor cells. These results suggest that CB2 agonists display potent hepatoregenrative properties, in addition to their antifibrogenic effects

Exercise protects against obesity induced semen abnormalities via downregulating stem cell factor, upregulating Ghrelin and normalizing oxidative stress

Increased oxidative stress and hormonal imbalance have been hypothesized to underlie infertility in obese animals. However, recent evidence suggests that Ghrelin and Stem Cell Factor (SCF) play an important role in fertility, in lean individuals. Therefore, this study aimed at investigating whether changes in the levels of Ghrelin and SCF in rat testes underlie semen abnormal parameters observed in obese rats, and secondly, whether endurance exercise or Orlistat can protect against changes in Ghrelin, SCF, and/or semen parameters in diet induced obese rats. Obesity was modelled in male Wistar rats using High Fat Diet (HFD) 12-week protocol. Eight week-old rats (n=40) were divided into four groups, namely, Group I: fed with a standard diet (12 % of calories as fat); Group II: fed HFD (40 % of calories as fat); Group III: fed the HFD with a concomitant dose of Orlistat (200 mg/kg); and Group IV: fed the HFD and underwent 30 min daily swimming exercise. The model was validated by measuring the levels of testosterone, FSH, LH, estradiol, leptin, triglycerides, total, HDL, and LDL cholesterol, and final change in body weight. Levels were consistent with published obesity models (see Results). As predicted, the HFD group had a 76.8 % decrease in sperm count, 44.72 % decrease in sperm motility, as well as 47.09 % increase in abnormal sperm morphology. Unlike the control group, in the HFD group (i.e. obese rats) Ghrelin mRNA and protein were elevated, while SCF mRNA and protein were diminished in the testes. Furthermore, in the HFD group, SOD and GPx activities were significantly reduced, 48.5±5.8 % (P=0.0012) and 45.6±4.6 % (P=0.0019), respectively, while TBARS levels were significantly increased (112.7±8.9 %, P≤0.0001). Finally, endurance exercise training and Orlistat administration individually and differentially protected semen parameters in obese rats. The mechanism includes, but is not limited to, normalizing the levels of Ghrelin, SCF, SOD, GPx and TBARS. In rat testes, diet induced obesity down regulates SCF expression, upregulates Ghrelin expression, and deteriorate oxidative stress levels, which are collectively detrimental to semen parameters. Exercise, and to a lesse r extent Orlistat administration, protected effectively against this detrimental effect

Monitoring and Assessing the Coastal Ecosystem at Hurghada, Red Sea Coast, Egypt

In the framework of the investment plan, the government of Egypt introduced an accelerated development of Hurghada in collaboration with the private sector, as   early as 1980's.  The government intended to construct tourist resort communities, which required establishment of infrastructures. The  demand  of  such  facilities, in absence of enforced environmental roles led owners  to implement  processes  of  landfilling  and  dredging  for the purpose of smoothing, paving and widening the beach in order to construct swimming pools, marinas and other recreational facilities. Such activities came on the expense of the marine ecosystem and especially assault on the coral reef communities. For monitoring and assessing such oppressive activities;  MSS,  TM,  ETM+,  and SPOT XS 4 satellite images acquired  during  1972,  1984,  1992,  2004  and 2011. Shoreline change detection from 1972 to 2011 reveals landfilling of some 7.56Km2 and dredging of 2.67km2, with loss of 5.34km2 of the reef tracts. At the same period, the region has witnessed expansions in urban and road network by 16.47km2 and 8.738km2 respectively. The Egyptian government issued the essential laws for regulating and saving the coastal ecosystem, yet mostly violated. Activation of such laws, applying judicial officers, toughening penalties and establishment of coastal building front line (CBFL), and a reef protection line (RPL) are important tasks especially south of Hurghada to the Egyptian-Sudanese borders to preserve the remnants of such unique coastal ecosystem. Keywords: Satellite images, Hurghada, Red Sea, coastal ecosystem, shoreline changes, urban, road network, environment law

Design, synthesis, docking and mechanistic studies of new thiazolyl/thiazolidinylpyrimidine-2,4-dione antiproliferative agents

In this article, we display on the synthesis and biological evaluation of a new series of thiazolylpyrimidine 3a-l and thiazolidinylpyrimidine derivatives 5a-e. The structures of the new compounds were confirmed by using different spectral techniques including NMR, IR, mass spectroscopy in addition to elemental analyses. The cell viability of the new compounds was assessed against normal human mammary gland epithelial (MCF-10A) cell line. Data revealed that none of the compounds examined exhibited cytotoxic effects, and the cell viability for the compounds examined at 50 µM was greater than 87%. The antiproliferative activity of 3a-l and 5a-e was evaluated against four human cancer cell lines where the compounds showed promising activity. The most potent derivatives were compounds 3a, 3c, 3f, 3i, and 5b with GI$_{50}$ values ranging from 0.90 µM to 1.70 µM against the four cancer cell lines in comparison to doxorubicin (GI$_{50}$ = 1.10 µM). Compounds 3a, 3c and 3i showed potent antiproliferative activity with dual inhibitory action against EGFR and BRAF$^{V600E}$. Compounds 3a, 3c, and 3i demonstrated promising AutoDock scores towards EGFR and BRAF$^{V600E}$ with values of − 9.1 and − 8.6, −9.0 and − 8.5, and − 8.4 and − 8.0 kcal/mol, respectively. The physicochemical and pharmacokinetic characteristics of 3a, 3c, and 3i were anticipated, demonstrating their oral bioavailability

Potential molluscicidal activity of the aqueous extracts of some plants and their powders against terrestrial snail Monacha obstructa (L. Pfeiffer, 1842) under laboratory and field conditions

As it is known that the excessive use of pesticides causes many environmental problems, the effects of four aqueous plant extracts and their powders [Solanum nigrum L., Withania somnifera (L.) Dunal, Salix mucronata Thunb. and Lawsonia inermis L.] were evaluated as natural molluscicides on the land snail Monacha obstructa (Family: Hygromiidae) under laboratory conditions. Three different bioassay methods were used: contact, leaf-dipping and bait techniques. The results indicated that, using all methods, S. Nigrum extract was the most toxic extract for the terrestrial snail M. obstructa. The contact technique of the tested plant extracts was the most effective method of application compared to other methods. Moreover, using plant extracts was better than using powders of these plants for controlling the terrestrial snail M. obstructa. In addition, the results indicated that the aqueous extract of S. nigrum gave the highest percentage of reduction in the snail population when assessed under field conditions. The obtained data showed that plant extracts were significantly effective against the terrestrial snail and could be used as alternatives to pesticides in integrated pest management

CD33+ HLA-DR– Myeloid-Derived Suppressor Cells Are Increased in Frequency in the Peripheral Blood of Type1 Diabetes Patients with Predominance of CD14+ Subset

INTRODUCTION: Type 1 Diabetes Mellitus (T1D) is an autoimmune disease that results from the destruction of insulin-producing beta cells of the pancreas by autoreactive T cells. Myeloid-derived suppressor cells (MDSCs) are a heterogeneous population of cells that can potently suppress T cell responses.AIM: To detect the presence of MDSCs in T1D and compare their percentage in T1D versus healthy individuals.METHOD: Thirty T1D patients were included in the study. Diabetic patients with nephropathy (n = 18) and diabetic patients without nephropathy (n = 12). A control group of healthy individuals (n = 30) were also included. CD33+ and HLA-DR– markers were used to identify MDSCs by flow cytometry. CD14 positive and negative MDSCs subsets were also identified.RESULTS: MDSCs was significantly increased in T1D than the control group and diabetic patient with nephropathy compared to diabetic patients without nephropathy. M-MDSCs (CD14+ CD33+ HLA–DR−) were the most abundant MDSCs subpopulation in all groups, however their percentage decrease in T1D than the control group.CONCLUSION: MDSCs are increased in the peripheral blood of T1D with a predominance of the CD14+ MDSCs subset. Future studies are needed to test the immune suppression function of MDSCs in T1D

Modulatory effect of thymol on the immune response and susceptibility to Aeromonas hydrophila infection in Nile tilapia fish exposed to zinc oxide nanoparticles

Zinc oxide nanoparticles (ZnO-NPs) have many exciting properties that make their use in a continuous increase in various biomedical, industrial, and agricultural applications. This is associated with accumulation in the aquatic ecosystems and fish exposure with consequent deleterious effects. To determine the potential of thymol to counteract the immunotoxic effects of ZnO-NPs, Oreochromis niloticus was exposed to ZnO-NPs (⅕ LC50 =1.14 mg/L, for 28 days) with or without feeding a thymol-incorporated diet (1 or 2 g/kg diet). Our data demonstrated a reduction of aquaria water quality, leukopenia, and lymphopenia with a decrease in serum total protein, albumin, and globulin levels in exposed fish. At the same time, the stress indices (cortisol and glucose) were elevated in response to ZnO-NPs exposure. The exposed fish also revealed a decline in serum immunoglobulins, nitric oxide, and the activities of lysozyme and myeloperoxidase, in addition to reduced resistance to the Aeromonas hydrophila challenge. The RT-PCR analysis showed downregulation of antioxidant (SOD) superoxide dismutase and (CAT) catalase gene expression in the liver tissue with overexpression of the immune-related genes (TNF-α and IL-1β). Importantly, we found that thymol markedly protected against ZnO-NPs-induced immunotoxicity in fish co-supplemented with thymol (1 or 2 g/kg diet) in a dose-dependent manner. Our data confirm the immunoprotective and antibacterial effects of thymol in ZnO-NPs exposed fish, supporting the potential utility of thymol as a possible immunostimulant agent

Discovery of new Schiff bases of the disalicylic acid scaffold as DNA gyrase and topoisomerase IV inhibitors endowed with antibacterial properties

DNA gyrase and topoisomerase IV show great potential as targets for antibacterial medicines. In recent decades, various categories of small molecule inhibitors have been identified; however, none have been effective in the market. For the first time, we developed a series of disalicylic acid methylene/Schiff bases hybrids (5a-k) to act as antibacterial agents targeting DNA gyrase and topoisomerase IV. The findings indicated that the new targets 5f-k exhibited significant antibacterial activity against Gram-positive and Gram-negative bacteria, with efficacy ranging from 75% to 115% of the standard ciprofloxacin levels. Compound 5h demonstrated the greatest efficacy compared to the other compounds tested, with minimum inhibitory concentration (MIC) values of 0.030, 0.065, and 0.060 μg/mL against S. aureus, E. coli, and P. aeruginosa. 5h had a MIC value of 0.050 μg/mL against B. subtilis, which is five times less potent than ciprofloxacin. The inhibitory efficacy of the most potent antibacterial derivatives 5f, 5h, 5i, and 5k against E. coli DNA gyrase was assessed. The tested compounds demonstrated inhibitory effects on E. coli DNA gyrase, with IC50 values ranging from 92 to 112 nM. These results indicate that 5f, 5h, 5i, and 5k are more effective than the reference novobiocin, which had an IC50 value of 170 nM. Compounds 5f, 5h, 5i, and 5k were subjected to additional assessment against E. coli topoisomerase IV. Compounds 5h and 5i, which have the highest efficacy in inhibiting E. coli gyrase, also demonstrated promising effects on topoisomerase IV. Compounds 5h and 5i exhibit IC50 values of 3.50 µM and 5.80 µM, respectively. These results are much lower and more potent than novobiocin’s IC50 value of 11 µM. Docking studies demonstrate the potential of compound 5h as an effective dual inhibitor against E. coli DNA gyrase and topoisomerase IV, with ADMET analysis indicating promising pharmacokinetic profiles for antibacterial drug development