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In this study, the anti-inflammatory effects of the methanolic extract (TE) of Plumeria obtusa L. (aerial parts) and its fractions were evaluated in vitro, and active fraction was evaluated in vivo. Among tested extracts, dichloromethane fraction (DCM-F) exhibited the strongest inhibition of lipopolysaccharide (LPS)-induced nitric oxide (NO) in RAW 264.7 macrophages. The effect of DCM-F on LPS-induced acute lung injury (ALI) in mice was studied. The animals were divided into five groups (n = 7) randomly; Gp I: negative control, GP II: positive control (LPS group), GP III: standard (dexamethasone, 2 mg/kg b.wt), GP IV and V: DCM-F (100 mg/kg), and DEM-F (200 mg/kg), respectively. DCM-F at a dose of 200 mg/kg suppressed the ability of LPS to increase the levels of nitric oxide synthase (iNOS), NO, tumor necrosis factor-α (TNF-α), and interleukin 6 (IL-6), as measured by ELISA. In addition, the expression of cyclooxygenase-2 (COX-2) was reduced (determined by immunohistochemistry) and the level of malondialdehyde (MDA) was decreased while that of catalase was restored to the normal values. Furthermore, the histopathological scores of inflammation induced by LPS were reduced. Twenty-two compounds were tentatively identified in DCM-F using LC/ESI-QToF with iridoids, phenolic derivatives and flavonoids as major constituents. Identified compounds were subjected to two different molecular docking processes against iNOS and prostaglandin E synthase-1 target receptors. Notably, protoplumericin A and 13-O-coumaroyl plumeride were the most promising members compared to the co-crystallized inhibitor in each case. These findings suggested that DCM-F attenuates the LPS-induced ALI in experimental animals through its anti-inflammatory and antioxidant potential.

Hepatocellular carcinoma (HCC) is the major life-threatening primary liver malignancy in both sexes all over the world. Unfortunately, the majority of patients are diagnosed at later stages because HCC does not elicit obvious symptoms during its early incidence. Consequently, most individuals escape the first-line HCC treatments and are treated with chemotherapy. Regrettably, the therapeutic outcomes for those patients are usually poor because of the development of multidrug resistance phenomena. Furthermore, most anti-HCC therapies cause severe undesired side effects that notably interfere with the life quality of such patients. Accordingly, there is an important need to search for an alternative therapeutic drug or adjuvant which is more efficient with safe or even minimal side effects for HCC treatment. Melatonin was recently reported to exert intrinsic antitumor activity in different cancers. However, the regulatory pathways underlying the antitumor activity of melatonin are poorly understood in resistant liver cells. Furthermore, a limited number of studies have addressed the therapeutic role of melatonin in HCC cells resistant to doxorubicin chemotherapy. In this study, we investigated the antitumor effects of melatonin in doxorubicin-resistant HepG2 cells and explored the regulatory pivotal targets underlying these effects. To achieve our aim, an MTT assay was used to calculate the 50% inhibitory concentration of melatonin and evaluate its antiproliferative effect on resistant cells. Additionally, qRT-PCR was used to quantify genes having a role in drug resistance phenotype (ABCB1, ABCC1, ABCC2, ABCC3, ABCC4, ABCC5, and ABCG2); apoptosis (caspases-3, and -7, Bcl2, Bax, and p53); anti-oxidation (NRF2); expression of melatonin receptors (MT1, MT2, and MT3); besides, programmed death receptor PD-1 gene. The active form of the caspase-3 enzyme was estimated by ELISA. A human inflammatory antibody membrane array was employed to quantify forty inflammatory factors expressed in treated cells. We observed that melatonin inhibited the proliferation of doxorubicin-resistant HepG2 cells in a dose-dependent manner after 24-h incubation time with a calculated IC50 greater than 10 mM (13.4 mM), the expression levels of genes involved in drug resistance response (ABCB1, ABCC1, ABCC5, and ABCG2) were downregulated. Also, the expression of caspase-3, Caspase-7, NRF2, and p53 genes were expressed at higher levels as compared to control (DMSO-treated cells). An active form of caspase-3 was confirmed by ELISA. Moreover, the anti-inflammatory effect of melatonin was detected through the calculated fold change to control which was reduced for various mediators that have a role in the inflammation pathway. The current findings introduce melatonin as a promising anti-cancer treatment for human-resistant HCC which could be used in combination with current chemotherapeutic regimens to improve the outcome and reduce the developed multidrug resistance.

Hepatocellular carcinoma (HCC) is the major lethal primary liver malignant worldwide. Although, melatonin has various antitumor bioactivities; there is a requirement for more investigations to elucidate the not discussed effects, and the controversial responses of the treatment with melatonin on targets mediated in HCC. To achieve the aim of the present study, HCC-HepG2 cells were treated with different concentrations of melatonin at various time intervals. The selected minimal proliferation inhibition doses of melatonin were then incubated with cells to examine the arresting effect of melatonin on dividing cells using flow cytometry. Furthermore, the molecular patterns of genes that contributed to apoptosis, drug resistance development, antioxidation, and melatonin crossing were quantified by qRT-PCR. Additionally, the Human inflammation antibody array membrane (40 targets) was used to check the anti-inflammatory effect of melatonin. Our results validated that, melatonin shows anti-proliferative action through preserving cells in G0/G1 phase (P P P

In the present work, the extensive biological activities of marine endophytic Streptomyces strains isolated from marine soft coral Sarcophyton convolutum have been demonstrated. Within fifty-one Streptomyces isolates evaluated for their hydrolytic enzymes and enzyme inhibitors productivities, six isolates showed the hyperactivities. Pharmaceutical metabolites productivities evaluated include enzymes (alkaline protease, L-asparaginase, L-glutaminase, tyrosinase, and L-methioninase) and enzyme inhibitors (inhibitors of α-amylase, hyaluronidase, β-lactamase, α-glucosidase, and β-glucosidase). These isolates were identified based on their morphological, biochemical, and genetic characteristics as Streptomyces sp. MORSY 17, Streptomyces sp. MORSY 22, Streptomyces sp. MORSY 25, Streptomyces sp. MORSY 36, Streptomyces sp. MORSY 45, and Streptomyces sp. MORSY 50. Moreover, in further evaluation, these strains exhibited wide spectrum of antimicrobial (against bacteria and fungi), antiviral (against hepatitis C virus), antibiofilm against biofilm-forming bacteria (methicillin-resistant Staphylococcus aureus and multidrug-resistant Pseudomonas species), and anti-proliferative activities (against liver and colon carcinoma cell lines). The GC–MS analysis of the hyperactive strains MORSY 17 and MORSY 22 revealed the presence of different bioactive agents in the ethyl acetate extract of both strains.

Tumor-associated macrophages (TAMs) have been shown to both aid and hinder tumor growth, with patient outcomes potentially hinging on the proportion of M1, pro-inflammatory/growth-inhibiting, to M2, growth-supporting, phenotypes. Strategies to stimulate tumor regression by promoting polarization to M1 are a novel approach that harnesses the immune system to enhance therapeutic outcomes, including chemotherapy. We recently found that nanotherapy with mesoporous particles loaded with albumin-bound paclitaxel (MSV-nab-PTX) promotes macrophage polarization towards M1 in breast cancer liver metastases (BCLM). However, it remains unclear to what extent tumor regression can be maximized based on modulation of the macrophage phenotype, especially for poorly perfused tumors such as BCLM. Here, for the first time, a CRISPR system is employed to permanently modulate macrophage polarization in a controlled in vitro setting. This enables the design of 3D co-culture experiments mimicking the BCLM hypovascularized environment with various ratios of polarized macrophages. We implement a mathematical framework to evaluate nanoparticle-mediated chemotherapy in conjunction with TAM polarization. The response is predicted to be not linearly dependent on the M1:M2 ratio. To investigate this phenomenon, the response is simulated via the model for a variety of M1:M2 ratios. The modeling indicates that polarization to an all-M1 population may be less effective than a combination of both M1 and M2. Experimental results with the CRISPR system confirm this model-driven hypothesis. Altogether, this study indicates that response to nanoparticle-mediated chemotherapy targeting poorly perfused tumors may benefit from a fine-tuned M1:M2 ratio that maintains both phenotypes in the tumor microenvironment during treatment.

In the pharmaceutical sector, tissue culture techniques for large-scale production of natural chemicals can be a less expensive alternative to large-scale synthesis. Although recent biotransformation research have used plant cell cultures to target a wide range of bioactive compounds, more compiled information and synopses are needed to better understand metabolic pathways and improve biotransformation efficiencies.This report reviews the biochemical transformation of phenolic natural products by plant cell cultures in order to identify potential novel biotechnological approaches for ensuring more homogeneous and stable phenolic production year-round under controlled environmental conditions.Articles on the use of plant cell culture for polyphenolic and flavonoid transformations (1988 - 2021) were retrieved from SciFinder, PubMed, Scopus, and Web of Science through electronic and manual search in English. Following that, the authors chose the required papers based on the criteria they defined. The following keywords were used for the online search: biotransformation, Plant cell cultures, flavonoids, phenolics, and pharmaceutical products.The initial search found a total of 96 articles. However, only 70 of them were selected as they met the inclusion criteria defined by the authors. The analysis of these studies revealed that plant tissue culture is applicable for the large-scale production of plant secondary metabolites including the phenolics, which have high therapeutic value.Plant tissue cultures could be employed as an efficient technique for producing secondary metabolites including phenolics. Phenolics possess a wide range of therapeutic benefits, as anti-oxidant, anti-cancer, and anti-inflammatory properties. Callus culture, suspension cultures, transformation, and other procedures have been used to improve the synthesis of phenolics. Their production on a large scale is now achievable. More breakthroughs will lead to newer insights and, without a doubt, to a new era of phenolics-based pharmacological agents for the treatment of a variety of infectious and degenerative disorders.

The agricultural by-products are a significant source of health benefiting bioactive compounds. In this trend, the phenolic and flavonoid contents and functional properties of date palm seeds (DPS) and saw palmetto seeds (SPS) extracts were evaluated in this study. Considerable phenolic and flavonoid contents of 11.8, 7.75 mg GAE/g seed and 3.13, 1.1 mg CE/g seed were detected in DPS ethanol and SPS acetone extracts, respectively. The protocatechuic acid was the major compound in SPS and DPS extracts and represented 1.41 and 1.1 mg/g seed, respectively as well as similar phenolic compounds were detected using HPLC analysis. The DPS and SPS phenolic compounds possessed a strong antioxidant activity with IC50 values of 10.0, 2.2 and 2.0, 0.6 µg GAE/mL, using the DPPH and ABTS assays, respectively. The phenolic compounds of DPS and SPS extracts showed a potent and broad anti-bacterial activity against clinical multiple drug resistance bacterial strains with lower MIC values besides an effective anti-fungal activity against a number of human pathogenic fungal strains. Interestingly, in a model of LPS-induced inflammation in RAW 264.7 cells, DPS and SPS showed efficient anti-inflammatory effects to inhibit the iNOS protein expression and activity (NO release).

In the present work, the extensive biological activities of marine endophytic Streptomyces strains isolated from marine soft coral Sarcophyton convolutum have been demonstrated. Within fifty-one Streptomyces isolates evaluated for their hydrolytic enzymes and enzyme inhibitors productivities, six isolates showed the hyperactivities. Pharmaceutical metabolites productivities evaluated include enzymes (alkaline protease, L-asparaginase, L-glutaminase, tyrosinase, and L-methioninase) and enzyme inhibitors (inhibitors of α-amylase, hyaluronidase, β-lactamase, α-glucosidase, and β-glucosidase). These isolates were identified based on their morphological, biochemical, and genetic characteristics as Streptomyces sp. MORSY 17, Streptomyces sp. MORSY 22, Streptomyces sp. MORSY 25, Streptomyces sp. MORSY 36, Streptomyces sp. MORSY 45, and Streptomyces sp. MORSY 50. Moreover, in further evaluation, these strains exhibited wide spectrum of antimicrobial (against bacteria and fungi), antiviral (against hepatitis C virus), antibiofilm against biofilm-forming bacteria (methicillin-resistant Staphylococcus aureus and multidrug-resistant Pseudomonas species), and anti-proliferative activities (against liver and colon carcinoma cell lines). The GC-MS analysis of the hyperactive strains MORSY 17 and MORSY 22 revealed the presence of different bioactive agents in the ethyl acetate extract of both strains.

A solvent extract of the soft coral Sarcophyton ehrenbergi afforded cembrene diterpenoids, sarcoehrenbergilid D–F (1–3). Chemical structures were established by modern spectroscopic techniques with absolute stereochemistries determined by circular dichroism (CD) and time-dependent density functional theory electronic CD calculations (TDDFT-ECD). Cytotoxicity activities for 1–3 were evaluated against three human cancer cell lines: lung (A549), colon (Caco-2) and liver (HepG2).

climate's change is one of the most important threats facing the world. That is because it causes a high ambient temperature. (UNEP, 2010). According to the report of the World Meteorological Organization (WMO, 2015), the period 2011- 2015 recorded the highest temperatures and was affected by Climate's change. Agriculture sector is strongly influenced by climatic conditions. A majority of works in agriculture are still performed outdoors under several weather conditions. High temperature, intensive insolation and elevated air humidity providing a dangerous work conditions. These weather conditions can lead to overheating (heat stress) and dehydration of the agricultural field workers. An index assessing heat stress in human beings, namely: Wet Bulb Globe Temperature (WBGT) was used in this study. This study presents the effect of heat stress from the point of view of agricultural field worker occupational health safety. Comparison of the three agricultural working conditions reveals significantly more severe heat stress in wheat threshing, rice transplanting and cotton harvesting, in terms of both the frequency of heat-stress episodes and the number of hours associated with heat stress. The WBGT maximum values during the time from 11 am up to 4 pm for wheat threshing, rice transplanting and cotton harvesting operations were 34.2 oC at 2 pm, 31.6 oC at 1 pm and 30.8 oC at 1:30 pm respectively. While the WBGT minimum values were 31.7 oC at 4 pm, 28.4 oC at 11 am, and 28.5 oC at 4 pmrespectively. The three presented work conditions are affirmed that a dangerous situation for agriculture field workers is stand. The values of the environmental parameters and its relation with heat stress during the day work hours under the previous field operations cleared that the heat stress has direct proportion with humidex and reversible proportion with air velocity and relative humidity. The agriculture field workers have exposure to hazard levels of heat stress resulting in high levels of body temperature. It is recommended to establish a sunshade for wheat thresher to provide a shade working area

Two new E/Z neo-clerodane diterpene isomers, trivially named stachaegyptin D (1) and E (2), together with known compounds, stachysolon monoacetate (3) and stachysolon diacetate (4), were isolated from an organic-solvent extract of the medicinal herb Stachys aegyptiaca. Structures were elucidated by a combination of spectroscopic methods, including HREIMS, 1H, 13C, DEPT, and 2D NMR analysis, as well as, first time X-ray analysis for stachysolone (3). All isolated metabolites showed some activity against the human hepatocellular cell line, HepG2. Compound 4 was the most active with an IC50 of 59.5 μM.

A polysaccharide characterized as galactomannan (GMann) with a molecular weight of 117.76 kDa was isolated from the aqueous extract of Caesalpinia gilliesii (C. gilliesii) seeds then assessed for antiproliferative potential against human hepatocellular carcinoma cell line (HepG2). Further, HCC was induced in Wister albino rats by Diethylnitrosamine (DEN) ip injection (200 mg/kg bw), and CCl4 orally (2 ml/kg bw) for two months then subjected to GMann orally treatment (2 mg/kg bw) for one month. In results, isolated GMann is constituted of sugars (89.99 ± 2.3%), moisture (6.89 ± 0.45%), ash (0.06 ± 0.2%), and protein (2.81%) and composed mainly of mannose and galactose in ratio M/G 3.79. In vitro study, data revealed a concentration-dependent potency of GMann to induce cell death of HepG2 cells with IC50 value of 0.375 µg/ml. Mechanistic studies revealed the potential of GMann to arrest cell cycle at G2/M phase with induction of apoptosis. Biochemical results in vivo showed a significant reduction in serum transaminases (ALT and AST) as well as hepatic malondialdehyde (MDA) and nitric oxide (NOx). Molecular analysis declared a significant down-regulation in mRNA gene expression of both nuclear factor kappa-B (NF-κB) and tumor necrosis factor (TNF-α). Furthermore, a significant down-regulation in the cellular oncogene-fos (C-fos) and marked up-regulation in Glycogen synthase kinase-3 (GSK-3β) level were observed. These results were supported with histopathological investigation. Whereas GMann improved inflammatory and apoptotic markers, it could be a promising new therapeutic agent for HCC suppression and this warrant further development as a possible drug candidate for HCC.

Forty-four endophytic fungal isolates obtained from marine sponge, Hyrtios erectus, were evaluated and screened for their hydrolase activities. Most of the isolates were found to be prolific producers of hydrolytic enzymes. Only 11 isolates exhibited maximum cellular contents of lipids, rhamnolipids, and protein in the fungal isolates under the isolation numbers MERVA5, MERVA22, MERVA25, MERVA29, MERVA32, MERVA34, MERV36, MERVA39, MERVA42, MERVA43, and MERVA44. These isolate extracts exhibit the highest reducing activities against carbohydrate-metabolizing enzymes including α-amylase, α-glucosidase, β-glucosidase, β-glucuronidase, and tyrosinase. Consequently, based on morphological and cultural criteria, as well as sequence information and phylogenetic analysis, these isolates could be identified and designated as Penicillium brevicombactum MERVA5, Arthrinium arundinis MERVA22, Diaporthe rudis MERVA25, Aspergillus versicolor MERVA29, Auxarthron alboluteum MERVA32, Dothiorella sarmentorum MERVA34, Lophiostoma sp. MERVA36, Fusarium oxysporum MERVA39, Penicillium chrysogenum MERVA42, Penicillium polonicum MERVA43, and Trichoderma harzianum MERVA44. The endophytic fungal species, D. rudis MERVA25, P. polonicum MERVA43, Lophiostoma sp. MERVA36, A. alboluteum MERVA32, T. harzianum MERVA44, F. oxysporum MERVA39, A. versicolor MERVA29, and P. chrysogenum MERVA42 extracts, showed significant hepatitis C virus (HCV) inhibition. Moreover, D. sarmentorum MERVA34, P. polonicum MERVA43, and T. harzianum MERVA44 extracts have the highest antitumor activity against human hepatocellular carcinoma cells (HepG2).

Triple-negative breast cancer (TNBC) is a highly aggressive malignancy with limited treatment options due to its heterogeneity and the lack of well-defined molecular targets. In our endeavour towards the development of novel anti-TNBC agents, herein we report a one-pot three-component synthesis of novel spirooxindoles 6a–p, and evaluation of their potential anti-proliferative activity towards TNBC MDA-MB-231 cells. Spirooxindoles 6a, 6e and 6i emerged as the most potent analogues with IC50 = 6.70, 6.40 and 6.70 µM, respectively. Compounds 6a and 6e induced apoptosis in MDA-MB-231 cells, as evidenced by the up-regulation of the Bax and down-regulation of the Bcl-2, besides boosting caspase-3 levels. Additionally, 6e displayed significant increase in the percent of annexin V-FITC positive apoptotic cells from 1.34 to 44%. Furthermore, spirooxindoles 6e and 6i displayed good inhibitory activity against EGFR (IC50 = 120 and 150 nM, respectively). Collectively, these data demonstrated that 6e might be a potential lead compound for the development of effective anti-TNBC agents.

Artificially designed miRNAs mimics and inhibitors that specifically target known oncogenes have attracted significant research attention. Herein, we aimed to explore whether MIR-375, MIR-145, and MIR-224 are involved in induction of apoptosis of CRC cells by regulating apoptosis-mediating genes MTDH, MAP3K1, PDK1, BAX, and BCL-XL. MTT assay was used to assess cell growth. Apoptosis was determined in terms of caspase activity measurement and phosphatidylserine detection using annexin V staining by flow cytometry. Quantitative real time PCR, Western blotting, and luciferase reporter assay were carried out to validate genes regulation and targeting by miRNAs. We found that ectopic expression of MIR-375 and MIR-145, and inhibition of MIR-224 can decrease cell growth and induce cell ability to undergo early apoptosis. At mRNA level, transfected cells displayed down-regulation of MTDH, PDK1 and BCL-XL, while BAX and MAP3K1 were up-regulated. Protein expression of MTDH was decreased in cells transfected with MIR-145 mimic and MIR-224 inhibitor but remained unchanged in MIR-375 mimic-transfected cells. Furthermore, MAP3K1 protein expression exibited a decreased level after MIR-375 transient expression with no significant change after MIR-145 mimic or MIR-224 inhibitor transfection. Luciferase reporter assay revealed that MIR-375 and MIR-145 can bind to 3'UTR of MTDH, supporting that MTDH is directly targeted by both miRNAs. Similarly, MAP3K1 was found to be directly regulated by MIR-375. The study concluded that the expression modulation of tumor suppressors MIR-375 and MIR-145, and oncomiR MIR-224 have the ability to induce apoptosis of CRC cells through regulation of apoptosis mediating genes MTDH, MAP3K1, PDK1, BCL-XL and BAX.

Multidrug resistance (MDR) remains a burden in cancer chemotherapy. Several members of ATP-binding cassette (ABC transporters) are responsible for the efflux of anticancer drugs outside cells decreasing the drug’s effective intracellular concentration. Therefore, extensive efforts have been conducted by researcher to circumvent the activity of these transporters to enhance the success of chemotherapy. In the present study, we questioned the role played by two microRNAs, namely miR-98 and miR-214 in controlling their bioinformatics’ predicted ABC efflux transporter targets ABCC5 and ABCC10, in addition to ABCB1 and ABCC1 in doxorubicin-resistant HCC cells (HepG2/Dox). miRNA mimics and inhibitors transfection were utilized to explore the role of both candidate molecules in MDR in HepG2/Dox cells. QRT-PCR and western blotting were used for quantitative gene and protein analyses. The study revealed that miR-214 mimics significantly upregulated ABCC1 and ABCC5. While, miR-98 and miR-214 inhibitors significantly down regulated ABCC5 and ABCC10, respectively. These results introduced a possible negative role played by both miR-98 and miR-214 on drug sensitization. Moreover, these findings clarified that the predicted targets for miR-98 and miR-214 were not confirmed experimentally.

Phytochemical investigation of Stachys aegyptiaca resulted in the characterization of three new diterpenes (1-3) together with eleven known compounds including four neo-clerodane diterpenes and seven flavonoid aglycones. Structure elucidation was performed by spectroscopic analysis by HRFABMS, 1D and 2D NMR and X-ray. Isolated compounds were screened for anti-inflammatory activity using a lipopolysaccharide-induced nitric oxide inhibition assay employing murine macrophage cells. Among the assayed compounds, 13 (calycopterin) showed a concentration-dependent inhibition of LPS-induced nitric oxide release with a IC50 of 62.5 μM.

Aportable compact precision plug trayvegetable seeder wasmanufactured in Agricultural Engineering Research Institute (AEnRI) workshop to plant fine and large vegetable seeds with low cost and high seed singulation ratio. The seeder was depended on a controlled negative and positive pressure passed through a set of nozzles to pickup and drop the seeds into the tray cells. For tomato seeds, four nozzles holders equipped with 209 nozzles with inner diameters of (0.47 mm, 0.62 mm, 0.76 mm and 1 mm for each set) were tested with negative pressure of (1, 1.25, 1.5 and 1.75 kPa). For cantaloupe-melon, four nozzles holders equipped with 84 nozzles with inner diameters of (0.76 mm, 1.00 mm, 1.2 mm and 1.4 mm) were tested with negative pressure of (6, 7, 8 and 9 kPa). The performance of the seeder was evaluated using seed singulation efficiency, seeding efficiency, seeder productivity, specific energy requirement and seeding cost. The machine succeeded to plant large and small seeds in different types of plug trays. The optimum nozzle diameter for planting tomato seeds was 0.62 mm operated at negative pressure of 1.25 kPa that gave percentage of single seed 89.95%, double seeds 4.79%, multiply seeds 2.39% and missed seeds 2.87%. Meanwhile, the optimum nozzle diameter for planting the cantaloupe-melon seeds was 1.20 mm operated at negative pressure 8.0 kPa that gave percentage of single seed 94.05%, double seeds 2.38%, multiple seeds 2.38% and missed seeds 1.19%. The productivity of precision vacuum trays seeder was 320 tray/ h (66880 and 26880 cells/ h) for tomato and cantaloupe-melon seeds respectively. The total power requirement for the seeder was 1.075 kW.h for tomato seeds and 1.216 kW.h for cantaloupe melon seeds. The consumed specific energy was (3.36×10-3 kWh/ tray) for tomato seeds and (3.80×10-3 kWh/ tray) for cantaloupe melon seeds. The total operating cost was 43.37 LE/h. The cost of one tray seeded by the machine was 0.14 LE/ tray comparing with (0.67 and 1.67) LE/try for hand seeding of (cantaloupe melon tray and tomato tray) respectively. The total fabrication cost of the seeding machine was 15000 LE with 2016 price level. The rental value of mechanical seeding per tray was 0.20 LE. The seeding machine indicated net present value (NPV) of 2930 LE at 11 % interest rate. The seeding machine payback period was about 1.3 year.

A solvent extract of the soft coral

BACKGROUND: Annona muricata (Soursop) has an antimicrobial activity toward various pathogenic microorganisms which support its ethnomedicinal for the treatment of many infectious diseases. AIM: Aim of the present study to evaluate the relation between antimicrobial activities of terpenoids extracted from different soursop parts with the isolated endophytic fungi. METHODS: Endophytic fungal species of pulp and peel of Annona fruit along with those of seeds were isolated. Salkowski test was used for qualitative screening of terpenoids in plant and the isolated endophytic Aspergillus niger strain SH3. RESULTS: Endophytic A. niger strain SH3 and Annona seed extract showed high terpenoid content indicated by the high intensity of reddish-brown colour. GC/Mass analysis revealed six compounds of terpenoids from endophytic A. niger strain SH3 extract and four compounds from seed extract with different retention times. The antimicrobial assay was performed using A. niger strain SH3 extract and Annona seed extract singly or in combinations against S. aureus, P. aeruginosa, E. coli and C. albicans. CONCLUSION: The results revealed the significant antimicrobial activity of both extracts. However, the combined extract showed some reduction in antimicrobial activity which could be attributed to the antagonistic effect exhibited by their constituents.

The alcoholic extract of Adhatoda vasica showed strong and reversible inhibition of the enzyme acetyl cholinesterase (AChE) with an IC50 = 294 μg/mL. Phytochemical study of the total alcoholic extract of A. vasica yielded four known compounds vasicine, vasicinone, vasicole and anisotine. Vasicine reversibly and competitively inhibited AChE with ki value 11.24 μM. On the other hand, rest of isolated alkaloids showed no/or weak inhibitory effect on AChE. Vasicine showed binding similarity to both galantamine and tacrine in the catalytic site. The obtained results support the multi-pharmacological properties of vasicine, which can be considered as a promising inhibitor for acetyl cholinesterase where it can be used directly or indirectly for the development of efficient anti-Alzheimer drug.

Medicinal plants from the Egyptian Sinai Peninsula are widely used in traditional Bedouin medicine to treat a range of conditions including cancer, and as such are a promising resource for novel anti-cancer compounds. To achieve scientific justification of traditional use and/or to recommend the use of those plants as medicinal herbs for cancer chemoprevention, a group of 11 Sinai plants of different species that belong to 3 families (Asteraceae, Lamiaceae, and Euphorbiaceae) were biologically screened for cancer preventive activity using the chemoprevention marker enzyme NAD(P)H:quinone oxidoreductase 1 (NQO1). Among the fractions assayed, a solvent extract from Pulicaria incisa had potent NQO1 inducing activity. Further analysis of the mechanism of induction revealed the concentration-dependent stabilization of the transcription factor NF-E2 p45-related factor 2 (Nrf2) and a coordinate upregulation of the Nrf2-dependent enzymes NQO1, heme oxygenase 1 and glutathione S-transferase-Pi. These results establish P. incisa as a promising target for future phytochemical characterization for cancer preventive components.

Background Statistics on cancer incidence and mortalities indicate that this disease still has a fatal outcome for a majority of patients due to non-sufficient treatment. The options available for cancer treatment include chemotherapy, which still commands a leading position in clinical oncology. A major obstacle to successful chemotherapy is the development of cellular resistance to multiple structurally unrelated anticancer drugs. This phenomenon has been termed multidrug resistance (MDR), which occurs in a majority of cancer patients. MDR is mainly due to the overexpression of ABC transporters which extrude chemotherapeutic drugs outside of cancer cells. A plethora of synthetic chemosensitizers have been described during the past decades that block ABC transporter function to reverse their MDR. However, none of them reached clinical routine application as of yet. In this review, we highlight the potential of natural products derived from plants, marine organisms, fungi, and other sources as chemosensitizers to the targeted major ABC transporters (ABCB1, ABCC1, and ABCG2). Conclusion Natural compounds may serve as lead compounds for the development of novel ABC transporter inhibitors with improved pharmacological features that can be used as adjuvant therapy to enhance the efficacy of chemotherapeutic drugs against MDR.

Chemoprevention can be defined as a means of controlling cancer in which the incidence of the disease can be entirely prevented, slowed down, or reversed. Chemoprevention is acquiring great attention because it is a cost-effective alternative to cancer treatment, such as chemotherapy or radio-therapeutic programs, which should reduce the burden on local and global economies. There is increasing interest in studying the chemoprevention potentiality of natural compounds against cancer as a result of the reduced cancer risk in people who consume high amounts of phytochemicals in their diet. Chemoprevention may involve the interruption or reversal of the initiation and progression of the disease by setting targets with the goal of preventing end stage invasiveness and metastasis. The initiation stage of cancer can be stopped by preventing reactive oxygen species and/or carcinogen activity (i.e., scavenging free radicals or trapping carcinogens) or by inhibiting their metabolic activation, thereby suppressing their interaction with cellular macromolecular targets, such as DNA, RNA, and proteins. This can be achieved by inducing of a set of phase II detoxifying and antioxidant enzymes, such as the chemopreventive marker NAD(P)H:quinone oxidoreductase 1 (NQO1) and heme oxygenase (HO-1). NQO1 is a ubiquitous flavoenzyme that plays a crucial role in protecting cells from endogenous and exogenous oxidative stressors by catalyzing two- and four-electron reductions of these substrates to their hydroquinone forms. The expression of NQO1 in different tissues is regulated by antioxidant response elements (AREs) under both basal and oxidative stress conditions. NQO1 is known to be regulated by nuclear factor erythroid-derived related factor 2 (Nrf2), which belongs to the basic leucine zipper transcription factor family, and binds to AREs, leading to the expression of many cytoprotective and antioxidant genes. Since Nrf2 binds to AREs and regulates the expression and induction of NQO1, Nrf2 knockout causes a reduction in the constitutive expression of NQO1 and impairs its induction. Several vegetables and fruits, including blueberries, cocoa beans, cabbage, broccoli, and cauliflower, are among the most protective agents against cancer. This is specifically due to their high content of active phytochemicals, such as sulforaphanes, isothiocyanates, polyphenols, and flavonoids. Upon entering cells these chemicals can directly counteract free radicals and induce electrophilic stress signals that trigger proteins linked to diverse cellular signaling pathways. This capability involves activation of the NQO1 gene and other phase II detoxification genes by activating the Nrf2/Kelch-like ECH-associated protein (Keap1) complex system. This chapter reports the chemopreventive effect of dietary components or their phytochemicals by activating the Nrf2–Keap1/ARE pathway and inducing NQO1.

Euphorbia species are rich in diterpenes. A solvent extraction of Euphorbia sanctae-catharinae, a species indigenous to the Southern Sinai of Egypt, afforded several premyrsinane diterpenoids (1–4) as well as previously reported metabolites (5–13) that included three flavonoids. Isolated compounds were chemically characterized by spectroscopic analysis. Identified compounds were bioassayed for anti-proliferative activity in vitro against colon (Caco-2) and lung (A549) tumor cell lines. Compound 9 exhibited robust anti-proliferative activity against A549 cells (IC50 = 3.3 µM). Absolute configurations for 8 versus 9 were determined by experimental and TDDFT-calculated electronic circular dichorism (ECD) spectra.

Diterpenoids salvimulticanol (1) and salvimulticaoic acid (2) together with known diterpenoid (3-6) were isolated from Salvia multicaulis. Structures were elucidated by spectroscopic techniques including HRESIMS as well as 1D-, and 2D-NMR. In-vitro cytotoxicity was assayed against human cancer cell lines. As several metabolites exhibited activity against drug-resistance lines, compounds were screened against a panel of human drug-sensitive and multidrug-resistant cancer lines. A proposed biosynthetic pathway for these new diterpenoids (1-2) as well as the cytotoxic structure-activity relationship of all identified compounds were discussed. Compound 1 and 6 showed the most potent cytotoxicity with IC50 11.58 and 4.13 towards leukemia cell lines CCRF-CEM and CEM-ADR5000, respectively.

Background There are increasing interests in natural compounds for cancer chemoprevention. Blocking agents represent an important class of chemopreventive compounds. They prevent carcinogens from undergoing metabolic activation and thereby suppressing their interaction with cellular macromolecular targets. Methods The effect of phenolic compounds isolated from Barleria cristata var. alba as chemopreventive agent was evaluated. The ethyl acetate fraction of B. cristata was subjected to different chromatographic techniques for isolation of its major phenolic compounds. The isolated compounds were evaluated for their potential to induce the cancer chemopreventive enzyme marker NAD(P)H quinonereductase 1 (NQO1) in murine Hepa-1c1c7 cell model. Results The ethyl acetate fraction of B. cristata var. alba yielded five known compounds identified as verbascoside (1), isoverbascoside (2), dimethoxyverbascoside (3), p-hydroxy benzoic acid (4), and apigenin-7-O-glucoside (5). Among the tested compounds, isoverbascoside (2) was shown to potently induce the activity of the enzyme in a dose –dependent manner. As a functional assay for detoxification, compound 2 was the strongest to protect Hepa-1c1c7 against the toxicity of menadione, a quinone substrate for NQO1. Conclusion This effect seemed to be attributed to the compound’s potential to induce both the catalytic activity and protein expression of NQO1 as revealed by enzyme assay and Western blotting, respectively. Electronic supplementary material The online version of this article (10.1186/s12906-018-2214-9) contains supplementary material, which is available to authorized users.

Multidrug resistance (MDR) in various kinds of cancers represents a true obstacle which hinders the successes of most of current available chemotherapies. ATP-binding cassette (ABC) trasporter proteins have been shown to contribute to the majority of MDR in various types of malignancies. c-myc has recently been reported to participate, at least partly, in MDR to some types of cancers. This study aimed to test whether c-myc could play a role, solely or with coordination with other ABCs, in the resistance of HepG2 cells to doxorubicin (Dox). MDR has been induced in wild-type HepG2 and has been verified both on gene and protein levels. Various assays including efflux assays as well as siRNA targeting ABCB1 and c-myc have been employed to explore the role of both candidate molecules in MDR in HepG2. Results obtained, with regard to ABCB1 silencing on HepG2/Dox cells, have shown that ABCB1-deficient cells exhibited a significant reduction in ABCC1 expression as compared to ABCB1-sufficient cells. However, these cells did not show a significant reduction in other tested ABCs (ABCC5 and ABCC10) while c-myc silencing had no significant effect on any of the studied ABCs. Moreover, silencing of ABCB1 on HepG2 significantly increased fluorescent calcein retention in HepG2 cells as compared to the control cells while downregulation of c-myc did not have any effect on fluorescent calcein retention. Altogether, this work clearly demonstrates that c-myc has no role in MDR of HepG2 to Dox which has been shown to be ABCB1-mediated in a mechanism which might involve ABCC1.

Elevation of acetylcholinesterase enzyme (AChE) has been reported to be implicated in the etiology of Alzheimer disease (AD). One of the encouraged strategies to fight AD is the plant-derived inhibitors. Amaryllidaceae species are enriched source of alkaloids. The inhibitory properties of roots and bulbs of Pancratium maritimum L. against AChE have been previously reported. In the present study, the flowers of the wild Egyptian P. maritimum were subjected to screening assays to evaluate its potency as inhibitor to AChE. Besides, its antioxidant and cytotoxic properties were also addressed. The acetylcholinesterase inhibitory properties of P. maritimum ; total extract and its alkaloid mixture were examined using Ellman’s assay. The direct antioxidant examination was carried out using DPPH assay whereas the indirect was monitored by the ability to protect Hepa1c1c7 cells against the induced cytotoxicity produced by tert-butyl hydroperoxide (TBHP). The cytotoxic effect of the total extract and crude alkaloid mixture was evaluated against the human liver hepatoma cell line (HepG2). P. maritimum flowers showed significant inhibitory activity against AChE. The potency of the alkaloid mixture, representing 5.0% of the flowers weight (IC 50 ; 22.02 ± 0.59 μg/ml) was about fourfold of its total extract (IC 50 ; 97.67 ± 4.06 μg/ml). The total extract was able to protect about 33.4% of Hepa1c1c7 against the induced intoxication that carried by TBHP rather than the alkaloid mixture. Weak antioxidant and cytotoxic activities were recorded by both examined samples. Flowers of the Egyptian P. maritimum L. could be an enriched source of AChE inhibitors.

MicroRNAs (miRNAs) trigger a two-layer regulatory network directly or through transcription factors and their co-regulators. Unlike miR-375, the role of miR-145 and miR-224 in inhibiting or driving cancer cell migration is controversial. This study is a step towards addressing the potential of miR-375, miR-145 and miR-224 expression modulation to inhibit colorectal carcinoma (CRC) cells migration in vitro through regulation of non-target genes VEGFA, TGFβ1, IGF1, CD105 and CD44. Transwell migration assay results revealed a significant subdue of migration ability of cells transfected with miR-375 and miR-145 mimics and miR-224 inhibitor. Real time PCR data showed that expression of VEGFA, TGFβ1, IGF1, CD105 and CD44 was downregulated as a consequence of exogenous re-expression of miR-375 and inhibition of miR-224. On the other hand, ectopic expression of miR-145 did not affect VEGFA, TGFβ1 and CD44 expression, while it elevated CD105 and suppressed IGF1 expression. MAP4K4, a predicted target of miR-145, was validated as a target that could play a role in miR-145-mediated regulation of migration. At mRNA level, no change was observed in expression of MAP4K4 in cells with restored expression of miR-145, while western blotting analysis revealed a 25% reduction of protein level. By applying luciferase reporter assay, a significant decrease in luciferase activity was observed, supporting that miR-145 directly target 3' UTR of MAP4K4. The study highlighted the involvement of non-target genes VEGFA, TGFβ1, IGF1, CD105 and CD44 in mediating anti- and pro-migratory effect of miR-375 and miR-224, respectively, and validated MAP4K4 as a direct target of anti-migratory miR-145.

New sesquiterpenes tanacetolide A–C (1–3) were isolated from a Tanacetum sinaicum extract together with known compounds (4–10). The structures were elucidated on the basis of MS and NMR spectroscopic data. All the compounds were evaluated for the inhibition of inducible nitric oxide (NO) production in a mouse peritoneal macrophage system. Iso-seco-tanapartholide-3-O-methyl ether (4) produced potent inhibition of NO production (IC50 = 1.0 μM). At the protein expression level, 4 elicited concentration-dependant down-regulation of inducible nitric oxide synthase.

Forty-four endophytic fungal isolates obtained from marine sponge, Hyrtios erectus, were evaluated and screened for their hydrolase activities. Most of the isolates were found to be prolific producers of hydrolytic enzymes. Only 11 isolates exhibited maximum cellular contents of lipids, rhamnolipids, and protein in the fungal isolates under the isolation numbers MERVA5, MERVA22, MERVA25, MERVA29, MERVA32, MERVA34, MERV36, MERVA39, MERVA42, MERVA43, and MERVA44. These isolate extracts exhibit the highest reducing activities against carbohydrate-metabolizing enzymes including α-amylase, α-glucosidase, β-glucosidase, β-glucuronidase, and tyrosinase. Consequently, based on morphological and cultural criteria, as well as sequence information and phylogenetic analysis, these isolates could be identified and designated as Penicillium brevicombactum MERVA5, Arthrinium arundinis MERVA22, Diaporthe rudis MERVA25, Aspergillus versicolor MERVA29, Auxarthron alboluteum MERVA32, Dothiorella sarmentorum MERVA34, Lophiostoma sp. MERVA36, Fusarium oxysporum MERVA39, Penicillium chrysogenum MERVA42, Penicillium polonicum MERVA43, and Trichoderma harzianum MERVA44. The endophytic fungal species, D. rudis MERVA25, P. polonicum MERVA43, Lophiostoma sp. MERVA36, A. alboluteum MERVA32, T. harzianum MERVA44, F. oxysporum MERVA39, A. versicolor MERVA29, and P. chrysogenum MERVA42 extracts, showed significant hepatitis C virus (HCV) inhibition. Moreover, D. sarmentorum MERVA34, P. polonicum MERVA43, and T. harzianum MERVA44 extracts have the highest antitumor activity against human hepatocellular carcinoma cells (HepG2).

While select eudesmane sesquiterpenes exhibit anti-neoplastic activity, tumor-inhibition for costic-acids has not been established. Here biological activity of 3-oxo-γ-costic acid (1), previously isolated from Chiliadenus montanus, as well as new sesquiterpenes (2–5) and the known derivative, 3-oxoeudesma-1,4,11(13)-trien-7-1061αH-l2-oic acid (6), all produced from 1 by the fungus Athelia rolfsii, are reported. Structures were elucidated using MS and NMR spectroscopy with activity-screening utilizing human colon- and lung-tumor lines, Caco-2 and A549 respectively. Compound 1 exhibited anti-proliferative activity against Caco-2 (IC50 39 µM) and 2 was active against A549 (IC50 74 µM) suggesting therapeutic potential for the original substrate and a bio-transformed product.

Hepatocellular carcinoma (HCC) is a hypervascular primary liver cancer characterized by rapid progression, besides, resistance to traditional chemotherapeutic agents. It has been shown that microRNAs play critical roles in regulation of tumor cell sensitivity to drugs through modulating the expression of genes involved in drug transport. The present study investigated whether restoration of miR-122 in HCC cells could alter the cell cycle distribution and the expression of multidrug resistance (MDR)-related genes (ABCB1, ABCC1, ABCG2 and ABCF2). After overexpression of miR-122 in HepG2 cells treated or untreated with doxorubicin doses, total RNAs and protein extracts were isolated for application of QRT-PCR and western blotting techniques. Moreover, cell cycle distribution was monitored by flow cytometry. Our results revealed that, the over expression of miR-122 in HepG2 cells treated or untreated with doxorubicin could modulate the sensitivity of cells to chemotherapeutic drug through downregulation of MDR-related genes, ABCB1 and ABCF2. Interpretation of cell cycle distribution revealed that, the anti-proliferative effect of miR-122 is associated with the accumulation of cells in G0/G1 phase. Moreover, treatment with miR-122 and doxorubicin resulted in high percentage of HCC cells in G0/G1 phase. Taken together, our findings revealed that, overexpression of miR-122 inhibited HCC cell growth by inducing cell cycle arrest and this arrest is associated with down-regulation of MDR-related genes.

Multidrug resistance (MDR) is a critical hindrance to the success of cancer chemotherapy. The main thing responsible for MDR phenotypes are plasma-membranes associated with adenosine triphosphate (ATP) Binding Cassette (ABC) drug efflux transporters, such as the P-glycoprotein (Pgp) transporter that has the broadest spectrum of substrates. Curcumin (CURC) is a Pgp inhibitor, but it is poorly soluble and bioavailable. To overcome these limitations, we validated the efficacy and safety of CURC, loaded in biocompatible solid lipid nanoparticles (SLNs), with or without chitosan coating, with the goal of increasing the stability, homogeneous water dispersibility, and cellular uptake. Both CURC-loaded SLNs were 5&ndash, 10-fold more effective than free CURC in increasing the intracellular retention and toxicity of doxorubicin in Pgp-expressing triple negative breast cancer (TNBC). The effect was due to the decrease of intracellular reactive oxygen species, consequent inhibition of the Akt/IKK&alpha, &beta, /NF-kB axis, and reduced transcriptional activation of the Pgp promoter by p65/p50 NF-kB. CURC-loaded SLNs also effectively rescued the sensitivity to doxorubicin against drug-resistant TNBC tumors, without signs of systemic toxicity. These results suggest that the combination therapy, based on CURC-loaded SLNs and doxorubicin, is an effective and safe approach to overcome the Pgp-mediated chemoresistance in TNBC.

Background and objectives Quinoa (Chenopodium quinoa Willd) is a plant species that belongs to Chenopodiaceae family. It has a high nutritional value as it is rich in proteins, lipids, and fiber, and has an extraordinary balance of essential amino acids, vitamins, and minerals, in addition to a high number of health-beneficial phytochemicals, including saponins and phytosterols. The present study aims to investigate the lipoidal components of C. quinoa and assessment of C. quinoa lipoidal components and different fractions (methanol, chloroform, ethylacetate, and butanol) cytotoxicity potential against three human cancer cell lines using MTT reduction assay. Materials and methods The seeds of C. quinoa were extracted by different solvents and the extracts prepared were tested for their lipiodial constituents and cytotoxic activities in three cancer cell lines. Results and conclusion The results obtained from Gas Liquid Chromatography (GLC) analysis of nonsaponifiable fraction of C. quinoa seeds indicated that it consists mainly of a mixture of a series of n-alkanes and sterols (79.96 and 7.91%. respectively). The oil was also found to be rich in linoleic acid (52.7%) and oleic acid (25.33%). The investigation of the cytotoxic potential of the plant’s low polarity fractions, including CHCl3, and nonsaponifiable fraction against the studied cell lines revealed the sensitivity of A549 human lung cancer cells. Further studies are needed to uncover the mechanism and chemical constituents of the obtained activity of C. quinoa.

Background The multidrug resistance (MDR) phenotype encounters a major challenge to the success of established chemotherapy in cancer patients. We hypothesized that cytotoxic medicinal plants with novel phytochemicals can overcome MDR and kill MDR-cells with similar efficacy as drug sensitive cells. Purpose We evaluated plant extracts from an unexplored ecosystem in Egypt with unusual climate and nutrient conditions for their activity against sensitive and multidrug-resistant cancer cell lines. Material and methods/study design Methylene chloride: methanol (1:1) and methanol: H2O (7:3) extracts of 40 plants were prepared resulting in a sum of 76 fraction containing compounds with varying polarity. The resazurin reduction assay was employed to evaluate the cytotoxicity of these extracts on five matched pairs of drug-sensitive and their drug-resistant cell lines. Flow cytometry and Western blotting was used to determine cell cycle analyses, apoptosis, and autophagy. Reactive oxygen species (ROS) were measured spectrophotometrically. Results Extracts derived from Withania obtusifolia (WO), Jasonia candicans (JC), Centaurea lippii (CL), and Pulicaria undulata (PU) were the most active ones among 76 extracts from 40 Egyptian medicinal plants. They showed a significant reduction of cell viability on drug-sensitive CCRF-CEM leukemia cell line with IC50 values less than 7 µg/ml. Low cross-resistance degrees were observed in multidrug-resistant CEM/ADR5000 cells towards CL (1.82-fold) and JC (6.09-fold). All other drug-resistant cell lines did not reveal cross-resistance to the four extracts. Further mechanistic assessment have been studied for these four extracts. Conclusion The methylene chloride: methanol (1:1) fractions of WO, JC, CL, and PU are promising cytotoxic extracts that could be used to combat MDR cancer cells through different cell death pathways.

An efficient, expeditious catalytic route for the synthesis of ethyl 6-amino-5-cyano-2-methyl-4-aryl-4H-pyran-3-carboxylates 2 was achieved via a three-component, one-pot reaction of malononitrile, ethyl acetoacetate, and various aromatic aldehydes in water as a solvent at room temperature. The key advantages are excellent yield, reaction time, and inexpensive catalyst. Also, cyclization of 4H-pyrans 2 to the corresponding 4H-pyrano[2,3-d]pyrimidines 3 using silica sulfuric acid in the presence of acetic anhydride was described. Some synthesized compounds exhibited promising antioxidant activities.

In continuation of our chemical investigation on some medicinal plants of the genus Achillea, chromatographic investigation of the methylene chloride/methanol (1:1) extract of the air-dried aerial part of Achillea biebersteinii Afan. (family Asteraceae) afforded a new natural monoterpene (2), in addition to two known sesquiterpenes (3 and 4). Compound 1 was isolated as light needle crystals. Structures were established on the basis of MS and NMR spectroscopic (1H, 13C, 1H-1H correlation spectroscopy, heteronuclear multiple-quantum coherence and heteronuclear multiple-bond correlation) data and in case of compound 1 were confirmed by X-ray analysis. All isolated compounds were examined for their anti-inflammatory activity to inhibit lipopolysaccharide-induced NO production in RAW264.7 macrophage cells. Compounds 3 and 4 produced a promising anti-inflammatory effect (76% and 80% inhibition, respectively). However, compounds 1 and 2 produced moderate inhibition of NO release recording a 41% and 36% inhibition of NO production, respectively.

Vibration can produce a wide variety of different effects to the operators. Farm equipment operators are usually exposed to whole-body vibration which transmitted via the seat or via the floor and feet. This vibration contributes to operator fatigue and can have a detrimental effect on job performance and safety. The objective of this study was to determine whether body mass index (BMI) influences the risk of low back pain (LBP) in a population exposed to whole body vibration (WBV). For this a survey conducted in nine farm machinery-servicing stations belong to the Ministry of Agriculture (MOA), Farm machinery station in Gemiza, Egyptian Project for improving the main crops production in Sakha, and the local sector of farm machinery during the years of 2008-2009 through periodic visits. Vibration measurements were performed according to ISO 2631-1, 1997. Two measurements were taken: stand height, and weight the results revealed that the tractor (Nasr model) which has no suspended seat and range of 60-65 horse power in the sample under study considers the highest equipment gives WBV data the frequency weighted RMS acceleration magnitude of the largest single orthogonal axis is in the vertical axis (Z) and also for VDV of weighted RMS acceleration. This constitutes a high risk on the labor body, followed by UTB tractor and rice combine. On the other hand, the WBV emission levels recorded during the harvesting by wheat combine and threshing tasks were low which constitute no risk on the labor body The results revealed that the highest number of injured labors was in the age group of (41-45) years (46.4%), followed by (46-50) years (28.6%), but the least number of injured labors was in the age group of (34-40) years (14.3%), and followed by (51-55) years (10.7%). Type of pain indicated that the highest number of pain was (47%) for temporary LBP, followed by (22.6%) for healthy body, and (8.3%) for chronic LBP. Results showed that there are significant differences between the different types of equipment during the variation of farm operations, significant correlation, and significant relationship between accidents factors.

From newly isolated sesquiterpenes (I), (II), and (III) only (I) shows intermediate inhibition of NO production in a mouse peritoneal macrophage system (IC50: 15.7 μM).

Aims To investigate effect of metallic nanoparticles, silver (AgNPs) and gold nanoparticles (AuNPs) as antitumor treatment in vitro against human breast cancer cells (MCF-7) and their associated mechanisms. This could provide new class of engineered nanoparticles with desired physicochemical properties and may present newer approaches for therapeutic modalities to breast cancer in women. Materials and methods A human breast cancer cell line (MCF-7) was used as a model of cells. Metallic nanoparticles were characterized using UV-visible spectra and transmission electron microscopy (TEM). Cytotoxic effects of metallic nanoparticles on MCF-7 cells were followed by colorimetric SRB cell viability assays, microscopy, and cellular uptake. Nature of cell death was further investigated by DNA analysis and flow cytometry. Results Treatment of MCF-7 with different concentrations of 5-10nm diameter of AgNPs inhibited cell viability in a dose-dependent manner, with IC50 value of 6.28μM, whereas treatment of MCF-7 with different concentrations of 13-15nm diameter of AuNPs inhibited cell viability in a dose-dependent manner, with IC50 value of 14.48μM. Treatment of cells with a IC50 concentration of AgNPs generated progressive accumulation of cells in the S phase of the cell cycle and prevented entry into the M phase. The treatment of cells with IC50 concentrations of AuNPs similarly generated progressive accumulation of cells in sub-G1 and S phase, and inhibited the entrance of cells into the M phase of the cell cycle. DNA fragmentation, as demonstrated by electrophoresis, indicated induction of apoptosis. Conclusions Our engineered silver nanoparticles effectively inhibit the proliferation of human breast carcinoma cell line MCF-7 in vitro at high concentration (1000 μM) through apoptotic mechanisms, and may be a beneficial agent against human carcinoma but further detailed study is still needed.

An efficient, expeditious catalytic route for the synthesis of ethyl 6-amino-5-cyano-2-methyl-4-aryl-4H-pyran-3-carboxylates 2 was achieved via a three-component, one-pot reaction of malononitrile, ethyl acetoacetate, and various aromatic aldehydes in water as a solvent at room temperature. The key advantages are excellent yield, reaction time, and inexpensive catalyst. Also, cyclization of 4H-pyrans 2 to the corresponding 4H-pyrano[2,3-d]pyrimidines 3 using silica sulfuric acid in the presence of acetic anhydride was described. Some synthesized compounds exhibited promising antioxidant activities.

Background Egyptians recognized the healing power of herbs and used them in their medicinal formulations. Nowadays, “Attarin” drug shops and the public use mainly the Unani medicinal system for treatment of their health problems including improvement of memory and old age related diseases. Numerous medicinal plants have been described in old literature of Arabic traditional medicine for treatment of Alzheimer’s disease (AD) (or to strengthen memory). Methods In this study, some of these plants were evaluated against three different preliminary bioassays related to AD to explore the possible way of their bio-interaction. Twenty three selected plants were extracted with methanol and screened in vitro against acetylcholinesterase (AChE) and cycloxygenase-1 (COX-1) enzymes. In addition, anti-oxidant activity using DPPH was determined. Results Of the tested plant extracts; Adhatoda vasica and Peganum harmala showed inhibitory effect on AChE at IC50 294 μg/ml and 68 μg/ml respectively. Moreover, A. vasica interacted reversibly with the enzyme while P. harmala showed irreversible inhibition. Ferula assafoetida (IC50 3.2 μg/ml), Syzygium aromaticum (34.9 μg/ml) and Zingiber officinalis (33.6 μg/ml) showed activity against COX-1 enzyme. Potent radical scavenging activity was demonstrated by three plant extracts Terminalia chebula (EC50 2.2 μg/ml), T. arjuna (3.1 μg/ml) and Emblica officinalis (6.3 μg/ml). Conclusion Interestingly, differential results have been obtained which indicate the variability of the mode of actions for the selected plants. Additionally, the reversible interaction of A. vasica against AChE and the potent activity of F. assafoetida against COX-1 make them effective, new and promising agents for treatment of AD in the future, either as total extracts or their single bioactive constituents.

Background The Egyptian government is considering embarking on a new wave of health sector reform. Although primary care is seen as central to the anticipated reforms, little is known about the current morbidity and utilization patterns in Egyptian publicly funded primary care. We conducted this survey study of patient encounters to describe the demographic characteristics of patients attending publicly-funded primary care practices, the relative frequency of conditions encountered in these practices, and the rates of drug prescription, investigation and referral. Method Cross-sectional survey of twelve primary care practices and 2458 patient consultations. Additional secondary data were collected from five of the twelve practices for preventive services provided at these practices i.e. immunizations, family planning and ante-natal care. Results 54% of the attendances were for people below the age of twenty, of which 54% were females. In patients above the age of twenty, women accounted for 73% of consultations. Upper respiratory tract infection was the most common reason for encounter, accounting for 24% of the presentations, followed by gastroenteritis (10%), intestinal parasites (5%), and lower respiratory tract infections (5%). Over 97% of patients were prescribed at least one drug, whereas investigation and referral rates were low (15% and 5% respectively). When the analysis was repeated for practices where data on both curative and preventive services were available (5 practices and 2146 consultations), substantial proportions of patients were found to seek care for immunizations (25%), family planning (12%), and ante-natal care (11%). Conclusion Most patients utilizing primary care practices in Egypt seek care for minor and preventive services with relatively few consultations for more serious conditions. There is also a pattern of prescribing drugs to most primary care patients which may reflect over-prescribing by primary care doctors.