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Several hepatic pathological conditions are correlated with the stimulation of hepatic stellate cells. This induces a cascade of events producing accretion of extracellular matrix components triggering fibrosis. Dunaliella salina , rich in carotenoids, was investigated for its potential antagonizing activity; functionally and structurally against thioacetamide (TAA) - induced hepatic fibrosis in rats. Adult male albino Wistar rats were treated with three dose levels of D. salina powder or extract (daily, p.o.); for 6 weeks, concomitantly with TAA injection. Serum levels of aspartate transaminase (AST), alanine transaminase (ALT), alkaline phosphatase (ALP), bilirubin and albumin were determined. Reduced glutathione (GSH), malondialdehyde (MDA), smooth muscle actin alpha (α-SMA) and collagen I hepatic contents were also estimated. Treatment with D. salina powder or extract caused a significant decline in serum levels of AST, ALT, ALP, bilirubin, MDA and hepatic contents of α-SMA and collagen I. Additionally, serum albumin and GSH hepatic content were highly elevated. Liver histopathological examination also indicated that D. salina reduced fibrosis, centrilobular necrosis, and inflammatory cell infiltration evoked by TAA. The results implied that D. salina exerts protective action against TAA-induced hepatic fibrosis in rats. The phytochemical investigation revealed high total carotenoid content prominently β-carotene (15.2 % of the algal extract) as well as unsaturated fatty acids as alpha-linolenic acid which accounts for the hepatoprotective activity., Competing Interests: The authors declare no conflict of interest., (© 2019 The Authors.)

Backgrounds: Osteoporosis prevailing in elderly involves a marked increase in bone resorption showing an initial fall in bone mineral density leading to a significant reduction in bone formation., Aim: The present study aimed to investigate the effect of Heamatococcus pluvialis microalgae on osteoporosis in D-galactose-treated rats. The underlying mechanism was tracked targeting the osteoprotegerin (OPG)/ nuclear factor-κβ ligand (RANKL) pathway using micro-computed tomography scanning., Methods: Osteoporosis was induced in rats by intraperitoneal injection of D-galactose (200 mg/kg/day) for eight consecutive weeks. Osteoporotic rats were orally treated with H. pluvialis biomass (BHP; 450 mg/kg), its polar (PHP; 30 mg/kg) and carotenoid (CHP; 30 mg/kg) fractions for the last 2 weeks of D-Gal injection. Twenty four hours after the last dose of the treatments, tibia bones of the rats were scanned using micro-computed tomography scanning for bone mineral density (BMD), bone volume fraction (BV/TV), trabecular thickness/separation/number (Tb.Th, Tb.Sp, Tb.N) evaluation, blood samples were withdrawn and sera were used for biochemical assessment. Moreover, femur bones were examined histopathologically using several stains., Results: Induction of osteoporosis was associated with a marked reduction in BMD, BV/TV, Tb.Th, Tb.Sp, Tb.N and in serum levels of phosphorus and catalase. On the other hand, a significant elevation in serum levels of calcium, bone alkaline phosphatase (BALP) and interleukin-6 was observed. Moreover, up-regulation of OPG was detected in osteoporotic rats. Oral treatment with BHP, and PHP incremented tibia BMD and serum phosphorus level along with the decrease in serum levels of calcium, BALP, interleukin-6, OPG and RANKL. However, treatment with CHP almost restored all the fore mentioned parameters to normal values. Furthermore, the histopathological evaluation emphasized the biochemical outcomes., Conclusion: H. pluvialis fractions rich in astaxanthin ameliorated bone loss in experimentally-induced osteoporosis in rats probably through the down-regulation of serum OPG in concurrence with up-regulation of serum RANKL., (Copyright © 2019 Elsevier Masson SAS. All rights reserved.)

Retinoids are essential during early cardiovascular morphogenesis. However, recent studies showed their important role in cardiac remodeling in rats with hypertension and following myocardial infarction. The present study aimed to investigate the effect of zeaxanthin heneicosylate (ZH); a carotenoid ester isolated from Dunaliella salina microalgae, on cardiac dysfunction ensuing d-galactose injection in rats. Rats injected with d-GAL (200 mg/kg; I.P) for 8 weeks were orally treated with ZH (250 μg/kg) for 28 consecutive days. Results showed that d-GAL injection caused dramatic electrocardiographic changes as well as marked elevation in serum levels of homocysteine, creatinine kinase isoenzyme and lactate dehydrogenase. A reduction in the cardiac contents of glucose transporter-4 and superoxide dismutase along with the elevation of inducible nitric oxide synthetase and interleukin-6 was also noticed. Oral administration of ZH significantly improved the above mentioned cardiac aging manifestations; this was further emphasized through histopathological examinations. The effect of ZH is mediated through the interaction with retinoid receptor alpha (RAR-α) as evidenced through a significant elevation of RAR-α expression in cardiac tissue following the lead of an in silico molecular docking study. In conclusion, zeaxanthin heneicosylate isolated from D. salina ameliorated age-associated cardiac dysfunction in rats through the activation of retinoid receptors.

Background: The genetic heterogeneity of tumor cells and the development of therapy-resistant cancer cells in addition to the high cost necessitate the continuous development of novel targeted therapies., Methods: In this regard, 14 novel benzoxazinone derivatives were synthesized and examined for anticancer activity against two human epithelial cancer cell lines; breast MCF-7 and liver HepG2 cells. 6,8-Dibromo-2- ethyl-4H-benzo[d][1,3]oxazin-4-one was subjected to react with nitrogen nucleophiles to afford quinazolinone derivatives and other related moieties (3-12). Benzoxazinone 2 responds to attack with oxygen nucleophile such as ethanol to give ethyl benzoate derivative 13. The reaction of benzoxazinone 2 with carbon electrophile such as benzaldehyde derivatives afforded benzoxazinone derivatives 14a and 14b.The structure of the prepared compounds was confirmed with spectroscopic tools including IR, 1H-NMR, and 13C-NMR., Results: Derivatives 3, 9, 12, 13, and 14b exhibited high antiproliferative activity and were selective against cancer cells showing no toxicity in normal fibroblasts. Derivative 3 with NH-CO group in quinazolinone ring was effective only against breast cells, while derivative 12 with NH-CO group in imidazole moiety was only effective against liver cells probably through arresting cell cycle and enabling repair mechanisms. The other derivatives (9, 13, and 14b) had broader antiproliferative activity against both cell lines. These derivatives enhance the expression of the p53 and caspases 9 and 3 to varying degrees in both cell lines. Derivative 14b caused the highest induction in the investigated genes and was the only derivative to inhibit the EGFR activity., Conclusions: The unique features about derivative 14b could be attributed to its high lipophilicity, high carbon content, or its extended conjugation through planar aromatic system. More investigations are required to identify the lead compound(s) in animal models., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Background: In a continuous combat against cancer, which is one of the leading causes of mortality now, chalcone and Schiff bases moieties have been incorporated and their antiproliferative activities and associated mechanisms against liver (HepG2) and breast (MCF-7) cell lines in addition to normal fibroblasts (WI-38) have been examined., Methods: Derivatives 4 and 5 of Schiff bases only and chalcone derivatives of Schiff bases 1 and 2 were devoid of any antiproliferative activity. All three compounds (3, 6, and 7) with significant antiproliferative activity were selective and caused no growth inhibition in normal fibroblasts. Derivative 3 was a chalcone only with IC50 of ~20 µM and has a very interesting signature where it enhanced apoptosis in HepG2 by stimulating the expression of downstream execution caspase 3 without affecting neither p53 nor initiator caspase 9. In spite of the structural similarity between compounds 6 and 7, compound 6 discerned itself with a unique IC50 of ~ 10 µM., Results: The antiproliferative activity of derivative 6 could be attributed to its unique capability of formation of free radicals such as phenoxide radicals which arrested the cell cycle through enhancing the expression of p53 and induced apoptosis by induction of both caspases 9 and 3. It was the only investigated derivative that inhibited the tyrosine kinase activity by 89%., Conclusions: The antiproliferative activity of the compounds under investigation considerably depended on the nature of the substituent at position 4 in phenyl rings of both chalcone and Schiff base fragments. Derivative 6 with electron withdrawing chlorine substitution on the phenyl ring of Schiff base fragment and an electron donating methoxy group on the phenyl ring of chalcone fragment was the most active member., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Background: Berberine and cinnamic acid are natural compounds that exhibit potent anticancer activities through distinct molecular mechanisms., Objective: In the present study, we aimed to investigate the proapoptotic potential of cinnamic acid and berberine in cancer cells by examining their effect on the expression of proapoptotic and antiapoptotic genes. Moreover, the effects of berberine and cinnamic acid on the antitumor activity of cisplatin were investigated in Ehrlich solid tumor-bearing mice., Methods: For the study, 90 male mice were inoculated intramuscularly with Ehrlich ascites tumor cells (2.5 × 106/mouse), and then on day 4, mice were randomly divided into six experimental groups (group 1-untreated Ehrlich solid tumor (EST), group 2-EST treated CDDP, group 3-EST treated CA, group 4-EST treated BER, group 5-EST treated CA + CDDP, and group 6-EST treated BER + CDDP)., Results: The results showed that berberine and cinnamic acid significantly decreased tumor growth and tumor volume (-74.8 and -75.5%, respectively) both as single agents and in combination with cisplatin. Moreover, both berberine and cinnamic acid increased the ratio of tumor growth inhibition (-91.5 and -92.6%, respectively), mean survival time (61.5 and 26 days, respectively), and percentage increase in lifespan (559 and 263%, respectively) of the treated mice. Our results also showed that both berberine and cinnamic acid-induced apoptosis by increasing the Bax/Bcl-2 ratio (74.1 and 45.1, respectively) and caspase-3 expression (14.3- and 11.6-fold increase, respectively). Additionally, berberine and cinnamic acid decreased oxidative stress markers, as shown by the decrease in lipid peroxidation and nitric oxide levels and an increase in reduced glutathione level., Conclusion: These results suggest that berberine and cinnamic acid have potential as antitumor and antioxidant agents derived from natural sources, which could be used alone or in combination with regular chemotherapeutic agents, such as cisplatin. These effects could be attributed to the proapoptotic activity of berberine and cinnamic acid., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Purpose: Aging is associated with hepatic morphological and physiological deterioration due to the accumulation of endogenous and exogenous free radicals and the resultant oxidative stress. The present study aims to investigate the effect of Haematococcus pluvialis microalgae on hepatic changes associated with D-galactose (D-Gal)-induced aging in rats. Methods: Aging was induced in rats by daily intraperitoneal injection of D-Gal (200 mg/kg/day) for eight consecutive weeks. D-Gal-injected rats were treated by astaxanthin (ATX)-rich H. pluvialis biomass, its carotenoid and polar fractions for two weeks. Twenty four hours after the last dose, blood samples were collected and the liver tissues were isolated for further biochemical and histopathological examinations. Results: D-Gal induced aging was associated with an elevation in serum liver function parameters, hepatic oxidative stress biomarkers viz., catalase (CAT), glutathione transferase (GST) and myeloperoxidase (MPO), as well as decreased expression of nuclear factor like-2 (Nrf2). Moreover, induction of aging exhibited an elevation of hepatic inflammatory cytokine; interleukin-6 (IL-6) and its modulator; nuclear factor Kappa B (NF-KB). However, treatment of D-Gal injected rats with ATX-rich H. pluvialis restored the serum liver function parameters as well as hepatic CAT, GST and MPO levels with an elevated expression of Nrf2. Treatment with ATX-rich H. pluvialis was also accompanied with a decrease in hepatic levels of NF-KB and IL-6. Histopathological examination emphasized all the previous results. Similarly, all trans-astaxanthin showed high affinity towards Nrf2 with -7.93 kcal/mol estimated free energy of binding as well as moderate affinities towards IL-6 and NF-KB through a docking study. Conclusion: ATX-rich H. pluvialis showed beneficial effects by ameliorating the hepatic changes associated with D-Gal induced aging in rats due to its modulatory role of the Nrf2/Keap pathway.

Microalgae represent a rich source that satisfies the growing need for novel ingredients of nutriceuticals, pharmaceuticals, and food supplements. Haematococcus pluvialis and Dunaliella salina microalgae are isolated from the Egyptian hydro-flora and are reported for their potent antioxidant activities. The cytotoxic activity of different fractions of both microalgae was investigated on 4 cell lines HePG2, MCF7, HCT116, and A549. The carotenoid rich fraction of H. pluvialis showed potent cytotoxic activity against colon cancer cell line and moderate activity against both liver and breast cancer cell lines. On the other hand, the carotenoid rich fraction of D. salina showed mild cytotoxic activity on breast and liver cancer cell lines. The carotenoid rich fraction of H. pluvialis was analysed using LC-DAD/ESI-MS and the major carotenoids were identified either free as well as bounded to fatty acids., (Copyright © 2017 John Wiley & Sons, Ltd.)

Objectives: To assess knowledge, attitude and practice (KAP) of healthcare staff regarding pharmaceutical waste management; and to determine the impact of an educational programme on the KAP survey items., Design: Pre-post-test intervention study., Methods: The pre-intervention phase was performed using a sample of 530 out of 1500 healthcare workers. A predesigned interview questionnaire was used to assess KAP. Next, an educational programme was designed and offered to a subsample of 69 healthcare workers. KAP were re-assessed for the programme attendees using the same interview questionnaire, both immediately (post-test) and six months after the end of the programme (follow-up test). The parametric paired sample t-test was used to assess the difference between pre-test and follow-up test results., Results: Poor knowledge and poor practice levels (scores 50%) detected in the pre-intervention phase were found to improve to satisfactory levels (scores ≥75%) in the follow-up phase. Attitude was found to be positive (score ≥75%) in all phases of the study., Conclusion: The educational programme led to a significant improvement in KAP of healthcare staff regarding pharmaceutical waste management (P<0.001)., (Copyright © 2016. Published by Elsevier Ltd.)

Objective: Opioid use disorders attributed to tramadol (OUD-T) is a public health problem in Egypt. The objective of this study was to assess the psychiatric comorbidity among patients with opioid use disorder attributed to tramadol., Methods: This study included 100 patients with opioid use disorders attributed to tramadol (according to DSM-IV-TR) and 100 control persons (matched for age, sex, and education), who were recruited from Zagazig University Hospital, Egypt. The participants were interviewed using Structured Clinical Interview for DSM disorders (SCID-I and SCID-II), Addiction Severity Index scale (patients), and urine screening for drugs., Results: Twenty-four percent of the patients used tramadol only (pure tramadol group), whereas 76% of the patients used other substances in addition to tramadol (polysubstance group). Most (91%) of the patients had tramadol dependence. Forty-nine percent of the patients had psychiatric comorbidity, especially mood disorders (59.2%), whereas only 24% of the control persons had psychiatric comorbidity, especially anxiety disorders (83.3%). The most common personality disorders among patients were borderline (24%) and antisocial (22%), whereas in control persons, the most common personality disorders were obsessive compulsive personality disorder (8%) and the avoidant personality disorder (7%). Cluster B (76.6%) was the most common category among patients (compared with 25.8% in control persons), whereas cluster C (51.6%) was the most common category among control persons (compared with 15.6% in patients)., Conclusions: Most of the patients were dependent on tramadol, and approximately 3 out of 4 used many substances. Almost half of the patients had psychiatric comorbidity, and approximately 3 out of 4 had cluster B personality disorders.

Luteolin-7-O-glycoside (LG), an abundant component in many edible plants, was found to be one of the major constituents of the aqueous methanol extract of Trifolium alexandrinum L. family Fabaceae, a fodder plant widely cultivated in Egypt. The estrogenic activity of LG concerning the effect on uterotrophy, lipid profile, weight gain and bone enhancement activity was determined in ovariectomized rat model at a dose of 5 mg/kg. Luteolin-7-O-glycoside showed significant estrogenic effect through the preservation of normal uterine weight and plasma estradiol level. It also significantly inhibited the bone turnover markers plasma bone-specific alkaline phosphatase, plasma osteocalsin, type I procollagen N-terminal, and C-telopeptide of type II collagen levels. It induced a significant improvement in plasma lipid profile. The effect of LG was comparable with estradiol with lower effect on uterine weight. Liver and kidney functions revealed a wide safety of LG at this dose level. The present study revealed that LG may be a promising hormone replacement therapy after being examined thoroughly on human. Copyright © 2016 John Wiley & Sons, Ltd., (Copyright © 2016 John Wiley & Sons, Ltd.)

Unlabelled: In health care facilities, pharmaceutical waste is generally discharged down the drain or sent to landfill. Poor knowledge about their potential downstream impacts may be a primary factor for improper disposal behavior. The objective of this study was to determine the impact of an intervention program on knowledge and practice of health care staff regarding pharmaceutical waste management. The study was designed as a pre/posttest intervention study. Total sample size was 530 in the pre-intervention phase, and then a subsample of 69 individuals was selected for the intervention and the post-intervention phases. Paired-sample t test was used to assess the difference between pretest and follow-up test results. A statistically significant improvement in knowledge and practice was achieved (P<0.001). Poor knowledge and poor practice levels (scores<50%) were found to improve to satisfactory levels (scores≥75%). Therefore, educational programs could be considered as an effective tool for changing health care staff practice in pharmaceutical waste management., Implications: In health care facilities, pharmaceutical waste is generally discharged down the drain or sent to landfill. A lack of knowledge about the potential impacts of this type of waste may be a leading factor in improper disposal behavior. Following an educational program, statistically significant improvement in knowledge and practice of health care staff as regards to pharmaceutical waste management (PWM) was achieved. It is thus recommended that authorities implement training-of-trainers (TOT) programs to educate health care staff on PWM and organize refreshment workshops regularly.

Background: According to the WHO, nearly 24% of the global disease burden is attributable to environmental risk factors (RFs). People living in periurban areas are particularly at risk due to lack of basic sanitation requirements., Objective: To investigate the possible association between environmental RFs and disease prevalence for a community living in a periurban area in Alexandria, Egypt., Materials and Methods: A cross-sectional study was conducted in 2012. The study sample consisted of 355 families. An interviewing questionnaire and an observation checklist were used for data collection. In addition, 10 drinking water samples were randomly collected for physical, chemical, and bacteriological analyses. The questionnaire included questions on indoor environmental RFs as well as morbidity in the study sample, and the observation checklist covered outdoor environmental RFs. The environmental risk was determined using a risk score whose calculation was based upon the presence/absence of 10 indoor and 12 outdoor environmental RFs. The association between risk scores and 14 morbidities was investigated using unconditional logistic regression analysis, expressed as odds ratio (OR) and 95% confidence interval (CI)., Results: A significant association was found between the total environmental risk score and respiratory diseases (OR=2.298, 95% CI: 1.231-4.291), diarrhea (OR=2.083, 95% CI: 1.102-3.939), liver diseases (OR=2.491, 95% CI: 1.067-5.819), skin diseases (OR=1.821, 95% CI: 1.012-3.310), and bronchial asthma (OR=2.228, 95% CI: 1.066-4.565). Noncommunicable diseases such as cardiovascular diseases and musculoskeletal diseases did not show any significant association with environmental RFs., Conclusion and Recommendations: Environmental RFs have an adverse impact on health within communities living in periurban areas. It is recommended that sanitation be improved and various outdoor environmental RFs be addressed in these underprivileged areas, as well as health education campaigns be organized aiming at raising the awareness of residents on indoor environmental RFs and ways to prevent them.

A combination of persulfate and hydrogen peroxide (S2O8(2-)/H2O2) was used to oxidizelandfill leachate. The reaction was performed under varying S2O8(2-)/H2O2 ratio (g/g), S2O8(2-)/H2O2 dosages (g/g), pH, and reaction time (minutes), so as to determine the optimum operational conditions. Results indicated that under optimum operational conditions (i.e. 120 min of oxidation using a S2O8(2-)/H2O2 ratio of 1 g/1.47 g at a persulfate and hydrogen peroxide dosage of 5.88 g/50 ml and8.63 g/50 ml respectively, at pH 11) removal of 81% COD and 83% NH3-N was achieved. In addition, the biodegradability (BOD5/COD ratio) of the leachate was improved from 0.09 to 0.17. The results obtained from the combined use of (S2O8(2-)/H2O2) were compared with those obtained with sodium persulfate only, hydrogen peroxide only and sodium persulfate followed by hydrogen peroxide. The combined method (S2O8(2-)/H2O2) achieved higher removal efficiencies for COD and NH3-N compared with the other methods using a single oxidizing agent. Additionally, the study has proved that the combination of S2O8(2-)/H2O2 is more efficient than the sequential use of sodium persulfate followed by hydrogen peroxide in advanced oxidation processes aiming at treatingstabilizedlandfill leachate., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Background: Colorectal cancer (CRC) is a major cause of morbidity and mortality, being the second most common type of cancer worldwide in both men and women. It accounts yearly for approximately 9% of all new cases of cancers. Furthermore, the current chemotherapeutic regimens seem unsatisfactory, so that exploration of novel therapeutic modalities is needed. The present study was undertaken to investigate the inhibitory effects of a crude alkaloid extract (CAERS) of a medicinal herb, Rhazya stricta, on proliferation of CRC HCT116 cells and to elucidate mechanisms of action. To achieve these aims, we utilized MTT, comet, DNA laddering and gene reporter assays, along with Western blot and RT-PCR analyses., Results: We found that CAERS inhibited cell proliferation and induced apoptotic cell death in HCT116 cells. Hallmarks of morphological and biochemical signs of apoptosis were clearly evident. CAERS down-regulated DNA-binding and transcriptional activities of NF-κB and AP-1 proteins, while up-regulating expression of the Nrf-2 protein. It also down-regulated expression levels of the ERK MAPK, Bcl-2, cyclin D1, CDK-4, survivin and VEGF and up-regulated levels of Bax, caspase-3/7 and -9, p53, p21, Nrf-2. Markedly, it promoted mRNA expression levels of cytoprotective genes including the hemeoxygenase-1, NAD(P)H quinine oxidoreductase 1 and UDP-glucuronyltransferase., Conclusions: These findings indicate that CAERS exerts antiproliferative action on CRC cells through induction of apoptotic mechanisms, and suggest CAERS could be a promising agent for studying and developing novel chemotherapeutic agents aimed at novel molecular targets for the treatment of CRC.

The objective of this study was to investigate the performance of employing H2O2 reagent in persulfate activation to treat stabilized landfill leachate. A central composite design (CCD) with response surface methodology (RSM) was applied to evaluate the relationships between operating variables, such as persulfate and H2O2 dosages, pH, and reaction time, to identify the optimum operating conditions. Quadratic models for the following two responses proved to be significant with very low probabilities (<0.0001): chemical oxygen demand (COD) and NH3-N removal. The obtained optimum conditions included a reaction time of 116 min, 4.97 g S2O8(2-), 7.29 g H2O2 dosage and pH 11. The experimental results were corresponding well with predicted models (COD and NH3-N removal rates of 81% and 83%, respectively). The results obtained in the stabilized leachate treatment were compared with those from other treatment processes, such as persulfate only and H2O2 only, to evaluate its effectiveness. The combined method (i.e., /S2O8(2-)/H2O2) achieved higher removal efficiencies for COD and NH3-N compared with other studied applications.

The current study investigated the effects of S2O8(2-) and S2O8(2-)/H2O2 oxidation processes on the biodegradable characteristics of an anaerobic stabilized leachate. Total COD removal efficiency was found to be 46% after S2O8(2-) oxidation (using 4.2 g S2O8(2-)/1g COD0, at pH 7, for 60 min reaction time and at 350 rpm shaking speed), and improved to 81% following S2O8(2-)/H2O2 oxidation process (using 5.88 g S2O8(2-) dosage, 8.63 g H2O2 dosage, at pH 11 and for 120 min reaction time at 350 rpm). Biodegradability in terms of BOD5/COD ratio of the leachate enhanced from 0.09 to 0.1 and to 0.17 following S2O8(2-) and S2O8(2-)/H2O2 oxidation processes, respectively. The fractions of COD were determined before and after each oxidation processes (S2O8(2-) and S2O8(2-)/H2O2). The fraction of biodegradable COD(bi) increased from 36% in raw leachate to 57% and 68% after applying S2O8(2-) and S2O8(2-)/H2O2 oxidation, respectively. As for soluble COD(s), its removal efficiency was 39% and 78% following S2O8(2-) and S2O8(2-)/H2O2 oxidation, respectively. The maximum removal for particulate COD was 94% and was obtained after 120 min of S2O8(2-)/H2O2 oxidation. As a conclusion, S2O8(2-)/H2O2 oxidation could be an efficient method for improving the biodegradability of anaerobic stabilized leachate., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Background and Aims: Colorectal cancer is one of the leading causes of death in the world. The aim of this study was to investigate the growth-suppression potentiality of a crude saponin extract (CSENS) prepared from medicinal herb, Nigella sativa, on human colon cancer cells, HCT116., Materials and Methods: HCT116 cells were subjected to increasing doses of CSENS for 24, 48 and 72 h, and then harvested and assayed for cell viability by WST-1. Flow cytometry analyses, cell death detection ELISA, fluorescent stains (Hoechst 33342 and acridine orange/ethidium bromide), DNA laddering and comet assays were carried out to confirm the apoptogenic effects of CSENS. Luciferase reporter gene assays, quantitative reverse transcription-polymerase chain reaction and Western blot analyses were performed to assess the impact of CAERS and CFEZO on the expression levels of key regulatory proteins in HCT116 cells., Results: The results demonstrated that CSENS inhibited proliferation and induced apoptosis. Apoptosis was confirmed by flow cytometry analyses, while CSENS-treated cells exhibited morphological hallmarks of apoptosis including cell shrinkage, irregularity in cellular shape, cellular detachment and chromatin condensation. Biochemical signs of apoptosis, such as DNA degradation, were observed by comet assay and gel electrophoresis. The pro-apoptotic effect of CSENS was caspase-3-independent and associated with increase of the Bax/Bcl-2 ratio. CSENS treatment down-regulated transcriptional and DNA-binding activities of NF-κB and AP-1 proteins, associated with down-regulation of their target oncogenes, c-Myc, cyclin D1 and survivin. On the other hand, CSENS up-regulated transcriptional and DNA-binding activities of Nrf2 and expression of cytoprotective genes. In addition, CSENS modulated the expression levels of ERK1/2 MAPK, p53 and p21., Conclusions: These findings suggest that CSENS may be a valuable agent for treatment of colon cancer.

Context: Boswellia species are trees (family: Bruseraceae) found in India, Northern Africa and the Middle East., Objective: This study aims at formulating low dose biologically active fraction from the oleogum resin of Boswellia carterii (BC) in transdermal (TD) microemulsions (MEs) to acquire promoted anti-inflammatory efficacy., Materials and Methods: The bioactive fraction of the oleogum resin of BC was tested for solubility in different components. The most efficient were selected for constructing phase diagrams for ME preparation. The bioactive fraction was assayed by high performance liquid chromatography for 3-acetyl-11-keto-β-boswellic acid (AKBA), at 210 nm. The bioactive fraction was incorporated in 6 MEs. ME systems were evaluated for drug content and optimized systems were tested for characterization, permeation, skin irritancy and in vivo evaluation of anti-inflammatory activity., Results and Discussion: Two systems were selected; ME1 and ME4 composed of Tween 80: PEG 400 at 1:1 and 2:1 ratio, with oil content 7.78 and 17.5%, respectively. The systems showed high encapsulation efficiency >83%, small droplet size <100 nm, and suitable pH for topical application. Permeation parameters for ME1 were higher compared to ME4. Both MEs were non irritant. ME1 showed significantly higher anti-inflammatory activity versus the standard TD anti-inflammatory piroxicam., Conclusions: Optimized TD BC MEs could be used as a safe, effective and long acting alternative to oral anti-inflammatories, providing higher and prolonged efficacy and better patient compliance.

Boswellia carterii (BC) Birdwood oleogum resin is an ancient remedy of inflammation processes known since Ancient Egyptian time. Of boswellic acids, 3-acetyl-11-keto-β-boswellic acid (AKBA) is the most potent anti-inflammatory active principle. Liquisolid systems of the biologically active fraction of BC oleogum resin were prepared for improving dissolution properties using low dose oral delivery to achieve enhanced anti-inflammatory activity, in comparison with the standard oral anti-inflammatory; Indomethacin. AKBA was assayed, employing an accurate and sensitive HPLC method. Detection was carried out at 210 nm using UV/Vis detector. A solubility study for the bioactive fraction was conducted. Microcrystalline cellulose and Aeroperl®300 Pharma were used as carrier and coating materials. Angle of slide, liquid load factor and Carr's flow index were estimated. Six systems were prepared using polyethylene glycol 400, solvent and two drug loading concentrations; 20 and 40 %. For each concentration, three carrier: coat ratios were dispensed; 20:1, 10:1, and 5:1. Dissolution study was performed and two systems were selected for characterization and in vivo evaluation by investigating upper GIT ulcerogenic effect and anti-inflammatory efficacy in rats. Results indicate absence of ulcers and significantly higher and prolonged anti-inflammatory efficacy for formulations F1 and F2, with carrier: coat ratio, 5:1 and drug loads of 20 and 40 %, respectively, compared with standard oral indomethacin. We conclude higher efficacy of BC bioactive fraction liquisolids compared with Indomethacin with greater safety on GIT, longer duration of action and hence better patient compliance.

Background: Wastewater discharged from electroplating industry contains different concentrations of heavy metals, which when released into the environment pose a health hazard to human beings., Objectives: The aim of this study was to assess the effectiveness of orange peel as an adsorbent in the recovery of Nickel (Ni) from electroplating wastewater., Materials and Methods: The effectiveness of orange peel as an adsorbent was assessed by determining the optimum conditions of adsorption (adsorbent dose, pH, and contact time), calculating the recovery percentage, and characterizing the orange peel sludge resulting from adsorption/desorption process as being hazardous or not., Results: Under optimum conditions for adsorption, orange peel was found to be an effective adsorbent of Ni from electroplating wastewater. It achieved 59.28% removal of the metal from a solution containing 528 mg/l, at a dose of 60 g/l, at pH 7, and for 1-h contact time. The nickel uptake capacity of orange peel was calculated to be 5.2 mg/g. Using HCl for desorption of adsorbed Ni, a recovery of 44.46% of Ni discharged in the wastewater could be reached. Orange peel resulting from the adsorption/desorption process was characterized as being nonhazardous., Conclusion and Recommendation: Orange peel was found to be effective in the recovery of nearly half of the amount of Ni discharged in electroplating wastewater. Further studies are required to determine (a) the impact of the recovered NiCl2 solution on the quality of the plated product, (b) the effect of activation of orange peel on the adsorption process, and (c) the number of cycles during which orange peel can be reused as an effective adsorbent.

The spider polyamine toxins Joro spider toxin-3 (JSTX-3) and Nephila polyamine toxins-1 and -8 (NPTX-1 and NPTX-8) are isolated from the venom of the orb-weaver spider Nephila clavata (Joro spider). They share a high degree of structural resemblance, their aromatic head groups being the only difference, and were recently found to be very potent open-channel blockers of ionotropic glutamate (iGlu) receptors. In this study we designed and synthesized a collection of 24 analogues of these toxins using a recently developed solid-phase synthetic methodology. Systematic variation in two regions of the toxins and subsequent evaluation of biological activity at AMPA and NMDA subtypes of iGlu receptors provided succinct information on structure-activity relationships. In particular, one set of analogues were found to display exquisite selectivity and potency for AMPA receptors relative to the natural products. Thus, this systematic SAR study has provided new pharmacological tools for studies of iGlu receptors., (© 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Aim: To investigate the effects of extracts from Rhazya stricta (R. stricta) and Zingiber officinale (Z. officinale) on human colorectal cancer cells., Methods: Human colorectal cancer cells (HCT116) were subjected to increasing doses of crude alkaloid extracts from R. stricta (CAERS) and crude flavonoid extracts from Z. officinale (CFEZO). Cells were then harvested after 24, 48 or 72 h and cell viability was examined by trypan blue exclusion dye test; clonogenicity and soft agar colony-forming assays were also carried out. Nuclear stain (Hoechst 33342), acridine orange/ethidium bromide double staining, agarose gel electrophoresis and comet assays were performed to assess pro-apoptotic potentiality of the extracts. Quantitative reverse transcription-polymerase chain reaction (qRT-PCR), using gene-specific primers and Western blot analyses were performed to assess the impact of CAERS and CFEZO on the expression levels of key regulatory proteins in HCT116 cells., Results: Treatment with a combination of CAERS and CFEZO synergistically suppressed the proliferation, colony formation and anchorage-independent growth of HCT116 cells. Calculated IC50, after 24, 48 and 72 h, were 70, 90 and 130 μg/mL for CAERS, 65, 85 and 120 μg/mL for CFEZO and 20, 25 and 45 μg/mL for both agents, respectively. CAERS- and CFEZO-treated cells exhibited morphologic and biochemical features of apoptotic cell death. The induction of apoptosis was associated with the release of mitochondrial cytochrome c, an increase in the Bax/Bcl-2 ratio, activation of caspases 3 and 9 and cleavage of poly ADP-ribose polymerase. CAERS and CFEZO treatments downregulated expression levels of anti-apoptotic proteins including Bcl-2, Bcl-X, Mcl-1, survivin and XIAP, and upregulated expression levels of proapoptotic proteins such as Bad and Noxa. CAERS and CFEZO treatments elevated expression levels of the oncosuppressor proteins, p53, p21 and p27, and reduced levels of the oncoproteins, cyclin D1, cyclin/cyclin-dependent kinase-4 and c-Myc., Conclusion: These data suggest that a combination of CAERS and CFEZO is a promising treatment for the prevention of colon cancer.

Background and Objectives: Breakfast skipping is prevalent among adolescents and young women, and deprives the body of important nutrients. This study was conducted to assess the correlation between breakfast eating and sociodemographic and lifestyle criteria., Participants and Methods: A cross-sectional study was carried out on a convenient sample of 400 female students selected from the female sector of King Abdulaziz University, Jeddah, Saudi Arabia. Home breakfast habit and other lifestyle characteristics were studied using a standardized questionnaire. Logistic regression was used to examine the relationship between home breakfast habit and different predictors., Results: Home breakfast skippers constituted 71.75% of the whole sample. Breakfast eaters had a significantly higher BMI compared with breakfast skippers (22.66±4.88 vs. 21.58±4.09 in home breakfast skippers; P=0.025). Irrespective of other sociodemographic and lifestyle variables, fathers' education lower than university level negatively predicted home breakfast eating [Exp B=0.40, confidence interval (CI)=0.21-0.77], and being employed positively predicted breakfast eating (Exp B=2.31, CI=1.04-5.15). Likewise, consuming less amount of junk food and fewer soft drinks (Exp B=2.57, CI=1.54-4.28, and Exp B=2.59, CI=1.39-4.81, respectively) and consuming more milk and dairy products (Exp B=1.91, CI=1.16-3.15) correlated positively with home breakfast eating., Conclusion and Recommendations: Breakfast skipping was prevalent among adolescents and young women in the studied sample. Unhealthy dietary habits, father's education lower than university level, and father being unemployed positively predicted breakfast skipping of daughters at home. This implies that breakfast eating can be encouraged by approaching parents in addition to their daughters.

Hitherto, limited clinical impact has been achieved in the treatment of glioblastoma (GBMs). Although phytochemicals found in medicinal herbs can provide mankind with new therapeutic remedies, single agent intervention has failed to bring the expected outcome in clinical trials. Therefore, combinations of several agents at once are gaining increasing attractiveness. In the present study, we investigated the effects of crude alkaloid (CAERS) and flavonoid (CFEZO) extracts prepared from medicinal herbs, Rhazya stricta and Zingiber officinale, respectively, on the growth of human GBM cell line, U251. R. stricta and Z. officinale are traditionally used in folkloric medicine and have antioxidant, anticarcinogenic, and free radical scavenging properties. Combination of CAERS and CFEZO treatments synergistically suppressed proliferation and colony formation and effectively induced morphological and biochemical features of apoptosis in U251 cells. Apoptosis induction was mediated by release of mitochondrial cytochrome c, increased Bax : Bcl-2 ratio, enhanced activities of caspase-3 and -9, and PARP-1 cleavage. CAERS and CFEZO treatments decreased expression levels of nuclear NF-κBp65, survivin, XIAP, and cyclin D1 and increased expression level of p53, p21, and Noxa. These results suggest that combination of CAERS and CFEZO provides a useful foundation for studying and developing novel chemotherapeutic agents for the treatment of GBM.

Background: Alamein Marina Lagoon is one of six lagoons, lying on the Egyptian Mediterranean Coast. Between 1988 and 1995, a large-scale recreational compound called Alamein Marina Touristic Village was established to contain most of these lakes. The study aims to assess the quality of Alamein Marina Lagoon water in an attempt to evaluate the environmental impact of the touristic summer activities on the lake and to determine at what level this recreational lagoon stands as a healthy resort, among the other resorts around the Mediterranean Sea Basin., Materials and Methods: Fourteen sampling stations were chosen to present the four sub-basins of the lagoon and its outlets on the Mediterranean Sea. Physical, chemical, and bacteriological characteristics of the lagoon water were determined., Results: Lagoon water pH was found to range between 6.8 and 7.9. Dissolved oxygen, biochemical oxygen demand, nitrates and phosphates were 6.5 mg/L, 1 mg/L, 0.5 μg/L, and 3.8 μg/L respectively. Fecal coliform were not detected in all sampling stations., Conclusion: Alamein Marina water characteristics were complying with the standards set by Egyptian legislations concerning recreational water all over the study period. They were also complying with the levels set by different international organizations such as the WHO and Blue Flag. Besides, by calculating the water quality index for Alamein Marina Lagoon and its four sub-basins, water was found to be of an 'excellent' quality.

Objective: This study examined whether there is a positive correlation existed between cervical and oral High Risk-Human Papilloma Viruses (HR-HPV) types 16, 18 infections in patients with clinically confirmed cervical lesions., Methods: In this study 50 participants were included (40 were cases and 10 were controls). One hundred DNA materials (50 were cervical and 50 were oral epithelial tissues) were analyzed using HR-HPV subtypes 16 and 18 specific PCR probes., Results: Of the 40 cases, HR-HPV 16, 18 were identified in 16/40 (40%), of the cervical tissues of whom 8/16 (50%) were positive for HPV 16; 6/16 (37.5%) were identified with HR-HPV 18, and 2/16 (12.5%) were detected with both HR-HPV subtypes. All of the clinically healthy cases were found negative. Only one oral tissue sample (case) was 1/40 (2.5%) was found positive for HPV subtype16., Conclusion: The frequency of infection with HR-HPV subtypes 16 and 18 is high among Sudanese women with cervical lesions and suggests a role of HR-HPV in the development of cervical cancer in Sudan. No correlation between cervical and oral HPV infection was noted. Further study with screening of large number of patients with cervical cancer is recommended for further clarification of these findings.

Background: Nutrition clearly plays a role during adolescent development. Nutritional habits are not in line with the recommendations among adolescents. Food habits that are seen more frequently among teens than in other age groups include irregular consumption of meals, and eating away from home (especially fast-food venues). In addition, many young people do not eat enough fruits and vegetables (FVs)., Aim: We aimed at exploring the knowledge, attitude, and behavior toward FV consumption among adolescent Saudi girls, using a transtheoretical model (TTM)., Participants and Methods: A cross-sectional study was conducted. The target group included adolescent girls aged 18-21 years, students at the Faculty of Applied Medical Sciences, at King Abdulaziz University, Kingdom of Saudi Arabia. Of a total sample of 205 participants, 73 were in the Clinical Nutrition Department. FV consumption was assessed among the whole sample, using a Food Frequency questionnaire, and then the TTM determinants were assessed., Results: The study detected significant differences between the two groups with regard to vegetable consumption. The most frequently reported stage of change in the nutrition department was action maintenance with regard to FV consumption; self-efficacy and pros were the most significant positive predictors for FV consumption, whereas the department type (determining knowledge) had a negligible effect. Finally, we detected that TTM determinants of FV intake and their stages of change clustered., Conclusion and Recommendations: Knowledge alone cannot predict FV intake in adolescent girls. TTM stages of change and determinants seem to be somewhat related in FV consumption. Therefore, an integrated dietary change approach for both FV consumption is recommended among adolescents.

Drinking water from bottle-less coolers may pose some public health risks to consumers due to either chemical or microbiological contamination. This study was carried out aiming at assessing the quality of water dispensed from some public coolers in order to determine its compliance with the drinking water standards (Egyptian, EPA) and with the WHO guidelines. Twenty water coolers were selected randomly from different districts. Water samples were collected thrice from these coolers and once from the mains supplying the coolers. Results of analysis of these samples revealed that 85% of water coolers were containing <0.5 mg/l free residual chlorine, 65% were containing lead higher than 0.01mg/l, and 55% were containing magnesium hardness higher than 150 mg/l. As for the biological contamination, 15% of the coolers were contaminated with Cryptosporidium parvum, 15% were containing total coliform group of bacteria, 5 % gave positive thermotolerent coliform test and 5% gave positive Streptococcus fecalis test. The study concluded that such contamination might be from failure to thoroughly clean the coolers on a regular basis. Consequently, the study recommends proper installation of the cooler, a maintenance agreement with the cooler supplier, testing cooler water at regular intervals by the Ministry of Health representatives, and -if possible- replacing these types of coolers with those with a water purification system.

Considering the serious environmental threats facing Egypt, environmental education (EE) that provides the knowledge, skills, and motivation to take individual or collective action is needed to create a sustainable quality of life. This study was carried out aiming at measuring the level of environmental knowledge among preparatory school students in Alexandria, determining their attitudes towards some environmental concepts, and assessing the effect of EE on these knowledge and attitudes. The study sample was selected by stratified random method, and the assessment was conducted using a questionnaire. Results of the study revealed that 77% of the students had poor level of environmental knowledge and that 23% had fair level. In addition, 80% of the students were found to have negative attitude toward the environment and the remainder 20% were indifferent. Such knowledge and attitudes were positively correlated to their socio-economic levels. Following six EE sessions, an improvement in their knowledge and attitudes was observed where 69% of the students had a satisfactory level of knowledge and 88% had positive attitude toward the environment. Attitude was found to be positively correlated to their level of knowledge prior to and following the EE sessions. These results support the need for development and implementation of environmental education programs as part of the regular school curriculum.

New Borg Al-Arab city includes 9 residential areas and 4 industrial zones. The four industrial zones are occupied by 266 running factories belonging to different industrial sectors. All the domestic sewage as well as the industrial wastewater is treated at an oxidation pond treatment plant and the plant effluent is used in irrigation of silviculture areas. The plant consists of 2 pond complexes. Each complex comprises 9 facultative ponds, arranged in 3 parallel series. Raw wastewater is pre-treated through screens and grit removal before entering the primary ponds. The study aims at assessment of the performance of the waste stabilization ponds. The results revealed that pre-treatment units were not functioning properly. The retention time was calculated to be 6 days in each pond of the first complex and 3 days in each pond of the second complex. The mean BOD surface loading rate was calculated to be 676 kg/ha/d for the first complex and 1584 kg/ha/d for the second. The plant was hydraulically and organically overloaded. The percentage removal of BOD, COD, SS, and NH3-N had an annual mean of 57%, 56%, 44%, and 39%, respectively for the first complex and 21%, 42%, 39%, and 25%, respectively for the second. Faecal coliforms were reduced by about 1 log10 unit in both complexes. The final pond effluent was not complying with the Egyptian law for reuse in irrigation. The study proposed some recommendations which can improve the efficiency of the plant as well as the effluent quality.