Comparative metabolomics analysis of Citrus medica var. sarcodactylis Swingle and Limonia acidissima Linn. Fruits and leaves cultivated in Egypt in context to their antiviral effects.

A comprehensive study of fruits and leaves extracts of Citrus medica var. sarcodactylis Swingle and Limonia acidissima L. family Rutaceae was accomplished to investigate their antiviral activity along with their zinc oxide nanoparticles formulation (ZnONPs) against the avian influenza H5N1 virus. A thorough comparative phytochemical investigation of C. medica and L.acidissima leaves and fruits was performed using UPLC-QTOF-MS-MS. Antiviral effects further aided by molecular docking proved the highly significant potential of using C. medica and L.acidissima extracts as medicinal agents. Antiviral potency is ascendingly arranged as L. acidissima leaves (LAL) > L. acidissima fruits (LAF) > C. medica leaves (CML) at 160 µg. Nano formulation of LAF has the most splendid antiviral upshot. The metabolomic profiling of CMF and LAL revealed the detection of 48 & 74 chromatographic peaks respectively. Docking simulation against five essential proteins in survival and replication of the influenza virus revealed that flavonoid di-glycosides (hesperidin, kaempferol-3-O-rutinoside, and kaempferol-7-neohesperidoside) have shown great affinity toward the five investigated proteins and achieved docking scores which approached or even exceeded that achieved by the native ligands. Hesperidin has demonstrated the best binding affinity toward neuraminidase (NA), haemagglutinin (HA), and polymerase protein PB2 (-10.675, -8.131, and -10.046 kcal/mol respectively. We propose using prepared crude methanol extracts of both plants as an antiviral agent.

The effect of hepatic steatosis on 18F-FDG uptake in PET-CT examinations of cancer Egyptian patients.

BACKGROUND: Hepatic steatosis is the most common chronic hepatic disease. Imaging diagnosis of hepatic steatosis has been evaluated as an alternative to invasive histological diagnosis. STUDY AIMS: The study aimed to assess the effect of hepatic steatosis on Flourine-18 fluorodeoxyglucose (18F-FDG) uptakes in cancer patients. PATIENTS AND METHODS: Blood samples were collected from 50 cancer patients and analyzed to calculate fatty liver index and Hepatic steatosis index (HIS). Hepatic steatosis examined using high-resolution ultrasound and positron emission tomography-computed tomography (PET-CT). Linear attenuation coefficient, standardized-uptake value (SUV) mean (SUV mean), and SUV maximum (SUVmax) were measured. Accordingly, patients were divided equally into non-fatty liver, and fatty liver groups. RESULTS: A significant increase in SUVmax and SUV mean was observed in the fatty liver group more than in the non-fatty liver group. HSI significantly increased in the fatty liver group compared to the non-fatty liver group. Liver tissue uptake FDG was significantly correlated with HSI values. SUV max significantly correlated with body mass index (BMI) in the non-fatty group only. CONCLUSION: Hepatic changes in cancer patients affect the liver metabolic activity and thus the 18 F-FDG uptake. Therefore, further corrections should be considered when the liver is used as a comparator for PET-CT scans of cancer patients.

Metabolomics analysis of Citrus medica var. sarcodactylis (Siebold ex Hoola van Nooten) Swingle and Limonia acidissima Linn. fruits and leaves in perspective to their antimicrobial potential.

Antimicrobial potential of Citrus medica var. sarcodactylis (Siebold ex Hoola van Nooten) Swingle and Limonia acidissima L. fruits and leaves extracts CMF, CML, LAF and LAL, respectively were evaluated. Gas chromatography-mass spectrometry (GC-MS) analysis for lipoidal matters revealed a high percentage of non-oxygenated compounds. Phytol was the major in LAL. Palmitic and linoleic acid were the major in CML and LAL, respectively. Rutin and P-hydroxy benzoic acid were the main compounds identified by High-performance liquid chromatography (HPLC) analysis. The antibacterial and antifungal activities of the plants extract were determined by the well diffusion method. Antimicrobial investigation for different successive fractions of active methanol extracts of CML, LAL, LAF and CMF showed the highest activity (CML), whereas the petroleum ether (CML PE) and MeOH (CML) fractions exhibit a significant antifungal activity against Candida albicans minimum inhibitory concentration (MIC) 12 and 15 µg/mL, respectively. The antifungal activity prevailed by C. medica leaves may be attributed to its polyphenolics (rutin, chlorogenic and rosmarinic acid) in addition to phenylated hydrocarbon.

Comparison of gdh polymerase chain reaction-restriction fragment length polymorphism and tpi assemblage-specific primers for characterization of Giardia intestinalis in children.

Background: Giardia is a diarrheagenic eukaryotic parasite that consists of at least eight morphologically identical but genetically distinct genotypes. Human giardiasis is caused mainly by A and B assemblages. Aim and objectives: The study aimed to compare the performance of gdh polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and tpi assemblage-specific primers in genotyping of G. intestinalis. Materials and Methods: Stool samples of 315 children were microscopically screened for G. intestinalis. Positive samples were genotyped using tpi assemblage-specific primers and gdh semi-nested PCR-RFLP techniques. Results: The prevalence of Giardia was 18.1%. The detected genotypes using tpi and gdh approaches were assemblage A (15.8% vs. 12.7%) and assemblage B (36.8% vs. 74.5%) as single infections and mixed assemblages A and B (47.4% vs. 12.7%). The two approaches showed a moderate agreement (kappa index = 0.413, P < 0.001). PCR-RFLP of gdh gene revealed that sub-assemblages BIII and BIV were equally detected (30.9% each). The remaining samples were equally divided between sub-assemblage AII, mixed BIII and BIV, and mixed AII and BIII (12.7% each). A significant association was detected between the retrieved sub-assemblages and the presence of symptoms. Conclusions: Although both approaches confirmed the predominance of assemblage B, the use of assemblage-specific primers is more effective in elucidating the true picture of mixed assemblage infection.

Detection of Giardia intestinalis assemblages A and B among children from three villages in the West Delta region, Egypt using assemblage specific primers.

Giardia intestinalis is a common diarrheagenic parasite infecting children globally. It has been classified into eight morphologically identical but genetically distinct genotypes. Human infection is mainly associated with A and B assemblages with variable geographical distribution. The present work aimed to study the epidemiology of assemblages A and B in children inhabiting different areas in Lower Egypt. Stool samples were collected from 315 children and examined microscopically for parasitic infections. Giardia positive samples were genotyped using tpi assemblage specific primers. The prevalence of Giardia was 18.1% among the examined children. Mixed assemblages A and B was more common (47.4%) than single assemblage B (36.8%) or A (15.8%). The distribution of different genotypes was significantly associated with the residence area, animal contact, and handwashing habits. A non-significant association was observed between Giardia assemblages and the clinical manifestations. Assemblage B is the predominant genotype among Egyptian children. The distribution of different Giardia assemblages is strongly associated with the studied area and the habits of its people.

Radiosensitizing and Phototherapeutic Effects of AuNPs are Mediated by Differential Noxa and Bim Gene Expression in MCF-7 Breast Cancer Cell Line.

To compare the apoptotic efficiency of AuNPs, ionizing and non-ionizing radiotherapy, phototherapy, and AuNPs-ionizing-radiotherapy), MCF-7 cells were used as a model for luminal B subtypes of breast carcinoma. A mixture of AuNPs [66% of Au-nanospheres (AuNSs) and 34% of Au-nanorods (AuNRs)] was synthesized and characterized by optical spectroscopy, zeta potential, and transmission electron microscopy (TEM). MCF-7 were divided into six groups (triplicates); after each treatment, cell viability was tested by MTT assay and relative gene expression levels of Bim and Noxa proapoptotic markers were assayed by qRT-PCR. A dose-dependent significant reduction in cell viability of MCF-7 was detected by all examined treatment protocols. Lower viability detected at extended exposure (48 hours) to AuNPs ( [Formula: see text]/ml) was mediated by the upregulation of Noxa gene expression. AuNS and AuNR in vitro PTTs were mediated by differential expression of Bim and Noxa while AuNPs mixture had a combined effect on both Bim and Noxa. Cellular recovery was observed two days-post x-rays irradiation at does < 3 Gy. AuNPs showed dose enhancement factor (DEF) > 12 indicating a high radiosensitizing effect that was partially mediated by Noxa. In conclusion, AuNPs combined therapies exert better anti-proliferative effects via differential regulation of Noxa and Bim gene expressions.

Post-irradiation protective effects of ectoine on brain and testicles in male mice.

BACKGROUND: The present study aimed to investigate the possible post-irradiation protective effects of ectoine on CNS and testes of male mice. METHODS: The study included thirty male Swiss albino mice (20-22 gm). Mice were divided into five groups (six each); controls (injected intraperitoneally with 0.2ml saline), irradiated group 1 (received six Gy whole body x-irradiation single dose, injected with saline, and sacrificed after one day), irradiated group 2 (x-irradiated, injected with saline, and sacrificed after one week), ectoine group 1 (x-irradiated, injected with 200mg/kg ectoine, and sacrificed after one day), and ectoine group 2 (x-irradiated, injected daily with 200mg/kg ectoine, and sacrificed after one week). IL-1ß, IL-6, IL-10, PGE2, MDA, GSH, GSSG, and GSH/GSSG ratio were evaluated in CNS and testes. RESULTS: IL-1ß, IL-6, IL-10, PGE2, and MDA are significantly elevated in the CNS and testes of x-irradiated groups when compared with controls. IL-1ß, IL-6, IL-10, and PGE2 significantly elevated at one week than one day while MDA significantly decreased. A significant decrease in the concentration of GSH and in the GSH/GSSG ratios coupled with an opposite effect on GSSG was noted. Ectoine treatment significantly ameliorated the biochemical effects induced by whole body x-irradiation. All the tested parameters tended to go back to near control values. It was noted that the modulating action was dependent on the accumulation of ectoine as it was more effective after repeated administration. CONCLUSION: Ectoine has post-irradiation protective effects on CNS and testes via its action on inflammatory and oxidative stress pathways.

Plasma TuM2-PK correlates with tumor size, CRP and CA 15-3 in metastatic breast carcinomas; short versus long term follow up study of the Egyptian breast cancer patients.

BACKGROUND: The key regulator of tumor metabolome is the glycolytic isoenzyme M2-PK which favors the generation of nucleic acid via glutaminolysis as hypoxic adaptive mechanism in the tumor cells. AIM: The study aimed to evaluate the prognostic role of M2-PK, CRP, and CA 15-3 in preoperative and metastatic breast carcinomas. PATIENTS AND METHODS: The study included 70 females; 15 controls, 33 preoperative primary breast carcinomas clinically metastasis free, and 22 clinically diagnosed metastatic breast carcinomas. M2-PK and CA 15-3 were detected by ELISA. CRP was quantified using the CRP LATEX kit. RESULTS: TuM2-PK significantly increased in metastatic and preoperative groups when compared to controls (p= 0.049, p= 0.001); respectively. Both CRP and CA 15-3 were significantly increased in metastatic than the preoperative group (p= 0.002). CA 15-3 was significantly increased in both groups when compared to controls (p= 0.016; p< 0.001; respectively). TuM2-PK level significantly related to tumor size in metastatic group (p= 0.006) and with menstruation status (p= 0.039), and liver metastasis (p= 0.036) in preoperative group. TuM2-PK significantly correlated with CRP (r= 0.793, p= 0.004), and CA 15-3 (r= 0.568, p= 0.006) in the metastatic group.Metastatic group with TuM2-PK ⩽ 15 U/ml had significantly higher survival rate than those with > 15 U/ml (χ2= 13.841, p< 0.001) within 3.3-4.2 but not after 10-20 years follow up period. Metastasis to bone and lymph nodes significantly increased in the metastatic than the preoperative group (p= 0.002, p= 0.013; respectively). Within 3.3-4.2 years, CA15.3 has the highest prognostic performance in metastatic group while both TuM2-PK and CRP have same specificity. On the other hand, TuM2-PK has the highest prognostic performance in preoperative group. After 20 years follow up period, there was neither significant difference in the performance of the three markers in predicting mortality in metastatic and preoperative groups nor in predicting metastasis in preoperative group. CONCLUSION: Current results document for the first time, a cross-talk between TuM2-PK and each of CRP and CA 15-3 in metastatic breast cancer.

Modulation of bone turnover in orchidectomized rats treated with raloxifene and risedronate.

Osteoporosis is a reduction in bone mineral density (BMD). It develops less often in men than in women. This study aimed to evaluate the bone protective effects of raloxifene (RAL), risedronate (RIS), and their combination on osteoporotic male rats. Forty male Wister rats (12 weeks) were randomly divided into five groups: sham-operated group (n = 8), orchidectomized (ORX) group (n = 7), RAL group (n = 9), RIS group (n = 7) and RAL + RIS group (n = 7). RAL was orally administered at 3 mg/kg three times/week, and RIS was given subcutaneously at 5 µg/kg, twice weekly. After 6 weeks of treatment, serum cathepsin-K, alkaline (ALP) and acid phosphatase activities, serum osteocalcin, serum Ca²âº, and Pi were determined. Urinary Ca²âº and deoxypyridinoline levels, BMD, and Ca²âº content of femur ash were estimated. Histochemical localization of ALP activity of tibia and histomorphometry was examined. As compared to sham, ORX rats showed a significant increase in bone turnover markers, and histochemical activity of ALP was increased markedly in proximal tibia of ORX rats, whereas BMD and Ca²âº content of femur ash were reduced after ORX. These changes were modulated after treatment with RAL and RIS or both to ORX rats; BMD of femur was improved by each treatment, and bone turnover markers were reduced as compared to ORX vehicle group. We concluded that orchidectomy induced osteoporosis and increased bone turnover in male rats because of withdrawal of sex hormones. Both RAL and RIS could treat osteoporosis in ORX rats; they reduced bone turnover markers and maintained BMD.