Essential Oil of Cestrum diurnum L.: GC/MS Analysis, in Vitro and in Silico Anti-HCoV-229E Effects and Inhibitory Activity against LPS-Induced Inflammation.

Cestrum diurnum L. (Solanaceae) is a fragrant ornamental tree cultivated in different parts around the world. In this study, the essential oil (EO) of the aerial parts was extracted by hydrodistillation (HD), steam distillation (SD) and microwave-assisted hydro-distillation (MAHD). GC/MS analysis of the three EOs revealed that phytol represents the major component in SD-EO and MAHD-EO (40.84 and 40.04 %, respectively); while in HD-EO it only represented 15.36 %. The SD-EO showed a strong antiviral activity against HCoV-229E with IC50 of 10.93 µg/mL, whereas, MAHD-EO and HD-EO showed a moderate activity with IC50 values of 119.9 and 148.2 µg/mL, respectively. The molecular docking of EO major components: phytol, octadecyl acetate and tricosane showed a strong binding to coronavirus 3-CL (pro). Moreover, the three EOs (50 µg/mL) decreased the levels of NO, IL-6 and TNF-α and suppressed IL-6 and TNF-α gene expression in LPS-induced inflammation model in RAW264.7 macrophage cell lines.

Analysis of Nuclear Receptor Coactivator 5 (NCOA5) Messenger RNA Expression and rs2903908 Single Nucleotide Polymorphism of NCOA5 in an Egyptian Cohort with Behçet's Disease: A Single-Center Case-control Study.

The nuclear receptor coactivator 5 (NCOA5) has been linked to several inflammatory disorders, including Behçet's disease (BD). We evaluated the expression of NCOA5 messenger RNA (mRNA) using real-time reverse transcription-polymerase chain reaction, and analyzed the rs2903908 T > C of NCOA5 using TaqMan allelic discrimination assay in 49 Egyptian BD patients and 50 controls. The NCOA5 mRNA levels were higher in patients compared to controls (p = .02), female patients compared to males (p = .037), and in patients with ocular involvement (p = .049). Non-CC genotype carriers had a higher frequency of articular manifestations compared with CC carriers (p = .047). Genotypes CC + CT were associated with reduced risk of cutaneous involvement (OR = 0.27, p = .04). CC carriers with active BD or cutaneous manifestations displayed significantly lower NCOA5 mRNA expression than TT carriers. Our results demonstrate that NCOA5 is linked to BD clinical findings and activity.

Role of ApoB-516C/T promoter gene polymorphism in the risk of Hepatitis C virus infection in Egyptian patients and in gender susceptibility.

At least 1 in 10 of the Egyptian population aged 15-59 is burdened with hepatitis C virus (HCV) infection, stamping Egypt the highest country harboring HCV worldwide. Considerable evidence supported the involvement of host genetic factors in the pathogenesis of HCV and the possibility of implementation in target therapies. ApoB gene polymorphisms are postulated to affect the susceptibility of HCV infection. Hence, we aimed to evaluate the relationship between ApoB-516C/T promoter gene polymorphism and HCV infection in a cohort of Egyptian patients and to explore whether higher levels of low-density lipoprotein (LDL) might compete with lipoviral particles (LVP) in the binding to LDL receptor (LDLR), thus escaping infection. Ninety-seven HCV patients and 96 matched controls were enrolled in this study. We genotyped ApoB-516C/T using PCR-RFLP method. ApoB concentrations were measured by immunoturbidimetric assay. The genotype and the allele frequencies of ApoB-516C/T promoter gene polymorphism in cases were statistically insignificant compared with healthy individuals (P = 0.109, 0.125, respectively). Sex stratification showed significantly lower counts of C/T genotype in female patients compared with female controls (P = 0.011, OR = 0.132, 95% CI = 0.026-0.657). Significantly higher levels of LDL and ApoB were detected in the control group (P < 0.001). This study shows that the ApoB-516C/T promoter gene polymorphism has no impact on the risk of HCV infection. However, the C/T genotype may be a protective factor for our female cohort. Further studies with larger samples are needed to verify this genetic gender diversity. Additionally, high levels of LDL and ApoB might prevent HCV infection.

Cytotoxic Oleanane-Type Saponins from the Leaves of Albizia anthelmintica Brongn.

Two new oleanane-type saponins: ß-d-xylopyranosyl-(1 → 4)-6-deoxy-α-l-mannopyranosyl-(1 → 2)-1-O-{(3ß)-28-oxo-3-[(2-O-ß-d-xylopyranosyl-ß-d-glucopyranosyl)oxy]olean-12-en-28-yl}-ß-d-glucopyranose (1) and 1-O-[(3ß)-28-oxo-3-{[ß-d-xylopyranosyl-(1 → 2)-α-l-arabinopyranosyl-(1 → 6)-2-acetamido-2-deoxy-ß-d-glucopyranosyl]oxy}olean-12-en-28-yl]ß-d-glucopyranose (2), along with two known saponins: (3ß)-3-[(ß-d-Glucopyranosyl-(1 → 2)-ß-d-glucopyranosyl)oxy]olean-12-en-28-oic acid (3) and (3ß)-3-{[α-l-arabinopyranosyl-(1 → 6)-[ß-d-glucopyranosyl-(1 → 2)]-ß-d-glucopyranosyl]oxy}olean-12-en-28-oic acid (4) were isolated from the acetone-insoluble fraction obtained from the 80% aqueous MeOH extract of Albizia anthelmintica Brongn. leaves. Their structures were identified using different NMR experiments including: 1 H- and 13 C-NMR, HSQC, HMBC and 1 H,1 H-COSY, together with HR-ESI-MS/MS, as well as by acid hydrolysis. The four isolated saponins and the fractions of the extract exhibited cytotoxic activity against HepG-2 and HCT-116 cell lines. Compound 2 showed the most potent cytotoxic activity among the other tested compounds against the HepG2 cell line with an IC50 value of 3.60µm. Whereas, compound 1 showed the most potent cytotoxic effect with an IC50 value of 4.75µm on HCT-116 cells.

Significant association between FasL gene -844T/C polymorphism and risk to hepatocellular carcinoma in Egyptian patients.

Fas/Fas ligand (FasL) system is the most critical apoptotic signaling entity in the extrinsic apoptotic pathway; hence mutations affecting this pathway may prevent the immune system from the removal of newly-formed tumor cells, and thus lead to tumor formation. The present study investigated the association between the FasL -844T/C polymorphism and the risk of hepatocellular carcinoma (HCC) in a cohort of Egyptian patients and explored the relationship of various clinical and pathological parameters with this single nucleotide polymorphism (SNP). Blood samples were withdrawn from hundred HCC patients and 100 age-, sex- and ethnically matched controls. The FasL -844T/C (rs763110) gene polymorphism was typed from genomic DNA using polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP) assay. Genotype distributions and allelic frequencies between patients and control subjects showed that the TT homozygous patients were two times more likely to develop HCC (p=0.011). Also, the T allele was found to be a significant risk factor for the disease (OR 1.970, 95% CI 1.250-3.105, p=0.003). No association was detected between different parameters of the disease and the SNP. For the first time, our results suggest that the -844T/C polymorphism in the FasL gene confers risk to HCC. The alarming increase in the incidence of HCC in Egypt encourages further studies to document our results in a larger sample, and recommends more genetic studies hoping to define a genomic risk prediction specific to this cancer in our population.

Reversion-Inducing-Cysteine-Rich Protein With Kazal Motifs (RECK) Gene Single Nucleotide Polymorphism With Hepatocellular Carcinoma: A Case-Control Study.

BACKGROUND: The reversion-inducing-cysteine-rich protein with kazal motifs (RECK) gene is a transformation suppressor gene that can negatively regulate matrix metalloproteinases (MMPs) and inhibit tumor invasion, angiogenesis, and metastasis. So, the aim of this study was to analyze the effect of RECK gene rs 11788747 single nucleotide polymorphism (SNP) on hepatocellular carcinoma (HCC) susceptibility and its relation to various clinical and laboratory data of the patients. METHODS: This is a case-control study including 200 HCC patients and 200 healthy controls. RECK rs 11788747 genotyping was performed using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). RESULTS: RECK rs 11788747 A/G and G/G genotypes frequencies were significantly higher in HCC patients compared to the healthy controls. The HCC patients possessing at least one polymorphic G allele were significantly at a higher risk of developing lymph nodes involvement and distant metastasis. CONCLUSION: This study revealed the role of RECK rs 11788747 SNP in HCC in Egyptian patients, which consequently might be used as a prognostic tool and could be added to its therapeutic strategies.