PNPLA3 and TNF-α G238A Genetic Polymorphisms in Egyptian Patients with Different Grades of Severity of NAFLD

Introduction: There is growing evidence that genetic and environmental factors play an important role in the development and progression of non-alcoholic fatty liver disease (NAFLD). We investigated the association of single nucleotide polymorphism (SNP) rs738409 in PNPLA3 gene and TNF-α G238A polymorphism with the development and severity of NAFLD in an overweight and obese Egyptian population. Material and Methods: 100 overweight and obese patients with NAFLD and 30 control subjects were enrolled. All NAFLD patients underwent a confirmatory biopsy. Laboratory investigations included fasting plasma glucose, kidney and liver function tests, liver enzymes, lipid profile and hepatitis markers. Abdominal ultrasound was performed and all subjects were genotyped for (rs738409) PNPLA3 and (rs361525) TNF-α gene polymorphisms using polymerase chain reaction and restriction fragment length polymorphism (PCR-RFLP). Results: The homozygous GG genotype of the PNPLA3 was most frequent among patients with NASH (26%) as compared to borderline NASH (20.5%) and simple steatosis (20%). Higher serum levels of transaminases were observed in NAFLD patients and controls who were carriers of the G allele of rs738409, but this was not statistically significant. Regarding the TNF-α G238A SNP;the frequency of the A allele was significantly higher in NAFLD patients (20%) compared to controls (5%) (p value = 0.006). The highest TNF G allele frequency was observed in the NASH group (88%) and this was statistically significant (p value = 0.009). Conclusion: Our study confirmed the association of the PNPLA3 (rs738409) and TNF-α promoter region G238A polymorphisms with susceptibility to NAFLD and its progression.

Association between IL-37 and VEGF Gene Expression in Psoriasis Pathogenesis in Egyptian Population

Background: Psoriasis is considered a common skin disease, marked by the production and elevation of inflammatory plaques that regularly shed scales resulting from extensive skin epithelial cell proliferation. T lymphocytes, neutrophils, and other leukocytes enter the irritated skin, resulting in epidermal keratinocyte hyperplasia, vascular hyperplasia, ectasia, and T lymphocyte, neutrophil other forms of leukocyte infiltration. Aim of the Work: the study aimed to investigate the role of IL-37 and VEGF gene expression in the pathogenesis of psoriasis in Egyptian patients. Methodology: Polymerase chain reaction techniques (PCR) were applied to detect VEGF in the skin homogenates of psoriasis patients. In addition, the ELIZA technique was applied to investigate IL-37 in skin homogenates. One hundred cases have been divided into two groups: 50 healthy volunteers as the group I healthy control;50 psoriasis patients as group II. PCR real-time technology was assessed through extracted DNA samples for VEGF amplification in skin homogenate. Result: Our results revealed that psoriasis patients significantly had a substantial reduction in IL-37 compared to the control group (p Conclusion: There is a significant inverse association between IL-37 and VEGF in psoriasis patients. Study findings revealed that IL-37 gene expression decreases while VEGF gene expression increases in psoriatic individuals. Such a measurement may be beneficial in determining the severity of the condition, as well as taking into consideration of the disease’s diagnosis.

Preparation, Characterization and in Vitro Evaluation of the Antitumor Activity of the Biologically Synthesized Silver Nanoparticles

This study was concentrated on the biosynthesis of silver nanoparticles from Penicillium aurantiogresium (IMI 89372) with a focus on its cytotoxicity in MCF-7 and MCT cancer cell lines as well as Vero (normal) cell line that was assessed by crystal violet assay after treatment with various concentrations (0.44 – 145 μg/ml) for 24 h. The cell morphology was examined by inverted light microscopy. Further, the radiosensitizing effect of silver nanoparticles (AgNPs) on MCF-7 was also demonstrated by assessing cell morphology, cell proliferation of MTT assay, LDH activity and induction of apoptosis through checking of some apoptotic genes that altered during carcinogenesis, including caspase-3, Bax and Bcl-2. Caspase-3 activity was also estimated. Synthesis of AgNPs was determined by UV-Visible spectrum and it was further characterized by TEM, FT-IR and X-Ray analysis (EDX, XRD). The biosynthesized AgNPs were spherical and of 12.7 nm in size as recorded by direct electron microscopy visualization. The biosynthesized AgNPs showed variation in cytotoxicity against MCF-7, MCT and Vero cell lines in a concentration dependant response with a varied degree of alteration in cell morphology. The result showed that AgNPs were highly toxic towards MCF-7 with IC50 value of 10.5 μg/ml. Treatment of MCF-7 (10.5 μg/ml) prior to irradiation improved the effect of irradiation dose (6 Gy) via increasing alteration of cell morphology, inhibition of cell proliferation, activation of the lactate dehydrogenase (LDH) and caspase-3 leading to induction of apoptosis which was further confirmed through increasing nuclear DNA damage and up regulation of caspase 3 and Bax genes and downrgulation of Bcl-2 genes. In conclusion, the present findings clearly indicated that AgNPs showed dose dependant cytotoxicity and verified that AgNPs acted as a potent radiosensitizer and could enhance gamma irradiation induced killing of MCF-7 breast cancer cells.