C677T MTHFR Gene Polymorphism is Contributing Factor in Development of Renal Impairment in Young Hypertensive Patients.

Homocysteine concentration affected by the activities of the enzymes methylene tetra-hyrdofolate reductase (MTHFR). Polymorphisms in MTHFR gene associated with an impairment of MTHFR activity. Hyperhomocysteinemia is a result of single nucleotide polymorphisms (SNPs) in MTHFR 677 C>T that can cause homocysteine levels in the blood to increase. The purpose of this study is to investigate the relationships between MTHFR C677T (rs1801133) gene polymorphism, changes in homocysteine concentrations and progress of renal impairment in young adult hypertensive patients. Two hundred young hypertensive patients (age 21-24 years) were involved in this study; they were classified into patients with and without renal impairment in addition to 200 age and sex matched healthy controls. All participants were submitted to laboratory investigations as assay of MTHFR gene polymorphism C677T (rs1801133) by PCR/RFLP, determination of lipid profile, homocysteine and folic acid concentrations in addition to urinary albumin creatinine ratio (UACR). The levels of both homocysteine and UACR in the TT genotype patients were higher than those in the CC genotype group. Individuals who carry the T allele were more risky to hypertension and progress to early renal impairment in young age compared with those carrying the C allele [OR 2.02 (1.33-3.08), P < 0.001]. Genetic variants of C677T MTHFR gene and hyperhomocysteinemia may be responsible for rapid progress of renal impairment in Egyptian young age hypertensive patients. TT genotype or T allele may be considered as a predisposing factor for both elevated Hcy levels and the development of renal impairment. This study believed that lowering of homocysteine level can reduce renal impairment of hypertensive patients.

Modulation of Early Mitotic Inhibitor 1 (EMI1) depletion on the sensitivity of PARP inhibitors in BRCA1 mutated triple-negative breast cancer cells.

Triple negative breast cancer (TNBC) represents approximately 10-15% of all breast cancers and has a poor outcome as it lacks a receptor target for therapy, and TNBC is frequently associated with a germline mutation of BRCA1. Poly (ADP-ribose) polymerase inhibitor (PARPi) drugs have demonstrated some effectiveness in treating BRCA1 or BRCA2 mutated breast and ovarian cancers but resistance to PARPi is common. Published results found that resistance to Olaparib, a PARPi, can be due to downregulation of EMI1 and the consequent upregulation of the RAD51 recombinase. Using a tissue culture-based cell viability assay, we extended those observations to another PARPi and to other chemotherapy drugs that affect DNA repair or the cell cycle. As we expected, EMI1 downregulation resulted in resistance to another PARPi drug, Talazoparib. EMI1 downregulation also led to resistance to other cytotoxic drugs, Cisplatin and CHK1 inhibitor. Notably, increasing the RAD51 protein expression only recapitulated some, but not all, of the effects of EMI1 depletion in conferring to the cell resistance to different PARPi and the other cytotoxic drugs. These results suggest that the downstream effects of EMI1 downregulation that contribute to PARPi resistance are increasing the concentration of RAD51 protein in the cell and blocking mitotic entry. We found that combining CHK1 inhibitor with olaparib results in restoration of sensitivity even when EMI1 expression is downregulated. This combination therapy may be a means to overcome the PARPi resistance in BRCA1-deficient TNBC cells.

Study of Angiopoietin-2 and vascular endothelial growth factor as markers of diabetic nephropathy onset in Egyptians diabetic patients with non-albuminuric state.

BACKGROUND: Vascular endothelial growth factor (VEGF) and angiopoietin (Ang-2) systems have a central role in vasculogenesis and neoangiogenesis during glomerular development. disruption, their levels are associated with alterations in the glomerular filtration barrier and proteinuria as in diabetic nephropathy. Aim of this study to assess the validity of blood Ang-2 and VEGF as biomarkers for early detection of diabetic nephropathy as well as to study the relation between them and inflammation in diabetic nephropathy patients. SUBJECTS AND METHODS: Cross-sectional study included 180 diabetic nephropathy patients. Patients were classified to non-albuminuric, microalbuminuria and macroalbuminuria patients. Patients with macroalbuminuria complicated to renal impairment and ESRD on top of diabetic nephropathy. Ang-2 and VEGF were measured beside urinary albumin creatinine ratio (UACR). RESULTS: Significant increase of Ang-2 and VEGF levels among patients with normoalbuminuric state compared to control but there is no significant difference of UACR between both groups. Ang-2 and VEGF concentrations were significantly higher in patients with microalbuminuria and macroalbuminuria compared to healthy. Ang-2 and VEGF levels increase with the progression of albuminuria. There were significant positive correlation between CRP and Ang-2 in addition to VEGF. Significant negative correlation between eGFR, Ang-2 and VEGF. CONCLUSION: VEGF and Ang-2 were significantly elevated in diabetic nephropathy patients without albuminuria, their levels steadily increase with the progress of albuminuria, So can use them as markers for diagnosis of diabetic nephropathy onset and progression specially in patients without an increase in albumin excretion.

Complement c1q tumor necrosis factor-related protein 3 a novel adipokine, protect against diabetes mellitus in young adult Egyptians.

C1q/TNF-related protein-3 (CTRP3) is a novel adipokine with anti-inflammatory and a multitude of biological effects on glucose and lipid metabolism however, the influence of CTRP3 on incidence of diabetes mellitus remain unclear. This study investigated the effects of CTRP3 levels in obese and normal body weight young adults on insulin resistance and occurrence of diabetes mellitus. SUBJECTS AND METHODS: In this case control study, Serum levels of CTRP3, HbA1c, Lipid profile, glucose and insulin levels were determined in 75 obese and 68 normal body weight individuals. RESULTS: In obese young adults CTRP3 concentrations were decreased compared to normal body weight young adults (NBW). The association between reduction of CTRP3 concentrations and the presence of diabetes is statistically significant. CTRP3 showed significant negative correlation with BMI, HOMA-IR and triglycerides as well as positive correlations with HDL - cholesterol while there is no association between CTRP3 and BMI within the NBW group. Higher HbA1C, HOMA-IR, and risk of diabetes development within obese subjects were related to lower CTRP3 concentration. CONCLUSIONS: This study shows that reduction of CTRP3 concentrations is likely to bring a concomitant increase in risk of diabetes in obese and normal body weight young adults. Decrease in CTRP3 concentration may have an essential role in the pathophysiology of metabolic disorders concomitant to obesity.

Serum elafin as a potential inflammatory marker in psoriasis.

BACKGROUND: Psoriasis is a distressing chronic skin disease. Its exact pathogenesis is still unclear, as many factors interplay in its occurrence. AIM: The aim of the study is to estimate elafin levels in the serum of both cases and controls and to correlate the levels with psoriasis severity and other markers of inflammation. SUBJECTS AND METHODS: Twenty-six psoriatic cases along with 26 healthy controls were assigned in this case-control study. Psoriasis severity was determined by Psoriasis Area and Severity Index score. Elafin levels were measured by ELISA in serum of both cases and controls. C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) were measured in the cases. RESULTS: Elafin levels show highly statistical significance difference (P < 0.001) between cases and controls. There is a statistical significant correlation between elafin levels and both psoriasis severity and inflammation markers as CRP and ESR. CONCLUSION: Elafin represents a mirror for psoriasis severity and inflammatory state.