CX3CR1 at V249M and T280M Gene Polymorphism and Its Potential Risk for End-Stage Renal Diseases in Egyptian Patients

CX3CL1-CX3CR1 pathway may be one of the future treatment targets to delay the progression of end-stage renal diseases. This study aimed to evaluate the CX3CR gene polymorphism in Egyptian patients with ESRD and its relation to fractalkine blood level. The study included 100 patients with ESRD on dialysis, 61 males and 39 females with mean age 51.02 ± 7.8 years. The V2491 genotype revealed a significant increase in the frequency of GG genotype in healthy control (83%) compared to patients [69%] with a significant increase in GA in patients [30%] compared to control subjects [15%], P = 0.03. T280M study showed a statistically significant prevalence of TT genotype in healthy control subjects [86%-OR 95% CI 1.7] compared to patients [70%] with a significant increase in the prevalence of TA in patients [29%] compared to control subjects [13%], P = 0.01. There was a significant increase in fractalkine levels in genotypes GA + AA [503.04±224.1] pg/ml compared to genotype GG [423.6 210.3], P = 0.03. Moreover, there was a significant increase in the blood level of fractalkine in genotype TA + AA [498.8 219.6] compared to genotype TT [426.8±212.8], P = 0.05. In conclusion, our study showed that both V2491-GA genotype and T280M-TA are associated with potential risk for end-stage renal disease in Egyptian patients

Computational and Experimental Approaches Exploring the Role of Hesperetin in Improving Autophagy in Rat Diabetic Retinopathy

Diabetic retinopathy (DR) is a debilitating diabetic disorder of the retinal microvasculature and the main cause of avoidable blindness in old people. Hesperetin is a plant flavanone largely abundant in citrus species with neuroprotective properties in animal models. This study aimed to explore the neuroprotective and autophagy-enhancing effect of hesperetin in rats with DR. Twenty-four male rats were utilized and allocated to groups: (i) the vehicle group, (ii) DR group and (iii–iv) the DR + hesperetin (50 and 100 mg/kg) groups. Treatment with hesperetin continued for 6 weeks. After the rats were euthanized, their eyes were dissected to detect the biochemical and histological changes in the retinas. Quantification of autophagy markers, beclin 1/LC3/p62, and inflammation markers was performed. Histopathologic changes were investigated after staining with hematoxylin and eosin and periodic acid–Schiff (PAS). Results demonstrated that hesperetin decreased the PAS staining in diabetic rats and attenuated histopathological changes and restored retinal organization and thickness of layers in hematoxylin and eosin staining. Moreover, hesperetin reduced the level of mRNA expression for TNF-α (4.9-fold), IL-1β (4.15-fold), IL-6 (4.6-fold) and NFκB (5.2-fold), as well as the protein level. This was accompanied by induction of autophagy proteins, beclin 1 and LC3-II. Our results afford evidence that hesperetin is effective in alleviating the pathology of DR via suppressing the inflammatory burden and induction of autophagy. After extensive clinical examinations, hesperetin may prove to be a useful option for treatment of DR

DataSheet1_Chemotherapeutic potential of betanin/capecitabine combination targeting colon cancer: experimental and bioinformatic studies exploring NFκB and cyclin D1 interplay.PDF

Introduction: Betanin (C₂₄H₂₆N₂O₁₃) is safe to use as food additives approved by the FDA with anti-inflammatory and anticancer effects in many types of cancer cell lines. The current experiment was designed to test the chemotherapeutic effect of the combination of betanin with the standard chemotherapeutic agent, capecitabine, against chemically induced colon cancer in mice.Methods: Bioinformatic approach was designed to get information about the possible mechanisms through which the drugs may control cancer development. Five groups of mice were assigned as, (i) saline, (ii) colon cancer, (iii) betanin, (iv) capecitabine and (v) betanin/capecitabine. Drugs were given orally for a period of six weeks. Colon tissues were separated and used for biological assays and histopathology.Results: In addition, the mRNA expression of TNF-α (4.58-fold), NFκB (5.33-fold), IL-1β (4.99-fold), cyclin D1 (4.07-fold), and IL-6 (3.55-fold) and protein levels showed several folds increases versus the saline group. Tumor histopathology scores in the colon cancer group (including cryptic distortion and hyperplasia) and immunostaining for NFκB (2.94-fold) were high while periodic-acid Schiff staining demonstrated poor mucin content (33% of the saline group). These pathologic manifestations were reduced remarkably in betanin/capecitabine group.Conclusion: Collectively, our findings demonstrated the usefulness of betanin/capecitabine combination in targeting colon cancer and highlighted that betanin is a promising adjuvant therapy to capecitabine in treating colon cancer patients.</p