Sickle cell disease (SCD) is associated with a pro-inflammatory state, characterized by an elevated baseline leukocyte count and inflammatory cytokines. Inflammation, white blood cell (WBC) adhesion to vascular endothelium with subsequent endothelial injury, and repeated ischemia-reperfusion injury contribute to disease pathogenesis. Identification of genetic polymorphisms that may modulate disease severity in SCD is becoming a field of interest. The Duffy blood group antigen has been identified as a receptor for various chemokines involved in neutrophil activation and trafficking. This study aimed at investigating the effect of RBCs' Duffy antigen expression and its genetic polymorphisms on modulating disease severity and its complications among Egyptian sickle cell patients. Methods We analyzed the association of Duffy genotypes and phenotypes with clinical expression of SCD in 100 Egyptian patients. The Duffy phenotype expression was detected by indirect anti-globulin test while Duffy genotyping was conducted with polymerase chain reaction-restriction fragment length polymorphism-based assay. Results Total WBC count was strongly associated with Duffy genotype. WBCs were significantly higher in Duffy-positive patients (P = 0.002). No statistical significance was evident between individual measures of disease severity (pulmonary dysfunction, avascular necrosis, central nervous system dysfunction, kidney dysfunction, and leg ulcers) and Duffy genotype. Conclusion Our study suggests that RBC Duffy expression increases levels of WBCs in SCD patients and that Duffy genotype may not be a potential biomarker for end-organ damage in SCD.
Background and Objectives: Acute myeloid leukemia (AML) known as cancer of blood and bone marrow is regarded as the commonest acute leukemia in adult patients. characterized by uncontrolled proliferation of hematopoietic progenitor cells with arrest of maturation and disruption of normal hematopoiesis. CD200 is a protein belonging to the immunoglobulin superfamily, it has an immunosuppressant effect by interacting with its receptor (CD200R). Aim: The main aim of this study is to investigate the expression of CD200 on leukemic myeloid cells. Various molecular prognostic markers and other clinical and laboratory findings were studied in relation to CD200 expression. Patients and Methods: The present study was conducted on newly diagnosed AML patients attending the adult Hematology/Oncology Clinic of the National Cancer Institute. The expression of CD200 was determined by flow cytometry using anti-CD200 monoclonal antibodies. CD200 expression considered positive if ≥20% and negative if <20%. Results: CD200 positive expression was found in 62/104 (59.5%) patients, CD200 was more expressed in CD34 positive cases (P= 0.012) and cases with gum hyperplasia (P= 0.046). FLT3/ITD mutation and NPM mutation were less detected in AML patients with positive CD200 (p=0.045 and p= 0.036 respectively). We found a statistically significant relation between inv16 and CD200 positive expression (p=0.005). Conclusion: CD200 could be used as a biological biomarker in AML pathophysiology, and could be incorporated in the initial diagnostic workup in patients treated within clinical trials for the discovery of new therapy which target malignant leukemic cells without harming other cells in AML.
Purpose Doxorubicin (DOX), a chemotherapeutic agent, can disrupt testicular function leading to male infertility. The present study aimed to explore the possible protective effect of natural flavone, acacetin (ACA), and protease of Bacillus Cereus bacteria (B. Cereus) as well as the potential role of miR-155/SIRT1/FOXO1 network in DOX-induced testicular toxicity. Methods Twenty-eight male Wistar rats were randomly allocated into four groups and treated as follows: Control (1% DMSO 1 mL/kg/day; p.o), DOX (1mg/kg, i.p) on every other day for 21 days with a cumulative dose equal to 10 mg/kg throughout the experimental period, pre-treated groups received ACA (5 mg/kg/day, p.o) or B. Cereus protease (36 mg/kg/day, p.o) for a week prior DOX administration. Results DOX challenge reduced serum testosterone, and testicular 17β-hydroxysteroid dehydrogenase (17β-HSD). DOX exhibited a significant increase in testicular oxidative stress, inflammatory and apoptotic markers. Aberrant testicular miR-34c, a germ-specific miRNA, and miR-155 expressions were observed, along with decreased protein expression of sirtuin1 (SIRT1) dependent forkhead box 1 (FOXO1) acetylation inducing apoptosis. Besides, abnormal histopathological architecture and a marked reduction in the testicular expression of proliferating cell nuclear antigen (PCNA) were detected. ACA or protease administration significantly improves the histopathological and immunohistochemical pictures compared to DOX alone and renovated testicular functions. Nevertheless, treatment with protease was more effective than treatment with ACA in ameliorating DOX-induced testicular toxicity. Conclusion This study reveals the prophylactic role of these two regimens on male fertility by exhibiting antioxidant, anti-inflammatory, and anti-apoptotic effects against DOX-elicited testicular toxicity, possibly via modulating miR-155/SIRT1/FOXO1 network.
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