Hepatocellular carcinoma (HCC) is one of the most critical cancers; thus, novel therapeutical regimens are of great need. In this study, we investigated the effects of umbilical cord mesenchymal stem cells (UC-MSCs) derived exosomes on HepG2 cell line, and the underlying mechanism to control HCC proliferation, to identify the potential clinical role of exosomes as a novel molecular therapeutic target. Proliferation, apoptosis, and angiogenesis effects were assessed together with the cell viability evaluation by MTT assay in HepG2 cells at 24/48 h. with or without UC-MSCs-derived exosomes. Gene expressions of TNF-α, caspase-3, VEGF, stromal cell-derived factor-1 (SDF-1), and CX chemokine receptor-4 (CXCR-4) were measured by quantitative real-time PCR technique. Expression of sirtuin-1 (SIRT-1) protein was detected by western blot. Treatment of HepG2 cells with UC-MSCs-derived exosomes for 24 and 48 h. demonstrated a significant reduction of cells survival compared to the control group (p < 0.05). The SIRT-1 protein, and VEGF, SDF-1, CXCR-4 expression levels were significantly lower, TNF-α and caspase-3 expression levels were significantly higher in exosomal-treated HepG2 cells for 24 and 48 h. than those in the control group. Moreover, our findings documented that the anti-proliferative, apoptotic, and anti-angiogenic effects were achieved in a time-dependent manner in which more effects were determined after 48 h supplementation compared to 24 h (p < 0.05). UC-MSCs-derived exosomes exert anticarcinogenic molecular effects on HepG2 cells through the involvement of SIRT-1, SDF-1, and CXCR-4. Hence, exosomes would be a potential novel therapy regimen against HCC. Large-scale studies are recommended to verify this conclusion.
Tobacco use is responsible for millions of preventable deaths due to cancer. Nicotine, an alkaloid chemical found in tobacco was proved to cause chronic inflammation and oxidative stress. The transcription factor STAT1 induces the expression of many proinflammatory genes and has been suggested to be a target for anti-inflammatory therapeutics. The following study investigated the effect of Nicotine on STAT1 pathway and oxidative stress in rat lung tissue.Thirty rats were divided into 3 groups; group I considered as control, group II; its rats were daily injected with Nicotine at a dose of 0.4 mg/100 gm body for 8 successive weeks and group III; its rats were daily injected with Nicotine as group II, but the injection was stopped for another 4 weeks. STAT1α protein was assessed by immunohistochemistry, COX-2 and iNOS genes expression were evaluated by real time PCR and thiobarbituric acid reactive substances (TBARS) and total thiols were measured using spectrophotometric methods in the lung tissues of the rats.The results of the study revealed that group II rats had the highest expression of STAT1α protein and COX-2 and iNOS genes and oxidative stress in their lung tissues. Nicotine cessation for 4 weeks caused a marked reduction in the expression of STAT1α protein, COX-2 and iNOS genes and oxidative stress.Induction of STAT1 pathway and the increase in oxidative stress may be the mechanisms through which Nicotine may induce its harmful effects.
// Asmaa M. Zahran 1 , Sanaa Shaker Aly 2 , Amal Rayan 3 , Omnia El-Badawy 4 , Maged Abdel Fattah 5 , Arwa Mohammed Ali 5 , Hala M. ElBadre 6 and Helal F. Hetta 4 1 Clinical Pathology Department, South Egypt Cancer Institute, Assiut University, Assiut, Egypt 2 Clinical and Chemical Pathology Department, Faculty of Medicine, South Valley University, Qena, Egypt 3 Clinical Oncology Department, Faculty of Medicine, Assiut University, Assiut, Egypt 4 Medical Microbiology and Immunology Department, Faculty of medicine, Assiut University, Assiut, Egypt 5 Medical Oncology Department, South Egypt Cancer Institute, Assiut University, Assiut, Egypt 6 Medical Biochemistry Department, Faculty of Medicine, Assiut University, Assiut, Egypt Correspondence to: Amal Rayan, email: amal3774rayan@gmail.com Keywords: acute myeloid leukemia; CD34+CD38-LSCs; CD34+CD38-CD123+LSCs; disease free survival; overall survival Received: April 23, 2018 Accepted: July 31, 2018 Published: September 25, 2018 ABSTRACT Background and aim : Acute myeloid leukemia (AML) is one of the most common leukemias in adults. AML is generally regarded as a stem cell disease characterized by an accumulation of undifferentiated and functionally heterogeneous populations of cells, The aim of the present study was to identify leukemia stem cells in patients with AML and their correlations with treatment outcomes namely remission status, disease free survival, and overall survival. Results : The mean percentages of CD34 + CD38 - and CD34 + CD38 low/− CD123 + LSCs were 2.2± 0.4and 22.3± 2.6, respectively. The percentages of CD34 + cells, CD34 + CD38 - and CD34 + CD38 low/− CD123 + LSCs were significantly lower in AML patients with complete remission than those without complete response ( P <0.001, P <0.004, P <0.001 respectively). The mean OS of all study patients was 20.03±1.2 months while the median OS was 21 months (95% CI=18.32-21.48). The mean DFS was 16.96±1.02 months and the median was 18 months (95% CI=8.9-11.4). DFS and OS were significantly higher among those who achieved CR than those without CR. In addition, there were significant negative effects of WBCs, CD34 + cells, CD34 + CD38 - and CD34 + CD38 - CD123 + LSCs on DFS and OS. Patients and methods : We investigated 30 patients with newly diagnosed AML; all patients underwent complete history taking, and thorough physical and clinical examination, complete blood count. Peripheral smears and bone marrow aspirates were also examined. Cytochemistry and immunophenotyping of leukemic cells were performed routinely in bone marrow using monoclonal antibodies. Flow cytometry was used to analyze leukemia stem cells and their expression of CD123. Conclusion : Our study elucidated that CD34+CD38-LSCs, with or without CD123+LSCs phenotype was present in a significant proportion of AML patients and it could be responsible for resistance to traditional treatments, and high percentage of MRD that was translated into significantly high number of non CR, poor DFS, and OS.
Although remarkable developments have been made in the management of cardiovascular disease, myocardial infarction (MI) remains the most common cause of death worldwide. MI is an acute condition of myocardial cell death that occurs as a result of imbalance between the coronary blood supply and myocardial requirements. Lipid peroxidation and excessive production of reactive oxygen species (ROS), such as superoxide anions (O2•-) and hydrogen peroxide, play a major role in the mechanism of MI. ROS directly damage the cell membrane and cause cell necrosis. However, ROS also stimulate signal transfer to upregulate inflammatory cytokines, for example, tumor necrosis factor-α in the ischemic area and the neighboring myocardium. The aims of this article were: (a) to determine serum selenium (Se) and the cut-off value in acute MI patients and the correlation between serum Se and other cardiac biomarkers such as troponin, creatine kinase (CK), creatine kinase myocardial brand (CK-MB), C-reactive protein, and lipogram; and (b) to determine the most predictor risk factor of MI. The study was carried out on 120 individuals (60 patients and 60 controls). The patients presented to the Internal Medicine Department and Coronary Care Unit at Assiut University Hospital. The healthy controls were selected and matched for age and sex, and only those who were found to be in good health and free from any signs of chronic diseases or disorders were included. The main finding of this analysis that there is a statistical difference between patients and controls in serum Se as the mean Se level in patients was 80.3±20.5 and in controls it was 97.2±14.0 and P value of less than 0.001, Thus, serum Se is significantly low in MI patients. Also, there was no statistical difference in serum Se in terms of sex, smoking, accompanying diseases (diabetes or hypertension), or type of infarction. This study supports a significant association between deficient serum Se concentration with cut-off value of up to 84ng/ml and MI. Strikingly, the most predictor of MI is serum Se, followed by total cholesterol, diabetes mellitus, low-density lipoprotein, and hypertension.
Oxidized low-density lipoprotein (ox-LDL) has an important role in the genesis of coronary atherosclerosis. Lectin-like ox-LDL receptor 1 (OLR1) contributes to the uptake and internalization of ox-LDL. Genetic polymorphisms have been associated with coronary artery disease (CAD). Here we explore the association of plasma levels of ox-LDL and 3' UTR OLR1 (rs1050286) SNP with CAD risk and in-hospital adverse outcomes.A case-control study enrolled 192 patients with ST-segment elevation myocardial infarction (STEMI), 100 patients with unstable angina, and 100 healthy controls. Baseline, clinical characteristics, and risk scores of the patients were determined. Plasma ox-LDL and other biochemical variables were measured. All subjects are genotyped for OLR1 (rs1050286) by RT-PCR with TaqMan SNP genotyping assay.Plasma ox-LDL was higher with enhanced sensitivity and specificity in identifying patients with STEMI and was found as a significant independent risk factor for CAD in those two groups. Levels of ox-LDL were increased with increasing poor prognostic factors in STEMI patients that are associated with an increased incidence of some adverse events and in-hospital mortality. Elevated STEMI risk was associated with T allele of OLR1 (rs1050286) (odds ratio of 4.9, 95% CI: 2.6-9.4, p< 0.001). STEMI patients who have T allele exhibited higher risk scores, coronary multivessel narrowing, and elevated incidence of in-hospital major adverse clinical events.These results suggest that plasma ox-LDL, as well as T allele of ORL-1 (rs1050286), is associated with the increased risk for developing STEMI and the associated adverse clinical outcomes.
Objectives: Congenital heart defect (CHD) represents almost 33% of all major congenital deformities, representing a worldwide health problem. The aim of the study is to identify the value of lecithin, cephalin, sphingomyelin & other phospholipids screening in the pathogenesis and prognosis of CHDs and consequently improve their management.
Methods: A total of 89 child with CHDs were included [35 atrial septal defect (ASD), 27 ventricular septal defect (VSD) and 27 patent ductus arteriosus (PDA)] and 34 child as a control group. Biochemical analysis of the plasma levels of total and different component of phospholipids for both CHD and control group were done by colorimetry and two-dimensional thin layer chromatography. Assay of plasma L-carnitine level was done by ELISA for both patients and control group.
Results:The overall results of the present study revealed a significant reduction in the total phospholipids among CHD patients in comparison to the control group; also, a significant change in the phospholipid profile. A significant lower plasma L-carnitine levels in the CHDs group when compared with the control group (p < 0. 001).
Conclusions: Disturbed total and differential types of phospholipids &plasma L-carnitine levels occurs in children with CHDs. Moreover, cell-specific targeting of L-carnitine and phospholipid biosynthetic pathways might serve as a possible strategy for helping favorable outcome in management of CHDs.
Background:Liraglutide is an incretin mimetic agent that approved recently in type-2 diabetes.The use of vitamin D was reported to be associated with an improvement in diabetic neuropathy. The aim of the study:Evaluation of the effect of liraglutide and vitamin D each alone and in combination with each other on diabetic neuropathy induced by streptozotocin in rats. Materials and Methods:Five groups of Wistar rats were used in the experiment.Diabetic neuropathy was induced in groups 2, 3, 4, and 5 using a single intraperitoneal(i.p.) injection of streptozotocin(STZ) in a dose of 60 mg/kg.The third, fourth, and fifth groups were treated for 4 weeks with liraglutide (0.8 mg/kg), vitamin D (12 µg/kg), and combination of the 2 drugs, respectively.Then the behavioral tests were done (hot plate, tail-flick, paw withdrawal pressure, and the rotarod tests).Blood samples were used for assessment of blood glucose, tumor necrosis factor -α (TNF-α) and interleukin-Iβ(IL-Iβ).Malondialdehyde(MDA) and glutathione (GSH)were measured in the sciatic nerve homogenate. Results:Liraglutide caused significant improvement in the behavioral tests of the diabetic rats with a significant reduction in blood glucose, TNF-α, IL-1β, and malondialdehyde.Vitamin D caused mild improvement in the behavioral tests, inflammatory and oxidative stress markers.The combined use of liraglutide with vitamin D caused more improvement in diabetic neuropathy tests, inflammatory and oxidative stress markers. Conclusion:Liraglutide has a moderate neuroprotective, anti-inflammatory, and antioxidant effects in cases of streptozotocin-induced diabetic neuropathy which are enhanced by the addition of vitamin D.
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