Mesenchymal stem cells (MSCs) therapy show different levels of effectiveness in the context of different types of liver damage, suggesting that the microenvironment of the injured liver is a key ...determinant for effective stem cell therapy. The objective was to assess the modulatory effect of hepatic stem cell niche components on the transplanted MSCs during liver injury induced by carbon tetrachloride (CCl
). Superparamagnetic iron oxide (SPIO)-labeled human MSCs were injected intravenously into mice treated with CCl
and subjected to hepatic macrophage-depletion. Liver tissues were collected at different intervals post transplantation for subsequent histopathological, morphometric, immunohistochemical, gene expression and ultrastructural studies. The homing of the transplanted MSCs was evidenced by tracing them within the niche by iron staining and immunohistochemical studies. MSCs differentiated into hepatocyte-like cells and intimal smooth muscle cells as evidenced by their expression of human albumin and α-smooth muscle actin with a concomitant increase in the level of mouse hepatocyte growth factor. A post transplantation reduction in the liver fibro-inflammatory reaction was found and was promoted by liver macrophages depletion. Thus, it could be concluded from the present study that prior manipulation of the microenvironment is required to improve the outcome of the transplanted cells.
Aim
As angiogenesis is an essential step for chorionic villi formation. Vascular endothelial growth factor (VEGF) is essential for endothelial cell proliferation. Endothelial nitric oxide synthase ...(eNOS) is a powerful playmaker in hypoxia‐induced angiogenesis. Thrombin‐activatable fibrinolysis inhibitor (TAFI) regulates both fibrinolysis and inflammation. Genetic alterations of these factors may lead to recurrent spontaneous abortion (RSA). We aimed to investigate the combined genetic variants of VEGF G‐1154A and two eNOS genetic variants: T‐786C promoter region and intron 4 variable number of tandom repeats in addition to TAFI C‐1040T among RSA patients.
Methods
The study included 50 patients with RSA and 50 healthy controls. Polymerase chain reaction and restriction fragment length polymorphism were used for genotyping.
Results
Both genetic alterations of eNOS confirmed at least a sixfold increase of RSA risk. Interestingly, they were associated with TAFI C‐1040Tgenetic variant in 21 patients, eight of them had both studied eNOS genetic alterations and TAFI C‐1040Tgenetic variant, while each eNOS genetic variant associated with TAFI C‐1040Tconfirmed an almost one and half fold increase risk of RSA.
Conclusion
These findings highlighted the role of eNOS and nitric oxide metabolism in RSA and opened the gate to investigate the interaction of vasoconstrictive and fibrinolytic inhibitor systems.
Recurrent spontaneous abortion (RSA) is defined as 3 or more consecutive pregnancy failures. Thrombin-activatable fibrinolysis inhibitor (TAFI) is a plasma zymogen that regulates both fibrinolysis ...and inflammation. The TAFI 1040C/T polymorphism could alter the circulating levels of TAFI with a reduced capacity to remove the fibrin clots from the circulation; therefore, it could be considered a molecular risk factor for RSA. The TAFI 1040C/T polymorphism was studied in 50 patients with RSA by polymerase chain reaction–restriction fragment length polymorphism technique and compared to 50 age- and gender-matched healthy volunteers as a control group to verify its possible association with RSA. In case group, the wild genotype (C/C) and heterozygous genotype (C/T) did not reduce the risk of RSA (odds ratio: 0.368 and 0.767, respectively), even when compared to the number of RSA (P = .71). A higher frequency of C allele in the control group and a higher frequency of T allele in the case group were observed but with no statistical significance. In conclusion, our study revealed that TAFI 1040C/T could not be considered a molecular predictive factor for RSA in Egyptians.
Background
Vitamin D is a fat-soluble vitamin that regulates calcium and phosphorous homeostasis to maintain a healthy mineralized skeleton. It can also influence immune responses and has ...immunomodulatory properties. Vitamin D receptor (VDR) is a nuclear receptor that mediates the activities of the hormonal form of vitamin D. VDR polymorphisms can alter immunity and susceptibility to infections by modulating VDR expression and vitamin D activity. This study aimed to investigate the levels of serum vitamin D as well as four VDR polymorphisms: FokI, BsmI, ApaI, and TaqI in fifty children admitted to intensive care unit (ICU) with a diagnosis of sepsis and one-hundred age- and sex-matched healthy children.
Methods
Vitamin D levels were measured in serum, in both patients and controls, using an enzyme-linked immunosorbent assay (ELISA) approach. VDR polymorphisms were also studied in both groups using specific restriction enzymes.
Results
Vitamin D levels were low in both patients and controls. Moreover, serum levels were unaffected by VDR polymorphisms, and their distribution was similar in both groups. Neither the need for mechanical ventilation or inotropic treatment nor the sepsis outcome was impacted by serum vitamin D levels or VDR polymorphisms.
Conclusion
In children admitted to pediatric ICU, neither vitamin D levels nor VDR polymorphisms were associated with sepsis. Further larger studies including different types of sepsis are recommended.
Highlights
• Vitamin D level was low in both pediatric septic ICU patients and age- and sex-matched healthy controls.
• Vitamin D levels were unaffected by VDR polymorphisms, and their distribution was similar in both groups.
• Neither the need for mechanical ventilation or inotropic treatment nor the sepsis outcome was impacted by vitamin D or VDR polymorphisms.
The risk of miscarriage is enhanced by genetic and environmental factors. Several studies indicated that there was an association between endothelial nitric oxide synthase activity, implantation, and ...the maintenance of pregnancy. However, the results of these studies remain controversial. The aim of our study was to determine the association between recurrent spontaneous miscarriage (RSM) in Egyptian women and two common polymorphisms of the endothelial nitric oxide synthase (eNOS) gene: intron 4 and T-786C. The study was conducted on a total number of 100 participants, 50 patients with RSM and 50 age-matched healthy controls. Patients and controls were investigated for the two polymorphisms. Genotyping of the eNOS intron 4 polymorphisms was performed by PCR assay. Our results indicated that there was a significant difference in the frequencies of the genotypes between case and control groups for the polymorphisms in both intron 4 (odds ratio (OR) 5.09, 95 % confidence interval (CI) 2.091–12.396,
P
< 0.001) and T-786C (OR 7.389, 95 % CI 3.043–17.942,
P
< 0.001). In our study, the eNOS polymorphisms (in intron 4 and T-786C) were found to be significantly associated with increased risk of RSM in Egyptian women.
Idiopathic thrombocytopenic purpura (ITP) is a heterogeneous immunologic disorder. Vitamin D has immune-modulatory effects. The pleiotropic effects of vitamin D are exerted via vitamin D receptor ...(VDR) and its genetic alterations could influence its functions. In our study, we measured the serum 25-hydroxyvitamin D levels in 98 Pediatric and Adolescent ITP patients, in addition to 100 apparently healthy controls. Genetic polymorphisms of the VDR gene FokI, BsmI, ApaI, and TaqI were tested using specific restriction enzymes for each polymorphism. Vitamin D deficiency in the studied Pediatric age was a dominant factor, but it was found not to be associated with Pediatric ITP. However, patients carrying the FokI CC genotype had statistically higher vitamin D levels compared with those carrying other genotypes (P=0.036). Patients who were carriers of the BsmI G allele had a nearly 2-fold higher risk of ITP (odds ratio: 2.203; 95% confidence interval: 1.467-3.309). Therefore, the BsmI polymorphism of VDR could be considered a molecular risk factor for ITP.
Deep vein thrombosis (DVT) is a common multi-factorial disease, with serious short- and long-term complications, and a potential fatal outcome. Many genes are involved in determining the ...interindividual variation in traits that define the onset and progression of disease, as well as the response to treatment. Several association studies have designed the relationship between factor XII C46T polymorphism and the risk of arterial and venous thrombosis. Some studies reported that FXII gene polymorphism is not associated with venous thrombosis, whereas other studies found an increased risk of venous thrombosis in carriers of a FXII-T variant. We constructed an age–gender–ethnic–matched case–control study including 52 DVT patients and 100 healthy volunteers. C46T polymorphism of the coagulation factor XII was carried out using allelic discrimination assay by real-time polymerase chain reaction for patients and controls, while plasma factor XII activity was detected by one-step clotting assay. FXII C46T genotyping in DVT patients revealed that 34.6% were heterozygous harboring the FXII-CT heterotype and 3.85% were homozygous; FXII-TT homotype, with no statistically significant difference in the distribution of the mutant genotypes between DVT patients and the control group. FXII activity was significantly reduced in DVT patients harboring the mutant genotypes. In the present study, FXII C46T gene polymorphism was not associated with increased risk of deep venous thrombosis.
Identifying leukemia stem cells (LSCs) is a challenge and a critical step in understanding their respective biology and may provide insights into a more efficient treatment of acute lymphoblastic ...leukemia (ALL). This cohort study aimed at detecting LSCs expressing CD19, CD34, and CD38
Low
in the bone marrow of 20 de novo Egyptian pediatric B-ALL patients at the time of the diagnosis and after the induction of chemotherapy. LSCs were detected in 80% of cases at the time of diagnosis and in 70% of the cases after the induction of chemotherapy. Patients were followed up for 12–18 months. No statistically significance difference was encountered between LSC-positive and LSC-negative patients as regards their clinical and laboratory data at the time of diagnosis. Furthermore, there was no statistically significant difference between the percentages of LSC-positive patients before or after induction of therapy. On follow-up, two patients died; they had residual LSCs after the induction therapy. However, the existence of LSCs did not affect the patient's 1-year disease-free survival rate. LSC may resist the traditional lines of treatment applied for childhood B-ALL; it may be used in minimal residual disease monitoring as well as being a target for new therapeutic lines to improve the outcome of treatment especially in patients with high-risk and relapsed ALL.
Sickle cell disease (SCD) is an autosomal recessive hemoglobinopathy characterized by increased cellular adhesiveness. Vaso-occlusion (VOC) is the most prevalent disease complication of SCD that ...could be altered by genetic factors. L-Selectin and integrin alpha 2 (ITGA2) are 2 adhesion molecules linked to vasculopathy and inflammation. The current study aimed at detecting the prevalence of genetic variants of L-selectin and ITGA2 as possible molecular modulators and novel therapeutic targets in a cohort of pediatric SCD patients. Genotyping was performed by polymerase chain reaction restriction fragment length polymorphism technique for 100 SCD patients and 100 age and gender-matched unrelated healthy controls. The homomutant genotype of ITGA2 C807T was significantly higher in SCD patients compared with controls (P=0.001) and confirmed almost a 3-fold increased risk of moderate and severe attacks of VOC. There are significant adverse effects caused by the polymorphisms of ITGA2, and hence Egyptian SCD patients could benefit from the targeted therapies specifically against ITGA2 to ameliorate the severe course of the disease and improve the quality of life. However, further studies of genotypes and expression levels of these adhesion molecules during the attacks of VOC are recommended.
Platelets have a central role in the pathophysiology of thrombosis. Adenosine diphosphate (ADP) plays a pivotal role as an agonist of platelet activation. Genetic polymorphisms of the P2Y12 ADP ...receptor might influence the activation of this receptor by ADP or the response of patients to platelet inhibitors. The present study was conducted on a total number of 80 participants, 40 patients were diagnosed with acute coronary syndrome and 40 sex and aged-matched healthy volunteers were included as controls. Platelet aggregation was assessed (before and 1 week after clopidogrel administration) and genotyping of the T744C genetic polymorphism of P2Y12 receptor gene was carried out using the restriction fragment length polymorphism polymerase chain reaction (PCR-RFLP) method. Platelet aggregation of the patients had a range of 54-183% before clopidogrel administration and had a range of 4-113% after its administration. Genotyping of the candidate gene revealed that 72.5% of the patients had a wild allele (TT), whereas 27.5% had a C allele (heterozygous CT, homozygous CC). On the contrary, 97.5% of controls had a wild allele (TT), whereas 2.5% had a C allele (heterozygous CT, homozygous CC). Our study elicited an association between the T744C polymorphism of the P2Y12 ADP receptor gene and platelet reactivity. Carrying the C allele at this position is associated with an increased platelet activation response to ADP.
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