216 research outputs found
Transcriptomic analysis of a 3D blood-brain barrier model exposed to disturbed fluid flow.
Cerebral aneurysms are more likely to form at bifurcations in the vasculature, where disturbed fluid is prevalent due to flow separation at sufficiently high Reynolds numbers. While previous studies have demonstrated that altered shear stress exerted by disturbed flow disrupts endothelial tight junctions, less is known about how these flow regimes alter gene expression in endothelial cells lining the blood-brain barrier. Specifically, the effect of disturbed flow on expression of genes associated with cell-cell and cell-matrix interaction, which likely mediate aneurysm formation, remains unclear. RNA sequencing of immortalized cerebral endothelial cells isolated from the lumen of a 3D blood-brain barrier model reveals distinct transcriptional changes in vessels exposed to fully developed and disturbed flow profiles applied by both steady and physiological waveforms. Differential gene expression, validated by qRT-PCR and western blotting, reveals that lumican, a small leucine-rich proteoglycan, is the most significantly downregulated gene in endothelial cells exposed to steady, disturbed flow. Knocking down lumican expression reduces barrier function in the presence of steady, fully developed flow. Moreover, adding purified lumican into the hydrogel of the 3D blood-brain barrier model recovers barrier function in the region exposed to fully developed flow. Overall, these findings emphasize the importance of flow regimes exhibiting spatial and temporal heterogeneous shear stress profiles on cell-matrix interaction in endothelial cells lining the blood-brain barrier, while also identifying lumican as a contributor to the formation and maintenance of an intact barrier
Lymphocyte subtype dysregulation in a group of children with simple obesity
Background: Obesity as a global public health problem is increasing in prevalence. Reports showed that obese children are more liable to infection than lean ones; it was claimed that obese subjects have altered peripheral blood total lymphocyte counts in addition to reduced lymphocyte proliferative response to mitogen stimulation as well as dysregulated cytokine expression.Objective: This study aimed to evaluate the effect of childhood obesity on cell mediated immunity as indicated by peripheral blood lymphocyte phenotyping.Methods: We enrolled 30 school-aged children (mean age 10±3.27 years). They comprised two groups; 20 obese children with a mean body mass index (BMI) of 39.2± 12.5 and 10 matched control subjects with mean BMI of 18.4± 1.9. They were subjected to detailed anthropometric evaluation including weight, height, and waist hip ratio in addition to calculation of BMI, complete blood counting, and flow cytometric assessment of T-helper (CD4), T-cytotoxic/suppressor (CD8), and natural killer (CD56) cell counts .Results: The absolute lymphocyte (CD3) and natural killer cell (CD56) counts were comparable in both groups. However, the CD4%, CD8%, CD4/CD8 ratio were significantly lower in the obese children (p=0.02, 0.03, 0.015 respectively). A significant negative correlation could be elicited between the CD4 count and bodyweight, BMI, and hip waist ratio (p = 0.00); the same was observed for CD4/CD8 ratio (p = 0.00). On the contrary, CD8 correlated positively to the bodyweight, BMI, and waist hip ratio (p = 0.00 for each) .Conclusion: Obesity has an impact on lymphocytic subset counts and further studies are needed to assess its effect on their function.Keywords: obesity, children immunology; CD markers; lymphocytes; BM
CXCR 3 expression on CD4+T cells and in renal tissue of pediatric systemic lupus erythematosus patients
Background: Pediatric systemic lupus erythematosus (pSLE) accounts for about 20% of all cases of Systemic Lupus Erythematosus (SLE), with nephritis occurring in approximately 50% of the patients. Objective: to evaluate the expression of CXCR3 in the kidneys and on CD4+ T cells in pSLE. Methods: This study was conducted on 45 patients with pSLE following up at the Allergy and Immunology Clinic, Childrenâs Hospital, Ain Shams University and 45 age and sex matched healthy children as a control group. Medical history, clinical examination and routine laboratory investigations for assessment of disease activity were done for all patients, the frequency of CXCR3, CD4+ T cells was determined in all patients and controls. Twenty-five Paraffin blocks of patients with lupus nephritis (LN) (available at the time of the study) underwent immunohistochemistry staining for the frequencies of Chemokine C receptor (CXCR3). Results: The absolute level and percentage of serum CD4+CXCR3+ were significantly lower among our patients as compared to healthy controls. A significant direct correlation was found between serum CD4+CXCR3+ and both the lymphocytic count and quantitative Systemic Lupus erythematosus disease activity index (SLEDAI), as well as a significant inverse correlation between it and 24 hours urinary proteins. Variable degrees of CXCR3expression seemed to have no impact on laboratory tests, British Isles Lupus Assessment Group (BILAG) score and cumulative doses of Immunosuppressives. Conclusion: Serum CD4+CXCR3+ and not renal CXCR3 may be a potential marker of LN activity
Wastewater Reclamation in Major Jordanian Industries: A Viable Component of a Circular Economy
Water scarcity remains the major looming challenge that is facing Jordan. Wastewater reclamation is considered as an alternative source of fresh water in semi-arid areas with water shortage or increased consumption. In the present study, the current status of wastewater reclamation and reuse in Jordan was analyzed considering 30 wastewater treatment plants (WWTPs). The assessment was based on the WWWTPsâ treatment processes in Jordan, the flowrates scale, and the effluentsâ average total dissolved solid (TDS) contents. Accordingly, 60% of the WWTPs in Jordan used activated sludge as a treatment technology; 30 WWTPs were small scale (<1 Ă 104 m3/day); and a total of 17.932 million m3 treated wastewater had low TDS (<1000 ppm) that generally can be used in industries with relatively minimal cost of treatment. Moreover, the analysis classified the 26 million m3 groundwater abstraction by major industries in Jordanian governorates. The results showed that the reclaimed wastewater can fully offset the industrial demand of fresh water in Amman, Zarqa, and Aqaba governorates. Hence, the environmental assessment showed positive impacts of reclaimed wastewater reuse scenario in terms of water depletion (saving of 72.55 million m3 groundwater per year) and climate change (17.683 million kg CO2Eq reduction). The energy recovery assessment in the small- and medium-scale WWTPs (<10 Ă 104 m3/day) revealed that generation of electricity by anaerobic sludge digestion equates potentially to an offset of 0.11â0.53 kWh/m3. Finally, several barriers and prospects were put forth to help the stakeholders when considering entering into an agreement to supply and/or reuse reclaimed water
Membrane endothelial protein C receptor expression in renal tissue of pediatric lupus nephritis patients
Background: Lupus nephritis (LN) is more common and more severe is pediatric systemic lupus erythematosus (pSLE). Endothelial protein C receptor (EPCR) is an inducer of anti-apoptotic pathways in endothelial cells. Recent studies have taken elevated anti-injury biomarkers as EPCR into consideration regarding their roles to antagonize LN.Objectives: to evaluate the membrane expression of endothelial protein C receptor (mEPCR) in the renal microvasculature in pediatric patients with LN.Methods: This study was conducted on 25 patients with pSLE following up at the Allergy and Immunology Clinic, Childrenâs Hospital, Ain Shams University. The 25 patients have LN proved by a previous renal biopsy. Medical history, clinical examination and routine laboratory investigations for assessment of disease activity were done for all patients. Paraffin blocks of patientsâ renal biopsies were subjected to immunohistochemistry staining for the frequency of mEPCR.Results: mEPCR was mainly expressed in the endothelium of the peritubular capillaries. Our results showed that an equal number of patients had nil and mild marker expression (8 patients each, 32%) while 9 patients (36%) showed moderate/strong marker expression. We found that 9 out of 10 (90%) of patients with class II had nil/mild marker expression, 5 patients out of 9 (55.5%) with class III had mild/moderate marker expression, while 5 patients 0ut of 6 (83.3%) with class IV and V had moderate/strong marker expression. We only found a significant statistical difference between the different degrees of mEPCR expression regarding 24 hours urinary proteins. No statistical significance was found between the different degrees of mEPCR expression and different immuno-suppressive therapy dose/kg or renal outcome using the renal British Isles Lupus Assessment Group (BILAG) score; in spite that most of the patients who got improved had nil/mild marker expression.Conclusion: mEPCR -bearing a statistically significant difference in relation to different LN classes- showed more expression in the more aggressive classes; a finding which might suggest a contribution of the endothelium of the renal parenchyma to the pathophysiology of more progressive LN. Hence the tissue marker might emerge as a potential new therapeutic target in the search for more selective treatment for SLE.Keywords: p SLE, mEPCR, renal biopsy, immunohistochemistry, BILAG, lupus nephriti
MSCâextracellular vesicle microRNAs target host cell-entry receptors in COVID-19 : in silico modeling for in vivo validation
The authors acknowledge technical and financial support from the Ministry of Education and the University of Hafr Al Batin, Saudi Arabia. The authors also thank AlMaarefa University, Riyadh, Saudi Arabia, for supporting this research.Peer reviewe
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