Phenotypic Analysis of Circulating Myeloid Derived Suppressor Cells and Their Subpopulations in Egyptian Females with Breast Cancer: A Single-Centre Case-Control Study.

BACKGROUND: Myeloid-derived suppressor cells (MDSC) are immature myeloid cells with suppressive function that has been thoroughly documented in the setting of cancer. Our purpose was to evaluate levels of MDSC and their subsets in a cohort of Egyptian patients with breast cancer. METHODS: Evaluation of peripheral blood total MDSC and its subset was done using multicolor flowcytometry in 30 malignant, 10 benign breast tumor patients and 10 healthy control females. RESULTS: BC patients had higher total MDSC levels compared to controls (p= 0.01) particularly the Monocytic MDSC (M-MDSC) and abnormal MDSC subsets (p = 0.001 and p <0.001, respectively). A tumor size > 2 cm exhibited significantly higher granulocytic MDSCs (G-MDSCs) compared to tumor size < 2 cm (p= 0.02) whereas abnormal MDSCs were significantly higher in patients with a tumor size < 2 cm (p = 0.037). CONCLUSION: MDSC and its subsets can be used as a prognostic marker of tumor size as well as a potential targets for treatment in breast cancer patients.

Role of dexmedetomidine in modifying immune paralysis in patients with septic shock: randomized controlled trial.

BACKGROUND: Immune paralysis can be defined as a hypoinflammatory state associated with the incapacity of the immune system to release proinflammatory mediators despite the clearance of pathogens by antimicrobials. Persistent immune paralysis leads to failure to eradicate primary infections with a substantial increase in the risk of multiorgan dysfunction and mortality. The state of immune paralysis is caused mainly by the diminished ability of monocytes to release proinflammatory cytokines in response to endotoxin. This phenomenon is known as endotoxin tolerance. This study aimed to assess the role of dexmedetomidine in modifying immune paralysis in septic shock patients. METHODS: Twenty-four patients with septic shock were randomized into two groups of 12 patients. A continuous intravenous infusion of dexmedetomidine started at 0.15 µg kg-1 hr-1 and adjusted by 0.15 µg kg-1 h-1 to a maximum of 0.75 µg kg-1 h-1 (10 ml h-1), while midazolam was started at 1 mg h-1 (2 mL hr-1) and adjusted by 1 mg h-1 to a maximum of 5 mg h-1 (10 mL h-1). All infusions were adjusted by increments of 2 mL/hr-1 to maintain blinding. Serum levels of CD42a+/CD14+, HLADR+/CD14+, CRP, IL-6, IL-10 and TNF-α were measured at baseline (T1), 12 h (T2), and 24 h (T3). RESULTS: Treatment with dexmedetomidine yielded no significant difference in CD42a+/CD14+, HLADR+/CD14, CD24b-MFI, HLADR-MFI, IL6 and TREM1 at all time points when compared with midazolam treatment. There was no significant difference in TLR levels between the two groups. Cardiac output in the dexmedetomidine group showed a significant decrease at 6, 12 and 24 h (P = 0.033, 0.021, and 0.005, respectively) compared with that in the midazolam group. CONCLUSION: Our results indicated that dexmedetomidine did not affect CD42a+/CD14+ and HLA-DR+/CD14+ expression in septic patients. Furthermore, cytokine production and inflammatory biomarkers did not change with dexmedetomidine infusion. Trial registration Clinical trial.gov registry (NCT03989609) on June 14, 2019, https://register. CLINICALTRIALS: gov .

Importance of circulating monocyte subpopulations and Fcγ receptors in immune thrombocytopenia.

Monocytes have been linked to the pathogenesis of immune thrombocytopenia (ITP) because of their role in autoantibody-mediated platelet phagocytosis. However, monocytes constitute unique populations with major differences in expression for surface Fcγ receptors (FcγRs). Thus, we evaluated monocytes in whole blood samples from patients with newly diagnosed and chronic ITP. Monocyte subpopulations were identified phenotypically by flow cytometry and defined according to the surface expression of CD14 (lipopolysaccharide receptor) and of CD16 (low-affinity Fcγ receptor III) into classical (CLM), intermediate (INTM) and nonclassical (non-CLM) monocytes. We also examined the expression of FcγRI/CD64 and FcγRIII/CD16 by monocyte subpopulations. Newly diagnosed patients showed a decrease in non-CLM, expressed as a relative percentage of total monocytes compared with controls and chronic ITP patients. Both non-CLM and INTM of newly diagnosed patients closely correlated with platelet count. These monocyte subpopulations showed significantly enhanced CD64 expression in newly diagnosed patients. On the contrary, patients with chronic ITP presented higher non-CLM in percentage than controls and concomitant lower CLM and total monocytes, in percentage and number. The expression of CD64 was increased by all monocyte subpopulations, CLM, INTM, and non-CLM in chronic patients. In conclusion, differences in monocyte subpopulations, together with enhanced expression of FcγRI/CD64 are evident in patients with ITP.

Vanillin attenuates thioacetamide-induced renal assault by direct and indirect mediation of the TGFß, ERK and Smad signalling pathways in rats.

Inflammation and fibrosis are two pathological features of chronic kidney disease (CKD). Renal fibrosis is considered to be one of the most important conditions, as it may be the result of excessive extracellular matrix protein production and deposition, or prolonged exposure to nephrotoxic substances or drugs. Unfortunately, no suitable therapies or medications are currently available to prevent renal fibrosis. We conducted this study for the evaluation of the protective potential of vanillin by reversing TAA (250 mg/kg TAA for 6 weeks) induced renal injury in rats. The concentrations of the proteins tumour necrosis factor alpha (TNFα), interleukin-6 (IL-6), extracellular signal regulated kinase 1/2 (Erk1/2), and transforming growth factor beta-1 (TGF-ß1) in kidney tissues were assessed using ELISA. Kidney Injury Molecule-1 (KIM-1) and mothers against decapentaplegic homologue 2, 3 (SMAD 2, 3) expressions were evaluated using real time PCR. We also estimated the expression of α-smooth muscle actin (α-SMA) using immunohistochemistry. Treatment with vanillin (100 mg/kg) significantly ameliorated kidney Injury and improved the kidney function. Vanillin treatment also significantly decreased the malondialdehyde (MDA) content, and elevated glutathione peroxidase (GPx) and catalase (CAT) activities in kidney tissues. Vanillin also reduced α-SMA renal expression and TNFα, IL-6, TGF-ß1, and Erk1/2 renal levels. Vanillin significantly decreased the expression of the genes encoding KIM-1 and SMAD 2, 3 and ameliorated histological abnormalities in kidney architecture. Our molecular docking findings showed that vanillin has a good binding mode inside TGF-ß type I receptors (ALK5) biding site.

The Role of Prebiotics and Probiotics as an Adjuvant Therapy in Children with Idiopathic Relapsing Nephrotic Syndrome: A Prospective Open-label Clinical Trial.

Idiopathic nephrotic syndrome (INS) is the most common cause of NS in children. It is characterized by the existence of edema, proteinuria, and hypoalbuminemia, as well as repeated relapses. The etiology remains unknown, but new evidence for its pathogenesis relates to the dysfunction of T-regulatory (T-reg) cells, which could be caused by dysbiosis of the gut microbiota. Our study aimed to investigate the effect of prebiotics and probiotics as adjuvant therapies for children with relapsing INS. The study was designed as a prospective open-label randomized clinical trial involving 30 children diagnosed with relapsing INS. The children were randomly divided into two groups. Group 1 was treated with prednisone only, and Group 2 was treated with prebiotics and probiotics in addition to prednisone. Fresh stool samples were collected from the children. Lactobacillus species were isolated and identified by conventional microbiological methods. The total number of Lactobacillus species was counted for each stool sample. The population of T-reg cells in the peripheral blood mononuclear cells was analyzed using flow cytometry. Children treated with prebiotics and probiotics in addition to steroids showed a significant increase in T-reg cells (CD4+/CD25+/FOXp3+) in the peripheral blood and a higher count of Lactobacillus species in their stool alongside a significant decrease in the rate of relapses in this group compared with Group 1. Treatment with prebiotics and probiotics signi-ficantly increased T-reg cells and decreased the rate of relapse in INS.

The aquaporin4-IgG status and how it affects the clinical features and treatment response in NMOSD patients in Egypt.

BACKGROUND: In Egypt, the characterization of Neuromyelitis Optica Spectrum Disorder (NMOSD) is lacking. OBJECTIVES: To determine the demographics, clinical features, aquaporin4 antibodies (AQP4-IgG) status, and neuroimaging of Egyptian NMOSD patients. METHODS: Retrospective analysis of 70 NMOSD patients' records from the MS clinic, Kasr Alainy hospital, between January 2013 and June 2018. RESULTS: Patients' mean age was 34.9 ± 9.2 years, and the mean at disease onset was 28.9 ± 10.5 years. Fifty-nine patients had an initial monosymptomatic presentation. AQP4-IgG was measured using either enzyme-linked immunosorbent assay (ELISA) (22 patients) or cell-based assay (CBA) (34 patients). Six and 29 patients had positive results, respectively (p < 0.001). 84% had typical NMOSD brain lesions. Longitudinally extensive myelitis was detected in 49 patients, and 9 had either short segments or normal cords. Treatment failure was higher in seropositive patients. Rituximab significantly reduced the annualized relapse rate (ARR) compared to Azathioprine with a percentage reduction of (76.47 ± 13.28) and (10.21 ± 96.07), respectively (p = 0.04). Age at disease onset was the only independent predictor for disability (p < 0.01). CONCLUSION: Treatment failure was higher in seropositive patients. However, there was no difference in clinical or radiological parameters between seropositive and seronegative patients. Patients, who are polysymptomatic or with older age of onset, are predicted to have higher future disability regardless of the AQP4-IgG status.