PROSPECTIVE SINGLE CENTER ANALYSIS OF OUTCOME STEM CELLS TRANSPLANTS IN PATIENTS WITH CEREBRAL PALSY.

OBJECTIVE: Aim: To evaluate efficacy and safety of autologous bone marrow-derived mononuclear stem cell transplantation intrathecal in children with cerebral palsy. PATIENTS AND METHODS: Materials and Methods: 35 children have levels I-V cerebral palsy aged 8-months to 8-years-old were enrolled from September (2021-2022) at Iraqi private hospital. Gross Motor Function was assessed by a pediatrician and neurologist specialist, 5 mcg/kg/day of G-CSF subcutaneous single injection daily for three consecutive days. Bone marrow harvested from posterior iliac crest under light general anesthesia. Bone marrow mononuclear cells (BMMNCs) separation was performed using density gradient centrifugation with Ficoll, the cell viability checked by propidium iodide dye in a TALI machine (Invitrogen) in average 98%. The viable BMMNCs injected intrathecal in L4-L5 over a period of 5-10 min. RESULTS: Results: Males accounted for 57.14% (20/35) while female 42.86% (15/35), and main neurological symptoms included spastic disorder spastic disorder (quadriplegia 24 (68.6), tetraplegia 2 (5.7), diplegia 5 (14.28), hemiplegia4 (11.42)). Gross Motor Function Classification System and Gross Motor Function Measure-66 (GMFM-66) showed II 10 (28.58), III 11(31.42) and IV 14 (40). On mean follow-up of 3 months post-stem cell transplant improvement was observed in 80% cases. The improvement showed in gross motor function (6/8) p=0.01, and speech (2/4) p=0.04, neck holding (5/5) p=0.0003, sitting balance (4/4) p=0.04, postural tone (5/5) p=0.0003, as well as significant reduction in seizure frequency (2/3) p=0.04 and improvement in cognition (6/7) p=0.01 were observed. CONCLUSION: Conclusion: Stem cell therapy for cerebral palsy shows a significant positive effect on the gross motor function, without long adverse effects.

Notch1 ligand signaling pathway activated in cervical cancer: poor prognosis with high-level JAG1/Notch1.

OBJECTIVE: Notch signalings are regulated multiple cellular processes during cancer progression. We aimed to investigate the significance and prognostic value of expression of Notch1 and JAG1 in cervical cancer to determine whether they could serve as prognostic predictors. METHODS/MATERIALS: The expression of Notch1/JAGD1 was investigated by real-time PCR, western blot assay and its association with overall survival of patients was analyzed by statistical analysis. RESULTS: Notch1 and JAGD1 expression level were significantly elevated in cervical cancer in comparison to normal specimens and other types of Notch receptors and ligands. It is also proved that Notch1 and JAGD1 expression were to be associated with cervical cancer invasion, lymph node metastasis, and FIGO system. In addition, survival analysis proved that elevated Notch1 and JAGD1 expression were associated with poor overall survival of patients (P = 0.01, P = 0.02 log-rank test), respectively. CONCLUSIONS: The present data proved the over-expression of Notch1/JAGD1 and its association with tumor progression in human cervical cancer, which might be a potential valuable biomarker for cervical cancer and further studies need.

Role of NF-κß and oxidative pathways in atherosclerosis: cross-talk between dyslipidemia and candesartan.

PURPOSE: The objective of this study is to assess the effect of the candesartan on the progression of atherosclerosis through the downregulation of NF-κß and interference with oxidative pathway. METHODS: Twenty-four rabbits were assigned to three groups: control group fed normal diet; induced untreated group fed 1% cholesterol diet; and treated candesartan group also fed 1% cholesterol diet. Plasma lipid profiles were measured, and ELISA for plasma cytokines and chemokine was performed. Analyses of NF-κß and VCAM-1 were performed using Western blotting with RT-PCR for NF-κB activity at mRNA. Doppler ultrasound was used to evaluate aortic intima-media thickness, and atheroma was detected by H&E staining. Immunofluorescent staining was performed to confirm accumulation of monocytes and PMNs. RESULTS: Candesartan markedly reduced the levels of the plasma lipid profile including total cholesterol [TC], triglycerides [TG], and LDL-C, while significantly elevating levels in the plasma HDL-C, in addition to reducing cytokine (TNF-α, IL-6, IL-1ß) and chemokine levels (MCP-1). Also, it decreased the aortic malondialdehyde (MDA) concentration and elevated the aortic glutathione (GSH) level compared with untreated animals (P < 0.05). The triplex Doppler ultrasound study confirmed that the candesartan attenuated intima-media thickness at 6 months of study. All candesartan-treated rabbits showed significantly attenuated atherosclerosis lesions with reduced accumulation of monocytes and had significantly reduced VCAM-1 expression and NF-κß activity. CONCLUSION: Candesartan retards the progression of atherosclerosis via interference with NF-κß and oxidative pathways.