ABSTRACT
Objectives: Studying the effect of melatonin pretreatment and ischemic preconditioning on renal ischemia-reperfusion injury (IRI). Materials and Methods: Forty-eight Wistar rats were randomized into six groups: control, sham operation, IRI (IRI in left kidney + right nephrectomy), IRI+ischemic preconditioning, IRI+Melatonin, and IRI+ischemic preconditioning+Melatonin groups. Melatonin (10 mg/kg) was intraperitoneally injected for 4 weeks before renal IRI. Ischemic preconditioning was performed by three cycles of 2 min-ischemia followed by 5 min-reperfusion period. A right nephrectomy was initially done and the left renal artery was clamped for 45 min. After 24 hr of ischemia-reperfusion, rats were decapitated. Kidney tissue samples were taken for histopathological assessment and the determination of kidney proinflammatory and anti-inflammatory cytokines, apoptotic protein caspase-3, oxidative stress markers, and activities of antioxidant enzymes. Serum creatinine and blood urea nitrogen (BUN) concentrations were measured for evaluation of renal function. Results: Renal IRI animals showed increased levels of creatinine, BUN, tumor necrosis factor-α (TNF-α), caspase-3, total nitrite/nitrate, and malondialdehyde (MDA), and decreased levels of interleukin-13 (IL-13), and activities of glutathione peroxidase (GPx) and superoxide dismutase (SOD). Melatonin pretreatment or ischemic preconditioning resulted in decreased creatinine, BUN, TNF-α, caspase-3, nitrite/nitrate, and MDA, and increased IL-13, GPx, and SOD, with improved histopathological changes. Combined melatonin and ischemic preconditioning showed more effective improvement in renal IRI changes rather than melatonin or ischemic preconditioning alone. Conclusion: Combined melatonin and ischemic preconditioning have better beneficial effects on renal IRI than applying each one alone.
ABSTRACT
Background: Schizophrenia (SCZ) is still a challenging, refractory, and severe disorder. It is not a fully understood disease with genetic and epigenetic susceptibility and about 80% substantial heritability. The CUB and Sushi multiple domains 1 (CSMD1) gene is implicated in neurogenesis, memory, immunity, neuropsychology, and monoamine metabolism. Thus, it is one of the powerful genes involved in the pathogenesis of SCZ. Purpose: To evaluate the possible role of the CSMD1 gene's mRNA expression and its serum protein as markers for the early diagnosis of the first-episode SCZ in familial high-risk (FHR) Egyptian children and young adults. Subjects and methods: This case-control study included 80 first-episode drug-naïve SCZ patients from FHR Egyptian children and young adults and 80 healthy participants, as controls, from the FHR-susceptible children and young adults but did not develop SCZ. In this study, the CSMD1 gene's mRNA expression and CSMD1 serum levels were measured in the peripheral blood, and these levels were correlated with the lipid profile of the study populations. Results: The CSMD1 gene's mRNA expression and its' protein levels were significantly decreased in the SCZ patients compared to controls. The receiver operating characteristic (ROC) curve analysis succeeded in distinguishing SCZ patients from those not having SCZ using cutoff points of ≤0.711 and ≤4.83 ng/mL for the CSMD1 gene's mRNA expression and serum protein level, respectively. At these levels, the diagnostic sensitivities were 93.75 and 91.25%; specificity was 92.5%; positive predictive value (PPV) were 92.6 and 92.4%; and negative predictive values (NPVs) were 93.7 and 91.4%, respectively. Also, the ROC curve analysis succeeded in discriminating those with suicidal tendencies. Conclusion: CSMD1 gene's mRNA expression might be a reliable and early diagnostic predictor of first-episode SCZ in the FHR Egyptian children and young adults.
ABSTRACT
BACKGROUND: Early diagnosis of ankylosing spondylitis (AS) is yet not elucidated, with a potential diagnostic glance of microRNAs (miRNAs). AIM: Study the expression profile of miRNA-451a and miRNA-125a in AS patients and their impact on disease activity and prognosis. METHODS: A cross-sectional study included 55 AS patients diagnosed according to modified New York criteria in 1984 with 55 matched healthy controls. History, clinical examination, and disease activity assessment with Bath ankylosing spondylitis disease activity index (BASDAI) were done. Full laboratory and radiological assessment along with expression profile of m iRNA-451a and miRNA-125a were tabulated and analyzed. RESULTS: Higher expression levels of miRNA-125a and lower of miRNA-451a in AS patients compared to controls. Furthermore, miRNA-125a expression was high in active AS patients compared to inactive patients and controls (7.0 ± 3.4 vs. 4.1 ± 2.1 vs. 2.6 ± 0.6, p < 0.001, respectively). miRNA-451a was significantly lower in active AS patients compared to inactive patients and controls (2.2 ± 1.1 vs. 4.1 ± 2.3 vs. 7.1 ± 4.5, respectively). Both miRNAs (miRNA-125a and miRNA-451a) had evident accuracy for AS diagnosis with areas under the curve (AUC) of 0.788 and 0.802, respectively. miRNA-125a had potential impact on AS activity with AUC of 0.777. Plasma levels of both miRNAs were able to distinguish AS patients with structural damage with AUCs 0.775 and 0.692, respectively. CONCLUSIONS: Both miRNA-451a and miRNA-125a were found to be of great value as sensitive noninvasive diagnostic, prognostic, and disease burden biomarker of AS patients in Egypt with suggested further studies for future therapeutic implications.
