The protective effect of melatonin on chronic paradoxical sleep deprivation induced metabolic and memory deficit in rats.

BACKGROUNDS: Impaired sleep is independent risk factor of neurodegeneration and dementia. Chronic insomnia impairs melatonin (MEL) production that is directly proportionate to its duration. The underlying mechanisms linking sleep loss to dementia and the possible therapeutic effect of melatonin have not been fully elucidated. Previous research showed great controversy concerning the effects of paradoxical sleep deprivation (PSD) on body weight, serum lipoproteins, and inflammatory cytokines. GOALS: To examine the effect of chronic paradoxical sleep deprivation (PSD) with and without MEL supplementation on memory using RAWM, parameters of metabolic syndrome (MS), liver enzymes, serum cortisol, and inflammatory cytokines as well as liver, colon, and brain histopathology. METHODS: Forty rats were divided into four groups ten animals each; C: control, G: grid group, SD: sleep deprivation group, and SD+MEL sleep deprivation treated with melatonin. RESULTS: MEL supplementation reversed PSD-induced memory deficits (P<0.05), the elevation of serum cortisol (P<0.001), glucose (P<0.05), ALT (P<0.05), AST (P<0.001), TNF-alpha (P<0.001), IL-10 (P<0.01) and improved colon, liver, and brain architecture. Melatonin reduced body weight (P<0.05), total cholesterol, LDL-c, and triglycerides as well as increased HDL-c (P<0.001). CONCLUSION: MEL has a protective effect against chronic PSD-induced metabolic malfunction and cognitive deterioration by reducing stress, improving immunity, and maintaining colonic wall integrity.

Spastic Paraplegia 20 and Serine/Threonine Protein Kinase 31 Expression for the Detection of Colorectal Cancer.

BACKGROUND/AIMS: Genetic alterations, including changes in the expression of spastic paraplegia 20 (SPG20) and serine/threonine protein kinase 31 (STK31), may play an important role in the carcinogenesis of colorectal cancer (CRC). Identification of such changes is suitable for the recognition of tumors at an early stage, which would significantly improve patient survival. While recent studies have identified that SPG20 and STK31 expression levels increase in CRC tissues, their use as a biomarker is yet to be investigated. Our aim was to determine whether circulating SPG20 and STK31 mRNAlevels could help distinguish between patients with CRC and healthy individuals. Additionally, we aimed to analyze the correlation between SPG20 and STK31 expression patterns and the tumor stage in patients with CRC. METHODS: Venous blood samples from 50 patients with CRC and 50 healthy controls were used. RNA extraction was performed, and the mRNA expression of SPG20 and STK31 was determined using RT-qPCR. RESULTS: STK31 and SPG20 mRNA levels were significantly upregulated in patients compared to those in controls. There was a strong positive correlation between the expression of the two potential tumor biomarkers, STK31 and SPG20 (R=0.636, p=0.000). However, there was no significant relationship between the expression of STK31 or SPG20 and patient data, including demographic, clinical, pathological, and laboratory data. Additionally, there was a significant correlation between the expression level of STK31, but not SPG20, and patient disease-free survival (DFS) and overall survival (OS). CONCLUSION: Circulating mRNA levels of SPG20 and STK31 could be used as ideal noninvasive biomarkers for early diagnosis of CRC. They could assist the oncologist in recommending appropriate management strategies for individual patients.

Trimetazedine with hyperinsulinimea-euoglycemia, N-acetyl cysteine, and vitamin C: A new approach concept for management of aluminum phosphide poisoning.

Aluminum phosphide (AlP) is commonly used as a powerful suicidal tool. The exact mechanism of acute toxicity has not been well defined despite high mortality rates as well as its supportive treatment including rapid decontamination and institution of resuscitative measures. The current study aimed to investigate a new combination therapy using trimetazidine, N-acetyl cysteine, vitamin C, and hyperinsulinemia-euglycemia to manage acute AlP poisoning. Acute AlP-induced cardiotoxicity, hemodynamic changes, and hepatotoxicity were evaluated using electrocardiogram, creatinine kinase MB iso-enzyme, troponin-1, blood pressure, random blood glucose level, liver function tests, and histopathological changes in both the heart and liver in a rabbit model of AlP poisoning. The results showed that the new regimen therapy ameliorates the toxic effect of AlP with significant improvement in survival, cardiovascular and hemodynamic parameters in addition to histopathological changes. These results highlight the strong cardioprotective, antioxidant, hepatoprotective effects of the new combined therapy along with correction of hemodynamic changes and hyperglycemia as a potential target in the management of acute AlP poisoning.