Evaluation of De Ritis (AST/ALT), ALP/ALT, and AST/ALP ratios as prognostic factors in patients with acute ischemic stroke.

BACKGROUND: Stroke is one of the leading causes of disability worldwide. Recently, stroke prognosis estimation has received much attention. This study investigates the prognostic role of aspartate transaminase/alanine transaminase (De Ritis, AAR), alkaline phosphatase/alanine transaminase (ALP/ALT), and aspartate transaminase/alkaline phosphatase (AST/ALP) ratios in acute ischemic stroke (AIS). METHODS: This retrospective cohort study involved patients who experienced their first-ever AIS between September 2019 and June 2021. Clinical and laboratory data were collected within the first 24 hours after admission. Functional and mortality outcomes were evaluated 90 days after hospital discharge in clinical follow-up. Functional outcome was assessed by a modified Rankin Scale (mRS). The correlation between the laboratory data and study outcomes was evaluated using univariate analysis. In addition, regression models were developed to evaluate the predictive role of AST/ALP, ALP/ALT, and AAR ratios on the study outcomes. RESULTS: Two hundred seventy-seven patients (mean age 69.10 ± 13.55, 53.1% female) were included. According to univariate analysis, there was a weak association between 3-months mRS, and both AST/ALT (r = 0.222, P < 0.001), and AST/ALP (r = 0.164, P = 0.008). Subsequently, higher levels of these ratios and absolute values of AST, ALT, and ALP were reported in deceased patients. Based on regression models adjusted with co-variable (age, gender, underlying disease, and history of smoking) AST/ALT and AST/ALP ratios had a significant independent association with 3-month mRS (CI:1.37-4.52, p = 0.003, and CI: 4.45-11,547.32, p = 0.007, respectively) and mortality (CI: 0.17-1.06, adjusted R2 = 0.21, p = 0.007, and CI: 0.10-2.91, p = 0.035, adjusted R2 = 0.20, respectively). CONCLUSIONS: Elevated AST/ALP and AAR ratios at admission were correlated with poorer outcomes at 3 months in patients with first-ever AIS. Prospective studies in larger cohorts are required to confirm our findings and to evaluate further whether the AST/ALP and De Ritis ratios may represent a useful tool for determining the prognosis of AIS patients.

Combined Effect of Co-administration of Stromal Cell-Derived Factor-1 and Granulocyte-Colony Stimulating Factor on Rat Model of Alzheimer's Disease.

Introduction: Alzheimer's disease (AD) is a neurodegenerative disease that is characterized by amyloid plaque deposits, neuronal cell loss, and memory impairment. Granulocyte-colony stimulating factor (G-CSF) is a growth factor associated with AD improvement. Stromal cell-derived factor-1 (SDF-1) mediates therapeutic effects of G-CSF. This study investigated the effect of combination treatment of G-CSF and SDF-1 on amyloid plaque deposits, apoptosis, and behavior of AD rats. Methods: Intracerebroventricular amyloid-beta [Aß(1-42)] peptide was used to induce AD in Aß rats. There were six groups including naive control, sham-operated, Aß, Aß + G-CSF, Aß + SDF-1, and Aß + G-CSF + SDF-1. SDF-1 intra-cerebroventricular (ICV), G-CSF Subcutaneous (SC), or a combination of them were administered to Aß rats weekly for 2 months. The cognition and memory were assessed using the novel object recognition, passive avoidance, and Morris water maze tests. Next, rat brains were removed and the amyloid plaque and apoptosis were detected in the brain and hippocampus using immunohistochemistry and TUNEL assay, respectively. Results: The amyloid-beta and apoptotic cell levels dropped in groups receiving SDF-1 and G-CSF combination compared to the Aß group. Also, number of microglial cells increased significantly in the combination group compared to other treatment groups. Moreover, learning and memory were significantly improved in the combination group compared to the Aß groups (P < 0.05). Conclusion: SDF-1 and G-CSF combination therapy can offer a promising strategy for AD.

Enriched environment effect on lipopolysaccharide-induced spatial learning, memory impairment and hippocampal inflammatory cytokine levels in male rats.

Neuro-inflammation is responsible for cognitive impairments and neurodegenerative diseases such as Alzheimer's disease. In this study, we aimed to investigate the enriched environment (EE) effect on learning and memory impairment as well as on pro-inflammatory cytokines changes induced by lipopolysaccharide (LPS). LPS injection (1 mg/kg/i.p, days 1, 3, 5, and 7) was used to develop the animal model of neuro-inflammation. Twenty-eight male Wistar rats were used in the experiment and randomly divided into 4 groups: 1) sham (S), 2) sham + enriched environment (SE), 3) LPS (L), and 4) LPS + EE (LE). Two different housing conditions, including standard environment (SE) and enriched environment, were used. The Morris Water Maze (MWM) test was used to examine animals learning and memory. IL-1ß, IL-10, and TNF-α levels were measured in the brain using ELISA. We found that LPS significantly impaired learning and memory (p < 0.05) in the MWM task, but EE could significantly improve learning and memory impairment (p < 0.05). IL-1 and IL-10 levels dramatically increased in the LPS group (P < 0.05), whereas EE could decrease and increase IL-1ß and IL-10 values in the LPS + EE group (P < 0.05), respectively. TNF-α levels were traced but had not detectable values in the hippocampus. Thus, we can conclude that EE has healing effects on LPS induced neuro-inflammation and can improve learning and memory deficit; however, further studies are needed to support the findings of our study.

An insight of microRNAs performance in carcinogenesis and tumorigenesis; an overview of cancer therapy.

Importance of dysregulation and expression of microRNAs (miRNAs) has been confiemed in many disorders comprising cancer. In this way, different approaches to induce reprogramming from one cell type to another in oerder to control the cell normal mechanisem, comprising microRNAs, combinatorial small molecules, exosome-mediated reprogramming, embryonic microenvironment and also lineage-specific transcription agents, are involved in cell situation. Meaningly, besides the above factors, microRNAs are so special and have an impressive role in cell reprogramming. One of the main applications of cancer cell reprogramming is it's ability in therapeutic approach. Many insights in reprogramming mechanism have been recommended, and determining improvment has been aknolwged to develop reprogramming efficiency and possibility, permiting it to appear as practical therapy against all cancers. Conspiciously, the recent studies on the fluctuations and performance of microRNAs,small endogenous non-coding RNAs, as notable factors in carcinogenesis and tumorigenesis, therapy resistance and metastasis and as new non-invasive cancer biomarkers has a remarkable attention. This is due to their unique dysregulated signatures throughout tumor progression. Recognising miRNAs signatures capable of anticipating therapy response and metastatic onset in cancers might enhance diagnosis and therapy. According to the growing reports on miRNAs as novel non-invasive biomarkers in various cancers as a main regulators of cancers drug resistance or metastasis, the quest on whether some miRNAs have the ability to regulate both simultaneously is inevitable, yet understudied. The combination of genetic diagnosis using next generation sequencing and targeted therapy may contribute to the effective precision medicine for cancer therapy. Here, we want to review the practical application of microRNAs performance in carcinogenesis and tumorigenesis in cancer therapy.

Epigenetic profiling of MUTYH, KLF6, WNT1 and KLF4 genes in carcinogenesis and tumorigenesis of colorectal cancer.

Colorectal cancer (CRC) is distinguished by epigenetic elements like DNA methylation, histone modification, histone acetylation and RNA remodeling which is related with genomic instability and tumor initiation. Correspondingly, as a main epigenetic regulation, DNA methylation has an impressive ability in order to be used in CRC targeted therapy. Meaningly, DNA methylation is identified as one of most important epigenetic regulators in gene expression and is considered as a notable potential driver in tumorigenesis and carcinogenesis through gene-silencing of tumor suppressors genes. Abnormal methylation situation, even in the level of promoter regions, does not essentially change the gene expression levels, particularly if the gene was become silenced, leaving the mechanisms of methylation without any response. According to the methylation situation which has a strong eagerness to be highly altered on CpG islands in carcinogenesis and tumorigenesis, considering its epigenetic fluctuations in finding new biomarkers is of great importance. Modifications in DNA methylation pattern and also enrichment of methylated histone signs in the promoter regions of some certain genes like MUTYH, KLF4/6 and WNT1 in different signaling pathways could be a notable key contributors to the upregulation of tumor initiation in CRC. These epigenetic alterations could be employed as a practical diagnostic biomarkers for colorectal cancer. In this review, we will be discuss these fluctuations of MUTYH, KLF4/6 and WNT1 genes in CRC.