Melatonin: a promising neuroprotective agent for cerebral ischemia-reperfusion injury

Cerebral ischemia-reperfusion (CIR) injury is initiated by the generation of reactive oxygen species (ROS), which leads to the oxidation of cellular proteins, DNA, and lipids as an initial event. The reperfusion process impairs critical cascades that support cell survival, including mitochondrial biogenesis and antioxidant enzyme activity. Failure to activate prosurvival signals may result in increased neuronal cell death and exacerbation of CIR damage. Melatonin, a hormone produced naturally in the body, has high concentrations in both the cerebrospinal fluid and the brain. However, melatonin production declines significantly with age, which may contribute to the development of age-related neurological disorders due to reduced levels. By activating various signaling pathways, melatonin can affect multiple aspects of human health due to its diverse range of activities. Therefore, understanding the underlying intracellular and molecular mechanisms is crucial before investigating the neuroprotective effects of melatonin in cerebral ischemia-reperfusion injury

Enhanced Anti-cancer Potency Using a Combination of Oleanolic Acid and Maslinic Acid to Control Treatment Resistance in Breast Cancer

Purpose: The phosphatidylinositol 3-kinase/AKT/mammalian target of rapamycin (PI3K/AKT/ mTOR) pathway is a complex intracellular metabolic pathway that leads to cell growth and tumor proliferation and plays a key role in drug resistance in breast cancer. Therefore, the anti-cancer effects of oleanolic acid (OA), maslinic acid (MA), and their combination were investigated to improve the performance of the treatment strategy. Methods: We investigated the effect of OA and MA on cell viability using the WST-1 method. The synergistic effect of the combination was analyzed by isobologram analysis. In addition, the effects of the two compounds, individually and in combination, on apoptosis, autophagy, and the cell cycle were investigated in MCF7 cells. In addition, changes in the expression of PI3K/AKT/mTOR genes involved in apoptosis, cell cycle and metabolism were determined by quantitative RT-PCR. Results: MA, OA, and a combination of both caused G0/G1 arrest. Apoptosis also increased in all treated groups. The autophagosomal LC3-II formation was induced 1.74-fold in the MA-treated group and 3.25-fold in the MA-OA-treated group. The combination treatment resulted in increased expression of genes such as GSK3B, PTEN, CDKN1B and FOXO3 and decreased expression of IGF1, PRKCB and AKT3 genes. Conclusion: The results showed that the combination of these two substances showed the highest synergistic effect at the lowest dose and using MA-OA caused cancer cells to undergo apoptosis. The use of combination drugs may reduce the resistance of cancer cells to treatment

MicroRNAs as Targets for Cancer Diagnosis: Interests and Limitations

MicroRNAs are small RNAs with ability to attach to the large number of RNA that regulate gene expression on post-transcriptional level via inhibition or degradation of specific mRNAs. MiRNAs in cells are the primary regulators of functions such as cell growth, differentiation, and apoptosis and considerably influence cell function. The expression levels of microRNAs change in human diseases, including cancer. These changes highlight their essential role in cancer pathogenesis. Ubiquitous irregular expression profiles of miRNAs have been detected in various human cancers using genome-wide identification techniques, which are emerging as novel diagnostic and prognostic cancer biomarkers of high specificity and sensitivity. The measurable miRNAs with enhanced stability in blood, tissues, and other body fluids provide a comprehensive source of miRNA-dependent biomarkers for human cancers. The leading role of miRNAs as potential biomarkers in human cancers is discussed in this article. In addition, the interests and difficulties of miRNAs as biomarkers have been explored

CAR T Cells: Cancer Cell Surface Receptors Are the Target for Cancer Therapy

Immunotherapy has become a prominent strategy for the treatment of cancer. A method that improves the immune system's ability to attack a tumor (Enhances antigen binding). Targeted killing of malignant cells by adoptive transfer of chimeric antigen receptor (CAR) T cells is a promising immunotherapy technique in the treatment of cancers. For this purpose, the patient's immune cells, with genetic engineering aid, are loaded with chimeric receptors that have particular antigen binding and activate cytotoxic T lymphocytes. That increases the effectiveness of immune cells and destroying cancer cells. This review discusses the basic structure and function of CAR-T cells and how antigenic targets are identified to treat different cancers and address the disadvantages of this treatment for cancer

Exploring potential serum levels of Homocysteine, interleukin-1 beta, and apolipoprotein B 48 as new biomarkers for patients with ischemic stroke

Background: Stroke is the second leading cause of death worldwide with heterogeneous characteristics. The subtypes of stroke are due to different pathophysiological regulations and causes. This study aimed to investigate the correlation of serum levels of apolipoprotein B 48, interleukin-1 beta and Homocysteine with BMI in patients with ischemic stroke (IS). Methods: Over one hundred controls (120) and an equal number of IS patients, including 31 women and 89 men, were recruited to participate in the case-control study conducted at Imam Reza Hospital (Tabriz, Iran) from February 2019 to March 2020. We measured serum levels of apolipoprotein B 48, interleukin-1 beta, and Homocysteine. Receiver operating characteristic analysis (ROC) was performed to evaluate the diagnostic value of these indices in patients and control groups. Results: The mean serum levels of apolipoprotein B 48, interleukin-1 beta, and Homocysteine, were significantly increased in the experimental group compared to the control group with a p-value of 0.001. The ROC curve analysis showed that the area under the curve for apo B48, IL-1 beta, hs-CRP, and Homocysteine serum levels were 0.94, 0.98, 0.99, and 1, respectively. Conclusions: The results of our current study show that the determination of serum levels of apolipoprotein B 48, interleukin-1 beta, and Homocysteine can potentially be used to monitor and diagnose IS patients. However, there was no statistically significant correlation between serum levels of apolipoprotein B 48, interleukin 1 beta and Homocysteine and BMI in the patient group. However, there was a statistically significant inverse correlation between serum levels of high-sensitivity C-reactive protein (hs-CRP) and BMI in the patient group.Research Vice-Chancellor of Tabriz University of medical sciences, Tabriz, IRAN [25992]The present study was supported by grants from the Research Vice-Chancellor of Tabriz University of medical sciences, Tabriz, IRAN grant no. 25992

Enhanced Anti-cancer Potency Using a Combination of Oleanolic Acid and Maslinic Acid to Control Treatment Resistance in Breast Cancer

Purpose: The phosphatidylinositol 3-kinase/AKT/mammalian target of rapamycin (PI3K/AKT/ mTOR) pathway is a complex intracellular metabolic pathway that leads to cell growth and tumor proliferation and plays a key role in drug resistance in breast cancer. Therefore, the anti-cancer effects of oleanolic acid (OA), maslinic acid (MA), and their combination were investigated to improve the performance of the treatment strategy. Methods: We investigated the effect of OA and MA on cell viability using the WST-1 method. The synergistic effect of the combination was analyzed by isobologram analysis. In addition, the effects of the two compounds, individually and in combination, on apoptosis, autophagy, and the cell cycle were investigated in MCF7 cells. In addition, changes in the expression of PI3K/AKT/mTOR genes involved in apoptosis, cell cycle and metabolism were determined by quantitative RT-PCR. Results: MA, OA, and a combination of both caused G0/G1 arrest. Apoptosis also increased in all treated groups. The autophagosomal LC3-II formation was induced 1.74-fold in the MA -treated group and 3.25-fold in the MA-OA-treated group. The combination treatment resulted in increased expression of genes such as GSK3B, PTEN, CDKN1B and FOXO3 and decreased expression of IGF1, PRKCB and AKT3 genes. Conclusion: The results showed that the combination of these two substances showed the highest synergistic effect at the lowest dose and using MA-OA caused cancer cells to undergo apoptosis. The use of combination drugs may reduce the resistance of cancer cells to treatment

Diagnostic Potential of Autophagy-5 Protein, Apolipoprotein B-48, and Oxidative Stress Markers in Serum of Patients with Early-Stage Ischemic Stroke

-OBJECTIVE: Strokes are among the leading causes of death worldwide and have different characteristics. Different physiopathological mechanisms characterize the -umerous subtypes of ischemic stroke (IS). In this study, we investigated the relationship between serum levels of autophagy-5 protein, apolipoprotein B-48, and oxidative stress markers in patients with ischemic stroke.-METHODS: For this study, 100 participants were recruited, of which 50 were patients with IS and 50 were healthy individuals. We conducted a case-control study at Imam Reza Hospital from March 2019 to April 2020. Serum levels of ATG5, apo B-48, and oxidative stress markers were determined in both groups. Our Receiver Operating Characteristic Analysis evaluated the additional diagnostic value of these factors in both groups. -RESULTS: Diabetes, smoking, age, sex, alcohol con-sumption, weight, and height did not differ significantly between the 2 groups (P > 0.05). However, the 2 groups had significant differences in hypertension and body mass in-dex (P 0.05). Fifty-four percent (27 patients) of patients with IS had an ischemic stroke in large vessels, while 46% (23 patients) had an ischemic stroke in small vessels. Serum levels of ATG5, apo B-48, and oxidative stress markers were higher in the case group than in the control group (P 0.0001).-CONCLUSIONS: In patients with IS, serum levels of ATG5, apoB-48, malonaldehyde, total oxidative stress, and total antioxidant capacity can be used as novel biomarkers to predict or treat the disease.This work was supported by a grant from the Vice Chancellor for Research, Tabriz University of Medical Sciences, Tabriz, IRAN. The grant number is IR.TBZMED.REC.1399.879.Tabriz University of Medical Sciences, Tabriz, IRAN [IR.TBZMED.REC.1399.879

Investigating the Expression level of miRNA-21, miRNA-155, miRNA-182, and miRNA-437 along with Inflammatory Markers in Cerebrospinal Fluid of Patients with Multiple Sclerosis

Background & objectives: Evidence suggests that microRNAs (miRNAs) are essential for immune cell differentiation and function. In addition, miRNAs play an essential role in regulating the expression of pro-inflammatory genes in neurons. Therefore, we investigated the relationship between miRNA expression and inflammatory markers in the CSF of patients with multiple sclerosis. Methods: RT-PCR analysis was performed on CSF samples from patients with multiple sclerosis (MS) and a control group to measure the expression level of miRNA-21, miRNA-155, miRNA-182, and miRNA-437. In addition, the levels of the inflammatory cytokines including IL-1β, IL-6, and TNF-α in CSF were measured using ELISA. A quantitative turbidimetric method was also used to measure high-sensitivity C-reactive protein (hs-CRP). Results: A significant difference was found in the expression level of miRNAs and inflammatory factors in the CSF of patients with MS compared with the control group (p<0.05). The results of receiver operating characteristic (ROC) analysis showed the area under the curve for miRNA-21 (AUC=0.97, p<0.0001), miRNA-182 (AUC=0.97, p<0.0001), and miRNA-155 (AUC=0.96, p<0.0001). The miRNA-155 level in CSF played a very important role in the accurate diagnosis of MS. Significant correlations were found between inflammatory cytokines and miRNA-21, miRNA-155, and miRNA-182, as well as an indirect and moderate correlation between miRNA-437 and hs-CRP. Conclusion: In MS patients, CSF levels of IL-1, IL-6, TNF-α, hs-CRP, and selected miRNAs can be used as biomarkers of CNS inflammation and neurodegenerative processes