Angioregulatory role of miRNAs and exosomal miRNAs in glioblastoma pathogenesis.

Glioblastoma (GB) is a highly aggressive cancer of the central nervous system, occurring in the brain or spinal cord. Many factors such as angiogenesis are associated with GB development. Angiogenesis is a procedure by which the pre-existing blood vessels create new vessels that play an essential role in health and disease, including tumors. Also, angiogenesis is one of the significant factors thought to be responsible for treatment resistance in many tumors, including GB. Hence, an improved understanding of the molecular processes underlying GB angiogenesis will pave the way for developing potential new treatments. Recently, it has been found that microRNAs (miRNAs) and exosomal miRNAs have a crucial role in inducing or inhibiting the angiogenesis process in GB development. A better knowledge of the miRNA's regulation pathway in the angiogenesis process in cancer offers unique mechanistic insight into the mechanism of tumor-associated neovascularization. Because of advancements in miRNA characterization and delivery methods, miRNAs can also be employed in clinical settings as potential biomarkers for anti-angiogenic treatment response as well as therapies targeting tumor angiogenesis. The recent finding and insights about miRNAs' angioregulatory role and exosomal miRNAs in GB are provided throughout the review. Also, we discuss the new concept of miRNAs-based therapies for GB in the future.

The role of lovastatin in the attenuation of COVID-19.

The mounting evidence regarding the pathogenesis of COVID-19 indicated that the cytokine storm has an axial role in the severity of this disease, which may lead to thrombotic complications, acute respiratory distress syndrome (ARDS), and myocardial damage, among other consequences. It has recently been demonstrated that statins are known to have anti-viral, anti-inflammatory, anti-thrombotic, and immunomodulatory features; however, their advantage has not been evaluated in COVID-19. This study aimed to investigate the protective effects of lovastatin in intensive care unit (ICU) patients with COVID-19. The case-control study consists of 284 ICU patients, which classified into three groups as follows: 1) the patients who no received lovastatin as a control (92 patients), 2) patients received 20 mg per day lovastatin (99 patients), and 3) patients received 40 mg per day lovastatin (93 patients). Each group's demographic and clinical parameters, along with CRP, interleukin (IL)-6, IL-8 levels, and mortality rate, were studied in three-time points. The results showed that there was no statistically significant difference between our study groups in terms of age and sex. (P > 0.05). Besides, in patients, receiving lovastatin the CRP, IL-6, IL-8 levels were significantly decreased from T1 to T3 than to the control group. Our results also showed that the use of lovastatin in COVID-19 patients significantly reduced the length of hospitalization in the ICU compared with the control group. In addition, our results showed that the mortality rate in patients receiving lovastatin was lower when compared to the control group; however, this difference was not statistically significant. Since the cytokine storm is a significant factor in the pathology of SARS-CoV-2, our findings highlighted the potential use of lovastatin to mitigate the inflammatory response induced by SARS-CoV-2 infection.

A possible pathogenic correlation between neutrophil elastase (NE) enzyme and inflammation in the pathogenesis of coronavirus disease 2019 (COVID-19).

A growing body of evidence indicates that neutrophil elastase (NE) is involved in the pathogenesis of respiratory infectious diseases, such as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). This study aimed to analyze the dynamic changes in serum levels of NE associated with inflammation, disease activity, and mortality rate in patients with COVID-19. We measured the serum concentrations of NE, C-Reactive protein (CRP), interleukin (IL)- 4, IL-6, IL-8, IL-10, and vitamin D levels in 83 ICU and 69 non-ICU patients compared with 82 healthy subjects (HS) in three-time points (T1-T3). Serum levels of NE, IL-6, IL-8, and CRP in ICU and non-ICU patients were significantly higher than HS (P < 0.001) in three-time points. Also, serum levels of NE, IL-6, IL-8, and CRP in ICU patients were significantly higher than in non-ICU patients (P < 0.05). On the day of admission (T1), the levels of NE, CRP, IL-6, IL-8 were gradually decreased from T1 to T3. At the same time, IL-4 and IL-10 were gradually increased from T1 to T2 and then reduced to T3. Further analyses demonstrated that the levels of NE, IL-6, and IL-8 in deceased patients were significantly higher than in recovered patients (P < 0.05). The ROC curve analysis demonstrated that markers, including NE, IL-6, and IL-8, were valuable indicators in evaluating the activity of COVID-19. Overall, our results signify the critical role of NE in the pathogenesis of COVID-19, and also, further support that NE has a potential therapeutic target for the attenuation of COVID-19 severity.

Is melatonin associated with pro-inflammatory cytokine activity and liver fibrosis in non-alcoholic fatty liver disease (NAFLD) patients?

AIM: The associations between serum levels of melatonin and concentrations of tumor necrosis factor (TNF)-a and interleukin (IL)-6 were assessed among patients with different degrees of non-alcoholic fatty liver disease. BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) has become a very common worldwide disease. METHODS: In this cross-sectional study, adult patients diagnosed with fatty liver disease by Fibroscan evaluation were included if they met the inclusion/exclusion criteria for NAFLD. The participants were categorized into the three following groups: 1) fibrosis> 9.1KP and steatosis >290 dbm; 2) fibrosis: 6-9.0 KP and steatosis 240-285; and 3) fibrosis < 5.8 KP and steatosis<240 dbm. Post-fasting, 5 ml of venous blood was collected for laboratory assessment, and a questionnaire including demographic, anthropometric, laboratories and clinical data was completed. RESULTS: A total of 97 participants were included. The mean age was 42.21±11 years, and 59 patients (60.0%) were female. Melatonin levels as well as pro-inflammatory cytokines levels were correlated with advancing fibrosis and steatosis in univariate analysis. A significant association was observed between these cytokines and advancing fibrosis, severe steatosis levels, and melatonin concentrations. Furthermore, in the multiple linear regression model, melatonin levels showed a significant association with these cytokines. CONCLUSION: Melatonin may have protective effects on tissue injury during advancing liver fibrosis via cytokines modulation. Therefore, it can be considered as a potential therapeutic management strategy for NAFLD.

The pathogenic, therapeutic and diagnostic role of exosomal microRNA in the autoimmune diseases.

Exosomes are a nano-vesicle surrounded by a bilipid layer that can release from almost all cells and could be detected in tissues and biological liquids. These vesicles contain lipids, proteins, and nucleic acids (including DNA, mRNA, and miRNA) inside and on the exosomes' surface constitute their content. Exosomes can transfer their cargo into the recipient cell, which can modify recipient cells' biological activities. Recently it has been deciphering that the miRNA pattern of exosomes reveals the cellular pathophysiological situation and modifies various biological processes. Increasing data regarding exosomes highlights that the exosomes and their cargo, especially miRNAs, are implicated in the pathophysiology of various disorders, such as autoimmune disease. The current evidence on the deciphering of mechanisms in which exosomal miRNAs contributed to autoimmunity was indicated that exosomal miRNA might hold information that can reprogram the function of many of the immune cells involved in autoimmune diseases' pathogenesis. In the present study, we summarized the pathogenic role of exosomal miRNAs in several autoimmune diseases, including myasthenia gravis (MG), psoriasis, inflammatory bowel disease (IBD), type 1 diabetes (T1D), multiple sclerosis (MS), systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), Sjogren's Syndrome (SS), systemic sclerosis (SSc), vitiligo, and autoimmune thyroid diseases (AITD). Moreover, in this work, we present evidence of the potential role of exosomal miRNAs as therapeutic and diagnostic agents in autoimmune diseases.

Evaluating tissue levels of the eight trace elements and heavy metals among esophagus and gastric cancer patients: A comparison between cancerous and non-cancerous tissues.

BACKGROUND: Considering the affecting role of environmental factors including trace elements and heavy metals on the upper gastrointestinal (GI) cancers, there is paucity of empirical research in tissue evaluations. OBJECTIVES: The present study aimed to measure the tissue content of some trace elements and heavy metals such as zinc (Zn), chromium (Cr), manganese (Mn), tin (Sn), copper (Cu), aluminum (Al), lead (Pb), and iron (Fe) in esophagus and gastric cancerous tissues compared to the adjacent healthy tissues. METHODS: In a cross-sectional study, the aforementioned trace elements and heavy metals were evaluated among patients with esophagus and gastric cancers. During endoscopy, multiple samples were taken from cancerous lesions and the adjacent healthy tissues. The classic flame atomic absorption spectroscopy (FAAS) method was employed as the study framework. RESULTS: Fifty patients with the mean age of 53.92 ± 8.73 were enrolled in the current study. Thirteen patients suffered from esophageal cancer and thirty-seven patients were afflicted with gastric cancer. The results revealed significant differences in the median concentrations of Zn, Cr, Sn and, Cu (P < 0.05) between the two groups. Although there were no significant changes in the tissue content in the esophageal samples, in the median concentrations of Zn, Cr and, Sn (P < 0.05) in gastric tissues, significant differences were observed. Further, the results indicated that gender enacted an affecting role in the level of some trace elements and heavy metals. CONCLUSION: The tissue contents of some elements were altered in gastric and esophageal cancers; this difference may reflect the underlying mechanism of cellular changing during the tumorigenesis or direct exposure of these elements. It seems that under the shade of other coexisting risk factors, larger cohort studies are suggested to be conducted to investigate other probable aspects in this area of interest.

Clinical features of pregnant women in Iran who died due to COVID-19.

BACKGROUND: To evaluate the clinical presentation of pregnant women in Iran who died due to COVID-19. METHODS: Data were evaluated of pregnant women who died following a laboratory diagnosis of COVID-19. The data were obtained from electronic medical records. Additionally, a questionnaire was completed for each patient, including demographic, clinical, laboratorial, imaging, and treatment data. In case of missing information, a member of the research team contacted the first-degree relatives via phone. RESULTS: Of 32 pregnant women who tested positive for COVID-19, 15 were enrolled into the study (mean age 30.0 ± 5.0 years). The mean time from first symptoms to death was 12 ± 7.0 days. Pre-existing comorbidities were seen in six patients. The main presentations at admission were fatigue and coughing, but most of the women had a fever below 38 °C. Increased white blood cell count and neutrophils were noticeable. A significant drop of saturation of O2 with ground glass and consolidation seen in both lungs were prominent. The most common complications were acute respiratory distress syndrome followed by respiratory failure. CONCLUSION: Computed tomography findings, O2 pressure, and regular blood assessment may be considered suitable indicators for the surveillance of patients.