Targeting Cytokine Storm to Manage Patients with COVID-19: A Mini-Review

Corona Virus Disease 2019 (COVID-19) pandemic is rapidly spreading all over the world. Excessive immune responses trigger life-threatening cytokine release syndrome (CRS) which can result in overproduction of pro-inflammatory cytokines including tumor necrosis factor alpha (TNFα), interleukin-6 (IL-6), and IL-1β with different pro-inflammatory roles. Anecdotal evidence suggests that the modulation of systemic immune responses may have a potential role in the treatment of patients with COVID-19. Given the importance of the issue and the lack of therapeutic treatment or vaccine; anti-cytokine therapy such as IL-6, TNFα and IL-1 antagonists have been suggested for the alleviation of hyper-inflammation status in these patients. In this mini-review, we addressed the inflammatory pathways of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and its relationship with the host cytokine storm. Furthermore, the proposed therapeutic options to reverse hyper-inflammation in infected patients were mentioned. © 2020 IMS

Downregulation of miR-1266-5P, miR-185-5P and miR-30c-2 in prostatic cancer tissue and cell lines

Over the latest decade, the role of microRNAs (miRNAs/miRs) has received more attention. miRNAs are small non-coding RNAs that may serve a role as oncogenes or tumor suppressor genes. Certain miRNAs regulate the apoptosis pathway by influencing pro- or anti-apoptotic genes. We hypothesized that increases in the expression of B cell lymphoma 2 (BCL2) and BCL2-like 1 (BCL2L1) genes, which have been reported in various types of cancer tissues, may be due to the downregulation of certain miRNAs. The present study aimed to identify miRNAs that target BCL2 and BCL2L1 anti-apoptotic genes in prostate cancer (PCa) clinical tissue samples. Certain candidate miRNAs were selected bioinfor-matically and their expression in PCa samples was analyzed and compared with that in benign prostatic hyperplasia (BPH) tissue samples. The candidate miRNAs that targeted BCL2 and BCL2L1 genes were searched in online databases (miRWalk, microRNA.org, miRDB and TargetScan). A total of 12 miRNAs that target the 3'-untranslated region of the aforementioned genes and/or for which downregulation of their expression has previously been reported in cancer tissues. A total of 30 tumor tissue samples from patients with PCa and 30 samples tissues from patients with BPH were obtained and were subjected to reverse transcription-quantitative polymerase chain reaction for expression analysis of 12 candidate miRNAs, and the BCL2 and BCL2L1 genes. Additionally, expression of 3 finally selected miRNAs and genes was evaluated in prostate cancer PC3 and DU145 cell lines and human umbilical vein endothelial cells. Among 12 miRNA candidates, the expression of miR-1266, miR-185 and miR-30c-2 was markedly downregulated in PCa tumor tissues and cell lines. Furthermore, downregulation of these miRNAs was associated with upregulation of the BCL2 and BCL2L1 genes. An inverse association between three miRNAs (miR-1266, miR-185 and miR-30c-2) and two anti-apoptotic genes (BCL2 and BCL2L1) may be considered for interventional miRNA therapy of PCa. © 2018, Spandidos Publications. All rights reserved

Hepatitis b vertical transfer and its risk factors in pregnant women in the eastern part of iran

One of the main causes of chronic hepatitis is mother to child transfer which is also known as vertical transfer (VT). Although there are several studies regarding the VT mechanism and its risk factors, none of these studies succeeded in explaining this process, completely. We conducted this study aiming at investigating VT mechanism and risk factors in this region. The present study was a descriptive-analytic cross-sectional study on HBS Ag positive pregnant women, which was conducted from March 2018 to March 2020 in Amir-AlMomenin Hospital in Zabol, Sistan-and-Baluchestan province, Iran. In this study all samples were tested for HBV markers (HBsAg, anti-HBs, HBeAg, anti-HBe, anti-HBc, and HBV-DNA) and anti-HCV by enzyme-linked immunosorbent assay (ELISA). All statistical analyzes were performed using SPSS version 22 software. Totally 43 infants of HBS antigen positive mothers were investigated. HBe antibody and HBe antigen were found in 25 (62.5%) and 2 (5%) of mothers, respectively. There was no significant difference between the newborns with and without hepatitis B infection regarding maternal age (p=0.216), duration of the infection in mother (p=0.892), AST (0.779), AL (0.449) and ALP (0.065). Mothers with positive viral load during pregnancy delivered newborns with positive HBS antigen much more than mothers with negative HBS antigen. However, this difference was not statistically significant (p=0.642). Although positive viral load was more common in neonates delivered from positive viral load mothers, the observed difference was also remained non-significant (p=0.978). Our study provided evidences regarding that demographic, immunologic and clinical characteristics of mothers with hepatitis B infection did not play considerable role in the vertical transmission of the infection to the newborns as well as the severity of the following infection. We also suggested the possibility of placenta acting as a source of infection in VT. Further longitudinal studies with larger sample sizes are needed to show the exact predictors of transmission of the infection from infected mothers to their children, Amirian S., Afshari M., Parooie F., Keikhaie K.R., Shahramian I., Bazi A., Ostadrahimi P., Sheikh M., Mirzaie H., Aminisefat A. One of the main causes of chronic hepatitis is mother to child transfer which is also known as vertical transfer (VT). Although there are several studies regarding the VT mechanism and its risk factors, none of these studies succeeded in explaining this process, completely. We conducted this study aiming at investigating VT mechanism and risk factors in this region. The present study was a descriptive-analytic cross-sectional study on HBS Ag positive pregnant women, which was conducted from March 2018 to March 2020 in Amir-AlMomenin Hospital in Zabol, Sistan-and-Baluchestan province, Iran. In this study all samples were tested for HBV markers (HBsAg, anti-HBs, HBeAg, anti-HBe, anti-HBc, and HBV-DNA) and anti-HCV by enzyme-linked immunosorbent assay (ELISA). All statistical analyzes were performed using SPSS version 22 software. Totally 43 infants of HBS antigen positive mothers were investigated. HBe antibody and HBe antigen were found in 25 (62.5%) and 2 (5%) of mothers, respectively. There was no significant difference between the newborns with and without hepatitis B infection regarding maternal age (p=0.216), duration of the infection in mother (p=0.892), AST (0.779), AL (0.449) and ALP (0.065). Mothers with positive viral load during pregnancy delivered newborns with positive HBS antigen much more than mothers with negative HBS antigen. However, this difference was not statistically significant (p=0.642). Although positive viral load was more common in neonates delivered from positive viral load mothers, the observed difference was also remained non-significant (p=0.978). Our study provided evidences regarding that demographic, immunologic and clinical characteristics of mothers with hepatitis B infection did not play considerable role in the vertical transmission of the infection to the newborns as well as the severity of the following infection. We also suggested the possibility of placenta acting as a source of infection in VT. Further longitudinal studies with larger sample sizes are needed to show the exact predictors of transmission of the infection from infected mothers to their childre

Downregulation of miR-1266-5P, miR-185-5P and miR-30c-2 in prostatic cancer tissue and cell lines

Over the latest decade, the role of microRNAs (miRNAs/miRs) has received more attention. miRNAs are small non-coding RNAs that may serve a role as oncogenes or tumor suppressor genes. Certain miRNAs regulate the apoptosis pathway by influencing pro- or anti-apoptotic genes. We hypothesized that increases in the expression of B cell lymphoma 2 (BCL2) and BCL2-like 1 (BCL2L1) genes, which have been reported in various types of cancer tissues, may be due to the downregulation of certain miRNAs. The present study aimed to identify miRNAs that target BCL2 and BCL2L1 anti-apoptotic genes in prostate cancer (PCa) clinical tissue samples. Certain candidate miRNAs were selected bioinfor-matically and their expression in PCa samples was analyzed and compared with that in benign prostatic hyperplasia (BPH) tissue samples. The candidate miRNAs that targeted BCL2 and BCL2L1 genes were searched in online databases (miRWalk, microRNA.org, miRDB and TargetScan). A total of 12 miRNAs that target the 3'-untranslated region of the aforementioned genes and/or for which downregulation of their expression has previously been reported in cancer tissues. A total of 30 tumor tissue samples from patients with PCa and 30 samples tissues from patients with BPH were obtained and were subjected to reverse transcription-quantitative polymerase chain reaction for expression analysis of 12 candidate miRNAs, and the BCL2 and BCL2L1 genes. Additionally, expression of 3 finally selected miRNAs and genes was evaluated in prostate cancer PC3 and DU145 cell lines and human umbilical vein endothelial cells. Among 12 miRNA candidates, the expression of miR-1266, miR-185 and miR-30c-2 was markedly downregulated in PCa tumor tissues and cell lines. Furthermore, downregulation of these miRNAs was associated with upregulation of the BCL2 and BCL2L1 genes. An inverse association between three miRNAs (miR-1266, miR-185 and miR-30c-2) and two anti-apoptotic genes (BCL2 and BCL2L1) may be considered for interventional miRNA therapy of PCa. © 2018, Spandidos Publications. All rights reserved

The effectiveness of ω-3 polyunsaturated fatty acid interventions during pregnancy on obesity measures in the offspring: an up-to-date systematic review and meta-analysis.

BACKGROUND: The potential role of ω-3 long chain polyunsaturated fatty acid (LCPUFA) supplementation during pregnancy on subsequent risk of obesity outcomes in the offspring is not clear and there is a need to synthesise this evidence. OBJECTIVE: A systematic review and meta-analysis of randomised controlled trials (RCTs), including the most recent studies, was conducted to assess the effectiveness of ω-3 LCPUFA interventions during pregnancy on obesity measures, e.g. BMI, body weight, fat mass in offspring. METHODS: Included RCTs had a minimum of 1-month follow-up post-partum. The search included CENTRAL, MEDLINE, SCOPUS, WHO's International Clinical Trials Reg., E-theses and Web of Science databases. Study quality was evaluated using the Cochrane Collaboration's risk of bias tool. RESULTS: Eleven RCTs, from ten unique trials, (3644 children) examined the effectiveness of ω-3 LCPUFA maternal supplementation during pregnancy on the development of obesity outcomes in offspring. There were heterogeneities between the trials in terms of their sample, type and duration of intervention and follow-up. Pooled estimates did not show an association between prenatal intake of fatty acids and obesity measures in offspring. CONCLUSION: These results indicate that maternal supplementation with ω-3 LCPUFA during pregnancy does not have a beneficial effect on obesity risk. Due to the high heterogeneity between studies along with small sample sizes and high rates of attrition, the effects of ω-3 LCPUFA supplementation during pregnancy for prevention of childhood obesity in the long-term remains unclear. Large high-quality RCTs are needed that are designed specifically to examine the effect of prenatal intake of fatty acids for prevention of childhood obesity. There is also a need to determine specific sub-groups in the population that might get a greater benefit and whether different ω-3 LCPUFA, i.e. eicosapentaenoic (EPA) vs. docosahexanoic (DHA) acids might potentially have different effects

Modulation of the peripheral blood transcriptome by the ingestion of probiotic yoghurt and acidified milk in healthy, young men

The metabolic health benefits of fermented milks have already been investigated using clinical biomarkers but the development of transcriptomic analytics in blood offers an alternative approach that may help to sensitively characterise such effects. We aimed to assess the effects of probiotic yoghurt intake, compared to non-fermented, acidified milk intake, on clinical biomarkers and gene expression in peripheral blood. To this end, a randomised, crossover study was conducted in fourteen healthy, young men to test the two dairy products. For a subset of seven subjects, RNA sequencing was used to measure gene expression in blood collected during postprandial tests and after two weeks daily intake. We found that the postprandial response in insulin was different for probiotic yoghurt as compared to that of acidified milk. Moreover changes in several clinical biomarkers were associated with changes in the expression of genes representing six metabolic genesets. Assessment of the postprandial effects of each dairy product on gene expression by geneset enrichment analysis revealed significant, similar modulation of inflammatory and glycolytic genes after both probiotic yoghurt and acidified milk intake, although distinct kinetic characteristics of the modulation differentiated the dairy products. The aryl hydrocarbon receptor was a major contributor to the down-regulation of the inflammatory genesets and was also positively associated with changes in circulating insulin at 2h after yoghurt intake (p = 0.05). Daily intake of the dairy products showed little effect on the fasting blood transcriptome. Probiotic yoghurt and acidified milk appear to affect similar gene pathways during the postprandial phase but differences in the timing and the extent of this modulation may lead to different physiological consequences. The functional relevance of these differences in gene expression is supported by their associations with circulating biomarkers

Risk of stroke in hospitalized SARS-CoV-2 infected patients: A multinational study

Background: There is an increased attention to stroke following SARS-CoV-2. The goal of this study was to better depict the short-term risk of stroke and its associated factors among SARS-CoV-2 hospitalized patients. Methods: This multicentre, multinational observational study includes hospitalized SARS-CoV-2 patients from North and South America (United States, Canada, and Brazil), Europe (Greece, Italy, Finland, and Turkey), Asia (Lebanon, Iran, and India), and Oceania (New Zealand). The outcome was the risk of subsequent stroke. Centres were included by non-probability sampling. The counts and clinical characteristics including laboratory findings and imaging of the patients with and without a subsequent stroke were recorded according to a predefined protocol. Quality, risk of bias, and heterogeneity assessments were conducted according to ROBINS-E and Cochrane Q-test. The risk of subsequent stroke was estimated through meta-analyses with random effect models. Bivariate logistic regression was used to determine the parameters with predictive outcome value. The study was reported according to the STROBE, MOOSE, and EQUATOR guidelines. Findings: We received data from 26,175 hospitalized SARS-CoV-2 patients from 99 tertiary centres in 65 regions of 11 countries until May 1st, 2020. A total of 17,799 patients were included in meta-analyses. Among them, 156(0.9) patients had a stroke�123(79) ischaemic stroke, 27(17) intracerebral/subarachnoid hemorrhage, and 6(4) cerebral sinus thrombosis. Subsequent stroke risks calculated with meta-analyses, under low to moderate heterogeneity, were 0.5 among all centres in all countries, and 0.7 among countries with higher health expenditures. The need for mechanical ventilation (OR: 1.9, 95 CI:1.1�3.5, p = 0.03) and the presence of ischaemic heart disease (OR: 2.5, 95 CI:1.4�4.7, p = 0.006) were predictive of stroke. Interpretation: The results of this multi-national study on hospitalized patients with SARS-CoV-2 infection indicated an overall stroke risk of 0.5(pooled risk: 0.9). The need for mechanical ventilation and the history of ischaemic heart disease are the independent predictors of stroke among SARS-CoV-2 patients. Funding: None. © 2020 The Author

Effect of surgical experience and spine subspecialty on the reliability of the {AO} Spine Upper Cervical Injury Classification System

OBJECTIVE The objective of this paper was to determine the interobserver reliability and intraobserver reproducibility of the AO Spine Upper Cervical Injury Classification System based on surgeon experience (< 5 years, 5–10 years, 10–20 years, and > 20 years) and surgical subspecialty (orthopedic spine surgery, neurosurgery, and "other" surgery). METHODS A total of 11,601 assessments of upper cervical spine injuries were evaluated based on the AO Spine Upper Cervical Injury Classification System. Reliability and reproducibility scores were obtained twice, with a 3-week time interval. Descriptive statistics were utilized to examine the percentage of accurately classified injuries, and Pearson’s chi-square or Fisher’s exact test was used to screen for potentially relevant differences between study participants. Kappa coefficients (κ) determined the interobserver reliability and intraobserver reproducibility. RESULTS The intraobserver reproducibility was substantial for surgeon experience level (< 5 years: 0.74 vs 5–10 years: 0.69 vs 10–20 years: 0.69 vs > 20 years: 0.70) and surgical subspecialty (orthopedic spine: 0.71 vs neurosurgery: 0.69 vs other: 0.68). Furthermore, the interobserver reliability was substantial for all surgical experience groups on assessment 1 (< 5 years: 0.67 vs 5–10 years: 0.62 vs 10–20 years: 0.61 vs > 20 years: 0.62), and only surgeons with > 20 years of experience did not have substantial reliability on assessment 2 (< 5 years: 0.62 vs 5–10 years: 0.61 vs 10–20 years: 0.61 vs > 20 years: 0.59). Orthopedic spine surgeons and neurosurgeons had substantial intraobserver reproducibility on both assessment 1 (0.64 vs 0.63) and assessment 2 (0.62 vs 0.63), while other surgeons had moderate reliability on assessment 1 (0.43) and fair reliability on assessment 2 (0.36). CONCLUSIONS The international reliability and reproducibility scores for the AO Spine Upper Cervical Injury Classification System demonstrated substantial intraobserver reproducibility and interobserver reliability regardless of surgical experience and spine subspecialty. These results support the global application of this classification system

Microbiological and Chemical Quality of Water in Food Industries with Low Content of Water at End Products

"n "nBackground and Objectives: In the production of some high-consumed food products like cake, biscuit, chocolate and spaghetti water is used in the preparing of primary material and in the kneading processes. At the present study microbiological and chemical quality of consumed water in food industries of East Azerbaijan Province were studied."nMaterials and Methods: Eleven factories with different products were selected. Water samples were collected and analyzed regarding the microbiological contamination and chemical parameters, and heavy metals. In addition, condition of water quality in selected industry was surveyed during the summer."nResults: According to the results, monitoring of water quality in the studied industries is not suitable. The chemical characteristics of consumed water in those industries had major differences. Ni, Cr, Zn, Fe and Mn were present in all analyzed water but in lower concentration than national Maximum Contaminant Level (MCL). Pb was measured in higher concentration than MCL in spaghetti factory no. 2 and close to MCL in wiener and frankfurter and sugar industries. Cd was close to MCL in spaghetti factory no. 2 and wiener and frankfurter industries."nConclusion: It was concluded that for the safety and health of food products the food industries should use the public water supply system as water source at least in food processing units or in the units of preparing of primary materials. Also for the preventing of chemical pollution of food products it is necessary, pay more attention to the subject of water quality control according to the special water standard of food industries, and using less volume of water in some food industry isn.t acceptable reason for neglecting of water quality monitoring and assessing. In addition it is required to analyze heavy metals in the final products of those industries