Ehsan Dadgostar

Neuropsychiatric and neurological disorders pose a significant global health burden, highlighting the need for innovative therapeutic approaches. Fingolimod (FTY720), a common drug to treat multiple sclerosis, has shown promising efficacy against various neuropsychiatric and neurological disorders. Fingolimod exerts its neuroprotective effects by targeting multiple cellular and molecular processes, such as apoptosis, oxidative stress, neuroinflammation, and autophagy. By modulating Sphingosine-1-Phosphate Receptor activity, a key regulator of immune cell trafficking and neuronal function, it also affects synaptic activity and strengthens memory formation. In the hippocampus, fingolimod decreases glutamate levels and increases GABA levels, suggesting a potential role in modulating synaptic transmission and neuronal excitability. Taken together, fingolimod has emerged as a promising neuroprotective agent for neuropsychiatric and neurological disorders. Its broad spectrum of cellular and molecular effects, including the modulation of apoptosis, oxidative stress, neuroinflammation, autophagy, and synaptic plasticity, provides a comprehensive therapeutic approach for these debilitating conditions. Further research is warranted to fully elucidate the mechanisms of action of fingolimod and optimize its use in the treatment of neuropsychiatric and neurological disorders.

Clearance of accumulated protein aggregates is one of the functions of autophagy. Recently, a clearer understanding of non-coding RNAs (ncRNAs) functions documented that ncRNAs have important roles in several biological processes associated with the development and progression of neurodegenerative disorders. Subtypes of ncRNA, including microRNA (miRNA), long noncoding RNA (lncRNA), and circular RNA (circRNA), are commonly dysregulated in neurodegenerative disorders such as Alzheimer and Parkinson diseases. Dysregulation of these non-coding RNAs has been associated with inhibition or stimulation of autophagy. Decreased miR-124 led to decreased/increased autophagy in experimental model of Alzheimer and Parkinson diseases. Increased BACE1-AS showed enhanced autophagy in Alzheimer disease by targeting miR-214-3p, Beclin-1, LC3-I/LC3-II, p62, and ATG5. A significant increase in NEAT1led to stimulated autophagy in experimental model of PD by targeting PINK1, LC3-I, LC3-II, p62 and miR-374c-5p. In addition, increased BDNF-AS and SNHG1 decreased autophagy in MPTP-induced PD by targeting miR-125b-5p and miR-221/222, respectively. The upregulation of circNF1-419 and circSAMD4A resulted in an increased autophagy by regulating Dynamin-1 and miR-29c 3p, respectively. A detailed discussion of miRNAs, circRNAs, and lncRNAs in relation to their autophagy-related signaling pathways is presented in this study. Graphical Abstract Autophagy-related non-coding RNAs in neurodegenerative diseases.

Evidence recommends that vitamin D might be a crucial supportive agent for the immune system, mainly in cytokine response regulation against COVID-19. Hence, we carried out a systematic review and meta-analysis in order to maximise the use of everything that exists about the role of vitamin D in the COVID-19. A systematic search was performed in PubMed, Scopus, Embase and Web of Science up to December 18, 2020. Studies focused on the role of vitamin D in confirmed COVID-19 patients were entered into the systematic review. Twenty-three studies containing 11 901 participants entered into the meta-analysis. The meta-analysis indicated that 41% of COVID-19 patients were suffering from vitamin D deficiency (95% CI, 29%-55%), and in 42% of patients, levels of vitamin D were insufficient (95% CI, 24%-63%). The serum 25-hydroxyvitamin D concentration was 20.3 ng/mL among all COVID-19 patients (95% CI, 12.1-19.8). The odds of getting infected with SARS-CoV-2 are 3.3 times higher among individuals with vitamin D deficiency (95% CI, 2.5-4.3). The chance of developing severe COVID-19 is about five times higher in patients with vitamin D deficiency (OR: 5.1, 95% CI, 2.6-10.3). There is no significant association between vitamin D status and higher mortality rates (OR: 1.6, 95% CI, 0.5-4.4). This study found that most of the COVID-19 patients were suffering from vitamin D deficiency/insufficiency. Also, there is about three times higher chance of getting infected with SARS-CoV-2 among vitamin-D-deficient individuals and about five times higher probability of developing the severe disease in vitamin-D-deficient patients. Vitamin D deficiency showed no significant association with mortality rates in this population.

Brain-related disorders are leading global health problems. Various internal and external factors are involved in the progression of brain-related disorders. Inflammatory pathways, oxidative stresses, apoptosis, and deregulations of various channels are critical players in brain-related disorder pathogenesis. Among these players, aquaporins (AQP) have critical roles in various physiological and pathological conditions. AQPs are water channel molecules that permit water to cross the hydrophobic lipid bilayers of cellular membranes. AQP4 is one of the important members of AQP family. AQPs are involved in controlling apoptosis pathways in brain-related disorders. In this regard, several reports have evaluated the pathological effects of AQP4 by targeting the apoptosis-related processes in brain-related disorders. Here, for the first time, we highlight the impact of AQP4 on apoptosis-related processes in brain-related disorders.

Background: Evidence recommends that vitamin D might be a crucial supportive agent for the immune system, mainly in cytokine response regulation against COVID-19. Hence, we carried out a systematic review and meta-analysis in order to maximize the use of everything that exists about the role of vitamin D in the COVID-19. Methods: A systematic search was performed in PubMed, Scopus, Embase, and Web of Science up to December 18, 2020. Studies focused on the role of vitamin D in confirmed COVID-19 patients were entered into the systematic review. Results: Twenty-three studies containing 11901participants entered into the meta-analysis. The meta-analysis indicated that 41% of COVID-19 patients were suffering from vitamin D deficiency (95% CI, 29%-55%), and in 42% of patients, levels of vitamin D were insufficient (95% CI, 24%-63%). The serum 25-hydroxyvitamin D concentration was 20.3 ng/mL among all COVID-19 patients (95% CI, 12.1-19.8). The odds of getting infected with SARS-CoV-2 is 3.3 times higher among individuals with vitamin D deficiency (95% CI, 2.5-4.3). The chance of developing severe COVID-19 is about five times higher in patients with vitamin D deficiency (OR: 5.1, 95% CI, 2.6-10.3). There is no significant association between vitamin D status and higher mortality rates (OR: 1.6, 95% CI, 0.5-4.4). Conclusion: This study found that most of the COVID-19 patients were suffering from vitamin D deficiency/insufficiency. Also, there is about three times higher chance of getting infected with SARS-CoV-2 among vitamin D deficient individuals and about 5 times higher probability of developing the severe disease in vitamin D deficient patients. Vitamin D deficiency showed no significant association with mortality rates in this population.

Background: Coronavirus Disease 2019 (COVID-19) has become a major global issue with rising the number of infected individuals and mortality in recent months. Among all therapeutic approaches, arguments have raised about hydroxychloroquine (HCQ) efficacy in the treatment of COVID-19. We carried out a systematic review and meta-analysis overcome the controversies regarding the effectiveness of hydroxychloroquine in the treatment of COVID-19. Methods: A systematic search was performed in PubMed, Scopus, Embase, Cochrane Library, Web of Science, Google Scholar and medRxiv pre-print database using all available MeSH terms for COVID-19 and hydroxychloroquine up to July 19, 2020. Studies focused on the effectiveness of HCQ with/without azithromycin (AZM) in confirmed COVID-19 patients were entered into the study. Two researchers have independently evaluated quality assessment of the studies and abstracted data for data extraction. Extracted data were analyzed using CMA v . 2.2.064. Heterogeneity was assessed using the I -squared ( I ² ) test, and fixed/random-effects model was used when appropriate for pooling of studies. Results: Out of 26 studies entered into our systematic review, 21 studies including 14 comparative studies with control group and seven observational studies containing 103,486 participants have entered into the meta-analysis. The results of the meta-analysis on comparative studies indicated no significant clinical effectiveness (negative in RT-PCR evaluation) for HCQ regimen in the treatment of COVID-19 in comparison to control group (RR: 1.03, 95% CI, 0.79-1.34). The same result was observed for the combination of HCQ+azithromycin (RR: 1.26, 95% CI, 0.91-1.74). No significant differences were found for both HCQ (RR: 0.92, 95% CI, 0.72-1.16) and HCQ+AZM (RR: 1.72, 95% CI, 0.86-3.42) mortality rate; however, mortality was affected by age differences according to meta-regression analysis (P<0.000001). No substantial difference was observed for disease exacerbation (RR: 1.23, 95% CI, 0.65-2.30) between HCQ group and controls. Also, radiological findings significantly improved in the HCQ group (OR: 0.32, 95% CI, 0.11-0.98). Odds of known HCQ adverse effects (diarrhea, vomiting, blurred vision, rash, headache, etc.) occurred in the HCQ regimen group was approximately 3.5 times of control group (OR: 3.40, 95% CI, 1.65-6.98), but no substantial differences were found regarding intubation odds between HCQ group and control group (OR: 2.11, 95% CI, 0.31-14.03). Meta-analysis indicated no significant prophylactic effects for HCQ (OR: 0.40, 95% CI, 0.04-3.65) Conclusion: This systematic review and meta-analysis showed no clinical benefits regarding HCQ treatment with/without azithromycin for COVID-19 patients. Although mortality rate was not significantly different between cases and controls, frequency of adverse effects was substantially higher in HCQ regimen group. However, due to that most of the studies were non-randomized and results were not homogenous, selection bias was unavoidable and further large randomized clinical trials following comprehensive meta-analysis should be taken into account in order to achieve more reliable findings. Also, it is worth mentioning that if this work does not allow to quantify a “value” of the HCQ, it allows at least to know what is not the HCQ and that it would be prudent not to continue investing in this direction.

Background: There are current trials investigating the effect of resveratrol supplementation on lipid profiles and liver enzymes among patients with metabolic syndrome (MetS) and related disorders; however, their findings are controversial. This systematic review and meta-analysis were aimed to determine the effects of resveratrol supplementation on lipid profiles and liver enzymes among patients with MetS and related disorders.Methods: We performed a comprehensive search of the following online databases up to November 2018: Cochrane Library, PubMed, Embase, and Web of Science. The relevant articles were assessed for quality of studies using the Cochrane risk of bias tool.Results: Out of 2459 citations, 31 articles were appropriate for including to the current meta-analysis. The pooled results indicated that resveratrol use significantly decreased total cholesterol [weighted mean difference (WMD) = − 7.65 mg/dL; 95% CI, − 12.93, − 2.37;P < 0.01; I²: 83.4%] and increased gamma-glutamyl transferase (GGT) concentrations (WMD = 1.76 U/l; 95% CI, 0.58, 2.94;P < 0.01; I²: 20.1%). We found no significant effect of resveratrol supplementation on triglycerides (WMD = − 5.84 mg/dL; 95% CI, − 12.68, 1.00;P = 0.09; I²: 66.8%), LDL- (WMD = -2.90 mg/dL; 95% CI, − 10.88, 5.09;P = 0.47; I²: 96.0%), HDL-cholesterol (WMD = 0.49 mg/dL; 95% CI, − 0.80, 1.78;P = 0.45; I²: 74.0%), alanine aminotransferase (ALT) (WMD = -0.14 U/l; 95% CI, − 3.69, 3.41;P = 0.93; I²: 79.6%), and aspartate aminotransferase (AST) (WMD = -0.34 U/l; 95% CI, − 2.94, 2.27;P = 0.80; I²: 88.0%) concentrations.Conclusions: This meta-analysis demonstrated that resveratrol supplementation among patients with MetS and related disorders significantly reduced total cholesterol and increased GGT concentrations, but did not affect triglycerides, LDL-, HDL-cholesterol, ALT, and AST concentrations. This data suggests that resveratrol may have a potential cardio-protective effect in patients with MetS and related disorders.