The key role of Calpain in COVID-19 as a therapeutic strategy

Inflammopharmacology - COVID-19 is one of the viral diseases that has caused many deaths and financial losses to humans. Using the available information, this virus appears to activate the host...     

Evaluation of admission levels of P,E and L selectins as predictors for thrombosis in hospitalized COVID-19 patients

Thromboembolic complications are the most reported cause of death in coronavirus disease-2019 (COVID-19). Hypercoagulability, platelets activation and endotheliopathy are well-recognized features in COVID-19 patients. The aim of this work was to evaluate circulating soluble selectins P, E and L at the time of hospital admission as predictors for upcoming thrombosis. This retrospective study included 103 hospitalized COVID-19 patients and 50 healthy volunteer controls. COVID-19 patients were categorized into two groups; group 1 who developed thrombosis during hospitalization and group 2 who did not. Soluble selectins were quantitated using ELISA technique. Higher levels of sP-selectin, sE-selectin and sL-selectin were detected in COVID-19 patients compared to controls. Furthermore, significantly higher levels were found in group 1 compared to group 2. Their means were [5.86 ± 1.72 ng/mL vs. 2.51 ± 0.81 ng/mL]; [50 ± 8.57 ng/mL vs. 23.96 ± 6.31 ng/mL] and [4.66 ± 0.83 ng/mL vs. 2.95 ± 0.66 ng/mL] for sP-selectin, sE-selectin and sL-selectin respectively. The elevated selectins correlated with the currently used laboratory biomarkers of disease severity. After adjustment of other factors, sP-selectin, sE-selectin and sL-selectin were independent predictors for thrombosis. At sP-selectin ≥ 3.2 ng/mL, sE-selectin ≥ 32.5 ng/mL and sL-selectin ≥ 3.6 ng/mL thrombosis could be predicted with 97.1%, 97.6% and 96.5% sensitivity. A panel of the three selectins provided 100% clinical sensitivity. Admission levels of circulating soluble selectins P, E and L can predict thrombosis in COVID-19 patients and could be used to identify patients who need prophylactic anticoagulants. E-selectin showed a superior clinical performance, as thrombo-inflammation biomarker, to the most commonly studied P-selectin.

     

Diterpenes and their derivatives as promising agents against dengue virus and dengue vectors: A literature‐based review

Dengue, a mosquito‐borne viral disease, causes about 100 million cases of infection annually. It is a major public concern, and if left untreated or improperly diagnosed, may cause serious health problems or even death. Historically, dengue has not considered priorities for pharmaceutical companies made the available treatment options. Therefore, medicinal scientists are revealing new insights and enabling novel interventions and approaches to dengue prevention and control. Diterpenes, a class of terpenes have gained much attention due to their diverse biological effects. This review aimed at summarizing available evidences of diterpenes and their derivatives acting against dengue virus and their vectors. For this, an updated search was made in the databases: PubMed and ScienceDirect by using specific keywords. Among the 117 published reports, a total of 30 articles was included in this review. Findings suggest that a number of diterpenes and/or their derivatives act against dengue virus and their two potential vectors namely Aedes aegypti and Ae. albopictus. In conclusion, diterpenes and their derivatives may have the potential alternative therapeutic tools for the management of dengue virus and some associated diseases transmitted by Aedes mosquito.     

A comprehensive insight into potential roles of Nigella sativa on diseases by targeting AMP-activated protein kinase: a review

ObjectivesNigella sativa (NS) is a known medicinal herb with numerous therapeutic effects such as antidiabetic, anti-proliferative, anti-inflammatory, and anti-cancer activities. It has been indicated that NS can regulate cellular metabolism by adjusting transduction signaling pathways. Adenosine monophosphate-activated protein kinase (AMPK) is one of the main physiological processes, such as energy hemostasis, cellular metabolism, and autophagy regulators. Herb-derived medicines have always been considered as one of the main AMPK activators, and surprisingly recent data has demonstrated that it can be a target for NS and its derivatives.Evidence acquisitionThe literature search was conducted in PubMed, SCOPUS, Embase, ProQuest, and Google Scholar electronic resources. Published articles up to September 2020 were considered, and those of which investigated Nigella sativa effects on the AMPK pathway after meeting the inclusion criteria were included.ResultsThe search was performed on several online databases such as PubMed, Scopus, Embase, ProQuest, and Google Scholar from inception until January 2020. Among the initial search, 245 studies were found. After removing duplicated data and meeting the inclusion criteria, only 14 studies were selected. They included the effects of NS and its bioactive compounds as anti-hyperglycemic (n = 5), on liver function (n = 4), cancers (n = 3), and on Neuroinflammation and Atherosclerosis (n = 2). Most of the included studies are animals or in-vitro investigations.ConclusionIn this review, we discuss the latest findings on the molecular mechanism of NS effecting the AMPK signaling pathway. We also focus on the therapeutic effects of NS, including the prevention and treatment of metabolic and pro-inflammatory disease by targeting the AMPK pathway.Graphical abstract     

Dietary fish oil,and to a lesser extent the fat-1 transgene,increases astrocyte activation in response to intracerebroventricular amyloid-β 1–40 in mice

Objectives: Increases in astrocytes and one of their markers, glial fibrillary acidic protein (GFAP) have been reported in the brains of patients with Alzheimer’s disease (AD). N-3 polyunsaturated fatty acids (PUFA) modulate neuroinflammation in animal models; however, their effect on astrocytes is unclear.

Methods: Fat-1 mice and their wildtype littermates were fed either a fish oil diet or a safflower oil diet deprived of n-3 PUFA. At 12 weeks, mice underwent intracerebroventricular infusion of amyloid-β 1-40. Astrocyte phenotype in the hippocampus was assessed at baseline and 10 days post-surgery using immunohistochemistry with various microscopy and image analysis techniques.

Results: GFAP increased in all groups in response to amyloid-β, with a greater increase in fish oil-fed mice than either fat-1 or wildtype safflower oil-fed mice. Astrocytes in this group were also more hypertrophic, suggesting increased activation. Both fat-1- and fish oil-fed mice had greater increases in branch number and length in response to amyloid-β infusion than wildtype safflower animals.

Conclusion: Fish oil feeding, and to a lesser extent the fat-1 transgene, enhances the astrocyte activation phenotype in response to amyloid-β 1-40. Astrocytes in mice fed fish oil were more activated in response to amyloid-β than in fat-1 mice despite similar levels of hippocampal n-3 PUFA, which suggests that other fatty acids or dietary factors contribute to this effect.     

The effect of nettle (Urtica dioica) supplementation on the glycemic control of patients with type 2 diabetes mellitus: A systematic review and meta‐analysis

Type 2 diabetes mellitus (T2DM) is a major health problem, worldwide, that is associated with increased morbidity and mortality. Several randomized controlled clinical trials (RCTs) have investigated the effect of nettle (Urtica dioica) supplementation on markers of glycemic status in patients with T2DM, with conflicting results. Therefore, the present study assessed the effect of nettle on some glycemic parameters in patients with T2DM. A comprehensive search was conducted in PubMed, Scopus, Cochrane Library, and Web of Science, from database inception up to June 2019, to identify RCTs investigating the effect of nettle supplementation on glycemic markers, including fasting blood sugar (FBS) concentrations, insulin levels, homeostasis model assessment‐estimated insulin resistance index, and glycosylated hemoglobin percentage in adults with T2DM. The Cochrane Collaboration tool was used to assess the methodological quality of the included studies. Results of this meta‐analysis were reported based on the random effects model. Eight RCTs, comprising 401 participants, were included in the present systematic review and meta‐analysis. Based on the Cochrane Collaboration risk of bias tool, five studies were considered as good quality, one was fair, and two studies were poor, respectively. The results of the meta‐analysis revealed a significant reduction in FBS concentrations (weighted mean difference [WMD]: ?18.01 mg/dl, 95% confidence interval [CI]: ?30.04 to ?5.97, p < .001, I² = 94.6%) following nettle supplementation. However, no significant reduction was observed in insulin levels (WMD: 0.83 Hedges' g, 95% CI: ?0.26 to 1.92, p = .13, I² = 89.4%), homeostasis model assessment‐estimated insulin resistance index (WMD: ?0.22, 95% CI: ?0.83 to 0.40, p = .49, I² = 69.2%), or glycosylated hemoglobin percentage (WMD: ?0.77%, 95% CI: ?1.77 to 0.22, p = .12, I² = 83.0%). The findings of the present study suggest that nettle supplementation may be effective in controlling FBS for T2DM patients. However, further studies are needed to confirm the veracity of these results.