Experimental Models of SARS-CoV-2 Infection: Possible Platforms to Study COVID-19 Pathogenesis and Potential Treatments.

In December 2019, a novel coronavirus crossed species barriers to infect humans and was effectively transmitted from person to person, leading to a worldwide pandemic. Development of effective clinical interventions, including vaccines and antiviral drugs that could prevent or limit theburden or transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is a global health priority. It is thus of utmost importance to assess possible therapeutic strategies against SARS-CoV-2 using experimental models that recapitulate aspects of the human disease. Here, we review available models currently being developed and used to study SARS-CoV-2 infection and highlight their application to screen potential therapeutic approaches, including repurposed antiviral drugs and vaccines. Each identified model provides a valuable insight into SARS-CoV-2 cellular tropism, replication kinetics, and cell damage that could ultimately enhance understanding of SARS-CoV-2 pathogenesis and protective immunity.

The Protective Effect of Crocin on Rat Bone Marrow Mesenchymal Stem Cells Exposed to Aluminum Chloride as an Endocrine Disruptor.

Background: Mesenchymal Stem Cells (MSCs) have the ability to self-renew and proliferate which gives them healing properties in various tissues. Aluminium chloride (AlCl3) is a chemical compound with harmful effects on health; oxidative stress caused by Aluminium has been reported previously. Crocin, a major component of Crocus sativus (saffron), has antioxidant properties and has shown therapeutic potential. Researchers have been looking for ways to reduce the harmful effects of AlCl3. Methods: To investigate whether crocin can reduce AlCl3 cytotoxicity, rat Bone Marrow Mesenchymal Stem Cells (BM-MSCs) were isolated, cultured and divided into four experimental groups. The first group was the control, which was untreated cells. The second and third groups were treated with crocin (50, 100, 250, 500 µM) and AlCl3 (20, 25, 30 mM) for 24 hr. The fourth group was pre-treated with crocin (250, 500 µM) for 24 hr and then treated with AlCl3 (20 mM) overnight. Cytotoxicity was assessed using the MTT assay. Mineralization was evaluated by alizarin red staining. Sox-2 and E-cadherin expression were measured using real-time PCR. Results: The results showed that AlCl3 caused cytotoxicity on BM-MSCs and decreased the mRNA expression of Sox-2 and E-cadherin, which are important for the maintenance of self-renewal and proliferation of BM-MSCs. In contrast, crocin protected the self-renewal characteristic of BM-MSCs by increasing Sox-2 expression and also preserved the proliferative effects on BM-MSCs by upregulating E-cadherin expression (***p≤0.001). Conclusion: Overall, the study suggests that crocin can protect BM-MSCs from AlCl3-induced cytotoxicity by upregulate Sox-2 expression and E-cadherin expression. This suggests that crocin may be a potential therapeutic agent for the treatment of AlCl3-induced toxicity.

Epicardial adipose tissue, inflammatory biomarkers and COVID-19: Is there a possible relationship?

BACKGROUND & AIMS: Adipose tissue is a biologically active organ with pro-immunogenic properties. We aimed to evaluate the prognostic value of epicardial adipose tissue (EAT) in COVID-19 and its correlation with other inflammatory biomarkers. MATERIAL AND METHODS: One-hundred patients with COVID-19 were enrolled. C-reactive protein (CRP), lactate dehydrogenase (LDH), neutrophil-to-lymphocyte ratio (NLR), lymphocyte-to-CRP ratio (LCR), and platelet-to-lymphocyte ratio (PLR) were evaluated on admission. EAT volume and density were measured by computed tomography. Patients were followed until death or discharge. Univariate and multivariate analysis was performed and ROC curve analysis was used to assess the ability of inflammatory markers in predicting survival. The relationship between EAT and other inflammatory markers was also investigated. RESULTS: The mean ± SD age of patients was 55.5 ± 15.2 years old; 68% were male. Univariate analysis revealed that increased lung involvement, blood urea nitrogen, LDH and NLR, and decreased platelet count were significantly associated with death. After adjustment, LDH was independently predictive of death (OR = 1.013, p-value = 0.03). Among inflammatory markers, LCR had the best ability for predicting survival with 79.7% sensitivity and 64.3% specificity at an optimal cut-off value of 20.8 (AUC = 0.744, 95% CI = 0.612-0.876, p-value = 0.004). EAT volume demonstrated positive correlation with NLR and PLR (p = 0.001 and 0.01), and a negative correlation with LCR (p = 0.02). EAT density was significantly different between decedents and survivors (p = 0.008). CONCLUSION: Routine laboratory tests that represent status of inflammation can be used as cost-effective prognostic markers of COVID-19. Also, the significant association between EAT volume and other inflammatory biomarkers might explain the more severe disease in obese patients.

The Association of CT-measured Cardiac Indices with Lung Involvement and Clinical Outcome in Patients with COVID-19.

RATIONALE AND OBJECTIVES: Cardiac indices can predict disease severity and survival in a multitude of respiratory and cardiovascular diseases. Herein, we hypothesized that CT-measured cardiac indices are correlated with severity of lung involvement and can predict survival in patients with COVID-19. MATERIALS AND METHODS: Eighty-seven patients with confirmed COVID-19 who underwent chest CT were enrolled. Cardiac indices including pulmonary artery-to-aorta ratio (PA/A), cardiothoracic ratio (CTR), epicardial adipose tissue (EAT) thickness and EAT density, inferior vena cava diameter, and transverse-to-anteroposterior trachea ratio were measured by non-enhanced CT. Logistic regression and Cox-regression analyses evaluated the association of cardiac indices with patients' outcome (death vs discharge). Linear regression analysis was used to assess the relationship between the extent of lung involvement (based on CT score) and cardiac indices. RESULTS: Mean (±SD) age of patients was 54.55 (±15.3) years old; 65.5% were male. Increased CTR (>0.49) was seen in 52.9% of patients and was significantly associated with increased odds and hazard of death (odds ratio [OR] = 12.5, p = 0.005; hazard ratio = 11.4, p = 0.006). PA/A >1 was present in 20.7% of patients and displayed a nonsignificant increase in odds of death (OR = 1.9, p = 0.36). Furthermore, extensive lung involvement was positively associated with elevated CTR and increased PA/A (p = 0.001). CONCLUSION: CT-measured cardiac indices might have predictive value regarding survival and extent of lung involvement in hospitalized patients with COVID-19 and could possibly be used for the risk stratification of these patients and for guiding therapy decision-making. In particular, increased CTR is prevalent in patients with COVID-19 and is a powerful predictor of mortality.

Investigating the synergic effects of valproic acid and crocin on BDNF and GDNF expression in epidermal neural crest stem cells.

Following nerve tissue damage, various events, such as inflammatory responses, microglial activation, endoplasmic reticulum stress, and apoptosis, can occur, which all lead to cell death, prevent axonal growth, and cause axonal circumvolution. So far, several researchers have tended to adopt strategies to reduce the harmful conditions associated with neurological disorders, and stem­cell­based therapy is one of those promising strategies. Epidermal neural crest stem cells (EPI­NCSCs) are a type of stem cell that has widely been employed for the treatment of various neurological disorders. It has been suggested that these stem cells perform their supportive actions primarily through the release of different neurotrophic factors. Hence, in this study, the neuroprotective impacts of valproic acid (VPA) and crocin were evaluated on the mRNA expression levels of brain­derived neurotrophic factor (BDNF) and glial­cell­derived neurotrophic factor (GDNF) in EPI­NCSCs. In this research, we isolated EPI­NCSCs from the hair follicles of the rat whisker pad. Then, the cells were treated with different concentrations of VPA and crocin for 72 h. Subsequently, an MTT assay was performed to define the suitable concentrations of drugs. Finally, real­time PCR was performed to evaluate the mRNA expression levels of BDNF and GDNF in these stem cells. The results of the MTT assay showed that the treatment of EPI­NCSCs with 1 mM VPA and 1.5 mM crocin, and the co­treatment with 1 mM VPA and 500 µM crocin, led to the survival and proliferation of these stem cells. Moreover, the real­time PCR results revealed that both VPA and crocin, both individually and in combination, can significantly increase the expression levels of BDNF and GDNF in EPI­NCSCs. According to the findings of this study, both VPA and crocin, alone and in combination, are potential candidates for enhancing the capacity of EPI­NCSCs to differentiate into neural lineages. Therefore, the co­treatment of EPI­NCSCs with these drugs can be employed for the treatment of various neurological disorders, such as spinal cord injury.