ABSTRACT

Although stroke is a major human neurological disease, there is a paucity of effective neuroprotectants that can improve its treatment. Casticin is a natural monomer drug with many biological effects such as anti‐inflammatory and anti‐tumor actions. However, it is not clear whether it has a neuroprotective effect in ischemic stroke. In this study, the neuroprotective effect of casticin in a rat middle cerebral artery occlusion (MCAO) model was investigated. Results showed that casticin reduced the volume of the cerebral infarction, mNSS scores, swimming distance, time to find the submerged platform, and serum concentrations of TNF‐α, TGF‐β, IL‐6 in MCAO rats. Moreover, casticin also decreased the expression of TLR4, NF‐κB p65, and NF‐κB p50 proteins and reversed the reduced expression of IκB protein in the brain tissue of MCAO rats. The in vitro study revealed that casticin decreased apoptosis of OGD/R‐PC12 cells, reduced the expression of TLR4, NF‐κB p65, and NF‐κB p50, while increased IκB protein expression. In conclusion, casticin improved the neurological functions of MCAO rats via inhibiting the TLR4/NF‐κB pathway and might have the potential to be developed into a neuroprotective agent for stroke patients.

It has been demonstrated that aldosterone (ALD) plays a direct profibrotic role in the kidney but the underlying mechanism remains unclear. We examined the role of Rho kinase signal pathway in epithelial-mesenchymal transition (EMT) process and extracellular matirx (ECM) synthesis induced by ALD in human renal proximal tubular epithelial (HK-2) cells in vitro. Rho kinase and collagen I, III protein expressions were detected by ELISA. E-cadherin, α-smooth muscle actin (SMA), collagen_I and collagen III mRNA expressions were detected by real time PCR. E-cadherin, and α-SMA protein expressions were measured by Western blot. Our results showed that ALD could significantly activate the Rho kinase in HK-2 cells, while in the presence of mineralocorticoid receptor (MR) antagonist eplerenone and Rho kinase inhibitor Y27632, the Rho kinase protein expression were almost completely prevented. Exposure of HK-2 cells to ALD for 48 h induced EMT as evidenced by loss of E-cadherin, and de novo expression of α-SMA. The EMT was completely blocked by eplerenone and Y27632. Meanwhile, ALD could significantly increase the mRNA and protein expressions of collagen I, III in HK-2 cells when compared with the control group, while eplerenone and Y27632 could almost reverse these effects. These observations suggest that ALD can activate Rho kinase pathway and Rho kinase pathway is likely responsible for the profibrotic actions of ALD in renal proximal tubular epithelial cells via inducing EMT and ECM excretion.

In December 2019, the first confirmed case of pneumonia caused by a novel coronavirus was reported. Coronavirus disease 2019 (COVID-19) is currently spreading around the world. The relationships among the pandemic and its associated travel restrictions, social distancing measures, contact tracing, mask-wearing habits and medical consultation efficiency have not yet been extensively assessed. Based on the epidemic data reported by the Health Commission of Wenzhou, we analysed the developmental characteristics of the epidemic and modified the Susceptible-Exposed-Infectious-Removed (SEIR) model in three discrete ways. (1) According to the implemented preventive measures, the epidemic was divided into three stages: initial, outbreak and controlled. (2) We added many factors, such as health protections, travel restrictions and social distancing, close-contact tracing and the time from symptom onset to hospitalisation (TSOH), to the model. (3) Exposed and infected people were subdivided into isolated and free-moving populations. For the parameter estimation of the model, the average TSOH and daily cured cases, deaths and imported cases can be obtained through individual data from epidemiological investigations. The changes in daily contacts are simulated using the intracity travel intensity (ICTI) from the Baidu Migration Big Data platform. The optimal values of the remaining parameters are calculated by the grid search method. With this model, we calculated the sensitivity of the control measures with regard to the prevention of the spread of the epidemic by simulating the number of infected people in various hypothetical situations. Simultaneously, through a simulation of a second epidemic, the challenges from the rebound of the epidemic were analysed, and prevention and control recommendations were made. The results show that the modified SEIR model can effectively simulate the spread of COVID-19 in Wenzhou. The policy of the lockdown of Wuhan, the launch of the first-level Public Health Emergency Preparedness measures on 23 January 2020 and the implementation of resident travel control measures on 31 January 2020 were crucial to COVID-19 control.