Acrylamide induces ferroptosis in HSC-T6 cells by causing antioxidant imbalance of the XCT-GSH-GPX4 signaling and mitochondrial dysfunction.

Acrylamide (AA) is a heat-induced food contaminant, mainly metabolized by the liver. Increasing evidences have proved that ferroptosis is linked to the pathogenesis of liver disease. In the current study, the underlying mechanism of AA-induced rat hepatic stellate (HSC-T6) cells ferroptosis was investigated by detecting changes in iron levels, expressions of ferroptosis-related proteins and indicators of mitochondrial dysfunction. The results showed that AA treatment led to iron levels increased and expressions of long-chain acyl-CoA synthase 4 (ACSL4), cyclooxygenase 2 (COX2) and ferritin heavy chain 1 (FTH1) proteins in HSC-T6 cells were all altered. Treatment with the ferroptosis inhibitor ferrostatin-1 (Fer-1) markedly reversed the impact of AA, suggesting that AA induced ferroptosis in HSC-T6 cells. Mechanistically, AA induced the onset of ferroptosis by affecting XCT-GSH-GPX4 antioxidant signaling. Moreover, AA created a peroxidative environment for ferroptosis by inducing oxidative stress in HSC-T6 cells through mitochondrial dysfunction, as evidenced by increased mitochondrial ROS (mtROS) release, mitochondrial membrane potential (MMP) depolarization, and decreased mitochondrial ATP. Our results indicated that AA resulted in mitochondrial dysfunction and ferroptosis, and dysregulation of XCT-GSH-GPX4 antioxidant signaling was a key factor in AA-induced ferroptosis.

Epidemiological characteristics of latent syphilis in Yancheng Cityfrom 2016 to 2020 / 预防医学

Objective@#To analyze the epidemiological characteristics of latent syphilis in Yancheng City from 2016 to 2020, so as to provide insights into syphilis control. @*Methods@#All reported cases with latent syphilis in Yancheng City from 2016 to 2020 was collected from the Communicable Disease Report System of China Disease Prevention and Control Information System, and the prevalence of latent syphilis was estimated and standardized by the seventh population census data in Yancheng City. The trends in the incidence of latent syphilis were evaluated using annual percent change (APC), and the temporal, regional and human distributions of latent syphilis patients were descriptively analyzed. In addition, the spatial clusters of latent syphilis incidence were identified using spatial autocorrelation analysis. @*Results@#A total of 7 790 cases with latent syphilis were reported in Yancheng City from 2016 to 2020, and the standardized incidence of latent syphilis increased from 15.35/105 in 2016 to 28.70/105 in 2020 (APC=17.54%, t=5.357, P=0.013). Latent syphilis cases were reported in each month, and no obvious seasonable characteristics were seen. During the period from 2017 to 2020, the highest incidence of latent syphilis was seen in residents at ages of 70 to 79 years, with incidence rates of 41.71/105, 43.04/105, 75.79/105 and 72.94/105, respectively, and most cases were farmers (4 711 cases, 60.47%). The three highest incidence of latent syphilis was reported in Funing County (191.40/105), Tinghu District (137.13/105) and Yandu District (126.23/105). There was a positive spatial correlation of latent syphilis incidence in Yancheng City from 2016 to 2020 (Moran's I=0.23, Z=4.457, P=0.001), and two high-high clusters were identified in 14 townships (streets) of Funing County, Binhai County, Tinghu District, Sheyang County and Yandu District and 3 low-low clusters in 7 townships (streets) in Jianhu County, Tinghu District, Dongtai City and Sheyang County. @*Conclusions@#The incidence of latent syphilis appeared a tendency towards a rise, and there were remarkable spatial clusters identified in latent syphilis incidence in Yancheng City from 2016 to 2020. The elderly people and farmers are at high risk of latent syphilis.

Allicin Ameliorates Intestinal Barrier Damage via Microbiota-Regulated Short-Chain Fatty Acids-TLR4/MyD88/NF-κB Cascade Response in Acrylamide-Induced Rats.

Acrylamide (AA) is a heat-induced toxicant, which can cause severe damage to health. In the present study, SD rats were used to investigate the potential therapeutic effects of allicin dietary supplementation in the rats with AA-induced intestinal injury. The elevated expression of occludin, claudin-1, zonula occludens-1 (ZO-1), mucin 2, and mucin 3 indicated that oral allicin alleviated the intestinal epithelial barrier breakage induced by AA, compared with the AA-treated group. In the gut microbiota, Bacteroides, Escherichia_Shigella, Dubosiella, and Alloprevotella related to the synthesis of short-chain fatty acids (SCFAs) were negatively affected by AA, while allicin regulated cascade response of the microbiota-SCFAs signaling to reverse the reduction of acetic acid and propionic acid by AA treatment. Allicin also dramatically down-regulated the expression of Toll-like receptor 4 (TLR4), myeloid differentiation factor 88 (MyD88), NF-κB signaling pathway proteins, and proinflammatory cytokines by promoting the production of SCFAs in AA-treated rats. Allicin relieved the intestinal barrier injury and inflammation caused by AA as evidenced by the regulation cascade response of the microbiota-SCFAs-TLR4/MyD88/NF-κB signaling pathway. In conclusion, allicin is highly effective in the treatment and prevention of AA-induced intestinal injury.

Rosmarinic acid attenuates acrylamide induced apoptosis of BRL-3A cells by inhibiting oxidative stress and endoplasmic reticulum stress.

Acrylamide (AA) is a common endogenous contaminant in food, with a complex toxicity mechanism. The study on liver damage to experimental animals caused by AA has aroused a great attention. Rosmarinic acid (RosA) as a natural antioxidant shows excellent protective effects against AA-induced hepatotoxicity, but the potential mechanism is still unclear. In the current study, the protective effect of RosA on BRL-3A cell damage induced by AA was explored. RosA increased the activity of SOD and GSH, reduced the content of ROS and MDA, and significantly reduced the oxidative stress (OS) damage of BRL-3A cells induced by AA. RosA pretreatment inhibited the MAPK signaling pathway activated by AA, and down-regulated the phosphorylation of JNK, ERK and p38. RosA pretreatment also reduced the production of calcium ions caused by AA. In addition, the key proteins p-IRE1α, XBP-1s, TRAF2 of the IRE1 pathway, and the expression of endoplasmic reticulum stress (ERS) characteristic proteins GRP78, p-ASK1, Caspase-12 and CHOP were also down-regulated by RosA. NAC blocked the activation of the MAPK signaling pathway and inhibited the ERS pathway. RosA reduced the rate of apoptosis and down-regulated the expression of Bax/Bcl-2 and Caspase-3, thereby inhibiting AA-induced apoptosis. In conclusion, RosA reduced the OS and ERS induced by AA in BRL-3A cells, thereby inhibiting cell apoptosis, and it could be used as a potential protective agent against AA toxicity.

Progress on the relationship between preeclampsia and long-term cardiovascular disease among women / 中国综合临床

Preeclampsia(PE) is a unique disease to pregnancy women,and women who had a history of preeclampsia significantly increased the risk of cardiovascular disease.Preeclampsia etiology and pathogenesis is not clear yet,it may have common pathophysiology with cardiovascular disease(CVD),such as oxidative stress,endothelial injury,insulin resistance,lipid metabolic disorder and so on.The article reviewed the relationship between preeclampsia and long-term cardiovascular disease among women,especially discussed the disease such as coronary heart disease,hypertension and stroke,to find the association and to explore the potential risk management options for these high-risk women.To block,intervene,and prevent cardiovascular disease starting with preeclampsia,it is of significance to the cardiovascular health of over 300 million women worldwide.