Hepatoprotective effects of aspirin on diethylnitrosamine-induced hepatocellular carcinoma in rats by reducing inflammation levels and PD-L1 expression.

Aspirin, as a widely used anti-inflammatory drug, has been shown to exert anti-cancer effects in a variety of cancers. PD-L1 is widely expressed in tumor cells and inhibits anti-tumor immunity. This study aims to clarify whether aspirin exerts its anti-hepatocellular carcinoma (HCC) effect by inhibiting PD-L1 expression. The rat model of HCC was established by drinking 0.01% diethylnitrosamine (DEN), and aspirin was given by gavage. The gross and blood biochemical indexes of rats were analyzed. CD4 and CD8 expression in liver tissues were investigated by immunohistochemistry. CCK8 assay was used to detect the inhibitory effect of aspirin on the proliferation of HCC cells. The regulatory effect of aspirin on PD-L1 expression was analyzed by western blot. As a result, the tumor number and liver weight ratio in the DEN + ASA group were lower than those in the DEN group (P = 0.006, P = 0.046). Compared with the DEN group, the expression of CD4 in the DEN + ASA group was significantly increased, while CD8 was decreased (all P < 0.01). Biochemical indexes showed that there were differences in all indexes between the DEN and control group (P < 0.05). The levels of DBIL, ALP, and TT in the DEN + ASA group were lower than those in the DEN group (P = 0.038, P = 0.042, P = 0.031). In the DEN group, there was an obvious fibrous capsule around the tumor, and the portal vein was dilated. The pathological changes were mild in the DEN + ASA group. Compared with the DEN group, the expression of PD-L1 in liver tissue of the DEN + ASA group was decreased (P = 0.0495). Cytological experiments further showed that aspirin could inhibit the proliferation and PD-L1 expression in Hep G2 and Hep 3B cells. In conclusion, aspirin can inhibit the proliferation of HCC cells and reduce tumor burden by reducing inflammation and targeting PD-L1.

Internal electric field induced photocarriers separation of nickel-doped pyrite/pyrite homojunction with rich sulfur vacancies for superior Cr(VI) reduction.

Improving the separation efficiency and transfer ability of photoinduced electrons/holes in pyrite (FeS2)-based photocatalytic materials is significant for the photoreduction of hexavalent chromium (Cr(VI)) but still remains a challenge. Herein, a novel homojunction was prepared through in-situ growth of nickel (Ni) doped FeS2 nanoparticles on FeS2 nanobelts (denoted as Ni-FeS2/FeS2). Systematical characterizations revealed that Ni doped FeS2 nanoparticles have been successfully in situ grown along the lattice of FeS2 nanobelts. Photoreduction experiments demonstrated that the Ni-FeS2/FeS2 homojunction with 2 mmol Ni doping contents (denoted as 2Ni-FeS2/FeS2) exhibited the optimum Cr(VI) reduction efficiency among the studied catalysts. Density Functional Theory (DFT) calculated results verified that Ni doping could not only be advantageous for the formation of sulfur vacancies but also modify the band gap and band structure of FeS2 nanoparticles. Moreover, several doping energy levels caused by Ni doping have also appeared near the Fermi level of FeS2 nanoparticles. The migration paths of electrons and the existence of internal electric field (IEF) in homojunction were further verified by the calculation of work function. To sum up, the doping energy levels and IEF that produced by homojunction played important roles in accelerating the separation efficiency of its photogenerated carriers.

The optimal transplantation strategy of umbilical cord mesenchymal stem cells in spinal cord injury: a systematic review and network meta-analysis based on animal studies.

OBJECTIVE: Umbilical cord mesenchymal stem cells (UCMSCs) have great potential in the treatment of spinal cord injury. However, the specific therapeutic effect and optimal transplantation strategy are still unclear. Therefore, exploring the optimal treatment strategy of UCMSCs in animal studies by systematic review can provide reference for the development of animal studies and clinical research in the future. METHODS: Databases of PubMed, Ovid-Embase, Web of Science, CNKI, WanFang, VIP, and CBM were searched for the literature in February 11, 2022. Two independent reviewers performed the literature search, identification, screening, quality assessment, and data extraction. RESULTS AND DISCUSSION: A total of 40 animal studies were included for combined analysis. In different subgroups, the results of traditional meta-analysis and network meta-analysis were consistent, that is, the therapeutic effect of high-dose (≥ 1 × 106) transplantation of UCMSCs was significantly better than that of low dose (< 1 × 106), the therapeutic effect of local transplantation of UCMSCs was significantly better than that of intravenous transplantation, and the therapeutic effect of subacute transplantation of UCMSCs was significantly better than that of acute and chronic transplantation. However, in view of the inherent risk of bias and limited internal and external validity of the current animal studies, more high-quality, direct comparison studies are needed to further explore the optimal transplantation strategy for UCMSCs in the future.

Aspirin Use and the Risk of Hepatocellular Carcinoma: A Meta-analysis.

INTRODUCTION AND AIM: The use of aspirin is a potential protective factor against the development of hepatocellular carcinoma (HCC). Therefore, we conducted a meta-analysis to evaluate the contribution of aspirin to the risk of HCC. METHODS: We searched for PubMed and EMBASE through September 2021. RESULTS: Eighteen studies (16 cohort, 2 case-control) were included. Aspirin users were less likely to develop HCC than nonusers [adjusted odds ratio (OR), 0.54; 95% confidence interval (CI): 0.44-0.66]. Stratified analysis showed that aspirin reduced the risk of HCC in Asian and Western populations (OR, 0.59 vs. 0.67). Besides, aspirin has protective effects against HCC after hepatitis B virus (OR, 0.70; 95% CI: 0.52-0.93) and hepatitis C virus infections (OR, 0.41; 95% CI: 0.23-0.73). Aspirin has protective effects on people with chronic liver disease (OR, 0.46; 95% CI: 0.31-0.67) and on the general population (OR, 0.65; 95% CI: 0.54-0.79). In addition, confounding factors have an important impact on the results of aspirin prevention of liver cancer before (OR, 0.28; 95% CI: 0.06-1.27) and after (OR, 0.58; 95% CI: 0.47-0.71) adjustment. Further studies have shown that those in the long duration group do not experience better effects in preventing HCC (OR, 0.62 vs. 0.63). A further meta-analysis of 3 articles showed that the use of aspirin did not increase the risk of bleeding in patients with HCC (OR, 1.19; 95% CI: 0.87-1.64). CONCLUSION: Our meta-analysis shows that the use of aspirin is associated with a lower risk of liver cancer.

DNA methylation and single-nucleotide polymorphisms in DDX58 are associated with hand, foot and mouth disease caused by enterovirus 71.

BACKGROUND: This research aimed to explore the association between the RIG-I-like receptor (RIG-I and MDA5 encoded by DDX58 and IFIH1, respectively) pathways and the risk or severity of hand, foot, and mouth disease caused by enterovirus 71 (EV71-HFMD). In this context, we explored the influence of gene methylation and polymorphism on EV71-HFMD. METHODOLOGY/PRINCIPAL FINDINGS: 60 healthy controls and 120 EV71-HFMD patients, including 60 mild EV71-HFMD and 60 severe EV71-HFMD patients, were enrolled. First, MiSeq was performed to explore the methylation of CpG islands in the DDX58 and IFIH1 promoter regions. Then, DDX58 and IFIH1 expression were detected in PBMCs using RT-qPCR. Finally, imLDR was used to detect DDX58 and IFIH1 single-nucleotide polymorphism (SNP) genotypes. Severe EV71-HFMD patients exhibited higher DDX58 promoter methylation levels than healthy controls and mild EV71-HFMD patients. DDX58 promoter methylation was significantly associated with severe HFMD, sex, vomiting, high fever, neutrophil abundance, and lymphocyte abundance. DDX58 expression levels were significantly lower in mild patients than in healthy controls and lower in severe patients than in mild patients. Binary logistic regression analysis revealed statistically significant differences in the genotype frequencies of DDX58 rs3739674 between the mild and severe groups. GeneMANIA revealed that 19 proteins displayed correlations with DDX58, including DHX58, HERC5, MAVS, RAI14, WRNIP1 and ISG15, and 19 proteins displayed correlations with IFIH1, including TKFC, IDE, MAVS, DHX58, NLRC5, TSPAN6, USP3 and DDX58. CONCLUSIONS/SIGNIFICANCE: DDX58 expression and promoter methylation were associated with EV71 infection progression, especially in severe EV71-HFMD patients. The effect of DDX58 in EV71-HFMD is worth further attention.