ObjectiveTo investigate the effect of shikosin （SHI） on psoriasis （PSO） and explore the underlying mechanism via the cyclic guanosine monophosphate-adenosine monophosphate synthase （cGAS）/stimulator of interferon genes （STING） signaling pathway. MethodHaCaT cells were classified into normal culture（Control）， a mixture of five proinflammatory cytokines（M5）， low-， medium-， and high-dose SHI （L-SHI， M-SHI， and H-SHI， respectively）， and SHI+ADU-S100 groups. The cells in the M5 group were stimulated with 10 μg·L^-1 interleukin （IL）-1α， IL-17， IL-22， tumor necrosis factor （TNF）-α， and oncostatin M （OSM） for 48 h. The cells in the L-SHI， M-SHI， and H-SHI groups were treated with 0.1， 1， 10 μmol·L^-1 SHI， respectively， on the basis of the treatment in the M5 group. The cells in the SHI+ADU-S100 group were treated with 10 μmol·L^-1 STING activator ADU-S100 on the basis of the treatment in the H-SHI group. The methyl thiazolyl tetrazolium （MTT） assay and colony formation assay were employed to examine the effect of SHI on the proliferation of HaCaT cells. The wound healing assay was employed to examine the effect of SHI on the migration of HaCaT cells. Flow cytometry was employed to detect the effect of SHI on the apoptosis of HaCaT cells. Enzyme-linked immunosorbent assay was employed to measure the levels of IL-1β， IL-6， IL-15， IL-23， and interferon-γ （IFN-γ） in HaCaT cells. Western blot was employed to determine the protein levels of cGAS and STING in HaCaT cells. ResultCompared with Control group， the M5 group showed decreased survival rate， colony formation， and would healing rate of HaCaT cells， increased apoptosis rate， elevated levels of IL-1β， IL-6， IL-15， IL-23， and IFN-γ， and up-regulated protein levels of cGAS and STING （P<0.01）. Compared with the M5 group， the L-SHI， M-SHI， and H-SHI groups showed increased survival rate， cell colony formation， and wound healing rate， decreased apoptosis rate， lowered levels of IL-1β， IL-6， IL-15， IL-23， and IFN-γ， and down-regulated protein levels of cGAS and STING （P<0.01）. Compared with the H-SHI group， the SHI+ADU-S100 group showed decreased survival rate， cell colony formation， and wound healing rate， increased apoptosis rate， risen levels of IL-1β， IL-6， IL-15， IL-23， and IFN-γ， and up-regulated protein levels of cGAS and STING （P<0.01）. ConclusionSHI can inhibit the inflammation in the cell model of PSO by inhibiting the cGAS/STING signaling pathway.

Cystatin, a cysteine protease inhibitor found in many parasites, plays important roles in immune evasion. This study analyzed the molecular characteristics of a cystatin from Fasciola hepatica (FhCystatin) and expressed recombinant FhCystatin (rFhcystatin) to investigate the immune modulatory effects on lipopolysaccharide-induced proliferation, migration, cytokine secretion, nitric oxide (NO) production, and apoptosis in mouse macrophages. The FhCystatin gene encoded 116 amino acids and contained a conserved cystatin-like domain. rFhCystatin significantly inhibited the activity of cathepsin B. rFhCystatin bound to the surface of mouse RAW264.7 cells, significantly inhibited cell proliferation and promoted apoptosis. Moreover, rFhCystatin inhibited the expression of cellular nitric oxide, interleukin-6, and tumor necrosis factor-α, and promoted the expression of transforming growth factor-β and interleukin-10. These results showed that FhCystatin played an important role in regulating the activity of mouse macrophages. Our findings provide new insights into mechanisms underlying the immune evasion and contribute to the exploration of potential targets for the development of new drug to control F. hepatica infection.

Background: Bovine papillomatosis is a type of proliferative tumor disease of skin and mucosae caused by bovine papillomavirus (BPV). As a transboundary and emerging disease in cattle, it poses a potential threat to the dairy industry. Objectives: The aim of this study is to detect and clarify the genetic diversity of BPV circulating in dairy cows in Xinjiang, China. Methods: 122 papilloma skin lesions from 8 intensive dairy farms located in different regions of Xinjiang, China were detected by polymerase chain reaction. The genetic evolution relationships of various types of BPVs were analyzed by examining this phylogenetic tree. Results: Ten genotypes of BPV (BPV1, BPV2, BPV3, BPV6, BPV7, BPV8, BPV10, BPV11, BPV13, and BPV14) were detected and identified in dairy cows. These were the first reported detections of BPV13 and BPV14 in Xinjiang, Mixed infections were detected, and there were geographical differences in the distribution of the BPV genotypes. Notably, the BPV infection rate among young cattle (< 1-year-old) developed from the same supply of frozen sperm was higher than that of the other young cows naturally raised under the same environmental conditions. Conclusions Genotyping based on the L1 gene of BPV showed that BPVs circulating in Xinjiang China displayed substantial genetic diversity. This study provided valuable data at the molecular epidemiology level, which is conducive to developing deep insights into the genetic diversity and pathogenic characteristics of BPVs in dairy cows.

Background: Bovine papillomatosis is a type of proliferative tumor disease of skin and mucosae caused by bovine papillomavirus (BPV). As a transboundary and emerging disease in cattle, it poses a potential threat to the dairy industry. Objectives: The aim of this study is to detect and clarify the genetic diversity of BPV circulating in dairy cows in Xinjiang, China. Methods: 122 papilloma skin lesions from 8 intensive dairy farms located in different regions of Xinjiang, China were detected by polymerase chain reaction. The genetic evolution relationships of various types of BPVs were analyzed by examining this phylogenetic tree. Results: Ten genotypes of BPV (BPV1, BPV2, BPV3, BPV6, BPV7, BPV8, BPV10, BPV11, BPV13, and BPV14) were detected and identified in dairy cows. These were the first reported detections of BPV13 and BPV14 in Xinjiang, Mixed infections were detected, and there were geographical differences in the distribution of the BPV genotypes. Notably, the BPV infection rate among young cattle (< 1-year-old) developed from the same supply of frozen sperm was higher than that of the other young cows naturally raised under the same environmental conditions. Conclusions Genotyping based on the L1 gene of BPV showed that BPVs circulating in Xinjiang China displayed substantial genetic diversity. This study provided valuable data at the molecular epidemiology level, which is conducive to developing deep insights into the genetic diversity and pathogenic characteristics of BPVs in dairy cows.

Objective:To compare the prevalence of non-alcoholic fatty liver disease (NAFLD) in women with or without polycystic ovary syndrome (PCOS), and to evaluate association between PCOS and NAFLD.Methods:A cross-sectional study was performed including 122 PCOS patients (PCOS group) and 107 age, and body mass index (BMI)-matched women (control group). Anthropometric parameters, liver enzyme, lipid profile, glucose and insulin levels, sex hormones and hepatic ultrasonography were measured in all subjects. The clinical features, laboratory parameters and prevalence of NAFLD were compared between PCOS group and control group. The related factors were evaluated between PCOS and NAFLD, finally the role of insulin resistance (IR) and hyperandrogenism (HA) was analysed.Results:Women with PCOS had a significantly higher prevalence of NAFLD than those without PCOS (62.6% vs. 76.2%, P=0.025). Logistic regression found that HOMA-IR and FAI were associated with NAFLD in PCOS women ( OR=1.686, 95% CI=1.279-2.223; OR=1.167, 95% CI=1.039-1.311), however, there was no significant correlation between FAI and NAFLD after adjustment for HOMA-IR ( P>0.05). Conclusion:NAFLD is more prevalent in women with PCOS than in those without. Insulin resistance and HA drive risk of NAFLD in young female with PCOS. IR may be an independent risk factor for NAFLD, and the association between HA and NAFLD is not independent but is mediated by IR.

Objective:To compare the prevalence of non-alcoholic fatty liver disease (NAFLD) in women with or without polycystic ovary syndrome (PCOS), and to evaluate association between PCOS and NAFLD.Methods:A cross-sectional study was performed including 122 PCOS patients (PCOS group) and 107 age, and body mass index (BMI)-matched women (control group). Anthropometric parameters, liver enzyme, lipid profile, glucose and insulin levels, sex hormones and hepatic ultrasonography were measured in all subjects. The clinical features, laboratory parameters and prevalence of NAFLD were compared between PCOS group and control group. The related factors were evaluated between PCOS and NAFLD, finally the role of insulin resistance (IR) and hyperandrogenism (HA) was analysed.Results:Women with PCOS had a significantly higher prevalence of NAFLD than those without PCOS (62.6% vs. 76.2%, P=0.025). Logistic regression found that HOMA-IR and FAI were associated with NAFLD in PCOS women ( OR=1.686, 95% CI=1.279-2.223; OR=1.167, 95% CI=1.039-1.311), however, there was no significant correlation between FAI and NAFLD after adjustment for HOMA-IR ( P>0.05). Conclusion:NAFLD is more prevalent in women with PCOS than in those without. Insulin resistance and HA drive risk of NAFLD in young female with PCOS. IR may be an independent risk factor for NAFLD, and the association between HA and NAFLD is not independent but is mediated by IR.

Disulfiram (DSF) has been widely used in clinical treatment of alcoholism.To date,in vivo and in vitro experiments have demonstrated that DSF has strong anti-cancer activity and could improve patient's survival,and the underlying mechanism has been elaborated.In addition,it was reported that,during radiotherapy,DSF could protect normal tissue and cells meanwhile enhance the radiosensitivity of tumor cells by forming complexes with copper ions,suppressing cancer stem cells and inhibiting ubiquitin-proteasome system activity in cancer cells.This review summarizes the completed and ongoing clinical trials of disulfiram,and its anti-tumor mechanisms and advances in radiation biology.