Oridonin Alters Hepatic Urea Cycle via Gut Microbiota and Protects against Acetaminophen-Induced Liver Injury.

Acetaminophen (APAP) hepatotoxicity is the leading cause of acute liver failure in the western world. Oridonin (OD), which is the major active ingredient of the traditional Chinese medicine Rabdosia rubescens, reportedly exerts anti-inflammatory and antioxidative effects. Here, we first find that OD protects against APAP-induced hepatotoxicity. The results of hepatic tissue-associated RNA-seq and metabolomics showed that the protective effects of OD were dependent upon urea cycle regulation. And such regulation of OD is gut microbiota partly dependent, as demonstrated by fecal microbiota transplantation (FMT). Furthermore, using 16S rRNA sequencing, we determined that OD significantly enriched intestinal Bacteroides vulgatus, which activated the nuclear factor erythroid 2-related factor 2 (Nrf2) pathway to regulate redox homeostasis against APAP by urea cycle. In conclusion, our study suggests that the Bacteroides vulgatus-urea cycle-Nrf2 axis may be a potential target for reducing APAP-induced liver injury, which is altered by OD.

[Interleukin?22 promotes proliferation of fibroblast?like synoviocytes from patients with rheumatoid arthritis by inducing STAT3 phosphorylation].

OBJECTIVE: To clarify the mechanism by which interleukin?22 (IL?22) promotes the proliferation of fibroblast?like synoviocytes (FLS) from patients with rheumatoid arthritis (RA). METHODS: FLS were isolated from the synovial tissues of patients with RA and identified by immunohistochemistry for vimentin/CD68. The cells were subcultured and incubated with different concentrations of IL?22 for 24, 48, or 72 h, and their proliferation was examined using MTT assay. After treatment of the cells with IL?22 and AG490, alone or in combination, the expressions of the total and phosphorylated proteins of STAT3, ERK1/2 and P38 were detected with Western blotting. RESULTS: IL?22 significantly increased the proliferation of FLS in a dose?dependent manner (P<0.05). The total protein of STAT3 in the cells showed no significant changes with extended time of IL?22 treatment (P=0.68), but the expression of phosphorylated STAT3 protein increased significantly (P<0.001). The total and phosphorylated proteins of ERK1/2 and P38 underwent no significant changes after IL?22 treatment (P>0.05). A combined treatment with 50 ng/mL IL?22 and 100 µmol/L AG490 resulted in a significant decrease in the proliferation of FLS as compared with IL?22 treatment alone (P<0.01). CONCLUSION: IL?22 can dose?dependently promote the proliferation of FLS from patients with RA by inducing phosphorylation of STAT3 protein but not through ERK1/2 or P38 signal pathway.

[Identification of Zaocys type II collagen and its effect on arthritis in mice with collagen-induced arthritis].

OBJECTIVE: To analyze the homology of Zaocys type 1I collagen ( ZC II ) with the C II collagen from other species, and to investigate the effect of ZC II on arthritis in mice with collagen-induced arthritis (CIA). METHODS: ZC II was purified with restriction pepsin digestion. Then SDS-PAGE gel electrophoresis and UV spectrophotometry were used to identify the protein,the homology of the ZC II peptide was analyzed with Mass Spectrometry. The model of CIA mice were induced by subcutaneous injection of Chicken C II into male C57BL/6 mice from the base of the tails. After immunization,ZC II [H,M,L:40,20 and 10 µg/(kgd) ]was administered orally to mice from day 21 to 28 accordingly. The severity of the arthritis in each limb was evaluated using a macroscopic scoring system, and his- topathological change of joint was observed by light microscope with HE staining. RESULTS: The molecular weight of ZC II protein deter- mined by SDS-PAGE gel electrophoresis was between 110 kD and 140 kD, and UV absorption peak appeared at around 230 nm in wave- length. The peptide mass fingerprinting(PMF) of the purified protein by Mass Spectrometry analysis showed that it had at least 4 peptides matched with other species,and the protein score was greater than 95%. Compared with normal group,the CIA model group had significantly higher scores for arthritis and histopathological changes (P <0. 05). Meanwhile,the same scores for the ZC II peptide-treated mice with CIA were significantly lower than the mice from CIA model group(P <0. 05). CONCLUSION: Results of Mass Spectrometry analysis demonstrate that ZC II has high homology with the C II from other species. Oral administration of ZC II can suppress arthritis in mice with CIA and ameliorate the histopathological changes of the joint.

Liver cancer mortality trends during the last 30 years in Hebei province: comparison results from provincial death surveys conducted in the 1970's, 1980's, 1990's and 2004-2005.

BACKGROUND AND AIMS: Liver cancer is a major health problem in low-resource countries. Approximately 55% of all liver cancer occurs in China. Hebei Province is one of the important covering nearly 6% of the population of China. The aim of this paper was to explore liver cancer mortality trends during past 30 years, and provide basic information on prevention strategies. METHODS: Hebei was covered covered all the three national surveys during 1973-1975, 1990-1992, and 2004-2005 and one provincial survey during 1984-1986. Subjects included all cases dying from liver cancer in Hebei Province. Liver cancer mortality trend and geographic differences across cities and counties were analyzed. RESULTS: There were 82,878 deaths in Hebei Province during 2004-2005 with an average mortality rate was 600.9/10,000, and an age-adjusted rate of 552.3/10,000. Those dying of cancer were 18,424 cases, accounting for 22.2% of all deaths, second only to cerebrovascular disease as a cause of death. Cancer mortality was 133.6/100,000 (age-adjusted rate was 119.2/100,000). Liver cancer ranked fourth in this survey with a mortality rate of 21.0/100,000, 28.4/100,000 in males and 13.35/10,000 in females, accounting for 15.7%, 17.1% and 13.4% of the total number of cancer deaths and in males and females, respectively. The sex ratio was 2.13. Since the 1970s, liver cancer deaths of Hebei province have been increasing slightly. The crude mortality rates in the four surveys were 11.3, 16.0, 17.4, 21.0 per 100,000, respectively, with age-adjusted rates fluctuating during the past 30 years, but the trend also being upwards. There is a tendency for the mortality rates to be higher in coastal than mountain areas, and is relative lower in the plain area, with crude mortality rates of 25.3, 22.1, and 19.1 per 100,000, respectively. There were no notable differences in cride data between urban and rural, but the age-adjusted mortality rate in rural was much higher. CONCLUSION: Our study indicated that the mortality of liver cancer in Hebei Province is lower than the national average level. There is a slightly increase trend, especially in some counties. Liver cancer is a major health problem and it is necessary to further promote prevention strategies in Hebei province.