Objective:To explore the effect and mechanism of CXCL10 on immune-mediated liver injury.Methods:The CXCL10 expression vector was injected into mice by hydrodynamic injection.The levels of CXCL10 in the liver were measured 72 hours after injection.Concanavalin A (ConA) was injected into mice to induce immune-mediated liver injury.The levels of alanine a minotransferase (ALT),tissue damage,IFN-γ,TNF-α and percentages and numbers of regulatory T cells were tested and compared between CXCL10 expression group and control group.Results:The levels of CXCL10 in the liver were significantly increased at 72 hours after CXCL10 expression vector was injected.The pretreatment of CXCL10 expression vector markedly reduced ConA-induced ALT levels,IFN-γlevels and TNF-α levels.Additionally,the pretreatment of CXCL10 expression vector increased the percentages and numbers of regulatory T ceils in the liver.Conclusion:The pretreatment of CXCL10 expression vector decreases the levels of inflammatory cytokines and attenuates ConA-induced liver injury,which might be beneficial for the treatment for immune-mediated liver injury.

Natural killer cells are the key effector cells in innate immune response,playing the role in pathogen clearance and tumor immunosurveillance by cytokine secretion and cytotoxicity.Hematopoietic stem cells go through developmental intermediates to generate mature NK cells under the progressive regulation of extrinsic factors and intrinsic factors.In the past thirty years, great progresses have been made in the developmental progress,niches,regulation of NK cells and the relationship between NK cells and dis-eases.In this review,we will discuss in detail the molecular mechanisms of NK cell development and the diseases caused by functional compromise of NK cells.

Objective To evaluate the strategy using cyanoacrylate tissue adhesive (CTA) in amniotic membrane transplantaton(AMT) to manage corneoscleral melting in severe ocular burns. Methods Twelve eyes from eleven patients with chemical or thermal burns of grade Ⅳ were recruited for this study.After medical treatment failed to arrest corneal or sclera melting,CTA were applied directly on the ulcerating corneal or sclera surface to augmented AMT. Results In all cases,all sclera ulcerations (five of eleven) were prevented or healed,epithelialization of burned cornea (eight of eleven) was complete,corneal ulceration in the rest three eyes was successfully arrested. Conclusion Tissue adhesive aided amniotic membrane transplantation is a promising altermnative in managing severe corneoscleral melting in chemical or thermal burns to maintain the integrity of the ocular wall.

BACKGROUND: Previous studies found that C57BL/6 mouse was susceptible to atherosclerosis, while BALB/c mouse was resistant to atherosclerosis. The stenosis of the culprit vessel and the severity of myocardial infarction were correlated to the levels of OX40L expression. Whether OX40L has differential expression between C57BL/6 and BALB/c mouse was not identified.OBJECTIVE: To observe the differential expression of OX40L mRNA and protein in C57BL/6 and BALB/c mouse.METHODS: Total RNA and protein were extracted by Trizol and RIPA Buffer from heart, brain, kidney, skeletal muscle and spleen tissues of C57BL/6 and BALB/c mice. RT-PCR and Western Blot were used to detect OX40L mRNA and protein expression in heart, brain, kidney, spleen and skeletal muscle of two kinds of mice. The differential expression of OX40L mRNA and protein between C57BL/6 and BALB/c mice was observed.RESULTS AND CONCLUSION: RT-PCR results showed that the mRNA expression level of OX40L in heart of C57BL/6 mice mouse was significantly higher than BALB/c mice (P ＜ 0.05); the mRNA expression level of OX40L in spleen of BALB/c mice was significantly higher than C57BL/6 mice (P ＜ 0.05). There were no significant differences in the brain, kidney and skeletal muscle between these two strains. The results of Western Blot showed that the protein expression level of OX40L in heart, brain and kidney of C57BL/6 mice were significantly higher than BALB/c mice (P ＜ 0.05). There were no significant differences in skeletal muscle and spleen between these two strains. The OX40L mRNA transcription level in heart was higher in C57BL/6 mouse than BALB/c mouse, while the expression in spleen was lower than the latter. The OX40L protein levels in C57BL/6 mouse heart, brainand kidney were higher than BALB/c mouse. The differences of OX40L expression between the two strains of mice indicated that OX40L may promote to C57BL/6 mouse susceptible to atherosclerosis.

Liver cancer is one of the most common neoplastic diseases with high mortality in China. Currently, antimicrotubule drugs such as paclitaxel (PTX) and vincristine (VCR), are used as the common agents in the clinical chemotherapy for liver cancer. However, the responses of patients to these drugs vary markedly. Successful identification of intracellular factors influencing liver cancer's sensitivity to antimicrotubule drugs would be of great clinical importance. In this study, by engineering human hepatoma cell HepG2 to overexpress synuclein-gamma (SNCG), we investigated if SNCG is a molecular factor associated with the sensitivity to antimicrotubule drug treatment. Real-time RT-PCR and Western blotting assays showed SNCG was successfully overexpressed in HepG2/ SNCG cells compared with HepG2/Neo cells. The overexpressed SNCG altered the proliferation activity in HepG2 cells, which was 66% higher than that of HepG2/Neo cells through MTT method. The overexpressed SNCG also reduced sensitivity of HepG2 cells to antimicrotubule drugs: after PTX or VCR treatment, the proportion of HepG2/SNCG cells in G2/M arrest was significantly lower than that in HepG2/Neo cells. Correspondingly, HepG2/SNCG cells showed significantly lower mitotic index than HepG2/Neo cells. Meanwhile, HepG2/SNCG cells showed higher resistance to PTX and VCR than HepG2/Neo cells, with resistance index 21 and 15 respectively. Our studies suggested that the overexpression of SNCG could confer resistance to antimicrotubule drugs in hepatoma cells; and it indicated that SNCG may be as a potential response marker for antimicrotubule drugs in liver cancer chemotherapy.

γδ T cells display unique developmental, distributional, and functional patterns and can rapidly respond to various insults and contribute to diverse diseases. Different subtypes of γδ T cells are produced in the thymus prior to their migration to peripheral tissues. γδ T cells are enriched in the liver and exhibit liver-specific features. Accumulating evidence reveals that γδ T cells play important roles in liver infection, non-alcoholic fatty liver disease, autoimmune hepatitis, liver fibrosis and cirrhosis, and liver cancer and regeneration. In this study, we review the properties of hepatic γδ T cells and summarize the roles of γδ T cells in liver diseases. We believe that determining the properties and functions of γδ T cells in liver diseases enhances our understanding of the pathogenesis of liver diseases and is useful for the design of novel γδ T cell-based therapeutic regimens for liver diseases.
Animals ; Cytokines ; immunology ; Humans ; Liver Diseases ; immunology ; Liver Regeneration ; immunology ; Mice ; T-Lymphocytes, Regulatory ; immunology

Three hundred and twenty endophytic actinobacterial strains were isolated from psammophytes collected from Taklamakan Desert and identified.Among them,three strains already had been identified as new species of two genera and sixteen isolates showed relatively low 16S rRNA similarities＜98.6％to validly described species.Seventy-five of the isolates were selected as representative strains to screen antibacterial activity and mechanism.Forty-seven strains showed antagonistic activity against at least one of the indicator bacteria.Two Streptomyces strains produced bioactive compounds inducing DNA damage,and two Streptomyces strains produced bioactive compounds with inhibitory activity on protein biosynthesis.Notably,the strain Streptomyces sp.8P21H-1 that demonstrated both strong antibacterial activity and inhibitory activity on protein biosynthesis was prioritized for exploring new antibiotics.Under the strategy of integrating genetics-based discovery program and MS/MS-based molecular networking,two new streptogramin-type antibiotics,i.e.,acetyl-griseoviridin and desulphurizing gri-seoviridin,along with known griseoviridin,were isolated from the culture broth of strain 8P21H-1.Their chemical structures were determined by HR-MS,and 1D and 2D NMR.Desulphurizing griseoviridin and griseoviridin exhibited antibacterial activities by inhibiting translation.

Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease worldwide. Fat accumulation "sensitizes" the liver to insult and leads to nonalcoholic steatohepatitis (NASH). G protein-coupled receptor 35 (GPR35) is involved in metabolic stresses, but its role in NAFLD is unknown. We report that hepatocyte GPR35 mitigates NASH by regulating hepatic cholesterol homeostasis. Specifically, we found that GPR35 overexpression in hepatocytes protected against high-fat/cholesterol/fructose (HFCF) diet-induced steatohepatitis, whereas loss of GPR35 had the opposite effect. Administration of the GPR35 agonist kynurenic acid (Kyna) suppressed HFCF diet-induced steatohepatitis in mice. Kyna/GPR35 induced expression of StAR-related lipid transfer protein 4 (STARD4) through the ERK1/2 signaling pathway, ultimately resulting in hepatic cholesterol esterification and bile acid synthesis (BAS). The overexpression of STARD4 increased the expression of the BAS rate-limiting enzymes cytochrome P450 family 7 subfamily A member 1 (CYP7A1) and CYP8B1, promoting the conversion of cholesterol to bile acid. The protective effect induced by GPR35 overexpression in hepatocytes disappeared in hepatocyte STARD4-knockdown mice. STARD4 overexpression in hepatocytes reversed the aggravation of HFCF diet-induced steatohepatitis caused by the loss of GPR35 expression in hepatocytes in mice. Our findings indicate that the GPR35-STARD4 axis is a promising therapeutic target for NAFLD.

Bacteremia is a life-threating syndrome often caused by methicillin-resistant (MRSA). Thus, there is an urgent need to develop novel approaches to successfully treat this infection. Staphylococcal accessory regulator A (SarA), a global virulence regulator, plays a critical role in pathogenesis and -lactam antibiotic resistance in . Hypericin is believed to act as an antibiotic, antidepressant, antiviral and non-specific kinase inhibitor. In the current study, we investigated the impact of hypericin on -lactam antibiotics susceptibility and mechanism(s) of its activity. We demonstrated that hypericin significantly decreased the minimum inhibitory concentrations of -lactam antibiotics (.., oxacillin, cefazolin and nafcillin), biofilm formation and fibronectin binding in MRSA strain JE2. In addition, hypericin significantly reduced expression, and subsequently decreased and virulence-related regulators (.., ) and genes (.., and ) expression in the studied MRSA strain. Importantly, the synergistic effect of hypericin with -lactam antibiotic (.., oxacillin) translated into therapeutic outcome in a murine MRSA bacteremia model. These findings suggest that hypericin plays an important role in abrogation of -lactam resistance against MRSA through inhibition, and may allow us to repurpose the use of -lactam antibiotics, which are normally ineffective in the treatment of MRSA infections (.., oxacillin).

(E)-Methyl-4-aryl-4-oxabut-2-enoate (YH-8) is a novel PKnB protein kinase inhibitor with good anti-tuberculosis activity. To evaluate its pharmacokinetics in rats, a sensitive and selective high performance liquid chromatography-tandem mass spectrometric (LC--MS/MS) method has been developed and validated for the quantification of YH-8 in rat plasma for the first time. Samples were pre-treated using a liquid--liquid extraction with ethyl acetate and the chromatographic separation was performed on a C18 column by gradient elution with methanol--water as the mobile phase. YH-8 was detected using a tandem mass spectrometer in positive selected reaction monitoring (SRM) mode. Method validation revealed good linearity over the range of 1-500 ng/mL for YH-8 with a lower limit of quantification (LLOQ) of 1 ng/mL. Intra- and inter-day precision of YH-8 assay in rat plasma samples were 2.0%-6.8%, with accuracy of the method being 100.69%-106.18%. Stability test showed that when spiked into rat plasma, YH-8 was stable for 12 h at room temperature, for up to 15 days at -70 °C, and after three freeze-thaw cycles. Extracted samples were found to be stable over 12 h in an auto-sampler. The method was successfully applied to the pharmacokinetic study of YH-8 in rats after oral administration at 100 mg/kg and 200 mg/kg.