[Effects of Faecalibacterium prausnitzii supernatant on Th17 cell and IL-17A in dextran sulfate sodium-induced ulcerative colitis mice].

OBJECTIVE: To explore the protective and therapeutic effects of Faecalibacterium prausnitzii (Fp) supernatant on ulcerative colitis (UC) in mice induced by dextran sulfate sodium (DSS) and the underlying mechanisms.
 METHODS: Forty male mice were randomly divided into a control group, a model group, a treatment group and a prevention group (n=10 in each group). The colorectal histopathologic damage score (HDS) were calculated; the proportion of helper T cell (Th17) in mononuclear cells (MNC) in spleen, the levels of IL-17A and IL-6 in plasma were detected; the mRNA levels of transcription factor retinoic acid-related orphan receptor-γt (ROR-γt), interleukin (IL)-17A and IL-6 in colon mucosa tissues were also determined.
 RESULTS: Compared with the model group, the colon HDS in the treatment group and the prevention group were significantly decreased (both P<0.05), but there was no significant difference in the treatment group and the prevention group (P>0.05). The proportion of Th17 cells in spleen in the treatment group and the prevention group was also remarkably lower than that in the model group (both P<0.01). The levels of IL-17A and IL-6 in plasma in the treatment group were significantly lower than those in the model group (both P<0.05). The mRNA expression of ROR-γt, IL-17A and IL-6 in the colon mucosa tissues in the treatment group were remarkably lower than those in the model group (all P<0.05). But there was no statistic difference in the level of IL-6 in the plasma and the colon mucosa tissues between the prevention group and the model group (P>0.05).
 CONCLUSION: Fp supernatant has protective and therapeutic effects on ulcerative colitis in mice induced by DSS, which might be mediated by decrease of Th17 and IL-17A levels in the plasma and the colon mucosa tissues. Fp supernatant also can decrease mice colitis by reducing IL-6 levels.

Drug rash with eosinophilia and systemic symptoms and severe renal injury induced by proton pump inhibitor therapy: A case report.

INTRODUCTION: Proton pump inhibitors (PPIs) are widely prescribed and generally well tolerated but can rarely cause severe allergic reactions, such as drug rash with eosinophilia and systemic symptoms (DRESS). We report a case of DRESS and renal injury induced by PPIs, and describe the therapeutic process. PATIENT CONCERNS: The patient was a 66-year-old female who complained of fever, pruritus, desquamation, erythema multiforme, and anuria caused by omeprazole taken for 2 weeks to treat abdominal distention. DIAGNOSIS: The clinical history revealed a similar episode of PPI-induced fever, eosinophilia, and acute kidney injury more than 1 year ago. The present laboratory tests revealed eosinophilia and oliguric renal failure. The renal biopsy was performed subsequently and proved the diagnosis of PPI-induced DRESS. INTERVENTIONS: After the suspected diagnosis of PPI-induced DRESS, omeprazole was discontinued and methylprednisolone infusion (40 mg qd) was initiated. Because of oliguric renal failure, the patient received intermittent hemodialysis. OUTCOMES: The patient initially responded to omeprazole discontinuation, hemodialysis, and glucocorticoids but later died from severe infection during the tapering of glucocorticoid therapy. CONCLUSION: Clinicians should remain on high alert for potential life-threatening complications when prescribing PPIs. If unexplained renal injury develops in a patient taking a PPI, renal biopsy may help in identifying the pathogenesis and might facilitate timely intervention.

Faecalibacterium prausnitzii supernatant ameliorates dextran sulfate sodium induced colitis by regulating Th17 cell differentiation.

AIM: To explore the preventive and therapeutic effects of Faecalibacterium prausnitzii (F. prausnitzii) supernatant on dextran sulfate sodium (DSS) induced colitis in mice. METHODS: Forty C57BL/6J male mice were randomly divided into four groups: control group, model group, treatment group, and prevention group. Mice were weighed daily. On day 10, the colon length was measured, the colorectal histopathologic damage score (HDS) was assessed, and plasma interleukin (IL)-17A, IL-6, and IL-4 levels were detected by enzyme-linked immunosorbent assay. The expression of transcription factor retinoic acid-related orphan receptor-γt (RORγt) and IL-17A in colon inflammatory mucosa tissue were determined by immunohistochemical assay, and the expression levels of RORγt mRNA, IL-17A mRNA, and IL-6 mRNA were detected by real-time quantitative polymerase chain reaction (PCR). The proportion of Th17 in mononuclear cells in spleen was assayed by fluorescence activated cell sorter. RESULTS: When compared with the model group, the colon length (P < 0.05) and body weight (P < 0.01) in the treatment and prevention groups were significantly increased, and the colon HDS was decreased (P < 0.05 and P < 0.01). There was no statistical difference between the treatment group and prevention group. After treatment with F. prausnitzii supernatant, the plasma levels of IL-17A and IL-6 (P < 0.05), the protein and mRNA expression of IL-17A and RORγt, and the Th17 cell ratio of spleen cells (P < 0.01) were significantly decreased compared to the model group. Plasma IL-4 level in the prevention group was significantly higher than that in the model group (P < 0.05), but there was no significant difference between these two groups in the expression of IL-6 in both the plasma and colon mucosa tissues. CONCLUSION: F. prausnitzii supernatant exerts protective and therapeutic effects on DSS-induced colitis in mice, probably via inhibition of Th17 differentiation and IL-17A secretion in the plasma and colon mucosa tissues. It can also improve colitis in mice by downregulating IL-6 and prevent colitis by upregulating IL-4.

AR-42 induces apoptosis in human hepatocellular carcinoma cells via HDAC5 inhibition.

Histone deacetylases (HDACs) play critical roles in apoptosis and contribute to the proliferation of cancer cells. AR-42 is a novel Class I and II HDAC inhibitor that shows cytotoxicity against various human cancer cell lines. The present study aims to identify the target of AR-42 in hepatocellular carcinoma (HCC) as well as evaluate its therapeutic efficacy. We found that HDAC5 was upregulated in HCC tissues compared to adjacent normal tissues, and this was correlated with reduced patient survival. CCK8 and colony-formation assays showed that HDAC5 overexpression promotes proliferation in HCC cell lines. Treatment with AR-42 decreased HCC cell growth and increased caspase-dependent apoptosis, and this was rescued by HDAC5 overexpression. We demonstrated that AR-42 can inhibit the deacetylation activity of HDAC5 and its downstream targets in vitro and in vivo. Taken together, these results demonstrate for the first time that AR-42 targets HDAC5 and induces apoptosis in human hepatocellular carcinoma cells. AR-42 therefore shows potential as a new drug candidate for HCC therapy.

[Genetic analysis of a heading-delayed mutant by T-DNA insertion in rice (Oryza sativa L.)].

Transposon tagging was used to isolate genes in higher plant. In this study, a delayed heading mutant caused by T-DNA insertion in rice was identified. Genetic analysis of the mutant showed that the three types of phenotype, normal heading, delayed heading and overly delayed heading in the segregating populations derived from the T-DNA heterozygotes fit the ratio of 1:2:1. Test for Basta resistance showed the delayed heading plants were all resistant while the normal heading plants were susceptible, and the ratio of resistant and susceptible plants was 3:1, which indicated that the delayed heading mutant was co-segregated with Basta resistance. The delayed heading mutant caused by T-DNA insertion was confirmed by T-DNA detection using PCR method. This delayed heading mutant will be used for isolation of the tagged gene in rice.