Berberine (BBR) is an isoquinoline alkaloid derived from various medicinal herbs. Previous studies have suggested that BBR exerts antimicrobial, antitumor, and antidiabetic effects and can be used to treat Helicobacter pylori-induced chronic gastritis. However, the exact mechanism by which BBR inhibits H. pylori infection is not fully understood. We investigated the anti-inflammatory properties and potential mechanism of BBR in H. pylori-infected mice with chronic gastritis. We found that BBR can suppress the expression of pro-inflammatory genes IL-6, TGF-β, and IL-1β and upregulate anti-inflammatory gene IL-10 expression in the mucosa and RAW 264.7 macrophages. Exposure to BBR also reduced the expression and accumulation of IL-17 in the mucosa and CD4 T cells activated by anti-CD3 and anti-CD28, and it decreased the frequency of IL-17-producing CD4 T cells. B cell-activating factor (BAFF) production was inhibited by BBR and by cultured dendritic and CD4 T cells. Furthermore, we demonstrated that BAFF can trigger the Th17 response by promoting the production of pro-Th17 cytokines IL-6, TGF-β, and IL-1β, which are strongly associated with the anti-inflammatory role of BBR in chronic gastritis caused by H. pylori. In conclusion, we determined that BBR has anti-inflammatory effects on H. pylori-induced chronic gastritis by attenuating the BAFF-triggered Th17 response.
BackgroundGastric cancer is among the most common types of cancer, with high morbidity and mortality. MicroRNAs (miRNAs) play vital roles in the tumorigenesis and biology of gastric cancer. This study aimed to reveal the role of miR-340 in gastric cancer cell proliferation and apoptosis and to elucidate the potential mechanisms.Material/MethodsHuman gastric cancer cells SGC-7901 were used in this study for cell transfection with miR-340 mimic or inhibitor. After transfection, cell viability, proliferation, and apoptosis were examined by MTT, BrdU, and flow cytometry assays, respectively. The protein level changes of p27, p21, Caspase 3 (CASP3), B cell lymphoma 2 (BCL2), BCL2-associated X protein (BAX), and v-AKT murine thymoma viral oncogene (AKT) were detected by Western blot.ResultsOverexpression of miR-340 significantly reduced cell viability and proliferation (P<0.01), and induced cell apoptosis (P<0.01) of SGC-7901. miR-340 elevated the protein level of cell cycle inhibitor p27, but did not affect the level of p21. Apoptosis-related factors pro-CASP3, cleaved-CASP3, and BAX were promoted, and BCL2 was inhibited by miR-340. miR-340 also suppressed the phosphorylation of AKT. Opposite effects were detected when SGC-7901 cells were transfected with miR-340 inhibitor.ConclusionsThese results indicate that miR-340 can inhibit proliferation and induce apoptosis of SGC-7901 cells, suggesting its roles in protecting against gastric cancer. The roles of miR-340 in gastric cancer cells may be associated with its regulation of the AKT pathway. Thus, miR-340 may be a potential therapeutic strategy for gastric cancer treatment.
Recently, impacts of microRNAs have been unraveled in human diseases, and we aimed to confirm the role of miR‐30b/30d in fulminant hepatic failure (FHF). Expression of miR‐30b/30d and CEACAM1 in serum of FHF patients and healthy people was measured by reverse transcription quantitative polymerase chain reaction (RT‐qPCR) and Western blot analysis. Mice FHF models were established by injection of D‐Galn and lipopolysaccharide, and were treated with miR‐30b/30d mimics. Oxidative stress, liver injury, and inflammatory reaction in mouse liver tissues were measured using oxidative stress‐related factor kits, hematoxylin–eosin staining and enzyme‐linked immunosorbent assay, respectively. Moreover, cell cycle distribution and apoptosis of hepatocytes of mice were determined by flow cytometry, and the target relation between miR‐30b/30d and CEACAM1 was confirmed by bioinformatic method and dual luciferase reporter gene assay. MiR‐30b/30d expression was positively, and CEACAM1 expression was negatively related to prognosis of FHF patients. Up‐regulation of miR‐30b/30d attenuated oxidative stress, liver injury, and inflammatory reaction, and improved survival rate of FHF mice. Furthermore, elevated miR‐30b/30d ameliorated apoptosis and cell cycle arrest of hepatocytes of FHF mice. CEACAM1 was a target gene of miR‐30b/30d. This study highlights that up‐regulated miR‐30b/30d attenuates the progression of FHF by targeting CEACAM1, which may be helpful to FHF treatment.
Objective To investigate the function and the mechanism of miR-125b in the invasion and metastasis of gastric cancer and provide experimental basis for finding and developing new therapeutic strategies for gastric cancer. Methods The difference of miR-125b expression in gastric cancer tissues and adjacent tissues was detected by qRT-PCR. The same test was performed in different gastric cancer cell lines. The effect of miR-125b on SGC-7901 and BGC-823 gastric cancer cell viability was examined using a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Transwell assay was used to detect the effect of miR-125b on invasion and metastasis of gastric cancer cells. The target gene STAT3 of miR-125b was identified and validated by dual luciferase reporter assay. Western blot assay and immunofluorescence staining were used to detect the effect of miR-125b on the expression and distribution of STAT3 protein. The inhibitor and activator of STAT3 were used to confirm the effect of STAT3 on invasion and metastasis of gastric cancer cells. Peritoneal metastasis experiment and IHC were used to study the inhibitory effect of miR-125b on the metastasis of gastric cancer in vivo. Results The results of qRT-PCR showed that 125b expression was significantly lower in gastric cancer than in adjacent tissues, which indicated poor prognosis for gastric-cancer patients. Furthermore, two gastric-cancer cell lines, SGC-7901 and BGC-823, exhibited lower miR-125b levels than the normal cell line HEK293. After treatment with miR-125b mimics, cell proliferation was markedly inhibited. Meanwhile, the invasion and metastasis of gastric cancer cells were also inhibited after treated with miR-125b mimics. We also identified the signal transducer and activator of transcription 3 (STAT3) as a potential target of miR-125b based on patient data from The Cancer Genome Atlas (TCGA). Dual luciferase assays revealed that miR-125b directly inhibited STAT3 by binding to its 3′-untranslated region (UTR). Immunofluorescence assay showed that miR-125b could affect the subcellular distribution of STAT3. Moreover, treatment with miR-125b mimics or stattic inhibited invasion and migration in the gastric cancer cell lines, and IL-6 could reverse the inhibitory effect. Finally, nude mice xenografted with gastric-cancer cells expressing miR-125b mimics exhibited smaller tumors and lower transfer rates than mice engrafted with control group cells. Conclusion These data suggested that miR-125b inhibited invasion and metastasis in gastric cancer by inhibiting STAT3; therefore, miR-125b and STAT3 could be potential therapeutic targets in the treatment of gastric cancer.
Esophageal squamous cell carcinoma (ESCC) has a high morbidity in China and its treatment depends greatly on adjuvant chemotherapy. However, DNA damage repair in cancer cells severely affects the outcome of treatment. This study investigated the potential mechanism regarding mediator of DNA-damage checkpoint 1 (MDC1) and minichromosome maintenance proteins (MCMs) during DNA damage in ESCC. Recombinant vectors of MDC1 and MCMs with tags were constructed and transfected into human ESCC cell line TE-1. Immunoprecipitation and mass spectrometry were performed to screen the MCMs interacting with MDC1, and direct interaction was confirmed by glutathione S-transferase (GST) pull-down assay in vitro. MCM2 and MCM6 were knocked down by shRNAs, after which chromatin fraction and foci forming of MDC1 upon bleomycin-induced DNA damage were examined. The results showed that MCM2/3/5/6 were immunoprecipitated by antibodies against the tag of MDC1 in TE-1 nuclei, and the GST pull-down assay indicated the direct interaction. Knockdown of MCM2 or MCM6 reduced the chromatin fraction of MDC1 according to Western blot results. Moreover, knockdown of MCM2 or MCM6 could significantly inhibit foci forming of MDC1 in TE-1 nuclei in response to bleomycin-induced DNA damage (p < 0.001). This study indicates the direct interaction between MDC1 and MCMs in TE-1 nuclei. Downregulation of MCMs can inhibit chromatin fraction and foci forming of MDC1 in TE-1 cells upon DNA damage, which suggests MCMs and MDC1 as potential targets to improve the outcome of chemotherapy in ESCC.
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