• Helicobacter
• cancer
• cholangiocarcinoma
• neoplasms

It has been documented that Helicobacter hepaticus (H. hepaticus) infection is linked to chronic hepatitis and fibrosis in male BALB/c mice. However, the mechanism underlying the mice model of H. hepaticus–induced hepatocellular carcinoma is not fully known. In this study, male BALB/c mice were infected with H. hepaticus for 3, 6, 12, and 18 months. H. hepaticus colonization, histopathology, expression of proinflammatory cytokines, key signaling pathways, and protein downstream high-mobility group box-1 (HMGB1) in the liver were examined. Our data suggested that the H. hepaticus colonization level in the colon and liver progressively increased over the duration of the infection. H. hepaticus–induced hepatic inflammation and fibrosis were aggravated during the infection, and hepatic preneoplasia developed in the liver of infected mice at 12 and 18 months post-inoculation (MPI). H. hepaticus infection increased the levels of alanine aminotransferase and aspartate aminotransferase in the infected mice. In addition, the mRNA levels of IL-6, Tnf-α, Tgf-β, and HMGB1 were significantly elevated in the liver of H. hepaticus–infected mice from 3 to 18 MPI as compared to the controls. In addition, Ki67 was increased throughout the duration of the infection. Furthermore, HMGB1 protein was activated and translocated from the nucleus to the cytoplasm in the hepatocytes and activated the proteins of signal transducers and activators of transcription 3 (Stat3) and mitogen-activated protein kinase (MAPK) [extracellular regulated protein kinases 1/2 (Erk1/2) and mitogen-activated protein kinase p38 (p38)] upon H. hepaticus infection. In conclusions, these data demonstrated that male BALB/c mice infected with H. hepaticus are prone to suffering hepatitis and developing into hepatic preneoplasia. To verify the effect of HMGB1 in the progression of liver preneoplasia, mice were infected by H. hepaticus for 2 months before additional HMGB1 recombinant adenovirus treatment. All mice were sacrificed at 4 MPI, and the sera and liver tissues from all of the mice were collected. Immunology and histopathology evaluation showed that HMGB1 knockdown attenuated the H. hepaticus–induced hepatic and fibrosis at 4 MPI. Therefore, we showed that H. hepaticus–induced liver preneoplasia is closely correlated with the activation and accumulation of HMGB1.

• HMGB1
• Helicobacter hepaticus
• hepatic preneoplasia
• mouse (BALB/c)
• mouse model

• Helicobacter
• bacteriophages
• dysbiosis
• oncoviruses
• periodontal pathogens
• sexually transmitted disease

• R01 DK105118, R01DK114126 NIH HHS
• CDMRP BC191198 Department of Defence
• I01BX004824-01 Veterans for America

• Bacterial exotoxins
• Carcinogenesis
• Colon cancer
• Dysbiosis
• Escherichia coli
• Gut microbiota
• Metabolites
• Oral microbiome
• Salmonella
• β-Catenin/Wnt

The presence of concomitant diseases is an independent predictive factor for non-Helicobacter pylori (H. pylori) peptic ulcers. Patients contracting concomitant diseases have an increased risk of developing ulcer disease through pathogenic mechanisms distinct from those of H. pylori infections. Factors other than H. pylori seem critical in peptic ulcer recurrence in end stage renal disease (ESRD) and cirrhotic patients. However, early H. pylori eradication is associated with a reduced risk of recurrent complicated peptic ulcers in patients with ESRD and liver cirrhosis. Resistances to triple therapy are currently detected using culture-based and molecular methods. Culture susceptibility testing before first- or second-line therapy is unadvisable. Using highly effective empiric first-line and rescue regimens can yield acceptable results. Sequential therapy has been included in a recent consensus report as a valid first-line option for eradicating H. pylori in geographic regions with high clarithromycin resistance. Two novel eradication regimens, namely concomitant and hybrid therapy, have proven more effective in patients with dual- (clarithromycin- and metronidazole-) resistant H. pylori strains. We aim to review the prevalence of and eradication therapy for H. pylori infection in patients with ESRD and cirrhosis. Moreover, we summarized the updated H. pylori eradication regimens.

• Concomitant diseases
• Helicobacter pylori
• Culture susceptibility
• Concomitant therapy
• Hybrid therapy

NAFLD model rats were established and divided into NAFLD model (MG group), SIRT1 RNAi (SI group), blueberry juice (BJ group), blueberry juice + bifidobacteria (BJB group), blueberry juice + SIRT1 RNAi (BJSI group), and blueberry juice + bifidobacteria + SIRT1 RNAi groups (BJBSI group). A group with normal rats was a control group (CG). BJB group ameliorated NAFLD, which was better than BJ group (P < 0.05). The lipid accumulation was lower in CG, BJ, and BJB groups than that in MG, SI, BJSI, and BJBSI groups (P < 0.05). The levels of SIRT1 and PPAR-α were higher in CG, BJ, and BJB groups than those in MG, SI, BJSI, and BJBSI groups (P < 0.05). The levels of SREBP-1c were lower in CG, BJ, and BJB groups than those in MG, SI, BJSI, and BJBSI groups (P < 0.05). The biochemical indexes SOD, GSH, and HDL-c were improved from CG to BJB group (P < 0.05). Inversely, the levels of AST and ALT, TG, TC, LDL-c, and MDA were decreased from CG to BJB group (P < 0.05). These changes enhance antioxidative capability and biochemical index of rats. Blueberry juice and bifidobacteria improve NAFLD by activating SIRTI-mediating signaling pathway.

Hepatocellular carcinoma (HCC) has a high incidence worldwide, with a low diagnostic rate in the early period and therefore a high death rate. Causes for some cases of liver cancer are not completely clear. The finding that the rate of liver cancer in male A/Jr mice is significantly higher makes researchers realize that Helicobacter hepaticus may cause HCC in human beings. To get a new perspective for exploring causes of liver cancer, this paper introduces the biological nature of and detecting methods for Helicobacter hepaticus, as well as the relationship between Helicobacter hepaticus infection and HCC. Helicobacter hepaticus infection may play an important role in some HCC cases.

• Helicobacter hepaticus
• Hepatocellular carcinoma
• Relationship

The purpose of this work was to develop nanostructured lipid carriers (NLCs) loaded simultaneously with oleanolic acid and gentiopicrin.

An aqueous dispersion of NLCs was prepared successfully using a film-ultrasonic method, with glycerin monostearate as the solid lipid and oleic acid as the liquid lipid. Poloxamer 188 was used as the surfactant. A central composite design was used to optimize the technologic parameters. The characteristics of the NLCs were then investigated.

The encapsulation efficiency was 48.34% ± 2.76%, drug loading was 8.06% ± 0.42%, particle size was 111.0 ± 1.56 nm, polydispersity index was 0.287 ± 0.01, and zeta potential was −23.8 ± 0.36 mV for the optimized NLCs. The other physicochemical properties were characterized by transmission electron microscopy and differential scanning calorimetry. Drug release followed first-order kinetics and release studies confirmed that oleanolic acid and gentiopicrin fitted a sustained-release model. Compared with NLCs loaded with oleanolic acid or gentiopicrin alone, NLCs loaded with both oleanolic acid and gentiopicrin produced drug concentrations which persisted for a significantly longer time in plasma, with a linear decrement following second-order kinetics. Aspartate and alanine aminotransferase levels were significantly lower on exposure to NLCs loaded with both oleanolic acid and gentiopicrin than in negative controls.

The results of this study confirm that oleanolic acid and gentiopicrin can be loaded simultaneously into NLCs. Compared with oleanolic acid and gentiopicrin loaded alone, sustained release and protective effects against hepatic injury were observed using NLCs loaded with both oleanolic acid and gentiopicrin.

• central composite design
• in vitro release
• nanostructured lipid carriers
• pharmacokinetics

• Female
• Gastrointestinal Diseases/diagnosis
• Helicobacter Infections/diagnosis
• Helicobacter hepaticus/isolation & purification
• Humans
• Liver Diseases/diagnosis
• Male

• Female
• Gastrointestinal Diseases/diagnosis
• Helicobacter Infections/diagnosis
• Helicobacter hepaticus/isolation & purification
• Humans
• Liver Diseases/diagnosis
• Male