Deficiency of SCAP inhibits HBV pathogenesis via activation of the interferon signaling pathway.

Hepatitis B virus (HBV) infects the liver and is a major risk factor for liver cirrhosis and hepatocellular carcinoma. Approaches for an effective cure are thwarted by limited knowledge of virus-host interactions. Herein, we identified SCAP as a novel host factor that regulates HBV gene expression. SCAP, sterol regulatory element-binding protein (SREBP) cleavage-activating protein, is an integral membrane protein located in the endoplasmic reticulum. The protein plays a central role in controlling lipid synthesis and uptake by cells. We found that gene silencing of SCAP significantly inhibited HBV replication; furthermore, knockdown of SREBP2 but not SREBP1, the downstream effectors of SCAP, reduced HBs antigen production from HBV infected primary hepatocytes. We also demonstrated that knockdown of SCAP resulted in activation of interferons (IFNs) and IFN stimulated genes (ISGs). Conversely, ectopic expression of SREBP2 in SCAP-deficient cells restored expression of IFNs and ISGs. Importantly, expression of SREBP2 restored HBV production in SCAP knockdown cells, suggesting that SCAP participates in HBV replication through an effect on IFN production via its downstream effector SREBP2. This observation was further confirmed by blocking IFN signaling by an anti-IFN antibody, which restored HBV infection in SCAP-deficient cells. This led to the conclusion that SCAP regulates the IFN pathway through SREBP, thereby affecting the HBV lifecycle. This is the first study to reveal the involvement of SCAP in regulation of HBV infection. These results may facilitate development of new antiviral strategies against HBV.

No significant association between non-Helicobacter pylori Helicobacter infection with gastritis-related indices and gastric cancer.

BACKGROUND: Non-Helicobacter pylori Helicobacter (NHPH) has recently been linked to various gastric diseases. However, the relationship between NHPH infection and gastric cancer remains controversial. This study aimed to identify the effect of NHPH infection on gastritis and gastric cancer development. MATERIALS AND METHODS: Formalin-fixed paraffin-embedded tissues were obtained from 73 patients with gastric cancer, of whom 21 cases were Helicobacter pylori (Hp) current infection, 37 cases were Hp previous infection, and 15 cases were Hp naïve infection, and were screened for NPHPs using polymerase chain reaction. The results were compared with NHPH infection rates in the patients with gastritis-related diseases reported in the previous study. We evaluated the association of NHPH infection with gastritis and clinicopathological features of gastric cancer. RESULTS: NHPH infection rates were 4/21 (19%) in "Hp current" patients, 4/37 (11%) in "Hp previous" infection patients, and 1/15 (7%) in "Hp naïve" patients, showing no significant difference in infection rates based on Hp infection status. NHPH infection rates in gastric cancer patients were similar to those in the patients with gastritis-related diseases reported in the previous study. A comparison of NHPH-positive and negative patients showed no significant differences in atrophic gastritis status, serum gastritis markers, or clinicopathological characteristics of gastric cancer, such as localization, size, gross type, differentiation, or depth. CONCLUSIONS: The association between gastric cancer and NHPH infection would have important implications for gastric cancer prevention, diagnostics, and treatment, however, no significant association was found in this particular population.

Serum Gastrin and Pepsinogen Levels after Administration of Acid Secretion Inhibitors for Ulcers due to Endoscopic Submucosal Dissection in Patients with Early Gastric Cancer.

Acid secretion inhibitors, such as proton pump inhibitors (PPIs) and potassium competitive acid blockers (PCABs), are used to treat ulcers after endoscopic submucosal dissection (ESD) for early gastric cancer. These drugs can influence serum gastrin and pepsinogen (PG) levels; however, their definite effects remain unclear. This open-label, randomized study investigated the effect of acid secretion inhibitors on the serum gastrin and pepsinogen levels. In total, 76 patients were enrolled in the study. They underwent gastric ESD and received a PPI (n = 21) or PCAB (n = 55). Changes in the serum gastrin and PG levels before and 4 weeks after administration were examined. Patient factors associated with the alteration of serum PG or gastrin levels were identified. The median serum levels of gastrin, PGI, and PGII before the administration of the acid secretion inhibitors were 110.5 pg/mL, 36.4 ng/mL, and 8.9 ng/mL, respectively; after administration, the levels increased to 300 pg/mL, 64.7 ng/mL, and 15.8 ng/mL, respectively (P < 0.01). Univariate analysis revealed that PCABs led to a more significant increase in the serum gastrin and PG levels as compared to PPIs. Furthermore, the PG levels were significantly increased in patients with previous Helicobacter pylori infections than in those with current infections. In conclusion, the serum gastrin and PG levels increased after the use of acid secretion inhibitors. This elevation was affected by the type of drug used, whereas the elevation in PGs was affected by the patient's background as well.