Ginseng has an anti-cancer effect in several cancer models. This study was to characterize active constituents of ginseng and their effects on proliferation of prostate cancer cell lines, LNCaP and PC3. Cell proliferation was measured by [3H]thymidine incorporation, the intracellular calcium concentration by a dual-wavelength spectrophotometer system, effects on mitogen-activated protein (MAP) kinases by Western blotting, and cell attachment and morphologic changes were observed under a microscope. Among 11 ginsenosides tested, ginsenosides Rg3 and Rh2 inhibited the proliferation of prostate cancer cells. EC50s of Rg3 and Rh2 on PC3 cells were 8.4 microM and 5.5 microM, respectively, and 14.1 microM and 4.4 microM on LNCaP cells, respectively. Both ginsenosides induced cell detachment and modulated three modules of MAP kinases activities differently in LNCaP and PC3 cells. These results suggest that ginsenosides Rg3 and Rh2-induced cell detachment and inhibition of the proliferation of prostate cancer cells may be associated with modulation of three modules of MAP kinases.

Background/AimsAlthough a small amount of fecal material can obscure significant colorectal lesions, it has not been well documented whether bowel preparation status affects the missing risk of colorectal polyps and adenomas during a colonoscopy.MethodsWe prospectively enrolled patients with one to nine colorectal polyps and at least one adenoma of >5 mm in size at the screening colonoscopy. Tandem colonoscopy with polypectomy was carried out within 3 months.ResultsA total of 277 patients with 942 polyps and 714 adenomas completed index and tandem examinations. At the index colonoscopy, 187 polyps (19.9%) and 127 adenomas (17.8%) were missed. The per-patient miss rate of polyps and adenomas increased significantly as the bowel cleansing rate declined from excellent to poor/inadequate on the Aronchick scale (polyps, p=0.024; adenomas, p=0.040). The patients with poor/inadequate bowel preparation were independently associated with an increased risk of having missed polyps (odds ratio [OR], 3.21; 95% confidence interval [CI], 1.13 to 9.15) or missed adenomas (OR, 3.04; 95% CI, 1.04 to 8.88) compared to the patients with excellent bowel preparation.ConclusionsThe risk of missing polyps and adenomas during screening colonoscopy is significantly affected by bowel preparation status. It seems appropriate to shorten the colonoscopy follow-up interval for patients with suboptimal bowel preparation.

Clevudine (CLV) is a nucleoside analog with potent antiviral activity against chronic hepatitis B virus (HBV)infection. Viral resistance to CLV in patients receiving CLV therapy has not been reported. The aim of this study was to characterize CLV-resistant HBV in patients with viral breakthrough (BT) during long-term CLV therapy. The gene encoding HBV reverse transcriptase (RT) was analyzed from chronic hepatitis B patients with viral BT during CLV therapy. Sera collected from the patients at baseline and at the time of viral BT were studied. To characterize the mutations of HBV isolated from the patients, we subjected the HBV mutants to in vitro drug susceptibility assays. Several conserved mutations were identified in the RT domain during viral BT, with M204I being the most common. In vitro phenotypic analysis showed that the mutation M204I was predominantly associated with CLV resistance, whereas L229V was a compensatory mutation for the impaired replication of the M204I mutant. A quadruple mutant (L129M, V173L, M204I, and H337N) was identified that conferred greater replicative ability and strong resistance to both CLV and lamivudine. All of the CLV-resistant clones were lamivudine resistant. They were susceptible to adefovir, entecavir, and tenofovir, except for one mutant clone. In conclusion, the mutation M204I in HBV RT plays a major role in CLV resistance and leads to viral BT during long-term CLV treatment. Several conserved mutations may have a compensatory role in replication. Drug susceptibility assays reveal that adefovir and tenofovir are the most effective compounds against CLV-resistant mutants. These data may provide additional therapeutic options for CLV-resistant patients.Chronic hepatitis B virus (HBV) infection is a major health problem worldwide and leads to chronic hepatitis, cirrhosis, and hepatocellular carcinoma (13). Antiviral treatment for chronic hepatitis B improves the outcome of the disease and prevents the development of hepatocellular carcinoma (14). Currently, several oral antiviral agents, including lamivudine (LMV), adefovir (ADV), and entecavir (ETV), have been approved for the treatment of chronic HBV infections (8). However, oral antiviral treatment does not provide a cure or durable remission and it has limited long-term efficacy due to the emergence of resistance (12). Long-term treatment with nucleos(t)ide analogs is associated with an increased risk of drug resistance. Antiviral drug resistance in patients infected with HBV is associated with subsequent virologic breakthrough (BT), viral rebound, and biochemical BT.Clevudine [1-(2-deoxy-2-fluoro-␤-arabinofuranosyl)thymine, L-FMAU] (CLV) is a pyrimidine analog with potent antiviral activity against HBV (4). CLV inhibits the DNA-dependent DNA activity of HBV polymerase, as well as reverse transcription and priming (1, 16). Phase III clinical trial results have shown that CLV therapy for 24 weeks has a potent and sustained antiviral effect in both HBeAg-positive and -negative chronic hepatitis B patients (23,24). Clinica...

Compound K (C-K), a protopanaxadiol ginsenoside metabolite, was previously shown to have immunomodulatory effects. Here, we describe a novel therapeutic role for C-K in the treatment of lethal sepsis through the modulation of Toll-like receptor (TLR) 4-associated signalling via glucocorticoid receptor (GR) binding. In mononuclear phagocytes, C-K significantly repressed the activation of TLR4/lipopolysaccharide (LPS)-induced NF-κB and mitogen-activated protein kinases (MAPKs), as well as the secretion of pro-inflammatory cytokines. However C-K did not affect the TLR3-mediated expression of interferon-β or the nuclear translocation of IRF-3. C-K competed with the synthetic glucocorticoid dexamethasone for binding to GR and activated glucocorticoid responsive element (GRE)-containing reporter plasmids in a dose-dependent manner. In addition, the blockade of GR with either the GR antagonist RU486 or a siRNA against GR substantially reversed the anti-inflammatory effects of C-K. Furthermore, TLR4-dependent repression of inflammatory response genes by C-K was mediated through the disruption of p65/interferon regulatory factor complexes. Importantly, pre- or post-treatment with C-K significantly rescued mice from Gram-negative bacterial LPS-induced lethal shock by lowering their systemic inflammatory cytokine levels and by reversing the lethal sequelae of sepsis. Collectively, these results demonstrate that C-K, as a functional ligand of GR, regulates distinct TLR4-mediated inflammatory responses, and suggest a novel therapy for Gram-negative septic shock.

Background and Aims An increase in the use of antibiotics leads to increased antibiotic resistance of Helicobacter pylori (H pylori). Consequently, it has been considered that the first‐line standard regimen should be changed. The main purpose of this study was to evaluate the efficacy of nonantibiotic (bismuth) supplements as a first‐line regimen for H pylori eradication. Methods We searched PubMed, EMBASE, CINAHL, and the Cochrane Library databases for randomized controlled trials (RCTs) reported in English and undertaken up until August 2018. A meta‐analysis of all randomized controlled trials comparing bismuth supplements with non‐bismuth‐containing regimens in H pylori eradication was performed. RCTs of classic bismuth‐containing quadruple therapy as a first‐line regimen were excluded. Results We identified twenty‐five randomized trials (3990 patients), and the total H pylori eradication rate, according to per protocol analyzed, was 85.8%. The odds ratio was 1.83 (95% confidence interval (CI). 1.57‐2.13). Among these RCTs, there were 7 RCTs for bismuth add‐on therapy, and the odds ratio was 2.81 (95% CI. 2.03‐3.89). When the studies were performed in a high clarithromycin resistance area (≥15%) or included patients with clarithromycin resistance, bismuth‐containing regimens were superior to non‐bismuth regimens. Moreover, the incidence of total side effects was insignificant. Conclusions Bismuth supplements as a first‐line regimen could be effective, with bismuth add‐on regimens being the most effective. Particularly, bismuth supplements showed the potential efficacy for clarithromycin‐resistant strains and would be the most viable alternative in clinical practice.