Characterization of the intestinal transport mechanism of polystyrene microplastics (MPs) and the potential inhibitory effect of green tea extracts on MPs intestinal absorption.

The aims of the current study included characterizing the intestinal transport mechanism of polystyrene microplastics (MPs) with different charges and sizes in the intestinal epithelial cell model and determining the inhibitory effect of green tea extracts (GTEs) on the intestinal absorption of MPs in Caco-2 cells. The smaller sizes, which included diameters of 0.2 µm, of amine-modified MPs compared to either larger size (1 µm diameter, or carboxylate-MPs (0.2 and 1 µm diameter) significantly lowered the cell viability of caco-2 cells that were measured by MTT assay (p < 0.05). The transported amount (particles/mL of the cell media) of amine-modified MPs by the Caco-2 cell, was not dependent according to the concentrations, energy, or temperature, but it was higher than the carboxylate-modified MPs. The co-treatment of GTEs with the amine-modified MPs inhibited Caco-2 cell cytotoxicity as well as reduced the production of intracellular reactive oxygen species (ROS) in HepG2 generated by the exposure of amine-modified MPs. The GTEs co-treatment also increased trans-epithelial electrical resistances (TEER) and reduced the transportation of Lucifer Yellow via the Caco-2 monolayer compared to only the amine-modified MPs exposure. The GTEs treatment led to a decrease in the number of amine-modified MPs transported to the basal side of the Caco-2 monolayer. The results from our study suggest that the consumption of GTEs could enhance the intestinal barrier function by recovering intestinal epithelial cell damage induced by MPs, which resulted in a decrease of the intestinal absorption of MPs.

High-resolution pancreatic computed tomography for assessing pancreatic ductal adenocarcinoma resectability: a multicenter prospective study.

OBJECTIVE: This prospective multicenter study aimed to evaluate the diagnostic performance of 80-kVp thin-section pancreatic CT in determining pancreatic ductal adenocarcinoma (PDAC) resectability according to the recent National Comprehensive Cancer Network (NCCN) guidelines. METHODS: We prospectively enrolled surgical resection candidates for PDAC from six tertiary referral hospitals (study identifier: NCT03895177). All participants underwent pancreatic CT using 80 kVp tube voltage with 1-mm reconstruction interval. The local resectability was prospectively evaluated using NCCN guidelines at each center and classified into three categories: resectable, borderline resectable, and unresectable. RESULTS: A total of 138 patients were enrolled; among them, 60 patients underwent neoadjuvant therapy. R0 resection was achieved in 103 patients (74.6%). The R0 resection rates were 88.7% (47/53), 52.4% (11/21), and 0.0% (0/4) for resectable, borderline resectable, and unresectable disease, respectively, in 78 patients who underwent upfront surgery. Meanwhile, the rates were 90.9% (20/22), 76.7% (23/30), and 25.0% (2/8) for resectable, borderline resectable, and unresectable PDAC, respectively, in patients who received neoadjuvant therapy. The area under curve of high-resolution CT in predicting R0 resection was 0.784, with sensitivity, specificity, and accuracy of 87.4% (90/103), 48.6% (17/35), and 77.5% (107/138), respectively. Tumor response was significantly associated with the R0 resection after neoadjuvant therapy (odds ratio [OR] = 38.99, p = 0.016). CONCLUSION: An 80-kVp thin-section pancreatic CT has excellent diagnostic performance in assessing PDAC resectability, enabling R0 resection rates of 88.7% and 90.9% for patients with resectable PDAC who underwent upfront surgery and patients with resectable PDAC after neoadjuvant therapy, respectively. KEY POINTS: • The margin-negative (R0) resection rates were 88.7% (47/53), 52.4% (11/21), and 0.0% (0/4) for resectable, borderline resectable, and unresectable pancreatic ductal adenocarcinoma (PDAC), respectively, on 80-kVp thin-section pancreatic CT in the 78 patients who underwent upfront surgery. • Among the 60 patients who underwent neoadjuvant therapy, the R0 rates were 90.9% (20/22), 76.7% (23/30), and 25.0% (2/8) for resectable, borderline resectable, and unresectable PDAC, respectively. • Tumor response, along with the resectability status on pancreatic CT, was significantly associated with the R0 resection rate after neoadjuvant therapy.

Effect of Clostridium butyricum on High-Fat Diet-Induced Intestinal Inflammation and Production of Short-Chain Fatty Acids.

BACKGROUND/AIMS: A high-fat diet (HFD) can cause intestinal inflammation and alter the gut microbiota; probiotics, however, are known to have anti-inflammatory effects. This study aimed to investigate the response of rat colon to HFD and the effect of Clostridium butyricum on HFD-induced intestinal inflammation and production of short-chain fatty acids (SCFAs) according to sex. METHODS: Male and female 6-week-old Fischer-344 rats were fed a chow diet or HFD for 8 weeks, and Biovita or three different concentrations of C. butyricum were orally gavaged. The levels of tight junction proteins (TJPs), inflammatory markers in the ascending colonic mucosa, and bile acids (BAs) and SCFAs in stool were measured. RESULTS: HFD significantly increased the histological inflammation scores and fat proportions. Fecal BA levels were higher in the HFD group than in the control group, with a more prominent increase in deoxycholic acid/cholic acid after probiotics administration in females; however, no statistically significant differences were observed. TJPs showed an opposite response to HFD depending on sex, and tended to increase and decrease after HFD in males and females, respectively. The HFD-reduced TJPs were recovered by probiotics, with some statistical significance in females. HFD-decreased butyric acid in stools appeared to be recovered by probiotics in males, but not in females. The expression of inflammatory markers (TNF-α) was increased by HFD in males and decreased with medium-concentration probiotic supplementation. The opposite was observed in females. MPO was increased by HFD in both sexes and decreased by probiotic supplementation. CONCLUSIONS: The probiotic C. butyricum improved indicators of HFD-induced colonic inflammation such as levels of inflammatory markers and increased the production of SCFAs and the expression of TJPs. These effects tended to be more pronounced in male rats, showing sex difference.

Acaricidal and Insecticidal Activities of Essential Oils and Constituents of Tasmannia lanceolata (Poir.) A.C.Sm. (Canellales: Winteraceae) Against Tetranychus urticae Koch (Trombidiformes: Tetranychidae) and Myzus persicae Sulzer (Hemiptera: Aphididae).

The negative side effects of synthetic pesticides have drawn attention to the need for environmentally friendly agents to control arthropod pests. To identify promising candidates as botanical pesticides, we investigated the acaricidal and insecticidal activities of 44 plant-derived essential oils (EOs) against Tetranychus urticae Koch and Myzus persicae Sulzer. Among the tested EOs, Tasmannia lanceolata (Poir.) A.C.Sm. (Tasmanian pepper) essential oil (TPEO) exhibited strong acaricidal and insecticidal activity. Mortality rates of 100% and 71.4% against T. urticae and M. persicae, respectively, were observed with TPEO at a concentration of 2 mg/ml. Polygodial was determined to be the primary active component after bioassay-guided isolation of TPEO using silica gel open-column chromatography, gas chromatography, and gas chromatography-mass spectrometry. Polygodial demonstrated acaricidal activity against T. urticae with mortality rates of 100%, 100%, 61.9%, and 61.6% at concentrations of 1, 0.5, 0.25, and 0.125 mg/ml, respectively. Insecticidal activity against M. persicae was also evident, with mortality rates of 88.5%, 85.0%, 46.7%, and 43.3% at respective concentrations of 1, 0.5, 0.25, and 0.125 mg/ml. Insecticidal and acaricidal activities of TPEO were greater than those of Eungjinssag, a commercially available organic agricultural material for controlling mites and aphids in the Republic of Korea. These findings suggest that TPEO is a promising candidate for mites and aphids control.

Acaricidal Activities of Dioscorea japonica Thunb. (Dioscoreales: Dioscoreaceae) Extract and its Constituents Against the Two-spotted Spider Mite, Tetranychus urticae Koch (Trombidiformes: Tetranychidae).

The acaricidal activities of 86 plant extracts were investigated under laboratory conditions. The ethanol extract of Dioscorea japonica Thunb. root showed the strongest acaricidal activity, with 89.3% mortality against two-spotted spider mite, Tetranychus urticae Koch adults at a 2 mg/ml concentration. Bioassay-guided isolation of D. japonica root extract using silica gel open column chromatography, gas chromatography (GC), and gas chromatography-mass spectrometry (GC-MS) identified palmitic acid as the primary active compound. The acaricidal activities of palmitic acid against T. urticae were 91.2% and 69.7% at concentrations of 1 and 0.5 mg/ml, respectively. Among nine saturated fatty acids with carbon chains ranging from C8 to C26, the most vigorous acaricidal activity was observed with octanoic acid, followed by palmitic acid, and decanoic acid at a 1 mg/ml concentration. The acaricidal activity of the other fatty acids was less than 40% mortality at a 1 mg/ml concentration. These results indicate that a suitable carbon length is essential for fatty acids to exhibit acaricidal activity. The acaricidal efficacy of Eungjinssag (EJSG), an organic agricultural material authorized for the management of mites in the Republic of Korea, was compared to D. japonica root extract. At concentrations above 1 mg/ml, the acaricidal activity of D. japonica root extract was stronger than that of EJSG. The results of this study show that D. japonica root extract and palmitic acid are promising candidates as new environmentally-friendly control agents against two-spotted spider mite, which is one of the most severely damaging agricultural arthropod pests.

[A Randomized, Double-blind, Active-controlled Exploratory Clinical Trial for the Evaluation of the Efficacy and Safety of Goodmorning S Granule® on Constipation].

Background/Aims: Constipation is a common gastrointestinal disease that reduces the quality of life and incurs considerable medical expenses. Bisacodyl and sodium docusate are generally used to treat constipation. This study assessed the effectiveness and safety of Goodmorning S Granule® (Hanpoong Pharm. Co., Ltd., Wanju, Korea) in functional constipation by a comparison with bisacodyl. Methods: A 2-week randomized, double-blind, active-controlled exploratory clinical trial was conducted to compare the treatment (Goodmorning S Granule®) with the control (bisacodyl). The efficacy was measured by the changes in transition, Bristol stool type, stomachache, clinical manifestation, defecation time after drug consumption, 36-item short-form survey (SF-36), and the results of improvement evaluation. The safety was evaluated by the incidence of adverse drug events and vital signs. Additional analyses were conducted by dividing the severity according to the proportion of Bristol Stool Scale types 1 and 2. Results: Subjects were randomized to the treatment (n=24) or control (n=26) groups. No significant differences were observed in demographics. After 2 weeks from the baseline, the changes in the complete spontaneous bowel movement (CSBM) were higher in the treatment (4.00±2.62) group than in the control group (1.40±2.34) (p<0.05). The treatment group exhibited significant improvement in the score on the SF-36 questionnaire. The clinical side effects, such as stomachache and borborygmus, were reduced in the moderate constipation patients in the treatment group, according to additional analyses. Conclusions: Goodmorning S Granule®, a herbal medicine, was more effective in improving quality of life and CSBM per week and safer in the moderate constipation groups because of the reduced clinical side effects.

Risk of Psoriasis in Postgastrectomy Gastric Cancer Survivors: A Nationwide Population-Based Cohort Study.

Background: Although patients with psoriasis have an increased risk of cancers, little is known about the risk of psoriasis in cancer patients. Objective: We aimed to comparatively analyze the incidence and risk factors of psoriasis in gastric cancer patients who underwent gastrectomy and in the general population. Methods: A nationwide retrospective cohort of 52,608 gastric cancer survivors (2007~2015) was compared to 123,438 matched controls from the general population to estimate the incidence and hazard ratio (HR) of new-onset psoriasis. We also calculated the HRs for psoriasis according to adjuvant cancer treatment, obesity, and vitamin B12 supplementation in gastric cancer survivors. Results: During a mean follow-up of 6.85 years, 645 of the 52,608 gastric cancer patients developed psoriasis, while 1,806 in the 123,438 matched control group developed psoriasis. Gastric cancer patients had a decreased risk of psoriasis (HR, 0.86; 95% confidence interval, 0.79~0.94), especially those who underwent subtotal gastrectomy. We found that vitamin B12 supplementation for more than 3 years had an additive effect on decreasing the risk of psoriasis in gastric cancer patients who underwent subtotal gastrectomy. Total gastrectomy, radio/chemotherapy, and obesity did not affect the risk of psoriasis in gastric cancer survivors. Conclusion: The incidence of psoriasis is slightly lower in gastric cancer survivors than in the general population. Our results suggest that the development of psoriasis may be reduced by removing the source of systemic inflammation caused by Helicobacter pylori infection through subtotal gastrectomy in gastric cancer survivors.

Gastrectomy, vitamin B12 supplementation and the risk of Parkinson's disease: A nationwide cohort study.

INTRODUCTION: Previous evidence has suggested roles for α-synuclein propagation and vitamin B12 (VitB12) deficiency in the pathogenesis of Parkinson's disease (PD). We investigated whether gastric cancer (GC) patients who underwent gastrectomy had a lower risk of PD and whether VitB12 supplementation modified the risk. METHODS: GC patients aged ≥50 years who underwent curative gastrectomy between 2007 and 2012 (n = 72,216) and matched comparison groups (n = 211,389) were identified from the Korean National Health Insurance database. The risks of PD were analyzed by Cox regression. RESULTS: Compared to their matched comparison groups, GC patients who underwent gastrectomy showed a decreased risk of PD (adjusted HR [aHR] 0.86; 95% confidence interval [CI] 0.75-0.98), but the significance disappeared after further adjustment with smoking and body mass index (BMI). To elaborate, subtotal gastrectomy (STG) was associated with decreased risk of PD (aHR 0.85; 95% CI 0.74-0.99) while total gastrectomy (TG) was not (aHR 0.89; 95% CI 0.66-1.19), although the risk reduction was not significant when further adjusted for smoking and BMI. Among the patients who underwent TG, their risk of PD was markedly lower when they had VitB12 supplementation after surgery (aHR 0.36; 95% CI 0.17-0.76), while the risk was higher when they did not have any (aHR 1.55; 95% CI 1.03-2.32). CONCLUSIONS: GC patients who underwent gastrectomy and received uninterrupted VitB12 supplementation had a decreased incidence of PD. This study provides indirect epidemiological evidence for the potential roles of gastrectomy and VitB12 in the pathogenesis of PD.

Monolithic 1 × 8 DWDM Silicon Optical Transmitter Using an Arrayed-Waveguide Grating and Electro-Absorption Modulators for Switch Fabrics in Intra-Data-Center Interconnects.

In this study, we propose an eight-channel monolithic optical transmitter using silicon electro-absorption modulators (EAMs) based on free-carrier injection by Schottky junctions. The transmitter consists of a 1 × 8 silicon arrayed-waveguide grating (AWG) and eight 500-µm-long EAMs on a 5.41 × 2.84 mm2 footprint. It generates eight-channel dense wavelength-division multiplexing (DWDM) outputs with 1.33 nm channel spacing (Δλ) in the C-band from a single broadband light source and modulates each channel with over 3 dB modulation depth at 6 V peak-to-peak. The experimental results showed that the feasibility of a homogeneous silicon DWDM transmitter with a single light source for switch fabrics in intra-data-center interconnects over heterogeneous integration with regards to more complementary metal-oxide-semiconductor (CMOS) compatibility.

Efficacy of DA-5204 (Stillen 2X) for patients with gastroesophageal reflux disease: A randomized, double-blind, placebo-controlled pilot study.

BACKGROUND/AIM: Proton pump inhibitor (PPI) alone is not satisfactory for the treatment of gastroesophageal reflux disease (GERD). Therefore, we investigated the efficacy of DA-5204 (Stillen 2X, 90 mg of Artemisia asiatica 95% ethanol extract per tablet) and PPI combination therapy on GERD in comparison to PPI alone. METHODS: This randomized, double-blind, placebo-controlled study randomly assigned 70 patients with endoscopically proven esophageal mucosal injury (Los Angeles classification grade A or B) into 2 groups: pantoprazole 40 mg once daily with DA-5204 twice daily (DA-5204 group) or pantoprazole 40 mg once daily with placebo twice daily (placebo group) for 4 weeks. The primary endpoint was endoscopic healing rate. The secondary endpoint was sufficient relief (≥50% reduction) of symptoms using GERD Questionnaire. RESULTS: Final analyses included 29 patients with the DA-5204 group and 30 patients with the placebo group. At weeks 4, there was no significant difference in the endoscopic healing rate between the 2 groups (DA-5204 vs placebo; 96.6% vs 93.3%; P = 1.000). However, the rate of residual minimal change was significantly lower in the DA-5204 group (5/28, 17.9%) than in the placebo group (17/28, 60.7%) (P < .001). The rates of symptom relief were not different between the DA-5204 group and the placebo group (all P > .05). CONCLUSION: Combined therapy with PPI and DA-5204 has no additional effect on the endoscopic healing rate compared to PPI alone. However, it may be beneficial in resolving minimal change.

Annual eradication rate of bismuth-containing quadruple therapy as second-line treatment for Helicobacter pylori infection: A 15-year prospective study at a tertiary hospital in Korea.

BACKGROUND: Bismuth-containing quadruple therapy is widely used as second-line treatment for Helicobacter pylori infection. This prospective study investigated the changes in the annual H. pylori eradication rates of quadruple therapy. METHODS: This study included an intention-to-treat (ITT) population of 452 subjects who failed first-line eradication therapy for H. pylori between 2003 and 2018. All subjects received a 14-day course of bismuth-containing quadruple therapy consisting of esomeprazole (40 mg twice daily), metronidazole (500 mg thrice daily), bismuth subcitrate (120 mg four times daily), and tetracycline (500 mg four times daily). Per-protocol (PP) analysis of data was performed in subjects who followed up with strict treatment adherence. Eradication was confirmed based on the results of the 13 C-urea breath test, rapid urease test (CLOtest® ), and histopathologic evaluation. Compliance and adverse effects were also investigated. A minimal inhibitory concentration test was performed on tissue samples obtained from 103 subjects. RESULTS: The overall eradication rates following ITT and PP analyses were 78.8% (356/452) and 89.5% (314/351), respectively. The annual eradication success rate did not show significant changes (P = .062 [ITT], P = .857 [PP]) over the 15-year study period. Adverse events were reported in 57.3% of the ITT population. The rates of resistance to metronidazole and tetracycline were 44.7% and 18.4%, respectively. CONCLUSIONS: Despite high antibiotic resistance rates, no significant reduction in annual eradication rates was observed during the study period.

Inhibition of the type III secretion system of Pseudomonas syringae pv. tomato DC3000 by resveratrol oligomers identified in Vitis vinifera L.

BACKGROUND: The bacterial type III secretion system (T3SS) is one of the virulence determinants of Gram-negative bacteria through which various effector and virulence proteins are translocated into host cells. RESULTS: We constructed an assay system to screen inhibitors of hrpA gene expression (a structural gene of Hrp pili) in Pseudomonas syringae pv. tomato DC3000. In a plant extract library screening, the root extract of Vitis vinifera L. displayed the most prominent activity. Three resveratrol oligomers, hopeaphenol, isohopeaphenol and ampelopsin A, were identified in grapevine root extract, which significantly reduced the transcription levels of the hrpA, hrpL and hopP1 genes without growth retardation. Additional resveratrol derivatives identified in other plant extracts were also examined for their inhibitory effect on hrpA expression. Another resveratrol oligomer, kobophenol A, also inhibited the transcription of the hrpA gene and other T3SS-related genes, while resveratrol monomers (resveratrol and piceatannol) were not effective. The severity of bacterial specks was reduced by each hopeaphenol, isohopeaphenol and ampelopsin A treatment. CONCLUSION: These results show the potential of resveratrol derivatives as anti-virulence agents for the control of plant diseases.

The Efficacy and Safety of GCWB104 (Flos Lonicera Extract) in Functional Dyspepsia: A Single-Center, Randomized, Double-Blind, Placebo-Controlled Study.

Background/Aims: The Flos Lonicera extract GCWB104 has been shown to have significant protective effects against gastritis and gastric ulcers in vivo. The aim of this study was to investigate the efficacy and safety of GCWB104 in subjects with functional dyspepsia (FD). Methods: In this single-center, double-blind, randomized clinical trial, 92 subjects diagnosed with FD using the Rome III criteria were allocated to either the test group (300 mg of GCWB104, containing 125 mg of Flos Lonicera extract, twice daily) or the placebo group (300 mg placebo, twice daily). The total score improvement on the Gastrointestinal Symptom Rating Scale (GSRS) for individual symptoms, changes in antioxidant levels, changes in dyspepsia-related quality of life according to the Nepean Dyspepsia Index (NDI), and adverse effects were compared before and after 8 weeks of treatment. Results: The differences in total GSRS scores and score improvements after 8 weeks of treatment were significant between the GCWB104 and control groups (p=0.0452 and p=0.0486, respectively). Thirteen of 15 individual symptoms on the GSRS improved in the GCWB104 group, while six symptoms improved in the control group. In addition, statistically significant changes in rumbling, loose stool, and stool urgency were observed in the GCWB104 group. Blood 8-hydroxy-2'-deoxyguanosine (8-OHdG) levels, known as antioxidants, showed significant reductions after 8 weeks of administration of GCWB104. There were no adverse events related to treatment with GCWB104. Conclusions: GCWB104 safely contributed to improvements in mild to moderate FD and irritable bowel syndrome symptoms. Antioxidant effects of GCWB104 were also suggested (Clinicaltrials.gov number NCT04008901).

Risk of Dementia in Gastric Cancer Survivors Who Underwent Gastrectomy: A Nationwide Study in Korea.

PURPOSE: This study was designed to compare the risk of dementia, including Alzheimer's disease (AD) and vascular dementia (VaD), between gastric cancer patients who underwent gastrectomy and the general population. METHODS: All patients (n = 63,998) aged ≥ 50 years who received a diagnosis of gastric cancer and underwent curative gastrectomy between 2007 and 2012 and a noncancer control population (n = 203,276), matched by age and sex, were identified from the Korean National Health Insurance Services and traced until 2017. Hazard ratios and 95% confidence intervals for dementia were calculated with a Cox regression analysis. RESULTS: Gastric cancer patients who received a gastrectomy showed an increased risk of AD [adjusted hazard ration (aHR) 1.08, 95% confidence interval (CI) 1.03-1.14], and the risk was especially marked for those who received a total gastrectomy (aHR 1.39, 95% CI 1.25-1.54). Gastric cancer survivors showed a decreased risk for VaD (aHR 0.85; 95% CI 0.73-0.98) regardless of operation type. Those who received continual vitamin B12 supplementation after a total gastrectomy were less likely than controls to develop AD (aHR 0.71; 95% CI 0.54-0.92). CONCLUSIONS: Compared with controls, gastric cancer patients who received a total gastrectomy had an increased incidence of AD and a decreased risk of VaD. Our results suggest that vitamin B12 deficiency might play a role in the development of AD and highlight the need for vitamin B12 supplementation after total gastrectomy.

[Inhibitory Effects of ß-caryophyllene on Helicobacter pylori Infection: A Randomized Double-blind, Placebo-controlled Study].

BACKGROUND/AIMS: Helicobacter pylori (H. pylori) infections, which cause a variety of gastrointestinal symptoms, are common in South Korea. Recent reports have shown a decline in the H. pylori eradication rates. ß-caryophyllene is a natural bicyclic sesquiterpene that occurs in a wide range of plant species, such as cloves, basil, and cinnamon. ß-caryophyllene has been reported to have anti-inflammatory and anti-bacterial effects. This study investigated the inhibitory effects of ß-caryophyllene on H. pylori and its potential role as an alternative gastrointestinal drug. METHODS: This 8-week, randomized double-blind, placebo-controlled trial categorized subjects into a ß-caryophyllene group (33 patients who received 126 mg/day of ß-caryophyllene) and a placebo group (33 patients who received a placebo preparation). The inflammation level of H. pylori infiltration and the eradication rates were evaluated endoscopically and with the urea breath test (UBT) in both groups before and after administering the medication. The serum cytokine levels (tumor necrosis factor-α, and interleukin [IL]-1ß and IL-6) were compared in both groups before and after administering the medication. RESULTS: Complete eradication was not observed in either group. Moreover, there was no significant change in the UBT and updated Sydney score. On the other hand, the ß-caryophyllene group showed significant improvement in nausea (p=0.025) and epigastric pain (p=0.018), as well as a decrease in the serum IL-1ß levels (p=0.038). CONCLUSIONS: ß-caryophyllene improves dyspepsia symptoms and can be considered a useful supplementary treatment for gastrointestinal disease.

Risk factors of rescue bismuth quadruple therapy failure for Helicobacter pylori eradication.

BACKGROUND AND AIM: Failure of bismuth quadruple therapy for Helicobacter pylori eradication is frequently observed. To increase the eradication rate, comprehensive analyses need to be performed regarding risk factors of bismuth quadruple therapy failure based on complete standard culture and antimicrobial susceptibility testing results. METHODS: Patients with history of failed first therapy who had H. pylori colonies isolated from culture and successful minimum inhibitory concentration (MIC) test were enrolled. Esomeprazole, bismuth, metronidazole, and tetracycline (quadruple) therapies for 7 or 14 days were given. Eradication rate, treatment compliance, adverse events, and risk factors for the failure of bismuth quadruple therapy were analyzed. RESULTS: A total 54 patients were enrolled. Overall eradication rate in the present study was 88.8%. The eradication rate for cases with metronidazole resistance such as MIC 8-16 µg/mL or 16-32 µg/mL was 92.8% (13/14). For cases with high level metronidazole resistance (MIC > 32 µg/mL), the eradication rate was only 60% (6/10). Multivariate analysis regarding compliance, treatment duration, age > 60, three kinds of metronidazole MICs, tetracycline MIC > 4 µg/mL, adverse events and any other parameters, "metronidazole resistance, high level (MIC > 32 µg/mL)" was the only independent risk factor for eradication failure (P = 0.007). CONCLUSION: For cases with metronidazole resistance at MIC > 32 µg/mL, rescue therapy other than bismuth-containing quadruple therapy is needed.

Whole tumor ablation of locally recurred hepatocellular carcinoma including retained iodized oil after transarterial chemoembolization improves progression-free survival.

OBJECTIVES: To evaluate and compare clinical outcomes of two different radiofrequency ablation (RFA) methods for locally recurred hepatocellular carcinoma (LrHCC) after locoregional treatment. METHODS: Our institutional review board approved this study with a waiver of informed consent. A total of 313 patients previously treated with transarterial chemoembolization (TACE) (n = 167) and RFA (n = 146) with a single LrHCC ≤ 3 cm was included from five tertiary referral hospitals. RFA was done for LrHCCs using either viable tumor alone ablation (VTA) method (VTA: n = 61 in the TACE group and n = 127 in the RFA group) or whole tumor ablation (WTA) method which includes both viable tumor and retained iodized oil or previously ablated zone (WTA: n = 106 in the TACE group and n = 19 in the RFA group). Local tumor progression (LTP)-free survival as well as progression-free survival (PFS) were estimated using the Kaplan-Meier method, and prognostic factors were evaluated using the Cox proportional hazards regression model. RESULTS: In 167 patients with LrHCC who underwent TACE, the 5-year LTP-free survival after RFA was significantly higher with the VTA method than with the WTA method (26.9% vs. 87.8%; p < 0.001; hazard ratio (HR) = 8.53 [4.16-17.5]). The estimated 5-year PFS after RFA for LrHCC after TACE using the VTA method was 5.7%, which was significantly lower than that with the WTA method (26.4%) (p = 0.014; HR = 1.62 [1.10-2.38]). However, in 146 patients with LrHCC after initial RFA, there were no significant differences in cumulative incidence of LTP (p = 0.514) or PFS (p = 0.905) after RFA between the two ablation methods. CONCLUSIONS: For RFA of LrHCC after TACE, the WTA method including both viable tumor and retained iodized oil could significantly lower LTP and improve PFS than VTA. KEY POINTS: • Whole tumor ablation (WTA) could provide significantly better local tumor control for locally recurred HCC (LrHCC) after TACE than viable tumor alone ablation (VTA). • WTA for LrHCC after TACE could also provide significantly better progression-free survival than VTA. • Regarding LrHCC after RFA, VTA would provide a comparable clinical outcome to WTA.

Oxyresveratrol Increases Energy Expenditure through Foxo3a-Mediated Ucp1 Induction in High-Fat-Diet-Induced Obese Mice.

The phytochemical oxyresveratrol has been shown to exert diverse biological activities including prevention of obesity. However, the exact reason underlying the anti-obese effects of oxyresveratrol is not fully understood. Here, we investigated the effects and mechanism of oxyresveratrol in adipocytes and high-fat diet (HFD)-fed obese mice. Oxyresveratrol suppressed lipid accumulation and expression of adipocyte markers during the adipocyte differentiation of 3T3-L1 and C3H10T1/2 cells. Administration of oxyresveratrol in HFD-fed obese mice prevented body-weight gains, lowered adipose tissue weights, improved lipid profiles, and increased glucose tolerance. The anti-obese effects were linked to increases in energy expenditure and higher rectal temperatures without affecting food intake, fecal lipid content, and physical activity. The increased energy expenditure by oxyresveratrol was concordant with the induction of thermogenic genes including Ucp1, and the reduction of white adipocyte selective genes in adipose tissue. Furthermore, Foxo3a was identified as an oxyresveratrol-induced gene and it mimicked the effects of oxyresveratrol for induction of thermogenic genes and suppression of white adipocyte selective genes, suggesting the role of Foxo3a in oxyresveratrol-mediated anti-obese effects. Taken together, these data show that oxyresveratrol increases energy expenditure through the induction of thermogenic genes in adipose tissue and further implicates oxyresveratrol as an ingredient and Foxo3a as a molecular target for the development of functional foods in obesity and metabolic diseases.

Effects of 17ß-Estradiol on Colonic Permeability and Inflammation in an Azoxymethane/Dextran Sulfate Sodium-Induced Colitis Mouse Model.

Background/Aims: Intestinal barrier dysfunction is a hallmark of inflammatory bowel diseases (IBDs) such as ulcerative colitis. This dysfunction is caused by increased permeability and the loss of tight junctions in intestinal epithelial cells. The aim of this study was to investigate whether estradiol treatment reduces colonic permeability, tight junction disruption, and inflammation in an azoxymethane (AOM)/dextran sodium sulfate (DSS) colon cancer mouse model. Methods: The effects of 17ß-estradiol (E2) were evaluated in ICR male mice 4 weeks after AOM/DSS treatment. Histological damage was scored by hematoxylin and eosin staining and the levels of the colonic mucosal cytokine myeloperoxidase (MPO) were assessed by enzyme-linked immunosorbent assay (ELISA). To evaluate the effects of E2 on intestinal permeability, tight junctions, and inflammation, we performed quantitative real-time polymerase chain reaction and Western blot analysis. Furthermore, the expression levels of mucin 2 (MUC2) and mucin 4 (MUC4) were measured as target genes for intestinal permeability, whereas zonula occludens 1 (ZO-1), occludin (OCLN), and claudin 4 (CLDN4) served as target genes for the tight junctions. Results: The colitis-mediated induced damage score and MPO activity were reduced by E2 treatment (p＜0.05). In addition, the mRNA expression levels of intestinal barrier-related molecules (i.e., MUC2, ZO-1, OCLN, and CLDN4) were decreased by AOM/DSS-treatment; furthermore, this inhibition was rescued by E2 supplementation. The mRNA and protein expression of inflammation-related genes (i.e., KLF4, NF-κB, iNOS, and COX-2) was increased by AOM/DSS-treatment and ameliorated by E2. Conclusions: E2 acts through the estrogen receptor ß signaling pathway to elicit anti-inflammatory effects on intestinal barrier by inducing the expression of MUC2 and tight junction molecules and inhibiting pro-inflammatory cytokines.

Effects of Alkaline-Reduced Drinking Water on Irritable Bowel Syndrome with Diarrhea: A Randomized Double-Blind, Placebo-Controlled Pilot Study.

OBJECTIVES: The purpose of this study was to investigate whether the ingestion of alkaline-reduced water (ARW) is helpful in improving the symptoms of diarrhea-predominant irritable bowel syndrome (IBS). METHODS: Twenty-seven patients (male, 25.9%; mean, 41.7 years old) with diarrhea-predominant IBS were randomly allocated to two groups. For eight weeks, the ARW group (n = 13) ingested at least 2 liters/day of ARW, while the control group (n = 14) ingested placebo water. IBS symptom scores (quality-of-life, abdominal pain/discomfort), stool form, and frequency were assessed before and after treatment via questionnaires. RESULTS: Eight patients (61.5%) in the ARW group and six patients (42.9%) in the control group indicated that their symptoms had improved in more than four out of the eight weeks of treatment (p = 0.449). The IBS quality-of-life score significantly improved from 57.2 to 30.8 in the ARW group; this improvement was significantly greater than the slight improvement from 48.7 to 42.2 observed in the control group (p = 0.029). The abdominal pain score improved from 1.8 to 0.9 in the ARW group and from 1.8 to 1.1 in the control group, with no significant group difference (p = 0.232). CONCLUSIONS: Drinking ARW for eight weeks improves the quality of life in patients with diarrhea-predominant IBS.