Effect of Trimebutine and Rifaximin on Breath Hydrogen and Methane by Glucose Breath Test in Patients With Functional Bloating: A Randomized Double-blind Clinical Trial.

Background/Aims: Drugs that stabilize intestinal motility may improve the efficacy of nonabsorbable antibiotics, such as rifaximin, against small intestinal bacterial overgrowth (SIBO). We compared the efficacy of rifaximin alone with that of its combination with trimebutine maleate against SIBO. Methods: We performed a randomized double-blind placebo-controlled trial (https://cris.nih.go.kr, no. KCT0004836) that included patients with functional bloating, no constipation, and SIBO using the hydrogen (H2)-methane (CH4) glucose breath test (GBT). Patients were randomized into 2 groups in a 1:1 ratio, namely rifaximin (1200 mg/day) + trimebutine maleate (600 mg/day) group and rifaximin + placebo group, for 2 weeks. Patients completed a symptom questionnaire and underwent a GBT at baseline and at 1 month after treatment withdrawal. The primary outcome was SIBO eradication. The secondary outcomes included changes in the concentrations of exhaled gases, symptoms, and presence of adverse events. Results: The complete eradication rate of SIBO was 35.9% (14/39) in the rifaximin group, and 34.1% (14/41) in the combined group with no significant differences. In both groups, no significant differences were observed in GBT profiles before and after the treatment, respectively. However total breath H2 and CH4 concentration were conspicuously decreased in the combined group after treatment. The combined group exhibited substantial relief of bloating. The adverse events were similar in the 2 groups. Conclusion: While the combination therapy was not superior over rifaximin alone for SIBO eradication, it improves the symptom of bloating with numerically reducing the concentration of breath H2/CH4.

Exploring the dietary and therapeutic potential of licorice (Glycyrrhiza uralensis Fisch.) sprouts.

ETHNOPHARMACOLOGICAL RELEVANCE: This research substantiates the traditional use of Glycyrrhiza uralensis Fisch. for liver health, with scientific evidence of the non-toxic and lipid-lowering properties of licorice sprout extracts. The sprouts' rich mineral and amino acid content, along with their strong antioxidant activity, reinforce their value in traditional medicine. These findings bridge ancient herbal practices with modern science, highlighting licorice's potential in contemporary therapeutic applications. AIM OF THE STUDY: The study aimed to investigate the dietary and medicinal potential of G. uralensis sprouts by assessing their safety, nutritional content, and antioxidant properties using both plant and animal models. Specifically, the study sought to determine the effects of different sizes of licorice sprouts on lipid metabolism in human liver cancer cells and their overall impact on rat health indicators. MATERIALS AND METHODS: The study examined the effects of aqueous and organic extracts from G. uralensis sprouts of varying lengths on the cytotoxicity, lipid metabolism, and antioxidant activity in HepG2 cells, alongside in vivo impacts on Sprague-Dawley rats, using MTT, ICP, and HPLC. It aimed to assess the potential health benefits of licorice sprouts by analyzing their protective effects against oxidative stress and their nutritional content. RESULTS: Licorice sprout extracts from G. uralensis demonstrated no cytotoxicity in HepG2 cells, significantly reduced lipid levels, and enhanced antioxidant activities, with the longest sprouts (7 cm) showing higher mineral, sugar, and arginine content as well as increased glycyrrhizin and liquiritigenin. In vivo studies with Sprague-Dawley rats revealed weight gain and improved antioxidant enzyme activities in blood plasma and liver tissues after consuming the extracts, highlighting the sprouts' dietary and therapeutic potential. CONCLUSIONS: This study is the first to demonstrate that G. uralensis sprouts, particularly those 7 cm in length, have no cytotoxic effects, reduce lipids, and have high mineral and antioxidant contents, offering promising dietary and therapeutic benefits.

Soil exposure modulates the immune response to an influenza challenge in a mouse model.

There is increasing evidence that early life microbial exposure aids in immune system maturation, more recently known as the "old friends" hypothesis. To test this hypothesis, 4-week-old mice were exposed to soils of increasing microbial diversity for four weeks followed by an intranasal challenge with either live or heat inactivated influenza A virus and monitored for 7 additional days. Perturbations of the gut and lung microbiomes were explored through 16S rRNA amplicon sequencing. RNA-sequencing was used to examine the host response in the lung tissue through differential gene expression. We determined that compared to the gut microbiome, the lung microbiome is more susceptible to changes in beta diversity following soil exposure with Lachnospiraceae ASVs accounting for most of the differences between groups. While several immune system genes were found to be significantly differentially expressed in lung tissue due to soil exposures, there were no differences in viral load or weight loss. This study shows that exposure to diverse microbial communities through soil exposure alters the gut and lung microbiomes resulting in differential expression of specific immune system related genes within the lung following an influenza challenge.

Significance of traditional herbal medicine for dyslipidemia.

Dyslipidemia is a multifactorial disorder that is a causative factor and risk factor for cardiovascular disease. The incidence of dyslipidemia is expected to increase because of the presence of comorbidities. Although several lipid-lowering drugs have been developed and approved, they are not completely effective and are associated with side effects. Traditional herbal medicine (THM) represents an alternative and complementary approach for managing dyslipidemia because of its low toxicity and beneficial effects, such as anti-inflammatory and antioxidant effects. This review focuses on our current understanding of the antidyslipidemic effect of THMs and discusses the associated regulatory mechanisms. The current findings indicate that THM may lead to the development of novel therapeutic regimens for dyslipidemia.

Cheong-sang-bang-pung-san alleviated hepatic lipid accumulation by regulating lipid metabolism in vitro and in vivo.

Introduction: The occurrence of fatty liver disease, resulting from the accumulation of excessive fat within the liver, has been showing a significant and rapid increase. This study aimed to evaluate the therapeutic effects of Cheong-sang-bang-pung-san extract (CB) on fatty liver disease, and to elucidate the underlying mechanisms. Methods: We used a high-fat diet (HFD)-fed fatty liver mice and free fatty acid (FFA) induced HepG2 cell lipid accumulation model. The levels of serum, hepatic, and intracellular lipid content were assessed. Histopathological staining was used to evaluate the extent of hepatic lipid accumulation. Real-time polymerase chain reaction and Western blotting were conducted to examine the expression of factors associated with lipid metabolism. Results: We demonstrated that treatment with CB dramatically reduced body weight, liver weight, and fat mass, and improved the serum and hepatic lipid profiles in HFD-induced fatty liver mice. Additionally, CB alleviated lipid accumulation in HFD-fed mice by controlling lipid metabolism, including fatty acid uptake, triglyceride and cholesterol synthesis, and fatty acid oxidation, at the mRNA as well as protein levels. In free fatty acid-treated HepG2 cells, CB significantly reduced intracellular lipid accumulation by regulating lipid metabolism via the activation of AMP-activated protein kinase. Conclusion: These findings provide insights into the mechanisms underlying CB's effects on liver steatosis and position of CB as a potential therapeutic candidate for managing lipid metabolic disorders.

Anti-Neuroinflammatory Effects of the Human Milk Oligosaccharide, 2'-Fucosyllactose, Exerted via Modulation of M2 Microglial Activation in a Mouse Model of Ischemia-Reperfusion Injury.

Cerebral ischemic stroke is one of the leading causes of death and disability worldwide. 2'-fucosyllactose (2'-FL), a human milk oligosaccharide, exerts anti-inflammatory effects and plays a protective role in arterial thrombosis; however, its role in ischemic stroke remains unclear. This study aimed to investigate the neuroprotective effects of 2'-FL and its potential mechanisms in a mouse model of ischemic stroke. Neurological score and behavior tests revealed that 2'-FL promoted the recovery of neurological deficits and motor function in middle cerebral artery occlusion (MCAO) mice, and that 2'FL led to a reduction in the size of cerebral infarct. Biochemical studies showed that administration of 2'-FL led to a reduction of reactive oxygen species (ROS)-related products in the brain of MCAO mice. 2'-FL upregulated IL-10 and downregulated TNF-α level. In addition, 2'-FL enhanced M2-type microglial polarization and upregulated CD206 expression at 7 days after MCAO. At 3 days after MCAO, 2'-FL increased IL-4 levels and activated STAT6. Our data show that 2'-FL reduced the neurological symptoms of ischemic stroke and ROS accumulation in the brain through IL-4/STAT6-dependent M2-type microglial polarization in MCAO mice. These results demonstrate that 2'-FL is a potentially effective therapeutic agent for ischemic stroke.

An optimized herbal medicine containing Scutellaria baicalensis Georgi, Alisma orientale Juzepzuk, and Atractylodes japonica Koidzumi has potent antiplatelet and antithrombotic activities.

Background and aim: Platelet-derived thrombosis is important in the pathogenesis of cardiovascular diseases. HTB is an optimized herbal medicine including Scutellaria baicalensis Georgi, Alisma orientale Juzepzuk, and Atractylodes japonica Koidzumi. It is widely used in traditional medicine due to its anti-inflammatory and antioxidant effects. However, its antiplatelet and antithrombotic activities have not been completely validated. The current study aimed to examine the inhibitory effect of the novel herb formula HTB against platelet activation and thrombus formation. Experimental procedure: The antiplatelet activities of HTB via platelet aggregation, granule secretion, reactive oxygen species generation, and intracellular calcium mobilization were evaluated. Moreover, the antithrombotic effect of HTB via FeCl3-induced arterial thrombus formation in vivo in mice was assessed. The inhibitory effect of HTB against primary hemostasis was investigated based on transection tail bleeding time. Results and conclusion: HTB treatment significantly inhibited glycoprotein VI-mediated platelet aggregation, granule secretion, reactive oxygen species generation, and intracellular calcium mobilization. Biochemical studies revealed that HTB inhibited glycoprotein VI-mediated platelet signal transduction during cell activation. Further, its antioxidant effect might be derived by reducing the phosphorylation of the p47phox/Hic5 axis signalosome. Oral HTB treatment was effective in decreasing FeCl3-induced arterial thrombus formation without prolonging the tail bleeding time. HTB can be an effective therapeutic agent against thrombotic diseases.

Role of Gasdermin E in the Biogenesis of Apoptotic Cell-Derived Exosomes.

The gasdermins are a family of pore-forming proteins that has recently been suggested to play a central role in pyroptosis. In this study, we describe the novel roles of gasdermins in the biogenesis of apoptotic cell-derived exosomes. In apoptotic human HeLa and HEK293 cells, GSDMA, GSDMC, GSDMD, and GSDME increased the release of apoptotic exosomes. GSDMB and DFNB59, in contrast, negatively affected the release of apoptotic exosomes. GSDME at its full-length and cleaved forms was localized in the exosomes and exosomal membrane. Full-length and cleaved forms of GSDME are suggested to increase Ca2+ influx to the cytosol through endosomal pores and thus increase the biogenesis of apoptotic exosomes. In addition, the GSDME-mediated biogenesis of apoptotic exosomes depended on the ESCRT-III complex and endosomal recruitment of Ca2+-dependent proteins, that is, annexins A2 and A7, the PEF domain family proteins sorcin and grancalcin, and the Bro1 domain protein HD-PTP. Therefore, we propose that the biogenesis of apoptotic exosomes begins when gasdermin-mediated endosomal pores increase cytosolic Ca2+, continues through the recruitment of annexin-sorcin/grancalcin-HD-PTP, and is completed when the ESCRT-III complex synthesizes intraluminal vesicles in the multivesicular bodies of dying cells. Finally, we found that GSDME-bearing tumors released apoptotic exosomes to induce inflammatory responses in the in vivo mouse 4T1 orthotropic model of BALB/c breast cancer. The data indicate that the switch from apoptosis to pyroptosis could drive the transfer of mass signals to nearby or distant living cells and tissues by way of extracellular vesicles, and that gasdermins play critical roles in that process.

2'-Fucosyllactose and 3-Fucosyllactose Alleviates Interleukin-6-Induced Barrier Dysfunction and Dextran Sodium Sulfate-Induced Colitis by Improving Intestinal Barrier Function and Modulating the Intestinal Microbiome.

Ulcerative colitis is an inflammatory bowel disease (IBD) with relapsing and remitting patterns, and it is caused by varied factors, such as the intestinal inflammation extent and duration. We examined the preventative effects of human milk oligosaccharides (HMOs) on epithelial barrier integrity and intestinal inflammation in an interleukin (IL)-6-induced cell model and dextran sodium sulfate (DSS)-induced acute mouse colitis model. HMOs including 2'-fucosyllactose (FL) and 3-FL and positive controls including fructooligosaccharide (FOS) and 5-acetylsalicylic acid (5-ASA) were orally administrated once per day to C57BL/6J mice with colitis induced by 5% DSS in the administered drinking water. 2'-FL and 3-FL did not affect the cell viability in Caco-2 cells. Meanwhile, these agents reversed IL-6-reduced intestinal barrier function in Caco-2 cells. Furthermore, 2'-FL and 3-FL reversed the body weight loss and the remarkably short colon lengths in DSS-induced acute colitis mice. Moreover, 2'-FL and 3-FL obviously protected the decreasing expression of zonula occluden-1 and occludin in colon tissue relative to the findings in the DSS-treated control group. 2'-FL and 3-FL significantly reduced IL-6 and tumor necrosis factor-α levels in serum relative to the control findings. The summary of these results shows that HMOs prevent colitis mainly by enhancing intestinal barrier function and advancing anti-inflammatory responses. Therefore, HMOs might suppress inflammatory responses and represent candidate treatments for IBD that protect intestinal integrity.

Melatonin Protects Bone Microarchitecture against Deterioration due to High-Fat Diet-Induced Obesity.

BACKGROUND: We evaluated the protective effects of melatonin against high-fat diet (HFD)-induced deterioration of bone microarchitecture using high-resolution peripheral quantitative computed tomography (HR-pQCT). METHODS: Four-week-old male C57BL/6 mice were divided into control (chow diet group), HFD, and HFD + melatonin-administered groups. Mice were sacrificed after 14 weeks, and the right femur was extracted. The microskeletal structure of the femur was analyzed using SkyScan1173 (version 1.6). A 3-dimensional image was reconstructed using the Nrecon (version 1.7.0.4) program. RESULTS: Bone volume (BV) was significantly increased in the HFD group compared with that in the normal diet group, and that of the melatonin group also increased significantly compared with BV of the normal diet group (p<0.05). Percent BV/total volume [TV] and bone surface/BV were significantly higher in both the HFD and melatonin groups than in the normal diet group (p<0.05), and the melatonin group had the highest BV/total volume (TV). BMD was lower in the HFD than in the normal diet group and was the highest in the melatonin group. CONCLUSIONS: This study shows that melatonin inhibited the deterioration of microarchitecture induced by a HFD. A better understanding of the protective effect of melatonin on bone microarchitecture and mechanisms could provide fracture prevention for people who are obese.

Lactase Deficiency Diagnosed by Endoscopic Biopsy-based Method is Associated With Positivity to Glucose Breath Test.

Background/Aims: Lactase deficiency, which has many similarities with small intestinal bacterial overgrowth (SIBO), causes various gastrointestinal symptoms. We estimate the prevalence of SIBO in patients with intestinal symptoms from dairy products and investigate the association between lactase deficiency (LD) and SIBO. Methods: This prospective study included patients with functional intestinal symptoms from dairy product indigestion. A questionnaire on gastrointestinal symptoms, a hydrogen (H2)-methane glucose breath test (GBT) for SIBO, and lactose intolerance quick test (LQT) for LD using upper gastrointestinal endoscopy were performed. Results: A total of 88 patients, 29 (33.0%) with severe and 36 (40.9%) with mild LD were included. Sixteen patients (18.2%) were GBT positive. Patients with LQT negativity indicating severe LD showed a higher positivity to GBT or GBT (H2) than the historic controls (27.6% vs 6.7%, P = 0.032). There was no difference in the items on the symptom questionnaire according to the presence of LD or SIBO, except for higher symptom scores for urgency in GBT-positive patients. There were more LQT-negative patients in the GBT (H2)-positive group than in the other groups (27.6% vs 10.2%, P = 0.036). Moreover, only GBT (H2)-positivity was significantly associated with a higher risk of LQT negativity in multivariate analysis (OR, 4.19; P = 0.029). Conclusions: SIBO producing H2 is common in patients with severe LD suspected lactose intolerance. SIBO may be a new therapeutic target for managing intestinal symptoms in patients with lactose intolerance.

Efficacies of prokinetics and rifaximin on the positivity of a glucose breath test in patients with functional dyspepsia: a randomized trial.

BACKGROUND AND AIM: prokinetics could eradicate small intestinal bacterial overgrowth. This study aimed to evaluate the efficacy of mosapride, rifaximin and a combination of mosapride and rifaximin for the treatment of small intestinal bacterial overgrowth. METHODS: we randomly assigned patients with functional dyspepsia diagnosed with small intestinal bacterial overgrowth in a 1:1:1 ratio to receive mosapride, rifaximin or a combination of both for two weeks. The hydrogen-methane glucose breath test and symptom questionnaire were surveyed before and after the treatment. Primary outcome was eradication rate of small intestinal bacterial overgrowth. Secondary outcomes were changes in the gas concentration, symptoms and safety. RESULTS: the eradication rates were 17.2 % (5/29) for mosapride, 32.1 % (9/28) for rifaximin, and 34.6 % (9/26) for the combined groups, with no significant differences among the three groups. Total hydrogen concentration during the glucose breath test significantly decreased in the rifaximin group (p = 0.001). Total methane concentration significantly decreased in the rifaximin and combined groups (p = 0.005). Significant symptomatic improvements were observed in chest and abdominal discomfort with mosapride, in flatulence with rifaximin, and in chest discomfort with the combined groups. Adverse events were similar between the groups. CONCLUSIONS: rifaximin has an advantage of reducing gas, whereas mosapride can help to decrease breath hydrogen concentration. Certain intestinal symptoms improved with mosapride alone or combined with rifaximin.

Efficacies of prokinetics and rifaximin on the positivity of a glucose breath test in patients with functional dyspepsia: a randomized trial

Background and aim: prokinetics could eradicate small intestinal bacterial overgrowth. This study aimed to evaluate the efficacy of mosapride, rifaximin and a combination of mosapride and rifaximin for the treatment of small intestinal bacterial overgrowth. Methods: we randomly assigned patients with functional dyspepsia diagnosed with small intestinal bacterial overgrowth in a 1:1:1 ratio to receive mosapride, rifaximin or a combination of both for two weeks. The hydrogen-methane glucose breath test and symptom questionnaire were surveyed before and after the treatment. Primary outcome was eradication rate of small intestinal bacterial overgrowth. Secondary outcomes were changes in the gas concentration, symptoms and safety. Results: the eradication rates were 17.2 % (5/29) for mosapride, 32.1 % (9/28) for rifaximin, and 34.6 % (9/26) for the combined groups, with no significant differences among the three groups. Total hydrogen concentration during the glucose breath test significantly decreased in the rifaximin group (p = 0.001). Total methane concentration significantly decreased in the rifaximin and combined groups (p = 0.005). Significant symptomatic improvements were observed in chest and abdominal discomfort with mosapride, in flatulence with rifaximin, and in chest discomfort with the combined groups. Adverse events were similar between the groups. Conclusions: rifaximin has an advantage of reducing gas, whereas mosapride can help to decrease breath hydrogen concentration. Certain intestinal symptoms improved with mosapride alone or combined with rifaximin (AU)

Effectiveness of electroacupuncture on anxiety: a systematic review and meta-analysis of randomized controlled trials.

This systematic review and meta-analysis aimed to comprehensively evaluate the effectiveness of electroacupuncture (EA) for patients with anxiety. Randomized controlled trials (RCTs) on the treatment of anxiety by EA up to November 2022 were searched and collected from nine databases. Hamilton Anxiety Rating Scale (HAMA), self-rating anxiety scale (SAS), and adverse reactions were used as outcome indicators. The quality of relevant articles was evaluated using the Cochrane Collaboration's risk of bias tool. The quality of evidence for each outcome was classified as "low risk," "unclear risk," or "high risk." RevMan 5.0 was used for data analysis. A total of 633 articles were identified from nine electronic databases; 37 RCTs were included, which measured anxiety changes by using EA alone compared to the control group. For the main outcome, EA significantly reduced the HAMA score [Mean difference (MD):-1.13 (95% CI:-2.55-0.29), I2:80%], and the quality of evidence was moderate. EA significantly reduced the SAS score (MD:-3.47 (95% CI,-6.57--0.36), I2:88%), and the quality of evidence was moderate. Our meta-analysis shows that EA reduces HAMA and SAS. This study suggests that EA can relieve anxiety. For various uses, additional research is needed on its effect when combined with other treatments. Systematic review registration: https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=345658, identifier (CRD42022345658).

Sinomenium acutum Modulates Platelet Aggregation and Thrombus Formation by Regulating the Glycoprotein VI-Mediated Signalosome in Mice.

Sinomenium acutum (SA) has long been used as a traditional medicine in China, Japan, and Korea to treat a wide range of diseases. It has been traditionally used to ameliorate inflammation and improve blood circulation. However, its role in platelet activation has not been thoroughly investigated. Hence, we conducted this study to assess the potential inhibitory effect of SA on platelet aggregation and thrombus formation. The antiplatelet activities of SA were evaluated by assessing platelet aggregation, granular secretion, intracellular Ca2+ mobilization, and the Glycoprotein (GP) VI-mediated signalosome. The thrombosis and bleeding time assays were used to investigate the effect of SA (orally administered at 50 and 100 mg/kg for seven days) in mice. SA treatment at concentrations of 50, 100, and 200 µg/mL significantly reduced GPVI-mediated platelet aggregation, granular secretion, and intracellular Ca2+ mobilization. Further biochemical studies revealed that SA inhibited spleen tyrosine kinase, phospholipase Cγ2, phosphatidylinositol 3-kinase, and AKT phosphorylation. Interestingly, oral administration of SA efficiently ameliorated FeCl3-induced arterial thrombus formation without prolonging the tail bleeding time. These findings suggest that SA has beneficial effects in thrombosis and hemostasis. Therefore, SA holds promise as an effective therapeutic agent for the treatment of thrombotic diseases.

Hemostatic powder with argon plasma coagulation in the management of gastric antral vascular ectasia after failure of APC therapy alone

A 62-year-old woman with a medical history of cirrhosis due to advanced primary biliary cholangitis was referred for recurrent severe anemia. Upper GI endoscopy revealed a gastric antral vascular ectasia (GAVE). The hemoglobin levels were measured between 3 and 6 mg/dl for 10 years, and she received blood transfusion 2-3 times a year and continued endoscopic treatment. In particular, for 2 years from 2018, the decrease in hemoglobin level continued to be more severe, and endoscopic hemostasis using argon plasma coagulation (APC) was performed 11 times in total, but there was no significant clinical improvement. (AU)

Bilateral Vocal Fold Paralysis After COVID-19 mRNA Vaccination: A Case Report.

Since severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was noted to cause coronavirus disease 2019 (COVID-19) in 2019, there have been many trials to develop vaccines against the virus. Messenger ribonucleic acid (mRNA) vaccine as a type of the vaccine has been developed and commercialized rapidly, but there was not enough time to verify the long-term safety. An 82-year-old female patient was admitted to the emergency room with dyspnea accompanied by stridor three days after the 3rd COVID-19 mRNA vaccination (Comirnaty, Pfizer-BioNTech, USA). The patient was diagnosed with bilateral vocal fold paralysis (VFP) by laryngoscope. Respiratory distress was improved after the intubation and tracheostomy in sequence. The brain, chest, and neck imaging tests, serological tests, cardiological analysis, and immunological tests were performed to evaluate the cause of bilateral VFP. However, no definite cause was found except for the precedent vaccination. Because bilateral VFP can lead to a fatal condition, a quick evaluation is necessary in consideration of VFP when dyspnea with stridor occurs after vaccination.

Clinical outcomes of metachronous recurrence of gastric epithelial neoplasia based on Helicobacter pylori infection status and microsatellite stability.

BACKGROUND/AIMS: Helicobacter pylori eradication may prevent the recurrence of gastric epithelial neoplasia after endoscopic treatment. However, H. pylori eradication therapy is unlikely to prevent gastric cancer. This study determined the longterm results and clinical outcomes of patients with gastric epithelial neoplasia based on H. pylori infection status and microsatellite stability (MSS). METHODS: Patients diagnosed with gastric epithelial neoplasia who underwent an endoscopic mucosal resection or submucosal dissection between 2004 and 2010 were included in this retrospective study. During the follow-up period (range, 4 to 14 years), disease recurrence was monitored, and tissue examinations were conducted for seven sets of microsatellite loci initially linked to the tumour suppressor gene locus. When H. pylori infection was identified, patients underwent eradication therapy. RESULTS: The patients (n = 120) were divided into three groups: H. pylori-negative with MSS, H. pylori-positive with MSS, and microsatellite instability (MSI). After H. pylori eradication, the rate of metachronous recurrence was significantly different in the MSI (28.2%) and MSS groups (3.7%, p < 0.01). The mean duration of recurrence was 77 months (range, 24 to 139) in the MSI group. There was no recurrence after eradication therapy in patients who were positive for H. pylori in the MSS group. CONCLUSION: H. pylori eradication could help prevent gastric cancer recurrence in patients with stable microsatellite loci. Careful, long-term monitoring is required in patients with unstable microsatellite loci.

Serum Pepsinogen and Gastrin Levels: Reliable Markers to Predict Small Intestinal Bacterial Overgrowth.

BACKGROUND: Serum pepsinogen, a useful indicator of gastric acidity, could reflect small intestinal bacterial overgrowth. The aim of this study is to evaluate the relationship between small intestinal bacterial overgrowth and profiles including pepsinogen or gastrin. METHODS: We conducted a prospective study with 62 patients with a functional gastrointestinal disorder. All patients underwent glucose breath test for small intestinal bacterial overgrowth, immediately followed by upper endoscopy to survey gastric injury and Campylobacter-like organism test for Helicobacter pylori and serum laboratory tests including gastrin, pepsinogen I and II. RESULTS: The positivity to small intestinal bacterial overgrowth was 17.7%. Significantly, low total hydrogen concentration during a glucose breath test, low prevalence for gastric injury, and high H. pylori positivity rate were shown in groups with pepsinogen I/II ratio ≤ 3.5 compared to those with pepsinogen I/II ratio > 3.5 or in groups with serum gastrin > 35.4 pg/mL comparing to those with serum ≤ 35.4 pg/mL, respectively. A high gastrin level was independently associated with H. pylori infection. A proportionally correlated tendency between pepsinogen I/II ratio and total hydrogen concentration was shown, whereas that of inverse proportion between H2 and gastrin was observed. Old age was solely independent predicting factor for small intestinal bacterial overgrowth (P = .03) in the multivariate analysis. CONCLUSION: Old age was significantly related to the presence of small intestinal bacterial overgrowth in functional gastrointestinal disorder patients. Although pepsinogen and small intestinal bacterial overgrowth seem irrelevant, elevated gastrin level may cautiously indicate a decreased breath hydrogen concentration. Further studies should consider the function of intestinal motility and gastric acidity in patients with hydrogen-producing small intestinal bacterial overgrowth.

Mechanism of Action of Cyanidin 3-O-Glucoside in Gluconeogenesis and Oxidative Stress-Induced Cancer Cell Senescence.

Cyanidin-3-O-glucoside (C3G) is a natural anthocyanin abundant in fruits and vegetables that interacts and possibly modulates energy metabolism and oxidative stress. This study investigated the effect of C3G on gluconeogenesis and cancer cell senescence. C3G activates adenosine monophosphate-activated protein kinase (AMPK), a cellular energy sensor involved in metabolism and the aging process. C3G suppressed hepatic gluconeogenesis by reducing the expression of gluconeogenic genes through the phosphorylation inactivation of CRTC2 and HDAC5 coactivators via AMPK. C3G did not directly interact with AMPK but, instead, activated AMPK through the adiponectin receptor signaling pathway, as demonstrated through adiponectin receptor gene knockdown experiments. In addition, C3G increased cellular AMP levels in cultured hepatocytes, and the oral administration of C3G in mice elevated their plasma adiponectin concentrations. These effects collectively contribute to the activation of AMPK. In addition, C3G showed potent antioxidant activity and induced cellular senescence, and apoptosis in oxidative-stress induced senescence in hepatocarcinoma cells. C3G increased senescence-associated ß-galactosidase expression, while increasing the expression levels of P16, P21 and P53, key markers of cellular senescence. These findings demonstrate that anthocyanin C3G achieves hypoglycemic effects via AMPK activation and the subsequent suppression of gluconeogenesis and exhibits anti-cancer activity through the induction of apoptosis and cellular senescence.