Objectives: . Hereditary hemorrhagic telangiectasia (HHT) is an autosomal dominant vascular disorder characterized by recurrent epistaxis, telangiectasia, and visceral arteriovenous malformations (AVMs). Activin A receptor-like type 1 (ACVRL1/ALK1) and endoglin (ENG) are the principal genes whose mutations cause HHT. No multicenter study has yet investigated correlations between genetic variations and clinical outcomes in Korean HHT patients. Methods: . Seventy-two members from 40 families suspected to have HHT based on symptoms were genetically screened for pathogenic variants of ACVRL1 and ENG. Patients with genetically diagnosed HHT were also evaluated. Results: . In the HHT genetic screening, 42 patients from 24 of the 40 families had genetic variants that met the pathogenic criteria (pathogenic very strong, pathogenic strong, pathogenic moderate, or pathogenic supporting) based on the American College of Medical Genetics and Genomics Standards and Guidelines for either ENG or ACVRL1: 26 from 12 families (50%) for ENG, and 16 from 12 families (50%) for ACVRL1. Diagnostic screening of 42 genetically positive HHT patients based on the Curaçao criteria revealed that 24 patients (57%) were classified as having definite HHT, 17 (41%) as having probable HHT, and 1 (2%) as unlikely to have HHT. Epistaxis was the most common clinical presentation (38/42, 90%), followed by visceral AVMs (24/42, 57%) and telangiectasia (21/42, 50%). Five patients (12%) did not have a family history of HHT clinical symptoms. Conclusion . Only approximately half of patients with ACVRL1 or ENG genetic variants could be clinically diagnosed as having definite HHT, suggesting that genetic screening is important to confirm the diagnosis.

We reviewed again the significance of the stable gastric pentadecapeptide BPC 157 as a likely mediator of Robert’s stomach cytoprotection/adaptive cytoprotection and organoprotection and as novel mediator of Selye’s stress coping response to reestablish homeostasis. Specific points of BPC 157 therapy and the original concept of Robert’s cytoprotection/adaptive cytoprotection/organoprotection are discussed, including the beneficial effects of BPC 157. First, BPC 157 protects stomach cells and maintains gastric integrity against various noxious agents (Robert’s killing cell by contact) and is continuously present in the gastric mucosa and gastric juice. Additionally, BPC 157 protects against the adverse effects of alcohol and nonsteroidal anti-inflammatory drugs on the gastric epithelium and other epithelia, that is, skin, liver, pancreas, heart (organoprotection), and brain, thereby suggesting its use in wound healing. Additionally, BPC 157 counteracts gastric endothelial injury that precedes and induces damage to the gastric epithelium and generalizes “gastric endothelial protection” to protection of the endothelium of other vessels (thrombosis, prolonged bleeding, and thrombocytopenia). BPC 157 also has an effect on blood vessels, resulting in vessel recruitment that circumvents vessel occlusion and the development of additional shunting and rapid bypass loops to rapidly reestablish the integrity of blood flow (ischemic/reperfusion colitis, duodenal lesions, cecal perforation, and inferior vena caval occlusion). Lastly, BPC 157 counteracts tumor cachexia, muscle wasting, and increases in pro-inflammatory/procachectic cytokines, such as interleukin-6 and tumor necrosis factor-α, and significantly corrects deranged muscle proliferation and myogenesis through changes in the expression of FoxO3a, p-AKT, p-mTOR, and p-GSK-3β (mitigating cancer cachexia).

COX-2 has been inappropriately overexpressed in various human malignancies, and is considered as one of the representative targetsfor the chemoprevention of inflammation-associated cancer. In order to assess the role of COX-2 in colitis-induced carcinogenesis,the selective COX-2 inhibitor celecoxib and COX-2 null mice were exploited in an azoxymethane (AOM)-initiated and dextransulfate sodium (DSS)-promoted murine colon carcinogenesis model. The administration of 2% DSS in drinking water for 1 week aftera single intraperitoneal injection of AOM produced colorectal adenomas in 83% of mice, whereas only 27% of mice given AOM alonedeveloped tumors. Oral administration of celecoxib significantly lowered the incidence as well as the multiplicity of colon tumors. Theexpression of COX-2 and inducible nitric oxide synthase (iNOS) was upregulated in the colon tissues of mice treated with AOM andDSS, and this was inhibited by celecoxib administration. Likewise, celecoxib treatment abrogated the DNA binding of NF-κB, a keytranscription factor responsible for regulating expression of aforementioned pro-inflammatory enzymes, which was associated withsuppression of IκBα degradation. In the COX-2 null (COX-2–/–) mice, there was about 30% reduction in the incidence of colon tumors,and the tumor multiplicity was also markedly reduced (7.7 ± 2.5 vs. 2.43 ± 1.4, P< 0.01). As both pharmacologic inhibition andgenetic ablation of COX-2 gene could not completely suppress colon tumor formation following treatment with AOM and DSS, it isspeculated that other pro-inflammatory mediators, including COX-1 and iNOS, should be additionally targeted to prevent inflammation-associated colon carcinogenesis.

BACKGROUND/AIMS: Among irritants causing gastric ulcer, Helicobacter pylori (H. pylori) might be pivotal, after which eradication became essential way in either inhibiting ulcerogenesis or preventing ulcer recurrence. Since threonine is essential in either mucus synthesis or cytoprotection, we hypothesized that the dietary threonine from Corynebacterium glutamicum (C. glutamicum) can mitigate the cytotoxicity of H. pylori infection.MATERIALS AND METHODS: RGM-1 cells were challenged with 100 multiplicity of infection H. pylori for 6 hours, during which threonine alone or combination with Corynebacterium sp. was administered and compared for anti-Helicobacter, anti-inflammation, anti-oxidative, and cytoprotective actions.RESULTS: Threonine alone or combination of threonine and C. glutamicum yielded significant bacteriostatic outcomes. The increased expressions of interleukin (IL)-1β, IL-8, Cox-2, and iNOS mRNA after H. pylori infection were significantly decreased with either threonine alone or the combination of threonine and C. glutamicum. The elevated expressions of NF-kB, HIF-1a, and c-jun after H. pylori infection were all significantly decreased with the combination of threonine and broth from C. glutamicum (P < 0.05), leading to significant decreases in 2′,7′-dichlorofluorescein-diacetate (P < 0.01). Tracing further host antioxidative response, the attenuated expression of heme oxygenase-1, Nrf2, and dehydrogenase quinone-1 after H. pylori infection was significantly preserved with combination of threonine and C. glutamicum. H. pylori infection led to significant increases in apoptosis accompanied with Bcl-2 decreases and Bax increases, while the combination of threonine and C. glutamicum significantly attenuated apoptosis, in which attenuated EGF, TGF-β, and VEGF were significantly regulated, while β-catenin did not change.CONCLUSIONS: Threonine synthesized from C. glutamicum significantly alleviated the cytotoxicity of H. pylori in gastric epithelial cells.
Apoptosis ; Corynebacterium glutamicum ; Corynebacterium ; Cytoprotection ; Epidermal Growth Factor ; Epithelial Cells ; Helicobacter pylori ; Heme Oxygenase-1 ; Interleukin-8 ; Interleukins ; Irritants ; Mucus ; NF-kappa B ; Oxidative Stress ; Oxidoreductases ; Recurrence ; RNA, Messenger ; Stomach Ulcer ; Thiram ; Threonine ; Ulcer ; Vascular Endothelial Growth Factor A

BACKGROUND/AIMS: A previous study showed that dietary intervention with Artemisia and green tea extracts, i.e., SD1003F, relieved Helicobacter pylori-associated chronic atrophic gastritis in a mouse model. We continue the research through the current randomized double-blind clinical trial to evaluate the efficacy and safety of the intervention for H. pylori-associated gastric discomfort. MATERIALS AND METHODS: Forty-nine volunteers who tested positive for H. pylori infection received either placebo or SD1003F for 10 weeks and their functional dyspepsia-related quality of life (QOL) was evaluated. H. pylori infection using a urea breath test (UBT), measurement of pepsinogen level using GastroPanel. Adverse effects with biochemical changes were also evaluated. RESULTS: SD1003F administration significantly improved health related-QOL, including dietary intake, emotional stability, life pattern, and social factors relevant to gastric discomfort, in comparison to the control (P < 0.05). The mean UBT measurement significantly decreased in the SD1003F group (P < 0.05). In 2 of the 24 volunteers, SD1003F alone eradicated H. pylori infection, with significant improvements in endoscopic findings. GastroPanel analysis revealed significant improvements that reflect rejuvenation of gastric atrophy in the SD1003F group. No significant side effect was observed in any participant. CONCLUSIONS: SD1003F (Artemisia and green tea extract), is a potential phytochemical to improve H. pylori-associated gastric discomfort.
Animals ; Artemisia ; Atrophy ; Breath Tests ; Gastritis, Atrophic ; Helicobacter pylori ; Helicobacter ; Mice ; Pepsinogen A ; Quality of Life ; Rejuvenation ; Tea ; Urea ; Volunteers

BACKGROUND/AIMS: Several lines of evidence from epidemiologic and laboratory studies have shown that the consumption of Artemisia or green tea extracts (MPGT) is inversely associated with the risk of alcohol-induced damage and other chronic diseases. Supported by previous studies showing that the combined extract of Artemisia and green tea, MPGT, exerted significantly either antioxidative or anti-inflammatory actions against Helicobacter pylori-associated gastric diseases, it was hypothesized that MPGT can offer protection against alcoholic gastritis. METHODS: Ethanol was administered to induce gastric damage in Wistar rats, which had been pretreated with various doses of MPGT, to measure the rescuing action of a MPGT pretreatment against ethanol-induced gastric damage. In addition, the molecular mechanisms for the preventive effects were examined. RESULTS: The MPGT pretreatment (100, 300, and 500 mg/kg) alleviated the ethanol-induced gastric damage, which was evidenced by the significant decrease in calcium-dependent phospholipase A2, MAPKs, and NF-κB levels compared to ethanol alone. Furthermore, the MPGT pretreatment preserved 15-prostaglandin dehydrogenase, whereas cyclooxygenase-2 was decreased significantly. All of these biochemical changes led to the significant alleviation of alcohol-associated gastric mucosal damage. Ethanol significantly increased the TUNEL positivity in the stomach, but MPGT decreased the apoptotic index significantly, which was associated with significantly lower pathological scores of ethanol-induced mucosal ulcerations. The significant protective changes observed alcoholic gastritis with MPGT were related to the increased expression of cytoprotective genes, such as heat-shock protein (HSP)27, HSP60, and PDGF. CONCLUSIONS: The efficient anti-inflammatory, anti-apoptotic, and regenerative actions of MPGT make it a potential nutrient phytoceutical to rescue the stomach from alcoholic gastritis.
Alcoholics* ; Artemisia* ; Chronic Disease ; Cyclooxygenase 2 ; Ethanol ; Gastritis* ; Heat-Shock Proteins* ; Helicobacter ; HSP27 Heat-Shock Proteins* ; Humans ; In Situ Nick-End Labeling ; Oxidoreductases ; Phospholipases A2 ; Rats, Wistar ; Stomach ; Stomach Diseases ; Tea* ; Ulcer

Precision medicine stands for 4Ps - precise, preventive, participatory, and personal; in which “precision” is important because the current modern medicine starts from “trial and error,” and “one does not fit all”. Current targeted therapies for cancer have changed treatment approaches and led the precision medicine; however, clinical use of liquid biopsy, using blood or other liquid specimens to characterize circulating tumor cells (CTC) or tumor genes instead of biopsies of tumor tissues, still awaits availability of more information regarding non-invasive cancer detection and characterization, prediction of treatment response, monitoring the disease course and relapse possibilities, identification of mechanisms of drug resistance, and newer pathogenesis. In this review, we will introduce the basic concept of CTC, circulating cell free DNA, and exosomes and their possible application for gastric cancer relevant with Helicobacter pylori infection.
Biopsy* ; DNA ; Drug Resistance ; Exosomes ; Helicobacter Infections* ; Helicobacter pylori ; Helicobacter* ; History, Modern 1601- ; Humans ; Neoplastic Cells, Circulating ; Precision Medicine ; Recurrence ; Stomach Neoplasms*

BACKGROUND/AIMS: In inflammatory bowel disease (IBD), repeated bouts of remission and relapse occur in patients and can impose a risk of colitis-associated cancer. We hypothesized that plant extracts of Atractylodes macrocephala (AM) or Taraxacum herba (TH) may be better than sulfasalazine for treating this disease because these extracts can promote additional regeneration. METHODS: Murine intestinal epithelial IEC-6 cells were pretreated with AM or TH before a lipopolysaccharide (LPS)-induced challenge. Acute colitis was induced with 7 days of dextran sulfate sodium (DSS) in male C57BL/6 mice, and extracts of AM and TH were administered for 2 weeks before DSS administration. RESULTS: In vitro studies demonstrated that AM or TH treatment reduced LPS-induced COX-2 and tumor necrosis factor-α mRNA levels but increased heme oxygenase-1 (HO-1). Oral preadministration of AM and TH rescued mice from DSS-induced colitis by inhibiting inflammatory mediators via inactivated extracellular signal regulated kinase and repressed nuclear factor κB and signal transducer and activator of transcription 3, but the effect was weaker for sulfasalazine than that for the extracts. Anti-inflammatory activities occurred via the inhibition of macrophage and T lymphocyte infiltrations. Unlike sulfasalazine, which did not induce HO-1, TH extracts afforded significant HO-1 induction. CONCLUSIONS: Because the AM or TH extracts were far superior in preventing DSS-induced colitis than sulfasalazine, AM or TH extracts can be considered natural agents that can prevent IBD relapse.
Animals ; Atractylodes* ; Colitis* ; Dextran Sulfate ; Heme Oxygenase-1* ; Heme* ; Humans ; In Vitro Techniques ; Inflammation ; Inflammatory Bowel Diseases ; Lymphocytes ; Macrophages ; Male ; Mice ; Necrosis ; Phosphotransferases ; Plant Extracts ; Recurrence* ; Regeneration ; RNA, Messenger ; STAT3 Transcription Factor ; Sulfasalazine* ; Taraxacum*

BACKGROUND/AIMS: We evaluated whether manometric subtype is associated with treatment outcome in patients with achalasia treated by peroral endoscopic myotomy (POEM). METHODS: High-resolution manometry data and Eckardt scores were collected from 83 cases at two tertiary referral centers where POEM is performed. Manometric tracings were classified according to the three Chicago subtypes. RESULTS: Among the 83 cases, 48 type I, 24 type II, and 11 type III achalasia cases were identified. No difference was found in pre-POEM Eckardt score, basal lower esophageal sphincter (LES) pressure, or integrated relaxation pressure (IRP) among the type I, type II, and type III groups. All three patient groups showed a significant improvement in post-POEM Eckardt score (6.1±2.1 to 1.5±1.5, p=0.001; 6.8±2.2 to 1.2±0.9, p=0.001; 6.6±2.0 to 1.6±1.4, p=0.011), LES pressure (26.1±13.8 to 15.4±6.8, p=0.018; 32.3±19.0 to 19.2±10.4, p=0.003; 36.8±19.2 to 17.5±9.7, p=0.041), and 4s IRP (21.5±11.7 to 12.0±8.7, p=0.007; 24.5±14.8 to 12.0±7.6, p=0.002; 24.0±15.7 to 11.8±7.1, p=0.019) at a median follow-up of 16 months. CONCLUSIONS: POEM resulted in a good clinical outcome for all manometric subtypes.
Esophageal Achalasia* ; Esophageal Sphincter, Lower ; Follow-Up Studies ; Humans ; Manometry ; Relaxation ; Tertiary Care Centers ; Treatment Outcome

With the accumulation of clinical trials demonstrating its efficacy and safety, peroral endoscopic myotomy (POEM) has emerged as a less invasive treatment option for esophageal achalasia compared with laparoscopic Heller myotomy. However, the difficulty in determining the exact extent of myotomy, a critical factor associated with the success and safety of the procedure, remains a limitation. Although the various endoscopic landmarks and ancillary techniques have been applied, none of these has been proven sufficient. As a solution for this limitation, the double-scope POEM technique with a second endoscope to assure the exact length of the submucosal tunnel has been applied since 2014. Before double-scope POEM was introduced, the second endoscope was applied only to confirm the accuracy of the procedure. In the present study, we performed double-scope POEM in the treatment of esophageal achalasia through a novel procedure of simultaneous application of the second endoscope to assist in the conventional POEM procedure.
Endoscopes ; Esophageal Achalasia*