Quality of healing of gastric ulcers: Natural products beyond acid suppression简

Gastric ulcer is a chronic disease featured with unexpected complications, including bleeding, stenosis and perforation, as well as a high incidence of recurrence. Clinical treatments for gastric ulcer have allowed the rapid development of potent anti-ulcer drugs during the last several decades. Gastric ulcer healing is successful with conventional treatments including H₂-receptor antagonists, and proton pump inhibitors (PPIs) have been essential for ulcer healing and prevention of complications. Additionally, Helicobacter pylori eradication therapy is effective in reducing ulcer recurrence and leads to physiological changes in the gastric mucosa which affect the ulcer healing process. However, in spite of these advancements, some patients have suffered from recurrence or intractability in spite of continuous anti-ulcer therapy. A new concept of the quality of ulcer healing (QOUH) was initiated that considers the reconstruction of the mucosal structure and its function for preventing ulcer recurrence. Although several gastroprotection provided these achievements of the QOUH, which PPI or other acid suppressants did not accomplish, we found that gastroprotection that originated from natural products, such as a newer formulation from either Artemisia or S-allyl cysteine from garlic, were very effective in the QOUH, as well as improving clinical symptoms with fewer side effects. In this review, we will introduce the importance of the QOUH in ulcer healing and the achievements from natural products.     

超声波联合扶正升血方穴位贴敷在肝硬化脾功能亢进患者中的应用

目的：探讨超声波联合扶正升血方穴位贴敷对肝硬化脾功能亢进患者白细胞、红细胞、血小板的影响及不良反应。方法：将65例入组患者,随机分为两组,对照组予利可君口服,疗程4周;治疗组在对照组治疗的基础上,加用超声波联合扶正升血方穴位贴敷。两组均检测治疗前后患者白细胞、红细胞、血小板水平,观察症状改善情况。结果：治疗组总有效率达84.37%,对照组总有效率达48.48%,差异具有统计学意义（P <0.05）;治疗组治疗前后症状积分有统计学意义（P < 0.05）,对照组治疗前后症状积分无统计学意义。结论：超声波联合扶正升血方穴位贴敷对肝硬化脾功能亢进具有良好的疗效,无明显不良反应。     

Anti-inflammatory and carbonic anhydrase restoring actions of yam powder (Dioscorea spp) contribute to the prevention of cysteamine-induced duodenal ulcer in a rat model

Increased acid output, accompanied with a defective defense system, is considered a fundamental pathogenesis of duodenal ulcer (DU). However, relapse of DU occurs despite proton pump inhibitors and H₂ receptor antagonists, hence imposing the enforcement of the defense system. Dried powder of the yam tuber (Dioscorea spp) has been used in traditional folk medicine as a nutritional fortification. We hypothesized that dried-yam powder would prevent DU through improvement of anti-inflammatory actions and carbonic anhydrase (CA) activity. Therefore, we investigated the preventive effects of dried-yam powder against the cysteamine-induced DU and elucidated the underlying mechanisms. Duodenal ulcers were induced in Sprague-Dawley rats by intragastric administration of 500 mg/kg cysteamine-HCl. The dried-yam powder was used as a pretreatment before the cysteamine-HCl. The number and size of DU were measured. The expressions of inflammation mediators were checked in duodenal tissues, and the expressions of CAs and malondialdehyde levels were also examined. Cysteamine provoked perforated DU, whereas dried-yam powder significantly prevented DU as much as pantoprazole and significantly reduced the incidence of perforation. The messenger RNA expressions of cyclooxygenase-2 and inducible nitric oxide synthase were remarkably decreased in the yam group compared with the cysteamine group, and the serum levels of proinflammatory cytokines including interleukin-1β, interleukin-6, and tumor necrosis factor were significantly attenuated in the yam group. Cysteamine significantly decreased the expression of CAs, whereas yam treatment significantly preserved the expressions of CA IX, XII, and XIV. In conclusion, dried-yam powder exerts a significant protective effect against cysteamine-induced DU by lowering the activity of inflammatory cytokines and free radicals and restoring the activity of CAs, except in CA IV.     

Quality of healing of gastric ulcers: Natural products beyond acid suppression

Gastric ulcer is a chronic disease featured with unexpected complications, including bleeding, stenosis and perforation, as well as a high incidence of recurrence. Clinical treatments for gastric ulcer have allowed the rapid development of potent anti-ulcer drugs during the last several decades. Gastric ulcer healing is successful with conventional treatments including H2-receptor antagonists, and proton pump inhibitors(PPIs) have been essential for ulcer healing and prevention of complications. Additionally, Helicobacter pylori eradication therapy is effective in reducing ulcer recurrence and leads to physiological changes in the gastric mucosa which affect the ulcer healing process. However, in spite of these advancements, some patients have suf-fered from recurrence or intractability in spite of continuous anti-ulcer therapy. A new concept of the quality of ulcer healing(QOUH) was initiated that considers the reconstruction of the mucosal structure and its function for preventing ulcer recurrence. Although several gastroprotection provided these achievements of the QOUH, which PPI or other acid suppressants did not accomplish, we found that gastroprotection that originated from natural products, such as a newer formulation from either Artemisia or S-allyl cysteine from garlic, were very effective in the QOUH, as well as improving clinical symptoms with fewer side effects. In this review, we will introduce the importance of the QOUH in ulcer healing and the achievements from natural products.     

Phase II study of gemcitabine and cisplatin as first-line chemotherapy in inoperable biliary tract carcinoma.

OBJECTIVES: The prognosis for patients with unresectable biliary tract cancer is poor and existing chemotherapy is relatively ineffective. Therefore, a need exists for new, effective chemotherapeutic regimens. The aim of this study was to determine the efficacy and safety profile of gemcitabine plus cisplatin in patients with unresectable biliary tract cancer (cholangiocarcinoma) and gall bladder cancer. METHODS: From December 2000 to July 2002, 43 patients received gemcitabine 1250 mg/m(2) in a 30-min i.v. infusion on d1, 8 and cisplatin 75 mg/m(2) in a 2-h i.v. infusion on d1 (with appropriate hydration), every 3 weeks. ELIGIBILITY: Normal hematologic parameters and creatinine levels; serum bilirubin < 5 mg/dl. RESULTS: Forty-three patients enrolled; 40 were assessable (three patients were not assessable due to incomplete treatment; they chose to discontinue chemotherapy after the first cycle). There were 23 males and 17 females, median age 50 years (range 31-69), median Karnofsky PS 80%. Tumor types: cholangiocarcinoma (39), gall bladder cancer (1). Median number of chemotherapy courses was four (range 1-8). Overall response rate was 27.5% (PR in 11 pts), with 32.5% SD and/or minor response. Median survival time was 36 weeks. Grade 3 hematologic toxicity: anemia (4.33%), leukopenia (1.73%). Non-hematologic toxicity (i.e. rash, nausea, vomiting, neuropathy and myalgia) ranged from mild to moderate. CONCLUSIONS: Gemcitabine plus cisplatin is active in biliary tract carcinoma. These data warrant further investigation of single-agent gemcitabine versus gemcitabine plus cisplatin or its derivative, i.e. oxaliplatin.     

Concerted actions of ameliorated colitis,aberrant crypt foci inhibition and 15‐hydroxyprostaglandin dehydrogenase induction by sonic hedgehog inhibitor led to prevention of colitis‐associated cancer

The sonic hedgehog (Shh) signaling has been known to contribute to carcinogenesis in organ, where hedgehog exerted organogenesis and in cancers, which are developed based on mutagenic inflammation. Therefore, colitis‐associated cancer (CAC) can be a good model to prove whether Shh inhibitors can be applied to prevent, as the efforts to discover potent anti‐inflammatory agent are active to prevent CAC. Here, under the hypothesis that Shh inhibitors can prevent CAC, mouse model was generated to develop CAC by azoxymethane (AOM)‐initiated, dextran sodium sulfate–promoted carcinogenesis. Shh inhibitors, cerulenin and itraconazole were treated by oral gavage and the mice were sacrificed at early phase of 3 weeks and late phase of 16 weeks. Compared to control group, the number of aberrant crypt foci at 3 weeks and tumor incidence at 16 weeks were all significantly decreased with Shh inhibitor. Significant attenuations of macrophage infiltration accompanied with significant decreases of IL‐6, COX‐2, STAT3 and NF‐κB as well as significant ameliorations of β‐catenin nuclear translocation, cyclin D1 and CDK4 were imposed with Shh inhibitors. Especially, CAC was accompanied with significant cancellation of 15‐hydroxyprostaglandin dehydrogenase (15‐PGDH), but their levels were significantly preserved with Shh inhibitors. Among inflammatory mediators, significantly decreased levels of IL‐6 and TNF‐α, regulated with repressed NF‐κb and STAT3, were prominent with Shh inhibitor, whereas significant inductions of apoptosis were noted with Shh inhibitors. In conclusion, Shh inhibitors significantly prevented CAC covering either ameliorating oncogenic inflammation or suppressing tumor proliferation, especially supported with significant inhibition of IL‐6 and STAT3 signaling, 15‐PGDH preservation and apoptosis induction.     

Perilla Seed Oil Alleviates Gut Dysbiosis,Intestinal Inflammation and Metabolic Disturbance in Obese-Insulin-Resistant Rats

Background: High-fat diet (HFD) consumption induced gut dysbiosis, inflammation, obese-insulin resistance. Perilla seed oil (PSO) is a rich source of omega-3 polyunsaturated fatty acids with health promotional effects. However, the effects of PSO on gut microbiota/inflammation and metabolic disturbance in HFD-induced obesity have not been investigated. Therefore, we aimed to compare the effects of different doses of PSO and metformin on gut microbiota/inflammation, and metabolic parameters in HFD-fed rats. Methods: Thirty-six male Wistar rats were fed either a normal diet or an HFD for 24 weeks. At week 13, HFD-fed rats received either 50, 100, and 500 mg/kg/day of PSO or 300 mg/kg/day metformin for 12 weeks. After 24 weeks, the metabolic parameters, gut microbiota, gut barrier, inflammation, and oxidative stress were determined. Results: HFD-fed rats showed gut dysbiosis, gut barrier disruption with inflammation, increased oxidative stress, metabolic endotoxemia, and insulin resistance. Treatment with PSO and metformin not only effectively attenuated gut dysbiosis, but also improved gut barrier integrity and decreased gut inflammation. PSO also decreased oxidative stress, metabolic endotoxemia, and insulin resistance in HFD-fed rats. Metformin had greater benefits than PSO. Conclusion: PSO and metformin had the beneficial effect on attenuating gut inflammation and metabolic disturbance in obese-insulin resistance.     

Non-microbial approach for Helicobacter pylori as faster track to prevent gastric cancer than simple eradication

Although the International Agency for Research on Cancer declared Helicobacter pylori(H.pylori)as a definite human carcinogen in 1994,the Japanese Society for Helicobacter Research only recently(February 2013)adopted the position that H.pylori infection should be considered as an indication for either amelioration of chronic gastritis or for decreasing gastric cancer mortality.Japanese researchers have found that H.pylori eradication halts progressive mucosal damage and that successful eradication in patients with non-atrophic gastritis most likely prevents subsequent development of gastric cancer.However,those who have already developed atrophic gastritis/gastric atrophy retain potential risk factors for gastric cancer.Because chronic perpetuated progression of H.pylori-associated gastric inflammation is associated with increased morbidity culminating in gastric carcinogenesis,a non-microbial approach to treatment that provides long-term control of gastric inflammation through nutrients and other interventions may be an effective way to decrease this morbidity.This non-microbial approach might represent a new form of prerequisite"rescue"therapy that provides a quicker path to the prevention of gastric cancer as compared to simple eradication.     

Protective Effect of Probiotics Isolated from Traditional Fermented Tea Leaves (Miang) from Northern Thailand and Role of Synbiotics in Ameliorating Experimental Ulcerative Colitis in Mice

This study aimed to investigate the protective effect of probiotics and synbiotics from traditional Thai fermented tea leaves (Miang) on dextran sulfate sodium (DSS)-induced colitis in mice, in comparison to sulfasalazine. C57BL/6 mice were treated with probiotics L. pentosus A14-6, CMY46 and synbiotics, L. pentosus A14-6 combined with XOS, and L. pentosus CMY46 combined with GOS for 21 days. Colitis was induced with 2% DSS administration for seven days during the last seven days of the experimental period. The positive group was treated with sulfasalazine. At the end of the experiment, clinical symptoms, pathohistological changes, intestinal barrier integrity, and inflammatory markers were analyzed. The probiotics and synbiotics from Miang ameliorated DSS-induced colitis by protecting body weight loss, decreasing disease activity index, restoring the colon length, and reducing pathohistological damages. Furthermore, treatment with probiotics and synbiotics improved intestinal barrier integrity, accompanied by lowing colonic and systemic inflammation. In addition, synbiotics CMY46 combined with GOS remarkedly elevated the expression of IL-10. These results suggested that synbiotics isolated from Miang had more effectiveness than sulfasalazine. Thereby, they could represent a novel potential natural agent against colonic inflammation.     

Targeted molecular ablation of cancer stem cells for curing gastrointestinal cancers

Introduction: Abundance of the ATPase-binding cassette (ABC) transporters and deranged self-renewal pathways characterize the presence of cancer stem cells (CSCs) in gastrointestinal cancers (GI cancers), which play crucial roles in tumorigenesis, chemotherapy resistance, tumor recurrence, and cancer metastasis. Therefore, in order to ensure high cure rates, chemoquiescence, CSCs should be ablated. Recent advances in either understanding CSCs or biomarker identification enable scientists to develop techniques for ablating CSCs and clinicians to provide cancer cure, especially in GI cancers characterized by inflammation-driven carcinogenesis.

Areas covered: A novel approach to ablate CSCs in GI cancers, including esophageal, gastric, and colon cancers, is introduced along with explored underlying molecular mechanisms.

Expert commentary: Though CSC ablation is still in the empirical stages and not in clinical practice, several strategies for ablating CSCs in GI cancers had been published, proton-pump inhibitors (PPIs) that regulate the membrane-bound ABC transporters, which underlie drug resistance; chloroquine (CQ) that inhibits autophagy, which is responsible for tumor survival; Hedgehog/Wnt/Notch inhibitors that influence the underlying stem-cell growth, and some natural products including Korean red ginseng, cancer-preventive kimchi, Artemisia extract, EGCG from green tea, and walnut extracts.