Dietary walnut as food factor to rescue from NSAID-induced gastrointestinal mucosal damages.

Nuclear factor erythroid-derived 2-like 2 (Nrf-2) is transcription factor implicated in the antioxidant response element-mediated induction of endogenous antioxidant enzyme such as heme oxygenase-1 (HO-1), glutamate-cysteine ligase, and NAD(P)H quinone dehydrogenase 1, among which HO-1 is an enzyme catalyzing the degradation of heme.producing biliverdin, ferrous iron, and carbon monoxide. In the stomach, as much as regulating gastric acid secretions, well-coordinated establishment of defense system stands for maintaining gastric integrity. In previous study, author et al. for the first time discovered HO-1 induction was critical in affording faithful gastric defense against various irritants including Helicobacter pylori infection, stress, alcohol, non-steroidal anti-inflammatory drugs (NSAIDs), aspirin, and toxic bile acids. In this review article, we can add the novel evidence that dietary walnut intake can be reliable way to rescue from NSAIDs-induced gastrointestinal damages via the induction of HO-1 transcribed with Nrf-2 through specific inactivation of Keap-1. From molecular exploration to translational animal model of indomethacin-induced gastrointestinal damages, significant induction of HO-1 contributed to rescuing from damages. In addition to HO-1 induction action relevant to walnut, we added the description the general actions of walnut extracts or dietary intake of walnut regarding cytoprotection and why we have focused on to NSAID damages.

Walnut polyphenol extracts inhibit Helicobacter pylori-induced STAT3Tyr705 phosphorylation through activation of PPAR-γ and SOCS1 induction.

The health beneficial effects of walnut plentiful of n-3 polyunsaturated fatty acid had been attributed to its anti-inflammatory and anti-oxidative properties against various clinical diseases. Since we have published Fat-1 transgenic mice overexpressing 3-desaturase significantly mitigated Helicobacter pylori (H. pylori)-associated gastric pathologies including rejuvenation of chronic atrophic gastritis and prevention of gastric cancer, in this study, we have explored the underlying molecular mechanisms of walnut against H. pylori infection. Fresh walnut polyphenol extracts (WPE) were found to suppress the phosphorylation and nuclear translocation of signal transducer and activator of transcription 3 (STAT3) induced by H. pylori infection in RGM-1 gastric mucosal cells. Notably, H. pylori infection significantly decreased suppressor of cytokine signaling 1 (SOCS1), but WPE induced expression of SOCS1, by which the suppressive effect of walnut extracts on STAT3Tyr705 phosphorylation was not seen in SOCS1 KO cells. WPE induced significantly increased nuclear translocation nuclear translocation of PPAR-γ in RGM1 cells, by which PPAR-γ KO inhibited transcription of SOCS1 and suppressive effect of WPE on p-STAT3Tyr705 was not seen. WPE inhibited the expression of c-Myc and IL-6/IL-6R signaling, which was attenuated in the RGM1 cells harboring SOCS1 specific siRNA. Conclusively, WPE inhibits H. pylori-induced STAT3 phosphorylation in a PPAR-γ and SOCS1-dependent manner.

Dolichos lablab L. extracts as pharmanutrient for stress-related mucosal disease in rat stomach.

Gastric stress-related mucosal disease (SRMD) presented from superficial gastritis to deep ulceration consequent to insufficient perfusion, ischemia, and oxidative stress. Though pharmacologic interventions to optimize tissue perfusion or to enhance defensive mechanism are essential, limited clinical outcome necessitates strong acid suppressors or natural agents. Under the hypothesis that Dolichos lablab L. (NKM 23-1) can enhance defense against SRMD, water immersion restraint stress (WIRS) were imposed to rats and additional groups pretreated with differing doses of NKM 23-1 were monitored. On gross and microscopic evaluation, they significantly rescued SRMD (p<0.01). The levels of inflammatory mediators such as IL-18, IL-1ß, IL-8, iNOS, TNF-α, caspase-1, NOXs as well as MMPs accompanied with NF-κB p50 activation were all significantly increased in WIRS, but their levels were significantly decreased in Groups pretreated with NKM 23-1. WIRS significantly increased apoptosis, but significantly decreased with NKM 23-1 accompanied with significantly increased levels of cyclin D/E and HSP70/HSP27. Gastric mucin was significantly preserved in Groups pretreated with NKM 23-1, while depleted in WIRS, accompanied with increased expressions of Muc5A. Gastric levels of HO-1 and NQO1 were significantly increased in Group treated with NKM 23-1 with transcriptional activation of Nrf2. Conclusively, preemptive intake of NKM 23-1 significantly rescued SRMD.

Dietary intake of probiotic kimchi ameliorated IL-6-driven cancer cachexia.

Cancer cachexia is a syndrome accompanying weight loss, skeletal muscle atrophy, and loss of adipose tissue in patients with advanced cancer. Since interleukin-6 (IL-6) is one of core mediators causing cancer cachexia and kimchi can modulate IL-6 response, we hypothesized dietary intake of kimchi can ameliorate cancer cachexia. In this study, we studied preemptive administration of kimchi can ameliorate mouse colon carcinoma cells colon (C26) adenocarcinoma-induced cancer cachexia and explored anti-cachexic mechanisms of kimchi focused on the changes of muscle atrophy, cachexic inflammation, and catabolic catastrophe. As results, dietary intake of kimchi significantly attenuated the development of cancer cachexia, presented with lesser weight loss, higher muscle preservation as well as higher survival from cancer cachexia in mice. Starting from significant inhibition of IL-6 and its signaling, kimchi afforded significant inhibition of muscle specific ubiquitin-proteasome system including inhibition of atrogin-1 and muscle ring finger protein-1 (MuRF-1) with other muscle related genes including mitofusin-2 (Mfn-2) and PGC-1α. Significant inhibition of lipolysis gene such as adipose triglyceride lipase (ATGL) and hormone-sensitive ligase (HSL) accompanied with significant induction of fatty acid synthase (FAS) and sterol response element binding protein 1 (SREBP1) was achieved with kimchi. As gene regulation, IL-6 and their receptor as well as Janus kinase 2 (JAK2) and signal transducer and activator of transcription 3 (STAT3) were significantly attenuated with kimchi. In conclusion, dietary intake of cancer preventive kimchi can be an anticipating option to ameliorate cancer cachexia via suppressive action of IL-6 accompanied with decreased muscle atrophy and lipolysis.

Role of omega-3 polyunsaturated fatty acids in preventing gastrointestinal cancers: current status and future perspectives.

INTRODUCTION: Although inflammation is defensive and healing process that maintains organ homeostasis, unresolved inflammation can lead to diseases. Polyunsaturated fatty acids (PUFAs), especially n-6 PUFAs abundant in Western diet, are precursors of pro-inflammatory mediators, whereas n-3 PUFAs possess anti-inflammatory properties. Therefore, interest in the cancer-preventive effect of n-3 PUFAs is increasing. Areas covered: We have observed significant reductions of gastrointestinal tumorigenesis in the Fat-1 transgenic mouse as evidenced that the decrease in Helicobacter pylori-infected gastric tumorigenesis, colon, biliary, and pancreatic cancer was seen in Fat-1 mice producing n-3 PUFAs. However, despite many studies showing benefits, evidence-based medicine regarding molecular pathology, epidemiology, and clinical achievement of cancer prevention of n-3 PUFAs are still limited. Expert commentary: Primary deficiency of eicosapentaenoic acids and docosahexaenoic acids in Western diets can explain the risk of cancer development and the importance of n-3/n-6 PUFA ratio in reducing cancer risk. Alteration of cell membrane composition during carcinogenesis is particularly important, due to increased rate of lipid/cholesterol synthesis in cancerous tissues. Here, we discuss that direct incorporation of n-3 PUFAs in the cell membrane corrects abnormal cellular proliferation and decreases inflammation-associated carcinogenesis. This is exemplified by cancer-preventive effects of n-3 PUFAs as fat sources for gastrointestinal cancers.

BPC157 as Potential Agent Rescuing from Cancer Cachexia.

Cancer cachexia, one of the metabolic syndromes caused by cancer, is a devastating and miserable condition encountered in more than 50% of terminal cancer patients presenting with significant weight loss associated with skeletal muscle atrophy and fat loss. Though cachexia may account for up to 20% of cancer deaths, no significant treatment is still lacking and is of urgent unmet medical need in cancer treatment. Therefore, understanding the underlying molecular mechanisms is essential for anticipating therapeutic approaches. Since the primary events driving cachexia are mediated via either the central nervous system relatedor inflammation related-anorexia, hypoanabolism, and hypercatabolism, therapy usually targets nutritional support to compensate reduced food intake along with some anti-inflammatory agents to cover specific inflammation-related metabolic derangement, and encourages exercise to supplement reduced physical activity, but all proven to be not so effective so far. Therefore, combination therapies such as a standard multi-modal package including an anorexic agent, megestrol acetate, and anti-inflammatory agent coupled with the development of potential novel therapeutics promise a new era in rescuing patients from cancer cachexia. In this review, we propose the potential application of BPC157, one of the active cytoprotective agents isolated from gastric juices for cancer cachexia. Before clinical trial, we introduced the evidence showing BPC157 rescued from cancer cachexia supported with explored mode of actions.

Mediastinal single nodal relapse of a nasal NK/T cell lymphoma.

A nasal NK/T cell lymphoma is a very aggressive form of lymphoma. Patterns of relapse after treatment have not been systematically evaluated, and mediastinal nodal relapse at a primary site has never been documented. We describe here a 40-year old man who presented with a nasal obstruction caused by a protruding mass that was identified as a nasal NK/T cell lymphoma. The initial work-up, including chest and abdominopelvic computed tomography (CT) and positron emission tomography (PET), showed no regional or distant metastasis. A CT scan performed following three cycles of chemotherapy with cyclophosphamide, doxorubicin, vincristine, and prednisolone (CHOP) showed that the mass had nearly disappeared. Radiation therapy undertaken following chemotherapy was given to the primary site. However, PET performed following radiotherapy revealed a single mediastinal lymphadenopathy, with no evidence of residual tumor in the nasal cavity. A biopsy using video-assisted thoracoscopy (VATS) showed the presence of a recurrent NK/T cell lymphoma with an immunophenotype identical to that of the primary nasal lymphoma. An additional three cycles of CHOP chemotherapy were administered, and the patient remains alive, with no evidence of disease 30 months after the initial relapse. These findings indicate that early detection with PET and prompt surgical excision with the use of VATS can lead to successful treatment of a relapsed nasal NK/T cell lymphoma.