Use of curcumin and its nanopreparations in the treatment of inflammatory bowel disease.

Inflammatory bowel disease (IBD) is a nonspecific inflammatory disease of the intestine that includes Crohn's disease and ulcerative colitis. Because IBD is difficult to heal and easily relapses, it could worsen patient quality of life and increase economic burdens. Curcumin (CUR) is a bioactive component derived from the rhizome of turmeric (Curcuma longa). Many basic and clinical studies have shown that CUR can efficiently treat IBD by decreasing the activity of proinflammatory cytokines by communicating with transcription factors and signaling molecules. However, due to the limitations of being almost insoluble in aqueous solutions and having low oral bioavailability, it is important to select appropriate pharmaceutical preparations.

Potential therapeutic targets for nonalcoholic fatty liver disease: Glucagon-like peptide 1.

Nonalcoholic fatty liver disease (NAFLD) is the most rapidly growing contributor to liver mortality and morbidity. Hepatocellular injury in nonalcoholic steatohepatitis (NASH) is caused by an increase in metabolic substrates (glucose, fructose, and fatty acids), leading fatty acids to participate in pathways that cause cellular injury and a poor response to injury. The pathogenesis of this disease is largely associated with obesity, type 2 diabetes, and increasing age. To date, there are no Food and Drug Administration-approved treatments for NAFLD/NASH or its associated fibrosis. Since one of the pathogenic drivers of NASH is insulin re-sistance, therapies approved for the treatment of type 2 diabetes are being evaluated in patients with NASH. Currently, the glucagon-like peptide-1 receptor agonist (GLP-1RA) semaglutide is a safe, well-studied therapeutic for NAFLD/ NASH patients. Existing research demonstrates that semaglutide can increase the resolution of NASH but not improve fibrosis. However, improving the fibrosis of NAFLD is the only way to improve the long-term prognosis of NAFLD. Given the complex pathophysiology of NASH, combining therapies with complementary mechanisms may be beneficial. Researchers have conducted trials of semaglutide in combination with antifibrotic drugs. However, the results have not fully met expectations, and it cannot be ruled out that the reason is the short trial time. We should continue to pay increasing attention to GLP-1RAs.

A novel therapeutic strategy for hepatocellular carcinoma: Immunomodulatory mechanisms of selenium and/or selenoproteins on a shift towards anti-cancer.

Selenium (Se) is an essential trace chemical element that is widely distributed worldwide. Se exerts its immunomodulatory and nutritional activities in the human body in the form of selenoproteins. Se has increasingly appeared as a potential trace element associated with many human diseases, including hepatocellular carcinoma (HCC). Recently, increasing evidence has suggested that Se and selenoproteins exert their immunomodulatory effects on HCC by regulating the molecules of oxidative stress, inflammation, immune response, cell proliferation and growth, angiogenesis, signaling pathways, apoptosis, and other processes in vitro cell studies and in vivo animal studies. Se concentrations are generally low in tissues of patients with HCC, such as blood, serum, scalp hair, and toenail. However, Se concentrations were higher in HCC patient tissues after Se supplementation than before supplementation. This review summarizes the significant relationship between Se and HCC, and details the role of Se as a novel immunomodulatory or immunotherapeutic approach against HCC.

Nicotinamide Ameliorates Dextran Sulfate Sodium-Induced Chronic Colitis in Mice through Its Anti-Inflammatory Properties and Modulates the Gut Microbiota.

Vitamin B (nicotinamide (NAM)), one of the most important nutritional components for humans, exerts anti-inflammatory activity. This study was aimed at investigating the effect of NAM on the gut microbiota and short-chain fatty acids (SCFAs) in mice with chronic colitis. Colitis was induced in C57BL/6 male mice by administration of 1.5% dextran sulfate sodium (DSS), and the mice were intraperitoneally injected with normal saline (NS) or NAM. NAM treatment ameliorated weight loss and changes in colon length, disease activity index (DAI) score, and histologic scores. Moreover, enzyme-linked immunosorbent assay (ELISA) analysis of LPL cells revealed that the level of interleukin- (IL-) 6, IL-12p70, IL-1ß, tumor necrosis factor- (TNF-) α, interferon- (IFN-) γ, IL-21, and IL-17A was increased, while IL-10 was reduced, in the chronic colitis group compared to the control group, but the levels of all these factors were restored after NAM treatment. Then, 16S rRNA sequencing of the large intestinal content was performed, and analysis of alpha diversity and beta diversity showed that the richness of the gut microbiota was decreased in the DSS group compared to the control group and restored after NAM treatment. In addition, NAM modulated specific bacteria, including Odoribacter, Flexispira, and Bifidobacterium, in the NAM+chronic colitis group. Phylogenetic Investigation of Communities by Reconstruction of Unobserved States (PICRUSt) analysis indicated that NAM treatment restored disruptions in the functions of the gut microbiota (replication and repair, cell motility) in mice with DSS-induced colitis. Furthermore, NAM also restored the reduction in valeric acid in mice with DSS-induced chronic colitis. Our results suggest that NAM treatment could alleviate DSS-induced chronic colitis in mice by inhibiting inflammation and regulating the composition and function of gut microbiota.

Tea polyphenols and their chemopreventive and therapeutic effects on colorectal cancer.

Colorectal cancer (CRC), a multifactorial disease, is usually induced and developed through complex mechanisms, including impact of diet and lifestyle, genomic abnormalities, change of signaling pathways, inflammatory response, oxidation stress, dysbiosis, and so on. As natural polyphenolic phytochemicals that exist primarily in tea, tea polyphenols (TPs) have been shown to have many clinical applications, especially as anticancer agents. Most animal studies and epidemiological studies have demonstrated that TPs can prevent and treat CRC. TPs can inhibit the growth and metastasis of CRC by exerting the anti-inflammatory, anti-oxidative or pro-oxidative, and pro-apoptotic effects, which are achieved by modulations at multiple levels. Many experiments have demonstrated that TPs can modulate several signaling pathways in cancer cells, including the mitogen-activated protein kinase pathway, phosphatidylinositol-3 kinase/Akt pathway, Wnt/ß-catenin pathway, and 67 kDa laminin receptor pathway, to inhibit proliferation and promote cell apoptosis. In addition, novel studies have also suggested that TPs can prevent the growth and metastasis of CRC by modulating the composition of gut microbiota to improve immune system and decrease inflammatory responses. Molecular pathological epidemiology, a novel multidisciplinary investigation, has made great progress on CRC, and the further molecular pathological epidemiology research should be developed in the field of TPs and CRC. This review summarizes the existing in vitro and in vivo animal and human studies and potential mechanisms to examine the effects of tea polyphenols on CRC.

Catechins and Their Therapeutic Benefits to Inflammatory Bowel Disease.

Catechins are natural polyphenolic phytochemicals that exist in food and medicinal plants, such as tea, legume and rubiaceae. An increasing number of studies have associated the intake of catechins-rich foods with the prevention and treatment of chronic diseases in humans, such as inflammatory bowel disease (IBD). Some studies have demonstrated that catechins could significantly inhibit the excessive oxidative stress through direct or indirect antioxidant effects and promote the activation of the antioxidative substances such as glutathione peroxidases (GPO) and glutathione (GSH), reducing the oxidative damages to the colon. In addition, catechins can also regulate the infiltration and proliferation of immune related-cells, such as neutrophils, colonic epithelial cells, macrophages, and T lymphocytes, helping reduce the inflammatory relations and provide benefits to IBD. Perhaps catechins can further inhibit the deterioration of intestinal lesions through regulating the cell gap junctions. Furthermore, catechins can exert their significant anti-inflammatory properties by regulating the activation or deactivation of inflammation-related oxidative stress-related cell signaling pathways, such as nuclear factor-kappa B (NF-κB), mitogen activated protein kinases (MAPKs), transcription factor nuclear factor (erythroid-derived 2)-like 2 (Nrf2), signal transducer and the activator of transcription 1/3 (STAT1/3) pathways. Finally, catechins can also stabilize the structure of the gastrointestinal micro-ecological environment via promoting the proliferation of beneficial intestinal bacteria and regulating the balance of intestinal flora, so as to relieve the IBD. Furthermore, catechins may regulate the tight junctions (TJ) in the epithelium. This paper elaborates the currently known possible molecular mechanisms of catechins in favor of IBD.

Green tea consumption and risk of esophageal cancer: a meta-analysis of published epidemiological studies.

We performed a meta-analysis to analyze the association of various levels of green tea consumption with risk of esophageal cancer. We searched MEDLINE, EMBASE, and the Cochrane Library for studies of green tea consumption and esophageal cancer and identified 12 observational studies. For esophageal cancer, the pooled relative risk (RR) was 1.09 [95% confidence interval (CI), 0.76-1.55] for greatest vs. non/least green tea consumption; however, there was significant heterogeneity across studies (P = 0.00, I(2) = 75.5%). Compared with subjects who drank no/least green tea, the pooled RR was 1.14 (95% CI = 0.97-1.35) for moderate drinkers, 0.94 (95% CI = 0.77-1.13) for those who drank little, and 0.97 (95% CI = 0.77-1.22) for all subjects who had ever drunk green tea. Subgroup analysis showed that the RR was 0.46 (95% CI = 0.29-0.73) for female subjects. The results of the present meta-analysis are that any association between green tea and risk of esophageal cancer remains unclear. Subgroup analyses indicated that greater consumption of green tea might reduce the risk of esophageal cancer in female subjects. However, the results are based on limited research. Further research is needed to confirm the results and clarify the likely biological mechanisms.

Consumption of coffee associated with reduced risk of liver cancer: a meta-analysis.

BACKGROUND: Epidemiologic studies have reported inconsistent results regarding coffee consumption and the risk of liver cancer. We performed a meta-analysis of published case-control and cohort studies to investigate the association between coffee consumption and liver cancer. METHODS: We searched Medline, EMBASE, ISI Web of Science and the Cochrane library for studies published up to May 2012. We performed a meta-analysis of nine case-control studies and seven cohort studies. RESULTS: The summary odds ratio (OR) for high vs no/almost never drinkers was 0.50 (95% confidence interval (CI): 0.42-0.59), with no significant heterogeneity across studies (Q = 16.71; P = 0.337; I2 = 10.2%). The ORs were 0.50 (95% CI: 0.40-0.63) for case-control studies and 0.48 (95% CI: 0.38-0.62) for cohort studies. The OR was 0.38 (95% CI: 0.25-0.56) in males and 0.60 (95% CI: 0.33-1.10) in females. The OR was 0.45 (95% CI: 0.36-0.56) in Asian studies and 0.57 (95% CI: 0.44-0.75) in European studies. The OR was 0.39 (95% CI: 0.28-0.54) with no adjustment for a history of liver disease and 0.54 (95% CI: 0.46-0.66) after adjustment for a history of liver disease. CONCLUSIONS: The results of this meta-analysis suggested an inverse association between coffee consumption and liver cancer. Because of the small number of studies, further prospective studies are needed.