Fucoidan is a kind of the polysaccharide, which comes from brown algae and comprises of sulfated fucose residues. It has shown a large range of biological activities in basic researches, including many elements like anti-inflammatory, anti-cancer, anti-viral, anti-oxidation, anticoagulant, antithrombotic, anti-angiogenic and anti-Helicobacter pylori, etc. Cancer is a multifactorial disease of multiple causes. Most of the current chemotherapy drugs for cancer therapy are projected to eliminate the ordinary deregulation mechanisms in cancer cells. Plenty of wholesome tissues, however, are also influenced by these chemical cytotoxic effects. Existing researches have demonstrated that fucoidan can directly exert the anti-cancer actions through cell cycle arrest, induction of apoptosis, etc., and can also indirectly kill cancer cells by activating natural killer cells, macrophages, etc. Fucoidan is used as a new anti-tumor drug or as an adjuvant in combination with an anti-tumor drug because of its high biological activity, wide source, low resistance to drug resistance and low side effects. This paper reviews the mechanism by which fucoidan can eliminate tumor cells, delay tumor growth and synergize with anticancer chemotherapy drugs in vitro, in vivo and in clinical trials.

Purpose: Inulin is a type of fermentable dietary fiber, which is non-digestible, and can improve metabolic function by modulating intestinal microbiota. This study aimed to evaluate the role of inulin in hyperuricemia and microbial composition of the gut microbiota in a mouse model of hyperuricemia established through knockout of Uox (urate oxidase) gene. Methods: KO (Uox-knockout) and WT (wild-type) mice were given inulin or saline by gavage for 7 weeks. The effect of inulin to combat hyperuricemia was determined by assessing the changes in serum UA (uric acid) levels, inflammatory parameters, epithelial barrier integrity, fecal microbiota alterations, and SCFA (short-chain fatty acid) concentrations in KO mice. Results: Inulin supplementation can effectively alleviate hyperuricemia, increase the expressions of ABCG2 in intestine, and downregulate expression and activity of hepatic XOD (xanthine oxidase) in KO mice. It was revealed that the levels of inflammatory cytokines and the LPS (lipopolysaccharide) were remarkably higher in the KO group than those in the WT group, indicating systemic inflammation of hyperuricemic mice, but inulin treatment ameliorated inflammation in KO mice. Besides, inulin treatment repaired the intestinal epithelial barrier as evidenced by increased levels of intestinal TJ (tight junction) proteins [ZO-1 (zonula occludens-1) and occluding] in KO mice. Moreover, serum levels of uremic toxins, including IS (indoxyl sulfate) and PCS (p-cresol sulfate), were reduced in inulin-treated KO mice. Further investigation unveiled that inulin supplementation enhanced microbial diversity and raised the relative abundance of beneficial bacteria, involving SCFAs-producing bacteria (e.g., Akkermansia and Ruminococcus). Additionally, inulin treatment increased the production of gut microbiota-derived SCFAs (acetate, propionate and butyrate concentrations) in KO mice, which was positively correlated with the effectiveness of hyperuricemia relief. Conclusions: Our findings showed that inulin may be a promising therapeutic candidate for the treatment of hyperuricemia. Moreover, alleviation of hyperuricemia by inulin supplementation was, at least, partially conciliated by modulation of gut microbiota and its metabolites.

Previous studies have demonstrated the effects of hyperuricemia on the damage to target organs, including the kidneys, joints and the heart. However, it is unclear whether hyperuricemia results in damage to the intestines. The aim of the present study was to investigate intestinal barrier dysfunction in a mouse model of hyperuricemia constructed by knocking out the urate oxidase (Uox) gene. The morphology of the intestine was assessed via hematoxylin and eosin, and alcian blue staining. The serum and intestinal tissue levels of uric acid, tumor necrosis factor (TNF)‑α and interleukin (IL)‑6, in addition to the presence of uremic toxins in the serum, were assessed. The levels of diamine oxidase (DAO), D‑lactate (D‑LAC) and endotoxins in the serum, which are markers of the intestinal permeability, were measured using ELISA. The expression of the intestinal tight junction proteins zona occludens‑1 (ZO‑1) and occludin were detected by reverse transcription‑quantitative polymerase chain reaction, western blotting and immunohistochemical analysis. The Uox‑knockout mice spontaneously developed hyperuricemia. Histopathological analysis indicated notable intestinal defects including sparse villi, mucosal edema and a declining mucus layer in hyperuricemic mice. The expression levels of ZO‑1 and occludin in the intestines were downregulated, and the serum levels of DAO, D‑LAC and endotoxins were higher in the hyperuricemic mice, compared with control mice. The serum and intestinal tissue levels of IL‑6 and TNF‑α were significantly increased. Additionally, the expression levels of the serum uremic toxins, serum creatinine, blood urea nitrogen were significantly increased in hyperuricemic mice compared with the control mice, while only a marked increase in indoxyl sulfate (IS) and p‑cresol sulfate was reported. Collectively, the results of the present study suggested that intestinal barrier dysfunction and subsequent enhanced intestinal permeability may occur as a result of hyperuricemia in mice. Furthermore, we proposed that the loss of intestinal epithelium barrier function may be associated with uric acid‑induced inflammatory responses; however, further investigation is required.

The goal of this study was to examine the role of sodium butyrate in preserving the intestinal mucosal barrier and reducing hyperuricemia (HUA). First, we established a mouse model of HUA via intraperitoneal injection of potassium oxonate together with a yeast-rich diet to detect the levels of serum uric acid (UA) and fecal short-chain fatty acids (SCFAs). Then, in vitro, different concentrations of UA and sodium butyrate (NaB) were used to treat LS174T and Caco2 cells. The effects of UA and NaB on the gut barrier were determined based on the expression levels of MUC2, ZO-1, and Occludin.Finally, C57BL/6 mice were used to model HUA, and these mice were administered 200 mg·kg^-1·d^-1 NaB by gavage to counter the HUA. The effect of NaB on HUA in the intestinal tract was elucidated by determining serum UA levels, inflammatory parameters, epithelial barrier integrity, and via histological analysis. The data showed that the content of fecal SCFAs in HUA mice decreased. Additionally, in LS174T and Caco2 cells, NaB reversed the decrease of ZO-1, Occludin, and MUC2 protein expression caused by high UA levels. Furthermore, NaB decreased serum UA of HUA mice, and reversed both the decreased expression of MUC2, ZO-1, Occludin, and ABCG2 proteins and the increased level of inflammatory factors in the intestinal tissues of these mice. The HUA mouse model showed intestinal barrier damage. NaB protected the intestinal barrier of HUA mice and reduced the serum UA level.

Background: The gut microbiota is closely linked to cholesterol metabolism-related diseases such as obesity and cardiovascular diseases. However, whether gut microbiota plays a causal role in cholelithiasis remains unclear.Aims: This study explored the causal relationship between gut microbiota and cholelithiasis. We hypothesize that the gut microbiota influences cholelithiasis development.Methods: A two-sample Mendelian randomization method was combined with STRING analysis to test this hypothesis. Summary data on gut microbiota and cholelithiasis were obtained from the MiBioGen (n=13,266) and FinnGen R8 consortia (n=334,367), respectively.Results: Clostridium senegalense, Coprococcus3, and Lentisphaerae increased the risk of cholelithiasis and expressed more bile salt hydrolases. In contrast, Holdemania, Lachnospiraceae UCG010, and Ruminococcaceae NK4A214 weakly expressed bile salt hydrolases and were implied to have a protective effect against cholelithiasis by Mendelian randomization analysis.Conclusion: Gut microbiota causally influences cholelithiasis and may be related to bile salt hydrolases. This work improves our understanding of cholelithiasis causality to facilitate the development of treatment strategies.

The aim of this study is to identify and consolidate reliable endoscopic features associated withH. pyloriinfection in gastric mucosa, which is one of the major causes of gastric cancer. A total of 256 Chinese patients with symptomatic stomach disturbances were enrolled. Pathological examination was conducted using a light microscope and biopsy specimens stained with hematoxylin-eosin. Endoscopic examination was performed using a high resolution video endoscope. The association between endoscopic features and pathologicalH. pyloridiagnosis was compared, and endoscopic features significantly associated withH. pyloriinfection were identified. A total of 14 endoscopic features were observed. Six of the 14 endoscopic features, including mucus on the gastric mucosa, diffuse redness, spotty redness of fundic mucosa, enlarged fold, mucosal edema, and RAC (type D and type I), were highly associated withH. pyloriinfection and were significantly sensitive and specific predictors forH. pyloridiagnosis. The type R RAC was not significantly associated withH. pyloridiagnosis. Our results indicate that conventional endoscopy features can be used to diagnoseH. pyloriin Chinese patients and can help determine the risk factor for gastric cancer.