Butyrate supplementation regulates expression of chromosome segregation 1­like protein to reverse the genetic distortion caused by p53 mutations in colorectal cancer.

The chromosome segregation 1­like (CSE1L) protein, which regulates cellular mitosis and apoptosis, was previously found to be overexpressed in colorectal cancer (CRC) cells harboring mutations. Therefore, regulating CSE1L expression may confer chemotherapeutic effects against CRC. The gut microflora can regulate gene expression in colonic cells. In particular, metabolites produced by the gut microflora, including the short­chain fatty acid butyrate, have been shown to reduce CRC risk. Butyrates may exert antioncogenic potential in CRC cells by modulating p53 expression. The present study evaluated the association between CSE1L expression and butyrate treatment from two non­transformed colon cell lines (CCD­18Co and FHC) and six CRC cell lines (LS 174T, HCT116 p53+/+, HCT116 p53­/­, Caco­2, SW480 and SW620). Lentiviral knockdown of CSE1L and p53, reverse transcription­quantitative PCR (CSE1L, c­Myc and p53), western blotting [CSE1L, p53, cyclin (CCN) A2, CCNB2 and CCND1], wound healing assay (cell migration), flow cytometry (cell cycle analysis) and immunofluorescence staining (CSE1L and tubulin) were adopted to verify the effects of butyrate on CSE1L­expressing CRC cells. The butyrate­producing gut bacteria Butyricicoccus pullicaecorum was administered to mice with 1,2­dimethylhydrazine­induced colon tumors before the measurement of CSE1L expression. The effects of B. pullicaecorum on CSE1L expression were then assessed by immunohistochemical staining for CSE1L and p53 in tissues from CRC­bearing mice. Non­cancerous colon cells with the R273H p53 mutation or CRC cells haboring p53 mutations were found to exhibit significantly higher CSE1L expression levels. CSE1L knockdown in HCT116 p53­/­ cells resulted in G1­and G2/M­phase cell cycle arrest. Furthermore, in HCT116 p53­/­ cells, CSE1L expression was already high at interphase, increased at prophase, peaked during metaphase before declining at cytokinesis but remained relatively high compared with that in HCT116 expressing wild­type p53. Significantly decreased expression levels of CSE1L were also observed in HCT116 p53­/­ cells that were treated with butyrate for 24 h. In addition, the migration of HCT116 p53­/­ cells was significantly decreased after CSE1L knockdown or butyrate treatment. Tumors with more intense nuclear p53 staining and weaker CSE1L staining were found in mice bearing DMH/DSS­induced CRC that were administered with B. pullicaecorum. Taken together, the results indicated that butyrate can impair CSE1L­induced tumorigenic potential. In conclusion, butyrate­producing microbes, such as B. pullicaecorum, may reverse the genetic distortion caused by p53 mutations in CRC by regulating CSE1L expression levels.

Germinated brown rice combined with Lactobacillus acidophilus and Bifidobacterium animalis subsp. lactis inhibits colorectal carcinogenesis in rats.

Colorectal cancer is a common cancer strongly associated with diet. Certain probiotics and prebiotics possess an inhibitory activity against colorectal cancer, while synbiotics may be more effective in preventing this cancer than either prebiotics or probiotics alone. Germinated brown rice (GBR) is considered as a candidate prebiotics with anticancer potential. However, the effect of GBR combined with probiotics on colorectal cancer is not clear. The present study investigated the preventive effect of combination of GBR and Lactobacillus acidophilus, Bifidobacterium animalis subsp. lactis, or both on colorectal carcinogenesis and the possible mechanism in rats treated with 1,2-dimethylhydrazine (DMH) and dextran sulfate sodium (DSS). DMH/DSS treatment induced preneoplastic aberrant crypt foci (ACF) and mucin-depleted foci (MDF), reduced superoxide dismutase (SOD) activity, increased anti-apoptotic Bcl-2 expression, and decreased the expression of pro-apoptotic p53, Bax, and caspase-3 in the colon. Germinated brown rice alone or combined with probiotics inhibited the formation of MDF in the middle colon, enhanced the colonic expression of p53 and Bax, and increased the ratio of Bax/Bcl-2. Combined treatment of GBR and probiotics inhibited the formation of ACF-producing sialomucin (SIM-ACF) and recovered the activity of SOD in the colon. Combination of GBR and L. acidophilus further increased caspase-3 expression and decreased Bcl-2 expression. These findings suggest that GBR combined with L. acidophilus and/or B. animalis subsp. lactis may inhibit colorectal carcinogenesis by enhancing antioxidative capacity and inducing apoptosis. This synbiotics may be a potential functional food or chemopreventive agent for controlling colorectal cancer.

Red Blood Cell Aggregation-Associated Dietary Pattern Predicts Hyperlipidemia and Metabolic Syndrome.

Red blood cell (RBC) aggregation and iron status are interrelated and strongly influenced by dietary factors, and their alterations pose a great risk of dyslipidemia and metabolic syndrome (MetS). Currently, RBC aggregation-related dietary patterns remain unclear. This study investigated the dietary patterns that were associated with RBC aggregation and their predictive effects on hyperlipidemia and MetS. Anthropometric and blood biochemical data and food frequency questionnaires were collected from 212 adults. Dietary patterns were derived using reduced rank regression from 32 food groups. Adjusted linear regression showed that hepcidin, soluble CD163, and serum transferrin saturation (%TS) independently predicted RBC aggregation (all p < 0.01). Age-, sex-, and log-transformed body mass index (BMI)-adjusted prevalence rate ratio (PRR) showed a significant positive correlation between RBC aggregation and hyperlipidemia (p-trend < 0.05). RBC aggregation and iron-related dietary pattern scores (high consumption of noodles and deep-fried foods and low intake of steamed, boiled, and raw food, dairy products, orange, red, and purple vegetables, white and light-green vegetables, seafood, and rice) were also significantly associated with hyperlipidemia (p-trend < 0.05) and MetS (p-trend = 0.01) after adjusting for age, sex, and log-transformed BMI. Our results may help dieticians develop dietary strategies for preventing dyslipidemia and MetS.

Improvement of abnormal liver enzymes after rosiglitazone treatment in Chinese type 2 diabetes.

OBJECTIVES: Insulin resistance is one of the important underlying abnormalities of type 2 diabetes. The effect of thiazolidinedione on liver functions has been controversial in different studies. In this study, we evaluated the effect of rosiglitazone on liver enzymes in subjects with type 2 diabetes with and without abnormal liver function. MATERIALS AND METHODS: Seventy-three patients with type 2 diabetes taking rosiglitazone 4 mg daily were enrolled in this 3-month study. Forty-two of them had normal liver function (NLF), and 31 had abnormal liver function (ABLF). Blood biochemistries were collected monthly during the treatment period. RESULTS: At baseline, other than age and liver enzymes, there were no differences in body mass index, fasting plasma glucose, hemoglobin A1c (HbA1c), and lipid profiles between the NLF and ABLF groups. At the end of the treatment, HbA1c was lowered in both groups, but only significantly in the ABLF group (P = 0.027). More importantly, serum concentrations of both aspartate aminotransferase (AST) and alanine aminotransferase (ALT) in the ABLF group decreased significantly (AST: 57.8 ± 26.5 to 47.5 ± 20.2 U/L, P = 0.006; ALT 66.6 ± 35.0 to 51.9 ± 23.5 UL, P = 0.004), while in the NLF group, a similar change was not found. CONCLUSION: After 3-month rosiglitazone treatment in subjects with type 2 diabetes with mildly elevated liver enzymes, significant improvement in AST and ALT were observed. Our study provides some hints that rosiglitazone might not be contraindicated in subjects with diabetes with abnormal liver function as previously thought, but further well-designed studies are necessary to clarify this issue.

Hyperosmolar hyperglycemic state induced myocardial infarction: a complex conjunction of chronic and acute complications with diabetes mellitus.

Diabetes mellitus is associated with acute and chronic complications that cause major morbidity and significant mortality. We report a 69-year-old man with unknown diabetes, presenting vague epigastric discomfort, polyuria, polydipsia, fatigue, anorexia, weight loss over 1 week and severe chest pain for 1 day. Electrocardiogram revealed ST-segment elevation in lead V1 through V6. Blood chemistry examination revealed a creatine kinase level of 2053 U/l, creatine kinase-MB (CK-MB) level 43 U/l, a troponin I level of 23.21 ng/ml, a blood sugar level of 957 mg/dl, blood osmolality of 324 mosm/kg and no ketonemia. The patient was diagnosed as hyperosmolar hyperglycemic state accompanying acute anterior wall ST-segment elevation myocardial infarction on unknown diabetes mellitus. Aggressive therapy failed to ameliorate the patient's clinical outcome.