[Banxia Xiexin Decoction inhibiting colitis-associated colorectal cancer infected with Fusobacterium nucleatum by regulating Wnt/ß-catenin pathway].

This paper investigates the intervention effect and mechanism of Banxia Xiexin Decoction(BXD) on colitis-associated colorectal cancer(CAC) infected with Fusobacterium nucleatum(Fn). C57BL/6 mice were randomly divided into a control group, Fn group, CAC group [azoxymethane(AOM)/dextran sulfate sodium salt(DSS)](AOM/DSS), model group, and BXD group. Except for the control and AOM/DSS groups, the mice in the other groups were orally administered with Fn suspension twice a week. The AOM/DSS group, model group, and BXD group were also injected with a single dose of 10 mg·kg~(-1) AOM combined with three cycles of 2.5% DSS taken intragastrically. The BXD group received oral administration of BXD starting from the second cycle until the end of the experiment. The general condition and weight changes of the mice were monitored during the experiment, and the disease activity index(DAI) was calculated. At the end of the experiment, the colon length and weight of the mice in each group were compared. Hematoxylin-eosin(HE) staining was used to observe the pathological changes in the colon tissue. Enzyme-linked immunosorbent assay(ELISA) was used to detect the levels of interleukin(IL)-2, IL-4, and IL-6 inflammatory factors in the serum. Immunohistochemistry(IHC) was used to detect the expression of Ki67, E-cadherin, and ß-catenin in the colon tissue. Western blot was used to detect the protein content of Wnt3a, ß-catenin, E-cadherin, annexin A1, cyclin D1, and glycogen synthase kinase-3ß(GSK-3ß) in the colon tissue. The results showed that compared with the control group, the Fn group had no significant lesions. The mice in the AOM/DSS group and model group had decreased body weight, increased DAI scores, significantly increased colon weight, and significantly shortened colon length, with more significant lesions in the model group. At the same time, the colon histology of the model group showed more severe adenomas, inflammatory infiltration, and cellular dysplasia. The levels of IL-4 and IL-6 in the serum were significantly increased, while the IL-2 content was significantly decreased. The IHC results showed low expression of E-cadherin and high expression of Ki67 and ß-catenin in the model group, with a decreased protein content of E-cadherin and GSK-3ß and an increased protein content of Wnt3a, ß-catenin, annexin A1, and cyclin D1. After intervention with BXD, the body weight of the mice increased; the DAI score decreased; the colon length increased, and the tumor decreased. The histopathology showed reduced tumor proliferation and reduced inflammatory infiltration. The levels of IL-6 and IL-4 in the serum were significantly decreased, while the IL-2 content was increased. Meanwhile, the expression of E-cadherin was upregulated, and that of Ki67 and ß-catenin was downregulated. The protein content of E-cadherin and GSK-3ß increased, while that of Wnt3a, ß-catenin, annexin A1, and cyclin D1 decreased. In conclusion, BXD can inhibit CAC infected with Fn, and its potential mechanism may be related to the inhibition of Fn binding to E-cadherin, the decrease in annexin A1 protein level, and the regulation of the Wnt/ß-catenin pathway.

[Tongxie Yaofang regulates tumor-associated macrophage polarization in colorectal cancer under chronic stress].

This study aims to investigate the intervention effect and mechanism of Tongxie Yaofang in regulating tumor-associated macrophage polarization on colorectal cancer under chronic stress. BALB/C mice were randomized into blank, control, model, mifepristone, and low-, medium-, and high-dose Tongxie Yaofang groups. The other groups except the blank and model groups were subjected to chronic restraint stress and subcutaneous implantation of colon cancer cells for the modeling of colon cancer under stress. Du-ring this period, the body mass and tumor size of each group of mice were recorded. The degree of depression in mice was assessed by behavioral changes. Enzyme-linked immunosorbent assay was employed to determine the levels of cortisol(CORT), 5-hydroxytryptamine(5-HT), norepinephrine(NE), M1-associated inflammatory cytokines [interleukin(IL)-1ß, IL-12, and tumor necrosis factor(TNF)-α], and M2-associated inflammatory cytokines(IL-4 and IL-10) in the serum. The tumor growth of mice in each group was regularly monitored by in vivo imaging. The histopathological changes of tumors in each group of mice were observed by hematoxylin-eosin staining. The proportions of CD86 and CD206 in the tumor tissue were detected by flow cytometry and immunofluorescence staining. Western blot was employed to determine the protein levels of Janus kinase(JAK)1, JAK2, JAK3, signal transducer and activator of transcription(STAT)3, and STAT6 in the tumor tissue. The results showed that chronic stress increased the immobility time of mice, elevated the serum levels of CORT, IL-4, and IL-10, lowered the levels of 5-HT, NE, IL-1ß, IL-12, and TNF-α, and promoted the growth of subcutaneous tumors. The tumor cells in the tumor tissue grew actively, with obvious atypia and up-regulated protein levels of CD206, JAK1, JAK2, JAK3, STAT3, and STAT6, and down-regulated protein level of CD86. The treatment with Tongxie Yaofang shortened the immobility time of mice, lowered the serum levels of CORT, IL-4, and IL-10, elevated the serum levels of 5-HT, NE, IL-1ß, IL-12, and TNF-α, and inhibited the growth of subcutaneous tumors in mice. Moreover, the treatment caused different degrees of necrosis in the tumor tissues, down-regulated the protein levels of CD206, JAK1, JAK2, JAK3, STAT3, and STAT6, and up-regulated the protein level of CD86. In summary, Tongxie Yaofang can promote the transformation of M2 macrophages to M1 macrophages and change the tumor microenvironment under chronic stress to inhibit the development of colorectal cancer, which may be related to the JAK/STAT signaling pathway.

Gender difference in the association of serum selenium with all-cause and cardiovascular mortality.

Objectives: The relationship between selenium and all-cause mortality has been inconsistent from observational studies and clinical trials. The present study aimed to reveal the relationship between serum selenium and all-cause and cardiovascular disease (CVD) mortality and the potential gender differences.Methods: All participants were recruited from the 1999-2006 National Health and Nutrition Examination Survey (NHANES). Participants with available serum selenium data were followed up until 31 December 2015. Cox proportional hazards models were performed to estimate adjusted hazard ratios (HRs) and 95% confidence intervals (CI) for all-cause and CVD mortality according to baseline selenium level in quartiles. Multivariable-adjusted spline curves were performed to detect non-linearity in relationships.Results: There were 2,903 subjects (50.7% female) included in this study. The mean age was 61.9 ± 13.7 years, and the mean selenium levels were 136.4 ± 19.6 ug/L. A total of 858 (29.6%) cases of all-cause mortality and 126 (4.3%) CVD mortality occurred during the median follow-up duration of 10.2 years. On average, deceased participants had lower serum selenium levels, (135.1 ± 22.3 vs. 137.0 ± 18.4 ug/L; P = 0.02). Serum selenium was also lower in female than male (134.7 ± 19.7 vs. 138.2 ± 19.4 ug/L; P < 0.01). Comparing with the lowest quartile, participants with the highest selenium concentration had a lower risk for all-cause (HR: 0.60, 95%CI: 0.45, 0.78; P < 0.01, P for trend<0.01) and CVD mortality (HR: 0.73, 95%CI: 0.37, 1.43; P = 0.36, P for trend = 0.90). Selenium was significantly associated with all-cause and CVD mortality among both males and females, but only associated with CVD mortality in among females.Conclusion: This study demonstrated significant relationship between serum selenium and all-cause mortality in both genders, but the relationship with CVD mortality was only significant in females.

Association of circulating selenium concentration with dyslipidemia: Results from the NHANES.

BACKGROUND: Observational studies have suggested that selenium levels might associate with the risk of cardio-metabolic diseases, but how circulating selenium is related to dyslipidemia remains inconclusive. OBJECTIVES: To investigate the association of circulating selenium levels with lipid profiles and dyslipidemia among US adults. METHODS: Using the data collected from the National Health and Nutrition Examination Survey (NHANES 1999-2006), we performed multivariate logistic regression to examine the association of circulating selenium levels (in quartiles) with total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), non-HDL-C, and atherogenic index (AI). RESULTS: We included 2903 adults (49.3 % male) (average age: 61.9) for analysis. Circulating selenium had non-linear association with TC, LDL-C, HDL-C, and AI (all p < 0.05). When comparing with the lowest quartile, subjects with the highest quartile of circulating selenium (>147.00 µg/L) had the higher odds of elevated TG (OR: 1.75, 95% CI = 1.14, 2.68), TC (OR: 2.47, 95% CI = 1.62, 3.76), LDL-C (OR: 2.52, 95% CI = 1.60, 3.96), non-HDL-C (OR: 2.17, 95% CI = 1.41, 3.33), AI (OR: 1.20, 95% CI = 0.73, 1.97) and low-HDL-C (OR: 2.10, 95% CI = 1.19, 3.72). Similar patterns were observed in subgroup analysis. CONCLUSIONS: Higher circulating selenium levels had non-linear association with lipid profiles and the increased odds of dyslipidemia.

[Effects of Reclamation on Soil Nutrients and Microbial Activities in the Huixian Karst Wetland in Guilin].

To investigate the effect of reclamation on soil quality in the Huixian Karst Wetland, samples from different soil levels were collected from marsh wetland, reclaimed paddy field, and reclaimed dry farmland, for analyzing soil nutrient (carbon, nitrogen, phosphorous, and potassium) contents, microbial biomass carbon/nitrogen (MBC/MBN), and microbial activity indicators[i.e. basal respiration (BR), potential respiration (PR), microbial quotient (qMB), and metabolic quotient (qCO2)]. The correlations between the soil nutrient contents and soil microbial activity indictors were examined. The results showed that:①Artificial reclamation led to the trend of slight acidity in the soil and a marked loss in soil nutrients, while, the pH value, soil water content (SWC), and the contents of soil organic carbon (SOC), total nitrogen (TN), available nitrogen (AN), total phosphorus (TP), available phosphorus (AP), total potassium (TK), and available potassium (AK) decreased with reclamation. ②Among all the microbes, bacteria were the most numerous, followed by actinomycetes, and fungi were the least numerous. The microbial quantity decreased with the increase in the soil depth on the whole. The proportion of bacteria and actinomycetes were much higher in the paddy field, and that of fungi was the highest in the dry farmland. ③ In total, protease, sucrase, urease, catalase, and polyphenol oxidase activities decreased with the increasing of soil depths. Soil reclamation reduced the soil enzyme activities. ④qCO2 decreased after an initial increase in the marsh wetland, while it rose gradually in the reclaimed paddy field and reclaimed dry farmland. The contents of MBC, MBN, BR, PR, and qMB were the highest in the marsh wetland, followed by those in the reclaimed paddy field, with the lowest contents occurring in the reclaimed dry farmland. The trend of qCO2 contents in the 0-10 cm and 10-20 cm soil layers followed the order of marsh wetland > paddy field > dry farmland, but in the 20-30 cm and 30-40 cm soil layers, it showed the order dry farmland > paddy field > marsh wetland. The continuation of reclamation resulted in the decrease in soil microbial activity, and soil quality as well, especially in the dry farmland. Meanwhile, we should reduce the areas of paddy fields and dry farmlands under reclamation during the process of wetland ecological restoration in future. Conversion of farmlands to wetlands or lakes, to improve and increase the size of wetland ecosystems of nearby lands, should be done gradually.