Icariside II suppressed tumorigenesis by epigenetically regulating the circß-catenin-Wnt/ß-catenin axis in colorectal cancer.

Icariside II, a flavonol glycoside, one of the major components of Traditional Chinese Medicine Herba epimedii. In the present study, we found that Icariside II suppressed the proliferation of CRC by inducing cell cycle arrest and apoptosis in vitro and inhibited tumor growth in vivo. The further mechanism investigation showed that Icariside II suppressed the expression of ß-catenin and led to the functional inactivation of Wnt/ß-catenin signaling. Circß-catenin was considered as a promising candidate for mediating the tumorigenesis and the activation of Wnt/ß-catenin signaling in CRC cells. Furthermore, Icariside II has been proven to suppress the biogenesis of circß-catenin via epigenetically targeting DNA methyltransferases (DNMTs) to decrease global DNA methylation levels in CRC cells. Taken together, our results indicated that Icariside II suppressed tumorigenesis by epigenetically silencing the activation of circß-catenin-Wnt/ß-catenin axis in colorectal cancer. More importantly, the information gained from this study suggest that Icariside II may have great potential to be developed as a therapeutic drug for CRC patients.

Apigenin promotes osteogenic differentiation of mesenchymal stem cells and accelerates bone fracture healing via activating Wnt/ß-catenin signaling.

Apigenin (API), a natural plant flavone, is abundantly found in common fruits and vegetables. As a bioactive flavonoid, API exhibits several activities including antiproliferation and anti-inflammation. A recent study showed that API could retard osteoporosis progress, indicating its role in the skeletal system. However, the detailed function and mechanism remain obscure. In the present study, API was found to promote osteogenic differentiation of mesenchymal stem cells (MSCs). And further investigation showed that API could enhance the expression of the critical transcription factor ß-catenin and several downstream target genes of Wnt signaling, thus activated Wnt/ß-catenin signaling. Using a rat femoral fracture model, API was found to improve new bone formation and accelerate fracture healing in vivo. In conclusion, our data demonstrated that API could promote osteogenesis in vitro and facilitate the fracture healing in vivo via activating Wnt/ß-catenin signaling, indicating that API may be a promising therapeutic candidate for bone fracture repair.NEW & NOTEWORTHY1) API promoted osteogenic differentiation of human MSCs in vitro; 2) API facilitated bone formation and accelerated fracture healing in vivo; 3) API stimulated Wnt/ß-catenin signaling during osteogenesis of human MSCs.

Urolithin B suppresses tumor growth in hepatocellular carcinoma through inducing the inactivation of Wnt/ß-catenin signaling.

Consumption of dietary ellagitannins (ETs) has been proven to benefit multiple chronic health disorders including cancers and cardiovascular diseases. Urolithins, gut microbiota metabolites derived from ETs, are considered as the molecules responsible for these health effects. Previous studies have demonstrated that urolithins exhibit antiproliferative effects on prostate, breast, and colon cancers. However, as for hepatocellular carcinoma (HCC), it remains elusive. Herein, we aim to investigate the function of urolithin B (UB), a member of urolithins family, in HCC. The effects of UB on cell viability, cell cycle and apoptosis were evaluated in HCC cells, and we found UB could inhibit the proliferation of HCC cells, which resulted from cell cycle arrest and apoptosis. Furthermore, UB could increase phosphorylated ß-catenin expression and block its translocation from nuclear to cytoplasm, thus inducing the inactivation of Wnt/ß-catenin signaling. Using a xenograft mice model, UB was found to suppress tumor growth in vivo. In conclusion, our data demonstrated that UB could inhibit the proliferation of HCC cells in vitro and in vivo via inactivating Wnt/ß-catenin signaling, suggesting UB could be a promising candidate in the development of anticancer drugs targeting HCC.

[Research progress on nurse effects of shrubs in ecological restoration]. / ç”Ÿæ€æ¢å¤ä¸­çŒä¸›ä¿è‚²æ•ˆåº”ç ”ç©¶è¿›å±•.

Shrubs are the major components of vegetation in arid and semi-arid areas, and play a pivotal role in maintaining ecosystem stability and function. The nurse effects of shrubs can help with the regeneration of native target plant species by alleviating the adverse influences that limit their growth and reproduction in degraded habitats. We summarized the main research results and application of shrub nurse effects in the last 20 years. We discussed several facilitation mechanisms of nurse shrubs, including microhabitat amelioration, fertile island formation, defense and resistance against herbivores, introduction of beneficial microorganism and propagule propagation or preservation, as well as changes in the patterns of interspecific competitive networks. Key factors affecting nurse effects were analyzed, including abiotic environments, biological disturbances, plant life history as well as growth and reproductive strategies. Prospects for future research were also considered from the aspects of improving theore-tical mechanisms of nurse effects by shrubs and building models involved in multiple plant species interaction affec-ted by multifactors.

An Updated Meta-Analysis of the Relationship Between Helicobacter pylori Infection and the Risk of Coronary Heart Disease.

Background: Coronary heart disease (CHD) is one of the leading causes of mortality in the world. Although the traditional risk factors for CHD have been identified, it seems that there are still many CHD cases without these factors. Previous studies have hypothesized that Helicobacter pylori (H. pylori) infection was associated with the risk of CHD. Objective: The association between H. pylori infection and the risk of CHD was studied using a systematic evaluation and meta-analysis method. Methods: In order to find relevant studies, four electronic databases were systematically searched until August 2021. According to the inclusion and exclusion criteria, studies were screened and data were extracted. Under the random-effects or the fixed-effects model, the odds ratio (OR) and 95% confidence interval (95% CI) were combined. All analyses were conducted using Review Manager software (RevMan 5.4). Results: Among the included studies, 2 studies were analyzed for H. pylori stool antigen test, 2 studies were analyzed for H. pylori histological staining test, 13 studies were analyzed for the anti-CagA test, and 38 studies were analyzed for the anti-H. pylori IgG test. The pooled results revealed that positive anti-H. pylori IgG was significantly associated with an increased risk of CHD (OR, 1.58; 95% CI: 1.34-1.87). Similarly, positive anti-CagA, positive H. pylori stool antigen, and positive H. pylori histological staining were significantly associated with the development of CHD with (OR: 1.33, 95% CI: 1.16-1.53), (OR: 3.50, 95% CI: 1.60-7.66), and (OR: 1.78, 95% CI: 1.12-2.83), respectively. Conclusion: This meta-analysis showed that H. pylori infection increased the risk of CHD. However, more studies are needed to further investigate whether early eradication of H. pylori may reduce the morbidity of CHD.

Troxerutin Stimulates Osteoblast Differentiation of Mesenchymal Stem Cell and Facilitates Bone Fracture Healing.

Troxerutin (TRX), a semi-synthetic derivative of the natural bioflavonoid rutin, is a bioactive flavonoid widely abundant in various fruits and vegetables. Known as vitamin P4, TRX has been demonstrated to have several activities including anti-inflammation, anti-oxidants, vasoprotection, and immune support in various studies. Although rutin, the precursor of troxerutin, was reported to have a protective role against bone loss, the function of TRX in skeletal system remains unknown. In the present study, we found that TRX promoted osteogenic differentiation of human mesenchymal stem cells (MSCs) in a concentration-dependent manner by stimulating the alkaline phosphatase (ALP) activity, calcium nodule formation and osteogenic marker genes expression in vitro. The further investigation demonstrated that TRX stimulated the expression of the critical transcription factor ß-catenin and several downstream target genes of Wnt signaling, thus activated Wnt/ß-catenin signaling. Using a femur fracture rats model, TRX was found to stimulate new bone formation and accelerate the fracture healing in vivo. Collectively, our data demonstrated that TRX could promote osteogenesis in vitro and facilitate the fracture healing in vivo, indicating that TRX may be a promising therapeutic candidate for bone fracture repair.

Gallic Acid Suppressed Tumorigenesis by an LncRNA MALAT1-Wnt/ß-Catenin Axis in Hepatocellular Carcinoma.

Gallic acid (3,4,5-trihydroxybenzoic acid; GA), a natural phenolic acid, is abundantly found in numerous natural products. Increasing evidence have demonstrated that GA plays anti-cancer roles in multiple cancers. However, its anti-tumor effects on hepatocellular carcinoma (HCC) and the underlying mechanism remain obscure. In the present study, we found that GA suppressed the in vitro cell viability and metastasis and inhibited the in vivo tumor growth of HCC cells. The underlying mechanism was further to investigate and it was showed that GA suppressed the expression of ß-catenin and led to the functional inactivation of Wnt/ß-catenin signaling. As a kind of significant regulators, the long noncoding RNA molecules (lncRNAs) have attracted widespread attentions for their critical roles in diverse biological process and human diseases. To further identify which lncRNA participated this GA-mediated process, several lncRNAs related to Wnt/ß-catenin signaling were chosen for examination of their expression profiling in the GA-treated HCC cells. Of which, Metastasis-Associated Lung Adenocarcinoma Transcript 1 (MALAT1) was the most promising candidate. And moreover, MALAT1 was significantly down-regulated by GA. Its overexpression partially reversed the GA-induced the inhibitory effects on cell proliferation and metastasis; and successfully abolished the suppressive effect of GA on Wnt/ß-catenin signaling. In conclusion, our results indicated that GA suppressed tumorigenesis in vitro and in vivo by the MALAT1-Wnt/ß-catenin signaling axis, suggesting that GA has great potential to be developed as a chemo-prevention and chemotherapy agent for HCC patients.

H19-Wnt/ß-catenin regulatory axis mediates the suppressive effects of apigenin on tumor growth in hepatocellular carcinoma.

Hepatocellular Carcinoma (HCC) is one of the leading causes of cancer-related deaths in the world. However, the effective pharmacological approaches remain scanty in clinical practice. As a bioactive flavonoid, apigenin (API) is enriched in common fruits and vegetables. Although pharmacological activities of API have been widely investigated, its biological function in HCC remains obscure. In the present study, we found that API strongly suppressed cell growth and induced apoptosis in HCC cells. Using a xenograft mice model, API was demonstrated to inhibit the in vivo tumor growth. It is known that the long non-coding RNA H19, which is frequently elevated in HCC, plays a vital role in mediating tumorigenesis and cancer progression. Our results demonstrated that H19 was down-regulated by API, and thereby induced the inactivation of the canonical Wnt/ß-catenin signaling. In conclusion, our results demonstrated that API was able to suppress tumor growth of HCC through H19-mediated Wnt/ß-catenin signaling regulatory axis, suggesting that API may be a promising candidate for developing novel therapeutic approaches against liver cancer.

Effect of Sevelamer on Calciprotein Particles in Hemodialysis Patients: The Sevelamer Versus Calcium to Reduce Fetuin-A-Containing Calciprotein Particles in Dialysis (SCaRF) Randomized Controlled Trial.

INTRODUCTION: Calciprotein particles (CPPs) are potentially modifiable mediators of phosphate toxicity in patients with kidney disease. We compared the effects of calcium carbonate (CC) and the non-calcium-based phosphate binder sevelamer on CPP levels in patients undergoing hemodialysis (HD). We hypothesized that treatment with sevelamer would achieve greater reductions in amorphous calcium phosphate-containing CPP (CPP-1) and hydroxyapatite-containing CPP (CPP-2) owing to reduced calcium loading and anti-inflammatory pleiotropic effects. METHODS: We conducted an open-label, randomized controlled trial (RCT) in which 31 stable prevalent HD patients were allocated to receive either sevelamer hydrochloride (SH), sevelamer carbonate (SC), or CC for 24 weeks. Dual primary endpoints were the between groups differences in serum CPP-1 and CPP-2 levels at 24 weeks in SH + SC-treated versus CC-treated patients. Effects on aortic pulse wave velocity (aPWV), inflammatory cytokines (interleukin-6 and -8), and effects across individual treatment arms were also assessed. RESULTS: Serum CPP-1, but not CPP-2, levels were lower in those randomly assigned to the sevelamer (SH + SC) group compared with the CC group at 24 weeks (-70%, 95% confidence interval [CI] -90% to -15%, P = 0.02). In subgroup analysis, this effect was confined to those receiving SC (-83.4%, 95% CI -95.7% to -36.8%, P = 0.01). aPWV and interleukin-8 levels were also lower in those who received sevelamer compared with CC at 24 weeks (-2.0 m/s, 95% CI -2.9 to -1.1; -57%, 95% CI -73% to -30%, respectively, both P = 0.01). Conventional markers of mineral metabolism remained stable across all treatment groups. DISCUSSION: Compared with treatment with CC, use of sevelamer for 24 weeks was associated with lower serum CPP-1 levels and a reduction in aPWV and systemic inflammation.

LincROR Mediates the Suppressive Effects of Curcumin on Hepatocellular Carcinoma Through Inactivating Wnt/ß-Catenin Signaling.

As one of the leading causes of cancer-related death in the world, hepatocellular carcinoma (HCC) has continued to attract growing attention in recent decades. The use of traditional Chinese herbs in medicine has been practiced for thousands of years, and holds the potential of being a possible treatment for HCC. Curcumin, a bioactive ingredient derived from Curcuma longa, exhibits anti-tumor activity in various cancers. Although the effects of Curcumin on HCC have been elucidated, the underlying mechanism remains unclear. In the present study, Curcumin was demonstrated to inhibit the proliferation of HCC cells via inducing cell cycle arrest and apoptosis. Several previously reported lncRNAs related to tumorigenesis were chosen for examination of their expression profiles, and lincROR was found to be the most down-regulated in the Curcumin-treated HCC cells. Furthermore, Curcumin was found to decrease ß-catenin expression and induce the inactivation of Wnt/ß-catenin signaling. Therefore, Curcumin suppressed tumor growth through a lincROR/ß-catenin regulatory pattern. In conclusion, our results demonstrated that Curcumin suppressed the cell proliferation via the down-regulation of lincROR and inactivation of Wnt/ß-catenin signaling, suggesting that it may be a potential anti-cancer candidate for HCC patients with activated Wnt/ß-catenin signaling.

[Effects of long-term fertilization on organic nitrogen fractions in aquic brown soil]. / 长期施肥对潮棕壤有机氮组分的影响.

The purpose of present research was to investigate how different fertilization regimes altered soil organic nitrogen fractions and their inter-annual dynamics based on a series of long-term experiment (initiated at 1990), including: CK (non-fertilization); M (recycled pig manure); NPK (chemical fertilizer NPK); NPK + M (recycled pig manure with chemical fertilizer NPK). The results showed that soil organic nitrogen components under the different fertilization treatments presented contrastive patterns from the establishment the experiments to 2015. Generally, acid hydrolysable organic nitrogen content increased year by year. The amino acid nitrogen content under CK and NPK treatments consistently declined, although amino acid nitrogen for M and NPK+M treatments showed a increasing trend. These phenomena were probably ascribed to the utilization of soil amino acids by microbes. From 1990 to 2015, NPK treatment substantially elevated the content of acid-released ammonium nitrogen by 31.1% compared with CK (mean value across the experiment), and for the treatments using organic manure (M and NPK+M), the contents of all fractions of soil organic nitrogen increased. Notably, the increase magnitudes for NPK+M were more dramatic than those of M. These results demonstrated that combined use of organic and inorganic fertilizers could more effectively elevate soil organic nitrogen, subsequently helping to improve the capacity of soil nitrogen supply and enhance the soil fertility.

[Detection of anti-Trichinella spiralis antibody by indirect ELISA using recombinant protein as antigen].

OBJECTIVE: To study the specificity, sensitivity of diagnostic antigen for Trichinella spiralis (T.s). METHODS: T668 recombinant protein from highly efficient expression of newborn larvae stage-specific gene of T.s in E. coli as diagnostic antigen. By using negative and positive sera from rabbit, pig, human as the first antibody, and goat-anti-rabbit IgG, goat-anti-pig IgG, goat-anti-human IgG labeled with HRP as the secondary antibody, indirect ELISA method was established for detecting anti-T.s antibody, while excretory-secretory (ES) antigen of T.s muscle larvae was used as control. RESULTS: Sera from rabbit, pig and human were detected by T668 recombinant protein as antigen, which showed a positive rate of 100% with 0.016 microg/well. There was no difference on the results between the T668 recombinant antigen and the ES antigen for diagnosing T.s-infection. CONCLUSION: The T668 recombinant antigen is promising in substituting ES antigen in the detection of anti-T.s antibody.