Feijun Luo

MiR‐29 mediates TGFβ1‐induced extracellular matrix synthesis through activation of PI3K‐AKT pathway in human lung fibroblasts

TGFβ1 is very important in the synthesis and degradation of extracellular matrix, and also in the mediation of human lung fibroblasts proliferation, and miR‐29 plays an important role in this process. To explore the interactions of miR‐29 family members and TGFβ1, the effects of transforming growth factor TGFβ1 on the expression of miR‐29 and whether miR‐29 is involved in pro‐survival signaling pathways mediated by TGFβ1 were examined in human lung fibroblasts. Treatment of the human embryonic lung fibroblast cell line IMR90 with TGFβ1 caused a decrease in expression of miR‐29a/b/c by real‐time PCR analysis. TGFβ1 stimulation increased cell proliferation, colony formation and up‐regulated expression of COL1A1; transfecting with miR‐29a/b/c mimics reverse TGFβ1‐induced phenotype changes in IMR90 cells. Western blot analyses showed that TGFβ1 treatment unchanged total protein expression levels of PI3K or AKT, but the expression levels of p‐PI3K, p‐AKT, and COL1A1 were increased; and miR‐19a/b/c mimics interfering blocked phosphorylation of PI3K or AKT and decreased expression of COL1A1 after TGFβ1 treatment. The results indicate that TGFβ1 beta uses the PI3k‐Akt pathway in these embryonic fibroblasts and miR29 blocks this activation pathway. It indicates a novel biological function of the PI3K‐Akt pathway in IMR90. Elevated expression of miR‐29 may play an important role in the pathogenesis of diseases related to fibrogenic reactions in human lung fibroblasts. J. Cell. Biochem. 114: 1336–1342, 2013.

Recent advances in bone-targeted therapies of metastatic prostate cancer

Prostate cancer is one of the most common malignancies affecting men worldwide, with bone being the most common site of metastasis in patients that progress beyond organ confinement. Bone metastases are virtually incurable and result in significant disease morbidity and mortality. Bone provides a unique microenvironment whose local interactions with tumor cells offer novel targets for therapeutic interventions. Several attractive molecules or pathways have been identified as new potential therapeutic targets for bone metastases caused by metastatic castration-resistant prostate cancer. In this review, we present the recent advances in molecular targeted therapies for prostate cancer bone metastasis focusing on therapies that target the bone cells and the bone microenvironment. The therapies covered in this review include agents that inhibit bone resorption, agents that stimulate bone formation, and agents that target the bone matrix. Suggestions to devise more effective molecular targeted therapies are proposed. Hopefully, with better understanding of the biology of the disease and the development of more robust targeted therapies, the survival and quality of life of the affected individuals could be significantly improved.

A review of the research progress on the bioactive ingredients and physiological activities of rice bran oil

Abstract Rice bran oil is not only a nutritious vegetable oil, but also a specialty oil with unique properties and many health benefits. Good stability, appealing flavor and long fry-life enable rice bran oil be used for frying and also to make margarine and shortening and advanced nutritional oils. More importantly, rice bran oil has been reported to have a high potential for making pharmaceuticals and cosmeceuticals. Rice bran oil has surprisingly high levels of nutraceutical components, such as oryzanol, fat-soluble vitamins, sitosterol, other plant sterols and other nutrients. Thus, rice bran oil has been a study focus in relation to its function and application in many countries in the world, as well as a family’s daily health edible oil. This paper summarizes the research progress on the bioactive ingredients and the physiological activities of rice bran oil.

Effects of Non-Starch Polysaccharides on Inflammatory Bowel Disease

The incidence of inflammatory bowel disease (IBD) has increased considerably over the past few decades. In the present review, we discuss several disadvantages existing in the treatment of IBD and current understandings of the structures, sources, and natures of various kinds of non-starch polysaccharides (NSPs). Available evidences for the use of different sources of NSPs in IBD treatment both in vitro and in vivo are analyzed, including glucan from oat bran, mushroom, seaweed, pectin, gum, prebiotics, etc. Their potential mechanisms, especially their related molecular mechanism of protective action in the treatment and prevention of IBD, are also summarized, covering the anti-inflammation, immune-stimulating, and gut microbiota-modulating activities, as well as short-chain fatty acids (SCFAs) production, anti-oxidative stress accompanied with inflammation, the promotion of gastric epithelial cell proliferation and tissue healing, and the reduction of the absorption of toxins of NSPs, thus ameliorating the symptoms and reducing the reoccurrence rate of IBD. In summary, NSPs exhibit the potential to be promising agents for an adjuvant therapy and for the prevention of IBD. Further investigating of the crosstalk between immune cells, epithelial cells, and gut microorganisms in addition to evaluating the effects of different kinds and different molecular weights of NSPs will lead to well-designed clinical intervention trials and eventually improve the treatment and prevention of IBD.

Requirement of miR-144 in CsA induced proliferation and invasion of human trophoblast cells by targeting titin

MicroRNAs (miRNAs) are endogenous 19–25 nucleotide noncoding single‐stranded RNAs that regulate gene expression by blocking the translation or decreasing the stability of mRNAs. In this study, with the treatment of CsA (Cyclosporin A), we showed that miR144 expression levels were decreased while titin mRNA expression levels were increased in human trophoblast (HT) cells, and identified titin as a novel direct target of miR‐144. Overexpression of miR‐144 suppressed titin and its downstream signaling molecule such as p‐ERK1/2 and MMP2/9 expression, and attenuated cell proliferation and invasion. Forced expression of titin can partly rescue the inhibitory effect of miR‐144 in the cells. Taken together, these findings will shed light to the role and mechanism of miR‐144 in regulating HT cells proliferation and invasion via miR‐144/titin axis, and miR‐144 may serve as a potential therapeutic target in HT in the future. J. Cell. Biochem. 115: 690–696, 2014.

Octacosanol Attenuates Inflammation in Both RAW264.7 Macrophages and a Mouse Model of Colitis

Octacosanol has multiple biological functions. In this study, the anti-inflammatory effect and molecular mechanism of octacosanol were evaluated by using dextran sulfate sodium (DSS)-induced ulcerative colitis model in mice and lipopolysaccharide (LPS)-stimulated mouse macrophage RAW264.7 cells. The colitis mouse model was induced by 3.0% DSS in 8-week ICR mice and octacosanol orally administered with 100 mg/kg/day. The results showed that octacosanol significantly improved the health status of mice and reduced DSS-induced pathological damage in the colonic tissues. Octacosanol obviously inhibited the mRNA and protein expression levels of pro-inflammatory factors of colonic tissues. In vitro, octacosanol administration significantly reduced the expression of mRNA or protein of pro-inflammatory cytokines and the phosphorylation of c-Jun N-terminal kinase and p38, and it also partly prevented LPS-induced translocations of NF-κB and AP-1. Octacosanol has anti-inflammatory effect, and its molecular mechanism may be involved in downregulating the expression of inflammatory factors and blocking of MAPK/NF-κB/AP-1 signaling pathway.

Oral administration of Lentinus edodes β-glucans ameliorates DSS-induced ulcerative colitis in mice via MAPK-Elk-1 and MAPK-PPARγ pathways

To evaluate the anti-inflammatory effect of β-glucans from Lentinus edodes, and its molecular mechanism, the dextran sulfate sodium salt (DSS) induced colitis model of mice and the LPS-stimulated RAW264.7 cell inflammation model were used in this study. 40 ICR male mice were randomly divided into 4 groups: Control, DSS (DSS treated only), DSS + low-βGs (500 mg kg-1 d-1) and DSS + high-βGs (1000 mg kg-1 d-1). The body weight of the mice with Lentinus edodes β-glucan supplementation increased significantly compared to the DSS group and the disease activity index (DAI) was improved in both βG-treated groups. Compared with the DSS group, histopathological analysis showed that the infiltration of inflammatory cells of both βG-treated groups decreased significantly in colonic tissues. Furthermore, oral administration of β-glucans decreases the concentration of malondialdehyde (MDA) and myeloperoxidase (MPO) and inhibits the expression of iNOS and several inflammatory factors: TNF-α, IL-1β and IL-6 as well as nitric oxide (NO) of the colonic tissues. The mitogen-activated protein kinase (MAPK) pathway is closely related to the expression of pro-inflammatory factors. In the DSS-induced colitis model and the LPS-stimulated RAW264.7 cell model, βGs inhibited the expression of pro-inflammatory factors and blocked the phosphorylation of JNK/ERK1/2 and p38; βGs also suppress the phosphorylation of Elk-1 at Ser84 and the phosphorylation of PPARγ at Ser112. Altogether, these results suggest that Lentinus edodes βGs could inhibit the DSS-induced ulcerative colitis and decrease inflammatory factor expressions. The molecular mechanism may be involved in suppressing MAPK signaling and inactivation of Elk-1 and activation of PPARγ.

Alliin, a garlic organosulfur compound, ameliorates gut inflammation through MAPK-NF-κB/AP-1/STAT-1 inactivation and PPAR-γ activation

SCOPE In this study, the anti-inflammatory effects and the molecular mechanism of alliin were analyzed in dextran sulfate sodium (DSS)-induced colitis mice and lipopolysaccharide-stimulated RAW264.7 cell model. METHODS The phenotype of mice was recorded in the DSS-induced and/or alliin (500 mg/kg) groups. Histopathological alterations were analyzed by H&E staining. MPO and MDA of colon tissues were measured. The mRNA expression levels of inflammatory factors were determined by qRT-PCR, and protein expressions of inflammatory factors or activation of kinases were determined by Western blotting. RESULTS Oral administration of alliin significantly inhibited the decrease of body weight, improved the DAI and decreased the infiltration of inflammatory cells in colonic tissues. The content of NO, MDA, and MPO, the expression of iNOS and inflammatory factors as well as MAPK and the phosphorylation of PPAR-γ were inhibited in alliin-treated group. Treatment with alliin significantly repressed the expression of inflammatory factors in LPS-stimulated RAW264.7 cells. Further research demonstrated that alliin repressed LPS-induced AP-1/NF-κB/STAT-1 activation by inhibiting the phosphorylations of p38, JNK, and ERK1/2-regulated PPAR-γ activation. CONCLUSION Our results show that alliin ameliorates DSS-induced ulcerative colitis and inhibits the inflammatory responses in LPS-stimulated RAW264.7 cells partly through inhibiting ERK1/2-, JNK-/PPAR-γ-stimulated NF-κB/AP-1/STAT-1 activations.

Oryzanol Modifies High Fat Diet-Induced Obesity, Liver Gene Expression Profile, and Inflammation Response in Mice

In Western countries and China, the dietary habit of high calories usually results in hyperlipidemia, which is closely associated with cardiovascular diseases. In the study, we investigated the antihyperlipidemic effect of oryzanol and its molecular mechanism in the high fat diet (HFD) mouse model. In total, 60 ICR mice were randomly divided into control group, HFD group, and HFD+Ory group. The mice from the HFD+Ory group were additionally fed with 100 mg/kg of oryzanol by intragastric administration. Our data indicated that oryzanol treatment for 10 weeks significantly reduced bodyweight, liver weight, and adipose tissues weight of the mice; lowered the contents of total cholesterol (TC), triglycerides (TG), and low density lipoprotein-cholesterol (LDL-C); and elevated high density lipoprotein-cholesterol (HDL-C) in the plasma of HFD mice. Compared with the HFD group, H&E staining showed that oryzanol treatment decreased the size of fat droplets of liver tissues and the size of adipocytes. Gene chip data found that oryzanol administration caused 32 genes to increase expressions while 60 genes had reduced expressions in the liver tissues of HFD mice. IPA software was used to analyze the protein interaction network and found that transcript factor NF-κB located in the central role of network, meaning NF-κB may have important function in the lipid-lowering effect of oryzanol. Western blotting and RT-qPCR confirmed that lipid metabolism-related gene expressions were obviously regulated by oryzanol administration. Oryzanol also inhibited expressions of inflammatory factor in the liver tissues of HDF mice. Taken together, our data indicate that oryzanol treatment can regulate lipid metabolism-related gene expressions and inhibit HDF-caused obesity in mice.

Anticancer properties of Monascus metabolites.

This review provides up-to-date information on the anticancer properties of Monascus-fermented products. Topics covered include clinical evidence for the anticancer potential of Monascus metabolites, bioactive Monascus components with anticancer potential, mechanisms of the anticancer effects of Monascus metabolites, and existing problems as well as future perspectives. With the advancement of related fields, the development of novel anticancer Monascus food products and/or pharmaceuticals will be possible with the ultimate goal of decreasing the incidence and mortality of malignancies in humans.