[Latest Findings on the Effect of Gastrointestinal Microecology Remodeling of Tumor Microenvironment on Tumor Stemness].

Gastrointestinal microecology (GM) system is composed of normal gut microbiota and its living environment. The impact of GM on human health and many diseases has been widely studied. The impact of GM system on tumors is mainly reflected in the remodeling of the tumor microenvironment (TME). TME, a special microenvironment that tumors live in, can regulate the characteristics of tumor cells and affect the occurrence and development of tumors through intercellular contact and the secretion of cytokines. At present, cancer stem cell (CSC) model is considered an important theory that explains the origin and malignant progression of tumors. The formation and proliferation of CSC usually represent increased tumor invasion, metastasis, and chemotherapy resistance, resulting in poor clinical prognosis in patients. Therefore, it is important to study the role and mechanism through which GM system affects the acquisition of CSC characteristics through remodeling TME, thereby affecting tumor invasion, metastasis, and chemotherapy resistance. Studies on this topic are of great significance for clinical understanding of tumor malignant progression and improving tumor treatment outcomes. However, due to the low content of single bacteria in the gastrointestinal model, high heterogeneity, and difficulty in tracing distant metastasis, there are still great limitations in the previous research. Herein, we reviewed the research progress in the effect of GM remodeling of TME on the acquisition of tumor stemness, tumor invasion and metastasis, and the resistance to chemotherapy.

[Material basis and mechanism of Curcuma longa tuberous roots with and without vinegar processing in treating primary dysmenorrhea].

Liquid chromatography-mass spectrometry was employed to analyze the chemical components in Curcuma longa tuberous roots(HSYJ), C. longa tuberous roots processed with vinegar(CHSYJ), and rat serum after the administration. The active components of HSYJ and CHSYJ absorbed in serum were identified based on the secondary spectrum of database and literature. The targets of primary dysmenorrhea was screened out from database. The protein-protein interaction network analysis, gene ontology(GO) functional annotation, and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment analysis were performed for the common targets shared by the drug active components in serum and primary dysmenorrhea, and the component-target-pathway network was constructed. AutoDock was used to conduct molecular docking between the core components and targets. A total of 44 chemical components were identified from HSYJ and CHSYJ, including 18 absorbed in serum. On the basis of network pharmacology, we identified 8 core components(including procurcumenol, isobutyl p-hydroxybenzoate, ferulic acid, and zedoarondiol) and 10 core targets \[including interleukin-6(IL-6), estrogen receptor 1(ESR1), and prostaglandin-endoperoxide synthase 2(PTGS2)\]. The core targets were mainly distributed in the heart, liver, uterus, and smooth muscle. The molecular docking results showed that the core components were well bound to the core targets, indicating that HSYJ and CHSYJ may exert therapeutic effect on primary dysmenorrhea via estrogen, ovarian steroidogenesis, tumor necrosis factor(TNF), hypoxia-inducible factor-1(HIF-1), IL-17 and other signaling pathways. This study clarifies the HSYJ and CHSYJ components absorbed in serum, as well as the corresponding mechanism, providing a reference for further elucidating the therapeutic material basis and clinical application of HSYJ and CHSYJ.

[Effect of processing with vinegar on efficacy of Curcuma longa in treatment of dysmenorrhea in rats with syndrome of liver depression and Qi stagnation].

This study compared the effects of Curcuma longa before and after processing with vinegar on the rat model of dysmenorrhea with the syndrome of liver depression and Qi stagnation to reveal the mechanism of vinegar processing in improving the role of C. longa in soothing liver and relieving pain. The rat model of dysmenorrhea with the syndrome of liver depression and Qi stagnation was established according to the Preparation of the Animal Model of Dysmenorrhea(Draft) and the chronic unpredictable stress me-thod. The changes in the body weight, organ indexes, writhing latency, writhing score, and serum levels of six liver function indicators, sex hormones, pain factors, and blood rheological indicators were measured to evaluate the efficacy of C. longa processed with vinegar or not in treating dysmenorrhea in the rats with syndrome of liver depression and qi stagnation. Compared with the model group, the C. longa group(processed with vinegar or not) showed slow weight loss, increase in writhing latency, and decrease in writhing response(P<0.05). The inhibition rates on writhing in raw C. longa, vinegar-processed C. longa, and positive groups were 33.780%, 64.611%, and 62.466%, respectively. The significantly higher inhibition rate of the vinegar processing group indicated that vinegar-processed C. longa demonstrated more significant therapeutic effect. The vinegar-processed C. longa group showed lower levels of alanine aminotransferase(ALT), alkaline phosphatase(ALP), aspartate aminotransferase(AST), direct bilirubin(DBIL), and total bilirubin(TBIL) and higher level of albumin(ALB)(P<0.05), which indicated that vinegar processing enhanced the therapeutic effect of C. longa on liver injury. The serum levels of estradiol(E_2) and oxytocin(OT) were lower in the vinegar-processed C. longa group(P<0.05), indicating that the vinegar-processed C. longa could regulate the sex hormone levels, reduce the activity of uterine smooth muscle and contraction of uterus, and alleviate the symptoms of dysmenorrhea in rats. Moreover, the vinegar-processed C. longa group showed lower interleukin-6(IL-6) and arginine vasopressin(AVP) levels and higher beta-endorphin(ß-EP) level(P<0.05), which indicated that vinegar-processed C. longa regulated the levels of pain factors to exert the pain-relieving effect. Drug intervention decreased the whole blood viscosity low-cut, medium-cut and high-cut values, plasma viscosity, whole blood reduction viscosity low-cut and high-cut values, erythrocyte cumulative pressure, and equation K value of erythrocyte sedimentation rate(P<0.05), and the vinegar-processed C. longa group outperformed other groups. This result indicated that vinegar processing enhanced the function of C. longa in improving the local blood rheology. C. longa processed with vinegar can enter the liver to relieve the da-mage to the heart, liver, kidney, and uterus, repair the liver function, and recover the sex hormone levels and immune function by regulating the levels of sex hormones and pain factors and improving the blood rheology. It activates the pain-relieving mechanism to relieve the pain, protect the liver, and fight inflammation, which is consistent with the theory that vinegar processing facilitates C. longa entering the liver to sooth liver and relieve pain.

Chuanxiongdiolides R4 and R5, phthalide dimers with a complex polycyclic skeleton from the aerial parts of Ligusticum chuanxiong and their vasodilator activity.

Chuanxiongdiolides R4-R6 (1-3), three novel phthalide dimers featuring two classes of unreported monomeric units (ligustilide/senkyunolide A and ligustilide/neocnidilide) with an unprecedented linkage style (3a,7'/7a,7'a), were isolated from the aerial parts of Ligusticum chuanxiong, together with three pairs of enantiomeric phthalide dimers [(-)/(+)-4a/4b, 5a/5b, and 6a/6b]. The bioassays revealed that compounds 1, 3, 4, 5, and 6 showed significant vasodilation effects, and the mechanism may be attributed to Cav1.2 activation blockade. Based on the established compounds library, the structure activity relationship of the phthalides was proposed. Our findings afford possible leads for developing new vasodilator against cardiovascular and cerebrovascular diseases such as hypertension and ischemic stroke.

[Study on effect of different processing methods on chemical components of Chuanxiong Rhizoma].

To determine the content of extracts in different processed products of Chuanxiong Rhizoma and the content of chlorogenic acid, ferulic acid, senkyunolide Ⅰ, coniferyl ferulate, senkyunolide A and ligustilide, in order to study the effect of different proces-sing methods on the alcohol-soluble extract and the content of six ingredients of Chuanxiong Rhizoma. The extract was determined according to the alcohol-soluble extract determination method set forth in item 2201 of the 2020 Chinese Pharmacopoeia Ⅳ; the content was determined by using Agilent TC-C_(18) column(4.6 mm×250 mm, 5 µm) for gradient elution, with acetonitrile(A)-0.5% acetic acid solution(B) as the mobile phase; the column temperature was at 30 ℃; the flow rate was 1.0 mL·min~(-1), the detection wavelength was 285 nm; and the injection volume was 10 µL. Compared with Chuanxiong Rhizoma, the extracts of processed products all increased significantly; by the degree of increase, the order was stir-frying Chuanxiong Rhizoma with honey>stir-frying Chuanxiong Rhizoma with rice wine>stir-frying Chuanxiong Rhizoma with Angelicae Dahuricae Radix decoction>stir-frying Chuanxiong Rhizoma with tea decoction; the HPLC method was convenient and reliable, with a high linear relationship of chlorogenic acid, ferulic acid, senkyunolide Ⅰ, coniferyl ferulate, senkyunolide A and ligustilide, and a high precision, repeatability, stability and the sample recovery rate in Chuanxiong Rhizoma and its processed products. There were 15 chromatographic peaks before and after processing, eight of them were identified. Compared with the pre-processing, two chromatographic peaks were added after the stir-frying with honey and rice wine; and four chromatographic peaks were added after the processing with Angelicae Dahuricae Radix decoction; the contents of chlorogenic acid, ferulic acid, senkyunolide Ⅰ, coniferyl ferulate, senkyunolide A, and ligustilide in stir-frying Chuanxiong Rhizoma with rice wine were all reduced. Except for the content of ferulic acid that increased, the content of the other five components decreased in stir-frying Chuanxiong Rhizoma with honey, stir-frying Chuanxiong Rhizoma with tea decoction, and stir-frying Chuanxiong Rhizoma with Angelicae Dahuricae Radix decoction. Rice wine, honey, decoction of tea and Angelicae Dahuricae Radix could all promote the dissolution of chemical components in Chuanxiong Rhizoma, and increase the content of extract; the changes in the contents of six components of different processed products could provide a certain basis for studying chemical composition and efficacy of different processed products of Chuanxiong Rhizoma.

Diverse regulatory manners of human telomerase reverse transcriptase.

Human telomerase reverse transcriptase (hTERT) is the core subunit of human telomerase and plays important roles in human cancers. Aberrant expression of hTERT is closely associated with tumorigenesis, cancer cell stemness maintaining, cell proliferation, apoptosis inhibition, senescence evasion and metastasis. The molecular basis of hTERT regulation is highly complicated and consists of various layers. A deep and full-scale comprehension of the regulatory mechanisms of hTERT is pivotal in understanding the pathogenesis and searching for therapeutic approaches. In this review, we summarize the recent advances regarding the diverse regulatory mechanisms of hTERT, including the transcriptional (promoter mutation, promoter region methylation and histone acetylation), post-transcriptional (mRNA alternative splicing and non-coding RNAs) and post-translational levels (phosphorylation and ubiquitination), which may provide novel perspectives for further translational diagnosis or therapeutic strategies targeting hTERT.

Iridoids from Valeriana jatamansi induce autophagy-associated cell death via the PDK1/Akt/mTOR pathway in HCT116 human colorectal carcinoma cells.

Chlorovaltrates U-W (1-3), three previously undescribed iridoids, together with four known analogues were isolated from the roots of Valeriana jatamansi. Their structures were elucidated by means of spectroscopic analyses (HRESIMS, NMR). The cytotoxicity of all isolates was evaluated. Compounds 5-7 exhibited selective cytotoxicity against HCT116 cells, with IC50 values of 9.3, 1.7 and 2.2 µM, respectively. The preliminary mechanistic study revealed that, the cytotoxicity effect of 6 was attributed to Akt/mTOR activation blockade via inhibition of PDK1 phosphorylation. Meanwhile, compound 6 could induce autophagosome formation in HCT116 cells via suppressing its downstream Akt/mTOR. These findings show that compound 6 could be of great importance to the development of anti-colon cancer agents.

Regulation of the master regulator FOXM1 in cancer.

FOXM1 (forkhead box protein M1) is a critical proliferation-associated transcription factor that is widely spatiotemporally expressed during the cell cycle. It is closely involved with the processes of cell proliferation, self-renewal, and tumorigenesis. In most human cancers, FOXM1 is overexpressed, and this indicates a poor prognosis for cancer patients. FOXM1 maintains cancer hallmarks by regulating the expression of target genes at the transcriptional level. Due to its potential role as molecular target in cancer therapy, FOXM1 was named the Molecule of the Year in 2010. However, the mechanism of FOXM1 dysregulation remains indistinct. A comprehensive understanding of FOXM1 regulation will provide novel insight for cancer and other diseases in which FOXM1 plays a major role. Here, we summarize the transcriptional regulation, post-transcriptional regulation and post-translational modifications of FOXM1, which will provide extremely important implications for novel strategies targeting FOXM1.

[Grading standard of processed Curcumae Radix].

As one of the three pillars of Chinese medicine industry, traditional Chinese medicines prepared in ready-to-use forms are important raw materials for clinical medication and production of Chinese patent drugs. By considering the literature of Curcumae Radix, a multi-source Chinese herb and the situation of market investigation, the modern evaluation method based on traditional grading was introduced for comprehensive evaluation of the processed Curcumae Radix. The correlation between traditional grading method and modern evaluation index was explored to establish the grading standard of Curcumae Radix. According to the comprehensive evaluation, Curcumae Radix was divided into four grades: superior, first, second and third grades under the guidance of the theory of traditional Chinese medicine. This study provides a new idea for the grading of multi-source processed Chinese medicine, achieving high quality and good price, which is helpful to improve the clinical efficacy.

The FOXM1-induced resistance to oxaliplatin is partially mediated by its novel target gene Mcl-1 in gastric cancer cells.

Myeloid cell leukemia-1 (Mcl-1) is an anti-apoptotic protein that belongs to the Bcl-2 family. The aberrant expression of Mcl-1 is important for sensitivity to chemotherapy drugs in gastric cancer. However, the regulatory mechanism of Mcl-1 in gastric cancer cells remains unclear. In this study, we first found that Forkhead box M1 (FOXM1) and Mcl-1 expression levels were positively correlated in human gastric cancer specimens and that both are associated with poor prognosis of patients treated with oxaliplatin. Second, we demonstrated that the expression level of Mcl-1 was correlated with FOXM1 expression in gastric cancer cells. Third, reporter assays showed that FOXM1 upregulated the promoter activity of the Mcl-1 gene. Electrophoretic mobility shift assays (EMSA) and chromatin immunoprecipitation (ChIP) assays further demonstrated that FOXM1 could bind to a particular site (-635acaaacaa-628) in the promoter region of the Mcl-1 gene. Moreover, CCK-8 assays and analyses of apoptosis revealed that the suppression of the FOXM1/Mcl-1 pathway induced apoptosis and thus increased sensitivity to oxaliplatin in gastric cancer cells, whereas the enhancement of the FOXM1/Mcl-1 pathway inhibited apoptosis and decreased sensitivity to oxaliplatin in gastric cancer cells. Taken together, this study is the first to not only show that Mcl-1 is a novel target gene of FOXM1 but also suggest that targeting FOXM1/Mcl-1 may be a novel strategy to enhance sensitivity to oxaliplatin in gastric cancer.

Long Noncoding RNA in Digestive Tract Cancers: Function, Mechanism, and Potential Biomarker.

Digestive tract cancers (DTCs) are a leading cause of cancer-related death worldwide. Current therapeutic tools for advanced stage DTCs have limitations, and patients with early stage DTCs frequently have a missed diagnosis due to shortage of efficient biomarkers. Consequently, it is necessary to develop novel biomarkers for early diagnosis and novel therapeutic targets for treatment of DTCs. In recent years, long noncoding RNAs (lncRNAs), a class of noncoding RNAs with >200 nucleotides, have been shown to be aberrantly expressed in DTCs and to have an important role in DTC development: the expression profiles of lncRNAs strongly correlated with poor survival of patients with DTCs, and lncRNAs acted as oncogenes or tumor suppressor genes in DTC progression. In this review, we summarized the functional lncRNAs and expounded on their regulatory mechanisms in DTCs.

Helicobacter pylori virulence factor CagA promotes tumorigenesis of gastric cancer via multiple signaling pathways.

Helicobacter pylori (H. pylori) infection is strongly associated with the development of gastric diseases but also with several extragastric diseases. The clinical outcomes caused by H. pylori infection are considered to be associated with a complex combination of host susceptibility, environmental factors and bacterial isolates. Infections involving H. pylori strains that possess the virulence factor CagA have a worse clinical outcome than those involving CagA-negative strains. It is remarkable that CagA-positive H. pylori increase the risk for gastric cancer over the risk associated with H. pylori infection alone. CagA behaves as a bacterial oncoprotein playing a key role in H. pylori-induced gastric cancer. Activation of oncogenic signaling pathways and inactivation of tumor suppressor pathways are two crucial events in the development of gastric cancer. CagA shows the ability to affect the expression or function of vital protein in oncogenic or tumor suppressor signaling pathways via several molecular mechanisms, such as direct binding or interaction, phosphorylation of vital signaling proteins and methylation of tumor suppressor genes. As a result, CagA continuously dysregulates of these signaling pathways and promotes tumorigenesis. Recent research has enriched our understanding of how CagA effects on these signaling pathways. This review summarizes the results of the most relevant studies, discusses the complex molecular mechanism involved and attempts to delineate the entire signaling pathway.

[Effect of Psoraleae Fructus and Myristicae Semen in "Ershen pill" on serum metabonomics in spleen-kidney Yang deficiency diarrhea rats before and after processing].

The metabonomics method was used to study the intervention effect of Psoraleae Fructus and Myristicae Semen in "Ershen pill" on the changes in serum endogenous metabolites in spleen-kidney Yang deficiency diarrhea rats before and after processing, screen out differentiated metabolites related to spleen-kidney Yang deficiency diarrhea and explore the metabolic patterns related to spleen-kidney Yang deficiency diarrhea and the processing synergy mechanism of Psoraleae Fructus and Myristicae Semen in "Ershen pill". Efforts were made to detect SOD and MDA of each group, test rat serum metabolic fingerprints in different stages by using GC-MS, analyze by PCA and PLS-DA methods and screen out potential biomarks through VIP and t test. The results revealed that "Ershen pill" could enhance the level of SOD and decrease the level of MDA and identified 10 differentiated metabolites related to spleen-kidney Yang deficiency diarrhea. Compared with the model group, all of metabolites recovered to varying levels after being intervened with "Ershen pill", with the best effect shown in the "Ershen pill" IV group (salt-processed Psoraleae Fructus + bran-roasted Myristicae Semen). It is speculated that that Psoraleae Fructus and Semen Myristicae in "Ershen pill" show a synergistic effect by inhibiting peroxide, improving aglucolipid, amino acids and energy metabolism, with multiple target sites.

[Metabolomics analysis revealing multiple compounds changed in rhubarb after processing].

Untargeted metabolomics analysis of rhubarb and stewed rhubarb samples shows that the determined samples clearly clustered in to two groups, indicating that the processing procedures caused changes in the composition and/or content of components in rhubarb. Ten components were identified by UHPLC-Q-TOF-MS/MS and references, which intensity declined in rhubarb after processing. Targeted metabolomics analysis of rhubarb and stewed rhubarb samples indicated that aloe-emodin, rhein, emodin and physcion were detected with lower intensity in stewed rhubarb samples than in rhubarb samples. Metabolomics analysis of rhubarb and stewed rhubarb indicated the various components of rhubarb changed after processing.

[Purgative activity difference and mechanism of raw and processed Rhei Radix et rhizoma].

OBJECTIVE: To investigate the purgative activity difference and mechanism of raw and processed Rhei Radix et Rhizoma. METHODS: Mail mice were divided into 9 groups:normal group (saline), model group, Tongbianling group (1 g/kg), raw Rhei Radix et Rhizoma groups (5.00, 2.50 and 1.25 g/kg), processed Rhei Radix et Rhizoma groups (5.00, 2.50 and 1.25 g/kg). After oral administration for 5 days, the diarrhea experiment and intestinal propelling test were carried out to evaluate the purgative effect difference of raw and processed Rhei Radix et Rhizoma. Wistar rats were divided into normal group (normal saline), model group, Tong-bianling group (0.5 g/kg), raw Rhei Radix et Rhizoma group (1.25 g/kg), processed Rhei Radix et Rhizoma group (1.25 g/kg). The changes of levels of gastin( GAS), motilin( MTL), vasoactive peptide (VIP), neurotensin (NT), somatostatin ( SS), acetylcholinesterase (AchE), substance P(SP) and endothelin (ET-1)in blood of the rats and gastin (GAS), motilin( MTL), vasoactive peptide (VIP) and neurotensin (NT) in colon of the rats were detected. RESULT: The levels of GAS, MTL, VIP, NT, SS, AchE, SP and ET-1 in serum of raw Rhei Radix et Rhizoma group, and GAS, MTL and VIP in colon of raw Rhei Radix et Rhizoma group were different obviously comparing with the processed one (P < 0.01). CONCLUSION: The raw Rhei Radix et Rhizoma and the processed one had obvious differences in regulating intestinal gastrointestinal hormone and neurotransmitter. This effect may be the reason or one of the reasons for purgative activity difference between raw and processed Rhei Radix et Rhizoma.

[Research on building method of spleen kidney Yang deficiency diarrhea rats model].

Spleen kidney Yang deficiency (SKYD) diarrhea is a common syndrome in tranditional Chinese medicine (TCM). Until now, there is not an ideal SKYD diarrhea rat model for the research. In this study, we compared single factor way (method I, injecting hydrocortisone and gavaging Sennae Folium) with compound factors way(method II, gavaging adenine, improper diet, exhaustion, and gavaging Sennae Folium) on establishing SKYD diarrhea rat model. After modelling, diarrhea index, D-xylose excretory rate, NOS/cGMP signal transduction system, organ index and histopathology examination were used to evaluate the two ways. The results showed that, compared with health group, all the assessment criterias of method I and method II had significant differences (P < 0.01, 0.05). In addition, the index such as diarrhea index, NOS/cGMP signal transduction system, organ index (kidney, testis and thymus) and histopathology examination had significant differences (P < 0.01, 0.05) between method I and method II. In conclusion, the compound factors modelling method better conforms to the symptom of diarrhoea model caused by SKYD. This new modelling method provides a basis for studying on TCM astringents warming and tonifying the spleen and kidney, relieving diarrhea.

HBV infection increases the risk of pancreatic cancer: a meta-analysis.

BACKGROUND: Hepatitis B virus (HBV) infection is reported to be associated with an increased risk of pancreatic cancer (PaC), but it remains controversial whether this is a causal relationship. In addition, it is unclear whether the status of HBV infection also affects PaC risk. Therefore, we conducted a meta-analysis to more closely examine the association between HBV infection and PaC. METHOD: The studies included in the meta-analysis were identified and retrieved from PubMed and several other databases. The literature search was conducted up until August 2012. We adopted the Cochrane Collaboration's RevMan 5.1 in a combined analysis of pooled relative risk (RR) with their corresponding 95 % confidence intervals (CIs) using a random-effects and a fixed-effects model. RESULTS: Nine studies including 6 case-control and 3 cohort studies met eligibility criteria. The meta-analysis showed that the PaC risk was positively correlated with HBV infection when comparing with 'never exposed to HBV' subgroup, the pooled RR was 1.39 (95 % CI 1.22-1.59, p < 0.00001) in chronic HBV carriers, 1.41 (95 % CI 1.06-1.87, p = 0.02) in past exposure to HBV, and 3.83 (95 % CI 1.76-8.36, p = 0.0007) in active HBV infection. Using a stratified analysis, we also found that the risk of PaC was independent of smoking, alcohol drinking, and diabetes. CONCLUSION: Findings from this meta-analysis strongly support that HBV infection is associated with an increased risk of PaC.

MicroRNA-613 represses lipogenesis in HepG2 cells by downregulating LXRα.

BACKGROUND: MicroRNAs (miRNAs) emerge as new important regulators of lipid homeostasis by regulating corresponding genes. MiR-613 is a newly discovered microRNA, of which the biological function is unknown. A recent report has shown that miR-613 downregulates liver X receptor α (LXRα), a ligand-activated nuclear receptor playing an important role in the regulation of lipid metabolism. The purpose of this study is to explore the effect and the molecular basis of miR-613 on lipogenesis in HepG2 cells. METHODS: HepG2 cells were transiently transfected with miR-613 mimic or control microRNA. Real time PCR, Western blot, Luciferase reporter assay and Oil Red O staining were employed to examine the expression of LXRα and its target genes involved in lipogenesis, binding site for miR-613 in 3'-untranslated region (3'-UTR) of LXRα mRNA and lipid droplet accumulation in the cells. RESULTS: MiR-613 dramatically suppressed the expression of LXRα and its target genes including sterol-regulatory element binding protein 1c (SREBP-1c), fatty acid synthase (FAS), carbohydrate responsive element-binding protein (ChREBP) and acetyl-CoA carboxylase (ACC). Reporter assay showed that miR-613 directly bound to 3'-UTR of LXRα mRNA. Moreover, miR-613 significantly repressed LXRα-induced lipid droplet accumulation in HepG2 cells. Ectopic expression of LXRα without 3'-UTR markedly attenuated the miR-613-mediated downregulation of LXRα's target genes and LXRα-induced lipid droplet accumulation. CONCLUSIONS: MiR-613 suppresses lipogenesis by directly targeting LXRα in HepG2 cells, suggesting that miR-613 may serve as a novel target for regulating lipid homeostasis.

microRNA-27b suppresses mouse MSC migration to the liver by targeting SDF-1αin vitro.

The SDF-1/CXCR4 axis is critical for inducing stem cell mobilization into the circulation, for homing stem cells to the site of injury, and for stem cell participation in the regeneration of liver tissue. In this study, we have gained insight into the molecular mechanisms involved in regulating the expression of SDF-1α by miRNAs. Using microarray and bioinformatics approaches, we identified six miRNAs with differential expression in damaged liver tissue (21 days after liver injury) compared to normal C57BL/6 murine liver tissue and further confirmed these observations by qPCR; miR-23a, which was identified by other researchers, was also included for comparative purposes. We found that miR-23a, miR-27a and miR-27b expression was significantly lower in the damaged liver than in the normal liver (p<0.05). We further confirmed that miR-27b could directly interact with the 3'UTR of SDF-1α to suppress SDF-1α protein expression using a luciferase reporter assay and Western blot analysis. In addition, we found that the over-expression of miR-27b significantly reduced the directional migration of primary cultured CRCX4-positive murine mesenchymal stem cells (mMSCs) in vitro using a transwell assay. These results suggest that miR-27b may be a unique signature of the stem cell niche in the damaged mouse liver and that mir-27b can suppress the directional migration of mMSCs by down-regulating SDF-1α expression by binding directly to the SDF-1α 3'UTR.

Strategies for enhancing vaccine-induced CTL antitumor immune responses.

Vaccine-induced cytotoxic T lymphocytes (CTLs) play a critical role in adaptive immunity against cancers. An important goal of current vaccine research is to induce durable and long-lasting functional CTLs that can mediate cytotoxic effects on tumor cells. To attain this goal, there are four distinct steps that must be achieved. To initiate a vaccine-induced CTL antitumor immune response, dendritic cells (DCs) must capture antigens derived from exogenous tumor vaccines in vivo or autologous DCs directly loaded in vitro with tumor antigens must be injected. Next, tumor-antigen-loaded DCs must activate CTLs in lymphoid organs. Subsequently, activated CTLs must enter the tumor microenvironment to perform their functions, at which point a variety of negative regulatory signals suppress the immune response. Finally, CTL-mediated cytotoxic effects must overcome the tolerance induced by tumor cells. Each step is a complex process that may be impeded in many ways. However, if these steps happen under appropriate regulation, the vaccine-induced CTL antitumor immune response will be more successful. For this reason, we should gain a better understanding of the basic mechanisms that govern the immune response. This paper, based on the steps necessary to induce an immune response, discusses current strategies for enhancing vaccine-induced CTL antitumor immune responses.