Tissue distribution of metabolites in Cordyceps cicadae determined by DESI-MSI analysis.

In this paper, we establish an in situ visualization analysis method to image the spatial distribution of metabolites in different parts (sclerotium, coremium) and different microregions of Cordyceps cicadae (C. cicadae) to achieve the in situ visual characterization of tissues for a variety of metabolites such as nucleosides, amino acids, polysaccharides, organic acids, fatty acids, and so on. The study included LC-MS chemical composition identification, preparation of C. cicadae tissue sections, DEDI-MSI analysis, DESI combined with Q-TOF/MS to obtain high-resolution imaging of mass-to-charge ratio and space, imaging of C. cicadae in positive-negative ion mode with a spatial resolution of 100 µm, and localizing and identifying its chemical compositions based on its precise mass. A total of 62 compounds were identified; nucleosides were mainly distributed in the coremium, L-threonine and DL-isoleucine, and other essential amino acids; peptides were mainly distributed in the sclerotium of C. cicadae; and the rest of the amino acids did not have a clear pattern; sugars and sugar alcohols were mainly distributed in the coremium of C. cicadae; organic acids and fatty acids were distributed in the nucleus of C. cicadae more than in the sclerotium, and the mass spectrometry imaging method is established in the research. The mass spectrometry imaging method established in this study is simple and fast and can visualize and analyse the spatial distribution of metabolites of C. cicadae, which is of great significance in characterizing the metabolic network of C. cicadae, and provides support for the quality evaluation of C. cicadae and the study of the temporal and spatial metabolic network of chemical compounds.

Current advances in the pain treatment and mechanisms of Traditional Chinese Medicine.

Traditional Chinese Medicine (TCM), as a unique medical model in China, has been shown to be effective in the treatment of many diseases. It has been proven that TCM can increase the pain threshold, increase the level of endorphins and enkephalins in the body, and reduce the body's response to adverse stimuli. In recent years, TCM scholars have made valuable explorations in the field of pain treatment, using methods such as internal and external application of TCM and acupuncture to carry out research on pain treatment and have achieved more satisfactory results. TCM treats pain in a variety of ways, and with the discovery of a variety of potential bioactive substances for pain treatment. With the new progress in the research of other TCM treatment methods for pain, TCM will have greater potential in the clinical application of pain.

Radiolytic Water Splitting Sensitized by Nanoscale Metal-Organic Frameworks.

High-energy radiation that is compatible with renewable energy sources enables direct H2 production from water for fuels; however, the challenge is to convert it as efficiently as possible, and the existing strategies have limited success. Herein, we report the use of Zr/Hf-based nanoscale UiO-66 metal-organic frameworks as highly effective and stable radiation sensitizers for purified and natural water splitting under γ-ray irradiation. Scavenging and pulse radiolysis experiments with Monte Carlo simulations show that the combination of 3D arrays of ultrasmall metal-oxo clusters and high porosity affords unprecedented effective scattering between secondary electrons and confined water, generating increased precursors of solvated electrons and excited states of water, which are the main species responsible for H2 production enhancement. The use of a small quantity (<80 mmol/L) of UiO-66-Hf-OH can achieve a γ-rays-to-hydrogen conversion efficiency exceeding 10% that significantly outperforms Zr-/Hf-oxide nanoparticles and the existing radiolytic H2 promoters. Our work highlights the feasibility and merit of MOF-assisted radiolytic water splitting and promises a competitive method for creating a green H2 economy.

[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.

Ambient γ-Rays-Mediated Noble-Metal Deposition on Defect-Rich Manganese Oxide for Glycerol-Assisted H2 Evolution at Industrial-Level Current Density.

Developing novel synthesis technologies is crucial to expanding bifunctional electrocatalysts for energy-saving hydrogen production. Herein, we report an ambient and controllable γ-ray radiation reduction to synthesize a series of noble metal nanoparticles anchored on defect-rich manganese oxides (M@MnO2-x , M=Ru, Pt, Pd, Ir) for glycerol-assisted H2 evolution. Benefiting from the strong penetrability of γ-rays, nanoparticles and defect supports are formed simultaneously and bridged by metal-oxygen bonds, guaranteeing structural stability and active site exposure. The special Ru-O-Mn bonds activate the Ru and Mn sites in Ru@MnO2-x through strong interfacial coordination, driving glycerol electrolysis at low overpotential. Furthermore, only a low cell voltage of 1.68 V is required to achieve 0.5 A cm-2 in a continuous-flow electrolyzer system along with excellent stability. In situ spectroscopic analysis reveals that the strong interfacial coordination in Ru@MnO2-x balances the competitive adsorption of glycerol and OH* on the catalyst surface. Theoretical calculations further demonstrate that the defect-rich MnO2 support promotes the dissociation of H2 O, while the defect-regulated Ru sites promote deprotonation and hydrogen desorption, synergistically enhancing glycerol-assisted hydrogen production.

Effect of Wuzi Yanzong prescription on oligoasthenozoospermia rats based on UPLC-Q-TOF-MS metabolomics.

CONTEXT: Wuzi Yanzong Prescription (WYP) has long been used to treat male infertility, with convincing clinical evidence. However, its mechanism of action is not clear. OBJECTIVE: WYP chemical components were quantified by HPLC, and the effect on oligoasthenozoospermia rats was explored based on UPLC-Q-TOF-MS metabonomics technology. MATERIALS AND METHODS: The solution was extracted by alcohol and water; the content of eight components in the extracting solution was determined by HPLC. Twenty-four Sprague-Dawley rats were randomly divided into control (CG), model (MG) and administration (PG) groups. Oligoasthenozoospermia was induced for 30 days in all, but the CG with daily oral doses of 20 mg/kg Tripterysium glycosides (TG). PG was given daily oral doses of WYP solution (1.08 g/kg), CG and MG received the same volume of distilled water, all administered for 30 days. After the last administration, the serum samples were collected and detected by UPLC-Q-TOF-MS. RESULTS: An HPLC method for simultaneous determination of chlorogenic acid (0.081%), ellagic acid (0.021%), hyperoside (0.032%), verbascoside (0.011%), isoquercitrin (0.041%), astragalin (0.026%), kaempferol (0.009%) and schisandrin (0.014%) was established. Moreover, the 74 potential biomarkers and eight metabolic pathways related to oligoasthenozoospermia were identified by multivariate analysis and metabolite profiling. WYP can regulate 36 markers, mainly involving amino acid metabolism, lipid metabolism and nucleotide metabolism. DISCUSSION AND CONCLUSIONS: This is a simple and accurate method for quality control of WYP. It further enriches the potential mechanism of WYP in the treatment of oligoasthenozoospermia. It can provide a theoretical basis for the rational application of WYP.

Radiolytic Approach for Efficient, Selective and Catalyst-free CO2 Conversion at Room Temperature.

The present study proposes a new approach for direct CO2 conversion using primary radicals from water irradiation. In order to ensure reduction of CO2 into CO2-. by all the primary radiation-induced water radicals, we use formate ions to scavenge simultaneously the parent oxidizing radicals H. and OH. producing the same transient CO2-. radicals. Conditions are optimized to obtain the highest conversion yield of CO2 . The goal is achieved under mild conditions of room temperature, neutral pH and 1 atm of CO2 pressure. All the available radicals are exploited for selectively converting CO2 into oxalate that is accompanied by H2 evolution. The mechanism presented accounts for the results and also sheds light on the data in the literature. The radiolytic approach is a mild and scalable route of direct CO2 capture at the source in industry and the products, oxalate salt and H2 , can be easily separated.

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.

CircMRPS35 suppresses gastric cancer progression via recruiting KAT7 to govern histone modification.

BACKGROUND: Aberrant expression of circular RNAs contributes to the initiation and progression of cancers, but the underlying mechanism remains elusive. METHODS: RNA-seq and qRT-PCR were performed to screen differential expressed circRNAs between gastric cancer tissues and adjacent normal tissues. Candidate circRNA (circMRPS35) was screened out and validated by qRT-PCR. Cell proliferation and invasion ability were determined by CCK-8 and cell invasion assays. RNA-seq, GO-pathway, RNA pull-down and ChIRP were further applied to search for detailed mechanism. RESULTS: Here, a novel circRNA named circMRPS35, was screened out by RNA-seq in gastric cancer tissues, whose expression is related to clinicopathological characteristics and prognosis in gastric cancer patients. Biologically, circMRPS35 suppresses the proliferation and invasion of gastric cancer cells in vitro and in vivo. Mechanistically, circMRPS35 acts as a modular scaffold to recruit histone acetyltransferase KAT7 to the promoters of FOXO1 and FOXO3a genes, which elicits acetylation of H4K5 in their promoters. Particularly, circMRPS35 specifically binds to FOXO1/3a promoter regions directly. Thus, it dramatically activates the transcription of FOXO1/3a and triggers subsequent response of their downstream target genes expression, including p21, p27, Twist1 and E-cadherin, resulting in the inhibition of cell proliferation and invasion. Moreover, circMRPS35 expression positively correlates with that of FOXO1/3a in gastric cancer tissues. CONCLUSIONS: Our findings not only reveal the pivotal roles of circMRPS35 in governing histone modification in anticancer treatment, but also advocate for triggering circMRPS35/KAT7/FOXO1/3a pathway to combat gastric cancer.

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.

hTERT promotes the invasion of gastric cancer cells by enhancing FOXO3a ubiquitination and subsequent ITGB1 upregulation.

BACKGROUND AND AIMS: Human telomerase reverse transcriptase (hTERT) plays an important role in cancer invasion, but the relevant mechanism is not well known. This study aims to investigate the role and mechanism of hTERT in gastric cancer metastasis. DESIGN: Proteomics analysis, qPCR and western blotting were used to screen for hTERT-regulated candidate molecules in gastric cancer invasion. Chromatin immunoprecipitation (ChIP) qPCR was performed to identify the binding sites of hTERT at the regulatory region of the integrin ß1 (ITGB1) gene. ChIP assays were further applied to elucidate the transcription factors that bound to the regulatory region. The interactions between hTERT and the transcription factors were tested by co-immunoprecipitation (Co-IP) and glutathione S-transferase (GST) pull-down experiments. Moreover, the revealed pathway was verified in tumour-bearing nude mice and human gastric cancer tissues. RESULTS: ITGB1 was identified as a downstream gene of hTERT, and there were two hTERT-binding regions within this gene. hTERT alleviated the binding of forkhead box O3 (FOXO3a) to FOXO3a binding element (+9972∼+9978), but it enhanced the binding of forkhead box M1 (FOXM1) to FOXM1 binding element (-1104∼-1109) in ITGB1 gene. Importantly, FOXO3a played a major role in hTERT-induced ITGB1 expression, and the hTERT/murine double minute 2 (MDM2) complex promoted the ubiquitin-mediated degradation of FOXO3a. Moreover, hTERT increased ITGB1 expression in xenograft gastric cancer, and the level of hTERT was positively correlated with that of ITGB1 in human gastric cancer tissues. CONCLUSIONS: The hTERT/MDM2-FOXO3a-ITGB1 pathway markedly contributes to hTERT-promoted gastric cancer invasion, suggesting that this pathway might be a novel target for the prevention and treatment of gastric cancer metastasis.

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.