Long-term remission achieved in a rare case of pyoderma gangrenosum and ulcerative colitis with surgery and postoperative infliximab.

Background Pyoderma gangrenosum (PG) is a rare extraintestinal manifestation of inflammatory bowel disease. In recent years, the use of biologics in PG has been on the rise and has shown promising results. The surgical treatment of PG remains a topic of debate, with limited reports on the use of postoperative biologic therapy. Case reprt: This case report describes a 52-year-old woman who presented with multiple skin ulcers, pus discharge, and bloody diarrhea. The patient was diagnosed with PG with ulcerative colitis based on medical history, ulcer appearance, histopathology, treatment response, and the presence of ulcerative colitis. Surgical intervention was performed to repair the ulcers and amputate the fourth finger and fourth toe of both feet. Additionally, infliximab induction therapy was initiated two weeks after the surgery. The patient's intestinal symptoms demonstrated improvement, and after 10 months of treatment, the lesions were completely healed with no recurrence of skin ulcers. Conclusions This case report highlights a rare instance of successful treatment for PG with ulcerative colitis through a combination of surgery and postoperative infliximab.

Comparative efficacy and safety of combination therapy with infliximab for Crohn's disease: a systematic review and network meta-analysis.

PURPOSE: There is not enough information to position medications for the treatment of Crohn's disease (CD). Therefore, using a network meta-analysis and systematic review, we evaluated the efficacy and safety of combination therapy and infliximab (IFX) monotherapy in CD patients. METHODS: We identified randomized controlled trials (RCTs) in CD patients who were given IFX-containing combination therapy versus IFX monotherapy. Induction and maintenance of clinical remission were the efficacy outcomes, while adverse events were the safety outcomes. The surface under cumulative ranking (SUCRA) probabilities was used to assess ranking in the network meta-analysis. RESULTS: In total, 15 RCTs with 1586 CD patients were included in this study. There was no statistical difference between different combination therapies in induction and maintenance of remission. In terms of inducing clinical remission, IFX + EN (SUCRA: 0.91) ranked highest; in terms of maintaining clinical remission, IFX + AZA (SUCRA: 0.85) ranked highest. There was no treatment that was significantly safer than the others. In terms of any adverse events, serious adverse events, serious infections, and infusion/injection-site reactions, IFX + AZA (SUCRA: 0.36, 0.12, 0.19, and 0.24) was ranked lowest for all risks; while IFX + MTX (SUCRA: 0.34, 0.06, 0.13, 0.08, 0.34, and 0.08) was rated lowest for risk of abdominal pain, arthralgia, headache, nausea, pyrexia, and upper respiratory tract infection. CONCLUSION: Indirect comparisons suggested that efficacy and safety of different combination treatments are comparable in CD patients. For maintenance therapies, IFX + AZA was ranked highest for clinical remission and lowest for adverse events. Further head-to-head trials are required.

Ligand Dilution Analysis Facilitates Aptamer Binding Characterization at the Single-Molecule Level.

Cell-specific aptamers offer a powerful tool to study membrane receptors at the single-molecule level. Most target receptors of aptamers are highly expressed on the cell surface, but difficult to analyze in situ because of dense distribution and fast velocity. Therefore, we herein propose a random sampling-based analysis strategy termed ligand dilution analysis (LDA) for easily implemented aptamer-based receptor study. Receptor density on the cell surface can be calculated based on a regression model. By using a synergistic ligand dilution design, colocalization and differentiation of aptamer and monoclonal antibody (mAb) binding on a single receptor can be realized. Once this is accomplished, precise binding site and detailed aptamer-receptor binding mode can be further determined using molecular docking and molecular dynamics simulation. The ligand dilution strategy also sets the stage for an aptamer-based dynamics analysis of two- and three-dimensional motion and fluctuation of highly expressed receptors on the live cell membrane.

Extracellular vesicles-derived microRNA-222 promotes immune escape via interacting with ATF3 to regulate AKT1 transcription in colorectal cancer.

BACKGROUND: Immunotherapy has been recently established as a new direction for the treatment of colorectal cancer (CRC), a gastrointestinal cancer. In this investigation, we aimed to expound how the posttranscriptional regulation modulated by microRNA-222 (miR-222) from mesenchymal stem cells-derived extracellular vesicles (MSC-EVs) affected the AKT pathway and the immune escape in CRC. METHODS: CRC cell malignant phenotype, including proliferation, migration, invasion, and apoptosis, was firstly detected after co-culture with MSC-EVs. miRNAs with differential changes in CRC cells before and after EVs treatment were filtered by microarray analysis. miR-222 was then downregulated to examine its role in CRC cells in response to EVs. Cells were implanted in mice to induce xenograft tumors, and infiltrating T cells was assessed by immunohistochemistry. The mRNA microarray was used to screen target genes, followed by rescue experiments. ChIP and western blot were conducted to validate the downstream biomolecule of ATF3. RESULTS: After treatment of CRC cells with MSC-EVs, the expression of miR-222 was upregulated, and cell activity was increased. Inhibition of miR-222 decreased CRC malignant aggressiveness in vitro and reduced tumorigenesis and immune escape in vivo. miR-222 targeted and bound to ATF3. Downregulation of ATF3 enhanced CRC cell malignant aggressiveness, tumorigenic capacity and immune escape. Mechanistically, ATF3 inhibited AKT1 transcription and mediated the AKT pathway. CONCLUSION: MSC-EVs carry miR-222 to promote CRC cell malignant aggressiveness and immune escape. miR-222 targets and binds to ATF3, which inhibits AKT1 transcriptional activity and thereby mediates the AKT pathway.

NEDD4 triggers FOXA1 ubiquitination and promotes colon cancer progression under microRNA-340-5p suppression and ATF1 upregulation.

NEDD4 is an E3 ubiquitin ligase that recognizes substrates through protein-protein interactions and is involved in cancer development. This study aimed to elucidate the function of NEDD4 in colon cancer (CC) progression and its mechanism of action. NEDD4 was abundantly expressed in CC tissues and cells, and the overexpression of NEDD4 promoted the growth and metastasis of xenograft tumours as well as the tumorigenesis rate of primary CC in mouse models. In in vitro experiments, the silencing (or upregulation) of NEDD4 inhibited (or increased) the viability, invasion, and epithelial-to-mesenchymal transition of CC cells. The binding relationships between NEDD4 and FOXA1, FOXA1 and microRNA (miRNA)-340-5p, and miR-340-5p and ATF1 were validated by Co-immunoprecipitation, chromatin immunoprecipitation and luciferase assays, and NEDD4 was demonstrated to trigger FOXA1 ubiquitination and degradation. FOXA1 transcriptionally activated miR-340-5p, which subsequently bound to ATF1 mRNA. The upregulation of FOXA1 or miR-340-5p or the downregulation of ATF1 blocked certain functions of NEDD4 in CC cells. Altogether, NEDD4 was demonstrated to trigger FOXA1 ubiquitination and promote CC progression under the involvement of microRNA-340-5p suppression and ATF1 upregulation.

Circ0106714 inhibits tumorigenesis of colorectal cancer by sponging miR-942-5p and releasing DLG2 via Hippo-YAP signaling.

This study aimed to investigate the role of circ0106714-miR-942-5p-discs large homolog 2 (DLG2), a novel interactome, in colorectal cancer (CRC). Circ0106714 was found to be the most significantly downregulated circular RNA in CRC using a bioinformatics method, and we researched whether the ability of circ0106714 to sponge miR-942-5p and release DLG2 could affect CRC development via Hippo-YES-associated protein (YAP) signaling. We first employed qRT-PCR and immunoblotting to detect messenger RNA (mRNA) and protein expression, respectively. Live imaging of mice tumor xenografts was then conducted to study the effect of circ0106714 on tumor progression in vivo. Reporter gene assays were subsequently conducted to verify the predicted targeting relationship between circ0106714, miR-942-5p, and DLG2 mRNA in SW480 and HCT116 cell lines. As well as using flow cytometry for both apoptosis and cell cycle profile analyses, CCK-8 and clone foci formation assays were performed to assess cell survival. Wound healing assay and transwell invasion assay were later carried out to evaluate the migration and invasion of the cell lines. Findings revealed that circ0106714 and DLG2 were significantly downregulated, while miR-942-5p was significantly upregulated in human CRC tissues and cell lines. However, circ0106714 upregulation significantly suppressed tumor progression in vivo and inhibited the malignancy phenotypes of tumor cells in vitro by targeting miR-942-5p. Also discovered in this research was that miR-942-5p could directly target DLG2 mRNA, thus enhancing the malignancy phenotypes of CRC cells. We even found that DLG2 overexpression resulted in enhanced phosphorylation of YAP, a critical downstream effector of DLG2. This downstream effector was demonstrated to have a tumor-suppressive capacity in CRC cell lines. In sum, circ0106714 could suppress CRC by sponging miR-942-5p and releasing DLG2, thus promoting YAP phosphorylation.

Silencing of TMEM158 Inhibits Tumorigenesis and Multidrug Resistance in Colorectal Cancer.

Transmembrane protein 158 (TMEM158) plays pivotal roles in many cancers, including colorectal cancer (CRC). It has been reported that it is a recently identified upregulated gene during Ras-induced senescence. However, the clinical significance and biological functions of TMEM158 in CRC remain largely unknown. In this study, we found that TMEM158 was highly expressed in CRC tissues and cell lines compared with the corresponding noncancerous samples and normal colon epithelial cells. In vitro studies showed that TMEM158 silencing inhibited proliferation, and migration and increased apoptosis of CRC cells, whereas overexpression of TMEM158 increased proliferation, migration, and apoptosis escape of CRC cells. Mechanically, the levels of drug resistance-associated molecules, including multidrug resistance 1 and multidrug resistance protein 1, as well as the expression of antiapoptotic Bcl-2 were significantly upregulated. In addition, TMEM158 knockdown significantly inhibited tumor growth in vivo. Collectively, these results demonstrated that TMEM158 is a significant regulator of tumorigenesis and drug resistance in CRC and provided evidence that TMEM158 may be a promising target for CRC therapy.

Transcriptionally activates CCL28 expression to inhibit M2 polarization of macrophages and prevent immune escape in colorectal cancer cells.

OBJECTIVE: This study aimed to investigate the potential molecular mechanism of SPDEF in immune evasion of colorectal cancer (CRC) and examine its impact on macrophage M2 polarization using the TCGA and GEO databases. METHODS: By combining TCGA and GEO databases, differential gene expression between CRC samples and standard tissue samples was analyzed to screen for immune-related genes (IRGs) associated with the prognosis of CRC patients. A predictive risk model was constructed based on 18 key IRGs, which were then validated using the GEO dataset. The relationship between transcription factors and IRGs was further explored to investigate their regulatory network in CRC. In vivo and in vitro experiments were carried out to validate these regulatory relationships and explore the function of SPDEF and CCL28 in CRC. RESULTS: Twelve key IRGs associated with clinical and pathological characteristics of CRC patients were identified. Among them, CCL28 significantly impacted macrophage infiltration in CRC cells and may be a critical factor in immune evasion. In both in vitro and in vivo experiments, overexpression of SPDEF upregulated CCL28 expression, thereby suppressing M2 polarization of macrophages and inhibiting CRC cell proliferation and tumor growth. Notably, interference with CCL28 could reverse the effect of SPDEF overexpression. CONCLUSION: SPDEF can suppress immune evasion of CRC cells by activating CCL28, which is achieved through the modulation of M2 polarization of macrophages. This provides a new research direction and potential therapeutic target for immunotherapy in CRC.

DNA-Based Molecular Machines: Controlling Mechanisms and Biosensing Applications.

The rise of DNA nanotechnology has driven the development of DNA-based molecular machines, which are capable of performing specific operations and tasks at the nanoscale. Benefitting from the programmability of DNA molecules and the predictability of DNA hybridization and strand displacement, DNA-based molecular machines can be designed with various structures and dynamic behaviors and have been implemented for wide applications in the field of biosensing due to their unique advantages. This review summarizes the reported controlling mechanisms of DNA-based molecular machines and introduces biosensing applications of DNA-based molecular machines in amplified detection, multiplex detection, real-time monitoring, spatial recognition detection, and single-molecule detection of biomarkers. The challenges and future directions of DNA-based molecular machines in biosensing are also discussed.

Iron nanoparticles surface decorated MXene via molten salts etching as selenium host for ultrafast sodium ion storage.

Sodium-selenium (Na-Se) batteries have gained attention due to their high energy density and power density, resulting from the liquid-liquid reaction at the interface in the dimethoxyethane electrolyte. Nevertheless, the pronounced shuttle effect of polyselenides causes low coulomb efficiency and inadequate cycling stability for Na-Se batteries. Herein, the iron nanoparticles surface modified accordion-like Ti3C2Tx MXene (MXene/Fe) synthesized via the molten salt etching is utilized as the host of Se species for high-performance Na-Se battery cathode. Benefiting from the layered structure and chemical adsorption of accordion-like MXene, the shuttle effect of the cathode is effectively inhibited. Simultaneously, electrochemical kinetics is boosted due to the catalytic effect of Fe nanoparticles, which facilitate the transformation of polyselenide from long-chain to short-chain, contributing to pseudocapacitive capacity. Consequently, the Se-based cathode delivers a steady capacity of 575.0 mA h g-1 at 0.2 A/g, and even a high capacity of 500 mAh/g at 50 A/g based on the mass of Se@MXene/Fe electrode, indicating the ultrafast Na+ ion storage. Most notably, this structure demonstrated remarkable long-term cycling stability for 5000 cycles with a high capacity retention of 97.4 %. The electrochemical energy storage mechanism is further revealed by in situ Raman. Herein, the confinement-catalysis structure shines light on inhibiting shuttling and facilitating ultrafast ion storage.

Integrated multi-omics reveal gut microbiota-mediated bile acid metabolism alteration regulating immunotherapy responses to anti-α4ß7-integrin in Crohn's disease.

Gut microbiota and related metabolites are both crucial factors that significantly influence how individuals with Crohn's disease respond to immunotherapy. However, little is known about the interplay among gut microbiota, metabolites, Crohn's disease, and the response to anti-α4ß7-integrin in current studies. Our research utilized 2,4,6-trinitrobenzene sulfonic acid to induce colitis based on the humanized immune system mouse model and employed a combination of whole-genome shotgun metagenomics and non-targeted metabolomics to investigate immunotherapy responses. Additionally, clinical cases with Crohn's disease initiating anti-α4ß7-integrin therapy were evaluated comprehensively. Particularly, 16S-rDNA gene high-throughput sequencing and targeted bile acid metabolomics were conducted at weeks 0, 14, and 54. We found that anti-α4ß7-integrin therapy has shown significant potential for mitigating disease phenotypes in remission-achieving colitis mice. Microbial profiles demonstrated that not only microbial composition but also microbially encoded metabolic pathways could predict immunotherapy responses. Metabonomic signatures revealed that bile acid metabolism alteration, especially elevated secondary bile acids, was a determinant of immunotherapy responses. Especially, the remission mice significantly enriched the proportion of the beneficial Lactobacillus and Clostridium genera, which were correlated with increased gastrointestinal levels of BAs involving lithocholic acid and deoxycholic acid. Moreover, most of the omics features observed in colitis mice were replicated in clinical cases. Notably, anti-α4ß7 integrin provided sustained therapeutic benefits in clinical remitters during follow-up, and long-lasting remission was linked to persistent changes in the microbial-related bile acids. In conclusion, gut microbiota-mediated bile acid metabolism alteration could play a crucial role in regulating immunotherapy responses to anti-α4ß7-integrin in Crohn's disease. Therefore, the identification of prognostic microbial signals facilitates the advancement of targeted probiotics that activate anti-inflammatory bile acid metabolic pathways, thereby improving immunotherapy responses. The integrated multi-omics established in our research provide valuable insights into potential mechanisms that impact treatment responses in complex diseases.

miR-143-3p shuttled by M2 macrophage-derived extracellular vesicles induces progression of colorectal cancer through a ZC3H12A/C/EBPß axis-dependent mechanism.

Extracellular vesicles (EVs) exhibit pivotal functions in cancer via intercellular communication through shuttling microRNA (miRNA) and protein. Therefore, we aim to elucidate the function of EVs containing miR-143-3p derived from M2 macrophages in colorectal cancer (CRC). EVs derived from M2 macrophages were isolated and characterized. Expression changes in miR-143-3p were calculated in the EVs. The effects of M2 macrophage-derived EV carrying miR-143-3p on cell biological processes and in vivo tumorigenic ability concerning ZC3H12A were examined. EVs derived from M2 macrophages could stimulate the aggressive tumor biology of CRC cells. Meanwhile, in vivo results showed that M2 macrophage-derived EVs facilitated tumor growth and epithelial-mesenchymal transition. M2 macrophage-secreted EVs could transfer miR-143-3p to CRC cells, in which miR-143-3p bound to the 3'UTR of ZC3H12A and inhibited its expression, leading to elevation of the expression of transcription factor C/EBPß. Overall, M2 macrophage-derived EV miR-143-3p inhibits ZC3H12A gene and increases C/EBPß expression to facilitate the development of CRC, which provides novel targets for the molecular treatment of CRC.

Horseradish Peroxidase-Coupled Ag3 PO4 /BiVO4 Photoanode for Biophotoelectrocatalytic Degradation of Organic Contaminants.

Photoelectrocatalysis (PEC) is regarded as a promising and sustainable process for removal of organic contaminants from wastewater. Meanwhile, enzymatic catalysis also provides an effective way to carry out polluted environment remediation under mild conditions. In this study, a biophotoelectrocatalytic (BPEC) system is designed to remove 4-nitrophenol (4-NP) based on a combination of PEC and enzymatic catalysis. The developed BPEC system is constructed with a Ag3 PO4 /BiVO4 photoanode and a horseradish peroxidase (HRP)-loaded carbon cloth (CC) cathode. On the photoanode, the construction of a direct Z-scheme Ag3 PO4 /BiVO4 heterojunction enhanced the separation efficiency of photogenerated carriers, which promoted the PEC degradation of 4-NP under visible light irradiation. After HRP was immobilized on the cathode, the degradation efficiency of 4-NP reached 97.1 % after 60 min PEC treatment. The result could be ascribed to the HRP-catalyzed oxidation reaction via in situ-generated H2 O2 from the CC cathode during the PEC process. Moreover, the possible degradation pathways of 4-NP in such a BPEC system are also discussed.

Retraction Notice to: lncRNA ILF3-AS1 promotes proliferation and metastasis of colorectal cancer cells by recruiting histone methylase EZH2.

[This retracts the article DOI: 10.1016/j.omtn.2021.04.007.].

Mechanism of annexin A1/N-formylpeptide receptor regulation of macrophage function to inhibit hepatic stellate cell activation through Wnt/ß-catenin pathway.

BACKGROUND: Hepatic fibrosis is a common pathological process of chronic liver diseases with various causes, which can progress to cirrhosis. AIM: To evaluate the effect and mechanism of action annexin (Anx)A1 in liver fibrosis and how this could be targeted therapeutically. METHODS: CCl4 (20%) and active N-terminal peptide of AnxA1 (Ac2-26) and N-formylpeptide receptor antagonist N-Boc-Phe-Leu-Phe-Leu-Phe (Boc2) were injected intraperitoneally to induce liver fibrosis in eight wild-type mice/Anxa1 knockout mice, and to detect expression of inflammatory factors, collagen deposition, and the role of the Wnt/ß-catenin pathway in hepatic fibrosis. RESULTS: Compared with the control group, AnxA1, transforming growth factor (TGF)-ß1, interleukin (IL)-1ß and IL-6 expression in the liver of mice with hepatic fibrosis induced by CCl4 was significantly increased, which promoted collagen deposition and expression of α-smooth muscle actin (α-SMA), collagen type I and connective tissue growth factor (CTGF), and increased progressively with time. CCl4 induced an increase in TGF-ß1, IL-1ß and IL-6 in liver tissue of AnxA1 knockout mice, and the degree of liver inflammation and fibrosis and expression of α-SMA, collagen I and CTGF were significantly increased compared with in wild-type mice. After treatment with Ac2-26, expression of liver inflammatory factors, degree of collagen deposition and expression of a-SMA, collagen I and CTGF were decreased compared with before treatment. Boc2 inhibited the anti-inflammatory and antifibrotic effects of Ac2-26. AnxA1 downregulated expression of the Wnt/ß-catenin pathway in CCl4-induced hepatic fibrosis. In vitro, lipopolysaccharide (LPS) induced hepatocyte and hepatic stellate cell (HSC) expression of AnxA1. Ac2-26 inhibited LPS-induced RAW264.7 cell activation and HSC proliferation, decreased expression of α-SMA, collagen I and CTGF in HSCs, and inhibited expression of the Wnt/ß-catenin pathway after HSC activation. These therapeutic effects were inhibited by Boc2. CONCLUSION: AnxA1 inhibited liver fibrosis in mice, and its mechanism may be related to inhibition of HSC Wnt/ß-catenin pathway activation by targeting formylpeptide receptors to regulate macrophage function.

Gut microbiota-related bile acid metabolism-FXR/TGR5 axis impacts the response to anti-α4ß7-integrin therapy in humanized mice with colitis.

The gut microbiota and bile acid metabolism are key determinants of the response of inflammatory bowel disease to biologic therapy. However, the molecular mechanisms underlying the interactions between the response to anti-α4ß7-integrin therapy and the gut microbiota and bile acid metabolism remain unknown. In this research, we investigated the role of gut microbiota-related bile acid metabolism on the response to anti-α4ß7-integrin therapy in a humanized immune system mouse model with colitis induced by 2,4,6-trinitrobenzene sulfonic acid. We found that anti-α4ß7-integrin significantly mitigated intestinal inflammation, pathological symptoms, and gut barrier disruption in remission-achieving colitis mice. Whole-genome shotgun metagenomic sequencing demonstrated that employing baseline microbiome profiles to predict remission and the treatment response was a promising strategy. Antibiotic-mediated gut microbiota depletion and fecal microbiome transplantation revealed that the baseline gut microbiota contained common microbes with anti-inflammatory effects and reduced mucosal barrier damage, improving the treatment response. Targeted metabolomics analysis illustrated that bile acids associated with microbial diversity were involved in colitis remission. Furthermore, the activation effects of the microbiome and bile acids on FXR and TGR5 were evaluated in colitis mice and Caco-2 cells. The findings revealed that the production of gastrointestinal bile acids, particularly CDCA and LCA, further directly promoted the stimulation of FXR and TGR5, significantly improving gut barrier function and suppressing the inflammatory process. Taken together, gut microbiota-related bile acid metabolism-FXR/TGR5 axis may be a potential mechanism for impacting the response to anti-α4ß7-integrin in experimental colitis. Thus, our research provides novel insights into the treatment response in inflammatory bowel disease.

RETRACTED ARTICLE: Down-regulation of lncRNA FEZF1-AS1 mediates regulatory T cell differentiation and further blocks immune escape in colon cancer.

Statement of RetractionWe, the Editors and Publisher of the journal Expert Review of Molecular Diagnostics, have retracted the following article:Sen Hong, Zhenkun Yan, YuMei Song, MiaoMiao Bi & Shiquan Li. Down-regulation of lncRNA FEZF1-AS1 mediates regulatory T cell differentiation and further blocks immune escape in colon cancer. Expert Review of Molecular Diagnostics. 2021. DOI: 10.1080/14737159.2022.2012157Since publication, significant concerns have been raised about the integrity of the data and reported results in the article. When approached for an explanation, the authors did not provide their original data or any necessary supporting information. As verifying the validity of published work is core to the integrity of the scholarly record, we are therefore retracting the article. The corresponding author listed in this publication has been informed.We have been informed in our decision-making by our policy on publishing ethics and integrity and the COPE guidelines on retractions.The retracted article will remain online to maintain the scholarly record, but it will be digitally watermarked on each page as 'Retracted'.

Effect of Highland Barley on Rheological Properties, Textural Properties and Starch Digestibility of Chinese Steamed Bread.

Highland barley has a different composition and structure to other crops. It has higher contents of total polyphenol (TPC), total flavonoid (TFC) and ß-glucan, which can be supplemented to improve the nutrition of wheat-flour-based food. In this study, the flours of three different grain-colored highland barley varieties Beiqing 6 (BQ), Dulihuang (DLH), and Heilaoya (HLY), were added to Jimai60 (JM, a wheat variety with medium gluten) wheat flour at different substitution levels to investigate their effects on the unextractable polymeric protein (UPP) content, micro-structure, rheological properties and mixing properties of dough, and the color, texture, flavor, and in vitro digestion of Chinese steam bread (CSB). The results showed that the moderate substitution of highland barley (20%) increased the UPP%, optimized the micro-structure of gluten, and improved its rheological properties by increasing dough viscoelasticity. The CSBs made from the composite flours exhibited a similar specific volume, cohesiveness, springiness and resilience to wheat CSB, while the firmness of composite CSBs (particularly JM-HLY-20) was delayed during storage. Importantly, the addition of highland barley increased the contents of TPC, TFC and ß-glucan, but decreased the in vitro starch digestibility of CSBs. A sensory evaluation showed that JM-HLY CSB was the most preferable. Taken together, highland barley can be used as a fine supplement to food products, with health-promoting properties.

Long non-coding RNA CERS6-AS1 facilitates the oncogenicity of pancreatic ductal adenocarcinoma by regulating the microRNA-15a-5p/FGFR1 axis.

The long non-coding RNA CERS6 antisense RNA 1 (CERS6-AS1) has critical regulatory roles in breast cancer progression. Here, we determined CERS6-AS1 expression in pancreatic ductal adenocarcinoma (PDAC) and the roles of CERS6-AS1 in PDAC carcinogenesis. The mechanisms underlying the regulatory actions of CERS6-AS1 in PDAC cells were elucidated in detail. CERS6-AS1 expression was evidently increased in PDAC tissues and cell lines. Patients with PDAC having high CERS6-AS1 expression had shorter overall survival periods than those having low CERS6-AS1 expression. Functionally, the knockdown of CERS6-AS1 attenuated the proliferation, migration, and invasion and stimulated apoptosis of PDAC cells in vitro. Additionally, CERS6-AS1 depletion decreased PDAC tumor growth in vivo. Mechanistically, CERS6-AS1 could competitively bind to microRNA-15a-5p (miR-15a-5p) and effectively work as a molecular sponge in PDAC cells, resulting in the upregulation of fibroblast growth factor receptor 1 (FGFR1), a direct target of miR-15a-5p. Rescue experiments revealed that miR-15a-5p downregulation or FGFR1 restoration rescued the effects of CERS6-AS1 knockdown on the behaviors of PDAC cells. In conclusion, CERS6-AS1 promoted the oncogenicity of PDAC by serving as a competing endogenous RNA to sequester miR-15a-5p and increase FGFR1 expression, which highlights the potential of the CERS6-AS1/miR-15a-5p/FGFR1 pathway as an effective target for cancer therapy.

Lysine demethylase 5B suppresses CC chemokine ligand 14 to promote progression of colorectal cancer through the Wnt/ß-catenin pathway.

AIMS: Epigenetic and genetic alterations are crucial events in the onset and progression of human cancers including colorectal cancer (CRC). This work aims to probe the relevance of lysine demethylase 5B (KDM5B) to the progression of CRC and the possible molecules involved. MATERIALS AND METHODS: KDM5B expression in CRC tissues and cells was determined. The association between KDM5B and the prognosis of patients was analyzed. Gain- and loss-of function studies of KDM5B were performed in HT-29 and KDM5B cells to explore the impact of KDM5B on cell behaviors. Expression of CC chemokine ligand 14 (CCL14) in CRC tissues and cells and its correlation with KDM5B were analyzed. Altered expression of CCL14 was introduced in CRC cells, and a Wnt/ß-catenin-specific antagonist KYA1797K was induced in cells as well. KEY FINDINGS: KDM5B was abundantly expressed while CCL14 was poorly expressed in CRC tissues and cells. High KDM5B expression was relevant to poor prognosis of patients. Downregulation of KDM5B suppressed proliferation and aggressiveness of HT-29 cells, and reduced the growth of xenograft tumors in mice, while upregulation of KDM5B in SW480 cells led to reverse results. KDM5B reduced CCL14 expression through demethylation modification of H3K4me3. Upregulation of CCL14 suppressed colony formation and invasiveness of CRC cells. KDM5B downregulated CCL14 to activate the Wnt/ß-catenin. Inhibition of ß-catenin by KYA1797K blocked the oncogenic roles of KDM5B in cells and in xenograft tumors. SIGNIFICANCE: This study suggested that KDM5B suppresses CCL14 through demethylation modification of H3K4me3, leading to activation of the Wnt/ß-catenin and the CRC progression.