DcR3-associated risk score: correlating better prognosis and enhanced predictive power in colorectal cancer.

Decoy receptor 3 (DcR3), a novel soluble protein belonging to the tumor necrosis factor receptor (TNFR) family, has been previously associated with tumorigenesis in various cancers. However, in our study, we unexpectedly found that DcR3 may promote patient survival time in colorectal cancer (CRC). Through an analysis of The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) datasets, we discovered that high levels of DcR3 are associated with improved overall survival (OS) and disease-free survival (DFS) in CRC patients. Further investigation revealed that DcR3 is correlated with favorable clinical features in Metastasis 0 (M0) and stage I/II CRC patients, suggesting it may act as a suppressive factor in CRC. Gene Set Enrichment Analysis (GSEA) demonstrated that the high DcR3 group is enriched in the IL-17 signaling pathway and other immune-related pathways, and Single Sample Gene Set Enrichment Analysis (ssGSEA) revealed a higher abundance of Tumor Infiltrating Lymphocytes (TIL) in the DcR3 high group. To better understand the function of DcR3, we constructed a DcR3-associated riskscore (DARS) model using machine learning, comprising three genes (DPP7, KDM3A, and TMEM86B). The DARS model indicated that high riskscore patients have an unfavorable prognosis, and it is associated with advanced stages (III/IV), T3/4 tumors, and N1/2 lymph node involvement. Additionally, high riskscore group exhibited more frequent gene mutations, such as TTN, MUC16, and SYNE1, with SYNE1 mutation being related to poor prognosis. Intriguingly, DcR3 showed higher expression in the low riskscore group. These results suggest that DcR3 could serve as a potential prognostic biomarker in CRC and may play a crucial role in favorably modulating the immune response in this malignancy.

Single-cell RNA reveals a tumorigenic microenvironment in the interface zone of human breast tumors.

BACKGROUND: The interface zone, area around invasive carcinoma, can be thought of as the actual tissue of the tumor microenvironment with precedent alterations for tumor invasion. However, the heterogeneity and characteristics of the microenvironment in the interface area have not yet been thoroughly explored. METHODS: For in vitro studies, single-cell RNA sequencing (scRNA-seq) was used to characterize the cells from the tumor zone, the normal zone and the interface zone with 5-mm-wide belts between the tumor invasion front and the normal zone. Through scRNA-seq data analysis, we compared the cell types and their transcriptional characteristics in the different zones. Pseudotime, cell-cell communication and pathway analysis were performed to characterize the zone-specific microenvironment. Cell proliferation, wound healing and clone formation experiments explored the function of differentially expressed gene BMPR1B, which were confirmed by tumor models in vivo. RESULTS: After screening, 88,548 high-quality cells were obtained and identified. Regulatory T cells, M2 macrophages, angiogenesis-related mast cells, stem cells with weak DNA repair ability, endothelial cells with angiogenic activity, fibroblasts with collagen synthesis and epithelial cells with proliferative activity form a unique tumorigenic microenvironment in the interface zone. Cell-cell communication analysis revealed that there are special ligand-receptor pairs between different cell types in the interface zone, which protects endothelial cell apoptosis and promotes epithelial cell proliferation and migration, compared to the normal zone. Compared with the normal zone, the highly expressed BMPR1B gene promotes the tumorigenic ability of cancer cells in the interface zone. CONCLUSIONS: Our work identified a unique tumorigenic microenvironment of the interface zone and allowed for deeper insights into the tumor microenvironment of breast cancer that will serve as a helpful resource for advancing breast cancer diagnosis and therapy.

Tumor necrosis factor-α induces proliferation and reduces apoptosis of colorectal cancer cells through STAT3 activation.

Tumor necrosis factor-alpha (TNF-α) is a potent pro-inflammatory factor that plays an important role in establishing a complicated connection between inflammation and cancer. TNF-α promotes tumor proliferation, migration, invasion, and angiogenesis according to numerous studies. Studies have shown the significant role of STAT3, a downstream transcription factor of another important inflammatory cytokine, IL-6 in the development and progression of different tumors especially colorectal cancer. In the present study, we investigated whether TNF-α has a role in proliferation and apoptosis of colorectal cancer cells through STAT3 activation. HCT116 cell line as human colorectal cancer cells was used in this study. Major assays were MTT assay, reverse transcription-PCR (RT-PCR), flow cytometric analysis, and ELISA. Results showed that TNF-α significantly increased the phosphorylation of STAT3 and expression of all the STAT3 target genes related to cell proliferation, survival, and metastasis compared with control. Moreover, our data showed that the STAT3 phosphorylation and expression of its target genes significantly were reduced in the presence of TNF-α + STA-21 compared with TNF-α-treated group demonstrating that the increase in genes expression partially was due to the TNF-α-induced STAT3 activation. On the other hand, STAT3 phosphorylation and mRNA levels of its target genes were partially decreased in the presence of TNF-α + IL-6R supporting the indirect pathway of STAT3 activation by TNF-α through inducing IL-6 production in cancer cells. Given the growing evidence for STAT3 as a key mediator of inflammation-induced colon cancer, our findings support further investigation of STAT3 inhibitors as potential cancer therapies.

Bifacial passivation towards efficient FAPbBr3-based inverted perovskite light-emitting diodes.

A unique technique to passivate both bottom and top sides of perovskite has been successfully developed to achieve highly efficient inverted perovskite light-emitting diodes (PeLEDs). For the bottom passivation, an organic/inorganic hybrid electron transporting layer (ETL) replaces the widely adopted inorganic ETL to overcome the disadvantages of the pure inorganic ETL. The ZPM (ZnO-in-polymer matrix) ETL, which consists of ZnO nanoparticles blended into polyvinylpyrrolidone, not only passivates the surface defects of ZnO nanoparticles, but also improves the morphology and stability of FAPbBr3 film. For the top passivation, smaller grains and a FAPbBr3/PEA2PbBr4 3D/2D hybrid structure are obtained by applying a small amount of PEABr solution. The synergetic interplay of organic/inorganic hybrid ETL and organic halide salt surface modification substantially shrinks the grain size to facilitate radiative recombination, and suppresses non-radiative recombination both at the interface of ETL/perovskite and HTL/perovskite, and in the perovskite layer. As a result, the highly efficient green PeLED sets a new record of device performance for FAPbBr3-based inverted PeLEDs, with current efficiency of 39.7 cd A-1, external quantum efficiency of 9.0%, power efficiency of 46.4 lm W-1, maximum luminance of 6.03 × 104 cd m-2, and half-lifetime of 297 minutes at an initial brightness of ∼100 cd m-2.

MicroRNA-769-5p Promotes The Growth Of Glioma Cells By Targeting Lysine Methyltransferase 2A.

BACKGROUND: Accumulating evidence supports the involvement of microRNAs (miRNAs) in the progression of human cancers including glioma. Recently, miR-769-5p has been reported to play a tumor suppressive role in colorectal cancer and lung cancer, whereas it exerts an oncogenic role in melanoma. However, the role of miR-769-5p and its related mechanism are poorly elucidated. METHODS: The levels of miR-769-5p in glioma tissues and adjacent non-tumor tissues were detected by qRT-PCR. In addition, the effects of miR-769-5p on cell proliferation and apoptosis were evaluated by CCK-8, EdU, colony formation and flow cytometric assays, respectively. Meanwhile, the dual-luciferase reporter assay was used to investigate the interaction of miR-769-5p and lysine methyltransferase 2A (KMT2A) in glioma. RESULTS: We found that miR-769-5p expression was strongly upregulated in glioma tissues and cell lines. Glioma tissues with high World Health Organization (WHO) grades had obvious higher levels of miR-769-5p compared to samples with low WHO grades. Interestingly, glioma patients highly expressing miR-769-5p showed prominent poorer survivals. Knockdown of miR-769-5p significantly suppressed cell proliferation and resulted in apoptosis in glioma cells. Additionally, miR-769-5p silencing restrained in vivo growth of glioma cells in mice. Interestingly, KMT2A was identified to be a direct target of miR-769-5p in glioma cells. The expression of KMT2A mRNA was downregulated in glioma tissues and inversely correlated with miR-769-5p level. KMT2A overexpression inhibited cell proliferation and induced the apoptosis of A172 cells. Moreover, siRNA-mediated KMT2A silencing could partially abolish miR-769-5p knockdown-induced suppressive effects on A172 cells. CONCLUSION: In summary, our findings suggest that targeting miR-769-5p/KMT2A axis may be a promising therapeutic target for glioma treatment.

Ku80 gene knockdown by the CRISPR/Cas9 technique affects the biological functions of human thyroid carcinoma cells.

In the present study, to evaluate the role of Ku80 in thyroid carcinoma (TC), 86 thyroid tissue samples from patients with a spectrum of thyroid disorders were examined for protein levels of Ku80, nuclear factor­κB (NF­κB) and RET/TC by immunohistochemistry. Furthermore, in TC cells, Ku80 mRNA was detected by reverse transcription­quantitative PCR analysis and silenced using the clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR­associated protein 9 (Cas9) technique to assess its role. An antibody array was used to identify Ku80­related regulatory genes. The protein levels of Ku80 in the TC tissues were significantly higher than those in non­neoplastic adjacent tissue samples (P<0.01). The activation of NF­kB and expression of RET/TC in the TC group were significantly increased (P<0.05) and were correlated with the protein expression of Ku80 (P<0.05). In papillary TC cells, the mRNA levels of Ku80 were high; Ku80 knockdown resulted in reductions in proliferation, invasion and colony formation, increased apoptosis, and reduced levels of proteins involved in MAPK signaling, cell proliferation and apoptosis. The high expression of Ku80 in TC was found to be associated with the expression of RET/TC and activation of NF­κB, and Ku80 knockdown decreased the malignancy of TC cells.

Effects of heating or ultrasound treatment on the enzymolysis and the structure characterization of hempseed protein isolates.

The effects of heating (90 °C/30 min) or ultrasound (200/400/600 W) treatment on antioxidant and angiotensin-converting enzyme inhibitory (ACEI) activity of hydrolysates from hempseed protein isolates (HPI) were studied. The secondary structure, surface hydrophobicity, intrinsic fluorescence, scanning electron microscopy (SEM) and sodium dodecyl sulfate-polyacrylamide gel electrophoresis of HPI treated by heating or ultrasound were measured. The results showed that hydrolysate from HPI treated with ultrasound at 200 W showed higher hydrolysis degree, proportion of lower molecular mass components (1.0-3.0 kDa), antioxidant and ACEI activity than those from heating or high-power treated. The changes in secondary structure, surface hydrophobicity and intrinsic fluorescence indicated the unfolding of HPI after ultrasound. The SEM results showed that HPI treated with ultrasound at 200 W exhibited decrease in particle size and deformation and further increased in power caused the aggregates of HPI. In conclusion, the ultrasound treatment at low-power was superior to 90 °C/30 min treatment in facilitating enzymatic release of antioxidant and ACEI peptides from HPI.

All-Solution-Processed Pure Formamidinium-Based Perovskite Light-Emitting Diodes.

All-solution-processed pure formamidinium-based perovskite light-emitting diodes (PeLEDs) with record performance are successfully realized. It is found that the FAPbBr3 device is hole dominant. To achieve charge carrier balance, on the anode side, PEDOT:PSS 8000 is employed as the hole injection layer, replacing PEDOT:PSS 4083 to suppress the hole current. On the cathode side, the solution-processed ZnO nanoparticle (NP) is used as the electron injection layer in regular PeLEDs to improve the electron current. With the smallest ZnO NPs (2.9 nm) as electron injection layer (EIL), the solution-processed PeLED exhibits a highest forward viewing power efficiency of 22.3 lm W-1 , a peak current efficiency of 21.3 cd A-1 , and an external quantum efficiency of 4.66%. The maximum brightness reaches a record 1.09 × 105 cd m-2 . A record lifetime T50 of 436 s is achieved at the initial brightness of 10 000 cd m-2 . Not only do PEDOT:PSS 8000 HIL and ZnO NPs EIL modulate the injected charge carriers to reach charge balance, but also they prevent the exciton quenching at the interface between the charge injection layer and the light emission layer. The subbandgap turn-on voltage is attributed to Auger-assisted energy up-conversion process.

Knockdown of POLE2 expression suppresses lung adenocarcinoma cell malignant phenotypes in vitro.

In the present study, we profiled ß­elemene­regulated gene expression and investigated the effects of the silencing of the DNA polymerase epsilon 2, accessory subunit (POLE2) in lung cancer cells. Differently expressed genes were profiled in A549 cells incubated in the presence or absence of ß­elemene by Affymetrix Human Gene Expression Array. POLE2 shRNA was then constructed to knock down POLE2 expression. Cells were counted and phenotypes were assessed via CCK­8, colony formation and caspase-3/-7 activity assays. PathScan antibody array analysis was used to identify shPOLE2­regulated genes. The cDNA microarray identified a total of 721 differentially expressed genes in the A549 cells. Furthermore, knockdown of POLE2 expression inhibited A549 and NCI­H1299 cell proliferation and apoptosis. The PathScan data indicated that expression levels of p­Akt (phosphorylated­protein kinase B, p­AKT/p­PKB), p­Smad2 (phosphorylated mothers against decapentaplegic homolog 2), p­p38 MAPK (phosphorylated mitogen­activated protein kinases p38), p­SAPK/JNK (phosphorylated c­Jun N­terminal protein kinase/stress activated protein kinase), cleaved caspase­7, IκBα (nuclear factor of κ light polypeptide gene enhancer in B­cell inhibitor, α), p­Chk1 (phosphorylated checkpoint kinase 1), p­IκBα, p­eIF2α (phosphorylated eukayotic translational initiation factor 2α), p­TAK1 (phosphorylated TGF­B­activated kinase 1), survivin and α­tubulin were significantly lower in shPOLE2 cells than these levels in the shCtrl cells. The PathScan data indicated that the expression levels of p­p53 (phosphorylated tumor protein 53) were significantly higher in the shPOLE2 cells than these levels in the shCtrl cells. ß­elemene can restrain human lung cancer A549 and NCI­H1299 cell proliferation and apoptosis by suppressing POLE2 expression.

A robust tissue laser platform for analysis of formalin-fixed paraffin-embedded biopsies.

Laser emission-based detection and imaging technology has attracted significant interest in biomedical research due to its high sensitivity, narrow linewidth, and superior spectral and spatial resolution. Recent advances have further revealed the potential to use laser emission to investigate chromatin dynamics, as well as to diagnose cancer tissues based on nuclear biomarkers. To move the laser emission based detection technology a step further towards practical use, in this work, we developed a highly robust tissue laser platform by microfabricating an SU8 spacer with a fixed height on the top mirror of the Fabry-Pérot (FP) cavity, which allows generation of reproducible and stable lasing results regardless of tissue thickness. Then we applied this platform to achieve lasing emission from formalin-fixed, paraffin-embedded (FFPE) lung tissues, which account for an overwhelming fraction of tissues collected for research and clinical use worldwide. We further showed that the cancer and normal FFPE lung tissues can be distinguished by their respective lasing thresholds. Two different tissue thicknesses (10 µm and 5 µm) commonly used in pathological labs were explored. Finally, we tested three additional types of tissues (colon, stomach, and breast) that were prepared independently by lab technicians in a pathology lab in China and shipped to the US in order to validate the general applicability and practicality of the laser emission-based technology as well as the corresponding sample preparation protocol and the tissue laser platform. Our work will not only vastly broaden the applications of laser emission-based detection/imaging technology but also help translate it from the laboratory to an automated system for clinical practice that may eventually benefit biomedicine and biological research.

Highly Efficient All-Solution Processed Inverted Quantum Dots Based Light Emitting Diodes.

In all-solution processed inverted quantum dots based light emitting diodes (QLEDs), the solvent erosion on the quantum dot (QD) layer prevents devices from reaching high performance. By employing an orthogonal solvent 1,4-dioxane for the hole transport layer (HTL) poly(9-vinlycarbazole) (PVK), the external quantum efficiencies (EQE) of red QLED is increased 4-fold, while the luminous efficiencies (LE) of blue QLED is enhanced by 25 times, compared to the previous devices' record. To further improve the device efficiency and reduce the efficiency roll-off, solution processed PVK/poly [(9,9-dioctylfluorenyl-2,7-diyl)-co-(4,4'-(N-(p-butylphenyl))diphenylamine)] (TFB) double-layer HTL is introduced to facilitate hole injection with stepwise energy level. By reducing the hole injection barrier, the turn-on voltage of QLEDs decreases from 3.4 to 2.7 V for red, from 5.1 to 2.7 V for green, and from 5.3 to 4.1 V for blue. The peak LE reach 22.1 cd/A, 21.4 cd/A, and 1.99 cd/A, while the maximum EQE reach 12.7%, 5.29%, and 5.99%, for red, green, and blue QLEDs, respectively. To the best of our knowledge, the red and blue QLEDs exhibit the best device performance among all the all-solution processed inverted QLEDs. In addition, the blue QLED is the champion among all the inverted QLEDs, including the devices fabricated by thermal evaporation.

Suppression of SIRT6 by miR-33a facilitates tumor growth of glioma through apoptosis and oxidative stress resistance.

microRNA-33a (miR-33a) belongs to the miR-33 family that is implicated in the progression of various types of cancers. Aberrant expression of miR-33a has been detected in several human cancers, and has been shown to regulate the migration and invasion as well as proliferation and apoptosis of tumor cells. However, the clinical significance and precise mechanisms underlying the dysfunction of miR-33a in glioma have not been well investigated in previous studies. In this study, overexpression of miR-33a was observed in clinical glioma specimens and cell lines. Clinicopathological detection revealed that miR-33a highly expressing patients showed large tumor sized and advanced World Health Organization (WHO) grade as well as reduced overall survival. Furthermore, the results of in vitro experiments confirmed that loss of miR-33a resulted in reduced proliferation and enhanced apoptosis in U251 cells, while miR-33a restoration showed opposite effects in U87 cells. Further studies indicated that miR-33a knockdown restrained tumor growth of glioma in vivo. miR-33a negatively regulated the expression of sirtuin 6 (SIRT6) at both mRNA and protein levels via targeting the 3'UTR of SIRT6 mRNA. SIRT6 was underexpressed and inversely correlated with miR-33a expression in the glioma tissues. Mechanistically, SIRT6 overexpression increased the levels of lactate dehydrogenase (LDH) and reactive oxygen species (ROS) while it reduced cell survival under H2O2 treatment. In addition, SIRT6 restoration led to apoptosis with alterative expression of Bax, Bcl-2, cleaved caspase-8, and inhibition of Janus kinase 2 (JAK2)/signal transducer and activator of transcription 3 (STAT3) pathway in glioma. Thus, our studies demonstrated that the deregulation of miR-33a may promote tumor development in human glioma by regulating the expression of its target gene, SIRT6.

Neuroglobin functions as a prognostic marker and promotes the tumor growth of glioma via suppressing apoptosis.

Neuroglobin (Ngb) has been reported to be upregulated by hypoxia and plays an anti-apoptotic function. Previous studies have reported that Ngb is expressed in human glioblastoma cells and up-regulated in hypoxic microregions of glioblastoma tumor xenografts. While, the clinical significance of Ngb and its function in human glioma keep unknown. Ngb expression was analyzed in 86 glioma tissues and 20 normal brain tissues. Results showed that Ngb was significantly overexpressed in glioma tissues compared to normal brain tissues. In addition, increased levels of Ngb also observed in glioma cell lines. Clinicopathological analysis verified that the positive expression of Ngb was associated with histological type and world health organization (WHO) grade of glioma. Moreover, Kaplan-Meier analysis found that Ngb overexpression led to a shorter survival. Multivariate Cox regression analysis demonstrated that Ngb expression was an independent prognostic marker. Further experiments illustrated that Ngb knockdown significantly inhibited proliferation and facilitated apoptosis in U251 cells. In vivo experiments further confirmed that Ngb silencing notably prohibited the tumor growth of glioma in nude mice. While, Ngb overexpression prominently promoted proliferation and suppressed apoptosis in U87 cells. Taken together, this work support the first evidence that Ngb can be potentially used as a promising biomarker and target for novel treatment of human glioma.

Safflower polysaccharide induces NSCLC cell apoptosis by inhibition of the Akt pathway.

Lung cancer is the leading cause of cancer death in the world. Safflower polysaccharide (SPS) has been used for the improvement of immunomodulatory activities and treatment of cancers. However, studies on the effect of SPS on the progression of lung cancer have rarely been reported. To study the antitumor effect of SPS on human lung cancer and its potential mechanism, non-small cell lung cancer cell lines (NSCLC), A549 and YTMLC-90 were treated with SPS at various concentrations ranging from 0.04 to 2.56 mg/ml and BALB/c nude tumor-bearing mice were injected intraperitoneally with SPS at concentrations ranging from 15 to 135 mg/kg. Results showed that SPS suppressed the proliferation of A549 and YTMLC-90 cells and induced apoptosis by increasing mRNA levels of bax and caspase-3, and inhibited tumor growth in vivo. SPS induced cell cycle arrest in the G2/M phase by decreasing the expression of cdc25B and cyclin B1. Moreover, SPS decreased the expression of Akt, p-Akt and PI3K. In mice, SPS injection enhanced immunomodulatory activities by increasing levels of TNF-α and IL-6 in tumor-bearing mice. Our findings suggest that SPS suppresses tumor growth by enhancing immunomodulatory activities and blocking the PI3K/Akt pathway. This study provides new insight into the anticancer mechanism of SPS.

Exosomes-Derived MiR-302b Suppresses Lung Cancer Cell Proliferation and Migration via TGFßRII Inhibition.

BACKGROUND/AIMS: Several studies have reported that tumor-derived exosomes contain kinds of miRNAs, including oncogenic miRNAs and tumor suppressor miRNAs. It has been reported that miR-302b could inhibit cancer progression by targeting oncogenes post-transcriptionally. Whether miR-302b is involved in the regulation of tumor-derived exosomes on lung cancer cells proliferation has not yet been demonstrated. This study aimed to examine the effect of exosomes-derived miR-302b on lung cancer cells proliferation and explain the potential mechanism. METHODS: The effect of exosomes derived from 95C cells and 95D cells with different metastatic ability on lung cancer cell proliferation and migration were analyzed by MTT assay and Transwell assays, respectively. Exosomes of 95C and 95D cells derived miR-302b was quantified by qRT-PCR, the effect of miR-302b on proliferation and migration of 95D cells was analyzed by MTT assays and Transwell assays respectively after transfection with miR-302b, while the expression of phosphorylated ERK1/2, MMP9 and TGFßRx2161; was analyzed by Western blot. The target gene of miRNA-302b was analyzed by Luciferase reporter assays. RESULTS: 95C-derived exosomes significantly decreased the migration ability of 95D cells. miRNA-302b was significantly overexpressed in 95C cells and 95C-derived exosomes compared with 95D cells and 95D-derived exosomes. Transfection of miR-302b into 95D cells significantly suppressed cells proliferation and migration capabilities along with the down-regulated expression of TGFßRII, phosphorylated ERK1/2 and MMP9 induced by TGF-ß1. CONCLUSIONS: Exosomes-derived miR-302b could suppress lung cancer cell proliferation and migration via the TGFßRII/ERK pathway and thus provides a potential target for human lung cancer therapy.

Identification of a novel miRNA from the ovine ovary by a combinatorial approach of bioinformatics and experiments.

MicroRNAs (miRNAs) are a class of short endogenous, single-stranded, non-coding small RNA molecules, about 19-25 nucleotides in length that regulate gene expression at the translation level and influence many physiological process, such apoptosis, metabolism, signal transduction, and occurrence and development of diseases. In this study, we constructed a library from the ovine luteal phase ovary by using next-generation sequencing technology (Solexa high-throughput sequencing technique) and identified 267 novel miRNAs by bioinformatics. One of the novel miRNAs (ovis_aries_ovary-m0033_3p), which expressed in the sheep ovary and testis, was confirmed by real time PCR and northern blot. Ovis_aries_ovary-m0033_3p was 21 nucleotides in length and located on chromosome 12, and it had 100% similarity to hsa-miR-214-3p, mmu-miR-214-3p, dre-miR-214and ssc-miR-214. Meanwhile, the pre-miRNA was 82 nucleotides in length and had a standard hairpin stem-loop structure. From the consistency of the sequence and structure, we speculated that ovis_aries_ovary-m0033_3p had a function similar to hsa-miR-214-3p, which is involved in the fine regulation of cell survival, embryonic development, breeding activities and resistance to ovarian cancer, so we defined it as oar-miR-214-3p. These experimental results will enrich the miRNA database for ovis aries and provide the basis for researching the regulation mechanism of miRNA in relation to breeding activities of seasonal breeding animals.

[Advance in studies on food allergy mechanism based on gut barrier].

Food allergies, as a type of adverse immune-mediated reactions to ingested food proteins, have become a serious public health issue that harms children and adults health, with increasing incidence year by year. However, without effective therapy for food allergies, doctors-have mostly advised to avoid allergens and provided symptomatic treatment. According to the findings of many studies, allergic diseases are correlated with intestinal barrier function injury, as evidenced by the significant increase in the intestinal permeability among patients with food allergies. In this paper, recent studies on correlations between food allergies and intestinal barrier functions, intestinal barrier function injury mechanisms of allergic foods and food allergy intervention strategies based on intestinal barrier functions were summarized to provide reference for laboratory researches and clinical treatment of food allergic diseases.

[Intervention effect and mechanism of compound Ginkgo biloba preparations on nonalcoholic fatty liver].

OBJECTIVE: To investigate the intervention effect and mechanism of compound Ginkgo biloba (CGB) preparations on nonalcoholic fatty liver disease (NAFLD). METHOD: The C57BL/6 mouse NAFLD model was induced with high fat diets. Since the 2nd week after modeling, the mice were orally administered with 600 and 200 mg x kg(-1) x d(-1) CGB for eight weeks. The levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), triglyceride (TG), cholesterol (CHOL) and LPS in serum, as well as pathological changes and expression of tumor necrosis factor-alpha (TNF-alpha) in hepatic tissues were observed. Changes in intestinal tight junction proteins ZO-1, Occludin, Claudin-1 in intestinal tissues were determined under microscopy. RESULT: Compared with the normal group, the model group showed obvious fatty degeneration in rat livers, with notable increase in TNF-alpha expression (P < 0.01), significant increases in ALT, AST, TG, CHOL and LPS in serum (P < 0.01, P < 0.05), injury in intestinal tight junction proteins, and remarkable declines in ZO-1, Occludin and Claudin-1 (P < 0.01). Compared with the model group, CGB high and low dose groups showed obvious relieves in fatty degeneration in rat livers and injury in intestinal tight junction proteins, significant reductions in TNF-alpha expression (P < 0.01, P < 0.05) and AST, TG, CHOL and LPS in serum (P < 0.01, P < 0.05) and remarkable increases in ZO-1 and Occludin expressions (P < 0.05). CONCLUSION: CGB can protect intestinal tight junction proteins, reduce intestinal leakage, relieve fatty degeneration and inflammations in livers and prevent NAFLD occurrence and development.

Effects of compound Ginkgo biloba on intestinal permeability in rats with alcohol-induced liver injury.

This study aimed to investigate the effects of Compound Ginkgo biloba (CGB) on alterations in intestinal permeability and inflammation caused by endotoxin in chronic alcohol-induced liver injury. CGB was prepared by Ginkgo biloba extract and Rosa roxburghii in a 1 : 1 proportion. Rats were divided into four groups: control, ethanol, high-dosage CGB (0.6 g kg(-1) d(-1)) and low-dosage CGB (0.2 g kg(-1) d(-1)) group. Rats in the control group ingested a Lieber-DeCarli control liquid diet, while rats in the ethanol and CGB-treated groups ingested a Lieber-DeCarli alcohol liquid diet for eight weeks. CGB was orally administered from the beginning of the third week until the end of the experiment. CGB was observed to significantly reduce the activities of serum ALT, AST, diamine oxidase (DAO) as well as levels of serum TG, D-lactic acid and plasma endotoxin in rats fed with Lieber-DeCarli ethanol liquid. Further, the hepatic steatosis was improved and the damage to intestinal tight junctions was also relieved effectively after CGB administration. Moreover, CGB significantly downregulated the expressions of TNF-α, lipopolysaccharide binding protein (LBP), CD14 and TLR4 in the liver and upregulated the expressions of tight junction proteins including ZO-1, occludin and claudin-1. In summary, this study demonstrated that CGB alleviated alcohol-induced liver injury and hepatic lipopolysaccharide signaling as well as gut barrier dysfunction through restoring tight junctions.

Development of Gut Microbiota in a Mouse Model of Ovalbumin-induced Allergic Diarrhea under Sub-barrier System.

This study aimed to present a mouse model of ovalbumin (OVA) induced allergic diarrhea under a sub-barrier system and investigate the development of gut microbiota in this model. Male BALB/c mice were systemically sensitized with OVA or sham-sensitized with saline, and followed by oral OVA intubation, leading to OVA-specific acute diarrhea. Compared with sham-sensitized mice, sera OVA-specific IgG1 and total IgE in OVA-sensitized mice were dramatically elevated, and the number of mast cells was greatly increased in the jejunum of the OVA-sensitized mice. Principle component analysis of the DGGE profile showed that samples from group of OVA-sensitized mice and group of sham-sensitized mice were scattered into two different regions. Real-time PCR analysis showed that the number of 16S rRNA gene copies of Lactobacillus in the colon of OVA-sensitized mice decreased significantly, while there was no significant difference in the number of Bifidobacterium and total bacteria. In conclusion, OVA-specific allergic diarrhea was successfully induced under a sub-barrier system, and changes of allergic reactions during induction was coupled with changes in gut microbiota, especially the number of colonic Lactobacillus, but the role of gut microbiota in the development of food allergic reactions needs to be further evaluated.