Three patterns of sensitization to mugwort, timothy, birch and their major allergen components revealed by Latent class analysis.

BACKGROUND: Mugwort, timothy, and birch are commonly spread pollen allergens across China. Although several studies have described the rates of sensitization to mugwort, timothy, and birch in China, most of them just on specific whole-allergen extracts but little was known about the co-sensitization characteristics of its allergen components. This study aimed to explore the patterns of sensitization to mugwort, timothy, birch, and their major allergen components. METHOD: Serum specific IgE (sIgE) levels of allergen components of mugwort, timothy, birch, and cross-reactive carbohydrate determinants (CCD) were detected in 160 patients whose serum showed positive results to at least one of mugwort, timothy, and birch allergens via EUROBlotMaster system. Skin prick testing was utilized to assess the allergic reaction of grass, weed, and tree allergens. Latent class analysis was used to identify underlying patterns of sensitization to a series of allergen components and their corresponding extracts. RESULTS: 88.8% of patients with allergic rhinitis and/or asthma were positive for mugwort-sIgE, 30% for timothy-sIgE, and 32.5% for birch-sIgE. By using the LCA model, three sensitization patterns as "Mugwort, Art v 4, Bet v 2 and Phl p 12 co-sensitized", "Timothy, mugwort, and CCD co-sensitized", "Mugwort and Art v 1 co-sensitized" were revealed based on optimal statistical fit in this study. Compared with other clusters, participants in "Mugwort, Art v 4, Bet v 2 and Phl p 12 co-sensitized" pattern were associated with higher sensitization rates of common grass and tree pollens allergen. The spearman's coefficient between CCD and timothy was larger than the corresponding values of CCD with mugwort or birch. CONCLUSION: CCD and profilin, as minor allergens in pollens, were associated with other pollen sIgE false positives presumably due to cross-reactivity. Patients sensitized with profilin had a significantly higher risk of sensitization to other pollens.

Vitamin C suppresses toxicological effects in MO/MФ and IgM+ B cells of Nile tilapia (Oreochromis niloticus) upon copper exposure.

Copper (Cu), as an essential micronutrient in human and animal metabolism, easily spreads and excessively accumulates in rearing water, which make it more susceptible to fish farms and threatens the health of aquatic animals. In this issue, the protective effect of vitamin C against oxidative damage caused by copper exposure was studied in monocytes/macrophages (MO/MФ) and IgM+ B cells of Nile tilapia (Oreochromis niloticus), the cell types possessing phagocytic activities. The significant increase of ROS level and up-regulation of proinflammatory factors accompanied by depletion of GSH and down-regulation of antioxidative molecules in MO/MФ and IgM+ B cells, when stressed with CuO NPs or Cu ions, indicated the induction of oxidative damage due to the toxicological effects with copper exposure. Copper induced cell apoptosis through mitochondrial-dependent pathway in these two cell populations was demonstrated with disruption of mitochondrial membrane potential (ΔΨm) and activation of apoptosis factor. Furthermore, the phagocytic abilities for microspheres and bioparticle uptake significantly decreased in these two cell populations upon CuO NPs or Cu ions; meanwhile, antigen presentation of MO/MФ and antibody production of IgM+ B cells were also inhibited. However, vitamin C supplementation reversed all these biochemical indices, as well as cell apoptosis and phagocytic abilities in MO/MФ and IgM+ B cells that were induced by CuO NPs or Cu ions. In conclusion, these results revealed that vitamin C exerts cytoprotective effects against oxidative damage through its antioxidant properties and may be of therapeutic use in preventing toxicological effects caused by copper exposure.

Solasodine, Isolated from Solanum sisymbriifolium Fruits, Has a Potent Anti-Tumor Activity Against Pancreatic Cancer.

BACKGROUND: Increasing evidences have revealed that solasodine, isolated from Solanum sisymbriifolium fruits, has multiple functions such as anti-oxidant, anti-tumor and anti-infection. However, its role in pancreatic cancer has not been well studied. METHODS: To explore the role of solasodine in pancreatic cancer, human pancreatic cell lines including SW1990 and PANC1 were treated with different concentrations of solasodine for 48 h, and cell viability was evaluated by MTT assay, cell invasion and migration were evaluated by Transwell assay. The effect of solasodine on the apoptosis of SW1990 and PANC1 cells was detected by flow cytometry. To further explore the antitumor effect of solasodine in vivo, an SW1990 tumor-bearing mouse model was constructed. The effects of solasodine on cytokines in the serum of SW1990 tumor-bearing mice were also evaluated by ELISA assay. RESULTS: Specifically, in vitro, solasodine could significantly inhibit the proliferation of pancreatic cancer cell lines SW1990 and PANC1 cells. Flow cytometric analysis indicated that solasodine could induce apoptosis of SW1990 and PANC1 cells. Western blot assay indicated that solasodine could significantly inhibit the activation of Cox-2/Akt/GSK3ß signal pathway. Meanwhile, the release of Cytochrome c from mitochondria to cytoplasm which can raise the caspases cascade (C-caspase 3 and C-caspase 9) was significantly enhanced by solasodine. In vivo, the results showed that solasodine had potent anti-tumor activities with a lower cytotoxicity. In addition, the serum TNF-α, IL-2 and IFN-γ levels in SW1990 tumor-bearing mice after the treatment of solasodine was significantly increased. CONCLUSION: Taken together, our results suggested that the solasodine could prevent the progression of pancreatic cancer by inhibiting proliferation and promoting apoptosis, as well as stimulating immunity, suggesting that solasodine might be a potential therapeutic strategy for pancreatic cancer.

Active and intelligent gellan gum-based packaging films for controlling anthocyanins release and monitoring food freshness.

Active and intelligent packaging films with multiple functions including antioxidant, antibacterial and colorimetric pH indicator properties were developed by incorporating Clitoria ternatea (CT) extract into gellan gum (G) film. G enhanced the stability of CT anthocyanins and allowed the anthocyanins to release from G film in a pH-responsive behavior. Heat-treated soy protein isolate (HSPI) was able to interact with G and CT anthocyanins through the formation of electrostatic forces and covalent bonds. G film blended with HSPI greatly reduced the swelling capacity of G/HSPI composite film and controlled the anthocyanins release at pH greater than 6.0. The physical and mechanical properties of G films such as hydrophobicity, water vapor permeability, swelling capacity and tensile strength were also significantly modified by addition of HSPI to G films. The smart films changed their color with the increase of total volatile basic nitrogen (TVBN) values during progressive spoilage of shrimp, revealing their potential application for monitoring seafood freshness.

Dysregulated Kras/YY1/ZNF322A/Shh transcriptional axis enhances neo-angiogenesis to promote lung cancer progression.

Angiogenesis enhances cancer metastasis and progression, however, the roles of transcription regulation in angiogenesis are not fully defined. ZNF322A is an oncogenic zinc-finger transcription factor. Here, we demonstrate a new mechanism of Kras mutation-driven ZNF322A transcriptional activation and elucidate the interplay between ZNF322A and its upstream transcriptional regulators and downstream transcriptional targets in promoting neo-angiogenesis. Methods: Luciferase activity, RT-qPCR and ChIP-qPCR assays were used to examine transcription regulation in cell models. In vitro and in vivo angiogenesis assays were conducted. Immunohistochemistry, Kaplan-Meier method and multivariate Cox regression assays were performed to examine the clinical correlation in tumor specimens from lung cancer patients. Results: We validated that Yin Yang 1 (YY1) upregulated ZNF322A expression through targeting its promoter in the context of Kras mutation. Reconstitution experiments by knocking down YY1 under KrasG13V activation decreased KrasG13V-promoted cancer cell migration, proliferation and ZNF322A promoter activity. Knockdown of YY1 or ZNF322A attenuated angiogenesis in vitro and in vivo. Notably, we validated that ZNF322A upregulated the expression of sonic hedgehog (Shh) gene which encodes a secreted factor that activates pro-angiogenic responses in endothelial cells. Clinically, ZNF322A protein expression positively correlated with Shh and CD31, an endothelial cell marker, in 133 lung cancer patient samples determined using immunohistochemistry analysis. Notably, patients with concordantly high expression of ZNF322A, Shh and CD31 correlated with poor prognosis. Conclusions: These findings highlight the mechanism by which dysregulation of Kras/YY1/ZNF322/Shh transcriptional axis enhances neo-angiogenesis and cancer progression in lung cancer. Therapeutic strategies that target Kras/YY1/ZNF322A/Shh signaling axis may provide new insight on targeted therapy for lung cancer patients.

LncRNA-Malat1 is Involved in Lipotoxicity-Induced ß-cell Dysfunction and the Therapeutic Effect of Exendin-4 via Ptbp1.

Increasing evidence indicates that long noncoding RNAs (lncRNAs) have crucial roles in various biological processes. However, the contribution of lncRNAs to ß-cell dysfunction and their roles in diabetes therapeutics remain poorly understood. The aim of this study was to identify the lncRNAs dysregulated in diabetic islets and to explore the lncRNAs involved in ß-cell function as potential therapeutic targets. By using RNA sequencing and real-time PCR, we identified thousands of lncRNAs in the islets of db/db mice and db/m littermate mice. Among the differentially expressed lncRNAs, lncRNA-Malat1 (metastasis-associated lung adenocarcinoma transcript 1) was reduced in the islets of db/db mice and palmitate-treated MIN6 cells. The results of TUNEL, Western blot and flow cytometric analyses, and GSIS assays revealed that Malat1 knockdown significantly induced ß-cell apoptosis and inhibited insulin secretion. Mechanistically, RNA immunoprecipitation showed that Malat1 enhanced polypyrimidine tract-binding protein 1 (Ptbp1) protein stability by direct interaction, thereby adjusting the ratio of pyruvate kinase muscle (PKM) isoforms 1 and 2 (PKM1/PKM2). Moreover, luciferase assay and chromatin immunoprecipitation indicated that Malat1 was transcriptionally activated by pancreatic and duodenal homeobox 1 (Pdx1), through which exendin-4 alleviated lipotoxicity-induced ß-cell damage. In summary, our findings suggested the involvement of Malat1 in ß-cell dysfunction under diabetic conditions via the Malat1/Ptbp1/PKM2 pathway. In addition, exendin-4 ameliorated ß-cell impairment by Pdx1-mediated Malat1 upregulation. Hence, Malat1 may serve as a therapeutic target for the treatment of type 2 diabetes.

Smac is another pathway in the anti-tumour activity of Trichosanthin and reverses Trichosanthin resistance in CaSki cervical cancer cells.

Trichosanthin (TCS), or Tin Hua Fen, is a renowned traditional Chinese medicine and is still used in Chinese clinics for midterm abortion and the treatment of choriocarcinoma. Many studies have demonstrated that TCS has anti-tumour action as a type I ribosome-inactivating protein. We hypothesized that there is another pathway of the anti-tumour activity of TCS. cDNA array analysis was applied to profile changes in gene expression of human CaSki in response to TCS stimulation. Smac, a mitochondrial protein, was identified as the highly upregulated protein in response to TCS treatment. The mRNA and protein levels of Smac were determined by real-time RT-PCR and Western blotting respectively. We analysed the methylation status of Smac using methylation-specific PCR (MSP) and indicates that TCS promotes Smac demethylation and increases its expression in cervical CaSki cells. Tumour cells develop resistance to TCS during prolonged treatment, as with other classic chemotherapeutic agents. Smac expression was downregulated and Twist was upregulated in TCS-resistant cells. These results indicate that TCS has demethylating activity and that Smac is involved in both TCS response and TCS resistance.