Extracellular adenosine triphosphate skews the T helper cell balance and enhances neutrophil activation in mice with food allergies.

Exposure to food allergens elicits fast changes in the intestinal microenvironment, which guides the development of allergic reactions. Investigating the key information about these changes may help in better understanding food allergies. In this research, we explored the relationship between a food allergy and extracellular adenosine triphosphate (ATP), a danger molecule that has been proved to regulate the onset of allergic asthma and dermatitis but has not been studied in food allergies, by developing a unique animal model through allergen-containing diet feeding. After consuming an allergen-containing diet for 7 days, the allergic mice exhibited severe enteritis with elevated luminal ATP levels. The dysregulated luminal ATP worsened food-induced enteritis by enhancing Th17 cell responses and increasing mucosal neutrophil accumulation. In vitro experiments demonstrated that ATP intervention facilitated Th17 cell differentiation and neutrophil activation. In addition, the diet-induced allergy showed noticeable gut dysbiosis, characterized by decreased microbial diversity and increased diet-specific microbiota signatures. As the first, we show that food-induced enteritis is associated with an elevated concentration of luminal ATP. The dysregulated extracellular ATP exacerbated the enteritis of mice to a food challenge by manipulating intestinal Th17 cells and neutrophils.

Novel Perspective on the Regulation of Offspring Food Allergy by Maternal Diet and Nutrients.

There has been a dramatic surge in the prevalence of food allergy (FA) that cannot be explained solely by genetics, identifying mechanisms of sensitization that are driven by environmental factors has become increasingly important. Diet, gut microbiota, and their metabolites have been shown to play an important role in the development of FA. In this review, we discuss the latest epidemiological evidence on the impact of two major dietary patterns and key nutrients in early life on the risk of offspring developing FA. The Western diet typically includes high sugar and high fat, which may affect the immune system of offspring and increase susceptibility to FA. In contrast, the Mediterranean diet is rich in fiber, which may reduce the risk of FA in offspring. Furthermore, we explore the potential mechanisms by which maternal dietary nutrients during a window of opportunity (pregnancy, birth, and lactation) influences the susceptibility of offspring to FA through multi-interface crosstalk. Finally, we discuss the limitations and gaps in the available evidence regarding the relationship between maternal dietary nutrients and the risk of FA in offspring. This review provides novel perspective on the regulation of offspring FA by maternal diet and nutrients.

Natural variations of chlorophyll fluorescence and ion transporter genes influenced the differential response of japonica rice germplasm with different salt tolerances.

Soil salinity seriously restricts rice growth, development, and production globally. Chlorophyll fluorescence and ion content reflect the level of injury and resistance of rice under salt stress. To understand the differences in the response mechanisms of japonica rice with varying degrees of salt tolerance, we analyzed the chlorophyll fluorescence characteristics and ion homeostasis of 12 japonica rice germplasm accessions by comprehensive evaluation of phenotype, haplotype, and expression of salt tolerance-related genes. The results revealed that salt-sensitive accessions were rapidly affected by the damage due to salinity. Salt tolerance score (STS) and relative chlorophyll relative content (RSPAD) were extremely significantly reduced (p<0.01), and chlorophyll fluorescence and ion homeostasis were influenced by various degrees under salt stress. The STS, RSPAD, and five chlorophyll fluorescence parameters of salt-tolerant accessions (STA) were significantly higher than that of salt-sensitive accessions (SSA). Principal component analysis (PCA) with 13 indices suggested three principal components (PCs), with a cumulative contribution rate of 90.254%, which were used to screen Huangluo (typical salt-tolerant germplasm) and Shanfuliya (typical salt-sensitive germplasm) based on the comprehensive evaluation D-value (DCI ). The expression characteristics of chlorophyll fluorescence genes (OsABCI7 and OsHCF222) and ion transporter protein genes (OsHKT1;5, OsHKT2;1, OsHAK21, OsAKT2, OsNHX1, and OsSOS1) were analyzed. The expressions of these genes were higher in Huangluo than in Shanfuliya under salt stress. Haplotype analysis revealed four key variations associated with salt tolerance, including an SNP (+1605 bp) within OsABCI7 exon, an SSR (-1231 bp) within OsHAK21 promoter, an indel site at OsNHX1 promoter (-822 bp), and an SNP (-1866 bp) within OsAKT2 promoter. Variation in OsABCI7 protein structure and differential expression of these three ion-transporter genes may contribute to the differential response of japonica rice to salt stress.

Rs11479 in Thymidine Phosphorylase Associated with Prognosis of Patients with Colorectal Cancer Who Received Capecitabine-Based Adjuvant Chemotherapy.

Objective: Thymidine Phosphorylase (TYMP) gene was of potential significance in the process of colorectal cancer (CRC) development and played an important role in capecitabine metabolism. This study was to identify the association between TYMP polymorphism and prognosis of postoperative patients with CRC who received capecitabine-based adjuvant chemotherapy. Methods: A total of 218 patients with CRC who were treated with surgical resection and capecitabine-based adjuvant chemotherapy were included in this study retrospectively. Peripheral blood and peripheral blood mononuclear cell (PBMC) specimen of the patients were collected for the genotyping of TYMP polymorphism and TYMP mRNA expression, respectively. Univariate analysis of genotypes and prognosis was carried out by Kaplan-Meier survival analysis, Cox regression analysis was adopted in multivariate analysis. The mRNA expression of TYMP according to genotype status was analyzed using non-parameter test. Results: Prevalence of rs11479 in TYMP among the 218 patients exhibited that minor allele frequency of rs11479 was 0.20 (GG 141 cases, GA 68 cases and AA 9 cases), which was in accordance with Hardy-Weinberg equilibrium (P=0.825). Association analysis suggested that the median disease-free survival (DFS) of patients with GG genotype and GA/AA genotype was 3.1 and 6.1 years, respectively (P=0.004). Furthermore, the median overall survival of patients with GG genotype and GA/AA genotype was 5.0 and 7.0 years, respectively (P=0.033). Multivariate Cox regression analysis exhibited that rs11479 polymorphism was an independent factor for DFS (HR = 1.64, P=0.009). Additionally, of the 65 PBMC specimens, mRNA expression results indicated that patients with GA/AA genotypes conferred significantly higher mRNA expression of TYMP than that of patients with GG genotype (P<0.001). Conclusion: Polymorphism rs11479 in TYMP gene might predict the prognosis of patients with CRC who received capecitabine-based adjuvant chemotherapy through mediation of the mRNA expression of TYMP. The conclusion of this study should be validated in prospective clinical trials subsequently.

Advanced Fabrication and Multi-Properties of Aluminum-Based Aerogels from Aluminum Waste for Thermal Insulation and Oil Absorption Applications.

Metal-based aerogels have attracted numerous studies due to their unique physical, structural, thermal, and chemical properties. Utilizing aluminum waste, a novel, facile, environmentally friendly approach to aluminum-based aerogels is proposed. In this work, the aluminum-based aerogels produced do not use toxic chemicals unlike conventional aerogel production. Aluminum powder, with poly(acrylic acid) and carboxymethyl cellulose as binders, is converted into aluminum-based aerogels using the freeze-drying method. The aluminum-based aerogels have low density (0.08-0.12 g/cm3) and high porosity (93.83-95.68%). The thermal conductivity of the aerogels obtained is very low (0.038-0.045 W/m·K), comparable to other types of aerogels and commercial heat insulation materials. Additionally, the aerogels can withstand temperatures up to 1000 °C with less than 40% decomposition. The aerogels exhibited promising oil absorption properties with their absorption capacity of 9.8 g/g and 0.784 g/cm3. The Young's modulus of the aerogels ranged from 70.6 kPa to 330.2 kPa. This study suggests that aluminum-based aerogels have potential in thermal insulation and oil absorption applications.

Effects of three processing technologies on the structure and immunoreactivity of α-tropomyosin from Haliotis discus hannai.

The subunit of tropomyosin (α-TM) from Haliotis discus hannai is an important allergen. The methods to reduce the immunoreactivity of α-TM are worth investigating. Thus, this study confirmed the reacted conditions of α-TM with transglutaminase (TG)-catalyzed cross-linking reaction, TG-catalyzed glycosylation, and glycation. Three processing technologies reduced significantly the contents of α-helix and hydrophobic force of α-TM and increased the surface hydrophobicity. A serological experiment confirmed that the glycated α-TM with xylose showed the lowest IgG/IgE-binding capacity. The inhabitation dot blot displayed that five epitope peptides could bind with the site-specific IgE prepared by the glycated α-TM. Three in nine glycated sites (M68, N202, and N203) were verified to modify-two epitopes (L-HTM-3 and L-HTM-7) of α-TM, which affected the immunoreactivity of α-TM during glycation. These results indicated that glycation would be desired for developing hypo-allergenic abalone products.

Effect of body mass index on surgical site wound infection, mortality, and postoperative hospital stay in subjects undergoing possibly curative surgery for colorectal cancer: A meta-analysis.

We performed a meta-analysis to evaluate the effect of body mass index on surgical site wound infection, mortality, and postoperative hospital stay in subjects undergoing possibly curative surgery for colorectal cancer. A systematic literature search up to March 2022 was performed and 2247 subjects with possibly curative surgery for colorectal cancer at the baseline of the studies; 2889 of them were obese, and 9358 were non-obese. Odds ratio (OR) and mean difference (MD) with 95% confidence intervals (CIs) were calculated to assess the effect of body mass index on surgical site wound infection, mortality, and postoperative hospital stay in subjects undergoing possibly curative surgery for colorectal cancer using the dichotomous or contentious methods with a random or fixed-effect model. The obese subjects had a significantly higher surgical site wound infection after colorectal surgery (OR, 1.87; 95% CI, 1.62-2.15, P < .001), and higher mortality (OR, 1.58; 95% CI, 1.07-2.32, P = .02) in subjects with possibly curative surgery for colorectal cancer compared with non-obese. However, obese did not show any significant difference in postoperative hospital stay (MD, 0.81; 95% CI, -0.030 to 1.92, P = .15) compared with non-obese in subjects with possibly curative surgery for colorectal cancer. The obese subjects had a significantly higher surgical site wound infection after colorectal surgery, higher mortality, and no significant difference in postoperative hospital stay compared with non-obese in subjects with possibly curative surgery for colorectal cancer. The analysis of outcomes should be with caution because of the low number of studies in certain comparisons.

Novel perspective on the regulation of food allergy by probiotic: The potential of its structural components.

Food allergy (FA) is a global public health issue with growing prevalence. Increasing evidence supports the strong correlation between intestinal microbiota dysbiosis and food allergies. Probiotic intervention as a microbiota-based therapy could alleviate FA effectively. In addition to improving the intestinal microbiota disturbance and affecting microbial metabolites to regulate immune system, immune responses induced by the recognition of pattern recognition receptors to probiotic components may also be one of the mechanisms of probiotics protecting against FA. In this review, it is highlighted in detail about the regulatory effects on the immune system and anti-allergic potential of probiotic components including the flagellin, pili, peptidoglycan, lipoteichoic acid, exopolysaccharides, surface (S)-layer proteins and DNA. Probiotic components could enhance the function of intestinal epithelial barrier as well as regulate the balance of cytokines and T helper (Th) 1/Th2/regulatory T cell (Treg) responses. These evidences suggest that probiotic components could be used as nutritional or therapeutic agents for maintaining immune homeostasis to prevent FA, which will contribute to providing new insights into the resolution of FA and better guidance for the development of probiotic products.

Protein Phosphatase PPM1B Inhibits Gastric Cancer Progression and Serves as a Favorable Prognostic Biomarker.

BACKGROUND: Protein phosphatase PPM1B, also named as PP2Cß, is a member of serine/threonine phosphatase family. Dysregulated expression of PPM1B has been reported in several malignancies; nevertheless, its role in gastric cancer remains unknown. Here, we aimed to initially investigate the expression and function of PPM1B in gastric adenocarcinoma. METHODS: We firstly evaluated the protein expression of PPM1B in our enrolled retrospective cohort (n=161) via immunohistochemistry staining. Univariate and multivariate analyses were conducted to assess its prognostic value. Cellular experiments and xenografts in mice model were also performed to validate the role of PPM1B in gastric adenocarcinoma progression. RESULTS: The advanced tumor stage was characterized with a lower PPM1B level. Lower PPM1B was associated with poor prognosis in both The Cancer Genome Atlas (TCGA) dataset and our cohort (P<0.05). Furthermore, Cox regression analysis demonstrated that PPM1B was a novel independent prognostic factor for gastric adenocarcinoma patients (hazard ratio=0.35, P=0.001). Finally, cellular and xenografts data confirmed that overexpressing PPM1B can remarkably attenuated gastric adenocarcinoma growth. CONCLUSION: Low expression of PPM1B may be a potential molecular marker for poor prognosis in gastric adenocarcinoma.

Reduction in Allergenicity and Induction of Oral Tolerance of Glycated Tropomyosin from Crab.

Tropomyosin (TM) is an important crustacean (Scylla paramamosain) allergen. This study aimed to assess Maillard-reacted TM (TM-G) induction of allergenic responses with cell and mouse models. We analyzed the difference of sensitization and the ability to induce immune tolerance between TM and TM-G by in vitro and in vivo models, then we compared the relationship between glycation sites of TM-G and epitopes of TM. In the in vitro assay, we discovered that the sensitization of TM-G was lower than TM, and the ability to stimulate mast cell degranulation decreased from 55.07 ± 4.23% to 27.86 ± 3.21%. In the serum of sensitized Balb/c mice, the level of specific IgE produced by TM-G sensitized mice was significantly lower than TM, and the levels of interleukins 4 and interleukins 13 produced by Th2 cells in spleen lymphocytes decreased by 82.35 ± 5.88% and 83.64 ± 9.09%, respectively. In the oral tolerance model, the ratio of Th2/Th1 decreased from 4.05 ± 0.38 to 1.69 ± 0.19. Maillard reaction masked the B cell epitopes of TM and retained some T cell epitopes. Potentially, Maillard reaction products (MRPs) can be used as tolerance inducers for allergen-specific immunotherapy.

Genomic profiling of a patient with quadruple synchronous colorectal cancer: a case report.

BACKGROUND: Synchronous colorectal cancer (SCRC) is featured by the presence of multiple primary tumor lesions in a single patient at initial diagnosis. It is less common with the prevalence of approximately 3.5% among colorectal cancer (CRC). Some studies of SCRC have been performed in patients with two tumor lesions. However, SCRC cases with three or more tumor lesions were rare and remained to be investigated. CASE PRESENTATION: In this case report, we presented a 56-year-old male SCRC case with quadruple tumor lesions which is rarely seen in clinical practice. After laparoscopic radical resection of sigmoid carcinoma and partial rectum resection, the four tumor samples were subjected to pathological evaluation and next-generation sequencing (NGS) based genetic profiling. The four tumor lesions included two adenocarcinomas with moderate differentiation at sigmoid colon and rectum respectively, a grade 1 neuroendocrine tumor (NET) at rectum and a high-grade intraepithelial neoplasia at ascending colon. Each tumor exhibited distinct histology types and mutation profiles. After surgical resection, the patient remained disease-free after four cycles of chemotherapy with oxaliplatin and capecitabine (XELOX). CONCLUSIONS: The tumor lesions in this case showed different pathological and genetic features which indicats the heterogeneity of SCRC. The genomic profilling might provide novel insights to understand SCRC at molecular level.

Effects of the Maillard reaction on the epitopes and immunoreactivity of tropomyosin, a major allergen in Chlamys nobilis.

Scallop (Chlamys nobilis) causes an IgE-mediated food allergy; however, studies of the allergens in its musculus are not sufficiently comprehensive. In this context, the target protein was purified from scallops and confirmed to be the major allergen tropomyosin (TM) using proteomic technology and serological testing. Subsequently, seven potential IgE epitopes of TM were obtained using phage display technology with IgE enrichment from the serum of scallop-sensitized patients and identified via inhibition enzyme-linked immunosorbent assays. A method for the Maillard reaction of TM and xylose was established, and Maillard-reacted TM (MR-TM) showed significantly decreased immunobinding activity and CD63 and CD203c expression in basophils compared with TM. Furthermore, shotgun proteomics analysis showed that eleven specific amino acids (K12, R15, K28, K76, R125, R127, K128, R133, R140, K146, and K189) of the six IgE epitopes of TM were modified after the Maillard reaction. Overall, the immunoactivity of MR-TM was reduced, which provides a theoretical reference for the development of hypoallergenic foods.

Inhibition of ALAS1 activity exerts anti-tumour effects on colorectal cancer in vitro.

BACKGROUND/AIMS: Colorectal cancer (CRC) is the third most common malignant tumour worldwide and the second leading cause of cancer-related deaths. Commonly, 5'-aminolevulinic acid synthase1 (ALAS1) is the rate-limiting enzyme for haem biosynthesis. Recent studies have shown that ALAS1 is involved in a number of cellular functions and has significant effects on non-small cell lung cancer (NSCLC). However, current concepts of disease pathogenesis fail to fully explain the role of ALAS1 expression and biological functions in CRC. MATERIALS AND METHODS: A total of 67 paired tumour tissues and adjacent colorectal tissues were used to detect ALAS1 levels and further analyse the correlation between ALAS1 expression levels and clinical features. Using HCT116 cell lines, we studied the impact of ALAS1 on biological function by knocking down or inhibiting ALAS1. RESULTS: We found an increase in the levels of ALAS1 in cancer tissues compared to adjacent colorectal tissues. The increase in ALAS1 expression was closely related to the invasion depth, N staging and tumour size of CRC patients. The proliferation and metastasis of CRC cells could be inhibited by suppressing ALAS1. CONCLUSIONS: The abnormal expression of ALAS1 is closely related to the proliferation and metastasis of CRC cells, suggesting that ALAS1 may be a novel therapeutic target for the treatment of CRC.

Cloning, Expression, and Epitope Identification of Myosin Light Chain 1: An Allergen in Mud Crab.

Mud crab (Scylla paramamosain) is a commonly consumed seafood as a result of its high nutritional value; however, it is associated with food allergy. The current understanding of crab allergens remains insufficient. In the present study, an 18 kDa protein was purified from crab muscle and confirmed to be myosin light chain 1 (MLC1) by matrix-assisted laser desorption/ionization-tandem time-of-flight mass spectrometry. Total RNA was isolated and amplified to obtain a MLC1 open reading frame of 462 bp, encoding 154 amino acids. A structural analysis revealed that recombinant MLC1 (rMLC1) expressed in Escherichia coli contained α-helix and random coil. Moreover, rMLC1 displayed strong immunoactivity by dot blot and a basophil activation test. Furthermore, seven allergenic epitopes of MLC1 were predicted, and five critical epitope regions were identified by an inhibition enzyme-linked immunosorbent assay and human mast cell degranulation assay. This comprehensive research of an allergen helps to conduct component-resolved diagnoses and immunotherapies related to crab allergies.

Effect of KNL1 on the proliferation and apoptosis of colorectal cancer cells.

OBJECTIVE: To identify the expression of kinetochore scaffold 1 (KNL1) in colorectal tumor tissues and to clarify the role of this gene in the proliferation capability of colorectal cancer cells. METHODS: A total of 108 paired colorectal tumor and normal tissue samples were collected from patients with colorectal cancer and subjected to quantitative polymerase chain reaction and immunohistochemistry analyses. Expression levels of KNL1 mRNA and protein were compared between tumor and normal tissues, and KNL1 levels were evaluated in relation to the patients' tumor differentiation, sex, lymph node metastasis, TNM stage, infiltration depth, age, and tumor location. Survival curves were also constructed and compared between patients with tumor samples with and without KLN1 protein expression. KNL1 was under-expressed in colorectal cancer cells in vitro using lentiviral transfection with short hairpin RNA, and its function was evaluated by proliferation, colony-formation, and apoptosis assays. Expression levels of BUB1 protein were also compared between tumor and normal tissues, and the correlation between KNL1 expression and BUB1 expression in colorectal cancer tissues was examined. RESULTS: KNL1 mRNA and protein were both highly expressed in colorectal tumor tissues compared with paired normal tissues. KNL1 downregulation significantly inhibited colorectal cancer cell proliferation and colony formation, and promoted apoptosis. KNL1 protein expression was significantly associated with tumor differentiation, but not with sex, lymph node metastasis, TNM stage, infiltration depth, age, or tumor location. KNL1 protein expression was also significantly associated with poorer survival. Moreover, there was a significant correlation between KNL1 and BUB1 in colorectal cancer tissues. CONCLUSIONS: KNL1 plays an effective role in decreasing apoptosis and promoting the proliferation of colorectal cancer cells, suggesting that its inhibition may represent a promising therapeutic approach in patients with colorectal cancer.

LncRNA LOXL1-AS1/miR-let-7a-5p/EGFR-related pathway regulates the doxorubicin resistance of prostate cancer DU-145 cells.

Our study aimed to investigate the effects of lncRNA LOXL1-AS1/miR-let-7a-5p/EGFR-axis on prostate cancer (PCa) progression. Microarray analysis was conducted to determine differentially expressed lncRNAs and mRNAs. Gene Set Enrichment analysis was implemented for verification of dys-regulated signaling pathways between DU-145 cells and doxorubicin-resistant prostate cancer DU-145 cells. Relative expression of lncRNA LOXL1-AS1 in doxorubicin-resistant prostate cancer DU-145 cells was analyzed by qRT-PCR. CCK-8 assay and flow cytometry analysis were employed to detect cell proliferation and apoptosis, respectively. Cell migration was performed by transwell assay. Furthermore, targeted relationships between lncRNA LOXL1-AS1 and miR-let-7a-5p, as well as miR-let-7a-5p and EGFR were predicted using bioinformatics analysis and validated by dual-luciferase reporter gene assay. Besides, tumor xenograft assay was utilized for verification of the roles of LOXL1-AS1 in PCa progression in vivo. Microarray analysis showed that lncRNA LOXL1-AS1 and EGFR were both downregulated, while miR-let-7a-5p was upregulated in doxorubicin-resistant prostate cancer DU-145 cells. MiR-let-7a-5p could target both lncRNA LOXL1-AS1 and EGFR to affect PCa progression. Upregulation of lncRNA LOXL1-AS1 promoted cell proliferation and migration, while suppressed cell apoptosis. Besides, it was further confirmed that EGFR was downregulated in drug-resistant PCa cells and negatively correlated with miR-let-7a-5p. Tumor xenograft assay verified that silence of lncRNA LOXL1-AS1 inhibited the tumor growth in vivo in DU-145 cells. Our results demonstrated that the lncRNALOXL1-AS1/miR-let-7a-5p/EGFR axis significantly affected proliferation, migration, and apoptosis of drug-resistant DU-145 Cells, which may provide us with a potential treatment strategy for drug-resistant PCa patients. © 2019 IUBMB Life, 2019.