Process and applications of alginate oligosaccharides with emphasis on health beneficial perspectives.

Alginates are linear polymers comprising 40% of the dry weight of algae possess various applications in food and biomedical industries. Alginate oligosaccharides (AOS), a degradation product of alginate, is now gaining much attention for their beneficial role in food, pharmaceutical and agricultural industries. Hence this review was aimed to compile the information on alginate and AOS (prepared from seaweeds) during 1994-2020. As per our knowledge, this is the first review on the potential use of alginate oligosaccharides in different fields. The alginate derivatives are grouped according to their applications. They are involved in the isolation process and show antimicrobial, antioxidant, anti-inflammatory, antihypertension, anticancer, and immunostimulatory properties. AOS also have significant applications in prebiotics, nutritional supplements, plant growth development and others products.

Distribution, phenotype, functional and clinical relevance of CD8+CD103+ tissue-resident memory T cells in human gastric cancer.

CD8+CD103+ tissue-resident memory T cells (TRMs) are involved in tumor immune response and linked to favorable clinical outcome in human cancer. However, the distribution, phenotype, functional properties and clinical relevance of these cells in gastric cancer (GC) remain elusive. Here, our data show that, in comparison to non-tumor tissues, the percentages of CD8+CD103+ TRMs in tumors are significantly decreased. Most tumor-infiltrating CD8+CD103+ TRMs are CD45RA-CCR7- effector-memory cells with higher PD-1 and 4-1BB expression than those from non-tumor tissues. Further, tumor-infiltrating CD8+CD103+ TRMs show impaired cytolytic capacity due to decreased granzyme B and perforin expression. Moreover, ex vivo PD-1 blockade could restore the cytolytic capacity of tumor-infiltrating CD8+CD103+ TRMs, and such anti-PD-1-mediated reinvigoration of CD8+CD103+ TRMs could be further enhanced by 4-1BB co-stimulation. Finally, lower levels of Tumor-infiltrating CD8+CD103+ TRMs are positively correlated with GC progression and poor patients' survival. Our data suggest that restoring CD8+CD103+ TRM function by combining PD-1 blockade and 4-1BB co-stimulation may be a promising strategy for treating GC.

Expression, regulation and clinical significance of B7-H3 on neutrophils in human gastric cancer.

Neutrophils are conspicuous components of gastric cancer (GC) tumors, increasing with tumor progression and poor patient survival. However, the phenotype, regulation and clinical relevance of neutrophils in human GC are presently unknown. Most intratumoral neutrophils showed an activated CD54+ phenotype and expressed high level B7-H3. Tumor tissue culture supernatants from GC patients induced the expression of CD54 and B7-H3 on neutrophils in time-dependent and dose-dependent manners. Locally enriched CD54+ neutrophils and B7-H3+ neutrophils positively correlated with increased granulocyte-macrophage colony stimulating factor (GM-CSF) detection ex vivo; and in vitro GM-CSF induced the expression of CD54 and B7-H3 on neutrophils in both time-dependent and dose-dependent manners. Furthermore, GC tumor-derived GM-CSF activated neutrophils and induced neutrophil B7-H3 expression via JAK-STAT3 signaling pathway activation. Finally, intratumoral B7-H3+ neutrophils increased with tumor progression and independently predicted reduced overall survival. Collectively, these results suggest B7-H3+ neutrophils to be potential biomarkers in GC.

Helicobacter pylori-induced REDD1 modulates Th17 cell responses that contribute to gastritis.

OBJECTIVE: Regulated in development and DNA damage responses-1 (REDD1) is a conserved and ubiquitous protein, which is induced in response to multiple stimuli. However, the regulation, function and clinical relevance of REDD1 in Helicobacter pylori-associated gastritis are presently unknown. APPROACH: Immunohistochemistry, real-time PCR and Western blot analyses were performed to examine the levels of REDD1 in gastric samples from H. pylori-infected patients and mice. Gastric tissues from Redd1-/- and wildtype (WT, control) mice were examined for inflammation. Gastric epithelial cells (GECs), monocytes and T cells were isolated, stimulated and/or cultured for REDD1 regulation and functional assays. RESULTS: REDD1 was increased in gastric mucosa of H. pylori-infected patients and mice. H. pylori induced GECs to express REDD1 via the phosphorylated cytotoxin associated gene A (cagA) that activated MAPKp38 pathway to mediate NF-κB directly binding to REDD1 promoter. Human gastric REDD1 increased with the severity of gastritis, and mouse REDD1 from non-marrow chimera-derived cells promoted gastric inflammation that was characterized by the influx of MHCII+ monocytes. Importantly, gastric inflammation, MHCII+ monocyte infiltration, IL-23 and IL-17A were attenuated in Redd1-/- mice. Mechanistically, REDD1 in GECs regulated CXCL1 production, which attracted MHCII+ monocytes migration by CXCL1-CXCR2 axis. Then H. pylori induced MHCII+ monocytes to secrete IL-23, which favored IL-17A-producing CD4+ cell (Th17 cell) polarization, thereby contributing to the development of H. pylori-associated gastritis. CONCLUSIONS: The present study identifies a novel regulatory network involving REDD1, which collectively exert a pro-inflammatory effect within gastric microenvironment. Efforts to inhibit this REDD1-dependent pathway may prove valuable strategies in treating of H. pylori-associated gastritis.

Upregulation of Tubulointerstitial nephritis antigen like 1 promotes gastric cancer growth and metastasis by regulating multiple matrix metallopeptidase expression.

BACKGROUND AND AIM: Tubulointerstitial nephritis antigen-like 1 (TINAGL1), as a novel matricellular protein, has been demonstrated to participate in cancer progression, whereas the potential function of TINAGL1 in gastric cancer (GC) remains unknown. METHODS: The expression pattern of TINAGL1 in GC was examined by immunohistochemistry, ELISA, real-time polymerase chain reaction, and Western blot. Correlation between TINAGL1 and matrix metalloproteinases (MMPs) was analyzed by the GEPIA website and Kaplan-Meier plots database. The lentivirus-based TINAGL1 knockdown, CCK-8, and transwell assays were used to test the function of TINAGL1 in vitro. The role of TINAGL1 was confirmed by subcutaneous xenograft, abdominal dissemination, and lung metastasis model. Microarray experiments, ELISA, real-time polymerase chain reaction, and Western blot were used to identify molecular mechanism. RESULTS: TINAGL1 was increased in GC tumor tissues and associated with poor patient survival. Moreover, TINAGL1 significantly promoted GC cell proliferation and migration in vitro as well as facilitated GC tumor growth and metastasis in vivo. TINAGL1 expression in GC cells was accompanied with increasing MMPs including MMP2, MMP9, MMP11, MMP14, and MMP16. GEPIA database revealed that these MMPs were correlated with TINAGL1 in GC tumors and that the most highly expressed MMP was MMP2. Mechanically, TINAGL1 regulated MMP2 through the JNK signaling pathway activation. CONCLUSIONS: Our data highlight that TINAGL1 promotes GC growth and metastasis and regulates MMP2 expression, indicating that TINAGL1 may serve as a therapeutic target for GC.

Literature Review of Proteomics Approach Associated with Coffee.

As a significant crop growing all across the world, coffee is mostly produced in the bean belt of our global atlas. Worldwide variations in environmental conditions are causing a decline in the yield and quality of coffee varieties. Coffee production is the main emphasis of several traditional breeding techniques. But conventional breeding methods are not sufficient to tackle the problems related to coffee. The field of genomics, which includes transcriptomics, proteomics, and metabolomics, has made great paces in the last ten years. Proteomics is a well-known technique used to enhance the growth, yield, breeding, and quality of different plants under stable and shifting environments. The regulation of specific enzymes, genes, protein expression, modification, translation, and other features played an important role in the enhancement of important plants. However, relatively less research on the proteomics approach for coffee has been published in the last few years. For this reason, some of the most important aspects of proteome profiling for coffee plants have been covered in this review, including growth, the somatic embryo technique, altitude, environmental adoption, drought, and the role that proteins and important enzymes play in the flavor and taste of coffee. This review can aid in the breeding of new cultivars and improve coffee attributes. Furthermore, the present literature can pave the way for proteomics research on coffee.

Analysis of the key aroma components of Pu'er tea by synergistic fermentation with three beneficial microorganisms.

Aroma is a key indicator of the quality and value of Pu'er tea. A total of 36 aroma components were detected,which Saccharomyces, Rhizopus, and Aspergillus niger, were in the ratios of 2:1:2, 2:2:2, and 2:3:2 inoculated to ferment Pu'er tea, comparing with natural fermentation. In addition, 12 key aroma compounds were identified by analysing ROAVs. Methoxyphenyl compounds and ß-ionone were the primary contributors to the formation of aged and woody aroma when fermenting Pu'er tea naturally or using Rhizopus, while linalool and its oxides, benzyl alcohol, hexanal, and limonene were the primary contributors to the formation of floral and fruity aroma when fermenting Pu'er tea using synergistic fermentation with Saccharomyces, Rhizopus, and Aspergillus niger. This study identified the key aroma components of the Pu'er tea fermented using five methods, which revealed and demonstrated the potential application of synergistic effects of different microorganisms in the changes of aroma of Pu'er tea.

Headspace solid-phase microextraction coupled with gas chromatography-mass spectrometry (HS-SPME-GC-MS) and odor activity value (OAV) to reveal the flavor characteristics of ripened Pu-erh tea by co-fermentation.

Introduction: Pu-erh tea is a geographical indication product of China. The characteristic flavor compounds produced during the fermentation of ripened Pu-erh tea have an important impact on its quality. Methods: Headspace solid-phase microextraction coupled with gas chromatography-mass spectrometry (HS-SPME-GC-MS) and odor activity value (OAV) is used for flavor analysis. Results: A total of 135 volatile compounds were annotated, of which the highest content was alcohols (54.26%), followed by esters (16.73%), and methoxybenzenes (12.69%). Alcohols in ripened Pu-erh tea mainly contribute flower and fruit sweet flavors, while methoxybenzenes mainly contribute musty and stale flavors. The ripened Pu-erh tea fermented by Saccharomyces: Rhizopus: Aspergillus niger mixed in the ratio of 1:1:1 presented the remarkable flavor characteristics of flower and fruit sweet flavor, and having better coordination with musty and stale flavor. Discussion: This study demonstrated the content changes of ripened Pu-erh tea's flavor compounds in the fermentation process, and revealed the optimal fermentation time. This will be helpful to further understand the formation mechanism of the characteristic flavor of ripened Pu-erh tea and guide the optimization of the fermentation process of ripened Pu-erh tea.

Tubulointerstitial nephritis antigen-like 1 is a novel matricellular protein that promotes gastric bacterial colonization and gastritis in the setting of Helicobacter pylori infection.

The interaction between the gastric epithelium and immune cells plays key roles in H. pylori-associated pathology. Here, we demonstrate a procolonization and proinflammatory role of tubulointerstitial nephritis antigen-like 1 (TINAGL1), a newly discovered matricellular protein, in H. pylori infection. Increased TINAGL1 production by gastric epithelial cells (GECs) in the infected gastric mucosa was synergistically induced by H. pylori and IL-1ß via the ERK-SP1 pathway in a cagA-dependent manner. Elevated human gastric TINAGL1 correlated with H. pylori colonization and the severity of gastritis, and mouse TINAGL1 derived from non-bone marrow-derived cells promoted bacterial colonization and inflammation. Importantly, H. pylori colonization and inflammation were attenuated in Tinagl1-/- and Tinagl1ΔGEC mice and were increased in mice injected with mouse TINAGL1. Mechanistically, TINAGL1 suppressed CCL21 expression and promoted CCL2 production in GECs by directly binding to integrin α5ß1 to inhibit ERK and activate the NF-κB pathway, respectively, which not only led to decreased gastric influx of moDCs via CCL21-CCR7-dependent migration and, as a direct consequence, reduced the bacterial clearance capacity of the H. pylori-specific Th1 response, thereby promoting H. pylori colonization, but also resulted in increased gastric influx of Ly6Chigh monocytes via CCL2-CCR2-dependent migration. In turn, TINAGL1 induced the production of the proinflammatory protein S100A11 by Ly6Chigh monocytes, promoting H. pylori-associated gastritis. In summary, we identified a model in which TINAGL1 collectively ensures H. pylori persistence and promotes gastritis.

Moisture contents and product quality prediction of Pu-erh tea in sun-drying process with image information and environmental parameters.

In this study, moisture contents and product quality of Pu-erh tea were predicted with deep learning-based methods. Images were captured continuously in the sun-drying process. Environmental parameters (EP) of air humidity, air temperature, global radiation, wind speed, and ultraviolet radiation were collected with a portable meteorological station. Sensory scores of aroma, flavor, liquor color, residue, and total scores were given by a trained panel. Convolutional neural network (CNN) and gated recurrent unit (GRU) models were constructed based on image information and EP, which were selected in advance using the neighborhood component analysis (NCA) algorithm. The evolved models based on deep-learning methods achieved satisfactory results, with RMSE of 0.4332, 0.2669, 0.7508 (also with R 2 of .9997, .9882, .9986, with RPD of 53.5894, 13.1646, 26.3513) for moisture contents prediction in each batch of tea, tea at different sampling periods, the overall samples, respectively; and with RMSE of 0.291, 0.2815, 0.162, 0.1574, 0.3931 (also with R 2 of .9688, .9772, .9752, .9741, .8906, with RPD of 5.6073, 6.5912, 6.352, 6.1428, 4.0045) for final quality prediction of aroma, flavor, liquor color, residue, total score, respectively. By analyzing and comparing the RMSE values, the most significant environmental parameters (EP) were selected. The proposed combinations of different EP can also provide a valuable reference in the development of a new sun-drying system.

FasL+ PD-L2+ Identifies a Novel Immunosuppressive Neutrophil Population in Human Gastric Cancer That Promotes Disease Progression.

Neutrophils constitute abundant cellular components in human gastric cancer (GC) tissues, but their protumorigenic subset in pathogenesis of GC progression is unclear. Here, it is found that patients with GC show significantly higher neutrophil infiltration in tumors that is regulated by CXCL12-CXCR4 chemotaxis. These tumor-infiltrating neutrophils express high level immunosuppressive molecules FasL and PD-L2, and this FasL+ PD-L2+ neutrophil subset with a unique phenotype constitutes at least 20% of all neutrophils in advanced GC and predicts poor patient survival. Tumor induces neutrophils to express FasL and PD-L2 proteins with similar phenotype to those in GC tumors in both time-dependent and dose-dependent manners. Mechanistically, Th17 cell-derived IL-17A and tumor cell-derived G-CSF can significantly induce neutrophil FasL and PD-L2 expression via activating ERK-NF-κB and JAK-STAT3 signaling pathway, respectively. Importantly, upon over-expressing FasL and PD-L2, neutrophils acquire immunosuppressive functions on tumor-specific CD8+ T-cells and promote the growth and progression of human GC tumors in vitro and in vivo, which can be reversed by blocking FasL and PD-L2 on these neutrophils. Thus, the work identifies a novel protumorigenic FasL+ PD-L2+ neutrophil subset in GC and provides new insights for human cancer immunosuppression and anti-cancer therapies targeting these pathogenic cells.

Theaflavin Chemistry and Its Health Benefits.

Huge epidemiological and clinical studies have confirmed that black tea is a rich source of health-promoting ingredients, such as catechins and theaflavins (TFs). Furthermore, TF derivatives mainly include theaflavin (TF1), theaflavin-3-gallate (TF2A), theaflavin-3'-gallate (TF2B), and theaflavin-3,3'-digallate (TF3). All of these TFs exhibit extensive usages in pharmaceutics, foods, and traditional medication systems. Various indepth studies reported that how TFs modulates health effects in cellular and molecular mechanisms. The available literature regarding the pharmacological activities of TFs has revealed that TF3 has remarkable anti-inflammatory, antioxidant, anticancer, antiobesity, antiosteoporotic, and antimicrobial properties, thus posing significant effects on human health. The current manuscript summarizes both the chemistry and various pharmacological effects of TFs on human health, lifestyle or aging associated diseases, and populations of gut microbiota. Furthermore, the biological potential of TFs has also been focused to provide a deeper understanding of its mechanism of action.

Granulocyte-Macrophage Colony-Stimulating Factor-Activated Neutrophils Express B7-H4 That Correlates with Gastric Cancer Progression and Poor Patient Survival.

Neutrophils are prominent components of gastric cancer (GC) tumors and exhibit distinct phenotypes in GC environment. However, the phenotype, regulation, and clinical relevance of neutrophils in human GC are presently unknown. Here, immunohistochemistry, real-time PCR, and flow cytometry analyses were performed to examine levels and phenotype of neutrophils in samples from 41 patients with GC, and also isolated, stimulated, and/or cultured neutrophils for in vitro regulation assays. Finally, we performed Kaplan-Meier plots for overall survival by using the log-rank test to evaluate the clinical relevance of neutrophils and their subsets. In our study, neutrophils in tumor tissues were significantly higher than those in nontumor tissues and were positively associated with tumor progression but negatively correlated with GC patient survival. Most intratumoral neutrophils showed an activated CD54+ phenotype and expressed high-level immunosuppressive molecule B7-H4. Tumor tissue culture supernatants from GC patients induced neutrophils to express CD54 and B7-H4 in both time-dependent and dose-dependent manners. Locally enriched CD54+ neutrophils and B7-H4+ neutrophils positively correlated with increased granulocyte-macrophage colony-stimulating factor (GM-CSF) detection ex vivo, and in vitro GM-CSF induced the expression of CD54 and B7-H4 on neutrophils in a time-dependent and dose-dependent manner. Moreover, GC tumor-derived GM-CSF activated neutrophils and induced neutrophil B7-H4 expression via Janus kinase (JAK)-signal transducer and activator of transcription 3 (STAT3) signaling pathway activation. Furthermore, higher intratumoral B7-H4+ neutrophil percentage/number was found in GC patients with advanced tumor node metastasis stage and reduced overall survival following surgery. Our results illuminate a novel regulating mechanism of B7-H4 expression on tumor-activated neutrophils in GC, suggesting that functional inhibition of these novel GM-CSF-B7-H4 pathways may be a suitable therapeutic strategy to treat the immune tolerance feature of GC.

Dietary 25-hydroxyvitamin D improves intestinal health and microbiota of laying hens under high stocking density.

The high stocking density is a major stress factor that adversely affects the health and performance of poultry. Therefore, the object of this study was conducted to explore whether dietary 25-hydroxyvitamin D (25-OH-D3) could improve gut health of laying hens reared under high stocking density. A 2 × 2 factorial design was used in this 16-week study, in which 800 45-week-old Lohmann laying hens were allocated into two levels of dietary 25-OH-D3 levels (0 and 69 µg/kg) and two rates of stocking densities [506 (low density, LD) and 338 (high density, HD) cm2/hen]. Compared with the layers with LD, the layers with HD had lower crypt depth in duodenum (P(Density) < 0.05), lower short chain fatty acid (propionic and butyric acid) contents in cecum (P(Density) < 0.05), and lower mRNA expression of intestinal barrier associated protein (claudin-1, mucin-1 and mucin-2). Exposed layer to HD also led to lower intestinal antioxidative capacity [superoxide dismutase (SOD), catalase (CAT), total antioxidant capacity (T-AOC), and higher malondialdehyde (MDA) content] in small intestine (P(Density) < 0.05), lower bacterial abundance of Bacteroidetes (phylum), Spirochaetes (phylum) and Bacteroides (genus; P(Density) < 0.05), higher bacterial enrichment of Lactobacillaceae (genus) and Firmicutes/Bacteroidetes ratio (P(Density) < 0.05) in cecum. Dietary 25-OH-D3 increased the villus height in duodenum and jejunum (P(25-OH-D3) < 0.05), decreased Chao 1 and ACE indexes in cecum (P(25-OH-D3) < 0.05), and it also up-regulated the mRNA expression of claudin-1, mucin-1 and mucin-2 (P(25-OH-D3) < 0.05). Layers treated with 25-OH-D3 led to an enhanced antioxidative enzyme activity of CAT (P(25-OH-D3) < 0.05). Additionally, the effect of 25-OH-D3 reversed the effect of HD on T-AOC and MDA content (P(Interaction) < 0.05). In HD layers, 25-OH-D3 administration decreased the enrichment of Bacteroidetes (phylum), increased Firmicutes (phylum), and Firmicutes/Bacteroidetes ratio (P(Interaction) < 0.05). These results suggest that supplementing 25-OH-D3 in diets may elevate gut health through the improvement of intestinal barrier function, antioxidant capacity and cecal microbiota composition in laying hens with high stocking density.

Dietary apple pectic oligosaccharide improves reproductive performance, antioxidant capacity, and ovary function of broiler breeders.

Reproduction performance is one of the most important economic traits for the poultry industry. Intriguingly, apple pectic oligosaccharide (APO) could promote gastrointestinal function and immune function to improve performance; however, literature about APO on reproduction performance in breeders is limited. This study aimed to determine whether APO administration can improve reproduction performance and ovary function of broiler breeders with different egg laying rates. Two hundred and fifty six Arbor Acres broiler breeders (48-week-old) were used in a 2 × 2 factorial design with 2 egg laying rates (average [AR] and low [LR]) and 2 dietary levels of APO (0 and 200 mg/kg APO). Results showed that the LR breeders presented higher egg weight but lower egg laying rate, qualified egg rate, and feed efficiency than the AR breeders (P(laying) < 0.05). Also, the LR breeders had decreased serum Anti-Müllerian hormone, leptin, and antioxidant enzyme (superoxide dismutase, total antioxidant capacity) levels than the AR breeders (P(laying) ≤ 0.05). Dietary supplementation with APO improved egg weight, feed efficiency, as well as egg albumen quality (higher albumen height and Haugh unit) (P(APO) < 0.05), and decreased the concentration of pro-inflammatory cytokine levels (interleukin [IL]-1ß, IL-8) in serum (P(APO) ≤ 0.05). The apoptosis rate and pro-apoptosis-related gene expression (caspase 9 and Bax) in the ovary of LR breeders were higher, while the anti-apoptosis-related gene expression (Bcl-2, PCNA) was lower in LR compared with the AR breeders (P(laying) < 0.05). Dietary supplementation with APO decreased the caspase 9 and Bax expression in LR breeders (P(interaction) < 0.05), and increased the Bcl-2 and PCNA expression in the 2 breeders (P(APO) < 0.05). These findings indicate that breeders with a lower egg laying rate exhibit lower antioxidant capacity and high cell apoptosis in the ovary. Dietary supplementation with APO might improve albumen quality and antioxidant capacity, and decrease the inflammatory factors and ovary apoptosis-related genes expression to improve ovary function. Moreover, the effect of APO on decreasing ovarian pro-apoptosis-related gene expression was more pronounced in lower reproductive breeders.

Activated neutrophils polarize protumorigenic interleukin-17A-producing T helper subsets through TNF-α-B7-H2-dependent pathway in human gastric cancer.

RATIONALE: Neutrophils constitute massive cellular constituents in inflammatory human gastric cancer (GC) tissues, but their roles in pathogenesis of inflammatory T helper (Th) subsets are still unknown. METHODS: Flow cytometry analysis and immunohistochemistry were used to analyze the responses and phenotypes of neutrophils in different samples from 51 patients with GC. Kaplan-Meier plots and Multivariate analysis for the survival of patients were used by log-rank tests and Cox proportional hazards models. Neutrophils and CD4+ T cells were purified and cultured for ex vivo, in vitro and in vivo regulation and function assays. RESULTS: GC patients exhibited increased tumoral neutrophil infiltration with GC progression and poor patient prognosis. Intratumoral neutrophils accumulated in GC tumors via CXCL6/CXCL8-CXCR1-mediated chemotaxis, and expressed activated molecule CD54 and co-signaling molecule B7-H2. Neutrophils induced by tumors strongly expressed CD54 and B7-H2 in both dose- and time-dependent manners, and a close correlation was obtained between the expressions of CD54 and B7-H2 on intratumoral neutrophils. Tumor-derived tumor necrosis factor-α (TNF-α) promoted neutrophil activation and neutrophil B7-H2 expression through ERK-NF-κB pathway, and a significant correlation was found between the levels of TNF-α and CD54+ or B7-H2+ neutrophils in tumor tissues. Tumor-infiltrating and tumor-conditioned neutrophils effectively induced IL-17A-producing Th subset polarization through a B7-H2-dependent manner ex vivo and these polarized IL-17A-producing Th cells exerted protumorigenic roles by promoting GC tumor cell proliferation via inflammatory molecule IL-17A in vitro, which promoted the progression of human GC in vivo; these effects could be reversed when IL-17A is blocked. Moreover, increased B7-H2+ neutrophils and IL-17A in tumors were closely related to advanced GC progression and predicted poor patient survival. CONCLUSION: We illuminate novel underlying mechanisms that TNF-α-activated neutrophils link B7-H2 to protumorigenic IL-17A-producing Th subset polarization in human GC. Blocking this pathological TNF-α-B7-H2-IL-17A pathway may be useful therapeutic strategies for treating GC.

Characterization of the Intestinal Microbiota of Broiler Breeders With Different Egg Laying Rate.

The gastrointestinal microbiota plays a pivotal role in maintaining animal health, immunity and reproductive performances. However, literature about the relationship between microbiota and reproductive performance is limited. The aim of the present study was to determine differences in the intestinal microbiota of broiler breeders with different egg laying rate. A total of 200 AA+ parent broiler breeders (41-week-old) were separated into two groups according to their different egg laying rate [average egg laying rate group (AR: 78.57 ± 0.20%) and high egg laying rate group (HR: 90.79 ± 0.43%). Feed conversion ratio (FCR), ovary cell apoptosis rate (ApoCR) and relative abdominal fat weight were lower (p = 0.01), while the hatchability rate of qualified egg was higher (p = 0.04) in HR group than that in AR group. Phascolarctobacterium abundance were lower (p = 0.012) in ileum of HR birds. Romboutsia (genus) in ileum was negatively related to the feed efficiency (r = -0.58, p < 0.05), Firmicutes (phylum) and Lactobacillus (genus) abundances in cecum were positively related to the egg laying rate (ELR) (r = 0.35 and 0.48, p < 0.05), feed efficiency (r = 0.42 and 0.43, p < 0.05), while Spirochaetes (phylum) and Sphaerochaeta (genus) abundances in cecum were negatively related to the ELR (r = -0.43 and -0.70, p < 0.05), feed efficiency (r = 0.54 and 0.48, p < 0.05), and positively related to ApoCR (r = 0.46 and 0.47, p < 0.05). Our results suggested that microbiota, such as Firmicutes (phylum) and Lactobacillus (genus) have positive relationship, while Spirochaetes (phylum) and Romboutsia (genus) abundances exert negative relationship with broiler breeders' reproductive performances.

Arrestin domain containing 3 promotes Helicobacter pylori-associated gastritis by regulating protease-activated receptor 1.

Arrestin domain containing 3 (ARRDC3) represents a newly discovered α-arrestin involved in obesity, inflammation, and cancer. Here, we demonstrate a proinflammation role of ARRDC3 in Helicobacter pylori-associated gastritis. Increased ARRDC3 was detected in gastric mucosa of patients and mice infected with H. pylori. ARRDC3 in gastric epithelial cells (GECs) was induced by H. pylori, regulated by ERK and PI3K-AKT pathways in a cagA-dependent manner. Human gastric ARRDC3 correlated with the severity of gastritis, and mouse ARRDC3 from non-BM-derived cells promoted gastric inflammation. This inflammation was characterized by the CXCR2-dependent influx of CD45+CD11b+Ly6C-Ly6G+ neutrophils, whose migration was induced via the ARRDC3-dependent production of CXCL2 by GECs. Importantly, gastric inflammation was attenuated in Arrdc3-/- mice but increased in protease-activated receptor 1-/- (Par1-/-) mice. Mechanistically, ARRDC3 in GECs directly interacted with PAR1 and negatively regulated PAR1 via ARRDC3-mediated lysosomal degradation, which abrogated the suppression of CXCL2 production and following neutrophil chemotaxis by PAR1, thereby contributing to the development of H. pylori-associated gastritis. This study identifies a regulatory network involving H. pylori, GECs, ARRDC3, PAR1, and neutrophils, which collectively exert a proinflammatory effect within the gastric microenvironment. Efforts to inhibit this ARRDC3-dependent pathway may provide valuable strategies in treating of H. pylori-associated gastritis.