Background Epidemiological studies have suggested an association between Helicobacter pylori ( H pylori ) infection and atherosclerosis through undefined mechanisms. Endothelial dysfunction is critical to the development of atherosclerosis and related cardiovascular diseases. The present study was designed to test the hypothesis that H pylori infection impaires endothelial function through exosome‐mediated mechanisms. Methods and Results Young male and female patients (18‐35 years old) with and without H pylori infection were recruited to minimize the chance of potential risk factors for endothelial dysfunction for the study. Endothelium‐dependent flow‐mediated vasodilatation of the brachial artery was evaluated in the patients and control subjects. Mouse infection models with CagA + H pylori from a gastric ulcer patient were created to determine if H pylori infection‐induced endothelial dysfunction could be reproduced in animal models. H pylori infection significantly decreased endothelium‐dependent flow‐mediated vasodilatation in young patients and significantly attenuated acetylcholine‐induced endothelium‐dependent aortic relaxation without change in nitroglycerin‐induced endothelium‐independent vascular relaxation in mice. H pylori eradication significantly improved endothelium‐dependent vasodilation in both patients and mice with H pylori infection. Exosomes from conditioned media of human gastric epithelial cells cultured with CagA + H pylori or serum exosomes from patients and mice with H pylori infection significantly decreased endothelial functions with decreased migration, tube formation, and proliferation in vitro. Inhibition of exosome secretion with GW 4869 effectively preserved endothelial function in mice with H pylori infection. Conclusions H pylori infection impaired endothelial function in patients and mice through exosome‐medicated mechanisms. The findings indicated that H pylori infection might be a novel risk factor for cardiovascular diseases.

Background and aims-Atherosclerosis is an important contributing factor to cardiovascular mortality. The role of Helicobacter pylori (H. pylori) infection in atherosclerosis is inconsistent and sometimes controversial. The present study aimed to determine if H. pylori infection is associated with carotid atherosclerosis. Methods-17,613 males and females with both carotid ultrasonic examination and 13 C-urea breath test for H. pylori infection were screened by a major Chinese university hospital from March 2012 to March 2017 for the study. Baseline demographics, cardiac risk factors, and laboratory studies were obtained. After exclusion for pre-specified conditions, 12,836 individuals were included in the analysis, including 8157 men (63.5%) and 4679 women (36.5%). Analysis was also made for 5-year follow-up data of 1216 subjects (869 males and 347 females) with and without H. pylori infection for development and progression of carotid atherosclerosis.

H. pylori induces a complicated local and systematic immune response and contributes to the carcinogenesis of gastric cancer. A primary type 1 immune response is evoked by H. pylori since its occurrence. However, it is not unusual that an inhibitory immunity is dominant in H. pylori-associated diseases, which are promoted by the formation of immunosuppressive microenvironment. But whether group 2 innate lymphoid cells (ILC2s) plays a critical role in H. pylori-induced skewed type 2 immunity is still unclear. In the present study, firstly, we confirmed that type 1 immunity was inhibited and type 2 immunity were undisturbed or promoted after H. pylori infection in vitro and in vivo. Secondly, GATA-3 was firstly found to be increased in the interstitial lymphocytes from H. pylori-associated gastric cancer, among them, Lin−GATA-3+ cells and Lin+GATA-3+ cells were also found to be enhanced, which indicated an important role for ILC2s in H. pylori infection. More importantly, ILC2s were found to be increased after H. pylori infection in clinical patients and animal models. In conclusion, our results indicated that ILC2-mediated innate immune response might play a potential role in dominant type 2 phenotype and immunosuppressive microenvironment in H. pylori infection.

Background/Aims: Primary splenic angiosarcoma is an aggressive malignancy originating from endothelial cells with a particularly poor outcome despite radical therapy. Owing to its extremely low incidence, available data for splenic angiosarcoma are limited. The present study aimed to address this limitation by presenting a thorough retrospective analysis of Chinese primary splenic angiosarcoma patients over a 53-year period (1963-2016). Methods: To determine the characteristics of Chinese primary splenic angiosarcoma and identify factors that impact the outcomes of this histology, we retrospectively retrieved reports of 110 Chinese primary splenic angiosarcoma cases published between 1963-2012. Results: In total, 61 males and 49 females diagnosed with primary splenic angiosarcoma were included in the present study. The median age at diagnosis was 50 years (range 2.5–76 years). Of these patients, 25.5% had received prior radiotherapy. The rate of splenic rupture was 59.11%. The 1-year overall survival rate was 19.1% with a median overall survival time of 8.1 months. Age, gender, and radiation history showed no correlation with survival rate. However, by univariate analysis, we found that significant adverse predictors of survival were splenic rupture before surgery and large tumor size (> 5 cm), while adjuvant chemotherapy was a favorable predictor. Furthermore, multivariate analysis revealed that splenic rupture and adjuvant chemotherapy were independent adverse and favorable predictors, respectively. Conclusion: Our large series describes and confirms the characteristics and poor prognosis of Chinese primary splenic angiosarcoma, thus indicating a critical role for early diagnosis and surgical intervention (prior to rupture) in management, and highlights the promising potential of adjuvant chemotherapy for improving the outcome in these cases.

BackgroundHelicobacter pylori (H. pylori) infection increases the risk for atherosclerosis, and ROS are critical to endothelial dysfunction and atherosclerosis. CagA is a major H. pylori virulence factor associated with atherosclerosis. The present study aimed to test the hypothesis that CagA+H. pylori effectively colonizes gastric mucosa, and CagA+H. pylori, but not CagA–H. pylori, infection impairs endothelial function through exosomes-mediated ROS formation.MethodsC57BL/6 were used to determine the colonization ability of CagA+H. pylori and CagA–H. pylori. ROS production, endothelial function of thoracic aorta and atherosclerosis were measured in CagA+H. pylori and CagA–H. pylori infected mice. Exosomes from CagA+H. pylori and CagA–H. pylori or without H. pylori infected mouse serum or GES-1 were isolated and co-cultured with bEND.3 and HUVECs to determine how CagA+H. pylori infection impairs endothelial function. Further, GW4869 was used to determine if CagA+H. pylori infection could lead to endothelial dysfunction and atherosclerosis through an exosomes-mediated mechanism.ResultsCagA+H. pylori colonized gastric mucosa more effectively than CagA–H. pylori in mice. CagA+H. pylori, not CagA–H. pylori, infection significantly increased aortic ROS production, decreased ACh-induced aortic relaxation, and enhanced early atherosclerosis formation, which were prevented with N-acetylcysteine treatment. Treatment with CagA-containing exosomes significantly increased intracellular ROS production in endothelial cells and impaired their function. Inhibition of exosomes secretion with GW4869 effectively prevented excessive aortic ROS production, endothelial dysfunction, and atherosclerosis in mice with CagA+H. pylori infection.ConclusionThese data suggest that CagA+H. pylori effectively colonizes gastric mucosa, impairs endothelial function, and enhances atherosclerosis via exosomes-mediated ROS formation in mice.

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Plant stomata which consist of a pair of guard cells, are not only finely controlled to balance water loss as transpiration and CO 2 absorption for photosynthesis, but also serve as the major sites to defend against pathogen attack, thus allowing plants to respond appropriately to abiotic and biotic stress conditions. The regulatory signaling network for stomatal movement is complex in nature, and plant peptides have been shown to be involved in signaling processes. Arabidopsis secreted peptide PIP1 was previously identified as an endogenous elicitor, which induced immune response through its receptor, RLK7. PIP1-RLK7 can activate stomatal immunity against the bacterial strain Pst DC3118. However, the molecular mechanism of PIP1 in stomatal regulation is still unclear and additional new factors need to be discovered. In this study, we further clarified that PIP1 could function as an important regulator in the induction of stomatal closure. The results showed that PIP1 could promote stomata to close in a certain range of concentrations and response time. In addition, we uncovered that PIP1-RLK7 signaling regulated stomatal response by activating S-type anion channel SLAC1. PIP1-induced stomatal closure was impaired in bak1 , mpk3 , and mpk6 mutants, indicating that BAK1 and MPK3/MPK6 were required for PIP1-regulated stomatal movement. Our research further deciphered that OST1 which acts as an essential ABA-signaling component, also played a role in PIP1-induced stomatal closure. In addition, ROS participated in PIP1-induced stomatal closure and PIP1 could activate Ca 2+ permeable channels. In conclusion, we reveal the role of peptide PIP1 in triggering stomatal closure and the possible mechanism of PIP1 in the regulation of stomatal apertures. Our findings improve the understanding of the role of PIP1 in stomatal regulation and immune response.