Cardiac Resolvin D2 ameliorates sepsis-induced cardiomyopathy via inhibiting Caspase-11/GSDMD dependent pyroptosis.

BACKGROUND: Sepsis-induced cardiomyopathy (SICM) is common complication in septic patients with a high mortality and is characterized by an abnormal inflammation response, which was precisely regulated by endogenous specialized pro-resolving mediators (SPMs). However, the metabolic changes of cardiac SPMs during SICM and the roles of SPMs subset in the development of SICM remain unknown. METHODS: In this work, the SPMs concentration was assessed using ultra-performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) of SICM mice and SICM patients. The cardiac function was measured by echocardiography after the treatment of a SPMs subset, termed Resolvin D2 (RvD2). Caspase-11-/-, GSDMD-/- and double deficient (Caspase-11-/-GSDMD-/-) mice were used to clarify the mechanisms of RvD2 in SICM. RESULTS: We found that endogenous cardiac SPMs were disorders and RvD2 was decreased significantly and correlated with left ventricular ejection fraction (LVEF) and ß-BNP, cTnT in Lipopolysaccharide/Cecum ligation and puncture (CLP) induced SICM models. Treatment with RvD2 attenuated lethality, cardiac dysfunction and cardiomyocytes death during SICM. Mechanistically, RvD2 alleviated SICM via inhibiting Caspase-11/GSDMD-mediated cardiomyocytes pyroptosis. Finally, the plasma levels of RvD2 were also decreased and significantly correlated with IL-1ß, ß-BNP, cTnT and LVEF in patients with SICM. Of note, plasma RvD2 level is indicator of SICM patients from healthy controls or sepsis patients. CONCLUSION: These findings suggest that decreased cardiac RvD2 may involve in the pathogenesis of SICM. In addition, treatment with RvD2 represents a novel therapeutic strategy for SICM by inhibiting cardiomyocytes pyroptosis.

Efficient pulmonary lymphatic drainage is necessary for inflammation resolution in ARDS.

The lymphatic vasculature is the natural pathway for the resolution of inflammation, yet the role of pulmonary lymphatic drainage function in sepsis-induced acute respiratory distress syndrome (ARDS) remains poorly characterized. In this study, indocyanine green-near infrared lymphatic living imaging was performed to examine pulmonary lymphatic drainage function in septic mouse models. We found that the pulmonary lymphatic drainage was impaired owing to the damaged lymphatic structure in sepsis-induced ARDS. Moreover, prior lymphatic defects by blocking vascular endothelial growth factor receptor-3 (VEGFR-3) worsened sepsis-induced lymphatic dysfunction and inflammation. Posttreatment with vascular endothelial growth factor-C (Cys156Ser) (VEGF-C156S), a ligand of VEGFR-3, ameliorated lymphatic drainage by rejuvenating lymphatics to reduce the pulmonary edema and promote draining of pulmonary macrophages and neutrophils to pretracheal lymph nodes. Meanwhile, VEGF-C156S posttreatment reversed sepsis-inhibited CC chemokine ligand 21 (CCL21), which colocalizes with pulmonary lymphatic vessels. Furthermore, the advantages of VEGF-C156S on the drainage of inflammatory cells and edema fluid were abolished by blocking VEGFR-3 or CCL21. These results suggest that efficient pulmonary lymphatic drainage is necessary for inflammation resolution in ARDS. Our findings offer a therapeutic approach to sepsis-induced ARDS by promoting lymphatic drainage function.

Sarcopenia as a predictor of mortality in women with breast cancer: a meta-analysis and systematic review.

BACKGROUND: Breast cancer is the most commonly diagnosed cancer and the leading cause of cancer death in women worldwide. Recently, studies have been published with inconsistent findings regarding whether sarcopenia is a risk factor for mortality in breast cancer patients. Therefore, the aim of this systematic review and meta-analysis was to systematically assess and quantify sarcopenia as a risk factor for mortality in breast cancer patients. METHODS: In a systematic literature review of PubMed, EMBASE, and the Cochrane CENTRAL Library, we searched for observational studies written in English (from database inception until April 30, 2019) that reported an association between sarcopenia and breast cancer in women who were 18 years or older. RESULTS: A total of six studies (5497 participants) were included in this meta-analysis. Breast cancer patients with sarcopenia were associated with a significantly higher risk of mortality, compared to breast cancer patients without sarcopenia (pooled HR-hazard ratio = 1.71, 95% CI: 1.25-2.33, I2 = 59.1%). In addition, the results of age subgroup analysis showed that participants younger than 55 years with sarcopenia had a lower risk of mortality than participants aged 55 years and older with sarcopenia (pooled HR = 1.46, 95% CI: 1.24-1.72 versus pooled HR = 1.99, 95% CI: 1.05-3.78), whereas both have an increased risk of mortality compared to non-sarcopenic patients. Subgroup analyses regarding stage at diagnosis revealed an increased risk of mortality in non-metastatic patients compared to participants without sarcopenia (pooled HR = 1.91, 95% CI: 1.32-2.78), whereas the association was not significant in metastatic breast cancer patients. Other subgroup analyses were performed using different follow-up periods (> 5 years versus ≤5 years) and the results were different (pooled HR = 1.81, 95% CI: 1.23-2.65 versus pooled HR = 1.70, 95% CI: 0.80-3.62). CONCLUSIONS: The present study found that sarcopenia is a risk factor for mortality among female early breast cancer patients. It is imperative that more research into specific interventions aimed at treating sarcopenia be conducted in the near future in order to provide evidence which could lead to decreased mortality rates in breast cancer patients.

Polyphasic taxonomic characterisation of a novel strain as Pararhizobium haloflavum sp. nov., isolated from soil samples near a sewage treatment tank.

A Gram-stain negative, aerobic, motile and ovoid- to rod-shaped bacteria strain, designated XC0140T, was isolated from soil samples near the sewage treatment tank of a chemical factory in Zhejiang Province, China, and subjected to polyphasic taxonomic investigation. Strain XC0140T grew at 10-37 °C and pH 6.0-9.0 (optimum, 35 °C and pH 7.5) and with 0-17% (w/v) NaCl (optimum, 1%). According to phylogenetic analysis based on 16S rRNA gene sequences, strain XC0140T was assigned to the genus Pararhizobium with high 16S rRNA gene sequence similarity of 95.97% to "Pararhizobium helanshanense CCNWQTX14T", followed by Pararhizobium sphaerophysae CCNWGS0238T (95.95%). Chemotaxonomic analysis showed that strain XC0140T contains ubiquinone-10 as the predominant respiratory quinone and possessed summed feature 8 (comprising C18: 1 ω7c and/or ω6c), 11-methyl C18:1 ω7c, C18: 0 and C16: 0 as predominant forms of fatty acids. The polar lipids of strain XC0140T consisted of seven phospholipids (PL), two aminolipids (AL), one glycolipid (GL) and three unidentified lipids (L1, L2 and L3). The DNA G+C content was 62.7 mol%. Based on the polyphasic taxonomic characterization, strain XC0140T is considered to represent a novel species of the genus Pararhizobium, for which the name Pararhizobium haloflavum sp. nov. is proposed. (type strain XC0140T = MCCC 1K03228T = KCTC 52582T).