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Angiotensin‐converting enzyme‐2 (ACE2) and Mas receptor are the major components of the ACE2/Ang 1‐7/Mas axis and have been shown to play a protective role in hypertension and hypertensive nephropathy individually. However, the effects of dual deficiency of ACE2 and Mas (ACE2/Mas) on Ang II‐induced hypertensive nephropathy remain unexplored, which was investigated in this study in a mouse model of hypertension induced in either ACE2 knockout (KO) or Mas KO mice and in double ACE2/Mas KO mice by subcutaneously chronic infusion of Ang II. Compared with wild‐type (WT) animals, mice lacking either ACE2 or Mas significantly increased blood pressure over 7‐28 days following a chronic Ang II infusion (P

BackgroundThymic stromal lymphopoietin (TSLP) is a mainly epithelial cell-derived cytokine that may be important in initiating T2 allergic inflammation. Anti-TSLP antibody inhibit allergic inflammation. Previous animal studies have evaluated the anti-allergic efficacy of injecting anti-TSLP antibody intraperitoneally, subcutaneously, or intravenously. However, transtracheal instillation, a less invasive route for anti-TSLP antibody administration, is hitherto unstudied. This study evaluates the efficacy of transtracheally instilling anti-TSLP antibody in inhibiting airway inflammation and hyperresponsiveness in OVA-induced asthma model Balb/c mice.MethodsBalb/c mice were randomly divided into four groups: the control group, the OVA-induced asthma model group, the anti-TSLP mAb treatment group (TSLP mAb group), and the IgG2a mAb control group (IgG2a mAb group). Each group contained nine to eleven mice. Mice in the asthma model group were sensitized with OVA to trigger allergic responses and were treated with transtracheal instillation of normal saline. Mice in the TSLP mAb group received transtracheal instillation of anti-TSLP mAb, while mice in the IgG2a group received transtracheal instillation of IgG2a mAb. Both of these groups were then subjected to OVA challenge. Airway responsiveness was measured as an enhanced pause (Penh) using noninvasive plethysmography. The severity of inflammation was evaluated by histopathological examination using the Underwood assessment of the lung sections. Changes in expression of TSLP, TSLP receptor (TSLPR), T-box transcription factor (T-bet), GATA binding protein 3 (GATA3) and forkhead box protein P3 (Foxp3) were assessed using RT-PCR and immunohistochemical staining. ResultsAirway hyperresponsiveness and infiltration of airway inflammatory cells in the TSLP mAb group were significantly reduced, compared with the OVA and the IgG2a mAb groups. Meanwhile，TSLP, GATA3 mRNA expression and GATA3 protein levels were significantly decreased in the TSLP mAb group, compared with the OVA and the IgG2a mAb groups (P＜0.05）. No significant differences were observed in either T-bet or Foxp3 in the lung section of mRNA and protein expression among these four groups (P＞0.05).ConclusionTranstracheal instillation of anti-TSLP antibody attenuated lung inflammation and airway hyperresponsiveness in OVA-induced asthmatic mice, possibly through downregulation of perivascular and peribronchiolar lymphocytes, neutrophils and GATA3 expression in the airway.

Cardiovascular diseases remain the major cause of death worldwide. Atherosclerosis is recognized as the common ground of cardiovascular diseases. Inflammatory cytokines-induced attachment of monocytes to endothelial cells is a significant event in the progression of atherosclerosis. As a highly selective dipeptidyl peptidase (DPP)-4 inhibitor, trelagliptin is used for the treatment of type 2 diabetes mellitus (T2DM). However, whether trelagliptin possesses an inhibitory effect on endothelial dysfunction and monocyte adhesion is unknown. In the current study, we tested the effect of trelagliptin in endothelial cells. We used human aortic endothelial cells (HAECs) exposed to interleukin (IL)-1β to mimic the microenvironment of atherosclerosis. Our results showed that trelagliptin inhibited the expression of pro-inflammatory chemokines including monocyte chemoattractant protein 1 (MCP-1), CXCL-1, and IL-6. Furthermore, trelagliptin suppressed the expression of adhesion molecules such as vascular cell adhesion molecule-1 (VCAM-1) and intercellular adhesion molecule-1 (ICAM-1). Mechanistically, trelagliptin suppressed the activation of activator protein-1 (AP-1) and NF-κB signaling pathways, which modulate the inflammatory process and monocyte adhesion. Collectively, our results showed that trelagliptin had a powerful inhibitory effect on the attachment of monocytes to endothelial cells, indicating that trelagliptin might have a protective effect on cardiovascular diseases such as atherosclerosis.

Lipoprotein (a) [Lp(a)] is a genetically determined risk factor of coronary artery disease (CAD). Previous genome-wide association studies (GWASs), which were mostly carried out in Caucasians, have identified many Lp(a)-associated SNPs. Here, we performed a GWAS on Lp(a) levels and further explored the relationships between Lp(a)-associated SNPs and CAD severity in 1,403 Han Chinese subjects. We observed that elevated Lp(a) levels were significantly associated with the increased synergy between percutaneous coronary intervention with TAXUS and cardiac surgery (SYNTAX) score and the counts of heavily calcified lesions and long-range lesions (LRLs; P < 0.05), which are defined as lesions spanning >20 mm. Moreover, we identified four independent SNPs, namely, rs7770628, rs73596816, and rs6926458 in LPA, and rs144217738 in SLC22A2, that were significantly associated with Lp(a) levels. We also found that rs7770628 was associated with high SYNTAX scores [odds ratio (OR) (95% CI): 1.37 (1.05–1.80), P = 0.0213, false discovery rate (FDR) = 0.0852], and that rs7770628 and rs73596816 were associated with high risk of harboring LRLs [OR (95% CI): 1.53 (1.17–2.01), P = 0.0018, FDR = 0.0072 and 1.72 (1.19–2.49), P = 0.0040, FDR = 0.0080, respectively]. Our study was a large-scale GWAS to identify Lp(a)-associated variants in the Han Chinese population. Our findings highlight the importance and potential of Lp(a) intervention and expand our understanding of CAD prevention and treatment.

Background Human angiostrongyliasis is an emerging food-borne public health problem, with the number of cases increasing worldwide, especially in mainland China. Angiostrongylus cantonensis is the causative agent of this severe disease. However, little is known about the genetics and basic biology of A. cantonensis. Results A cDNA library of A. cantonensis fourth-stage larvae was constructed, and ~1,200 clones were sequenced. Bioinformatic analyses revealed 378 cDNA clusters, 54.2% of which matched known genes at a cutoff expectation value of 10-20. Of these 378 unique cDNAs, 168 contained open reading frames encoding proteins containing an average of 238 amino acids. Characterization of the functions of these encoded proteins by Gene Ontology analysis showed enrichment in proteins with binding and catalytic activity. The observed pattern of enzymes involved in protein metabolism, lipid metabolism and glycolysis may reflect the central nervous system habitat of this pathogen. Four proteins were tested for their immunogenicity using enzyme-linked immunosorbent assays and histopathological examinations. The specificity of each of the four proteins was superior to that of crude somatic and excretory/secretory antigens of larvae, although their sensitivity was relatively low. We further showed that mice immunized with recombinant cystatin, a product of one of the four cDNA candidate genes, were partially protected from A. cantonensis infection. Conclusion The data presented here substantially expand the available genetic information about the human pathogen A. cantonensis, and should be a significant resource for angiostrongyliasis researchers. As such, this work serves as a starting point for molecular approaches for diagnosing and controlling human angiostrongyliasis.

To evaluate the effectiveness of small interfering RNA (siRNA) on inhibiting severe acute respiratory syndrome (SARS)-associated coronavirus replication, and to lay bases for the future clinical application of siRNA for the treatment of viral infectious diseases.Vero-E6 cells was transfected with siRNA before SARS virus infection, and the effectiveness of siRNA interference was evaluated by observing the cytopathic effect (CPE) on Vero-E6 cells.Five pairs of siRNA showed ability to reduce CPE dose dependently, and two of them had the best effect.siRNA may be effective in inhibiting SARS-associated coronavirus replication.