Heterozygous CARD9 mutation favors the development of allergic bronchopulmonary aspergillosis / 中华医学杂志(英文版)

BACKGROUND@#Previous research demonstrated that a homozygous mutation of g.136372044G>A (S12N) in caspase recruitment domain family member 9 ( CARD9 ) is critical for producing Aspergillus fumigatus -induced ( Af -induced) T helper 2 (T H 2)-mediated responses in allergic bronchopulmonary aspergillosis (ABPA). However, it remains unclear whether the CARD9S12N mutation, especially the heterozygous occurrence, predisposes the host to ABPA.@*METHODS@#A total of 61 ABPA patients and 264 controls (including 156 healthy controls and 108 asthma patients) were recruited for sequencing the CARD9 locus to clarify whether patients with this heterozygous single-nucleotide polymorphisms are predisposed to the development of ABPA. A series of in vivo and in vitro experiments, such as quantitative real-time polymerase chain reaction, flow cytometry, and RNA isolation and quantification, were used to illuminate the involved mechanism of the disease.@*RESULTS@#The presence of the p.S12N mutation was associated with a significant risk of ABPA in ABPA patients when compared with healthy controls and asthma patients, regardless of Aspergillus sensitivity. Relative to healthy controls without relevant allergies, the mutation of p.S12N was associated with a significant risk of ABPA (OR: 2.69 and 4.17 for GA and AA genotypes, P = 0.003 and 0.029, respectively). Compared with patients with asthma, ABPA patients had a significantly higher heterozygous mutation (GA genotype), indicating that p.S12N might be a significant ABPA-susceptibility locus ( aspergillus sensitized asthma: OR: 3.02, P = 0.009; aspergillus unsensitized asthma: OR: 2.94, P = 0.005). The mutant allele was preferentially expressed in ABPA patients with heterozygous CARD9S12N , which contributes to its functional alterations to facilitate Af -induced T H 2-mediated ABPA development. In terms of mechanism, Card9 wild-type ( Card9WT ) expression levels decreased significantly due to Af -induced decay of its messenger RNA compared to the heterozygous Card9S12N . In addition, ABPA patients with heterozygous CARD9S12N had increased Af -induced interleukin-5 production.@*CONCLUSION@#Our study provides the genetic evidence showing that the heterozygous mutation of CARD9S12N , followed by allele expression imbalance of CARD9S12N , facilitates the development of ABPA.

Effects of astragaloside IV on experimental ventricular remodeling in mice and its mechanism from matrix metalloproteinase aspect / 中国药科大学学报

Aim: To study the effects of astragaloside IV on experimental ventricular remodeling in mice and its mechanism from matrix metalloproteinase aspect.Method: Ventricular remodeling in mice was induced by con-secutively subcutaneous injection of isoproterenol for 14 days.Astragaloside IV(40,80 mg/kg)and propranolol(40 mg/kg,positive control)were administered by gavage to mice.Echocardiography was used to observe the left ventricular end diastolic diameter(LVIDd),left ventricular end systolic diameter(LVIDs),fractional shortening(FS)and ejection fraction(EF).The myocardial pathological pattern was detected by HE staining.Expressions of matrix metalloproteinases(MMP2,MMP9)and tissue inhibitor of metalloproteinases(TIMP1,TIMP2)mRNA in myocardium were detected by RT-PCR.Activities of MMP2 and MMP9 were assayed by zymography.Results:Compared with those of control mice,LVIDd and LVIDs were increased,FS and EF were decreased in the model group.Myocardial injury and fibrosis existed in histop at hological slices of the model group.In addition,the mRNA expressions and activities of MMP2 and MMP9 were increased in the model group.However,there were no markable changes to TIMP1 and TIMP2.Treatment with astragaloside IV reduced LVIDd and LVIDs,increased FS and EF,attenuated myocardial injury,and down-regulated mRNA expressions and activities of MMP2 and MMP9 compared with the model group.Conclusion: Astragaloside IV can greatly improve ventricular remodeling and dysfunction via decreasing MMP2 and MMP9 mRNA expression and activities in cardiac ventricles.

Quality Evaluation of Warfarin Sodium Tablets from Different Pharmaceutical Manufacturers / 中国药房

0.01).The dissolution of tablets from A and D manufacturers were same to each other while both of them were larger than those from B and C manufacture.CONCLUSIONS:The qualities of Warfarin sodium tablets from four manufacturers are different from one another.The quality of products from A and D manufacturers are superior to those from manufacturer B.The products from manufacturer C are the worst.