OBJECTIVETo investigate the association between the genetic variant of miRNA-1 target gene COG6 rs9548934 C→T and the risk of premature coronary artery disease (pCAD).

METHODSThis study included 226 pACD patients and 275 gender and age matched pCAD-free controls hospitalized in our hospital, diagnosis was made based on coronary angiography (CAG) results. The genotypes of miRNA-1 target gene COG6 rs9548934 C→T were detected by PCR-RFLP.

RESULTSCompared with the wide genotype CC, subjects with the variant genotypes CT of rs9548934 C→T was associated with a 45% lower risk of pACD (adjusted OR = 0.55, 95%CI = 0.36 - 0.82, P = 0.003), and the subjects with CT/TT genotypes were also associated with a significantly lower risk of pACD (adjusted OR = 0.64, 95%CI = 0.44 - 0.92, P = 0.015). Using the median serum TG level (1.20 mmol/L) in control group as the cutoff value, subjects with higher serum TG levels were associated with increased risk of pACD after adjustment for age, gender and BMI (adjusted OR = 2.32, 95%CI = 1.57 - 3.41, P < 0.001). In addition, subjects with higher HDL-C levels were associated with significantly lower risk of pACD (adjusted OR = 0.48, 95%CI = 0.31 - 0.75, P = 0.001). Stratified analyses showed that the risk reduction for pCAD in CT/TT genotypes carriers was more significant in the female subjects (adjusted OR = 0.54, 95%CI = 0.30 - 0.97, P = 0.040), and in subjects with lower TG, TC, HDL-C and LDL-C levels (adjusted OR = 0.62, 95%CI = 0.39 - 0.98, P = 0.040; adjusted OR = 0.55, 95%CI = 0.35 - 0.85, P = 0.008; adjusted OR = 0.43, 95%CI = 0.22 - 0.87, P = 0.018; adjusted OR = 0.49, 95%CI = 0.32 - 0.75, P = 0.001, respectively).

CONCLUSIONThe polymorphism of miRNA-1 target gene COG6 rs9548934C→T is associated with lower risk of pCAD, especially in female subjects and subjects with lower serum lipid levels.

Adaptor Proteins, Vesicular Transport ; genetics ; Adult ; Case-Control Studies ; Coronary Artery Disease ; genetics ; Female ; Gene Frequency ; Genotype ; Humans ; Male ; MicroRNAs ; genetics ; Middle Aged ; Polymorphism, Single Nucleotide

After treating with chemotherapy or immunosuppressant, malignant diseases of hematopoietic system such as leukemia, malignant lymphoma and aplastic anemia usually induced severe infection such as sepsis. Sepsis which is hard to be diagnosed causes high death rate. This study was purposed to establish an experimental sepsis mouse model so as to provide a basis for pathogenesis and intervention study. A classic caecal ligation and puncture (CLP) was used to establish experimental sepsis model. ELISA was used to detect levels of C5a, IL-6, TNFalpha, and IFN-gamma. Flow Cytometry was applied to measure apoptosis of lymphocytes in thymus and mesentery. The pathologic changes of thymus and spleen were confirmed by HE staining. The results showed that almost 70%-80% mice died at 72 hours after CLP. Only approximate 20% animal survived during finite time, mice in CLP group had significant weight lose. Meanwhile large release of different inflammatory mediators which are related with sepsis (C5a, IL-6, TNF-alpha, and IFN-gamma) was observed after CLP. Apoptosis of lymphocytes in thymus and mesentery lymphonodus was enhanced markedly after CLP. Significantly pathologic injury was also observed in thymus and spleen. It is concluded that a mouse model of experimental sepsis was successfully established by caecal ligation and puncture which can well mimic the clinical symptom of sepsis. The experimental sepsis mouse model provides an excellent tool for exploring the pathogenesis and intervention ways for sepsis accompanied with complicated malignant hematological diseases in vivo.
Animals ; Apoptosis ; Cecum ; injuries ; Complement C5a ; metabolism ; Disease Models, Animal ; Interferon-gamma ; metabolism ; Interleukin-6 ; metabolism ; Male ; Mice ; Mice, Inbred C57BL ; Sepsis ; metabolism ; pathology ; Spleen ; pathology ; Thymus Gland ; pathology ; Tumor Necrosis Factor-alpha ; metabolism

Two novel Mannich base derivatives of silybin, SLB-DEA and DHSLB-PIP, were designed and synthesized. All the structures of new Mannich base derivatives of silybin were characterized by ¹H NMR and HR-MS. Their protective action against CCl₄-induced liver injury in mice were investigated. The changes of alanine aminotransferase (ALT), aspartate transaminase (AST), lactate dehydrogenase (LDH), total cholesterol (TC) and triglyceride (TG) were determined and the histopathological changes in liver tissues were examined. Pretreatment with a higher dosage of DHSLB-PIP (40 mg·kg^-1) prevented CCl₄-induced liver injury as indicated by the reduced levels of ALT, AST, LDH and TG. Meanwhile, liver histopathological improvement was observed in the model groups. The pharmacokinetics study in rats showed that the relative bioavailability of SLB-DEA and DHSLB-PIP were 172.5% and 259.8% compared with silybin. All the results suggest that SLB-DEA and DHSLB-PIP may protect liver against injury by CCl₄ and the relative bioavailability was significantly increased, which is worth of further investigation for their druggability.