Insufficiency of Mrpl40 disrupts testicular structure and semen parameters in a murine model

Approximately 31%of patients with 22q11.2 deletion syndrome(22q11.2DS)have genitourinary system disorders and 6%of them have undescended testes.Haploinsufficiency of genes on chromosome 22q11.2 might contribute to the risk of 22q11.2DS.In this study,we used mice with single-allele deletion in mitochondrial ribosomal protein L4o(Mrpl40-)as models to investigate the function of Mrpl40 in testes and spermatozoa development.The penetrance of cryptorchidism in Mrpl40+-mice was found to be higher than that in wild-type(WT)counterparts.Although the weight of testes was not significantly different between the WT and Mrpl40+-mice,the structure of seminiferous tubules and mitochondrial morphology was altered in the Mrpl40+-mice.Moreover,the concentration and motility of spermatozoa were significantly decreased in the Mrpl4O+-mice.In addition,data-independent acquisition mass spectrometry indicated that the expression of genes associated with male infertility was altered in Mrpl40+-testes.Our study demonstrated the important role of Mrpl40 in testicular structure and spermatozoa motility and count.These findings suggest that Mrpl4o is potentially a novel therapeutic target for cryptorchidism and decreased motility and count of spermatozoa.

Effects of rosuvastatin on the production and activation of matrix metalloproteinase-2 and migration of cultured rat vascular smooth muscle cells induced by homocysteine

Objective:To test the influence of homocysteine on the production and activation of matrix metalloproteinase-2 (MMP-2) and tissue inhibitors of matrix metalloproteinase-2 (TIMP-2) and on cell migration of cultured rat vascular smooth muscle cells (VSMCs). Also, to explore whether rosuvastatin can alter the abnormal secretion and activation of MMP-2 and TIMP-2 and migration of VSMCs induced by homocysteine. Methods:Rat VSMCs were incubated with different concentrations of homocysteine (50-5 000 μmol/L). Western blotting and gelatin zymography were used to investigate the expressions and activities of MMP-2 and TIMP-2 in VSMCs in culture medium when induced with homocysteine for 24, 48, and 72 h. Transwell chambers were employed to test the migratory ability of VSMCs when incubated with homocysteine for 48 h. Different concentrations of rosuvastatin (10-9-10-5 mol/L) were added when VSMCs were induced with 1 000 μmol/L homocysteine. The expressions and activities of MMP-2 and TIMP-2 were examined after incubating for 24, 48, and 72 h, and the migration of VSMCs was also examined after incubating for 48 h. Results:Homocysteine (50-1 000 μmol/L) increased the production and activation of MMP-2 and expression of TIMP-2 in a dose-dependent manner. However, when incubated with 5 000 μmol/L homocysteine, the expression of MMP-2 was up-regulated, but its activity was down-regulated. Increased homocysteine-induced production and activation of MMP-2 were reduced by rosuvastatin in a dose-dependent manner whereas secretion of TIMP-2 was not significantly altered by rosuvastatin. Homocysteine (50-5 000 μmol/L) stimulated the migration of VSMCs in a dose-dependent manner, but this effect was eliminated by rosuvastatin. Conclusions:Homocysteine (50-1 000 μmol/L) significantly increased the production and activation of MMP-2, the expression of TIMP-2, and the migration of VSMCs in a dose-dependent manner. Additional extracellular rosuvastatin can decrease the excessive expression and activation of MMP-2 and abnormal migration of VSMCs induced by homocysteine.

AST-to-ALT ratio and coronary artery lesions among patients with Kawasaki disease

Background The aim of this study was to explore the associations between the aspartate aminotransferase-to-alanine aminotransferase ratio(AST/ALT)and coronary artery lesions(CALs)among patients with Kawasaki disease(KD).Methods Medical records of KD patients presenting to a single center between January 2019 and December 2020 were retrospectively collected and analyzed.Univariate,multivariable-adjusted analyses,subgroup analyses,restricted cubic spline test,and fitted curves were used to evaluate the associations between AST/ALT and CALs.Results A total of 831 patients were enrolled,of which 201(24.2%)had CALs on admission and 21(2.5%)developed CALs de novo after intravenous immunoglobulin(IVIG).Multivariable-adjusted analyses models revealed that a lower AST/ALT was associated with an increased risk of CALs on admission when AST/ALT was a continuous variable(P=0.007)and when it was a categorical variable(P for trend=0.004).Each unit increase in AST/ALT was associated with a 22%lower risk of CALs on admission(odds ratio=0.78,95%confidence interval 0.65-0.94).A negative linear relationship was noted between AST/ALT and the risk of CALs on admission in both observed and fitted models.However,such associations were not observed in AST/ALT and CALs de novo after IVIG.None of the variables significantly modified the association between AST/ALT and CALs on admission and CALs de novo after IVIG(P>0.05).Conclusion Our findings suggested that AST/ALT was a risk factor of CALs,but was not associated with progressive CALs.

Clinical characteristics of Kawasaki disease and concurrent pathogens during isolation in COVID-19 pandemic

Background The aim of this study is to explore the characteristics of Kawasaki disease(KD)and concurrent pathogens due to a stay-at-home isolation policy during coronavirus disease 2019(COVID-19)epidemic.Methods All patients with KD admitted between February and April in 2015-2020,were classified into before(group 1,in 2015-2019)and after(group 2,in 2020)isolation groups.A total of 4742 patients[with KD(m=98)and non-KD(n=4644)]referred to Mycoplasma pneumoniae(MP)and virus detection were analyzed in 2020.Clinical characteristics,laboratory data,and 13 pathogens were analyzed retrospectively.Results Group 2 had a significantly increased incidence of KD(0.11%)with 107 patients compared to that of group 1(0.03%)with 493 patients.The comparisons of oral mucosal change,strawberry tongue,desquamation of the fingertips,cervical lymphadenopathy and neutrophil percentage decreased in group 2 compared to group 1.The infection rate of MP increased significantly in group 2(34.7%)compared to group 1(19.3%),while the positive rate of viruses decreased significantly in group 2(5.3%)compared to group 1(14.3%).In 2020,the positive rate of MP infection increased significantly in patients with KD compared to the increase in patients with non-KD.The infection rate of MP for younger children aged less than 3 years old was higher in group 2 than in group 1.Conclusion Compared with the characteristics of KD from 2015 to 2019 years,the incidence of KD was increased in 2020 and was accompanied by a high incidence of MP infection,especially in younger children(less than 3 years old)during the isolation due to COVID-19 pandemic.