ABSTRACT
Myocarditis is a common cardiovascular disease and frequently occurs in children and teenagers. It is believed to be caused by both endogenous and exogenous factors, among which FAS/FASL gene pair-induced cell apoptosis is a major mechanism of myocardial cell injury. A previous study has detected low expression of microRNA (miR)-98 in myocarditis patients. Therefore, in this study we investigated the functional implications of miR-98 with respect to the disease. We carried out a case-control study including 50 myocarditis patients and 50 healthy individuals. Total RNA was extracted from peripheral blood plasma. Expression levels of miR-98 and the FAS/FASL gene pair were determined by real-time fluorescent quantitative polymerase chain reaction. The interaction between miR-98 and the FAS/FASL pair was visualized by dual-luciferase reporter assay. The expression of the FAS/FASL gene pair was further detected by transfecting with an miR-98 mimic or an miR-98 inhibitor. The content of miR-98 in the peripheral blood of the myocarditis patients was significantly lower than in the healthy individuals. However, the FAS/FASL genes were upregulated by 1.68-fold in the myocarditis patients. miR-98 was shown to interact with the 3'-untranslated region of the FAS/FASL gene pair. The inhibition/facilitation of miR-98 expression in myocardial cells can modulate apoptosis. miR-98 was downregulated in the peripheral blood of myocarditis patients. It may interact with the FAS/FASL gene pair to further modulate cell apoptosis.
Subject(s)
Fas Ligand Protein/biosynthesis , MicroRNAs/biosynthesis , Myocarditis/genetics , fas Receptor/biosynthesis , Apoptosis/genetics , Case-Control Studies , Fas Ligand Protein/genetics , Female , Gene Expression Regulation , Humans , Male , MicroRNAs/genetics , Myocarditis/pathology , Myocardium/pathology , fas Receptor/geneticsABSTRACT
Brain natriuretic peptide (BNP) has a protective effect on acute injury of the heart, brain, and lung. However, its role in acute kidney injury (AKI) remains unclear. The aim of this study was to investigate the effect of lyophilized recombinant human BNP (lrh-BNP) on AKI and the underlying molecular mechanisms. An experimental model for AKI was established using an ischemia/reperfusion (I/R) procedure. Healthy adult BALB/c mice were randomized to the sham, I/R, and lrh-BNP-treated post-I/R (BNP + I/R) groups. Post-operatively, the BNP + I/R group was subcutaneously injected with lrh-BNP (0.03 µg·kg(-1)·min(-1)), whereas the other groups received saline at the same dose. Serum creatinine (Scr) and blood urea nitrogen levels were examined; tissue staining was performed to evaluate the degree of I/R injury (IRI). Ki67 positive staining of renal tubular epithelial cells was observed using immunofluorescence confocal laser scanning to assess the effect of BNP on cell proliferation after IRI. Inflammatory factor expression levels were detected to evaluate the effect of BNP on renal inflammation. Compared with the sham group, the I/R group showed increased Scr levels, severe tubular injury of the renal outer medulla, increased Kim-1 mRNA expression, an increased number of infiltrative macrophages in the renal interstitium, and increased TNF-α, IL- 1ß, IL-6, MCP-1, and HIF-1α mRNA expression. BNP delivery significantly reduced all pathological changes in the I/R group. The protective role of BNP in murine renal IRI may be associated with its inhibition of renal interstitial inflammation and hypoxia and its promotion of renal tubule repair.
Subject(s)
Acute Kidney Injury/pathology , Acute Kidney Injury/physiopathology , Natriuretic Peptide, Brain/pharmacology , Protective Agents/pharmacology , Recombinant Proteins/pharmacology , Reperfusion Injury/pathology , Reperfusion Injury/physiopathology , Acute Kidney Injury/drug therapy , Acute Kidney Injury/etiology , Acute Kidney Injury/metabolism , Animals , Disease Models, Animal , Epithelium/blood supply , Epithelium/drug effects , Epithelium/metabolism , Epithelium/pathology , Humans , Hypoxia/drug therapy , Hypoxia/etiology , Hypoxia/metabolism , Inflammation/drug therapy , Inflammation/etiology , Inflammation/pathology , Kidney Function Tests , Kidney Tubules/blood supply , Kidney Tubules/drug effects , Kidney Tubules/metabolism , Kidney Tubules/pathology , Male , Mice , Natriuretic Peptide, Brain/administration & dosage , Protective Agents/administration & dosage , Recombinant Proteins/administration & dosage , Reperfusion Injury/drug therapy , Reperfusion Injury/metabolismABSTRACT
Polymorphisms of the CART gene were investigated by PCR-single-strand conformation polymorphism analysis in 540 samples from 10 goat breeds. Ten novel single-nucleotide polymorphisms as well as three microsatellites were detected; a mutation, 77T â C, led to an amino acid change (Leu â Ser). Associations between polymorphic loci and reproductive traits were analyzed in Chuandong White, Guizhou White and Gulin Ma breeds. Mutation at position 524 had no significant effect on litter size in these three goat breeds. The polymorphism 539C â A differed significantly among the three breeds (P < 0.05); C(7)T(8)/C(9)T(8) at 939 was associated with larger litter size (P < 0.05) than genotypes C(7)T(8)/C(7)T(8) and C(7)T(8)/C(8)T(8). No significant association of birth weight was found with gene variation (524C â T, 539C â A and 939 CnTn). These findings could be valuable for marker-assisted selection for goat breeding.