ABSTRACT
Vascular dementia (VD) a heterogenous group of brain disorders in which cognitive impairment is attributable to vascular risk factors and cerebrovascular disease. A common phenomenon in VD is a dysfunctional cerebral regulatory mechanism associated with insufficient cerebral blood flow, ischemia and hypoxia. Under hypoxic conditions oxygen supply to the brain results in neuronal death leading to neurodegenerative diseases including Alzheimer's (AD) and VD. In conditions of hypoxia and low oxygen perfusion, expression of hypoxia-inducible factor 1 alpha (HIF-1α) increases under conditions of low oxygen and low perfusion associated with upregulation of expression of hypoxia-upregulated mitochondrial movement regulator (HUMMR), which promotes anterograde mitochondrial transport by binding with trafficking protein kinesin 2 (TRAK2). Schisandrin B (Sch B) an active component derived from Chinese herb Wuweizi prevented ß-amyloid protein induced morphological alterations and cell death using a SH-SY5Y neuronal cells considered an AD model. It was thus of interest to determine whether Sch B might also alleviate VD using a rat bilateral common carotid artery occlusion (BCAO) dementia model. The aim of this study was to examine the effects of Sch B in BCAO on cognitive functions such as Morris water maze test and underlying mechanisms involving expression of HIF-1α, TRAK2, and HUMMR levels. The results showed that Sch B improved learning and memory function of rats with VD and exerted a protective effect on the hippocampus by inhibition of protein expression of HIF-1α, TRAK2, and HUMMR factors. Evidence indicates that Sch B may be considered as an alternative in VD treatment.
Subject(s)
Dementia, Vascular , Lignans , Neuroblastoma , Polycyclic Compounds , Rats , Humans , Animals , Dementia, Vascular/drug therapy , Dementia, Vascular/etiology , Dementia, Vascular/metabolism , Maze Learning/physiology , Hypoxia , Cognition , Hippocampus , Oxygen/pharmacology , CyclooctanesABSTRACT
This study was aimed to analyze the ß-globin gene sequence and single nucleotide polymorphisms of the ß-globin gene in ß-thalassaemia patients from Shenzhen area, and to explore linkage relationships between ß-globin gene mutations and single nucleotide polymorphisms. Genomic DNA was extracted from peripheral leukocytes in 125 ß-thalassaemia patients from Shenzhen population. ß-globin gene was amplified by polymerase chain reaction, mutations and single nucleotide polymorphisms in the ß-globin gene were determined by DNA sequencing. The results indicated 10 types of mutation and 12 single nucleotide polymorphism loci were found in the ß-globin gene of 114 ß-thalassaemia patients. Linkage disequilibrium between mutations and single nucleotide polymorphisms was found in 6 loci including 6 haplotypes among these single nucleotide polymorphism loci in the ß-globin gene. It is concluded that a number of single nucleotide polymorphisms is found in the ß-globin gene, where an average of one single nucleotide polymorphism every 230 bp there is. Linkage disequilibrium occurs between ß-thalassaemia mutations and some haplotypes in single nucleotide polymorphism loci. This study may be helpful to gene diagnosis for ß-thalassaemia patients.
Subject(s)
Polymorphism, Single Nucleotide , beta-Globins/genetics , beta-Thalassemia/genetics , Adolescent , Adult , Case-Control Studies , Child , Child, Preschool , China , DNA/genetics , Female , Haplotypes , Humans , Male , Middle Aged , Mutation , Young AdultABSTRACT
OBJECTIVE: To investigate the splice variants of the calpain 3 gene existing in human skeletal muscle tissue and white blood cells, and to explore the feasibility of gene diagnosis using CAPN3 mRNA extracted from peripheral leukocytes. METHODS: Total RNA was extracted from peripheral blood and skeletal muscle tissue in healthy individuals. CAPN3 cDNAs were determined by reverse transcriptase polymerase chain reaction and DNA sequencing. CAPN3 cDNAs from peripheral leukocytes were compared with sequences obtained from skeletal muscle tissue. RESULTS: RT-PCR and DNA sequencing showed that the CAPN3 cDNAs comprised 24 exons in human skeletal muscle tissue, while the number of exons was 23 in white blood cells. Exon 15 was spliced out in human white blood cells. CONCLUSION: Splice variants exist in human skeletal muscle tissue and white blood cells. Gene diagnosis may omit the mutations of exon 15 using mRNA extracted from peripheral leukocytes. These findings suggest that mutation analysis of the CAPN3 cDNA should use skeletal muscle tissue as materials instead of peripheral blood.
Subject(s)
Calpain/genetics , Leukocytes/metabolism , Muscle Proteins/genetics , Muscle, Skeletal/metabolism , DNA Mutational Analysis , DNA, Complementary/genetics , Exons/genetics , Humans , Reverse Transcriptase Polymerase Chain ReactionABSTRACT
OBJECTIVE: Duchenne muscular dystrophy (DMD) usually occurs prior to 3 years old. The value of serum creatine kinase changes with clinical progression and age in patients with DMD. This study aimed to investigate the regularity in the changes of serum creatine kinase activities in children with DMD. METHODS: Peripheral blood samples were obtained from 40 children with DMD (ranged from 3-14 years). Serum creatine kinase levels were assayed by kinetic UV test. RESULTS: Serum creatine kinase level in the 40 DMD patients (ranged from 2 595- 45 495 U/L) was remarkably higher than the reference value (35-174 U/L). The highest serum creatine kinase level (average: 27750-31173 U/L) was found in 3-5 years old patients. Afterwards, serum creatine kinase level decreased with clinical progression and age, with a yearly average rate of decline was 8.7%. CONCLUSIONS: Serum creatine kinase level reaches a peak between 3 and 5 years old and then reduces with increasing age in children with DMD. The characteristic changes of serum creatine kinase are suspected to reflect the rate of muscle decay.
