ABSTRACT
BACKGROUND: The hereditary antithrombin (AT) deficiency caused by SERPINC1 gene mutation is an autosomal dominant thrombotic disorder. An increasing number of studies have shown that mutations in the SERPINC1 rs2227589 polymorphic site are correlated with a risk of venous thromboembolism (VTE) at common sites, such as lower extremity deep venous thrombosis and pulmonary thromboembolism. Currently, there are no reports of cerebral venous sinus thrombosis (CVST), a VTE site with a low incidence rate and rs2227589 polymorphism. CASE SUMMARY: Here, we report a Chinese CVST case with a mutation of the SERPINC1 rs2227589 polymorphic site, which did not cause significant AT deficiency. In a 50-year-old male patient presenting with multiple cerebral venous sinus thromboses no predisposing factors were detected, although a relative had a history of lower extremity deep venous thrombosis. We performed sequencing of the SERPINC1 gene for the patient and his daughter, which revealed the same heterozygous mutation at the rs2227589 polymorphic site: c.41+141G>A. CONCLUSION: The results showed that more studies should be conducted to assess the correlation between rs2227589 polymorphism and CVST.
ABSTRACT
Cell-derived exosomes (EXs) can modulate target cell differentiation via microRNAs (miRs) that they carried. Previous studies have shown that miR126 is highly expressed in hematopoietic stem cells (HSCs) and plays a role in hematopoiesis via modulating the Notch pathway that participates in progenitors' cell fate decisions. In this study we investigated whether HSC-derived EXs (HSC-EXs) could affect the differentiation of mouse embryonic stem cells (ESCs) into HSCs. We prepared HSC-EXscon, HSC-EXssc and HSC-EXsmiR126 from control HSCs and the HSCs transfected with scramble control or miR126 mimics, respectively. HSC-EXs were isolated by ultracentrifugation and analyzed using nanoparticle tracking analysis. We incubated the collected EXs with mouse ESCs over a 10-d differentiation induction period, during which HSC-EXs and a Notch pathway activator (Jagged1, 100 ng/mL) were added to the cultures every 3 d. After the 10-d differentiation period, the expression levels of miR126, SSEA1, CD117, Sca1, Notch1 and Hes1 in ESCs were assessed. The generated HSCs were validated by flow cytometry using antibodies against HSC markers (CD117, CD34 and Sca1). Our results revealed that: (1) transfection with miR126 mimics significantly increased miR126 levels in HSC-EXsmiR126. (2) HSC-EX co-culture promoted mouse ESCs differentiation into HSCs with the most prominent effect found in the HSC-EXsmiR126 co-culture. (3) HSC differentiation was verified by reduced SSEA1 expression and increased CD117 and Sca1 expression. (4) All the effects caused by HSC-EXs were accompanied by significant reduction of Notch1 and Hes1 expression, thus inhibition of the Notch1/Hes1 pathway, whereas activation of Notch by Jagged1 abolished the effects of HSC-EXsmiR126. In conclusion, HSC-EXs promote hematopoietic differentiation of mouse ESCs in vitro by inhibiting the miR126/Notch1 pathway.
Subject(s)
Cell Differentiation/drug effects , Exosomes/metabolism , MicroRNAs/antagonists & inhibitors , Receptor, Notch1/antagonists & inhibitors , Signal Transduction/drug effects , Animals , Cell Self Renewal , Hematopoietic Stem Cells/metabolism , Jagged-1 Protein/metabolism , Mice , MicroRNAs/metabolism , Mouse Embryonic Stem Cells/drug effects , Mouse Embryonic Stem Cells/metabolism , Receptor, Notch1/metabolismABSTRACT
Accumulating evidence from animal and human research indicate that adult hippocampal neurogenesis plays a key role in cognition. Meanwhile, cognitive decline is well known to associate with ageing-related neurodegenerative diseases such as Alzheimer's disease (AD) and Parkinson's disease (PD). Therefore, prevention of hippocampal neurogenesis reduction should be critical for these diseases. Physical exercise, a potent enhancer of adult hippocampal neurogenesis, has emerged as a potential therapy or an adjunctive therapeutic strategy for cognitive decline. In this review, we discuss the recent findings on hippocampal neurogenesis and the incorporation of new born neurons into the neuronal network in humans and in rodents. By focusing on hippocampal neurogenesis, we illustrate the role and possible mechanisms of physical exercise in cognition preservation.
Subject(s)
Cognition Disorders/prevention & control , Exercise , Hippocampus/physiology , Neurogenesis/physiology , Animals , Hippocampus/cytology , Humans , Nerve Net/physiologyABSTRACT
The present study examined sequence variations in three mitochondrial DNA (mtDNA) regions, namely, NADH dehydrogenase subunit 5 (nad5), adenosine triphosphate subunit 6 (atp6) and cytochrome c oxidase subunit 3 (cox3), among Oesophagostomum asperum isolates from different regions in Shaanxi and Hunan provinces, China. The lengths for partial sequences of nad5 (pnad5), atp6 (patp6) and cox3 (pcox3) were 427 bp, 381 bp and 337 bp, respectively. The intra-specific sequence variations among all O. asperum samples were 0-2.11%, 0-1.84% and 0-1.48% for pnad5, patp6 and pcox3, respectively, while the inter-specific sequence differences among Oesophagostomum species in pig and small ruminants were 18-21.3% for pnad5, 18.3-24.5% for patp6 and 10.6-13.7% for pcox3. A phylogenetic analysis based on combined sequences of three mtDNA fragments indicated that all O. asperum isolates were grouped in one solid clade, and the Oesophagostomum spp. from pig were located in another clade. However, these mtDNA fragments could not reveal genetic relationships of geographical isolates of O. asperum in China. These results provided valuable information for studying population genetics of Oesophagostomum spp., and for controlling Oesophagostomum infection in animals as well as humans.
Subject(s)
Genes, Helminth , Genetic Variation , Genome, Mitochondrial , Strongylida/genetics , Animals , Base Sequence , China , DNA Primers , DNA, Mitochondrial/genetics , Phylogeny , Polymerase Chain ReactionABSTRACT
OBJECTIVE: To explore the frequencies of heterozygosity in X-linked G6PD, P55, BTK, and FHL-1 gene exonic polymorphic loci among Chinese females and the value of determination of hematopoietic clonality by detection of these X-chromosome exonic polymorphisms based on X-chromosome inactivation patterns (XCIP)-transcription-based clonality assays (TCA). METHODS: Genomic DNA was extracted from peripheral blood of 446 Chinese healthy females. Allele-specific PCR (ASPCR) or PCR-restriction enzyme digestion method was applied for detecting G6PD, P55, BTK and FHL-1 polymorphisms. Those heterozygotic loci were used as markers to examine the hematopoietic clonality of bone marrow mononuclear cells by TCA from essential thrombocythemia (ET) patients with JAK2V617F mutation and myelodysplastic syndrome (MDS) patients with abnormal karyotype. RESULTS: Among the total 446 genomic DNA samples, the frequencies of heterozygosity in G6PD, P55, BTK and FHL-1 loci were 12.8%, 29.4%, 52.0% and 46.4%, respectively. About 81.4% of females were heterozygous at one or more loci. All 10 ET patients with JAK2V617F mutation and 2 MDS patients with abnormal karyotype, which were heterozygotic in either locus, had monoclonal/oligoclonal hematopoiesis. CONCLUSION: Clonality detection based on X chromosome inactivation patterns-transcription based clonality assays is applicable to about 80% of Chinese females.
Subject(s)
Chromosomes, Human, X , Genes, X-Linked , Hematopoiesis/genetics , Polymorphism, Single Nucleotide , Adolescent , Adult , Aged , Aged, 80 and over , Alleles , Asian People/genetics , Exons , Female , Genetic Carrier Screening , Genetic Linkage , Glucosephosphate Dehydrogenase/genetics , Humans , Middle Aged , Polymerase Chain Reaction/methods , X Chromosome Inactivation , Young AdultABSTRACT
OBJECTIVE: To investigate the relationship between DNA homologous recombination (HR) repair genes RAD51-G135C/XRCC3-C241T polymorphisms and development of acute myeloid leukemia (AML) with recurrent chromosome translocation. METHODS: Genomic DNA was extracted from bone marrow cells of 625 de novo AML patients and peripheral blood cells of 806 patient family members and 704 unrelated volunteers. Genotypes of RAD51-G135C and XRCC3-C241T were analyzed by PCR-RFLP. Cell lines with genotypes differed from XRCC3-C241T were selected and irradiated in vitro. The CBFß-MYH11 fusion gene was detected by TaqMan real-time PCR. RESULTS: The XRCC3-C241T variant (C/T + T/T) showed 6.22-fold and 6.99-fold increase in the risk of developing the AML with inv(16)/t(16;16)/CBFß-MYH11 as compared with the volunteer and family member controls respectively; the RAD51-G135C homozygote-type (C/C) variant showed 0.87-fold (P = 0.010) and 1.15-fold (P = 0.001) respectively increase in the risk of this subtype AML. In the irradiated group, the CBFß-MYH11 mRNA level in HL-60 cells was 59.49 times increased than that in KG1a cells. However, the RAD51-G135C and XRCC3-C241T variants had no correlations with the risk of development of t(15;17)/PML-RARα(+)AML, t(8;21)/AML1-ETO(+) AML and 11q23 AML subtypes. CONCLUSION: The XRCC3-C241T variant and the RAD51-G135C homozygote-type significantly increase the risk of the development of AML with inv(16)/t(16;16)/CBFß-MYH11.
Subject(s)
DNA-Binding Proteins/genetics , Leukemia, Myeloid, Acute/genetics , Rad51 Recombinase/genetics , Adolescent , Adult , Aged , Aged, 80 and over , Case-Control Studies , Child , Child, Preschool , Female , Genetic Predisposition to Disease , Genotype , Humans , Leukemia, Myeloid, Acute/etiology , Male , Middle Aged , Oncogene Proteins, Fusion/genetics , Polymorphism, Single Nucleotide , Translocation, Genetic , Young AdultABSTRACT
OBJECTIVE: To investigate NPM1 gene mutations in patients with primary myelodysplastic syndromes (MDS) and the clinical characteristics of patients with NPM1 mutants. METHODS: Genomic DNA corresponding to exon 12 of NPM1 gene was amplified by polymerase chain reaction (PCR) in 232 patients with primary MDS. Identification of mutants was by direct sequencing and classification of mutation types by sequencing followed by plasmid cloning. RESULTS: NPM1 mutants were found in 9 patients (3.9%). All the mutants were type A. As compared with those with NPM1 wild type, patients with the mutant were of lower ANC \[0.60 (0.12 - 2.91) × 10(9)/L vs 1.02 (0 - 10.23) × 10(9)/L, P = 0.046\], higher blast percent in bone marrow \[0.050 (0 - 0.090) vs 0.025 (0 - 0.190), P = 0.035\], decreased BFU-E \[0 (0 - 0)/10(5) BMMNC vs 6 (0 - 40)/10(5) BMMNC, P = 0.038\] and increased serum vitamin B(12) \[936.40 (373.80 - 2400.00) pmol/L vs 557.85 (17.00 - 3032.10) pmol/L, P = 0.045\] The chromosomal karyotypes of patients with NPM1 mutant were predominantly normal. CONCLUSION: MDS patients with NPM1 gene mutations have some unique clinical and laboratory features. The results give new hint for the pathogenesis of MDS development and progression.