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1.
Zhongguo Gu Shang ; 36(12): 1136-41, 2023 Dec 25.
Artigo em Chinês | MEDLINE | ID: mdl-38130221

RESUMO

OBJECTIVE: To explore pro-oxidative state of rotator cuff tissue and expression levels of Beclin-1 and mam-malian target of rapamycin(mTOR) in patients with acute and chronic rotator cuff injury, and then analyzed relationship between rotator cuff injury and oxidative stress and autophagy. METHODS: Forty patients with rotator cuff injury were seleceted from July 2019 to December 2020, and divided into male chronic injury group, male acute injury group, female chronic injury group, and female acute injury group, 10 patients in each group. All patients were performed rotator cuff repair under arthroscopy. The sample of tendon at the rotator cuff injury site of the patient was taken during operation, and total reactive oxygen species (ROS) and superoxide dismutase(SOD) were detected by detection kit;expression of Beclin-1 and mTOR mRNA were detected by reverse transcription-polymerase chain reaction (RT-PCR), and Western-blot was applied to detect protein expression of Beclin-1 and p-mTOR/mTOR. RESULTS: There were no significant difference in expression of ROS, SOD, Beclin-1mRNA and mTOR mRNA between male and female chronic injury groups, and between male and female acute injury groups (P>0.05); ROS, SOD and Beclin-1mRNA in male chronic injury group were higher than those in male chronic injury group, while mTOR mRNAand protein decreased (P<0.05);ROS, SOD and Beclin-1 mRNA in female chronic injury group were up-regulated compared with female acute injury group, while mTOR mRNA was down-regulated (P<0.05). CONCLUSION: Chronic rotator cuff injury is more likely to stimulate the pro-oxidation state of rotator cuff tissue than acute rotator cuff injury, which could up-regulating expression of autophagy factor Beclin-1 and down-regulating expression of mTOR. Therefore, patients with chronic rotator cuff injury may have higher levels of oxidative stress and autophagy.


Assuntos
Lesões do Manguito Rotador , Feminino , Humanos , Masculino , Proteína Beclina-1/genética , Proteína Beclina-1/metabolismo , Espécies Reativas de Oxigênio/metabolismo , RNA Mensageiro/metabolismo , Manguito Rotador/cirurgia , Lesões do Manguito Rotador/cirurgia , Superóxido Dismutase/metabolismo , Serina-Treonina Quinases TOR/genética , Serina-Treonina Quinases TOR/metabolismo
2.
Front Pediatr ; 11: 975696, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37009283

RESUMO

Background: Ataxia-telangiectasia (A-T) is an autosomal recessive disorder with high clinical heterogeneity. A-T may present in complicated variable forms, including classic A-T and milder form of AT. Contrary to the classic A-T, the milder form does not present the cardinal features of A-T such as ataxia and telangiectasia. A few ATM mutations have been reported in variant A-T cases manifesting isolated generalized or segmental dystonia without any signs of classical A-T. Methods: An A-T pedigree with predominant dystonia was collected. Genetic testing was performed by targeted panel of genes involved in movement disorders. The candidate variants were further confirmed by Sanger sequencing. We then reviewed previously published literatures of genetically confirmed A-T cases with predominant dystonia and summarized the clinical characteristics of dystonia-dominant A-T. Results: Two novel ATM mutations, p.I2683T and p.S2860P, were identified in the family. The proband presented isolated segmental dystonia without any signs of ataxia and telangiectasias. We reviewed the literatures and found that the patients with dystonia-dominant A-T tend to have a later-onset and slower progression of the disease. Conclusion: To our knowledge, this is the first report of A-T patient with predominant dystonia in China. Dystonia may appear as one of the predominant manifestations or initial symptom of A-T. Early ATM genetic testing should be considered for those patients with predominant dystonia, despite without accompanying ataxia or telangiectasia.

3.
Biomed Environ Sci ; 35(10): 888-898, 2022 Oct 20.
Artigo em Inglês | MEDLINE | ID: mdl-36443266

RESUMO

Objective: The aim was to identify the gene expressions of human cytomegalovirus (HCMV)-infected human umbilical vein endothelial cells (HUVECs) and to study its possible pathogenic mechanism on atherosclerosis using microarray technology. Methods: The gene expression differences in HCMV AD169 strain-infected HUVECs were studied by the microarray technology to explore the potential molecular mechanism of HCMV infection. The qPCRs were performed to verify the transcriptome results. Results: A total of 2,583 differentially expressed genes, including 407 down-regulated genes and 2,176 up-regulated genes, were detected by the systematic bioinformatics analysis. The Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses showed that the significantly differentially expressed genes were mainly involved in regulating protein kinase activity, inflammatory response, ubiquitination, protein phosphorylation, cell metabolism, and exosomes, among which 12 genes had significant changes and were screened by protein-protein interaction (PPI) analysis and verified by qPCR. The experimental qPCR results were consistent with the microarray results. Conclusion: The GO and KEGG analyses revealed that the regulation of protein kinase activity, inflammatory response, ubiquitination, protein phosphorylation, and cell metabolism played important roles in the process of endothelial cell infection. Furthermore, 12 genes were involved in the process of HCMV infection of endothelial cells and contributed to the current understanding of the infection and pathogenic mechanisms of atherosclerosis.


Assuntos
Aterosclerose , Citomegalovirus , Humanos , Citomegalovirus/genética , Células Endoteliais da Veia Umbilical Humana , Proteínas Quinases , RNA Mensageiro
4.
Eur Neurol ; 85(3): 235-244, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35108712

RESUMO

BACKGROUND: At present, symptomatic treatment may improve the life quality of Parkinson's disease (PD) patients to a certain extent but cannot completely cure PD. Therefore, it is urgent medical problem to be solved for improving the efficacy and safety of PD treatment. METHODS: SH-SY5Y and SK-N-SH cells were treated with 1-methyl-4-phenylpyridinium (MPP+) to establish PD model cells. miR-126-5p and specific protein-1 (SP1) expression levels were detected by quantitative Real-Time PCR (qRT-PCR). Western blot was applied to measure protein levels of SP1, Bax, and Bcl-2. The viabilities and apoptosis rates of treated cells were measured using cell counting kit-8 assay and flow cytometry analysis. Enzyme-linked immunosorbent assay was performed to measure TNF-α and IL-1ß releases. Interaction between miR-126-5p and SP1 was examined by dual-luciferase reporter assay. RESULTS: MPP+ treatment greatly downregulated miR-126-5p expression while upregulated SP1 expression in SH-SY5Y and SK-N-SH cells in a time- and does-dependent manner. Overexpression of miR-126-5p facilitated cell viability, while reduced cell apoptosis and inflammatory responses induced by MPP+ treatment. Moreover, SP1 was a target of miR-126-5p and could be negatively regulated by miR-126-5p. Overexpression of SP1 could reverse the effects of miR-126-5p on MPP+-administrated cells. CONCLUSION: Our results suggested that miR-126-5p attenuated the neurotoxicity induced by MPP+ in vitro through targeting SP1 (Graphical abstract), which further enhanced our understanding of the pathological mechanism of PD.


Assuntos
MicroRNAs , Doença de Parkinson , Fator de Transcrição Sp1 , 1-Metil-4-fenilpiridínio/farmacologia , Apoptose/genética , Linhagem Celular Tumoral , Humanos , MicroRNAs/genética , Doença de Parkinson/patologia , Fator de Transcrição Sp1/genética
5.
Plant Physiol ; 189(1): 215-229, 2022 05 03.
Artigo em Inglês | MEDLINE | ID: mdl-35148397

RESUMO

Nitrate allocation in Arabidopsis (Arabidopsis thaliana) represents an important mechanism for mediating plant environmental adaptation. However, whether this mechanism occurs or has any physiological/agronomic importance in the ammoniphilic plant rice (Oriza sativa L.) remains unknown. Here, we address this question through functional characterization of the Nitrate transporter 1/Peptide transporter Family (NPF) transporter gene OsNPF7.9. Ectopic expression of OsNPF7.9 in Xenopus oocytes revealed that the gene encodes a low-affinity nitrate transporter. Histochemical and in-situ hybridization assays showed that OsNPF7.9 expresses preferentially in xylem parenchyma cells of vasculature tissues. Transient expression assays indicated that OsNPF7.9 localizes to the plasma membrane. Nitrate allocation from roots to shoots was essentially decreased in osnpf7.9 mutants. Biomass, grain yield, and nitrogen use efficiency (NUE) decreased in the mutant dependent on nitrate availability. Further analysis demonstrated that nitrate allocation mediated by OsNPF7.9 is essential for balancing rice growth and stress tolerance. Moreover, our research identified an indica-japonica divergent single-nucleotide polymorphism occurring in the coding region of OsNPF7.9, which correlates with enhanced nitrate allocation to shoots of indica rice, revealing that divergent nitrate allocation might represent an important component contributing to the divergent NUE between indica and japonica subspecies and was likely selected as a favorable trait during rice breeding.


Assuntos
Arabidopsis , Oryza , Arabidopsis/genética , Arabidopsis/metabolismo , Transportadores de Nitrato , Nitratos/metabolismo , Nitrogênio/metabolismo , Oryza/metabolismo , Melhoramento Vegetal , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo
6.
World J Clin Cases ; 9(27): 8114-8119, 2021 Sep 26.
Artigo em Inglês | MEDLINE | ID: mdl-34621869

RESUMO

BACKGROUND: Empyema is a severe complication following pneumonectomy that is associated with high morbidity and mortality rates. Although there are a wide variety of treatment options, successful management remains challenging when this condition is combined with a large cavity in very thin patients who had previously undergone a posterolateral thoracotomy. CASE SUMMARY: We reported the case of a thin, 63-year-old man with a progressive pulmonary cyst who underwent left pneumonectomy via posterolateral thoracotomy 23 years ago. After an initially uneventful postoperative course, he was readmitted with empyema and a large cavity 21 years after surgery. He was successfully treated with limited thoracoplasty, followed by free vastus lateralis musculocutaneous flap transposition. CONCLUSION: This case highlights that the treatment mode of limited thoracoplasty and free vastus lateralis musculocutaneous flap transposition is safe and effective for the management of postpneumonectomy empyema with a large cavity in thin patients who had previously undergone a posterolateral thoracotomy.

7.
Vaccines (Basel) ; 9(10)2021 Oct 09.
Artigo em Inglês | MEDLINE | ID: mdl-34696263

RESUMO

Capsular type A and D strains of Pasteurella multocida are the main epidemic serogroups in pigs in China. In this study, we preliminarily evaluated the immune protective efficacy of the two traditional vaccines, an inactivated C44-1 aluminum-hydroxide-gel-adjuvanted (Alh-C44-1) vaccine and a live EO630 vaccine, against currently circulating strains of P. multocida in a mouse model. Mice immunized twice with conventional vaccines generated higher antibody titers, and significantly higher levels of IgG were observed in the mice inoculated with the inactivated Alh-C44-1 vaccine on day 35 (p < 0.05) than those with the live EO630 vaccine. The mice immune protection test showed that the vaccination groups had a 57% or 71% protection effect against the serogroup B strain, but had no protective effect against epidemic strains. In conclusion, our study found that the widely used traditional P. multocida vaccines in China provide good protection against homologous strains, but could not provide cross-protection against heterologous strains in a mouse model.

8.
Mol Genet Genomic Med ; 9(5): e1627, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33638609

RESUMO

OBJECTIVE: Hereditary spastic paraplegias (HSP) is a clinically and genetically heterogeneous group of neurodegenerative disorders. We describe the genetic and clinical features of a cohort of five HSP families from central-southern China. METHODS: Using targeted exome-sequencing technology, we investigated the genetic and clinical features in five HSP families. We reviewed the clinical histories of these patients as well as the molecular and functional characterization of the associated gene variants. We also performed functional analysis of an intron variant of SPAST in vitro. RESULTS: We identified a known SPAST mutation (p.Pro435Leu) in a family with autosomal dominant HSP (AD-HSP) and four novel variants in two HSP families and a sporadic case. These identified four novel variants included a variant in SPG11 (p.Val1979Ter), two variants in B4GALNT1 (p.Ser475Phe and c.1002 + 2 T > G), and a splicing site variant in SPAST (c.1245+5G>A). Minigene analysis of the splicing variant in SPAST (c.1245+5G>A) revealed that the mutation resulted in mRNAs with a loss of exon 9. The SPG4 family carrying c.1245+5G>A variant in SPAST exhibited genetic anticipation, with a decreased age at onset and increased severity in successive generations. The proband with p.Val1979Ter variant in SPG11 showed characteristic clinical features of early-onset, severe spasticity, and corpus callosum atrophy which were highly suggestive of the diagnosis of SPG11-associated HSP. CONCLUSIONS: Our findings strongly support variable phenotype of B4GALNT1-related SPG26 and also expand the clinical and mutation spectrum of HSP caused by mutations in SPAST, SPG11, and B4GALNT1. These results will help to improve the efficiency of early diagnosis in patients clinically suspected of HSP.


Assuntos
Mutação , Fenótipo , Paraplegia Espástica Hereditária/genética , Adolescente , Adulto , Criança , China , Feminino , Células HEK293 , Humanos , Masculino , Pessoa de Meia-Idade , N-Acetilgalactosaminiltransferases/genética , Proteínas/genética , Paraplegia Espástica Hereditária/patologia , Espastina/genética
9.
Biosens Bioelectron ; 176: 112954, 2021 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-33412428

RESUMO

CRISPR/Cas system have drawn increasing attention in accurate and sensitive nucleic acids detection. Herein, we reported a novel Cas12a-based electrochemiluminescence biosensor for target amplification-free human papilloma virus subtype (HPV-16) DNA detection. During this detection process, Cas12a employed its two-part recognition mechanism to improve the specificity and trans-cleavage capability to achieve signal amplification, while L-Methionine stabilized gold nanoclusters (Met-AuNCs) were served as high-efficiency ECL emitters to achieve ECL signal transition. Given the unique combination of Cas12a with ECL technique, the detection limit was determined as 0.48 pM and the whole detection could be completed within 70 min. We also validated the practical application of the proposed biosensor by using undiluted human blood samples, which gives impetus to the design of new generations of CRISPR/Cas detection system beyond the traditional ones with ultimate applications in sensing analysis and diagnostic technologies.


Assuntos
Técnicas Biossensoriais , Sistemas CRISPR-Cas , DNA/genética , Ouro , Humanos , Técnicas de Amplificação de Ácido Nucleico
10.
Math Biosci Eng ; 17(4): 3240-3251, 2020 04 24.
Artigo em Inglês | MEDLINE | ID: mdl-32987527

RESUMO

A stochastic two-species competition system with saturation effect and distributed delays is formulated, in which two coupling noise sources are incorporated and every noise source has effect on two species' intrinsic growth rates in nonlinear form. By transforming the two-dimensional system with weak kernel into an equivalent four-dimensional system, sufficient conditions for extinction of two species and the existence of a stationary distribution of the positive solutions to the system are obtained. Our main results show that the two coupling noises play a significant role on the long time behavior of system.

11.
Biomed Environ Sci ; 33(8): 573-582, 2020 Aug 20.
Artigo em Inglês | MEDLINE | ID: mdl-32933609

RESUMO

OBJECTIVE: To investigate the relationship between human cytomegalovirus (HCMV) infection and peripheral blood CD14 +CD16 + monocytes in the pathogenesis of coronary heart disease (CHD), and to elucidate the mechanism of pathogenesis in CHD by analyzing the correlation between infection, inflammation, and CHD, to provide a basis for the prevention, evaluation, and treatment of the disease. METHODS: In total, 192 patients with CHD were divided into three groups: latent CHD, angina pectoris, and myocardial infarction. HCMV-IgM and -IgG antibodies were assessed using ELISA; CD14 +CD16 + monocytes were counted using a five-type automated hematology analyzer; mononuclear cells were assessed using fluorescence-activated cell sorting; and an automatic biochemical analyzer was used to measure the levels of triglyceride, cholesterol, high- and low-density lipoprotein cholesterols, lipoprotein, hs-CRp and Hcy. RESULTS: The positive rates of HCMV-IgM and -IgG were significantly higher in the CHD groups than in the control group. HCMV infection affects lipid metabolism to promote immune and inflammatory responses. CONCLUSION: HCMV infection has a specific correlation with the occurrence and development of CHD. The expression of CD14 +CD16 + mononuclear cells in the CHD group was increased accordingly and correlated with acute HCMV infection. Thus, HCMV antibody as well as peripheral blood CD14 +CD16 + mononuclear cells can be used to monitor the occurrence and development of CHD.


Assuntos
Angina Pectoris/epidemiologia , Doença das Coronárias/epidemiologia , Infecções por Citomegalovirus/complicações , Citomegalovirus/fisiologia , Inflamação/epidemiologia , Infarto do Miocárdio/epidemiologia , Angina Pectoris/virologia , China/epidemiologia , Doença das Coronárias/virologia , Humanos , Incidência , Inflamação/etiologia , Contagem de Leucócitos , Monócitos/metabolismo , Infarto do Miocárdio/virologia
12.
World J Psychiatry ; 10(6): 125-138, 2020 Jun 19.
Artigo em Inglês | MEDLINE | ID: mdl-32742946

RESUMO

A spectrum of neuropsychiatric disorders is a common complication from stroke. Neuropsychiatric disorders after stroke have negative effects on functional recovery, increasing the rate of mortality and disability of stroke survivors. Given the vital significance of maintaining physical and mental health in stroke patients, neuropsychiatric issues after stroke have raised concerns by clinicians and researchers. This mini-review focuses on the most common non-cognitive functional neuropsychiatric disorders seen after stroke, including depressive disorders, anxiety disorders, post-traumatic stress disorder, psychosis, and psychotic disorders. For each condition, the clinical performance, epidemiology, identification of the therapeutic implication, and strategies are reviewed and discussed; the main opinions and perspectives presented here are based on the latest controlled studies, meta-analysis, or updated systematic reviews. In the absence of data from controlled studies, consensus recommendations were provided accordingly.

13.
J Phys Chem A ; 124(1): 82-89, 2020 Jan 09.
Artigo em Inglês | MEDLINE | ID: mdl-31815471

RESUMO

A new terbium (III) luminescent compound {[Tb2(PDC)2(ox)(H2O)4](H2O)2}n was synthesized by the self-assembly of Tb3+ ions with 3,5-pyridinedicarboxylate (PDC) and oxalate (ox) ligands and characterized by fluorescence spectroscopy and single-crystal X-ray diffraction. The density functional theory (DFT) and high-level correlated ab initio wave function methods with Spin-Orbit Coupling correction (CASSCF/SO and CAS-NEVPT2/SOC) were successfully applied to predict the absorption and emission spectra of this strongly correlated lanthanide system in excellent agreement with the experimental results.

14.
Obes Surg ; 30(1): 279-289, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31605365

RESUMO

BACKGROUND: Duodenal-jejunal bypass (DJB) can dramatically improve type 2 diabetes independent of weight loss and food restriction. Increasing evidence has demonstrated that brain insulin signaling plays an important role in the pathophysiology of type 2 diabetes. This study explores whether the antidiabetic effect of DJB is involved in brain insulin signaling activation and brain glucose utilization. METHODS: A diabetic rat model was established by high-fat and high-glucose diet. DJB or sham surgery was performed in diabetic rats. 18F-FDG PET scanning was used to detect glucose uptake in different organs, particularly in the brain. The levels of glucose transporters, glucose utilization-related proteins (HK1 and PFK2), insulin, and insulin signaling pathway-related proteins (InsR, IRS1/2, PI3K, and p-Akt) in the brain tissues were evaluated and analyzed. RESULTS: The results showed that DJB significantly improved basal glycemic parameters and reversed the decreasing glucose uptake in the brains of type 2 diabetic rats. DJB significantly increased not only the expression levels of brain insulin, IRS1/2, PI3K, and p-Akt but also the levels of the glucose utilization enzymes HK1 and PFK2 in the brain. CONCLUSION: These results indicate that enhanced brain insulin signaling transduction and brain glucose utilization play important roles in the antidiabetic effect of DJB.


Assuntos
Encéfalo/metabolismo , Diabetes Mellitus Tipo 2/cirurgia , Duodeno/cirurgia , Derivação Gástrica/métodos , Glucose/metabolismo , Insulina/metabolismo , Jejuno/cirurgia , Animais , Glicemia/metabolismo , Diabetes Mellitus Experimental/metabolismo , Diabetes Mellitus Experimental/patologia , Diabetes Mellitus Experimental/cirurgia , Diabetes Mellitus Tipo 2/metabolismo , Diabetes Mellitus Tipo 2/patologia , Duodeno/patologia , Resistência à Insulina/fisiologia , Jejuno/patologia , Fígado/metabolismo , Masculino , Ratos , Ratos Wistar , Transdução de Sinais/fisiologia , Resultado do Tratamento , Redução de Peso
15.
Aging Dis ; 10(6): 1199-1206, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31788332

RESUMO

Amyotrophic lateral sclerosis (ALS) is a progressive, fatal neurodegenerative disease characterized by selective impairment of upper and lower motor neurons. We aimed to investigate the genetic spectrum and variability in Chinese patients with ALS. A total of 24 familial ALS (FALS) and 21 early-onset sporadic ALS (SALS) of Chinese ancestry were enrolled. Targeted next-generation sequencing (NGS) was performed in the probands, followed by verification by Sanger sequencing and co-segregation analysis. Clinical features of patients with pathogenic or likely pathogenic variants were present. The mutation frequency of ALS-related genes was then analyzed in Chinese population. In this cohort, 17 known mutations (9 SOD1, 5 FUS, 2 TARDBP and one SETX) were identified in 14 FALS and 6 early-onset SALS. Moreover, 7 novel variants (SOD1 c.112G>C, OPTN c.811C>T, ERBB4 c.965T>A, DCTN1 c.1915C>T, NEFH c.2602G>A, NEK1 c.3622G>A, and TAF15 c.1535G>A) were identified. In southeastern Chinese FALS, the mutation frequency of SOD1, FUS, and TARDBP was 52.9%, 8.8%, 8.8% respectively. In early-onset SALS, FUS mutations were the most common (22.6%). In Chinese ALS cases, p.H47R is most frequent SOD1 mutations, while p.R521 is most common FUS mutation and p.M337V is most common TARDBP mutation. Our results revealed that mutations in SOD1, FUS and TARDBP are the most common cause of Chinese FALS, while FUS mutations are the most common cause of early-onset SALS. The genetic spectrum is different between Chinese ALS and Caucasian ALS.

16.
Aging Dis ; 10(5): 1003-1011, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31595198

RESUMO

Huntington's disease (HD) is an autosomal dominant inherited neurodegenerative disorder caused by CAG triplet repeats expansion in exon 1 of the Huntingtin gene (HTT). In China, HD is considered to have a low prevalence. The goal of this study was to describe the clinical characteristic and genetic profiles of HD in a Chinese cohort. A total of 322 individuals with expanded CAG repeats were consecutively recruited from the neurologic clinics of three medical centers in Southeastern China between 2008 and 2018. Among them, 80 were pre-symptomatic mutation carriers and 242 were symptomatic patients. The mean age at onset (AAO), defined here as the age at motor symptom onset, of the 242 manifest HD individuals was 40.3 ± 11.9 years and the mean CAG repeat length was 46.1 ± 7.5 in the group of symptomatic patients. Initial symptoms were abnormal movements in 88.8% of the patients with psychiatric symptoms in 6.2%, cognitive impairment in 3.3% and others in 1.7%. The AAO of motor was negatively correlated with the CAG repeat length in an exponential regression analysis (R 2 = 0.74, P<0.001). Analysis of 46 parent-child pairs showed that the CAG repeat length was longer in the offspring group (45.8 ±7.6) than in the parent group (43.8 ±3.0) (p=0.005). Overall, this study provides clinical and genetic profiles in a cohort of Chinese patients with HD, which should contribute to a better understanding of this disorder.

17.
Transl Neurodegener ; 8: 19, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31289639

RESUMO

BACKGROUND: Although many causative genes of hereditary spastic paraplegia (HSP) have been uncovered in recent years, there are still approximately 50% of HSP patients without genetically diagnosis, especially in autosomal recessive (AR) HSP patients. Rare studies have been performed to determine the genetic spectrum and clinical profiles of recessive HSP patients in the Chinese population. METHODS: In this study, we investigated 24 Chinese index AR/sporadic patients by targeted next-generation sequencing (NGS), Sanger sequencing and multiplex ligation-dependent probe amplification (MLPA). Further functional studies were performed to identify pathogenicity of those uncertain significance variants. RESULTS: We identified 11 mutations in HSP related genes including 7 novel mutations, including two (p.V1979_L1980delinsX, p.F2343 fs) in SPG11, two (p.T55 M, p.S308 T) in AP5Z1, one (p.S242 N) in ALDH18A1, one (p.D597fs) in GBA2, and one (p.Q486X) in ATP13A2 in 8 index patients and their family members. Mutations in ALDH18A1, AP5Z1, CAPN1 and ATP13A2 genes were firstly reported in the Chinese population. Furthermore, the clinical phenotypes of the patients carrying mutations were described in detail. The mutation (p.S242 N) in ALDH18A1 decreased enzyme activity of P5CS and mutations (p.T55 M, p.S308 T) in AP5Z1 induced lysosomal dysfunction. CONCLUSION: Our results expanded the genetic spectrum and clinical profiles of AR-HSP patients and further demonstrated the efficiency and reliability of targeted NGS diagnosing suspected HSP patients.

18.
J Cell Mol Med ; 23(8): 4991-5005, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31207106

RESUMO

Melanoma is one of the most malignant skin tumours with constantly increasing incidence worldwide. Previous studies have demonstrated that microRNA-374 (miR-374) is a novel biomarker for cancer therapy. Therefore, this study explores whether miR-374 targeting tyrosinase (TYR) affects melanoma and its underlying mechanism. We constructed subcutaneous melanoma models to carry out the following experiments. The cells were transfected with a series of miR-374 mimics, miR-374 inhibitors or siRNA against TYR. Dual luciferase reporter gene assay was used for the verification of the targeting relationship between miR-374 and TYR. Reverse transcription quantitative polymerase chain reaction and western blot analysis were conducted to determine the expression of miR-374, TYR, ß-catenin, B-cell leukaemia 2 (Bcl-2), Bcl-2 associated X protein (Bax), Low-density lipoprotein receptor-related protein 6 (LRP6), Leucine-rich repeat G protein-coupled receptor 5 (LGR5) and CyclinD1. Cell proliferation, migration, invasion, cell cycle distribution and apoptosis were evaluated using cell counting kit-8 assay, scratch test, transwell assay and flow cytometry respectively. TYR was proved as a putative target of miR-374 as the evidenced by the result. It was observed that up-regulated miR-374 or down-regulated TYR increased expression of Bax and decreased expressions of TYR, ß-catenin, LRP6, Bcl-2, CyclinD1 and LGR5, along with diminished cell proliferation, migration, invasion and enhanced apoptosis. Meanwhile, cells with miR-374 inhibitors showed an opposite trend. These findings indicated that up-regulated miR-374 could inhibit the expression of TYR to suppress cell proliferation, migration, invasion and promote cell apoptosis in melanoma cells by inhibiting the Wnt signalling pathway.


Assuntos
Melanoma/metabolismo , MicroRNAs/metabolismo , Monofenol Mono-Oxigenase/metabolismo , Neoplasias Cutâneas/metabolismo , Animais , Apoptose/genética , Linhagem Celular Tumoral , Movimento Celular/genética , Proliferação de Células/genética , Ciclina D1/genética , Ciclina D1/metabolismo , Regulação Neoplásica da Expressão Gênica/genética , Humanos , Proteína-6 Relacionada a Receptor de Lipoproteína de Baixa Densidade/genética , Proteína-6 Relacionada a Receptor de Lipoproteína de Baixa Densidade/metabolismo , Masculino , Melanoma/genética , Melanoma/patologia , Camundongos , Camundongos Nus , MicroRNAs/genética , Monofenol Mono-Oxigenase/genética , Proteínas Proto-Oncogênicas c-bcl-2/genética , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , RNA Interferente Pequeno , Receptores Acoplados a Proteínas G/genética , Receptores Acoplados a Proteínas G/metabolismo , Pontos de Checagem da Fase S do Ciclo Celular/genética , Neoplasias Cutâneas/genética , Neoplasias Cutâneas/patologia , Transplante Heterólogo , Via de Sinalização Wnt/genética , Proteína X Associada a bcl-2/genética , Proteína X Associada a bcl-2/metabolismo , beta Catenina/genética , beta Catenina/metabolismo
19.
Math Biosci Eng ; 16(4): 2371-2390, 2019 03 15.
Artigo em Inglês | MEDLINE | ID: mdl-31137218

RESUMO

This study adopted the uniform interpolation method to obtain five gradation types (labeled A, B, C, D, and E, from "coarse-grained" to "fine-grained" types) based on the skeleton dense structure and cement-stabilized macadam (CSM) aggregate gradation range recommended by current specifications. The optimum water content of the CSM exhibited a linear increase with gradation, whereas the maximum dry density exhibited a variation that can be described by a quadratic curve, for which the peak maximum dry density was near the maximum dry density of the Type B gradation. In the CSM structure, the skeleton void effect of the coarse-grained aggregate, the filling effect of the fine-grained aggregate, and the cementation effect of the cement and aggregate exhibited corresponding fluctuations. The ability to resist temperature shrinkage deformation was reduced. Additionally, the optimum values of the compressive strength and compression rebound modulus of the CSM plotted near the curve of the Type D gradation.


Assuntos
Materiais de Construção , Polienos/química , Algoritmos , Força Compressiva , Engenharia/métodos , Teste de Materiais , Estresse Mecânico , Temperatura , Água
20.
J Clin Med ; 9(1)2019 Dec 31.
Artigo em Inglês | MEDLINE | ID: mdl-31906103

RESUMO

Atrial fibrillation (AF) is responsible for significant morbidity and mortality in patients with heart failure (HF). Modern pacemakers provide an index of intrathoracic fluid status (OptiVol fluid index-OVFI) by measuring daily intrathoracic impedance. This study aimed to determine whether OVFI is associated with increased atrial tachycardia/fibrillation (AT/AF) events in patients with a preserved ejection fraction (EF). We retrospectively reviewed data from patients with Medtronic Advisa pacemakers between 2012 and 2014 in our hospital. The association and temporal relationship between OVFI and AT/AF events were determined. A total of 150 patients with 211 follow-up visits (mean 1.4 visits per patient) were evaluated. The device-detected AT/AF prevalence was 47%. Device-measured OVFI ≥ 20 Ω-days was significantly associated with the onset of AT/AF ≥ 4 h. OVFI threshold crossing preceded AT/AF events in 55.1% of cases, followed by AT/AF events in only 18.7%. Fluid overload represented by OVFI may trigger AT/AF episodes in patients with a preserved EF more often than that previously reported in patients with a reduced EF. Our findings support the view that worsening pulmonary congestion is associated with increased AT/AF frequency and suggests that fluid overload could trigger and perpetuate AT/AF events in patients with a preserved EF.

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