Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 33
Filtrar
1.
Brain Res ; 1828: 148774, 2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-38244758

RESUMO

Cat superior colliculus (SC) neurons commonly combine information from different senses, which facilitates event detection and localization. Integration in SC multisensory neurons depends on the spatial and temporal relationships between cross-modal cues. Here, we revealed the parallel process of short-term plasticity in the temporal/spatial integration process during adulthood that adapts multisensory integration to reliable changes in environmental conditions. Short-term experience alters the temporal preferences of SC multisensory neurons, and this short-term plasticity in the temporal/spatial integration process is limited to changes in cross-modal timing (a factor commonly induced by events at different distances from the receiver). However, this plasticity was not evident in response to changes in the cross-modal spatial configuration.


Assuntos
Sensação , Colículos Superiores , Colículos Superiores/fisiologia , Estimulação Acústica , Estimulação Luminosa , Sensação/fisiologia , Neurônios/fisiologia , Percepção Auditiva/fisiologia , Percepção Visual/fisiologia
2.
J Orthop Surg Res ; 18(1): 270, 2023 Apr 03.
Artigo em Inglês | MEDLINE | ID: mdl-37013614

RESUMO

BACKGROUND: This study was designed to investigate whether intraoperative electrical nerve stimulation has effects on the short-term recovery of cubital tunnel syndrome patients after ulnar nerve release. METHODS: Patients diagnosed as cubital tunnel syndrome were selected. At the same time, they received conventional surgery treatment. The patients were divided by a randomized digits table into two groups. The control group underwent conventional surgery, and the electrical stimulation (ES) group underwent intraoperative electrical stimulation. All the patients were tested for sensory and motor functions, grip strength, key pinch strength, motor conductivity velocity (MCV), and maximum compound muscle action potential (CMAP) before operation and 1 month and 6 months after operation. RESULTS: In patients treated with intraoperative ES, the sensory and motor functions and the strength of muscle were significantly improved after 1-month and 6-month follow-up than the control group. After the follow-up, the patients in the ES group had significantly higher grip strength and key pinch strength than the control group. After the follow-up, the patients in the ES group had significantly higher MCV and CMAP than the control group. CONCLUSION: Intraoperative electrical stimulation of nerve muscle can significantly promote the short-term recovery of nerve and muscle functions after the surgery in cubital tunnel syndrome patients.


Assuntos
Síndrome do Túnel Ulnar , Humanos , Síndrome do Túnel Ulnar/cirurgia , Síndrome do Túnel Ulnar/diagnóstico , Nervo Ulnar/cirurgia , Força da Mão/fisiologia , Procedimentos Neurocirúrgicos , Descompressão Cirúrgica
3.
PLoS One ; 17(12): e0278157, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36525417

RESUMO

OBJECTIVE: To investigate the risk factors for venous thromboembolism (VTE) in hospitalized patients with rheumatic diseases in China. The efficacy of the Padua scale was evaluated and an improved model for predicting VTE in hospitalized patients with rheumatic diseases was developed. METHODS: Records of 2282 patients hospitalized in the department of rheumatology of the Sichuan Provincial People's Hospital were retrospectively reviewed. The risk factors for VTE were analyzed. The efficacy of the Padua scale was evaluated, Padua-combined prediction model and the independent risk factor-combined prediction model for predicting VTE were assessed using the receiver operating curve (ROC). RESULTS: A total of 50 patients in the VTE group and 2232 in the non-VTE group were included. Antiphospholipid syndrome (APS), VTE history, a hospital stay of over 3 days, high D-dimer (D-D), and decreased serum albumin were independent risk factors for VTE. APS was very closely associated with VTE (OR = 19.446). Padua scores in the VTE group and the non-VTE group were 3 (2, 6) and 2 (1, 2) points, respectively (p < 0.05), and the proportion of high-risk patients were 48.0% and 7.4%, respectively (p < 0.05). The incidence of VTE in the high-risk (Padua score ≥4) and low-risk (Padua score <4) groups was 12.7% and 1.2%, respectively (p < 0.05). The area under curve (AUC) of the Padua scale, Padua combined prediction model (Padua scale along with D-D and serum albumin), and the independent risk factor-combined prediction model was 0.771, 0.836, and 0.873, respectively. CONCLUSION: The Padua scale has limited predictive efficacy of VTE in hospitalized rheumatic patients. The independent risk factor-combination prediction model was superior in predicting VTE compared to Padua scale and Padua-combined prediction model.


Assuntos
Doenças Reumáticas , Tromboembolia Venosa , Humanos , Tromboembolia Venosa/etiologia , Tromboembolia Venosa/epidemiologia , Estudos Retrospectivos , População do Leste Asiático , Medição de Risco , Fatores de Risco , Doenças Reumáticas/complicações , Albumina Sérica
4.
Mol Genet Genomic Med ; 10(3): e1878, 2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-35106951

RESUMO

BACKGROUND: Hereditary multiple exostosis (HME) is an autosomal dominant skeletal disorder characterized by the development of multiple cartilage-covered tumors on the external surfaces of bones (osteochondromas). Most of HME cases result from heterozygous loss-of-function mutations in EXT1 or EXT2 gene. METHODS: Clinical examination was performed to diagnose the patients: Whole exome sequencing (WES) was used to identify pathogenic mutations in the proband, which is confirmed by Sanger sequencing and co-segregation analysis: qRT-PCR was performed to identify the mRNA expression level of EXT1 in patient peripheral blood samples: minigene splicing assay was performed to mimic the splicing process of EXT1 variants in vitro. RESULTS: We evaluated the pathogenicity of EXT1 c.1056 + 1G > T in a Chinese family with HME. The clinical, phenotypic, and genetic characterization of patients in this family were described. The variant was detected by whole-exome sequencing (WES) and confirmed by Sanger sequencing. Sequencing of the RT-PCR products from the patient's blood sample identified a large deletion (94 nucleotides), which is the whole exome 2 of the EXT1 cDNA. Splicing assay indicated that the mutated minigene produced alternatively spliced transcripts, which cause a frameshift resulting in an early termination of protein expression. CONCLUSIONS: Our study establishes the pathogenesis of the splicing mutation EXT1 c.1056 + 1G > T to HME and provides scientific foundation for accurate diagnosis and precise medical intervention for HME.


Assuntos
Exostose Múltipla Hereditária , China , Exostose Múltipla Hereditária/genética , Humanos , N-Acetilglucosaminiltransferases/genética , Linhagem , Splicing de RNA
5.
Front Public Health ; 10: 948652, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36726623

RESUMO

Objective: To explore the clinical characteristics and risk factors of common systemic rheumatism concomitant with tuberculosis (TB). Methods: A total of 3,906 patients of RA, SLE, and SS diagnosed in the People's Hospital of Sichuan Province from January 2007 to January 2017 were collected. One hundred and five patients with TB were included as TB group, including 42 RA, 41 SLE, and 22 SS patients. In the non-TB group, 84 RA, 82 SLE, and 44 SS patients were randomly selected during the same period. Results: Fever was the most common symptom among RA, SLE, and SS patients with TB, accounting for 83.3%, 92.7%, and 68.2%, respectively. Cough, weight loss or fatigue were the next common. RA patients with TB were mostly pulmonary TB (PTB), accounting for 64.3%. The proportion of PTB for SLE and SS were 46.3%, 59.01%, respectively. In TB group, 59% RA, 57% SLE, and 62% SS with PTB had two or more chest CT findings. There were 48 TB cases received both Interferon Gamma Release Assay (IGRA) and Tuberculin skin test (TST) with positive rates of 91.8%, 45.8%, respectively. The daily average dose of glucocorticoids within 1 year in TB group was higher than that in non-TB group of SLE patients, lower counts of CD4+ T cell count were found in TB group (P < 0.05), while no such differences were found in RA and SS patients. Conclusion: RA patients with TB are mainly pulmonary TB. For SLE and SS patients, the chance of PTB and extrapulmonary tuberculosis is similar. Daily average dose of glucocorticoids within 1 year may be a common risk factor for RA, SLE and SS patients developing TB. Decreased CD4+ T cell count may also be a risk factor for SLE patients with TB. Symptoms of RA, SLE, SS with TB, are similar with the primary disease or other infection. It is recommended to conduct both TST and IGRA to help diagnose TB.


Assuntos
Tuberculose Latente , Lúpus Eritematoso Sistêmico , Doenças Reumáticas , Tuberculose Pulmonar , Tuberculose , Humanos , Tuberculose Latente/complicações , Tuberculose Latente/diagnóstico , Tuberculose/complicações , Tuberculose/epidemiologia , Testes de Liberação de Interferon-gama , Doenças Reumáticas/complicações , Doenças Reumáticas/epidemiologia , Tuberculose Pulmonar/complicações , Tuberculose Pulmonar/epidemiologia , Lúpus Eritematoso Sistêmico/complicações , Lúpus Eritematoso Sistêmico/epidemiologia
6.
J Nat Prod ; 85(1): 301-305, 2022 01 28.
Artigo em Inglês | MEDLINE | ID: mdl-34933562

RESUMO

Bitetracenomycin A (1) and its diastereomers [(±)-bitetracenomycin B, (±)-2] were discovered from the cultures of Streptomyces sp. HDN154193. Compounds 1 and (±)-2 were the first tetracenomycin dimers obtained from a natural source with sp3 methine protons at the bridge positions (C-12/12'), which also exhibited broad-spectrum antibacterial activity. The racemate (±)-2 was semisynthesized and separated into enantiomers (+)-2 and (-)-2, and the absolute configurations were determined by specific rotation and ECD data. These metabolites exhibited potent antibacterial activity especially against drug-resistant strains (MRSA and MRCNS) with MIC values ranging from 1.0 to 1.9 µg/mL.


Assuntos
Naftacenos/isolamento & purificação , Streptomyces/química , Antibacterianos/química , Antibacterianos/isolamento & purificação , Antibacterianos/farmacologia , Clima Desértico , Dimerização , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Testes de Sensibilidade Microbiana , Estrutura Molecular , Naftacenos/química , Naftacenos/farmacologia , Análise Espectral/métodos , Estereoisomerismo
7.
Zhonghua Yi Xue Yi Chuan Xue Za Zhi ; 38(11): 1106-1109, 2021 Nov 10.
Artigo em Chinês | MEDLINE | ID: mdl-34729753

RESUMO

OBJECTIVE: To analyze the pathogenic variant of preaxial polydactyly in a Chinese Han pedigree and identify the cause of polydactyly. METHODS: The peripheral blood DNA of the proband and her parents was extracted. The polydactyly-related genes were detected by trio whole exome sequencing, and the suspected pathogenic gene was screened out. Sanger sequencing was applied to other members of the pedigree. RESULTS: The results of gene sequencing showed that the LMBR1 gene had a heterozygous variant of c.423+4909(IVS5)C>T in 6 patients of the pedigree. The same variant was not detected in family members with normal phenotype. Based on the ACMG guidelines, c.423+4909(IVS5)C>T of the LMBR1 gene was predicted to be pathogenic (PM1+PM2+PP1-S(PS)+PP4+PP5). CONCLUSION: The heterozygous C>T variant at position 4909 of intron 5 of the LMBR1 gene probably underlies the disease in this pedigree.


Assuntos
Polidactilia , China , Feminino , Humanos , Mutação , Linhagem , Polidactilia/genética , Polegar , Sequenciamento do Exoma
8.
Zhonghua Yi Xue Yi Chuan Xue Za Zhi ; 38(12): 1224-1227, 2021 Dec 10.
Artigo em Chinês | MEDLINE | ID: mdl-34839512

RESUMO

OBJECTIVE: To explore the genetic basis for a Chinese patient with amyotrophic lateral sclerosis (ALS). METHODS: Peripheral blood samples were collected from the patient and his parents for the extraction of genomic DNA. Genetic variant was identified by whole exome sequencing. Candidate variant was verified by Sanger sequencing of his parents and healthy controls. RESULTS: The patient was found to harbor a heterozygous c.420C>G (p.Asn140Lys) variant of the SOD1 gene. The same variant was not detected in his parents and 100 healthy controls. The variant has not been included in HGMD, dbSNP and other databases. CONCLUSION: The c.420C>G variant of the SOD1 gene may underlie the ALS in this patient. Above finding has enriched the spectrum of SOD1 gene variants.


Assuntos
Esclerose Amiotrófica Lateral , Esclerose Amiotrófica Lateral/genética , China , Heterozigoto , Humanos , Superóxido Dismutase-1/genética , Sequenciamento do Exoma
9.
J Foot Ankle Surg ; 60(5): 881-886, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33781640

RESUMO

Few studies have characterized the clinical outcomes of 45S5 Bioglass® applied as a bone graft to that of allogeneic bone applied in calcaneal open curettage. Therefore, the purpose of the present investigation was to compare the outcomes of patients with calcaneal tumors and tumor-like lesions treated by open curettage with 45S5 Bioglass® or allogeneic bone. Of the 31 patients who underwent open curettage (18 cases of unicameral bone cysts, 7 cases of aneurysmal bone cysts, and 6 cases of intraosseous lipoma), 16 (52%) received grafts with 45S5 Bioglass® and 15 (48%) with allogeneic bone. All the feet achieved bone fusion according to the modified Neer radiographic classification system at the last follow-up examination. The mean bone ingrowth time for the grafts with 45S5 Bioglass® versus allogeneic bone was 3.71 ± 0.86 versus 4.46 ± 1.04 months (p = .038), the mean bone healing time was 4.86 ± 0.93 versus 5.73 ± 1.07 months (p = .021), and the mean incision drying time was 7.2 ± 1.8 versus 8.2 ± 1.5 days (p = .047), respectively. No differences were found in the postoperative American Orthopaedic Foot and Ankle Society ankle-hindfoot scale scores between the 2 groups (p = .213). These results show that 45S5 Bioglass® can better facilitate the formation of new bone with a faster drying time of the incision than allogeneic bone. Although both materials can benefit the clinical outcomes of calcaneal tumors and tumor-like lesions, further studies are needed to observe the long-term complications and lesion recurrence rates.


Assuntos
Calcâneo , Transplante de Células-Tronco Hematopoéticas , Calcâneo/diagnóstico por imagem , Calcâneo/cirurgia , Curetagem , Vidro , Humanos , Recidiva Local de Neoplasia
10.
J Nat Prod ; 84(4): 1226-1231, 2021 04 23.
Artigo em Inglês | MEDLINE | ID: mdl-33600172

RESUMO

Assisted by MS/MS-based molecular networking and X-ray diffraction analysis, five new p-terphenyl derivatives, namely, nocarterphenyls D-H (1-5), were obtained and characterized from the cultures of the marine sediment-derived actinomycete Nocardiopsis sp. HDN154086. The skeleton of nocarterphenyl D (1) was defined to possess a rare 2,2'-bithiazole scaffold, naturally occurring for the first time, and nocarterphenyls E-H (2-5) are p-terphenylquinones with unusual thioether linked fatty acid methyl ester substitutions. Compound 1 showed promising activity against multiple bacteria with MIC values ranging from 1.5 to 6.2 µM, and 2 exhibited notable antibacterial activity against MRSA which surpassed the positive control ciprofloxacin.


Assuntos
Antibacterianos/farmacologia , Nocardiopsis/química , Compostos de Terfenil/farmacologia , Antibacterianos/isolamento & purificação , China , Sedimentos Geológicos/microbiologia , Testes de Sensibilidade Microbiana , Estrutura Molecular , Oceano Pacífico , Compostos de Terfenil/isolamento & purificação
11.
Zhonghua Yi Xue Yi Chuan Xue Za Zhi ; 38(1): 47-51, 2021 Jan 10.
Artigo em Chinês | MEDLINE | ID: mdl-33423257

RESUMO

OBJECTIVE: To detect the mutation site in a pedigree affected with autosomal dominant polycystic kidney disease (ADPKD) and verify its impact on the protein function. METHODS: Peripheral blood samples were collected from the proband and his pedigree members for the extraction of genomic DNA. Mutational analysis was performed on the proband through whole-exome sequencing. Suspected variant was verified by Sanger sequencing. A series of molecular methods including PCR amplification, restriction enzyme digestion, ligation and transformation were also used to construct wild-type and mutant eukaryotic expression vectors of the PKD2 gene, which were transfected into HEK293T and HeLa cells for the observation of protein expression and cell localization. RESULTS: The proband was found to harbor a c.2051dupA (p. Tyr684Ter) frame shift mutation of the PKD2 gene, which caused repeat of the 2051st nucleotide of its cDNA sequence and a truncated protein. Immunofluorescence experiment showed that the localization of the mutant protein within the cell was altered compared with the wild-type, which may be due to deletion of the C-terminus of the PKD2 gene. CONCLUSION: The c.2051dupA (p. Tyr684Ter) mutation of the PKD2 gene probably underlay the pathogenesis of ADPKD in this pedigree.


Assuntos
Mutação da Fase de Leitura , Rim Policístico Autossômico Dominante , Proteínas Quinases , Análise Mutacional de DNA , Feminino , Células HEK293 , Células HeLa , Humanos , Masculino , Linhagem , Rim Policístico Autossômico Dominante/genética , Rim Policístico Autossômico Dominante/fisiopatologia , Proteína Quinase D2 , Proteínas Quinases/genética , Transporte Proteico/genética , Sequenciamento do Exoma
12.
Comput Methods Biomech Biomed Engin ; 24(8): 897-904, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33331162

RESUMO

Expansions were carried out in finite element (FE) models of disc hernia including symmetric (median, lateral, paramedian) and asymmetric types. In all models, lubricous disk bulging that applied a linear compression to the anterior part of the cord was observed at the posterior surfaces of the expansion zone, respectively. The shape and position of protrusions varyed with the temperature, magnitude, and location of expanding elements. The geometric deformation and stress distribution of the spinal cord increased as the extent of compression grew. This method is in possession of enormous potential in promoting further individualized research of cervical spondylotic myelopathy.


Assuntos
Vértebras Cervicais/fisiopatologia , Degeneração do Disco Intervertebral/fisiopatologia , Deslocamento do Disco Intervertebral/fisiopatologia , Doenças da Medula Espinal/fisiopatologia , Espondilose/fisiopatologia , Simulação por Computador , Progressão da Doença , Análise de Elementos Finitos , Humanos , Disco Intervertebral , Modelos Anatômicos , Modelos Teóricos , Pescoço , Medula Espinal/fisiopatologia , Temperatura
13.
Comput Methods Programs Biomed ; 200: 105862, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33309302

RESUMO

BACKGROUND: Magnetic resonance imaging (MRI) has been known to replace computed tomography (CT) for bone and skeletal joint examination. The accurate automatic segmentation of bone structure in shoulder MRI is important for the measurement and diagnosis of bone injury and disease. Existing bone segmentation algorithms cannot achieve automatic segmentation without any prior knowledge, and their versatility and accuracy are relatively low. Therefore, an automatic segmentation combining pulse coupled neural network (PCNN) and full convolutional neural networks (FCN) is proposed. METHODOLOGY: By constructing the block-based AlexNet segmentation model and U-Net-based bone segmentation module, we implemented the humeral segmentation model, articular bone segmentation model, humeral head and articular bone segmentation model synthesis model. We use this four kinds of segmentation models to obtain candidate bone regions, and accurately detect the positions of humerus and articular bone by voting. Finally, we perform an AlexNet segmentation model in the detected bone area in one step to segment accuracy at the pixel level. RESULTS: The experimental data came from 8 groups of patients in Shengjing Hospital affiliated to China Medical University. The scanning volume of each group is approximately 100 images. Five fold cross-validations and for training were recorded, and five sets of data were carefully separated. After using our technique in the three groups of patients tested, the positive predictive value of dice coefficient (PPV) and the average accuracy of sensitivity were very significant, which reached 0.96±0.02, 0.97±0.02 and 0.94±0.03, respectively. CONCLUSION: The method used in the experiment in this paper is based on a small amount of patient sample data. The deep learning required for the experiment needs to be performed through 2D medical images. The shoulder segmentation data obtained in this way can be very accurate.


Assuntos
Articulação do Ombro , China , Humanos , Processamento de Imagem Assistida por Computador , Imageamento por Ressonância Magnética , Redes Neurais de Computação , Articulação do Ombro/diagnóstico por imagem
14.
Mar Drugs ; 18(11)2020 Oct 26.
Artigo em Inglês | MEDLINE | ID: mdl-33114712

RESUMO

Three new aspochracin-type cyclic tripeptides, sclerotiotides M-O (1-3), together with three known analogues, sclerotiotide L (4), sclerotiotide F (5), and sclerotiotide B (6), were obtained from the ethyl acetate extract of the fungus Aspergillus insulicola HDN151418, which was isolated from an unidentified Antarctica sponge. Spectroscopic and chemical approaches were used to elucidate their structures. The absolute configuration of the side chain in compound 4 was elucidated for the first time. Compounds 1 and 2 showed broad antimicrobial activity against a panel of pathogenic strains, including Bacillus cereus, Proteus species, Mycobacterium phlei, Bacillus subtilis, Vibrio parahemolyticus, Edwardsiella tarda, MRCNS, and MRSA, with MIC values ranging from 1.56 to 25.0 µM.


Assuntos
Antibacterianos/farmacologia , Antineoplásicos/farmacologia , Aspergillus/metabolismo , Bactérias/efeitos dos fármacos , Peptídeos/farmacologia , Poríferos/microbiologia , Animais , Regiões Antárticas , Antibacterianos/química , Antineoplásicos/química , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Humanos , Peptídeos/química , Conformação Proteica
15.
Comput Methods Programs Biomed ; 197: 105754, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32957059

RESUMO

OBJECTIVE: Bone age prediction can be performed by medical experts manually assessment of X-ray images of the hand bone. In practice, the workload is huge, resource consumption is large, measurement takes a long time, and it is easily influenced by human factors. As such, manual estimation of bone age takes a long time and the results fluctuate greatly depending on the proficiency of the radiologist. METHODS: The left-hand X-ray image data was identified and pre-processed. X-ray image analysis method using on deep neural network was used to automatically extract the key features of the left-hand joint bone age, and evaluation performance of the model was implemented. RESULTS: In this paper, the deep learning method can be used to obtain the X-ray bone image features, and the convolutional neural network is used to automatically assess the age of bone. The feature region extraction method based on deep learning can extract feature information with superior performance compared to the traditional image analysis technique. Based on the residual network (ResNet) model in the deep learning algorithm, the average absolute error of the age of bones detected by the bone age assessment model is 0.455 better than traditional methods and only end-to-end deep learning methods. When the learning rate is greater than 0.0005, the MAE of Inception Resnet v2 model is higher than most models. Accuracy of bone age prediction is as high as 97.6%. CONCLUSION: In comparison with the traditional machine learning feature extraction technique, the convolutional neural network based on feature extraction has better performance in the bone age regression model, and further improves the accuracy of image-based age of bone assessment.


Assuntos
Ossos da Mão , Redes Neurais de Computação , Algoritmos , Humanos , Processamento de Imagem Assistida por Computador , Aprendizado de Máquina
16.
Mol Genet Genomic Med ; 8(9): e1366, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32588564

RESUMO

BACKGROUND: Osteogenesis imperfecta (OI), a rare autosomal inheritable disorder characterized by bone fragility and skeletal deformity, is caused by pathogenic variants in genes impairing the synthesis and processing of extracellular matrix protein collagen type I. With the use of next-generation sequencing and panels approaches, an increasing number of OI patients can be confirmed and new pathogenic variants can be discovered. This study sought to identify pathogenic gene variants in a Chinese family with OI I. METHODS: Whole-exome sequencing was used to identify pathogenic variants in the proband, which is confirmed by Sanger sequencing and cosegregation analysis; MES, HSF, and Spliceman were used to analyze this splicing variant;qRT-PCR was performed to identify the mRNA expression level of COL1A1 in patient peripheral blood samples; Minigene splicing assay was performed to mimic the splicing process of COL1A1 variants in vitro; Analysis of evolutionary conservation of amino acid residues and structure prediction of the mutant protein. RESULTS: A novel splicing pathogenic variant (c.3814+1G>T) was identified in this OI family by using whole-exome sequencing, Sanger sequencing, and cosegregation analysis. Sequencing of RT-PCR products from the COL1A1 minigene variant reveals a 132-nucleotide (nt) insertion exists at the junction between exons 48 and exon 49 of the COL1A1 cDNA. Splicing assay indicates that the mutated minigene produces an alternatively spliced transcript which may cause a frameshift resulting in early termination of protein expression. The molecular analysis suggested that the altered amino acid is located at the C-terminus of type I procollagen. CONCLUSION: Our study reveals the pathogenesis of a novel COL1A1 splicing pathogenic variant c.3814+1G>T in a Chinese family with OI I.


Assuntos
Colágeno Tipo I/genética , Osteogênese Imperfeita/genética , Adulto , Idoso , Colágeno Tipo I/metabolismo , Cadeia alfa 1 do Colágeno Tipo I , Feminino , Células HEK293 , Humanos , Masculino , Pessoa de Meia-Idade , Osteogênese Imperfeita/patologia , Linhagem , Mutação Puntual , Splicing de RNA
17.
Artigo em Inglês | MEDLINE | ID: mdl-31245305

RESUMO

Rheumatoid arthritis (RA) is a common autoimmune disease linked to chronic inflammation. Dysbiosis of the gut microbiota has been proposed to contribute to the risk of RA, and a large number of researchers have investigated the gut-joint axis hypothesis using the collagen-induced arthritis (CIA) rats. However, previous studies mainly involved short-term experiments; very few used the CIA model to investigate changes in gut microbiota over time. Moreover, previous research failed to use the CIA model to carry out detailed investigations of the effects of drug treatments upon inflammation in the joints, hyperplasia of the synovium, imbalance in the ratios of Th1/Th2 and Th17/Treg cells, intestinal cytokines and the gut microbiota following long-term intervention. In the present study, we carried out a 16-week experiment to investigate changes in the gut microbiota of CIA rats, and evaluated the modulatory effect of total glucosides of paeony (TGP), an immunomodulatory agent widely used in the treatment of RA, after 12 weeks of administration. We found that taxonomic differences developed in the microbial structure between the CIA group and the Control group. Furthermore, the administration of TGP was able to correct 78% of these taxonomic differences, while also increase the relative abundance of certain forms of beneficial symbiotic bacteria. By the end of the experiment, TGP had reduced body weight, thymus index and inflammatory cell infiltration in the ankle joint of CIA rats. Furthermore, the administration of TGP had down-regulated the synovial content of VEGF and the levels of Th1 cells and Th17 cells in CIA rats, and up-regulated the levels of Th2 cells and Treg cells. The administration of TGP also inhibited the levels of intestinal cytokines, secretory immunoglobulin A (SIgA) and Interferon-γ (IFN-γ). In conclusion, the influence of TGP on dynamic changes in gut microbiota, along with the observed improvement of indicators related to CIA symptoms during 12 weeks of administration, supported the hypothesis that the microbiome may play a role in TGP-mediated therapeutic effects in CIA rats. The present study also indicated that the mechanism underlying these effects may be related to the regulation of intestinal mucosal immunity remains unknown and deserves further research attention.


Assuntos
Artrite Experimental/tratamento farmacológico , Colágeno/efeitos adversos , Microbioma Gastrointestinal/efeitos dos fármacos , Glucosídeos/farmacologia , Paeonia/química , Animais , Articulação do Tornozelo/patologia , Artrite Experimental/induzido quimicamente , Artrite Experimental/patologia , Artrite Reumatoide/tratamento farmacológico , Bactérias/classificação , Bactérias/efeitos dos fármacos , Peso Corporal/efeitos dos fármacos , Citocinas/metabolismo , Modelos Animais de Doenças , Medicamentos de Ervas Chinesas , Disbiose , Fezes/microbiologia , Microbioma Gastrointestinal/genética , Microbioma Gastrointestinal/fisiologia , Imunidade , Imunidade nas Mucosas , Imunoglobulina A Secretora , Imunomodulação , Inflamação , Interferon gama/metabolismo , Masculino , Ratos , Ratos Sprague-Dawley , Simbiose , Linfócitos T Reguladores/efeitos dos fármacos , Células Th1/efeitos dos fármacos , Células Th17/efeitos dos fármacos , Células Th2/efeitos dos fármacos , Fator A de Crescimento do Endotélio Vascular
18.
Mol Genet Genomic Med ; 7(3): e537, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30693673

RESUMO

BACKGROUND: Hearing impairment is one of most frequent birth defects, which affects nearly 1 in every 1,000 live births. However, the molecular etiology of non-syndromic deafness in China is not well studied. Here, we have investigated the presence of mutations in three genes commonly mutated in non-syndromic deafness patients in Shanxi Province, which has the highest frequency of birth defects in China. METHODS: In total, 1,201 unrelated non-syndromic deafness patients and 300 healthy individuals were enrolled. The hearing ability was confirmed by audiologic evaluation. Three major deafness-related genes (GJB2, SLC26A4 (PDS), and mtDNA 12S rRNA) of all individuals enrolled were analyzed by Sanger sequencing. RESULTS: The results showed that GJB2 mutations accounted for 21.23% (255/1,201) in the patient group, with c.235delC, a hotspot mutation, accounting for 10.99% (132/1,201). Moreover, 11 new GJB2 mutations were identified. SLC26A4 mutations accounted for 9.33% (112/1,201) in the patient group, with IVS7-2A>G as the most prevalent mutation accounting for 4.75% (57/1,201). In addition, 15 patients (1.25%) were found to carry mtDNA 12S rRNA c.1555A>G mutation, while only two cases had the mtDNA 12S rRNA c.1494C>T. CONCLUSION: In our research, it was found that c.235delC in GJB2 and c.919-2A>G (IVS7-2A>G) in SLC26A4 were the highest frequency pathogenic variants in Shanxi Province. Taken together, our data will enrich the database of deafness mutations and will help clinical diagnosis, treatment, and genetic counseling of hearing impairment.


Assuntos
Surdez/genética , Taxa de Mutação , Adolescente , Adulto , Criança , Pré-Escolar , China , Conexina 26 , Conexinas/genética , Feminino , Humanos , Lactente , Masculino , RNA Ribossômico/genética , Transportadores de Sulfato/genética
19.
Artigo em Inglês | MEDLINE | ID: mdl-30420891

RESUMO

Xueshuan Xinmaining Tablet (XXT) is a widely used traditional Chinese medicine for the treatment of stroke, chest pain, coronary heart disease, and angina pectoris caused by blood stasis. Having a multiple-component preparation, it is still far from meeting the requirements of modernization and standardization because its detailed chemical basis and action mechanism have not been clarified. In this work, the different batches of XXT samples were analyzed by HPLC and the typical sample was analyzed by UPLC-ESI-Q-TOF/MS to understand its chemical profiling. As a result, 77 chromatographic peaks were detected, among which 63 constituents were identified or tentatively characterized based on the comparison of retention time and UV spectra with authentic compounds as well as by summarized MS fragmentation rules and matching of empirical molecular formula with those of published components. This is the first systematic report on the chemical profiling of the commercial XXT products, which provides the sufficiently chemical evidence for the global quality evaluation of XXT products.

20.
J Clin Neurosci ; 27: 154-60, 2016 May.
Artigo em Inglês | MEDLINE | ID: mdl-26810470

RESUMO

microRNA-21 (miR-21) contributes to anti-apoptosis, proliferation and migration in many cells, but its role in inhibiting apoptosis in bone marrow mesenchymal stem cells (BMSC) remains unclear. The aim of this study was to determine the role of miR-21 in H2O2-induced BMSC apoptosis. We used quantitative real time-polymerase chain reaction (RT-PCR) to demonstrate the level of miR-21 after treatment of BMSC with H2O2. BMSC apoptosis was induced by different concentrations of H2O2 and was decreased in miR-21-upregulated cells. The expression of PTEN, a functional target gene of miR-21 in BMSC, was regulated by miR-21. The RT-PCR results indicated that miR-21 was significantly up-regulated, and western blot analysis indicated that Bcl-2 was up-regulated, whereas the apoptosis-related genes caspase 3/9 and Bax were down-regulated in miR-21-up-regulated cells. The miR-21-up-regulated cells had significantly enhanced Akt phosphorylation, as measured by western blot analysis. LY294002, an inhibitor of Akt activation, abolished the protective effects of miR-21-up-regulated cells. These results suggest that miR-21 contributes to inhibition of apoptosis in BMSC by down-regulating PTEN, potentially via the PI3K/Akt pathway.


Assuntos
Apoptose/efeitos dos fármacos , Células da Medula Óssea/efeitos dos fármacos , Peróxido de Hidrogênio/farmacologia , Células-Tronco Mesenquimais/efeitos dos fármacos , MicroRNAs/genética , Caspases/biossíntese , Caspases/genética , Cromonas/farmacologia , Inibidores Enzimáticos/farmacologia , Humanos , Morfolinas/farmacologia , PTEN Fosfo-Hidrolase/genética , Fosfatidilinositol 3-Quinases/genética , Inibidores de Fosfoinositídeo-3 Quinase , Fosforilação , Reação em Cadeia da Polimerase , Proteínas Proto-Oncogênicas c-akt/biossíntese , Proteínas Proto-Oncogênicas c-akt/genética , Regulação para Cima/efeitos dos fármacos , Proteína X Associada a bcl-2/biossíntese , Proteína X Associada a bcl-2/genética
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...