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1.
NPJ Genom Med ; 6(1): 69, 2021 Aug 13.
Artigo em Inglês | MEDLINE | ID: mdl-34389718

RESUMO

Neurodegenerative dementias are a group of diseases with highly heterogeneous pathology and complicated etiology. There exist potential genetic component overlaps between different neurodegenerative dementias. Here, 1795 patients with neurodegenerative dementias from South China were enrolled, including 1592 with Alzheimer's disease (AD), 110 with frontotemporal dementia (FTD), and 93 with dementia with Lewy bodies (DLB). Genes targeted sequencing analysis were performed. According to the American College of Medical Genetics (ACMG) guidelines, 39 pathogenic/likely pathogenic (P/LP) variants were identified in 47 unrelated patients in 14 different genes, including PSEN1, PSEN2, APP, MAPT, GRN, CHCHD10, TBK1, VCP, HTRA1, OPTN, SQSTM1, SIGMAR1, and abnormal repeat expansions in C9orf72 and HTT. Overall, 33.3% (13/39) of the variants were novel, the identified P/LP variants were seen in 2.2% (35/1592) and 10.9% (12/110) of AD and FTD cases, respectively. The overall molecular diagnostic rate was 2.6%. Among them, PSEN1 was the most frequently mutated gene (46.8%, 22/47), followed by PSEN2 and APP. Additionally, the age at onset of patients with P/LP variants (51.4 years), ranging from 30 to 83 years, was ~10 years earlier than those without P/LP variants (p < 0.05). This study sheds insight into the genetic spectrum and clinical manifestations of neurodegenerative dementias in South China, further expands the existing repertoire of P/LP variants involved in known dementia-associated genes. It provides a new perspective for basic research on genetic pathogenesis and novel guiding for clinical practice of neurodegenerative dementia.

2.
Aging (Albany NY) ; 13(8): 11352-11362, 2021 04 04.
Artigo em Inglês | MEDLINE | ID: mdl-33833133

RESUMO

BACKGROUND: Three polymorphisms in the Methylenetetrahydrofolate reductase (MTHFR) gene (C677T, A1298C, and A1793G) were reported associated with AD. However, their genotype distributions and associations with age at onset (AAO), homocysteine, and white matter lesions (WML) were unclear in the Chinese AD population. METHOD: We determined the presence of C677T, A1298C, and A1793G polymorphisms in the MTHFR gene using Sanger sequencing in a Chinese cohort comprising 721 AD patients (318 early-onset AD patients (EOAD) and 403 late-onset AD patients (LOAD)) and 365 elderly controls. Additionally, the homocysteine level and WML were evaluated in 121 AD patients. RESULTS: The frequency of allele T of C677T polymorphism was significantly higher in AD patients than in controls (P = 0.040), while no statistical difference was observed in A1298C and A1793G (P > 0.05). Besides, genotype distributions of C677T and A1298C polymorphisms statistically varied between AD patients and controls (P = 0.021, P = 0.012). Moreover, the AAO was significantly lower in CT/TT (C677T) genotypes carriers (P = 0.042) and higher in AC/CC (A1298C) and AG/GG (A1793G) genotypes carriers (P = 0.034, P = 0.009) in patients with LOAD. We also found that patients with CT/TT (C677T) genotypes were prone to present an increased homocysteine level (P = 0.036) and higher Fazekas score (P = 0.024). In comparison, patients with AG/GG genotypes (A1793G) had a significantly lower Fazekas score (P = 0.013). CONCLUSIONS: The genotype distributions of C677T and A1298C polymorphisms are associated with AD in the Chinese population. Moreover, AD patients with C677T polymorphism are prone to present an earlier onset, higher homocysteine level, and more severe WML.


Assuntos
Doença de Alzheimer/genética , Predisposição Genética para Doença , Homocisteína/sangue , Metilenotetra-Hidrofolato Redutase (NADPH2)/genética , Substância Branca/patologia , Idade de Início , Idoso , Alelos , Doença de Alzheimer/sangue , Doença de Alzheimer/epidemiologia , Doença de Alzheimer/patologia , Apolipoproteínas E/genética , Grupo com Ancestrais do Continente Asiático/genética , Estudos de Casos e Controles , China/epidemiologia , Feminino , Homocisteína/metabolismo , Humanos , Masculino , Metilenotetra-Hidrofolato Redutase (NADPH2)/metabolismo , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único
3.
Anal Sci ; 37(10): 1413-1418, 2021 Oct 10.
Artigo em Inglês | MEDLINE | ID: mdl-33775977

RESUMO

Saikosaponin a and saikosaponin d are used as chemical standards for the quality evaluation of Bupleurum chinense DC. by the high-performance liquid chromatography method in current Chinese Pharmacopoeia. However, other saikosaponins, such as saikosaponin c and saikosaponin b2, also possess pharmaceutical activity, but are not used as chemical standards. In this study, a quantitative proton nuclear magnetic resonance (1H NMR) method was developed to determine the total mass percentage (mg/g) of SSa, SSb1, SSb2 and SSd in B. chinense DC., using the H-24 (δH 0.71) signal. Furthermore, the molality (mol/kg) of type I saikosaponins (epoxy-ether structure) was also determined by quantitative 1H NMR in the area of H-11 (δH 5.95) for a more accurate quality evaluation. Validation of the method confirmed that it has acceptable selectivity, precision, stability, and repeatability. The results indicated that this method has the potential to be a reliable method for the quantification of saikosaponins in Bupleurum scorzonerifolium Willd., vinegar baked B. chinense DC. and B. scorzonerifolium Willd., Chaihu Koufuye (oral liquid of Chaihu).

4.
Artigo em Inglês | MEDLINE | ID: mdl-33538206

RESUMO

Backgbround: Frontotemporal dementia (FTD) is the second most common presenile dementia, characterized by prominent behavioral, language, and cognitive impairment, which has a strong genetic component contributing to its pathogenesis. Due to geographical and ethnic variability, the prevalence of the causative genes of FTD may be different. Methods: To explore the genetics of FTD in the Chinese population, we reviewed 97 closely related studies that were searched in PubMed and Web of Science. In this review, we summarized the characteristics of each FTD gene. We also reassessed their pathogenicity and revised some mutations from pathogenic to uncertain significance according to the American College of Medical Genetics and Genomics (ACMG). Results: Thirty-two rare variants in genes of MAPT, GRN, C9orf72, CHCHD10, VCP, and TBK1 were identified in Chinese FTD populations, including 25 pathogenic mutations and seven variants of uncertain significance (VUS). Among them, the frequency of rare variants in the CHCHD10 gene was the highest. Surprisingly, twelve variants reported as pathogenic mutations were revised as VUS by ACMG. The correlations between genes and clinical manifestations were MAPT and frontotemporal dementia and parkinsonism linked to chromosome 17 (FTDP-17), GRN and frontotemporal lobar degeneration with TDP-43 proteinopathy (FTLD-TDP), C9orf72/CHCHD10/TBK1 and amyotrophic lateral sclerosis (ALS)-FTD spectrum, and VCP corresponds inclusion body myopathy associated with Paget disease of bone and frontotemporal dementia (IBMPFD). Conclusions: It is necessary to strictly interpret the contributions of genes to diseases by ACMG. MAPT is the most common pathogenic gene for FTD in China.


Assuntos
Esclerose Amiotrófica Lateral , Demência Frontotemporal , Degeneração Lobar Frontotemporal , China/epidemiologia , Demência Frontotemporal/epidemiologia , Demência Frontotemporal/genética , Humanos , Mutação/genética
5.
Appl Environ Microbiol ; 87(3)2021 01 15.
Artigo em Inglês | MEDLINE | ID: mdl-33158898

RESUMO

Periodontitis is a highly prevalent oral inflammatory disease triggered by dysbiotic subgingival microbiota. For the development of microbiome modulators that can reverse the dysbiotic state and reestablish a health-associated microbiota, a high-throughput in vitro multispecies biofilm model is needed. Our aim is to establish a model that resembles a dysbiotic subgingival microbial biofilm by incorporating the major periodontal pathogen Porphyromonas gingivalis into microcosm biofilms cultured from pooled saliva of healthy volunteers. The biofilms were grown for 3, 7, and 10 days and analyzed for their microbial composition by 16S rRNA gene amplicon sequencing as well as measurement of dipeptidyl peptidase IV (DPP4) activity and butyric acid production. The addition of P. gingivalis increased its abundance in saliva-derived microcosm biofilms from 2.7% on day 3 to >50% on day 10, which significantly reduced the Shannon diversity but did not affect the total number of operational taxonomic units (OTUs). The P. gingivalis-enriched biofilms displayed altered microbial composition as revealed by principal-component analysis and reduced interactions among microbial species. Moreover, these biofilms exhibited enhanced DPP4 activity and butyric acid production. In conclusion, by adding P. gingivalis to saliva-derived microcosm biofilms, we established an in vitro pathogen-enriched dysbiotic microbiota which resembles periodontitis-associated subgingival microbiota in terms of increased P. gingivalis abundance and higher DPP4 activity and butyric acid production. This model may allow for investigating factors that accelerate or hinder a microbial shift from symbiosis to dysbiosis and for developing microbiome modulation strategies.IMPORTANCE In line with the new paradigm of the etiology of periodontitis, an inflammatory disorder initiated by dysbiotic subgingival microbiota, novel therapeutic strategies have been proposed targeting reversing dysbiosis and restoring host-compatible microbiota rather than eliminating the biofilms unselectively. Thus, appropriate laboratory models are required to evaluate the efficacy of potential microbiome modulators. In the present study, we used the easily obtainable saliva as an inoculum, spiked the microcosm biofilms with the periodontal pathogen Porphyromonas gingivalis, and obtained a P. gingivalis-enriched microbiota, which resembles the in vivo pathogen-enriched subgingival microbiota in severe periodontitis. This biofilm model circumvents the difficulties encountered when using subgingival plaque as the inoculum and achieves microbiota in a dysbiotic state in a controlled and reproducible manner, which is required for high-throughput and large-scale evaluation of strategies that can potentially modulate microbial ecology.


Assuntos
Disbiose/microbiologia , Gengiva/microbiologia , Porphyromonas gingivalis/fisiologia , Saliva/microbiologia , Biofilmes , Ácido Butírico/metabolismo , Dipeptidil Peptidase 4/metabolismo , Humanos , Microbiota/genética , Microbiota/fisiologia , Porphyromonas gingivalis/enzimologia , Porphyromonas gingivalis/genética , RNA Ribossômico 16S/genética
6.
Front Aging Neurosci ; 12: 581524, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33192475

RESUMO

Amyloid protein deposition is a common mechanism of hereditary amyloidosis (HA) and Alzheimer's disease (AD). Mutations of gelsolin (GSN), cystatin C (CST3), transthyretin (TTR), and integral membrane protein 2B (ITM2B) genes can lead to HA. But the relationship is unclear between these genes and AD. Genes targeted sequencing (GTS), including GSN, CST3, TTR, and ITM2B, was performed in a total of 636 patients with clinical AD and 365 normal controls from China. As a result, according to American College of Medical Genetics and Genomics (ACMG) guidelines, two novel likely pathogenic frame-shift mutations (GSN:c.1036delA:p.K346fs and GSN:c.8_35del:p.P3fs) were detected in five patients with AD, whose initial symptom was memory decline, accompanied with psychological and behavioral abnormalities later. Interestingly, the patient with K346fs mutation, presented cerebral ß-amyloid protein deposition, had an early onset (48 years) and experienced rapid progression, while the other four patients with P3fs mutation had a late onset [(Mean ± SD): 69.50 ± 5.20 years] and a long course of illness [(Mean ± SD): 9.24 ± 4.86 years]. Besides, we also discovered 17 variants of uncertain significance (VUS) in these four genes. To our knowledge, we are the first to report AD phenotype with GSN mutations in patients with AD in the Chinese cohort. Although mutations in the GSN gene are rare, it may explain a small portion of clinically diagnosed AD.

7.
Hum Reprod ; 35(11): 2439-2453, 2020 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-33047116

RESUMO

STUDY QUESTION: Does osteoprotegerin (OPG) promote human endometrial stromal decidualization? SUMMARY ANSWER: OPG is essential for human endometrial stromal decidualization through its interaction with syndecan-1 to decrease Akt phosphorylation. WHAT IS KNOWN ALREADY: OPG (a cytokine receptor) levels are significantly increased in the circulation of pregnant women. However, the role and mechanism of OPG in human endometrial stromal cell (ESC) decidualization remain elusive. STUDY DESIGN, SIZE, DURATION: We analyzed the endometrial expression of OPG in endometrial tissue samples collected from women with regular menstrual cycles (ranging from 25 to 35 days), and decidual tissue samples collected from woman with normal early pregnancy or recurrent pregnancy loss (RPL) who visited the Department of Gynecology and Obstetrics at a tertiary care center from January to October 2018. None of the subjects had hormonal treatment for at least 3 months prior to the procedure. In total, 16 women with normal early pregnancy and 15 with RPL were selected as subjects for this study. The function of OPG in decidualization was explored in a human endometrial stromal cell (HESC) line and primary cultures of HESCs. PARTICIPANTS/MATERIALS, SETTING, METHODS: We collected endometrial tissues (by biopsy) from the subjects during their menstrual cycle and decidual tissues from subjects with a normal early pregnancy and those with RPL at the time of dilation and curettage. The control group comprised randomly selected women who underwent termination of an apparently normal early pregnancy. The endometrial OPG expression was analyzed using immunohistochemical staining and quantitative RT-PCR (qRT-PCR). Immunofluorescence staining and western blot, and qRT-PCR were used to explore the mRNA and protein expression, respectively, of OPG in an immortalized HESC line and in primary cultures of HESC during proliferation and decidualization. siRNA-mediated knockdown experiments were performed to examine the function of OPG in HESC proliferation and decidualization. Flow cytometry and the cell proliferation MTS assay were performed to further examine the role of OPG in HESC proliferation. We also analyzed decidual marker gene expression by qRT-PCR to assess the consequences of OPG loss for HESC decidualization. A co-immunoprecipitation (IP) assay was used to determine the potential interaction between the OPG and Syndecan-1. Western blot analysis of the rescue experiments performed using the phosphatidylinositol 3-kinase (PI3K) signaling-specific inhibitor LY294002 was used to investigate the downstream signaling pathways through which OPG could mediate HESC decidualization. MAIN RESULTS AND THE ROLE OF CHANCE: OPG was expressed in both the human endometrium and in vitro decidualized ESCs. Knockdown experiments revealed that OPG loss impaired the expression of IGF-binding protein-1 (IGFBP-1) (P < 0.05) and prolactin (PRL) (P < 0.05), two specific markers of decidualization, in HESC undergoing decidualization. We also uncovered that OPG knockdown induced the aberrant activation of Akt (protein kinase B) during HESC decidualization (P < 0.05). The inhibition of Akt activation could rescue the impaired expression of the decidual markers PRL (P < 0.05) and IGFBP-1 (P < 0.05) in response to OPG knockdown. Syndecan-1 was considered a potential receptor candidate, as it was expressed in both the endometrium and in vitro cultured stromal cells. Subsequent co-IP experiments demonstrated the interaction between OPG and Syndecan-1 during decidualization. In addition, Syndecan-1 knockdown not only clearly attenuated the decidualization markers PRL (P < 0.05) and IGFBP-1 (P < 0.05) but also induced the aberrant enhancement of Akt phosphorylation in decidualized cells, consistent with the phenotype of OPG knockdown cells. Finally, we revealed that the transcript and protein expression of both OPG and Syndecan-1 was significantly lower in the decidual samples of women with RPL than in those of women with normal pregnancy (P < 0.05). LARGE SCALE DATA: N/A. LIMITATIONS, REASONS FOR CAUTION: In this study, based on a number of approaches, it was demonstrated that OPG mediated the repression of Akt that occurs during human stromal cell decidualization, however, the molecular link between OPG and Akt signaling was not determined, and still requires further exploration. WIDER IMPLICATIONS OF THE FINDINGS: OPG is required for decidualization, and a decrease in OPG levels is associated with RPL. These findings provide a new candidate molecule for the diagnosis and potential treatment of RPL. STUDY FUNDING/COMPETING INTEREST(S): This work was supported in part by the National Natural Science Foundation of China U1605223 (to G.S.), 81701457 (to Y.J.) and 81601349 (to Y.J.). The authors have no conflicts of interest to disclose.


Assuntos
Decídua , Proteínas Proto-Oncogênicas c-akt , Células Cultivadas , China , Decídua/metabolismo , Endométrio/metabolismo , Feminino , Humanos , Osteoprotegerina/genética , Osteoprotegerina/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Fosforilação , Gravidez , Proteínas Proto-Oncogênicas c-akt/metabolismo , Células Estromais/metabolismo , Sindecana-1/genética , Sindecana-1/metabolismo
8.
Minerva Chir ; 2020 Jul 16.
Artigo em Inglês | MEDLINE | ID: mdl-32672434

RESUMO

BACKGROUND: To compare the clinical efficacy of different methods for treating cesarean scar pregnancy (CSP). METHODS: The clinical data of 134 patients diagnosed with CSP in the Third Affiliated Hospital of Guangzhou Medical University were retrospectively analyzed. Grouped by treatment plan: pretreatments +ultrasound guided Curettage group (group A), pretreatments+ laparotomy (group B). Group A was sub-grouped according to the pretreatments: ultrasound guided uterine evacuation (A1), uterine arterial embolism (UAE) + ultrasound guided uterine evacuation (A2), high-intensity focused ultrasound (HIFU) + ultrasound guided uterine evacuation (A3); Group B was sub-groups according to pretreatments: laparotomy (B1), UAE + laparotomy (B2) . RESULTS: The success rates of treatment in groups A and B were 72.73%、100%, and it was statistically significant (P <0.05) There were no statistically significant in the blood loss and the degree of decrease of ß - hCG in these two group (P > 0.05). The operation time, length of stay and cost were statistically significant between curettage group and laparotomy group (P < 0.05); there was no significant difference in the degree of ß-HCG decrease (%) and surgical bleeding volume. The success rate in group A1-A3 was 64.10%, 96.52% and 100% respectively, which was statistically significant (P < 0.05). No statistically significant were showed in operation time, Length of stay and the degree of decrease of ß - hCG within 5 days after operation in A1-A3 group (P > 0.05). The blood loss and cost between A1 and A3 groups were statistically significant (P < 0.05). The success rate in group B1-B2 were both 100%, with no statistically significant (P> 0.05). There were no statistically significant in operation time, blood loss, degree of decrease of ß- hCG, length of stay between the two groups (P > 0.05). The cost between the two groups was statistically significant (P < 0.05). CONCLUSIONS: Ultrasound-guided uterine Curettage can be used as a better treatment for type I and II scar pregnancy. UAE or HIFU before Curettage can reduce uterine bleeding, while UAE before the laparotomy did not reduce uterine bleeding.

9.
Eur J Neurosci ; 52(8): 4009-4017, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32506655

RESUMO

Recently, functional studies have demonstrated that legumain (LGMN) cleaves both amyloid ß-protein precursor and tau, promoting senile plaques and formation of neurofibrillary tangles, which may play a crucial role in the pathogenesis of Alzheimer's disease (AD). However, the genetic role of LGMN in AD has not been clearly elucidated. Here, we used Sanger sequencing to investigate the single independent (single-variant association test) and cumulative (gene-based association test) effects of variants in the LGMN gene as potential susceptibility factors for AD, in a cohort comprising 676 AD cases and 365 elderly controls from the Han population of South China. In single-variant association analysis, none of the common variants in LGMN were statistically significant. In gene-based analysis, the LGMN gene also showed no association with AD. The results of our replication study in the Alzheimer's Disease Neuroimaging Initiative cohort also showed no association between LGMN and AD. These findings suggest that the LGMN gene may not be a critical factor for AD development.


Assuntos
Doença de Alzheimer , Idoso , Doença de Alzheimer/genética , Peptídeos beta-Amiloides , China , Cisteína Endopeptidases , Humanos , Polimorfismo de Nucleotídeo Único
10.
J Neuroimmunol ; 341: 577165, 2020 04 15.
Artigo em Inglês | MEDLINE | ID: mdl-32007786

RESUMO

Neuroinflammation has been considered to be involved in the development of schizophrenia. This study aimed to study circulating autoantibodies for inflammatory cytokines in first-episode schizophrenia. A total of 181 patients and 197 controls were recruited for detection of plasma IgG antibodies against peptide antigens derived from interleukin 1α (IL1α), IL1ß, IL6, IL8 and tumour necrosis factor alpha (TNFα). The major finding was that patients with schizophrenia had significantly higher levels of anti-IL1ß IgG, anti-IL6 IgG and anti-IL8 IgG, and a significantly lower level of anti-IL1α IgG. This study suggests that inflammatory response may contribute to the development of schizophrenia.


Assuntos
Autoanticorpos/sangue , Autoantígenos/imunologia , Citocinas/imunologia , Imunoglobulina G/sangue , Esquizofrenia/imunologia , Adulto , Especificidade de Anticorpos , Área Sob a Curva , Grupo com Ancestrais do Continente Asiático , Autoanticorpos/imunologia , Biomarcadores , Estudos de Casos e Controles , Feminino , Humanos , Imunoglobulina G/imunologia , Masculino , Pessoa de Meia-Idade , Curva ROC , Esquizofrenia/sangue , Esquizofrenia/etnologia , Adulto Jovem
11.
Neurobiol Aging ; 89: 142.e1-142.e7, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32081467

RESUMO

Recently, the (GGC)n repeat expansion in the NOTCH2NLC gene has been identified to be associated with neuronal intranuclear inclusion disease (NIID). Given the clinical overlap of dementia-dominant NIID with neurodegenerative dementia, we therefore hypothesized that the NOTCH2NLC repeat expansion might also contribute to these diseases. In the present study, repeat primed polymerase chain reaction (RP-PCR) and GC-rich PCR were conducted to detect the repeats of NOTCH2NLC in a cohort of 1004 patients with neurodegenerative dementias from mainland China. As a result, 4 sporadic patients were found to carry the NOTCH2NLC repeats expansion, totally accounting for 0.4% of all dementia individuals, and the accurate repeated sizes were 110, 133,120 and 76 respectively. Of 4 mutation carriers, three and one were clinically diagnosed Alzheimer's disease (AD) and frontotemporal dementia (FTD) respectively. In addition, 3 out of them revealed leukoencephalopathy in T2-Flair imaging. This study revealed that although rare, the NOTCH2NLC repeat expansions may be associated with AD or FTD-like phenotype as well as leukoencephalopathy.


Assuntos
Doença de Alzheimer/genética , Expansão das Repetições de DNA , Demência Frontotemporal/genética , Leucoencefalopatias/genética , Doenças Neurodegenerativas/genética , Receptor Notch2/genética , Idoso , China , Estudos de Coortes , Feminino , Estudos de Associação Genética , Humanos , Corpos de Inclusão Intranuclear/genética , Masculino , Pessoa de Meia-Idade
12.
ACS Appl Mater Interfaces ; 12(10): 11600-11606, 2020 Mar 11.
Artigo em Inglês | MEDLINE | ID: mdl-32073819

RESUMO

Self-standing and cost-effective electrodes for high-performance oxygen evolution reaction (OER) are vital for emerging energy storage and conversion technologies. We report a scalable binder-free OER electrode with open hollow nanocubes of Ni-doped CuOx on Ni foam (hNC/NF) through spontaneous galvanic displacement followed by simple electrochemical oxidation. Face-selective etching for the unique structure of hollow nanocubes with large open ends is achieved by utilizing the different accessibility of the top and side faces of cubes to solution species, more specifically the depletion of reactants between the densely supported nanocubes. Besides, the in situ deposition on Ni foam allows spontaneous Ni doping, which, as revealed by DFT calculations, fortunately strengthens the adsorption of oxygenated intermediates and therefore could optimize the free energy path of OER on Cu oxides. Benefiting further from the high accessible surface area of the unique open hollow architecture, the hNC/NF exhibits an outstanding OER activity with a small overpotential (η = 305 mV at 10 mA cm-2) as well as excellent stability without significant decay after 120 h operation. To our knowledge, this should represent the best OER performance of Cu-based electrocatalysts and is competitive with those based on Fe-group metals. Besides, the hNC/NF-based water electrolyzer delivers a performance of 1.50 V cell voltage at 10 mA cm-2, offering great promise for practical application.

13.
Med Sci Monit ; 26: e921502, 2020 Feb 18.
Artigo em Inglês | MEDLINE | ID: mdl-32066649

RESUMO

BACKGROUND Circular RNAs (circRNAs) are key regulators that take part in the carcinogenesis and development of breast cancer. The current study aimed to identify the expression of and explored the function of circRNA-0001283 in breast cancer. MATERIAL AND METHODS Breast cancer tissue samples were tested using high-throughput sequencing to identify the levels of relative genes; and proteins were addressed by using quantitative real-time polymerase chain reaction (qRT-PCR) and western-blot. Cell ability and cell apoptosis were investigated by Cell Counting Kit-8 (CCK-8) and flow cytometry. Invasion was detected by Transwell invasion assay. The identification of target genes was analyzed by dual-luciferase reporter assay. RESULTS Downregulation of circRNA-0001283 expression was observed in breast cancer tissue samples. Ectopic expression of circRNA-0001283 remarkably suppressed cell viability and invasion, and induced apoptosis in breast cancer cells. Furthermore, circRNA-0001283 bound to miR-187 and decreased the expression of miR-187, which resulted in inhibition in cell growth and invasion. Finally, we showed that circRNA-0001283 positively regulated HIPK3 expression by sponging miR-187. CONCLUSIONS The results reveal a new functional circRNA-0001283 in breast cancer and may provide targets for developing novel therapeutic strategies for breast cancer.


Assuntos
Neoplasias da Mama/genética , Neoplasias da Mama/patologia , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , MicroRNAs/metabolismo , Proteínas Serina-Treonina Quinases/metabolismo , RNA Circular/metabolismo , Transdução de Sinais , Apoptose/genética , Sequência de Bases , Linhagem Celular Tumoral , Proliferação de Células/genética , Regulação para Baixo/genética , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , NF-kappa B/metabolismo , Invasividade Neoplásica , RNA Circular/genética
14.
Front Microbiol ; 11: 66, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32063898

RESUMO

Periodontal disease is one of the most common diseases of the oral cavity affecting up to 90% of the worldwide population. Smoking has been identified as a major risk factor in the development and progression of periodontal disease. It is essential to assess the influence of smoking on subgingival microflora that is the principal etiological factor of the disease to clarify the contribution of smoking to periodontal disease. Therefore, this article reviews the current research findings regarding the impact of smoking on subgingival microflora and discusses several potential mechanisms. Cultivation-based and targeted molecular approaches yield controversial results in determining the presence or absence of smoking-induced differences in the prevalence or levels of certain periodontal pathogens, such as the "red complex." However, substantial changes in the subgingival microflora of smokers, regardless of their periodontal condition (clinical health, gingivitis, or periodontitis), have been demonstrated in recent microbiome studies. Available literature suggests that smoking facilitates early acquisition and colonization of periodontal pathogens, resulting in an "at-risk-for-harm" subgingival microbial community in the healthy periodontium. In periodontal diseases, the subgingival microflora in smokers is characterized by a pathogen-enriched community with lower resilience compared to that in non-smokers, which increases the difficulty of treatment. Biological changes in key pathogens, such as Porphyromonas gingivalis, together with the ineffective host immune response for clearance, might contribute to alterations in the subgingival microflora in smokers. Nonetheless, further studies are necessary to provide solid evidence for the underlying mechanisms.

15.
Front Microbiol ; 10: 2693, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31824464

RESUMO

Objectives: Our aim of this work was to investigate the regrowth of implant-related biofilms after various antimicrobial treatments in vitro. Methods: Saliva-derived microcosm biofilms were grown on titanium discs in an active attachment model. Treatments including hydrogen peroxide (HP), citric acid (CA), chlorhexidine (CHX), and distilled water (control), at different concentrations, were applied to 2-day biofilms for 1 or 5 min. The viability, lactic acid production, and composition of the biofilms were followed for 3 days. The biofilm composition was analyzed by 16S rDNA amplicon sequencing. Results: The short treatments of CA, CHX, and HP resulted in a 2-3 log reduction in biofilm viability and lactic acid production immediately. However, both parameters returned to the pre-treatment level within 2 days due to biofilm regrowth. The alpha diversity of the regrown biofilms in antimicrobial-treated groups tended to decrease, whereas the diversity of those in water-treated group increased. The composition of the regrown biofilms altered compared to those before treatments. Streptococcus and Enterobacteriaceae were enriched in the regrown biofilms. Conclusions: Although the antimicrobial treatments were efficient, the multi-species biofilms were indeed able to regrow within 2 days. The regrown biofilms display an altered microbial diversity and composition, which in the oral cavity may lead to an aggressive infection.

16.
BMC Bioinformatics ; 20(1): 444, 2019 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-31455207

RESUMO

BACKGROUND: Mining epistatic loci which affects specific phenotypic traits is an important research issue in the field of biology. Bayesian network (BN) is a graphical model which can express the relationship between genetic loci and phenotype. Until now, it has been widely used into epistasis mining in many research work. However, this method has two disadvantages: low learning efficiency and easy to fall into local optimum. Genetic algorithm has the excellence of rapid global search and avoiding falling into local optimum. It is scalable and easy to integrate with other algorithms. This work proposes an epistasis mining approach based on genetic tabu algorithm and Bayesian network (Epi-GTBN). It uses genetic algorithm into the heuristic search strategy of Bayesian network. The individual structure can be evolved through the genetic operations of selection, crossover and mutation. It can help to find the optimal network structure, and then further to mine the epistasis loci effectively. In order to enhance the diversity of the population and obtain a more effective global optimal solution, we use the tabu search strategy into the operations of crossover and mutation in genetic algorithm. It can help to accelerate the convergence of the algorithm. RESULTS: We compared Epi-GTBN with other recent algorithms using both simulated and real datasets. The experimental results demonstrate that our method has much better epistasis detection accuracy in the case of not affecting the efficiency for different datasets. CONCLUSIONS: The presented methodology (Epi-GTBN) is an effective method for epistasis detection, and it can be seen as an interesting addition to the arsenal used in complex traits analyses.


Assuntos
Algoritmos , Mineração de Dados , Epistasia Genética , Teorema de Bayes , Redes Reguladoras de Genes , Loci Gênicos , Humanos , Degeneração Macular/genética , Modelos Genéticos , Polimorfismo de Nucleotídeo Único/genética
17.
J Oral Microbiol ; 11(1): 1643205, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31448061

RESUMO

The COX-2/PGE2 axis can play roles in mediating the progression of tumor. COX-2 induction was observed in oral cancer. In our previous study, we found Staphylococcus aureus, a pathogen prevalent in oral cancer, can activate the COX-2/PGE2 pathway in human oral keratinocyte (HOK) cells. Here, we investigated the proliferation of HOK cells affected by COX-2 induction and the role of COX-2 induction in the malignant transformation of HOK cells. We found S. aureus was able to facilitate HOK cell proliferation through upregulating COX-2 expression. With the induction of COX-2, expression of oral cancer-associated genes cyclin D1 was upregulated and p16 was downregulated. Transcriptome analysis showed that the "NF-kappa B signaling pathway" and "TNF signaling pathway" had the highest enrichment of differentially expressed genes (DEGs) with COX-2 over-expression. Seven upregulated genes (jun, tlr4, cxcl1, lif, cxcl3, tnfrsf1ß, and il1ß) in these two pathways were critical for the increased proliferation of HOK cells and might be associated with COX-2. Malignant transformation of cells was evaluated by soft agar colony formation assay and S. aureus infection promoted HOK cell colony formation. These results suggest the potential of S. aureus to induce the infection-associated malignant transformation of oral epitheliums through COX-2 activation.

18.
FEBS Open Bio ; 9(10): 1705-1712, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31336035

RESUMO

It was recently reported that levels of plasma IgG antibodies against peptide antigens derived from proteins encoded by schizophrenia-associated genes are altered in individuals with schizophrenia treated with antipsychotics. This study aimed to replicate the initial finding in antipsychotic-naïve patients with first-episode schizophrenia and to explore the possible mechanism by which immune tolerance of B cells may be altered in this disease. A total of 408 case-control plasma samples were collected for analysis of circulating IgG antibodies against fragments derived from TCF4, TSNARE1, ZNF804A, TRANK1, ERCC4, DPYD and CD25 using an in-house ELISA. The Mann-Whitney U-test revealed that patients with schizophrenia had a significant change in plasma anti-TSNARE1 and anti-CD25 IgG levels; male patients mainly contributed to the increased levels of anti-TSNARE1 IgG and anti-CD25 IgG. Receiver operating characteristic (ROC) curve analysis revealed that the anti-TSNARE1 IgG assay had an area under the ROC curve of 0.625 with a sensitivity of 15.7% and a specificity of 95.2%. Work on a B-cell model revealed that TRANK1-derived antigen treatments could enhance the proportions of CD83+ cells and apoptotic B cells when compared with TSNARE1-derived antigen and vehicle treatment. We conclude that there is a gender difference in autoimmune responses in schizophrenia and suggest that anti-TSNARE1 IgG may be indicative of schizophrenia in a subgroup of male patients.


Assuntos
Imunoglobulina G/sangue , Imunoglobulina G/imunologia , Proteínas SNARE/imunologia , Esquizofrenia/sangue , Caracteres Sexuais , Adulto , Grupo com Ancestrais do Continente Asiático , China , Feminino , Humanos , Masculino
19.
Bioorg Med Chem Lett ; 29(4): 681-683, 2019 02 15.
Artigo em Inglês | MEDLINE | ID: mdl-30611616

RESUMO

Lysine specific demethylase (LSD1) plays a pivotal role in epigenetic modulation of gene expression. Abberrant expression of LSD1 was associated with the progress and oncogenesis of multiple human cancers. Herein, we report the preliminary anti-LSD1 evaluation of the synthetic vanadium (V) complexes. Among them, complex 2 showed a moderate inhibitory effect against LSD1 with IC50 value of 19.0 µM, as well as good selectivity over MAO-A/B. Complex 2 is the first vanadium based LSD1 inhibitor, which provides a novel scaffold for the development of LSD1 inhibitor.


Assuntos
Histona Desmetilases/antagonistas & inibidores , Bases de Schiff/química , Compostos de Vanádio/química , Humanos , Ligantes , Simulação de Acoplamento Molecular , Relação Estrutura-Atividade
20.
Psychiatry Res ; 272: 454-457, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30611964

RESUMO

A recent study suggested that digestion-resistant peptides derived from wheat gluten (mainly gliadin) could induce the secretion of anti-gliadin IgG antibodies in patients with schizophrenia. This research was then designed to replicate this initial finding in 134 drug-naïve patients with first-episode schizophrenia and 160 healthy controls. An enzyme-linked immunosorbent assay was developed in-house with 8 gliadin-derived peptide antigens to test anti-gliadin IgG antibodies in the circulation. The results showed that schizophrenia patients had significantly higher levels of plasma anti-AL2G2 IgG and anti-ABO3a IgG than healthy controls. Based on the specificity of 95%, anti-AL2G2 IgG assay had a sensitivity of 12.7% and anti-ABO3a IgG assay had a sensitivity of 17.2% for anti-ABO3a IgG assay. Increased levels of anti-AL2G2 and anti-ABC3a IgG antibodies were not correlated with total IgG levels in either the patient group or the control group. In conclusion, circulating IgG against AL2G2 and ABO3a may be useful biomarkers for identification of a gluten-sensitive subgroup of schizophrenia in the Chinese population although the present results are rather different from the work performed in a British population.


Assuntos
Autoanticorpos/sangue , Gliadina/sangue , Vigilância da População , Esquizofrenia/sangue , Esquizofrenia/epidemiologia , Adulto , Biomarcadores/sangue , China/epidemiologia , Ensaio de Imunoadsorção Enzimática/métodos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Vigilância da População/métodos , Esquizofrenia/diagnóstico
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