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1.
Ann Hematol ; 2024 Jul 16.
Artigo em Inglês | MEDLINE | ID: mdl-39012515

RESUMO

INTRODUCTION: Lymphoma tissue biopsies cannot fully capture genetic features due to accessibility and heterogeneity. We aimed to assess the applicability of circulating tumor DNA (ctDNA) for genomic profiling and disease surveillance in classic Hodgkin lymphoma (cHL), primary mediastinal large B-cell lymphoma (PMBCL), and diffuse large B-cell lymphoma (DLBCL). METHODS: Tumor tissue and/or liquid biopsies of 49 cHLs, 32 PMBCLs, and 74 DLBCLs were subject to next-generation sequencing targeting 475 genes. The concordance of genetic aberrations in ctDNA and paired tissues was investigated, followed by elevating ctDNA-based mutational landscapes and the correlation between ctDNA dynamics and radiological response/progression. RESULTS: ctDNA exhibited high concordance with tissue samples in cHL (78%), PMBCL (84%), and DLBCL (78%). In cHL, more unique mutations were detected in ctDNA than in tissue biopsies (P < 0.01), with higher variant allele frequencies (P < 0.01). Distinct genomic features in cHL, PMBCL, and DLBCL, including STAT6, SOCS1, BTG2, and PIM1 alterations, could be captured by ctDNA alone. Prevalent PD-L1/PD-L2 amplifications were associated with more concomitant alterations in PMBCL (P < 0.01). Moreover, ctDNA fluctuation could reflect treatment responses and indicate relapse before imaging diagnosis. CONCLUSIONS: Lymphoma genomic profiling by ctDNA was concordant with that by tumor tissues. ctDNA might also be applied in lymphoma surveillance.

2.
Fa Yi Xue Za Zhi ; 39(6): 579-585, 2023 Dec 25.
Artigo em Inglês, Zh | MEDLINE | ID: mdl-38228477

RESUMO

OBJECTIVES: To investigate the technical performance of IDentifier DNA typing kit (YanHuang34) and evaluate its forensic application value. METHODS: Following the Criterion of Forensic Science Human Fluorescence STR Multiplex Amplification Reagent (GB/T 37226-2018), IDentifier DNA typing kit (YanHuang34) was verified in 11 aspects of species specificity, veracity, sensibility, adaptability, inhibitor tolerance, consistency, balance, reaction condition verification, mixed samples, stability and inter batch consistency. The system efficiency of IDentifier DNA typing kit (YanHuang34) was compared with the PowerPlex® Fusion 6C System, VersaPlex® 27PY System and VeriFilerTM Plus PCR Amplification Kit. The IDentifier DNA typing kit (YanHuang34) was used to detect the swabs of biological samples in daily cases and the STR performances were observed. RESULTS: IDentifier DNA typing kit (YanHuang34) had good species specificity, veracity, adaptability, inhibitor tolerance and balance. The sensibility was up to 0.062 5 ng. It was able to detect different types of samples, degraded samples and inhibitor mixed samples. Complete DNA typing could be obtained for samples with the mixture ratio less than 4∶1. The system efficiency of IDentifier DNA typing kit (YanHuang34) was very high, with TDP up to 1-1.08×10-37, CPEtrio and CPEduo up to 1-5.47×10-14 and 1-6.43×10-9, respectively. For the touched biological samples in actual cases, the effective detection rate was 21.05%. The system efficiency of kinship, single parent and full sibling identifications was effectively improved. CONCLUSIONS: The IDentifier DNA typing kit (YanHuang34) is adaptive to the GB/T 37226-2018 requirements. It can be used for individual identification and paternity identification, and is suitable for application in the field of forensic science.


Assuntos
Impressões Digitais de DNA , Repetições de Microssatélites , Humanos , Reação em Cadeia da Polimerase , Paternidade , Especificidade da Espécie
3.
BMC Infect Dis ; 21(1): 853, 2021 Aug 21.
Artigo em Inglês | MEDLINE | ID: mdl-34418991

RESUMO

BACKGROUND: Malaria causes major public health problems globally and drug resistance hinders its control and elimination. Molecular markers associated with drug resistance are considered as a beneficial tool to monitor the disease trends, evolution and distribution so as to help improve drug policy. METHODS: We collected 148 Plasmodium falciparum and 20 Plasmodium vivax isolates imported into Hangzhou city, China between 2014 and 2019. k13 gene of P. falciparum and k12 of P. vivax were sequenced. Polymorphisms and prevalence of k13 and k12 were analyzed. RESULTS: Most (98.65%, 146/148) P. falciparum infections were imported from Africa, and half P. vivax cases came from Africa and the other half from Asia. Nucleotide mutation prevalence was 2.03% (3/148) and the proportion of amino acid mutations was 0.68% (1/148). The amino acid mutation, A676S, was observed in an isolate from Nigeria. No mutation of k12 was observed from the parasites from African and Asian countries. CONCLUSIONS: Limited polymorphism in k13 gene of P. falciparum isolates imported from African countries, but no evidence for the polymorphism of k12 in P. vivax samples from African and Asian countries was found. These results provide information for drug policy update in study region.


Assuntos
Antimaláricos , Malária Falciparum , Antimaláricos/uso terapêutico , Ásia , China/epidemiologia , Resistência a Medicamentos , Humanos , Malária Falciparum/tratamento farmacológico , Malária Falciparum/epidemiologia , Nigéria , Plasmodium falciparum/genética , Plasmodium vivax/genética , Proteínas de Protozoários/genética
4.
Biol Pharm Bull ; 36(4): 579-84, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-23386194

RESUMO

Carvacrol (CAR), a naturally occurring phenolic monoterpene, has been shown to possess diverse biological activities. The present study was undertaken to evaluate the cardioprotective potential of CAR against myocardial ischemic damage in a rat model of acute myocardial infarction. CAR significantly diminished the infarct size and myocardial enzymes including creatine kinase (CK), the MB isoenzyme of creatine kinase (CK-MB), lactate dehydrogenase (LDH) and cardiac troponin T (cTnT). Reduced level of malondialdehyde (MDA), obviously elevated activities of superoxide dismutase (SOD) and non-enzymatic scavenger glutathione (GSH) as well as glutathione peroxidase (GSH-PX) were also found in CAR-treated groups. Treatment with CAR remarkably inhibited the protein expressions of caspase-3 and Bax, but increased the level of Bcl-2 protein in infarcted rats by Western blot analysis. The finding suggests that the cardioprotection of CAR associate with its anti-oxidative and anti-apoptotic properties in acute myocardial infarction of rats.


Assuntos
Antioxidantes/farmacologia , Cardiotônicos/farmacologia , Monoterpenos/farmacologia , Infarto do Miocárdio/tratamento farmacológico , Animais , Antioxidantes/uso terapêutico , Apoptose/efeitos dos fármacos , Cardiotônicos/uso terapêutico , Caspase 3/metabolismo , Creatina Quinase Forma MB/sangue , Cimenos , Glutationa/metabolismo , Glutationa Peroxidase/metabolismo , L-Lactato Desidrogenase/sangue , Masculino , Malondialdeído/metabolismo , Monoterpenos/uso terapêutico , Infarto do Miocárdio/metabolismo , Infarto do Miocárdio/patologia , Ratos , Ratos Wistar , Superóxido Dismutase/metabolismo , Troponina T/sangue
5.
Appl Biochem Biotechnol ; 195(5): 3477-3490, 2023 May.
Artigo em Inglês | MEDLINE | ID: mdl-36607481

RESUMO

In cell biological functions and viability, cyclin-dependent kinase 1 (CDK1) takes an essential part. miR-195-5p is pivotal in pathogenesis and development of hepatocellular carcinoma (HCC). But in HCC, whether there is a connection between CDK1 and miR-195-5p remains an unanswered question. In view of this, this study focuses on exploring the mechanism of miR-195-5p/CDK1 in the progression of HCC. The bioinformatics method was applied to predict target mRNA and upstream miRNAs, and further analyzes the signal enrichment pathway of target mRNA. We utilized qRT-PCR and Western blot for detecting expression of genes, as well as their corresponding protein levels. Cell cycle was assayed through flow cytometry. As for the examination of DNA replication, the EDU staining was employed. Cell proliferation was determined via plate colony formation assay. The combined application of bioinformatics analysis and dual-luciferase gene assay assisted in figuring out the binding relationship between miR-195-5p and CDK1. DNA damage was marked by immunofluorescence staining. CDK1 was overexpressed in HCC cells, and enriched in cell cycle and DNA replication pathway. Silencing CDK1 modulated cell cycle of HCC cells and inhibited DNA replication and proliferation. In HCC cells, miR-195-5p targeted and reduced CDK1 expression, inhibited the G1 phase-to-S phase transition, induced DNA damage response, and inhibited DNA replication and proliferation. miR-195-5p targeted CDK1 and repressed synthesis of new DNA in HCC cells, thus restraining HCC cell proliferation.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , MicroRNAs , Humanos , Carcinoma Hepatocelular/patologia , Neoplasias Hepáticas/patologia , Proteína Quinase CDC2/genética , Proteína Quinase CDC2/metabolismo , MicroRNAs/genética , MicroRNAs/metabolismo , Proliferação de Células/genética , Replicação do DNA , RNA Mensageiro , Linhagem Celular Tumoral , Regulação Neoplásica da Expressão Gênica , Movimento Celular
6.
Spectrochim Acta A Mol Biomol Spectrosc ; 303: 123169, 2023 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-37517266

RESUMO

In this work, under simulated physiological conditions (pH = 2.2, glycine hydrochloric acid buffer solution), the interactions of cinnamic acid (CA), m-hydroxycinnamic acid (m-CA) and p-hydroxycinnamic acid (p-CA) with pepsin were studied by fluorescence spectroscopy, ultraviolet-visible absorption spectroscopy, circular dichroism (CD) spectroscopy, Fourier transform infrared spectroscopy (FTIR), molecular docking and molecular dynamic simulation (MD). The spectrogram results showed that these three kinds of CA had a strong ability to quench the intrinsic fluorescence of pepsin, and the quenching effects were obvious with the increase of concentration of these three kinds of molecules. The quenching mechanism of CA, m-CA and p-CA on the fluorescence of pepsin was static quenching. In addition, a stable complex was formed between three kinds of CA with pepsin. Thermodynamic data and docking information suggested that three kinds of CA combine with pepsin were mainly driven by electrostatic force and hydrogen bond. The binding constant and the number of binding sites were determined. The interaction of CA, m-CA and p-CA with pepsin was spontaneous, and accompanied by non-radiative energy transfer. The results from CD, FTIR, UV-Vis and synchronous fluorescence spectra measurements manifested that the secondary structure of pepsin was changed by the binding of three kinds of CA. The ß-sheet of pepsin increased after the interaction with three kinds of CA. The assay results of pepsin activity showed that three kinds of CA led to a decrease in pepsin activity within the investigated concentrations. Molecular docking investigation revealed the formation of polar hydrogen bonds as well as hydrophobic interactions between three kinds of CA with pepsin, and the ligand within the binding pocket of pepsin. MD results implied the formation of a stable complex between three kinds of CA and pepsin. The research suggested that cinnamic acid and its derivatives could be a potential effect on the structure and properties of digestive enzyme.


Assuntos
Pepsina A , Simulação de Acoplamento Molecular , Pepsina A/química , Espectrofotometria Ultravioleta , Sítios de Ligação , Espectrometria de Fluorescência , Termodinâmica , Ligação Proteica , Dicroísmo Circular
7.
Medicine (Baltimore) ; 101(35): e30316, 2022 Sep 02.
Artigo em Inglês | MEDLINE | ID: mdl-36107507

RESUMO

RATIONALE: A remarkable concurrence of an EGFR mutation and an EML4-ALK fusion (double positive) occasionally occurs within a narrow number of patients. Previous studies using targeted therapy on EGFR/ALK co-mutated patients have commonly focused on single tyrosine kinase inhibitors (TKIs) or on the sequential use of EGFR-TKIs and ALK-TKIs. At present, no consensus exists regarding the treatment of patients with double positive mutations. The effectiveness of precision therapy also remains unknown. PATIENT CONCERNS: A 53-year-old female non-smoker who described recurrent coughing and blood in her sputum over a month-long interval was examined at a local hospital. DIAGNOSIS: Using computed tomography (CT) and positron emission tomography CT (PET-CT), the patient was diagnosed with Stage IVb lung adenocarcinoma (T4N3M1). INTERVENTIONS: The patient had a novel ALK-RAB10 rearrangement identified using DNA sequencing, which, at the transcript level, was actually a canonical ALK fusion that caused a response to alectinib therapy. OUTCOMES: The patient has achieved partial remission (PR), with a progression free survival (PFS) of 16 months, and continues to benefit. LESSONS: Our results may indicate differential sensitivities to TKIs in patients harboring an EGFR mutation and an ALK rearrangement. Our patient's response to alectinib, instead of to EGFR-TKIs, may lead to an expanded list of alectinib beneficiaries who have rare gene co-alterations in lung adenocarcinoma.


Assuntos
Adenocarcinoma de Pulmão , Neoplasias Pulmonares , Adenocarcinoma de Pulmão/tratamento farmacológico , Adenocarcinoma de Pulmão/genética , Quinase do Linfoma Anaplásico/genética , Carbazóis , Receptores ErbB/genética , Feminino , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , Pessoa de Meia-Idade , Piperidinas , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Inibidores de Proteínas Quinases/farmacologia , Inibidores de Proteínas Quinases/uso terapêutico
8.
Front Oncol ; 12: 945843, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36185247

RESUMO

Adenosquamous carcinoma (ASC) of the lung is a relatively rare tumor with strong aggressiveness and poor prognosis. The analysis of mutational signatures is becoming routine in cancer genomics and has implications for pathogenesis, classification, and prognosis. However, the distribution of mutational signatures in ASC patients has not been evaluated. In this study, we sought to reveal the landscape of genomic mutations and mutational signatures in ASC. Next-generation sequencing (NGS) technology was used to retrieve genomic information for 124 ASC patients. TP53 and EGFR were the most prevalent somatic mutations observed, and were present in 66.9% and 54.8% of patients, respectively. CDKN2A (21%), TERT (21%), and LRP1B (18.5%) mutations were also observed. An analysis of gene fusion/rearrangement characteristics revealed a total of 64 gene fusions. The highest frequency of variants was determined for ALK fusions, with six ALK-EML4 classical and two intergenic ALK fusions, followed by three CD74-ROS1 fusions and one ROS1-SYN3 fusion. EGFR 19del (45.6%), and EGFR L858R (38.2%) and its amplification (29.4%) were the top three EGFR mutations. We extracted mutational signatures from NGS data and then performed a statistical analysis in order to search for genomic and clinical features that could be linked to mutation signatures. Amongst signatures cataloged at COSMIC, the most prevalent, high-frequency base changes were for C > T; and the five most frequent signatures, from highest to lowest, were 2, 3, 1, 30, and 13. Signatures 1 and 6 were determined to be associated with age and tumor stage, respectively, and Signatures 22 and 30 were significantly related to smoking. We additionally evaluated the correlation between tumor mutational burden (TMB) and genomic variations. We found that mutations ARID2, BRCA1, and KEAP1 were associated with high TMB. The homologous recombination repair (HRR) pathway-related gene mutation displayed a slightly higher TMB than those without mutations. Our study is the first to report comprehensive genomic features and mutational signatures in Chinese ASC patients. Results obtained from our study will help the scientific community better understand signature-related mutational processes in ASC.

9.
Spectrochim Acta A Mol Biomol Spectrosc ; 251: 119442, 2021 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-33461141

RESUMO

In this work, the interaction between ferulic acid (FA) and pepsin was explored by UV-visible absorption spectroscopy, fluorescence spectroscopy, synchronous fluorescence, circular dichroism (CD) spectroscopy, Fourier transform infrared spectroscopy (FT-IR) and molecular docking. The results of fluorescence revealed that FA had a strong ability to quench the intrinsic fluorescence of pepsin through a static quenching procedure. The binding constant and the number of binding sites were determined. Thermodynamic dates and docking information suggest that FA combine with pepsin is mainly driven via electrostatic force. It also requires synergistic drive of hydrophobic and hydrogen bonding. The consequences from UV-Vis, synchronous, CD and FT-IR spectra measurements manifested that the secondary structure of pepsin was changed and the microenvironments of certain amino acid residues was modulated by the binding of FA. FA induced conformational changes in pepsin. The ß-sheet, α-Helix, and Random fractions of pepsin increased and the ß-turn decreased with the treatment of FA. In addition, analysis of pepsin activity assay measurements confirmed that FA reduced enzymatic activity of pepsin within the investigated concentrations. This work studied the inhibitory effects and revealed mechanisms of the interaction between FA and pepsin in vitro, and suggested that FA could be a potential component to affect the structure and properties of digestive enzyme.


Assuntos
Pepsina A , Sítios de Ligação , Dicroísmo Circular , Ácidos Cumáricos , Simulação de Acoplamento Molecular , Ligação Proteica , Espectrometria de Fluorescência , Espectroscopia de Infravermelho com Transformada de Fourier , Termodinâmica
10.
RSC Adv ; 11(16): 9121-9129, 2021 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-35423426

RESUMO

This study proposes an easy bottom-up method for the synthesis of photoluminescent (PL) graphene quantum dots (GQDs) using citric acid as the carbon source. The obtained GQDs were characterized by high-resolution transmission electron microscopy (HRTEM), UV-vis absorption spectroscopy, fluorescence spectroscopy, and Fourier transform infrared spectroscopy (FT-IR). The synthesised GQDs have an average diameter of 4.76 ± 0.96 nm, with a lattice spacing of 0.24 nm. The GQDs exhibit excitation-independent PL emission. The surface of the GQDs has a variety of functional groups (hydroxyl, carboxyl, and ether groups etc.) to enhance its stability and water solubility. In this study, a fluorescent "on-off" sensor is developed for the selective detection of vanillin in chocolates using GQDs as a fluorescent probe. Under optimal conditions, fluorescence intensity of the GQDs has a good linear relationship with the vanillin concentration (0.0-2.1 × 10-5 mol L-1), with a limit of detection of 2.5 × 10-8 mol L-1. For detection in real samples, the percent recovery of vanillin and the relative standard deviation were 88.0-108.9% and 0.90-5.4%, respectively. Thus, this GQDs-based method has good accuracy and precision and can be used for vanillin detection in practical applications.

11.
J Healthc Eng ; 2021: 6668885, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33976755

RESUMO

In recent years, with the rapid development of colorectal surgery technology and laparoscopic instruments, laparoscopic radical resection of colorectal cancer has been widely used. Although laparoscopic surgery has the characteristics of small trauma, less blood loss, less hospitalization days, and low incidence of adverse reactions such as incision infection, it is still inevitable to have different degrees of gastrointestinal dysfunction after surgery. This paper mainly studies the recovery nursing of gastrointestinal peristalsis after abdominal mirror in rectal cancer patients based on intelligent electronic medicine. In this paper, an intelligent medical monitoring system is designed for the posterior care of rectal cancer patients with abdominal mirror image, which can realize the collection and transmission of wireless sign parameters of postoperative rectal cancer patients and improve the efficiency of postoperative monitoring in medical work. All parameter data are sent to the Lora base station in real time via Lora wireless communication, which is then uploaded to the medical monitoring platform. The experimental results showed that the first postoperative exhaust time of the treatment group using the intelligent medical monitoring system was significantly shortened, and the difference was statistically significant (P < 0.05). The first defecation time was shortened, and the difference was statistically significant (P < 0.05). The recovery time of total fluid diet was shortened, and the difference was statistically significant (P < 0.05). The above results indicate that the intelligent medical monitoring device designed in this paper has positive significance for improving the work efficiency of the hospital, the clinical experience of patients after abdominal mirror surgery for rectal cancer, and the real-time monitoring of signs of patients in intensive care.


Assuntos
Peristaltismo , Neoplasias Retais , Eletrônica , Humanos , Recuperação de Função Fisiológica , Neoplasias Retais/cirurgia , Estudos Retrospectivos , Resultado do Tratamento
12.
R Soc Open Sci ; 7(3): 191141, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32269782

RESUMO

This study proposes a strategy for the rapid and simple synthesis of gold nanoparticles (CGA-AuNPs) with different particle sizes using trisodium citrate (TSC) as the first reducing agent and chlorogenic acid (CGA) as the second reducing agent. And the antibacterial activity of CGA-AuNPs with different particle sizes in vitro was checked by measuring the growth curves of Escherichia coli (ATCC 25922) and Staphylococcus aureus (ATCC 25923). The CGA-AuNPs obtained by the analysis of transmission electron microscope (TEM) images and ultraviolet-visible (UV-Vis) spectra were mainly spherical, and the average diameters were 18.94 ± 1.81, 30.42 ± 6.32, 37.86 ± 3.80 and 48.72 ± 6.47 nm, respectively. High-resolution transmission electron microscopy (HRTEM) and selected area electron diffraction (SAED) showed that these nanoparticles were polycrystalline gold structures. Both CGA-AuNPs and CGA have excellent antibacterial activity, and CGA-AuNPs with small particle size has a stronger antibacterial effect than the larger one. UV-Vis absorption spectrum data revealed that the synthesized CGA-AuNPs without adding other stabilizing agent were well maintained even after 26 days. This work provides a special idea to regulate the size of CGA-AuNPs with CGA by chemical synthesis, and the potent antibacterial activity of these CGA-AuNPs may be applied in the field of antibacterial in the future.

13.
Emerg Microbes Infect ; 9(1): 889-899, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32284015

RESUMO

In the present study, a total of 7793 samples from 5 different types of hosts were collected and tested, with a seroprevalence of 2.4% (184/7793). Although the seroprevalence of human and animal brucellosis is relatively low, numbers of human brucellosis cases reported have increased continuously from 2004 to 2018. A total of 118 Brucella strains containing 4 biotypes were obtained, including Brucella melitensis bv.1 (n = 8) and bv.3 (n = 106), Brucella abortus bv.3 (n = 3) and bv.7 (n = 1). Twenty-one shared MLVA-16 genotypes, each composed of 2 to 19 strains obtained from different hosts, suggest the occurrence of a brucellosis outbreak epidemic with multiple source points and laboratory infection events. Moreover, 30 shared MLVA-16 genotypes were observed among 59.6% (68/114) B. melitensis isolates from Zhejiang and strains from other 21 different provinces, especially northern provinces, China. The analysis highlighted the imported nature of the strains from all over the northern provinces with a dominant part from the developed areas of animal husbandry. These data revealed a potential transmission pattern of brucellosis in this region, due to introduced infected sheep leading to a brucellosis outbreak epidemic, and eventually causing multiple laboratory infection events. It is urgent to strengthen the inspection and quarantine of the introduced animals.


Assuntos
Brucella/classificação , Brucelose/epidemiologia , Brucelose/transmissão , Infecção Laboratorial/microbiologia , Ovinos/microbiologia , Animais , Técnicas de Tipagem Bacteriana , Brucella abortus/genética , Brucella melitensis/genética , China/epidemiologia , DNA Bacteriano/genética , Surtos de Doenças , Variação Genética , Genótipo , Humanos , Repetições Minissatélites , Tipagem de Sequências Multilocus , Filogenia , Estudos Soroepidemiológicos
14.
Artigo em Inglês | MEDLINE | ID: mdl-28678169

RESUMO

Objective: The association between thyroid hormones, thyroid autoantibodies, and thyroid nodules are still not clear. The cross-sectional study, conducted in Hangzhou, China in 2010, aimed to identify the relationship of thyroid hormones and autoantibodies with thyroid nodules. Methods: Information regarding social demography was collected by a questionnaire. Thyroid hormones (triiodothyronine, thyroxin, free triiodothyronine, free thyroxin, thyrotropin), thyroid autoantibodies (thyroid peroxidase antibody, antithyroglobulin antibody), and thyroid nodules (diagnosed by ultrasonography) was measured in 1271 adults. The association of thyroid hormones and thyroid autoantibodies with thyroid nodules was evaluated using multiple logistic regression models. Results: The prevalence of thyroid nodules among males and females was 29.49% and 33.15%, respectively. The thyroid hormone level in the thyroid nodules group was significantly higher than the non-nodules group (all p values < 0.05), except reversely in TSH (thyroid stimulating hormone) (p = 0.0532) and TGAb (thyroglobulin antibody) (p = 0.0004). High levels of TPOAb (thyroid peroxidase antibody) (OR (Odds Ratio) = 1.51, 95% CI (confidence interval): 0.99-2.30) and TGAb (OR = 2.86, 95% CI: 1.49-5.51) were associated with increased risk of thyroid nodules, compared with corresponding low levels. However, following sub-analyses in two genders, the similar associations were only observed in females (TPOAb: OR = 1.63, 95% CI: 0.99-2.68; TGAb: OR = 3.13, 95% CI: 1.53-6.40). Conclusions: The present study indicated that thyroid autoantibodies were positively associated with the risk of thyroid nodules in Chinese coastal adults.


Assuntos
Autoanticorpos/imunologia , Iodeto Peroxidase/imunologia , Nódulo da Glândula Tireoide/epidemiologia , Nódulo da Glândula Tireoide/etiologia , Adulto , China/epidemiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Tireoglobulina/imunologia , Nódulo da Glândula Tireoide/imunologia
15.
Int J Mol Med ; 40(4): 1125-1133, 2017 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-28791345

RESUMO

Neuro-oncological ventral antigen 1 (Nova1) is a well known brain-specific splicing factor. Several studies have identified Nova1 as a regulatory protein at the top of a hierarchical network. However, the function of Nova1 during hypoxia remains poorly understood. This study aimed to investigate the protective effect of Nova1 against cell hypoxia and to further explore the Bax/Bcl-2/caspase-3 pathway as a potential mechanism. During hypoxia, the survival rate of pheochromocytoma PC12 cells was gradually decreased and the apoptosis rate was gradually increased, peaking at 48 h of hypoxia. At 48 h after transfection of PC12 cells with pCMV-Myc-Nova1, the expression of Nova1 was significantly increased, with wide distribution in the cytoplasm and nucleus. Moreover, the survival rate was significantly increased and the apoptosis rate was significantly decreased. Additionally, the mRNA and protein expression levels of Bax and caspase-3 were significantly increased in the pCMV-Myc group and significantly decreased in the pCMV­Myc-Nova1 group, whereas that of Bcl-2 was significantly decreased in the pCMV-Myc group and significantly increased in the pCMV-Myc-Nova1 group. This study indicated that Nova1 could be linked to resistance to the hypoxia-induced apoptosis of PC12 cells via the Bax/Bcl-2/caspase-3 pathway, and this finding may be of significance for exploring novel mechanisms of hypoxia and the treatment of hypoxia-associated diseases.


Assuntos
Caspase 3/genética , Proteínas Proto-Oncogênicas c-bcl-2/genética , Proteínas de Ligação a RNA/genética , Transdução de Sinais/genética , Proteína X Associada a bcl-2/genética , Animais , Apoptose/efeitos dos fármacos , Caspase 3/metabolismo , Hipóxia Celular/genética , Núcleo Celular/genética , Núcleo Celular/metabolismo , Sobrevivência Celular/efeitos dos fármacos , Citoplasma/genética , Citoplasma/metabolismo , Regulação da Expressão Gênica , Antígeno Neuro-Oncológico Ventral , Oxigênio/farmacologia , Células PC12 , Plasmídeos/química , Plasmídeos/metabolismo , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Proteínas de Ligação a RNA/metabolismo , Ratos , Transfecção , Proteína X Associada a bcl-2/metabolismo
16.
Curr Med Res Opin ; 32(3): 555-62, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-26652645

RESUMO

OBJECTIVES: To investigate the effects of angiogenesis inhibitors in the treatment of patients with advanced or recurrent ovarian cancer, a meta-analysis was performed and overall survival (OS), progression-free survival (PFS), and toxicity were assessed. PATIENTS AND METHODS: The PubMed and Embase databases, and the Cochrane Central Register of Controlled Trials were searched for publications between January 2000 and June 2015. Hazard ratios (HRs) with their 95% confidence intervals (CIs), or data for calculating HRs with 95% CIs were derived. RESULTS: The 12 trials in this meta-analysis were divided into three groups: four trials with a VEGF inhibitor (the bevacizumab group), six trials with VEGFR inhibitors (the VEGFRIs group), and two trials with an angiopoietin inhibitor (the trebananib group). PFS improvement was seen in all groups (HR = 0.61, 95% CI 0.48 to 0.79, P < 0.001 for bevacizumab; HR = 0.71, 95% CI 0.59 to 0.87, P = 0.001 for VEGFRIs; and HR = 0.67, 95% CI 0.62 to 0.72, P < 0.001 for trebananib). Regarding OS, bevacizumab showed a trend of improvement (HR = 0.90, 95% CI 0.80 to 1.01, P = 0.079), VEGFRIs showed no improvement (HR = 0.92, 95% CI 0.75 to 1.11, P = 0.368), and trebananib demonstrated a significant prolongation (HR = 0.81, 95% CI 0.67 to 0.99, P = 0.036). Bevacizumab was associated with more class-specific adverse events (RR = 4.05, 95% CI 1.99 to 8.27, P < 0.001). Although the toxicity profiles differed, VEGFRIs developed common higher incidences of hypertension, diarrhea, and fatigue. A higher incidence of edema was reported in the trebananib group (RR = 2.60, 95% CI 0.84 to 8.00, P = 0.097). CONCLUSIONS: Anti-angiogenic therapy showed clear PFS benefit with increased toxicity, but its role in OS was undefined for ovarian cancer which emphasized the need for patient selection.


Assuntos
Inibidores da Angiogênese/administração & dosagem , Bevacizumab/administração & dosagem , Neoplasias Ovarianas/tratamento farmacológico , Inibidores da Angiogênese/efeitos adversos , Bevacizumab/efeitos adversos , Intervalo Livre de Doença , Feminino , Humanos , Inibidores de Proteínas Quinases/administração & dosagem , Inibidores de Proteínas Quinases/efeitos adversos , Ensaios Clínicos Controlados Aleatórios como Assunto
17.
Sheng Wu Gong Cheng Xue Bao ; 32(4): 507-517, 2016 Apr 25.
Artigo em Zh | MEDLINE | ID: mdl-28853272

RESUMO

The aim of this study was to construct the eukaryotic expression vector of pCMV-Myc-NOVA1 based on NOVA1 gene, and to screen the optimum expression condition after transfecting to PC12 cells, and further to explore the distribution of NOVA1 protein in PC12 cells using cell immunohistochemistry, and to identifyits anti-hypoxia activity. According to the NOVA1 gene sequence of NCBI database, we designed the upstream and downstream primers, and performed polymerase chain reaction (PCR) to amplify the full length cDNA coding sequence using pCR4-TOPO-NOVA1 as a template. The products were digested by restriction endonuclease SalⅠand XhoⅠ, and conjugated to the eukaryotic expression vector ofpCMV-Myc followed by validating by digestion and direct sequencing. Subsequently, the validated pCMV-Myc-NOVA1 was transfected to PC12 cells followed by optimizing of transfection ratio and transfection time, and identified by qPCR, Western blotting and cell immunohistochemistry respectively. After validation by digestion and direct sequencing, the eukaryotic expression vector of pCMV-Myc-NOVA1 was correctly constructed. The optimum transfection ratio of plasmid to Lipo 2000 was 1:2.5, and the optimum transfection time was 72 h. At the optimum transfection condition, the expression level of NOVA1 mRNA and protein significantly increased, and after transfection of pCMV-Myc-NOVA1, NOVA1 protein mainly distributed in cell nucleus and cytoplasm. After 6 h hypoxia, the cell proliferation activity was significantly increased compared to that of the control and pCMV-Myc group. Our findings provided a reference for exploring the mechanism of NOVA1, and also a technical support for potential drug development of NOVA1.


Assuntos
Proteínas de Ligação a RNA/metabolismo , Animais , Western Blotting , Hipóxia Celular , Vetores Genéticos , Humanos , Antígeno Neuro-Oncológico Ventral , Células PC12 , Plasmídeos , RNA Mensageiro , Proteínas de Ligação a RNA/genética , Ratos , Transfecção
18.
BMJ Open ; 5(12): e008452, 2015 Dec 21.
Artigo em Inglês | MEDLINE | ID: mdl-26692553

RESUMO

OBJECTIVE: Previous studies have found that overweight and obesity are related to numerous diseases, including thyroid cancer and thyroid volume. This study evaluates the relationship between body size and the presence of thyroid nodules in a Chinese population. METHODS: A total of 6793 adults and 2410 children who underwent thyroid ultrasonography were recruited in this cross-sectional study in Hangzhou, Zhejiang Province, China, from March to October, 2010. Sociodemographic characteristics and potential risk factors of thyroid nodules were collected by questionnaire. Height and weight were measured using standard protocols. Associations of height, weight, body mass index (BMI) and body surface area (BSA) with the presence of thyroid nodules were evaluated using multiple logistic regression models. RESULTS: After adjustment for potential risk factors, an increased risk of thyroid nodule incidence was associated with height (OR 1.15, 95% CI 1.02 to 1.30), weight (OR 1.40, 95% CI 1.24 to 1.58), BMI (OR 1.26, 95% CI 1.11 to 1.42) and BSA (OR 1.43, 95% CI 1.27 to 1.62) in all adults, but most obviously in women. In children, similar associations were observed between risk of thyroid nodule incidence and weight, BMI and BSA, but not height. BSA was the measurement most significantly associated with thyroid nodules in both adults and children. CONCLUSIONS: This study identified that the presence of thyroid nodules was positively associated with weight, height, BMI and BSA in both women and girls. It suggests that tall, obese individuals have increased susceptibility to thyroid nodules. TRIAL REGISTRATION NUMBER: NCT01838629.


Assuntos
Povo Asiático , Obesidade/epidemiologia , Glândula Tireoide/patologia , Neoplasias da Glândula Tireoide/prevenção & controle , Nódulo da Glândula Tireoide/patologia , Adolescente , Adulto , Estatura , Índice de Massa Corporal , Criança , China/epidemiologia , Estudos Transversais , Suscetibilidade a Doenças , Feminino , Humanos , Incidência , Masculino , Obesidade/complicações , Fatores de Risco , Glândula Tireoide/diagnóstico por imagem , Neoplasias da Glândula Tireoide/epidemiologia , Neoplasias da Glândula Tireoide/patologia , Nódulo da Glândula Tireoide/diagnóstico por imagem , Nódulo da Glândula Tireoide/epidemiologia , Ultrassonografia
19.
PLoS One ; 9(7): e102726, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-25068269

RESUMO

OBJECTIVE: The controversy that iodized salt may increase the risk of thyroid disorders has been aroused in China during the past decade. Most of studies focused on adult rather than children. We aimed to explore whether iodized salt was associated with an increased risk of thyroid nodule in Chinese children. METHODS: The cross-sectional study was conducted in Hangzhou, China, in 2010. Iodized salt intake, urine iodine concentration (UIC) and thyroid nodule (by ultrasonography) were measured in 3026 children. The associations of iodized salt with thyroid nodule were evaluated using multiple logistic regression models. RESULTS: The prevalence of thyroid nodule was 10.59% among Chinese children. Girls (11.89%) had higher prevalence of thyroid nodule than boys (9.26%). No significant association was observed between type of salt and thyroid nodule in pooled samples, boys and girls, respectively. Similar associations were observed between UIC and thyroid nodule. There was no significant association between milk consumption and thyroid nodule as well. CONCLUSION: The present study indicated that non-iodized salt may not increase the risk of thyroid nodules among Chinese children. Similar associations were observed between milk consumption, UIC and thyroid nodules.


Assuntos
Cloreto de Sódio/efeitos adversos , Nódulo da Glândula Tireoide/induzido quimicamente , Criança , China , Feminino , Humanos , Iodo/análise , Masculino , Pessoa de Meia-Idade
20.
Am J Clin Nutr ; 98(3): 684-92, 2013 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-23842457

RESUMO

BACKGROUND: The controversy that iodized salt may increase the risk of thyroid disorders has arisen in China during the past several years. OBJECTIVE: This study aimed to explore whether iodized salt increased the risk of thyroid nodule among a Chinese population. DESIGN: A cross-sectional study was conducted in Hangzhou, China, in 2010. Iodized salt intake, urinary iodine concentration (UIC), and thyroid nodule (by ultrasonography) were measured in 9412 adults. The associations of iodized salt with thyroid nodule were evaluated by using multiple mixed logistic regression models. RESULTS: The prevalence of thyroid nodule among men and women was 24.1% and 34.7%, respectively. Adults consuming noniodized salt had an increased risk of thyroid nodule (OR: 1.36; 95% CI: 1.01, 1.83). Similarly, compared with moderate salt appetite, mild salt appetite was associated with an increased risk of thyroid nodule among all adults (OR: 1.19; 95% CI: 1.03, 1.37) and among women (OR: 1.23; 95% CI: 1.03, 1.46). Furthermore, those who consumed neither iodized salt nor milk had a higher risk of thyroid nodule (OR: 1.72; 95% CI: 1.21, 2.43) than did those who consumed both iodized salt and milk. In addition, an increased risk of thyroid nodule (OR: 1.25; 95% CI: 1.07, 1.45) was observed among both pooled samples and women with low UIC. CONCLUSIONS: These findings indicate that low iodine intake may increase the risk of thyroid nodule in a Chinese population, particularly in women. Hence, the Universal Salt Iodization program may be indispensable for a coastal Chinese population such as that living in Hangzhou. This trial was registered at clinicaltrials.gov as NCT01838629.


Assuntos
Iodo/deficiência , Cloreto de Sódio na Dieta/administração & dosagem , Glândula Tireoide/patologia , Nódulo da Glândula Tireoide/etiologia , Adulto , Idoso , Animais , Apetite , Estudos Transversais , Feminino , Humanos , Iodo/administração & dosagem , Iodo/uso terapêutico , Masculino , Pessoa de Meia-Idade , Leite , Prevalência , Fatores de Risco , Fatores Sexuais , Cloreto de Sódio na Dieta/uso terapêutico , Nódulo da Glândula Tireoide/epidemiologia , Nódulo da Glândula Tireoide/prevenção & controle
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