Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 84
Filtrar
1.
Mol Biol Rep ; 50(10): 8111-8120, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37548867

RESUMO

BACKGROUND: Endothelial cells are crucial in maintaining the homeostasis of the blood-brain barrier. Girders of actin filament (Girdin) and phosphor (p)-Girdin are essential for the engulfment of human brain microvascular endothelial cells (HBMECs) into platelets (PLTs), but the potential mechanism remains unclear and requires further study. METHODS: Following PLT and cytochalasin D treatment, Hoechst 33,342 detected apoptosis. The transfection efficiency of the short hairpin RNA targeting Girdin (sh-Girdin) or overexpressing Girdin (OE-Girdin) was determined using western blotting. Sh-Girdin, OE-Girdin, mutated Girdin (m-Girdin), and microfilament binding region deleted Girdin (Del-Girdin) were transfected into HBMECs under PLT conditions. Subsequently, the engulfment of HBMECs by PLTs was detected by flow cytometry and transmission electron microscopy. Girdin and phosphorylated (p)-Girdin levels were quantified by western blot. The positive expression of Girdin was measured by immunohistochemistry (IHC). The localization of PLT, Girdin, and p-Girdin and the engulfment of HBMECs in PLTs were analyzed by confocal microscopy. RESULT: Cytochalasin D overturned the inhibitory effect of PLT on cell apoptosis. OE-Girdin enhanced the fluorescent intensity of PLT-labelling and the engulfment of HBMECs by PLTs, while sh-Girdin, m-Girdin, and Del-Girdin ran reversely. OE-Girdin elevated the Girdin and p-Girdin levels, while sh-Girdin and Del-Girdin were the opposite, but m-Girdin did not affect the p-Girdin and Girdin levels. CONCLUSION: Girdin and p-Girdin were co-located with PLTs in HBMECs. The over-expression of Girdin was identified as being associated with the increasing engulfment of PTLs. Girdin may be an effective target to alleviate endothelial cell apoptosis.


Assuntos
Plaquetas , Células Endoteliais , Humanos , Apoptose , Plaquetas/metabolismo , Citocalasina D/farmacologia , Citocalasina D/metabolismo , Células Endoteliais/metabolismo , Regulação para Cima
2.
BMC Nephrol ; 24(1): 238, 2023 08 15.
Artigo em Inglês | MEDLINE | ID: mdl-37582785

RESUMO

BACKGROUND: To study the influencing factors for coronary artery calcification (CAC) in maintenance hemodialysis (MHD) patients and the relationship between CAC and bone metabolism markers and to attempt to find a reliable marker linking vascular calcification and bone metabolism in MHD patients. METHODS: A total of 123 patients were enrolled. CAC was assessed by multislice spiral computed tomography (MSCT), and the CAC score (CACS) was evaluated using the Agaston method. Routine laboratory parameters, including triglycerides (TG), total cholesterol (TC), glucose (Glu), calcium (Ca), phosphorus (P), magnesium (Mg), etc., were measured. Serum markers of bone metabolism, such as alkaline phosphatase(ALP), calcitonin (CT), 25-hydroxy vitamin D [25-(OH)D], intact parathyroid hormone (iPTH), total type I procollagen amino-terminal peptide (tPINP), N-terminal mid-fragment of osteocalcin (N-MID OC), and ß-type I collagen crosslinked carboxyl-terminal peptide (ß-CTX), were also measured. RESULTS: Among 123 MHD patients, 37 patients (30.08%) did not have CAC, and 86 patients (69.92%) had CAC, including 41 patients (47.67%) with mild calcification and 45 patients (52.33%) with moderate to severe calcification. Age, Body Mass Index(BMI), the prevalence of hypertension and diabetes mellitus, TC, Glu, P, and Ca×P in the calcification group were higher than those in the noncalcification group, whereas Mg, iPTH, tPINP, N-MID OC, and ß-CTX were lower than those in the noncalcified group (P < 0.05). Compared with the mild calcification group (0 0.05). A logistic regression model was used to evaluate the influencing factors for CAC. The results showed that age, BMI, TC, Glu, P, and Ca×P were risk factors for CAC and its severity in MHD patients, whereas diabetes mellitus, Mg, and N-MID OC were protective factors for CAC in MHD patients. In addition, N-MID OC was a protective factor for the severity of CAC. After adjusting for the corresponding confounding factors, the results of the risk factors were consistent, and N-MID OC was still an independent protective factor for CAC and its severity. CONCLUSIONS: Elevated serum P and Ca×P were independent risk factors for CAC in MHD patients, and serum Mg may be an independent protective factor for CAC. CAC was closely related to abnormal bone metabolism and bone metabolic markers in MHD patients. Relatively low bone turnover can promote the occurrence and development of CAC. N-MID OC may be a reliable bone metabolic marker linking vascular calcification and bone metabolism in MHD patients.


Assuntos
Doença da Artéria Coronariana , Calcificação Vascular , Humanos , Diálise Renal/efeitos adversos , Doença da Artéria Coronariana/diagnóstico por imagem , Doença da Artéria Coronariana/epidemiologia , Hormônio Paratireóideo , Calcificação Vascular/diagnóstico por imagem , Calcificação Vascular/epidemiologia , Calcificação Vascular/etiologia , Peptídeos , Fosfatase Alcalina
3.
Zhongguo Zhong Yao Za Zhi ; 48(24): 6749-6764, 2023 Dec.
Artigo em Chinês | MEDLINE | ID: mdl-38212035

RESUMO

In this study, based on network pharmacology and molecular docking method, the mechanism of anti-hyperplasia of mammary glands of Xihuang Pills blood-entering components was explored, and the efficacy and key targets of Xihuang Pills blood-entering components were experimentally verified by MCF-10A proliferation model of human mammary epithelial cells. In order to clarify the material basis and mechanism of Xihuang Pills in realizing anti-hyperplasia of mammary glands, the blood-entering components of Xihuang Pills were qualitatively analyzed by UPLC-Q-TOF-MS, and 22 blood-entering components were identified. By taking the blood-entering components as the research object, the network pharmacology prediction and molecular docking verification were carried out, and finally, three key targets were screened out, namely JAK1, SRC, and CDK1. In vitro experiments show that Xihuang Pills can inhibit the proliferation of MCF-10A cells, promote the apoptosis of MCF-10A cells, and reduce the expression of JAK1, SRC, and CDK1 targets in cells. To sum up, Xihuang Pills can promote the apoptosis of mammary epithelial cells by regulating the expression of JAK1, SRC, and CDK1 and then play an anti-hyperplasia role, which provides an experimental basis for clarifying the material basis of Xihuang Pills for anti-hyperplasia effect.


Assuntos
Medicamentos de Ervas Chinesas , Farmacologia em Rede , Humanos , Cromatografia Líquida de Alta Pressão , Simulação de Acoplamento Molecular , Apoptose , Hiperplasia , Medicamentos de Ervas Chinesas/farmacologia
4.
J Neurosci ; 40(48): 9169-9185, 2020 11 25.
Artigo em Inglês | MEDLINE | ID: mdl-33097641

RESUMO

Myosin X (Myo X) transports cargos to the tips of filopodia for cell adhesion, migration, and neuronal axon guidance. Deleted in Colorectal Cancer (DCC) is one of the Myo X cargos that is essential for Netrin-1-regulated axon pathfinding. The function of Myo X in axon development in vivo and the underlying mechanisms remain elusive. Here, we provide evidence for the role of Myo X in Netrin-1-DCC-regulated axon development in developing mouse neocortex. The knockout (KO) or knockdown (KD) of Myo X in cortical neurons of embryonic mouse brain impairs axon initiation and contralateral branching/targeting. Similar axon deficits are detected in Netrin-1-KO or DCC-KD cortical neurons. Further proteomic analysis of Myo X binding proteins identifies KIF13B (a kinesin family motor protein). The Myo X interaction with KIF13B is induced by Netrin-1. Netrin-1 promotes anterograde transportation of Myo X into axons in a KIF13B-dependent manner. KIF13B-KD cortical neurons exhibit similar axon deficits. Together, these results reveal Myo X-KIF13B as a critical pathway for Netrin-1-promoted axon initiation and branching/targeting.SIGNIFICANCE STATEMENT Netrin-1 increases Myosin X (Myo X) interaction with KIF13B, and thus promotes axonal delivery of Myo X and axon initiation and contralateral branching in developing cerebral neurons, revealing unrecognized functions and mechanisms underlying Netrin-1 regulation of axon development.


Assuntos
Axônios/fisiologia , Cinesinas/fisiologia , Proteínas de Membrana/fisiologia , Miosinas/fisiologia , Netrina-1/fisiologia , Animais , Células Cultivadas , Córtex Cerebral/citologia , Córtex Cerebral/crescimento & desenvolvimento , Receptor DCC/genética , Receptor DCC/fisiologia , Feminino , Cinesinas/genética , Masculino , Proteínas de Membrana/genética , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Miosinas/genética , Neocórtex/citologia , Neocórtex/crescimento & desenvolvimento , Netrina-1/genética , Gravidez
5.
J Hum Genet ; 65(9): 797-803, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32313196

RESUMO

Aksay Kazakhs are the easternmost branch of Kazakhs, residing in Jiuquan city, the forefront of the ancient Silk Road. However, the genetic diversity of Aksay Kazakhs and its relationships with other Kazakhs still lack attention. To clarify this issue, we analyzed the non-recombining portion of the Y-chromosome from 93 Aksay Kazakhs samples, using a high-resolution analysis of 106 biallelic markers and 17 STRs. The lowest haplogroup diversity (0.38) was observed in Aksay Kazakhs among all studied Kazakh populations. The social and cultural traditions of the Kazakhs shaped their current pattern of genetic variation. Aksay Kazakhs tended to migrate with clans and had limited paternal admixture with neighboring populations. Aksay Kazakhs had the highest frequency (80%) of haplogroup C2b1a3a1-F3796 (previous C3*-Star Cluster) among the investigated Eurasian steppe populations, which was now seen as the genetic marker of Kerei clan. Furthermore, NETWORK analysis indicated that Aksay Kazakhs originated from sub-clan Kerei-Abakh in Kazakhstan with DYS448 = 23. TMRCA estimates of three recent descent clusters detected in C2*-M217 (xM48) network, one of which incorporate nearly all of the C2b1a3a1-F3796 Aksay Kazakhs samples, gave the age range of 976-1405 YA for DC1, 1059-1314 YA for DC2, and 1139-1317 YA for DC3, respectively; this is coherent with the 7th to the 11th centuries Altaic-speaking pastoral nomadic population expansion.


Assuntos
Povo Asiático/genética , Cromossomos Humanos Y/genética , Etnicidade/genética , China , Marcadores Genéticos , Variação Genética , Genética Populacional , Haplótipos , Humanos , Masculino , Filogenia , Polimorfismo de Nucleotídeo Único
6.
Eur Radiol ; 30(5): 2912-2921, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32002635

RESUMO

OBJECTIVE: To investigate externally validated magnetic resonance (MR)-based and computed tomography (CT)-based machine learning (ML) models for grading clear cell renal cell carcinoma (ccRCC). MATERIALS AND METHODS: Patients with pathologically proven ccRCC in 2009-2018 were retrospectively included for model development and internal validation; patients from another independent institution and The Cancer Imaging Archive dataset were included for external validation. Features were extracted from T1-weighted, T2-weighted, corticomedullary-phase (CMP), and nephrographic-phase (NP) MR as well as precontrast-phase (PCP), CMP, and NP CT. CatBoost was used for ML-model investigation. The reproducibility of texture features was assessed using intraclass correlation coefficient (ICC). Accuracy (ACC) was used for ML-model performance evaluation. RESULTS: Twenty external and 440 internal cases were included. Among 368 and 276 texture features from MR and CT, 322 and 250 features with good to excellent reproducibility (ICC ≥ 0.75) were included for ML-model development. The best MR- and CT-based ML models satisfactorily distinguished high- from low-grade ccRCCs in internal (MR-ACC = 73% and CT-ACC = 79%) and external (MR-ACC = 74% and CT-ACC = 69%) validation. Compared to single-sequence or single-phase images, the classifiers based on all-sequence MR (71% to 73% in internal and 64% to 74% in external validation) and all-phase CT (77% to 79% in internal and 61% to 69% in external validation) images had significant increases in ACC. CONCLUSIONS: MR- and CT-based ML models are valuable noninvasive techniques for discriminating high- from low-grade ccRCCs, and multiparameter MR- and multiphase CT-based classifiers are potentially superior to those based on single-sequence or single-phase imaging. KEY POINTS: • Both the MR- and CT-based machine learning models are reliable predictors for differentiating high- from low-grade ccRCCs. • ML models based on multiparameter MR sequences and multiphase CT images potentially outperform those based on single-sequence or single-phase images in ccRCC grading.


Assuntos
Carcinoma de Células Renais/diagnóstico por imagem , Carcinoma de Células Renais/patologia , Interpretação de Imagem Assistida por Computador/métodos , Neoplasias Renais/diagnóstico por imagem , Neoplasias Renais/patologia , Imageamento por Ressonância Magnética/métodos , Tomografia Computadorizada por Raios X/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Diagnóstico Diferencial , Feminino , Humanos , Rim/diagnóstico por imagem , Rim/patologia , Aprendizado de Máquina , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Reprodutibilidade dos Testes , Estudos Retrospectivos , Adulto Jovem
7.
Am J Physiol Cell Physiol ; 316(6): C830-C843, 2019 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-30576236

RESUMO

Long noncoding RNAs (lncRNAs) are commonly associated with various biological functions, in which the function of lncRNA maternally expressed gene 3 (MEG3) has been identified in various cancers. Strikingly, an association between MEG3 with microRNAs (miRNAs), mRNAs, and proteins has been reported. This study investigates the role of MEG3 in vascular endothelial cell (VEC) senescence. Expression of Girdin and miR-128 was monitored in the blood vessel samples of young and old mice/healthy volunteers, along with the measurement of human umbilical vein endothelial cells (HUVECs). The relationship between MEG3/Girdin and miR-128 was determined and verified. Loss- and gain-of-function approaches were applied to analyze the regulatory effects of MEG3 on platelet phagocytosis and lipoprotein oxidation of HUVEC membrane. In addition, the effect of MEG3 on HUVEC senescence was evaluated by detection of the reactive oxygen species, telomerase activity, and telomere length. To further analyze the MEG3-mediated regulatory mechanism, miR-128 upregulation and inhibition were introduced into the HUVECs. Downregulated Girdin and upregulated miR-128 were found in the blood vessels of old individuals and old mice, as well as in senescent HUVECs. MEG3 downregulation was found to be capable of inhibiting Girdin but enhancing miR-128 expression. It was also indicated to inhibit platelet phagocytosis and reduce telomerase activity and telomere length, while enhancing lipoprotein oxidation and reactive oxygen species production, which ultimately contributed in preventing and protecting HUEVCs from senescence. These findings provide evidence supporting that MEG3 leads to miR-128 downregulation and Girdin upregulation, which promotes platelet phagocytosis, thus protecting VECs from senescence.


Assuntos
Senescência Celular/fisiologia , Regulação para Baixo/fisiologia , Células Endoteliais da Veia Umbilical Humana/metabolismo , MicroRNAs/metabolismo , Proteínas dos Microfilamentos/metabolismo , RNA Longo não Codificante/biossíntese , RNA Longo não Codificante/metabolismo , Proteínas de Transporte Vesicular/metabolismo , Idoso , Idoso de 80 Anos ou mais , Animais , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Masculino , Camundongos , MicroRNAs/antagonistas & inibidores
8.
Int J Mol Sci ; 18(2)2017 Jan 25.
Artigo em Inglês | MEDLINE | ID: mdl-28125064

RESUMO

Arsenic trioxide (As2O3) has recently become one of the most effective drugs for treatment of patient with acute promyelocytic leukemia (APL), and its molecular mechanism has also been largely investigated. However, it has been reported that As2O3 resistant patients are frequently found in relapsed APL after consolidation therapy, which is due to the point mutations in B-box type 2 motifs of promyelocytic leukemia (PML) gene. In the present study, we for the first time establish whether organic arsenic species phenylarsine oxide (PAO) could induce the mutant PML-IV (A216V) protein solubility changes and degradation. Here, three different PML protein variants (i.e., PML-IV, PML-V and mutant PML-A216V) were overexpressed in HEK293T cells and then exposed to PAO in time- and dose-dependent manners. Interestingly, PAO is found to have potential effect on induction of mutant PML-IV (A216V) protein solubility changes and degradation, but no appreciable effects were found following exposure to high concentrations of iAsIII, dimethylarsinous acid (DMAIII) and adriamycin (doxorubicin), even though they cause cell death. Our current data strongly indicate that PAO has good effects on the mutant PML protein solubility changes, and it may be helpful for improving the therapeutic strategies for arsenic-resistant APL treatments in the near future.


Assuntos
Arsenicais/farmacologia , Arsenitos/farmacologia , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Resistencia a Medicamentos Antineoplásicos/genética , Mutação , Proteína da Leucemia Promielocítica/química , Proteína da Leucemia Promielocítica/genética , Expressão Gênica , Células HEK293 , Humanos , Processamento de Proteína Pós-Traducional , Proteólise , Solubilidade/efeitos dos fármacos
9.
J BUON ; 22(4): 1017-1021, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28952222

RESUMO

PURPOSE: This study sought to identify and evaluate the diagnostic value of T-cell immunoglobulin domain and mucin-3 (TIM-3) and forkhead box protein J1 (FOXJ1) expression in prostate cancer. METHODS: Thirty prostate cancer patients and 30 individuals with benign prostatic hyperplasia diagnosed and treated at the Central Hospital of Enshi Autonomous Prefecture between March 2016 and October 2016 were selected for this study. The expression of TIM-3 and FOXJ1 in patient prostate tissue was detected by immunohistochemistry and reverse transcription-polymerase chain reaction (RT-PCR). TIM-3 and FOXJ1 expression diagnostic value for prostate cancer was analyzed by using the receiver operating curve (ROC). RESULTS: Expression of TIM-3 and FOXJ1 in prostate cancer tissues was significantly higher than those in normal prostate tissues (p<0.05), and expression of TIM-3 and FOXJ1 in prostate cancer tissues were positively correlated with Gleason score and clinical stage (p<0.05). However, the expression of the two proteins were not correlated with age, PSA level, pathological type, or the maximum tumor diameter (p>0.05). ROC analysis indicated that TIM-3 mRNA could be used to diagnose prostate cancer with an accuracy of 0.824, a sensitivity of 85.9% and a specificity of 91.2%, while the diagnostic accuracy, sensitivity, and specificity of FOXJ1 were 0.843, 86.3%, and 82.7%, respectively. CONCLUSION: TIM-3 and FOXJ1 exhibited abnormally high expression levels in prostate cancer, and can therefore be important indicators for the diagnosis of this disease.


Assuntos
Fatores de Transcrição Forkhead/metabolismo , Receptor Celular 2 do Vírus da Hepatite A/metabolismo , Neoplasias da Próstata/metabolismo , Idoso , Humanos , Masculino , Pessoa de Meia-Idade , Gradação de Tumores/métodos , Hiperplasia Prostática/metabolismo , Hiperplasia Prostática/patologia , Neoplasias da Próstata/patologia , RNA Mensageiro/metabolismo , Sensibilidade e Especificidade
10.
Guang Pu Xue Yu Guang Pu Fen Xi ; 36(4): 1240-4, 2016 Apr.
Artigo em Chinês | MEDLINE | ID: mdl-30052355

RESUMO

This paper proposes the analyzing method of adopting wavelength dispersive X-ray fluorescence spectrometry to measure the content of Cu and Zn in PM2.5. PTFE membrane is used to prepare standard samples and atmospheric particulate samples; a research into sample cup's structure,using polypropylene film of 6.7 µm to help to improved sample cup to package atmospheric particulate samples. The improved sample cup is used to measure the content of Cu and Zn in atmospheric particulate, which can obviously reduce background, improve peak/background ratio and decrease detection limit to target element; discussion is made on the measurement condition of Cu and Zn in PM2.5: taking Kα line as analysis line of Cu and Zn, selecting PX10 as analyzer crystal, using 300 µm pitch collimator, adopting scintillation detector for the Kα of Zn, applying the integrating of flow-gas proportional counter and closed-end proportional counter to the Kα of Cu, setting 50 kV, 50 mA as operating voltage and current. The prepared Cu and Zn standard sample is used to set up working curve, the results show that their linear correlations are better, accuracy are higher, relative standard deviations of Cu and Zn are 2.43% and 2.00%(n=8), detection limit are 0.028 and 0.021 µg·cm-2respectively, and analysis of the single sample only need 60 s. To sum up, this method can quickly and accurately analyze the content of Cu and Zn in PM2.5, and provide scientific basis for study the element content characteristics and source apportionment.

11.
Chem Res Toxicol ; 28(3): 351-3, 2015 Mar 16.
Artigo em Inglês | MEDLINE | ID: mdl-25166275

RESUMO

Arsenic is a known carcinogen; however, there is no information on the toxic effects of inorganic arsenic and its intermediate metabolites, monomethylarsonous acid (MMA(III)) and dimethylarsinous acid (DMA(III)), during the differentiation of embryonic stem (ES) cells into cardiomyocytes. The objective of this study was to evaluate the effects of arsenic compounds on ES cell differentiation into cardiomyocytes in vitro and to predict the associated toxic effects. Although iAs(III) is known to be toxic, here we found that iAs(III) and DMA(III) did not influence ES cellular differentiation, whereas MMA(III) inhibited ES cell differentiation into cardiomyocytes, suggesting that MMA(III) has adverse effects on embryonic stem cells.


Assuntos
Arsênio/toxicidade , Ácido Cacodílico/análogos & derivados , Células-Tronco Embrionárias Murinas/efeitos dos fármacos , Miócitos Cardíacos/citologia , Compostos Organometálicos/toxicidade , Animais , Ácido Cacodílico/toxicidade , Diferenciação Celular/efeitos dos fármacos , Linhagem Celular , Camundongos , Células-Tronco Embrionárias Murinas/citologia
12.
BMC Public Health ; 15: 1216, 2015 Dec 08.
Artigo em Inglês | MEDLINE | ID: mdl-26646580

RESUMO

BACKGROUND: The WHO Framework Convention on Tobacco Control was shown to effectively lower smoking prevalence in in high income countries, however knowledge for low and middle income settings is sparse. The objective of this study was to describe WHO MPOWER policy measures in thirteen West-African countries and to investigate their correlation with smoking prevalence. METHODS: Age-standardized smoking prevalence data and policy measures were collected from various WHO reports. For analysis MPOWER measures from 2008 and 2010, were combined with prevalence data from 2009 and 2011. Multiple linear regression models were set up. RESULTS: In West-Africa mean smoking prevalence was approximately 20% among males and approximately 3% among females. Policy measures were mostly at a middle or low level. Regression analysis showed that tobacco cessation programs, health warnings on cigarettes, and higher price of cigarettes were negatively correlated with smoking prevalence. Significant effects were observed for only one policy measure (tobacco cessation programs) and only within the male population where smoking prevalence is generally higher. CONCLUSIONS: Tobacco control policies are enforced at relatively low levels in West-African countries. However, improving tobacco control policy implementation according to the WHO Framework Convention on Tobacco Control should assist in the reduction of smoking prevalence in African countries, thereby counteracting pro-smoking initiatives set forth by the tobacco industry.


Assuntos
Países em Desenvolvimento , Política Pública , Abandono do Hábito de Fumar , Prevenção do Hábito de Fumar , África Ocidental/epidemiologia , Feminino , Humanos , Masculino , Modelos Teóricos , Prevalência , Fatores Sexuais , Fumar/epidemiologia , Nicotiana , Indústria do Tabaco , Produtos do Tabaco
13.
BMC Cell Biol ; 15: 7, 2014 Feb 24.
Artigo em Inglês | MEDLINE | ID: mdl-24564184

RESUMO

BACKGROUND: Recently, evidence indicated that the rapamycin-eluting stent which was used worldwide may contribute to an increased risk for thrombosis. On the contrary, other researchers found it was safe. Thus, it is necessary to clarify the effect of rapamycin on thrombosis and the corresponding mechanisms. RESULTS: The effects of rapamycin in vivo were evaluated by modified deep vein thrombosis animal model. The platelets were from healthy volunteers and the platelet-endothelium (purchased from ATCC) adhesion in cultured endothelial cells was assessed. Membrane rufflings in endothelial cells were examined by confocal and electron microscope. Thrombus formation increased in rats that were injected with rapamycin. Electron microscope analysis exhibited microvilli on the rapamycin-treated endothelium in rats. Rapamycin enhanced membrane ruffling in human umbilical vein endothelial cells (HUVECs) and adhesion of platelets to HUVECs. The platelet-HUVECs adhesion was attenuated when cells were treated with cytochalacin B. Inhibition of autophagy by 3-methyladenine led to suppression of membrane ruffles in HUVECs and augmentation of platelet-endothelial adhesion. CONCLUSIONS: In conclusion, we found that endothelial membrane remodeling induced by rapamycin is crucial for the adhesion of platelets to endothelial cells and thereby for thrombosis in vivo, and that the endothelial membrane remodeling is autophagy dependent.


Assuntos
Plaquetas/efeitos dos fármacos , Sirolimo/farmacologia , Adenina/análogos & derivados , Adenina/farmacologia , Animais , Autofagia/efeitos dos fármacos , Plaquetas/citologia , Adesão Celular/efeitos dos fármacos , Membrana Celular/efeitos dos fármacos , Membrana Celular/fisiologia , Citocalasina B/farmacologia , Modelos Animais de Doenças , Células Endoteliais da Veia Umbilical Humana , Humanos , Masculino , Ratos , Ratos Sprague-Dawley , Sirolimo/uso terapêutico , Trombose/tratamento farmacológico , Trombose/metabolismo , Trombose/patologia
14.
Quant Imaging Med Surg ; 14(1): 986-994, 2024 Jan 03.
Artigo em Inglês | MEDLINE | ID: mdl-38223038

RESUMO

Background: The early diagnosis of thrombosis and fat embolism is important for subsequent treatment regimens. Spectral computed tomography (CT) virtual non-contrast (VNC) scanning can not only accurately diagnose thrombosis and medium fat embolism but can also reduce the radiation dose and scanning time. However, there is a relative paucity of studies on what contrast concentration and exposure conditions are best for the quality of VNC images. To address this issue, this study aimed to investigate the effects of different exposure conditions and contrast concentrations on the quality of VNC images of low-density substances in spectral CT. Methods: Four solution groups [i.e., groups A (15 mgI/mL), B (10 mgI/mL), C (5 mgI/mL), and D (the control group)] were matched with normal saline and contrast agent groups. Four groups of solution, duck blood clots, and fat were injected into four sections of the pig large intestine, respectively. CT scans with different exposure amounts were performed under the condition of 120 KV. Comparing the true non-contrast (TNC) image based on solution D group with the VNC images of the other three solution groups. The differences in the CT values, standard deviation (SD) values, and contrast noise ratio (CNR) values of the duck blood and fat under different iodine concentrations and exposures were compared. The image quality was evaluated using a three-point method and the Kappa consistency test was performed. The consistency of the tissue CT values in the TNC and VNC images was analyzed by drawing Bland-Altman scatter plots. Results: The CT values of the duck blood in the VNC20mAs and VNCC groups were lower than those in the TNC groups (P<0.05). Under different exposures and contrast agent concentrations, the CT value of the fat in the VNC group was higher than that in the TNC group (P<0.05). The SD values of the duck blood and fat in three groups (i.e., groups A, B, and C) were lower than those in the TNC group (P<0.05). The CNR value of the duck blood in the VNC20mAs group was lower than that in the TNC group (Z=-2.10, P=0.04), and the CNR values of the duck blood and fat in the VNC group were higher than those in the TNC groups in the remaining different exposure and concentration groups (P<0.05). The CT values of the lesions in the two groups were consistent, and there were no statistically significant differences between the subjective scores of the TNC and VNC images (z=-1.34, P=0.18); the subjective evaluations of the two physicians had good consistency (K=0.80). Conclusions: Under the conditions of higher contrast agent concentrations and proper exposure conditions, the VNC images were better able to restore the CT values of the blood clots, reduce the SD values of the blood clots and fat. In addition, and improve the CNR values of the blood clots and fat. In addition, the quality of the two images was similar.

15.
Zhonghua Nan Ke Xue ; 19(6): 501-5, 2013 Jun.
Artigo em Chinês | MEDLINE | ID: mdl-23862226

RESUMO

OBJECTIVE: To study the inhibitory effect of Akt inhibitor deguelin on PC-3 human prostate cancer cell lines and its possible mechanism. METHODS: PC-3 human prostate cancer cells were cultured in deguelin at the concentrations of 10, 100, 500 and 1 000 nmol/L for 24, 48 and 72 hours, respectively. Then the inhibitory effect of deguelin on the proliferation of the PC-3 cells was determined by MTT assay and that on the cell cycle was detected by flow cytometry. The expression levels of MDM2 and GSK3beta mRNA were measured by RT-PCR and those of MDM2 and GSK3beta proteins by Western blot. RESULTS: At 24, 48 and 72 hours, the inhibition rates of deguelin on the proliferation of the PC-3 prostate cancer cells were (91.10 +/- 3.75), (86.39 +/- 1.16) and (79.51 +/- 2.63)% at 10 nmol/L, (82.46 +/- 3.65), (76.84 +/- 0.97) and (69.69 +/- 2.30) % at 100 nmol/L, (81.46 +/- 0.41), (75.56 +/- 1.12) and (54.07 +/- 3.21)% at 500 nmol/L, and (66.77 +/- 2.82), (58.22 +/- 0.35) and (39.34 +/- 2.40)% at 1000 nmol/L, all with statistically significant differences from the control group (P < 0.01). Deguelin at 10, 100, 500 and 1 000 nmol/L increased the cell cycles blocked in the G0/G1 phase ([62.4 +/- 2.2], [63.6 +/- 1.1 ], [65.0 +/- 0.3] and [66.5 +/- 1.9]%, P < 0.01) and reduced the percentage of the S-phase cells ([14.7 +/- 2.4], [11.1 +/- 5.2], [5.8 +/- 1.1] and [7.0 +/- 0.6]%, P < 0.01). RT-PCR and Western blot showed markedly up-regulated expressions of GSK3 P3 a3beta down-regulated expressions of MDM2 mRNA and proteins in the PC-3 cells treated with deguelin. CONCLUSION: Akt inhibitor deguelin can inhibit the proliferation of PC-3 human prostate cancer cells by affecting the down-stream signal molecules GSK3P3 and betaDM2 in the Akt pathway.


Assuntos
Quinase 3 da Glicogênio Sintase/metabolismo , Neoplasias da Próstata/metabolismo , Proteínas Proto-Oncogênicas c-akt/antagonistas & inibidores , Rotenona/análogos & derivados , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Glicogênio Sintase Quinase 3 beta , Humanos , Masculino , Proteínas Proto-Oncogênicas c-mdm2/metabolismo , Rotenona/farmacologia
16.
Nutrients ; 15(2)2023 Jan 07.
Artigo em Inglês | MEDLINE | ID: mdl-36678179

RESUMO

Arterial stiffness, an age-dependent phenomenon, is improved with exercise, which in turn may prevent cardiovascular diseases in women. However, there is a lack of consolidated information on the impact of exercise on arterial stiffness among healthy women. The aim of this review was to (i) analyse the effect of exercise on arterial stiffness in healthy young, middle-aged, and older women, and (ii) recommend types, intensity, and frequency for each age group. Database searches on PubMed, ScienceDirect, Web of Science, and Scopus were conducted using PRISMA guidelines until September 2022. The keywords were: exercise, women/female, and arterial stiffness. The inclusion criteria were: healthy women, supervised exercise, and arterial stiffness measures. Study quality and bias were assessed using the PEDro scale. Fifty-one papers were classified into young (n = 15), middle-aged (n = 14), and older (n = 22) women. Improvements in arterial stiffness were observed among: young women (Pulse Wave Velocity, PWV: 4.9-6.6 m/s), following an 8-week high-intensity aerobic (3 days/week) or hypoxic high-intensity interval training; middle-aged women (PWV: 5.1-7.9 m/s), aerobic exercise with moderate intensity or stretching exercise at "moderate to heavy" (Borg Scale), 20-30 s per site, 10 s of rest interval for 30 min; and for older women (PWV: 7.9-15.6 m/s), resistance training at light intensity, aerobic exercise at any intensity, or a combination of the two exercises. This review shows that arterial stiffness increases with age in healthy women and has an inverse relationship with exercise intensity. Therefore, when prescribing exercise to improve arterial stiffness, age and arterial stiffness measures should be accounted for.


Assuntos
Treinamento Resistido , Rigidez Vascular , Pessoa de Meia-Idade , Humanos , Feminino , Idoso , Análise de Onda de Pulso , Exercício Físico , Terapia por Exercício
17.
Artigo em Inglês | MEDLINE | ID: mdl-36777631

RESUMO

The electronic medical records (EMRs) of traditional Chinese medicine (TCM) include a wealth of TCM knowledge and syndrome diagnosis information, which is crucial for improving the quality of TCM auxiliary decision-making. In practical diagnosis, one disease corresponds to one syndrome, posing considerable hurdles for the informatization of TCM. The purpose of this work was to create an end-to-end TCM diagnostic model, and the knowledge graph (KG) created in this article is used to improve the model's information and realize auxiliary decision-making for TCM disorders. We approached auxiliary decision-making for syndrome differentiation in this article as a multilabel classification task and presented a knowledge-based decision support model for syndrome differentiation (KDSD). Specifically, we created a KG based on TCM features (TCMKG), supplementing the textual representation of medical data with embedded information. Finally, we proposed fusing medical text with KG entity representation (F-MT-KER) to get prediction results using a linear output layer. After obtaining the vector representation of the medical record text using the BERT model, the vector representation of various KG embedded models can provide additional hidden information to a certain extent. Experimental results show that our method improves by 1% (P@1) on the syndrome differentiation auxiliary decision task compared to the baseline model BERT. The usage of EMRs can aid TCM development more efficiently. With the help of entity level representation, character level representation, and model fusion, the multilabel classification method based on the pretraining model and KG can better simulate the TCM syndrome differentiation of the complex cases.

18.
Heliyon ; 9(6): e17613, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-37408924

RESUMO

Objective: Hyperlipidemia is a risk factor for cardiac damage that can lead to many cardiovascular diseases. A recent study reported the cardioprotective effects of luteolin in vitro and in vivo. In this study, we aimed to investigate the possible protective effects of luteolin against hyperlipidemia-induced cardiac damage in Sprague-Dawley (SD) rats. Methods: Six-week-old male SD rats were randomly divided into five groups: a normal diet (ND) group; a high-fat diet (HFD) group; and three high-fat diet mixed with luteolin (HFD + LUT) groups, where in a luteolin dosage 50, 100, or 200 mg/kg/day was administered. All groups were fed their respective diets for 12 weeks. Results: Left ventricular ejection fraction and fractional shortening (parameters of cardiac function) were lower in the HFD + LUT (100 mg/kg/day) group than in the HFD group. Metabolic parameters were lower in the HFD + LUT (100 mg/kg/day) group than in the HFD group. Collagen I, collagen III, and TGF-ß expression levels were lower in the cardiac tissues of the HFD + LUT (100 mg/kg/day) group, compared to those of the HFD group. Expression of the profibrotic genes MMP2 and MMP9 was suppressed in the cardiac tissues of the HFD + LUT (100 mg/kg/day) group, compared to those of the HFD group. Furthermore, CD36 and lectin-like oxidized low-density lipoprotein receptor-1 protein levels were lower in the cardiac tissues of the HFD + LUT (100 mg/kg/day) group, compared to those of the HFD group. Conclusion: These findings would provide new insights into the role of luteolin in hyperlipidemia-induced cardiac damage and contribute to the development of novel therapeutic interventions to treat cardiovascular disease progression.

19.
Front Cardiovasc Med ; 10: 1189750, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37502183

RESUMO

Objective: This study aimed to conduct a meta-analysis evaluating the optimal timing for endovascular repair of acute versus subacute uncomplicated Type B Aortic Dissection. Method: PubMed, EMBASE, web of science and Cochrane Library was interrogated to identify Electronic bibliographic studies updated to January 2023 to collect studies compared the clinical outcomes of endovascular repair for Acute Versus Subacute Uncomplicated Type B Aortic Dissection. Data were aggregated as pooled odds ratios (OR) using the fixed or random effects models according to the significance of heterogeneity, Pooled odds ratios (OR) were calculated by RevMan 5.3 and applied with fixed or random-effect models. Result: A comprehensive literature search found 322 citations published and finally among them 6 studies containing 3,769 patients (acute group 2,642, subacute group 1,127) were included in review. There is an increased risk of 30-day complications (OR = 1.51,95%CI,1.26-1.81) 30-day mortality (OR = 2.39,95%CI, 1.55-3.67) and 1-year mortality (OR = 1.71,95%CI,1.27-2.30) for an acute uTBAD group compared to subacute ones. Similarly, reintervention was more likely in the acute group than in the subacute group (OR = 1.42,95%CI,1.05-1.91). However, no significant differences were found in long-term mortality. Conclusion: This meta-analysis confirmed that there was no significant difference in the long-term prognosis between the acute and subacute phases in the timing of surgery. However, considering the high incidence of complications, high re-intervention rate and one-year mortality probably caused by high intima fragility in the acute phase, endovascular repair at subacute phase appears to favorably compare with acute strategy. But future studies with adequate patient numbers and longer-term follow-up are necessary to further verify the study conclusion. Systematic Review Registration: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42021247609, identifier PROSPERO CRD42021247609.

20.
Sci Rep ; 13(1): 13453, 2023 08 18.
Artigo em Inglês | MEDLINE | ID: mdl-37596395

RESUMO

To analyze the relationship between the composition of urinary stones and various influencing factors in the Enshi region. We used FT-IR to examine the composition of 1092 stone samples. Combined with the relevant clinical materials, the data were analyzed using both one-dimensional statistical methods and multivariate statistical methods. The study included 1092 stone samples, classified as follows: 457 (41.8%) with a single component, 453 (41.5%) with two components, 149 (13.6%) with three components, and 33 (3.0%) with four components. Stones were categorized into five types: Calcium Oxalate (CaOx) (76.4%), carbapatite (CaP) (9.3%), Struvite (ST) (8.3%), Uric Acid (UA) (4.9%), and Others (1.0%). Age, gender, urinary tract infection (UTI), family history of urinary stones (FH), hyperuricemia (HUA) and stone location were significantly associated with stone type. Logistic regression revealed that females and UTI were relative risk factors for predicting CaP and ST, while FH and HUA were relative risk factors for predicting UA. Our study indicates that the overall composition of urinary tract stones in the Enshi region is consistent with that of the entire China. Additionally, the predisposing factors for stone formation vary in terms of gender, age, FH, UTI, hyperuricemia HUA, and stone location.


Assuntos
Hiperuricemia , Cálculos Urinários , Urolitíase , Feminino , Humanos , Espectroscopia de Infravermelho com Transformada de Fourier , População do Leste Asiático , Minorias Étnicas e Raciais , Etnicidade , Estudos Retrospectivos , Grupos Minoritários
SELEÇÃO DE REFERÊNCIAS
Detalhe da pesquisa