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1.
Zhonghua Gan Zang Bing Za Zhi ; 30(7): 770-776, 2022 Jul 20.
Artigo em Chinês | MEDLINE | ID: mdl-36038349

RESUMO

Objective: To investigate the molecular mechanism of sorafenib against hepatocellular carcinoma. Methods: Sorafenib efficacy was screened and verified by the hepatocellular carcinoma patient-derived tumor xenograft (PDX) model. Veterinary B-mode ultrasonography and in vivo confocal laser scanning microscopy were used to observe PDX angiogenesis. Immunohistochemistry was used to observe the expression of proliferation and angiogenesis-related proteins in PDX tissue. Real-time quantitative PCR technology was used to observe the RUNX3 gene in PDX tissues. SPSS 17.0 statistical software was used for statistical analysis. Results: Four cases of PDX were used to screen the efficacy of sorafenib. PDX1 had a significant response to sorafenib, with an inhibition rate of 68.07%. Compared with the control group, sorafenib had significantly inhibited PDX1 relative tumor volume (5.76±2.14 vs. 11.71±2.87, P<0.05). Cell division index (39.50±7.72 vs. 67.10±9.14, P<0.05) and Ki67 expression (288.6±43.40 vs. 531.70±55.60, P<0.05) were significantly decreased. Veterinary B-mode ultrasonography showed evident blood flow signals in PDX1 tumors. In vivo confocal laser scanning microscopy results showed that sorafenib had significantly reduced the total vessel length (1573.00±236.21 vs. 2675.03±162.00, P<0.05) and area (11 145.33±1931.97 vs. 20 105.37±885.93, P<0.05)) of PDX1 tumors. Immunohistochemical results showed that sorafenib had significantly down-regulated the protein expressions of CD34 (27.55±3.76 vs. 45.47±5.57, P<0.05), VEGF (16.33±2.86 vs. 22.77±3.20, P<0.05) and MVD (38.75±6.01 vs. 55.50±8.61, P<0.05). Real-time PCR results showed that sorafenib had significantly up-regulated RUNX3 gene expression (2.14±0.71 vs. 1.00±0.36, P<0.05). However, there was a negative correlation between the expression of RUNX3 gene and the ratio of VEGF-positive cells in sorafenib group (R2=0.509 7). Conclusion: Sorafenib may inhibit the PDX angiogenesis and the growth of hepatocellular carcinoma by regulating the RUNX3-VEGF pathway.


Assuntos
Antineoplásicos , Carcinoma Hepatocelular , Subunidade alfa 3 de Fator de Ligação ao Core/metabolismo , Neoplasias Hepáticas , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Carcinoma Hepatocelular/patologia , Linhagem Celular Tumoral , Humanos , Neoplasias Hepáticas/patologia , Neovascularização Patológica/metabolismo , Neovascularização Patológica/patologia , Niacinamida/uso terapêutico , Compostos de Fenilureia/uso terapêutico , Sorafenibe/farmacologia , Sorafenibe/uso terapêutico , Fator A de Crescimento do Endotélio Vascular
2.
Zhonghua Liu Xing Bing Xue Za Zhi ; 40(5): 596-600, 2019 May 10.
Artigo em Chinês | MEDLINE | ID: mdl-31177745

RESUMO

Objective: To investigate the association between the preterm birth and low birth weight and parental thalassemia. Methods: Pregnant women and their husbands receiving prenatal examination in local hospitals or maternal and child health centers in Jingxi and Debao in Guangxi from January to December 2017 were selected as study subjects. A total of 758 pregnant women with pregnancy outcomes and their husbands, who were both or alone diagnosed with thalassemia through thalassemia gene detection, were selected as case group and 758 pregnant women with pregnancy outcomes and their husbands, who were negative in thalassemia gene detection and hemoglobin electrophoresis test were selected as control groups. The case group were further divided into mother group, father group and both mother and farther group. Clinical and pregnancy outcome data of the study subjects were collected for the analysis on the association between parental thalassaemia and preterm birth or low birth weight by the independent sample t test, χ(2) test and Cox regression analysis. Results: The incidence of preterm birth in case group and control group was about 6.5% and 1.6% and the incidence of low birth weight in case group and control group was about 7.3% and 0.8%. After adjusting for possible confounding factors, Cox regression analysis results showed that mother suffering from thalassemia (aRR=3.45, 95%CI: 1.35-8.81, P=0.010), fathers suffering from thalassemia (aRR=4.93, 95%CI: 2.16-11.21, P<0.001) and both mother and farther suffering from thalassemia (aRR=5.13, 95%CI: 2.62-10.04, P<0.001) were associated with preterm birth. Mother suffering from thalassemia (aRR=12.98, 95%CI: 4.91-34.30, P<0.001), fathers suffering from thalassemia (aRR=9.40, 95%CI: 3.40-25.95, P<0.001) and both mother and farther suffering from thalassemia (aRR=10.74, 95%CI: 4.44-26.00, P<0.001) were associated with low birth weight. The newborn whose parent all suffered from thalassemia had higher risks for preterm birth (χ(2)=22.72, P<0.001)and low birth weight (χ(2)=34.03, P<0.001) compared with those only with mother or father suffering from thalassemia. Conclusion: Parental thalassaemia, including both sides and single side, might increase the risks of preterm birth and low birth weight for newborn, and the risks might be higher in newborn with both mother and father suffering from thalassaemia.


Assuntos
Recém-Nascido de Baixo Peso , Nascimento Prematuro/epidemiologia , Talassemia/epidemiologia , Peso ao Nascer , Criança , China/epidemiologia , Feminino , Humanos , Incidência , Recém-Nascido , Masculino , Pais , Gravidez , Resultado da Gravidez , Talassemia/diagnóstico
3.
J Dent Res ; 95(6): 642-9, 2016 06.
Artigo em Inglês | MEDLINE | ID: mdl-26976131

RESUMO

We previously reported that dental stem cell-mediated bioengineered tooth root (bio-root) regeneration could restore tooth loss in a miniature pig model. As a potential new method for tooth restoration, it is essential to compare this method with the widely used commercial dental implant-based method of tooth restoration. Tooth loss models were created by extracting mandibular incisors from miniature pigs. Allogeneic periodontal ligament stem cells (PDLSCs) and dental pulp stem cells (DPSCs) were isolated and cultured. A PDLSC sheet was prepared by adding 20.0 µg/mL vitamin C to the culture medium; in addition, a hydroxyapatite tricalcium phosphate (HA/TCP)/DPSC graft was fabricated and cultured in a 3-dimensional culture system. A total of 46 bio-root implantations and 9 dental implants were inserted, and crown restorations were performed 6 mo after implantation. Histological, radiological, biomechanical, and elemental analyses were used to evaluate and compare tissue-engineered bio-roots and dental implants to the natural tooth roots. After 6 mo, both computed tomography scans and histological examinations showed that root-like structures and dentin-like tissues had formed. Three months after crown restoration, clinical assessments revealed that tooth function was equivalent in the regenerated bio-root and the dental implant. Biomechanical testing showed that the bio-roots were similar to natural tooth roots in compressive strength, modulus of elasticity, and torsional force; however, these properties were significantly higher in the dental implants. Elemental analysis revealed a higher similarity in elemental composition between bio-roots and natural tooth roots than between bio-roots and dental implants. However, the dental implant success rate was 100% (9 of 9) and the bio-root success rate was only 22% (10 of 46). Taken together, we showed that an allogeneic HA/TCP/DPSC/PDLSC sheet could successfully build a bio-root with structure and function similar to the natural tooth root; however, tissue engineering procedures must be optimized further to improve the success rate.


Assuntos
Implantes Dentários , Transplante de Células-Tronco Mesenquimais , Células-Tronco Mesenquimais/citologia , Engenharia Tecidual/métodos , Raiz Dentária/fisiologia , Animais , Ácido Ascórbico/farmacologia , Fenômenos Biomecânicos , Células Cultivadas , Coroas , Polpa Dentária/citologia , Módulo de Elasticidade , Hidroxiapatitas/farmacologia , Teste de Materiais , Células-Tronco Mesenquimais/fisiologia , Ligamento Periodontal/citologia , Regeneração/fisiologia , Suínos , Porco Miniatura , Alicerces Teciduais , Tomografia Computadorizada por Raios X , Transplante Homólogo
4.
Cells Tissues Organs ; 199(5-6): 353-63, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-25823370

RESUMO

It remains unclear how the expression of microRNAs (miRNAs) in human periodontal ligament stem cells (PDLSCs) might respond to mechanical stretch. To investigate specific miRNA expression in stretched PDLSCs, we used a Flexcell® FX-5000™ tension system to achieve external mechanical stimulation. Then, a custom-designed microarray assay was performed to investigate and describe the genome-wide differential expression of miRNAs in normal and stretched PDLSCs. Finally, we implemented integrative miRNA target prediction and network analysis approaches to construct an interaction network of the key miRNAs and their putative targets. We found that stretching induced morphological changes and increased alkaline phosphatase (ALP) activity, runt-related transcription factor 2 (RUNX2), osteocalcin (OCN), and bone sialoprotein (BSP) expression in PDLSCs. The microarray data showed that 53 miRNAs were differentially expressed with stretching. With an interaction network, we examined the connections between 10 selected key miRNAs and their putative target genes, which were related to mechanical force. The results from the interaction network provided a basis for postulating the functional roles of miRNAs in PDLSCs.


Assuntos
MicroRNAs/metabolismo , Ligamento Periodontal/metabolismo , Células-Tronco/metabolismo , Diferenciação Celular , Células Cultivadas , Humanos , Análise em Microsséries , Estresse Mecânico
5.
Orthod Craniofac Res ; 16(3): 185-92, 2013 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-23458154

RESUMO

OBJECTIVES: To investigate rapid palatal expansion (RPE)-induced metabolic changes in human dental pulp by measuring the expression and activity of aspartate aminotransferase (AST). METHODS: mRNA and protein levels of AST in human dental pulp were measured by quantitative real-time polymerase chain reaction and Western blot, respectively. Furthermore, the activity of AST was measured by a full automatic biochemical analyzer. RESULTS: AST mRNA and protein levels were found to be expressed in normal dental pulp. Moreover, the expression of AST was increased significantly after 14 days of RPE and then decreased at 1 month in retention. Three and 6 months after RPE, the AST expression level was gradually decreased to its baseline level. Similarly, AST activity was significantly elevated after 14 days of RPE, which was then down-regulated at 1 month in retention but was still kept at a higher level as compared with the control group. The enzymatic activity of AST was slowly decreased to its baseline level at 3 and 6 months in retention. CONCLUSIONS: These results showed that significant reversible metabolic changes occurred in dental pulp during RPE, which revealed the high capacity of the pulp tissue for adaptation to this orthopedic method.


Assuntos
Aspartato Aminotransferases/análise , Polpa Dentária/enzimologia , Técnica de Expansão Palatina , Adaptação Fisiológica/fisiologia , Adolescente , Aspartato Aminotransferases/genética , Dente Pré-Molar/enzimologia , Western Blotting , Criança , Feminino , Seguimentos , Humanos , Masculino , Desenho de Aparelho Ortodôntico , Contenções Ortodônticas , Técnica de Expansão Palatina/instrumentação , RNA Mensageiro/análise , Reação em Cadeia da Polimerase em Tempo Real , Fatores de Tempo , Regulação para Cima
6.
Am J Physiol Heart Circ Physiol ; 297(1): H304-12, 2009 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-19411288

RESUMO

Exposure to prolonged hypoxia can result in pulmonary vascular remodeling and pulmonary hypertension. Hypoxia induces pulmonary vascular smooth muscle cell (PVSMC) proliferation and vascular remodeling by affecting cell adhesion and migration and secretion of extracellular matrix proteins. We previously showed that acute hypoxia decreases cGMP-dependent protein kinase (PKG) activity in PVSMC and that PKG plays a role in maintaining the differentiated contractile phenotype in normoxia. In this study, we investigated the effect of hypoxia on PVSMC adhesion and migration and the role of PKG in these functions. Ovine fetal pulmonary artery SMC were incubated in normoxia (Po(2) approximately 100 Torr) or hypoxia (Po(2) approximately 30-40 Torr) or treated with the PKG inhibitor DT-3 for 24 h in normoxia. To further study the role of PKG in the modulation of adhesion and migration, PVSMC were transiently transfected with a full-length PKG1alpha [PKG-green fluorescent protein (GFP)] or a dominant-negative construct (G1alphaR-GFP). Cell adhesion to extracellular matrix proteins was determined, and integrin-mediated adhesion was assessed by alpha/beta-integrin-mediated cell adhesion array. Exposure to hypoxia (24 h) and pharmacological inhibition of PKG1 by DT-3 significantly promoted adhesion mediated by alpha(4)-, beta(1)-, and alpha(5)beta(1)-integrins to fibronectin, laminin, and tenacin and also resulted in increased cell migration. Likewise, inhibition of PKG by expression of a dominant-negative PKG1alpha construct increased cell adhesion and migration, comparable to that induced by hypoxia. Dynamic actin reorganization associated with integrin-mediated cell adhesion is partly regulated by the actin-binding protein cofilin, the (Ser3) phosphorylation of which inhibits its actin-severing activity. We found that increased PKG expression and activity is associated with decreased cofilin (Ser3) phosphorylation, implying a role for PKG in the modulation of cofilin activity and actin dynamics. Together, these findings identify cGMP/PKG1 signaling as central to the functional differences between PVSMC exposed to normoxia versus hypoxia.


Assuntos
Adesão Celular/fisiologia , Hipóxia Celular/fisiologia , Movimento Celular/fisiologia , Proteínas Quinases Dependentes de AMP Cíclico/fisiologia , Músculo Liso Vascular/patologia , Fatores de Despolimerização de Actina/metabolismo , Animais , Western Blotting , Células Cultivadas , Proteínas Quinases Dependentes de AMP Cíclico/antagonistas & inibidores , Proteínas Quinases Dependentes de AMP Cíclico/genética , Inibidores Enzimáticos/farmacologia , Proteínas da Matriz Extracelular/metabolismo , Integrinas/fisiologia , Ovinos , Transfecção
7.
Drug Discov Ther ; 1(2): 86-8, 2007 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-22504392

RESUMO

To study the prevalence of drug resistance mutations among HAART (highly active anti-retroviral therapy) naive subjects with HIV-1 subtype B infection, evaluate the correlation between major mutations and viral loads. Additionally, to investigate the primary resistance spectrum in the central plains of China and provide some guidance for the choice of antiretroviral drugs (ARV). Drug resistance mutations and viral loads were measured in 78 treatment-naïve patients with HIV infection and the results were analyzed with descriptive statistical and multiple statistical analysis. The most common mutations were L63P, V77I and I93L, which belong to minor mutations of the proteinase gene, and none of which had any relation to viral loads. The major mutations, which were mainly K103N and Q151M, were less frequent in China than those in other countries. There was a certain correlation between viral loads and I93IL according to stepwise regression analysis. The incidence of primary mutations among HAART naïve patients was lower in China's central plains than that in other countries, and the most common mutations had no relation to viral loads. Though major mutations affecting choice of ARV are not common in China, they deserve further attention.

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