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1.
Proc Natl Acad Sci U S A ; 118(19)2021 05 11.
Artigo em Inglês | MEDLINE | ID: mdl-33941674

RESUMO

Tissue-on-chip systems represent promising platforms for monitoring and controlling tissue functions in vitro for various purposes in biomedical research. The two-dimensional (2D) layouts of these constructs constrain the types of interactions that can be studied and limit their relevance to three-dimensional (3D) tissues. The development of 3D electronic scaffolds and microphysiological devices with geometries and functions tailored to realistic 3D tissues has the potential to create important possibilities in advanced sensing and control. This study presents classes of compliant 3D frameworks that incorporate microscale strain sensors for high-sensitivity measurements of contractile forces of engineered optogenetic muscle tissue rings, supported by quantitative simulations. Compared with traditional approaches based on optical microscopy, these 3D mechanical frameworks and sensing systems can measure not only motions but also contractile forces with high accuracy and high temporal resolution. Results of active tension force measurements of engineered muscle rings under different stimulation conditions in long-term monitoring settings for over 5 wk and in response to various chemical and drug doses demonstrate the utility of such platforms in sensing and modulation of muscle and other tissues. Possibilities for applications range from drug screening and disease modeling to biohybrid robotic engineering.

2.
Sci Adv ; 7(7)2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33568482

RESUMO

Accurate, real-time monitoring of intravascular oxygen levels is important in tracking the cardiopulmonary health of patients after cardiothoracic surgery. Existing technologies use intravascular placement of glass fiber-optic catheters that pose risks of blood vessel damage, thrombosis, and infection. In addition, physical tethers to power supply systems and data acquisition hardware limit freedom of movement and add clutter to the intensive care unit. This report introduces a wireless, miniaturized, implantable optoelectronic catheter system incorporating optical components on the probe, encapsulated by soft biocompatible materials, as alternative technology that avoids these disadvantages. The absence of physical tethers and the flexible, biocompatible construction of the probe represent key defining features, resulting in a high-performance, patient-friendly implantable oximeter that can monitor localized tissue oxygenation, heart rate, and respiratory activity with wireless, real-time, continuous operation. In vitro and in vivo testing shows that this platform offers measurement accuracy and precision equivalent to those of existing clinical standards.

3.
DNA Cell Biol ; 39(2): 244-254, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31928425

RESUMO

Extracellular matrix metalloproteinase inducer (EMMPRIN) had been reported to be involved in the occurrence and development of coronary heart disease (CHD) in previous studies. This study aimed to investigate whether single nucleotide polymorphisms of EMMPRIN and matrix metalloproteinase-9 (MMP-9) contributed to the onset and severity of CHD. One thousand seventy patients suspected to have CHD were enrolled into the study. Each patient had undergone coronary angiogram, and the severity of coronary artery stenosis was assessed by Gensini score. Eight hundred twelve patients were confirmed to have CHD, while 258 patients were selected as non-CHD control. All patients were genotyped for five EMMPRIN polymorphisms (rs8259, rs28915400, rs4919859, rs6758, and rs8637) and one MMP-9 polymorphism (rs3918242) by polymerase chain reaction-restriction fragment length polymorphism and confirmed by direct sequencing. EMMPRIN polymorphism rs8259 and MMP-9 polymorphism rs3918242 were found to be associated with CHD (rs8259: AT vs. AA, adjusted odds ratio [OR] = 2.038, adjusted 95% confidence interval [CI] = 1.080-3.847, p = 0.028; rs3918242: CT vs. CC, adjusted OR = 0.607, adjusted 95% CI = 0.403-0.916, p = 0.017, TT vs. CC, adjusted OR = 2.559, adjusted 95% CI = 1.326-4.975, p = 0.006). No crossover effects were observed although a single environmental or genetic factor had an impact on the occurrence of CHD. The value of the Gensini score revealed that severity of CHD decreased in the rs3918242 CT carriers in both the male and female population. Our study suggested that EMMPRIN rs8259 and MMP-9 rs3918242 polymorphisms may contribute to pathological process of CHD. It could play a critical role in the prediction of CHD.


Assuntos
Basigina/genética , Doença da Artéria Coronariana/genética , Predisposição Genética para Doença/genética , Metaloproteinase 9 da Matriz/genética , Polimorfismo de Nucleotídeo Único/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Frequência do Gene , Estudos de Associação Genética , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Polimorfismo de Fragmento de Restrição/genética , Fatores de Risco
4.
Int J Mol Med ; 44(3): 927-938, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31257476

RESUMO

The present study aimed to further investigate the effects of high glucose on the function of circulating fibrocytes and its underlying mechanisms. The total peripheral blood mononuclear cells were obtained from normal glucose tolerance patients and type 2 diabetic mellitus patients. Circulating fibrocytes were stimulated with different glucose concentrations for different time periods (24, 48 and 72 h). Cell proliferation was determined by Cell Counting Kit­8 assay. The expression of connective tissue growth factor (CTGF) was detected by western blotting. The expression of COL­I was detected by flow cytometry. The apoptotic bodies of cells were detected by fluorescence microscopy after Hoechst33258 staining. The invasive and migration abilities of fibrocytes were detected by Transwell chamber assay. Secretion of stromal cell­derived factor 1 (SDF­1) was measured by ELISA. The circulating fibrocytes showed a typical spindle­shape and were double­positive for cluster of differentiation 45 (green) and COL­I (red). Compared with the 5.5 mmol/l glucose group, a high glucose concentration significantly promoted the proliferation of circulating fibrocytes and showed the most significant effects at 30 mmol/l after treatment for 48 h. AMD3100 showed no effects on the proliferation of circulating fibrocytes. Flow cytometry revealed that 30 mmol/l glucose significantly promoted the expression of COL­I vs. 5.5 mmol/l glucose group (P<0.01), while AMD3100 reversed this (P<0.05). Hoechst33258 staining showed no differences in the apoptotic bodies between experimental groups (P>0.05). Western blotting revealed that the expression of CTGF was decreased significantly by AMD3100 pretreatment (P<0.01). Transwell chamber assay showed that 30 mmol/l glucose significantly promoted the invasive and transfer abilities (P<0.01) of fibrocytes when compared with the 5.5 mmol/l glucose group. While AMD3100 reversed the cell migratory effects induced by high glucose (P<0.01). In addition, the secretion of SDF­1 stimulated by 30 mmol/l glucose DMEM showed no differences compared with 5.5 mmol/l glucose DMEM (P>0.05). High glucose stimulated the expressions of CTGF and COL­I, and promoted migration of circulating fibrocytes via the CXC chemokine receptor 4/SDF­1 axis.


Assuntos
Glicemia , Células do Tecido Conjuntivo/metabolismo , Glucose/metabolismo , Idoso , Apoptose , Benzilaminas , Movimento Celular/efeitos dos fármacos , Proliferação de Células , Células Cultivadas , Quimiocina CXCL12/genética , Quimiocina CXCL12/metabolismo , Células do Tecido Conjuntivo/efeitos dos fármacos , Ciclamos , Diabetes Mellitus Tipo 2/metabolismo , Feminino , Regulação da Expressão Gênica , Glucose/farmacologia , Compostos Heterocíclicos/farmacologia , Humanos , Masculino , Pessoa de Meia-Idade , Receptores CXCR4/metabolismo , Transdução de Sinais
5.
Sci Adv ; 5(3): eaaw0873, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30873435

RESUMO

Monitoring regional tissue oxygenation in animal models and potentially in human subjects can yield insights into the underlying mechanisms of local O2-mediated physiological processes and provide diagnostic and therapeutic guidance for relevant disease states. Existing technologies for tissue oxygenation assessments involve some combination of disadvantages in requirements for physical tethers, anesthetics, and special apparatus, often with confounding effects on the natural behaviors of test subjects. This work introduces an entirely wireless and fully implantable platform incorporating (i) microscale optoelectronics for continuous sensing of local hemoglobin dynamics and (ii) advanced designs in continuous, wireless power delivery and data output for tether-free operation. These features support in vivo, highly localized tissue oximetry at sites of interest, including deep brain regions of mice, on untethered, awake animal models. The results create many opportunities for studying various O2-mediated processes in naturally behaving subjects, with implications in biomedical research and clinical practice.


Assuntos
Fontes de Energia Elétrica , Oximetria/instrumentação , Próteses e Implantes , Tecnologia sem Fio/instrumentação , Animais , Substitutos Sanguíneos/análise , Corpo Estriado/metabolismo , Corpo Estriado/cirurgia , Hipóxia/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Modelos Animais , Oxigênio/análise , Ratos , Ratos Sprague-Dawley , Materiais Inteligentes
6.
Endocrine ; 58(1): 97-105, 2017 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-28822077

RESUMO

BACKGROUND: Recent evidence indicates a pivotal role for fetuin B, one of the cystatin superfamily of cysteine protease inhibitors, in the pathogenesis of metabolic diseases. This study investigated whether serum fetuin B levels are associated with the presence of coronary artery disease. METHODS: Serum fetuin B levels were assessed in 87 patients with coronary artery disease (41 with acute coronary syndromes and 46 with stable angina pectoris) and 87 healthy controls using an enzyme-linked immunosorbent assay. The association of serum fetuin B levels with cardiac risk factors was analyzed. RESULTS: Serum fetuin B levels were significantly higher in patients with coronary artery disease than those in healthy controls (90.7 ± 32.1 vs. 110.0 ± 32.7 µg/ml, P < 0.001), extremely elevated in group with acute coronary syndromes (115.0 ± 35.2 µg/ml). Pearson correlation analysis showed that serum fetuin B levels were positively associated with the levels of total cholesterol (r = 0.276, P < 0.001), low-density lipoprotein cholesterol (r = 0.363, P < 0.001), and fasting blood glucose (r = 0.159, P < 0.05). In addition, multiple logistic regression analyses revealed that fetuin B was independently associated with the presence of coronary artery disease (OR, 1.019; 95% CI, 1.009 to 1.029; P < 0.001) and acute coronary syndromes (OR, 1.017; 95% CI, 1.006 to 1.028; P < 0.01). CONCLUSIONS: Our data revealed that high fetuin B levels are associated with the presence of coronary artery disease and acute coronary syndromes, and that fetuin B may serve as a potential biomarker for coronary artery disease.


Assuntos
Doença da Artéria Coronariana/sangue , Fetuína-B/análise , Síndrome Coronariana Aguda/sangue , Idoso , Idoso de 80 Anos ou mais , Angina Pectoris/metabolismo , Biomarcadores/sangue , Glicemia/metabolismo , Colesterol/sangue , HDL-Colesterol/sangue , LDL-Colesterol/sangue , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Curva ROC , Fatores de Risco
7.
Clin Invest Med ; 36(6): E282-9, 2013 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-24309224

RESUMO

PURPOSE: Leukotriene B4 (LTB4) and extracellular matrix metalloproteinase (EMMPRIN) have been suggested as modulators of atherosclerotic plaque instability. This study sought to evaluate the potential diagnostic implication of LTB4 and EMMPRIN in patients with acute coronary syndrome (ACS). METHODS: Patients (n=153) who underwent coronary angiography, including 105 patients diagnosed with ACS, were divided into four groups: stable angina pectoris (SAP, n=19), unstable angina pectoris (UAP, n=39), acute myocardial infarction (AMI, n=66) and control (with normal coronary angiography, n=29). EMMPRIN expression in peripheral blood mononuclear cells was determined by flow cytometry and serum LTB4 levels were measured by ELISA. To examine whether LTB4 can regulate the expression of EMMPRIN and matrix metalloproteinases (MMPs) in macrophages, differentiated THP-1 macrophages were stimulated with different concentrations of LTB4 (10-10-10-7mmol/L). Expression of EMMPRIN was evaluated by Western blotting. MMP-9 mRNA expression and enzymatic activity were determined by RT-PCR and SDS-PAGE gelatin zymography. RESULT: Serum LTB4 concentration was significantly higher in AMI and UAP groups, compared with control and SAP groups (p < 0.01). Subgroups analysis showed that LTB4 was significantly higher in the AMI < 24h group, compared with the AMI > 24h group. Expression of EMMPRIN on circulating monocytes was significantly higher in patients with UAP and AMI (> 24h), compared with control, SAP and AMI (< 24h) groups (p < 0.05). In vitro study showed LTB4 up-regulated the expression of EMMPRIN, as well as the expression and activity of MMP-9, in cultured THP-1-derived macrophages (p < 0.05). CONCLUSION: LTB4 and EMMPRIN are associated with the pathogenesis of ACS and may be potential biomarkers for patients with ACS.


Assuntos
Síndrome Coronariana Aguda/sangue , Basigina/sangue , Leucotrieno B4/sangue , Idoso , Idoso de 80 Anos ou mais , Linhagem Celular , Feminino , Regulação da Expressão Gênica , Humanos , Macrófagos/metabolismo , Masculino , Metaloproteinase 9 da Matriz/biossíntese , Pessoa de Meia-Idade
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