RESUMO
Metalation of metal-organic frameworks (MOFs) has been developed as a prominent strategy for materials functionalization for pore chemistry modulation and property optimization. By introducing exotic metal ions/complexes/nanoparticles onto/into the parent framework, many metallized MOFs have exhibited significantly improved performance in a wide range of applications. In this review, we focus on the research progress in the metalation of metal-organic frameworks during the last five years, spanning the design principles, synthetic strategies, and potential applications. Based on the crystal engineering principles, a minor change in the MOF composition through metalation would lead to leveraged variation of properties. This review starts from the general strategies established for the incorporation of metal species within MOFs, followed by the design principles to graft the desired functionality while maintaining the porosity of frameworks. Facile metalation has contributed a great number of bespoke materials with excellent performance, and we summarize their applications in gas adsorption and separation, heterogeneous catalysis, detection and sensing, and energy storage and conversion. The underlying mechanisms are also investigated by state-of-the-art techniques and analyzed for gaining insight into the structure-property relationships, which would in turn facilitate the further development of design principles. Finally, the current challenges and opportunities in MOF metalation have been discussed, and the promising future directions for customizing the next-generation advanced materials have been outlined as well.
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Adipose dysfunction in lipodystrophic SEIPIN deficiency is associated with multiple metabolic disorders and increased risks of developing cardiovascular diseases, such as atherosclerosis, cardiac hypertrophy, and heart failure. Recently, adipose transplantation has been found to correct adipose dysfunction and metabolic disorders in lipodystrophic Seipin knockout mice; however, whether adipose transplantation could improve lipodystrophy-associated cardiovascular consequences is still unclear. Here, we aimed to explore the effects of adipose transplantation on lipodystrophy-associated metabolic cardiovascular diseases in Seipin knockout mice crossed into atherosclerosis-prone apolipoprotein E (Apoe) knockout background. At 2 months of age, lipodystrophic Seipin/Apoe double knockout mice and nonlipodystrophic Apoe knockout controls were subjected to adipose transplantation or sham operation. Seven months later, mice were euthanized. Our data showed that although adipose transplantation had no significant impact on endogenous adipose atrophy or gene expression, it remarkably increased plasma leptin but not adiponectin concentration in Seipin/Apoe double knockout mice. This led to significantly reduced hyperlipidemia, hepatic steatosis, and insulin resistance in Seipin/Apoe double knockout mice. Consequently, atherosclerosis burden, intraplaque macrophage infiltration, and aortic inflammatory gene expression were all attenuated in Seipin/Apoe double knockout mice with adipose transplantation. However, adipocyte morphology, macrophage infiltration, or fibrosis of the perivascular adipose tissue was not altered in Seipin/Apoe double knockout mice with adipose transplantation, followed by no significant improvement of vasoconstriction or relaxation. In conclusion, we demonstrate that adipose transplantation could alleviate lipodystrophy-associated metabolic disorders and atherosclerosis but has an almost null impact on perivascular adipose abnormality or vascular dysfunction in lipodystrophic Seipin/Apoe double knockout mice.NEW & NOTEWORTHY Adipose transplantation (AT) reverses multiply metabolic derangements in lipodystrophy, but whether it could improve lipodystrophy-related cardiovascular consequences is unknown. Here, using Seipin/Apoe double knockout mice as a lipodystrophy disease model, we showed that AT partially restored adipose functionality, which translated into significantly reduced atherosclerosis. However, AT was incapable of reversing perivascular adipose abnormality or vascular dysfunction. The current study provides preliminary experimental evidence on the therapeutic potential of AT on lipodystrophy-related metabolic cardiovascular diseases.
Assuntos
Tecido Adiposo , Aterosclerose , Subunidades gama da Proteína de Ligação ao GTP , Lipodistrofia , Camundongos Knockout , Animais , Camundongos , Tecido Adiposo/metabolismo , Tecido Adiposo/transplante , Apolipoproteínas E/genética , Apolipoproteínas E/deficiência , Apolipoproteínas E/metabolismo , Aterosclerose/genética , Aterosclerose/metabolismo , Aterosclerose/patologia , Subunidades gama da Proteína de Ligação ao GTP/deficiência , Subunidades gama da Proteína de Ligação ao GTP/genética , Subunidades gama da Proteína de Ligação ao GTP/metabolismo , Proteínas Heterotriméricas de Ligação ao GTP/genética , Proteínas Heterotriméricas de Ligação ao GTP/metabolismo , Resistência à Insulina , Leptina/sangue , Leptina/metabolismo , Lipodistrofia/metabolismo , Lipodistrofia/genética , Lipodistrofia/patologia , Camundongos Endogâmicos C57BLRESUMO
It is of great significance to solve the environmental problems caused by the unreasonable treatment of coal gasification slag. This study successfully produced Si-Fe-Al-Ca alloy from low-carbon fine slag with petroleum coke as reducing agent in a plasma furnace with an alternating current magnetic field, which solved the problem of the high reactivity requirement of carbon reductant for plasma smelting. The optimum carbon content of the mixed low-carbon fine slag and petroleum coke is 105% of the theoretical value. As the strength of the alternating current magnetic field increased (from 0% to 100% of the maximum power), the yield of the alloy (from 25.46% to 58.19%) and the recovery ratios of each element (Si, Fe, Al, Ca, Ti) increased. In addition, as the magnetic field strength increased, the pores inside the alloy became smaller, the composition of the alloy became more homogeneous, and a better separation of the alloy from the slag was observed. The main composition of the alloy at the strongest alternating current magnetic field is Si: 51.14 wt%, Fe: 28.41 wt%, Al: 9.14 wt%, Ca: 7.15 wt%, Ti: 2.03 wt%. We attribute the enhanced smelting effect of the alternating current magnetic field to the resistive heat and Lorentz force produced by the induced current. In addition, the skin effect concentrated the induced current on the surface of the oxide particles and carbon particles, which increased the temperature of the reaction interface and promoted the carbothermal reduction reaction.
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Coque , Petróleo , Carvão Mineral , Ligas , CarbonoRESUMO
OBJECTIVE: To explore the clinical characteristics and variant of CREBBP gene in a fetus with Rubinstein-Taybi syndrome (RSTS). METHODS: A fetus with RSTS diagnosed at the Third Affiliated Hospital of Zhengzhou University in August 2022 was selected as the study subject. Clinical data, amniotic fluid sample of the fetus and peripheral blood samples of its parents were collected for whole exome sequencing (WES). Candidate variant was verified by Sanger sequencing. RESULTS: Foot malformation, cerebellar vermis agenesis, brain agenesis, polysyndactyly of the big toes and other phenotypes were found by prenatal ultrasound. WES revealed that the fetus has harbored a heterozygous c.4684G>T (p.E1562*) variant in exon 28 of the CREBBP gene (NM_004380.3), which was de novo in origin. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), the variant was predicted to be pathogenic (PVS1+PS2_Moderate+PM2_Supporting). After genetic counseling, the couple had opted to terminate the pregnancy and refused autopsy of the fetus. CONCLUSION: The c.4684G>T (p.E1562*) variant of the CREBBP gene probably underlay the RSTS in this fetus. The newly discovered variant has enriched the mutational spectrum of the CREBBP gene and illustrated that WES is an efficient tool for the prenatal diagnosis of RSTS.
Assuntos
Proteína de Ligação a CREB , Sequenciamento do Exoma , Diagnóstico Pré-Natal , Síndrome de Rubinstein-Taybi , Humanos , Síndrome de Rubinstein-Taybi/genética , Feminino , Gravidez , Proteína de Ligação a CREB/genética , Adulto , Feto/anormalidades , Feto/diagnóstico por imagem , Mutação , Masculino , Ultrassonografia Pré-NatalRESUMO
AIMS: The medical capillary catheters occupy a high proportion of medical diagnosis, monitoring, and treatment devices, and will cause serious cross-infection without being disinfected adequately. This paper presents a new plasma structure for efficient inactivation of harmful microorganisms in medical capillaries. METHODS AND RESULTS: An innovative coaxial-dual-gap dielectric barrier discharge reactor powered by nanosecond-pulsed power supply was designed for disinfection of Escherichia coli (E. coli) inside and outside medical capillary catheters in this work. Atmospheric helium plasma (AHP) and atmospheric air plasma (AAP) were successfully obtained inside and outside capillary (0.6 mm inner diameter and 1.0 mm outer diameter), respectively. The electrical and optical characteristics of AHP and AAP were investigated. As the threshold of applied voltage amplitude (Uamp) was <7.0 kV, only one helium glow discharge was generated inside the capillary at the rising and falling stages of pulse voltage. As the Uamp exceeded the threshold, two helium glow discharges were generated that further caused generation of air discharge. Under the Uamp of 9.0 kV, the production of AHP lowered the breakdown voltage in air gap, resulting in the formation of high-volume and uniform AAP, which was conducive to the realization of full inactivation. The inactivation rates of E. coli reached 98.13% and 99.99% by 2 min AHP and 0.5 min AAP treatment, respectively. CONCLUSIONS: The electrical stress of AHP and the reactive oxygen and nitrogen species produced by AAP were contributed to the inactivation of E. coli. The results of SEM (Scanning Electron Microscope) show that plasma treatment can destroy the cellular structure of E. coli.
Assuntos
Escherichia coli , Hélio , Escherichia coli/fisiologia , Capilares , Descontaminação , OxigênioRESUMO
PURPOSE: To explore the relationship between ankle-brachial blood pressure index (ABPI) and all-cause or cardiovascular mortality in adults without arterial stiffness. METHODS: A total of 6784 participants without arterial stiffness were enrolled from National Health and Nutrition Examination Survey 1999-2004. The hazard ratio (HR) and 95% confidence interval (CI) of ABPI associating with the risk of all-cause and cardiovascular mortality was calculated by Cox proportional regression models adjusted for demographic and traditional risk factors. Dose-response relationship was explored with restricted cubic spines. RESULTS: After an average follow-up of 12.1 years, 1844 all-cause deaths and 299 cardiovascular deaths occurred. Compared with the lowest ABPI quartile, the second quartile was associated with the lowest risk of all-cause mortality (HR 0.89, 95%CI 0.79-0.98; p = 0.036) and cardiovascular mortality (HR 0.75, 95%CI 0.56-0.98; p = 0.048). Besides, dose-response analysis revealed that ABPI was nonlinearly correlated to all-cause mortality (p for nonlinearity < 0.001) and linearly correlated to cardiovascular mortality (p for nonlinearity = 0.459). CONCLUSIONS: The relationship between ABPI and all-cause and cardiovascular mortality followed a L-shape curve. A lower ABPI was independently associated with an increased risk of all-cause and cardiovascular mortality in adults without arterial stiffness.
Assuntos
Doenças Cardiovasculares , Rigidez Vascular , Humanos , Pressão Sanguínea , Tornozelo/irrigação sanguínea , Inquéritos Nutricionais , Índice Tornozelo-Braço/efeitos adversos , Fatores de RiscoRESUMO
Cervical cancer is an important topic in the study of global health issues, ranking fourth among women's cancer cases in the world. It is one of the nine major cancers that China is focusing on preventing and treating, and it is the only cancer that can be prevented through vaccination. Systematic and effective screening for human papilloma (HPV) infection, which is closely linked to the development of cervical cancer, can reduce cervical cancer incidence and mortality. In this paper, an electrochemical sensor was designed to detect HPV 16 using dual-signal amplification. An APTES-modified glassy carbon electrode was used for improved stability. Gold nanoparticles and a chain amplification reaction were combined for signal amplification. The limit of detection (LOD) of this electrochemical sensor was 1.731 × 10-16 mol/L, and the linear response of the target detector range was from 1.0 × 10-13 mol/L to 1.0 × 10-5 mol/L (R2 = 0.99232). The test of serum sample recovery showed that it has good anti-interference, and the performance of all aspects was improved to different degrees compared with the previous research from the team. The designed sensor is centered around the principles of low cost, high sensitivity and stability, which provides new ideas for the future development of cervical cancer prevention and electrochemical biosensors.
Assuntos
Nanopartículas Metálicas , Neoplasias do Colo do Útero , Humanos , Feminino , Neoplasias do Colo do Útero/diagnóstico , Neoplasias do Colo do Útero/prevenção & controle , Ouro , Papillomavirus Humano 16 , DNARESUMO
Long noncoding RNAs (lncRNAs) are known to play a crucial role in the onset and progression of cervical cancer (CC). Here, the results of RNA microarray and RNA-sequencing dataset analysis showed that lncRNA DLEU2 was significantly upregulated in CC tissues. Clinicopathologic analysis indicated that lncRNA DLEU2 was closely related to tumor topography. Functional experiments and bioinformatics analysis revealed that lncRNA DLEU2 promoted CC cell proliferation and accelerated the cell cycle. Mechanistically, lncRNA DLEU2 promoted the progression of the cell cycle and inhibited the activity of the Notch signaling pathway by inhibiting p53 expression. Additionally, lncRNA DLEU2 probably interacted with ZFP36 Ring Finger Protein (ZFP36) to inhibit the expression of p53. In conclusion, this study revealed the function of lncRNA DLEU2 in CC tumorigenesis, suggesting new therapeutic targets in CC.
Assuntos
Carcinogênese/genética , RNA Longo não Codificante/genética , Tristetraprolina/genética , Proteína Supressora de Tumor p53/genética , Neoplasias do Colo do Útero/genética , Ciclo Celular/genética , Linhagem Celular Tumoral , Movimento Celular/genética , Proliferação de Células/genética , Feminino , Regulação Neoplásica da Expressão Gênica/genética , Inativação Gênica , Humanos , Receptores Notch/genética , Transdução de Sinais/genética , Neoplasias do Colo do Útero/patologiaRESUMO
OBJECTIVES: This retrospective study aimed to investigate the correlations between phenotypes of fetal renal abnormalities on prenatal ultrasound and genetic aetiologies detected using chromosomal microarray analysis (CMA) and whole-exome sequencing (WES). METHODS: Fetuses with renal abnormalities were subjected to CMA and were further analysed by WES when CMA-negative. The detection rates for chromosomal abnormalities and monogenic variants among different types of isolated renal abnormalities and those with extrarenal abnormalities (non-isolated cases) were determined and compared. RESULTS: CMA detected chromosomal abnormalities in 78 of 577 fetuses (13.52%). WES detected monogenic variants in 31 of 160 fetuses (19.38%) that had non-diagnostic CMA results. In cases of isolated hyperechogenic kidney, polycystic kidney disease, and multicystic dysplastic kidney, the detection rates of copy number variants (CNVs) by CMA and monogenic variants by WES were not significantly different (p > 0.05). However, monogenic variants were more frequently detected than CNVs when kidney abnormalities were accompanied by reduced amniotic fluid (p < 0.05). Other renal abnormalities identified on prenatal ultrasound had different detection rates. CONCLUSIONS: Our findings contribute to the overall knowledge of genetic variants associated with prenatally identified renal anomalies and may aid in decision making regarding prenatal genetic testing options for affected pregnancies.
Assuntos
Variações do Número de Cópias de DNA , Diagnóstico Pré-Natal , Aberrações Cromossômicas , Feminino , Humanos , Análise em Microsséries , Gravidez , Diagnóstico Pré-Natal/métodos , Estudos Retrospectivos , Ultrassonografia Pré-NatalRESUMO
Alpha-synuclein (αS) has been proposed as a potential biomarker for the diagnosis of Parkinson's disease (PD). However, the detection of αS using a simple, rapid and sensitive approach is still challenging. Herein, we construct a new type of biosensor for the detection of αS, combining the stimuli-responsiveness of liquid crystals (LCs) and the specific interaction of a DNA aptamer with proteins. In principle, the positively charged surfactant hexadecyltrimethylammonium bromide (CTAB) binds with the negatively charged DNA aptamer via electrostatic interactions; in the presence of αS, the DNA aptamer specifically binds with αS and releases CTAB, which is an amphiphilic molecule and subsequently assembles at the LC-aqueous interface, resulting in a homeotropic alignment of LCs with a dark optical signal. In the absence of αS, CTAB binds with the DNA aptamer without affecting the alignment of LCs, which shows planar anchoring with a bright optical signal. The response time of LCs towards αS is rapid and can be down to minutes. The LC biosensor established here has a good specificity for αS and can recognize αS even from a mixture of proteins. The LC biosensor also exhibits high sensitivity with a limit of detection of αS as low as 10 pM, which is comparable to that of the enzyme-linked immunosorbent assay. This work provides a new strategy for the detection of αS in a simple, rapid and sensitive manner, possessing promising potentials towards early diagnosis and clinical applications.
Assuntos
Aptâmeros de Nucleotídeos , Técnicas Biossensoriais , Cristais Líquidos , Doença de Parkinson , Humanos , Doença de Parkinson/diagnóstico , alfa-SinucleínaRESUMO
Severe asthenozoospermia is a common cause of male infertility. Recent studies have revealed that SPEF2 mutations lead to multiple morphological abnormalities of the sperm flagella (MMAF) without primary ciliary dyskinesia (PCD) symptoms in males, but PCD phenotype was also found in one female individual. Therefore, whether there is a phenotypic continuum ranging from infertile patients with PCD to MMAF patients with no or low noise PCD manifestations remains elusive. Here, we performed whole-exome sequencing in 47 patients with severe asthenozoospermia from 45 unrelated Chinese families. We identified four novel biallelic mutations in SPEF2 (8.9%, 4/45) in six affected individuals (12.8%, 6/47), while no deleterious biallelic variants in SPEF2 were detected in 637 controls, including 219 with oligoasthenospermia, 195 with non-obstructive azoospermia, and 223 fertile controls. Notably, all six patients exhibited PCD-like symptoms, including recurrent airway infections, bronchitis, and rhinosinusitis. Ultrastructural analysis revealed normal 9 + 2 axonemes of respiratory cilia but consistently abnormal 9 + 0 axoneme or disordered accessory structures of sperm flagella, indicating different roles of SPEF2 in sperm flagella and respiratory cilia. Subsequently, a Spef2 knockout mouse model was used to validate the PCD-like phenotype and male infertility, where the subfertility of female Spef2-/- mice was found unexpectedly. Overall, our data bridge the link between MMAF and PCD based on the association of SPEF2 mutations with both infertility and PCD in males and provide basis for further exploring the molecular mechanism of SPEF2 during spermiogenesis and ciliogenesis.
Assuntos
Anormalidades Múltiplas/patologia , Proteínas de Ciclo Celular/genética , Cílios/patologia , Transtornos da Motilidade Ciliar/patologia , Infertilidade Masculina/patologia , Proteínas/fisiologia , Cauda do Espermatozoide/patologia , Anormalidades Múltiplas/genética , Animais , Cílios/genética , Transtornos da Motilidade Ciliar/genética , Feminino , Humanos , Infertilidade Masculina/genética , Masculino , Camundongos , Camundongos Knockout , Fenótipo , Motilidade dos Espermatozoides , Cauda do Espermatozoide/metabolismoRESUMO
Based on measuring the polarimetric parameters which contain specific physical information, polarimetric imaging has been widely applied to various fields. However, in practice, the noise during image acquisition could lead to the output of noisy polarimetric images. In this paper, we propose, for the first time to our knowledge, a learning-based method for polarimetric image denoising. This method is based on the residual dense network and can significantly suppress the noise in polarimetric images. The experimental results show that the proposed method has an evident performance on the noise suppression and outperforms other existing methods. Especially for the images of the degree of polarization and the angle of polarization, which are quite sensitive to the noise, the proposed learning-based method can well reconstruct the details flooded in strong noise.
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An aptasensor is described for the electrochemical determination of bisphenol A (BPA). Gold-coated multiwalled carbon nanotubes (Au/MWCNTs) and a single-stranded DNA-dye complex are used as a double signal-amplification system. The BPA-binding aptamer was assembled on a disposable electrode modified with Au/MWCNTs. Methylene blue (MB) was then intercalated into the immobilized aptamer with an approximately molecular ratio of 4 to form a complex. Upon interaction with BPA, the immobilized aptamer underwent a conformational change. This causes the intercalated MB to be released from the complex into solution. As a result, the electrochemical signal of the intercalated MB, typically measured using square wave voltammetry at a potential of -0.20 V (vs. Ag/AgCl (saturated KCl)) decreases. The fabrication of the aptasensor was characterized by the scanning electron microscopy, atomic force microscopy, and electrochemical techniques. Under optimal experimental conditions, the current drops linearly with the logarithm of BPA concentrations over the range from 10 fM to 1 nM, and the limit of detection is 8 fM. The assay was applied to the determination of BPA in plastic drinking bottles, tap water, and milk. Graphical AbstractSchematic illustration of fabricating the aptasensor for bisphenol A (BPA) based on double signal amplification via gold-coated multiwalled carbon nanotubes (Au/MWCNT) and an aptamer-dye complex. PET: poly(ethylene terephthalate).
Assuntos
Aptâmeros de Nucleotídeos/química , Compostos Benzidrílicos/análise , Técnicas Biossensoriais , Técnicas Eletroquímicas , Técnicas de Amplificação de Ácido Nucleico , Fenóis/análise , DNA de Cadeia Simples/química , Ouro/química , Azul de Metileno/química , Nanotubos de Carbono/química , Tamanho da Partícula , Propriedades de SuperfícieRESUMO
This paper presents a simple, rapid, and green method based on a static headspace gas chromatography-mass spectrometry for determining 58 fragrance allergens in plush toys. This study is the first to meet the requirement for simultaneously determining 66 fragrances, except for eight natural extracts restricted by the European Toy Safety Directive 2009/48/EC. A minimal amount of sample (20 mg) and acetone solvent (20 µL) were placed in a headspace vial. A gas-solid equilibration of fragrances between the headspace and the sample was achieved within 10 min under the vapor atmosphere of acetone at 200°C, which allowed the fragrances in the sample to be measured by gas chromatography-mass spectrometry. Results showed that the interference caused by different sample matrices was negligible. The proposed method exhibited determination results that were highly similar to those of traditional ultrasonic extraction with sufficient sensitivity (limits of quantification: 0.02-10 mg/kg) for 58 fragrances, indicating its accuracy and reliability. The average recoveries ranged from 71.3 to 137.4%, and the relative standard deviation (n = 6) varied from 1.1 to 18.0%. Finally, the method was applied to monitor the fragrances in 20 commercial toys. This study provides a good reference for rapidly and greenly determining the semi-volatile analytes in toys, textiles, and other products.
Assuntos
Alérgenos/análise , Cromatografia Gasosa-Espectrometria de Massas , Química Verde , Odorantes/análise , Perfumes/análise , Jogos e Brinquedos , Acetona/análise , Automação , Gases , Pressão , Padrões de Referência , Reprodutibilidade dos Testes , Solventes , Temperatura , Têxteis , UltrassomRESUMO
This study aimed to quantify whether there is association between music-based movement therapy and motor dysfunction in patients with Parkinson's disease, and, if so, whether music-based movement therapy can be used as first-line non-pharmacological treatment. To conduct a systematic review and meta-analysis of clinical trials that examined the effect of music-based movement therapy on patient-relevant and disease-specific outcomes. Comprehensive literature was searched of PubMed, EMbase, and the Cochrane Library from inception to November 2016. Randomized controlled trial of patients with Parkinson's disease was searched to identify trials comparing music-based movement therapy with no music care. A total of 8 studies (11 analyses, 241 subjects) were included; all of them had acceptable quality by PEDro scale score. Studies based on any type of Parkinson's disease patients were combined and subgroup analyzed. Compared with the control group, the SMD of Berg Balance Scale score was 0.85(0.46 to 1.25), -0.60 (-0.98 to -0.22) in Parkinson Disease Questionnaire-39 summary index, -0.90s (-1.56 to -0.23) in Time Up and Go text, and -0.43 (-1.11 to 0.25) in Unified Parkinson's Disease Rating Scale Motor Subscale 3 as instrument methods for motor function. Secondary outcomes included cognitive function and quality of life. There was positive evidence to support the use of music-based movement therapy on treatment of motor function; there was neutral evidence to support the use of music for the treatment of cognitive function quality of life.
Assuntos
Musicoterapia , Doença de Parkinson/terapia , Modalidades de Fisioterapia , Humanos , Movimento , Musicoterapia/métodos , Doença de Parkinson/fisiopatologiaRESUMO
BACKGROUND: Coronary artery disease (CAD) is a major problem worldwide. As an endothelium-enriched microRNA (miRNA), miR-126 has been reported to serve as a potential biomarker of acute myocardial infarction. However, the relationship between miR-126 and the severity of CAD remains unknown. This study was designed to test whether circulating miR-126 levels are associated with the severity of CAD. METHODS: The present study enrolled 40 patients who had risk factors for CAD without angiographically significant CAD, and 110 patients presenting with stable angina pectoris, who were validated left main coronary artery disease (LMCA) and/or multi-vessel disease by coronary angiography. The expression levels of plasma miR-126-5p from all enrolled subjects were estimated by quantitative real-time polymerase chain reaction (qRT-PCR). Then, the relationships between plasma miR-126-5p levels, number of diseased vessels and the corresponding Synergy between PCI with Taxus and Cardiac surgery (SYNTAX) score were analyzed. RESULTS: The expression of circulating miR-126-5p was affected by some CAD risk factors including aging, dyslipidemia and DM. Furthermore, plasma miR-126-5p levels were significantly down-regulated in CAD patients with multi-vessel disease, higher SYNTAX score, rather than isolated LMCA and low SYNTAX score. CONCLUSION: Circulating miR-126-5p has emerged as a potential biomarker for complexity and severity of CAD in patients with stable angina pectoris.
Assuntos
Angina Estável/genética , Doença da Artéria Coronariana/genética , MicroRNAs/genética , Fatores Etários , Idoso , Angina Estável/complicações , Angina Estável/diagnóstico por imagem , Angina Estável/patologia , Biomarcadores/sangue , Estudos de Casos e Controles , Angiografia Coronária , Doença da Artéria Coronariana/complicações , Doença da Artéria Coronariana/diagnóstico por imagem , Doença da Artéria Coronariana/patologia , Diabetes Mellitus/patologia , Dislipidemias/patologia , Feminino , Regulação da Expressão Gênica , Humanos , Masculino , MicroRNAs/sangue , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase em Tempo Real , Fatores de Risco , Índice de Gravidade de DoençaRESUMO
Metastasis is the leading cause of death in patients with breast cancer and aberrantly expressed microRNAs (miRNAs) are highly associated with this process. A previous study has shown that miR-335 is downregulated in breast cancer and can suppress tumor invasion and metastasis. Emerging evidences indicate that c-Met is implicated in cell scattering, migration, and invasion. However, little is known about the relationship between miR-335 expression and c-Met alteration in breast cancer. In the present study, we found that miR-335 expression was downregulated and c-Met protein expression was upregulated in two human breast cell lines. MiR-335 was found to negatively regulate c-Met protein level by directly targeting its 3' untranslated region (UTR). Forced expression of miR-335 decreased c-Met expression at protein levels and consequently diminished hepatocyte growth factor (HGF)-induced phosphorylation of c-Met and subsequently inhibited HGF promotion of breast cancer cell migration in a c-Met-dependent manner. MiR-335 expression was increased after 5-aza-2'-deoxycytidine (5-AZA-CdR) treatment, and 5-AZA-CdR treatment resulted in the same phenotype as the effect of miR-335 overexpression. Taken together, these results demonstrate that miR-335 suppresses breast cancer cell migration by negatively regulating the HGF/c-Met pathway.
Assuntos
Neoplasias da Mama/genética , Fator de Crescimento de Hepatócito/metabolismo , MicroRNAs/biossíntese , Proteínas Proto-Oncogênicas c-met/biossíntese , Azacitidina/administração & dosagem , Azacitidina/análogos & derivados , Neoplasias da Mama/patologia , Movimento Celular/efeitos dos fármacos , Proliferação de Células/genética , Decitabina , Feminino , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Células MCF-7 , MicroRNAs/genética , Invasividade Neoplásica/genética , Proteínas Proto-Oncogênicas c-met/genéticaRESUMO
BACKGROUND: Tanshinone IIA (TSN) is one of the main components isolated from Danshen, which is widely used for the treatment of cardiovascular diseases. The transforming growth factor beta (TGF-ß) signaling pathway and microRNA (miR)-29b play important roles in the progression of cardiac fibrosis and the modulation of cardiac fibroblast (CF) function. Our study investigated the role of miR-29b in the cardioprotective effects of TSN in postinfarct cardiac remodeling. METHODS AND RESULTS: Echocardiography demonstrated that medium-dose TSN (TSN-M) and high-dose TSN (TSN-H) significantly inhibited postinfarct cardiac fibrosis and improved the impaired left ventricular function in rats subjected to acute myocardial infarction. Moreover, quantitative real-time polymerase chain reaction and Western blot demonstrated that TSN-M and TSN-H downregulated the expression of TGF-ß1, Col1a1, Col3a1, and α-SMA but upregulated the expression of miR-29b. CFs treated with TSN showed inhibited TGF-ß signaling pathway, downregulated expression of Col1a1, Col3a1, and α-SMA, and upregulated miR-29b expression in vitro. Furthermore, treatment with a miR-29b inhibitor dramatically inhibited these TSN-induced antifibrotic effects, suggesting that miR-29b may be responsible for the antifibrotic effects of TSN. In addition, treatment with Smad3 siRNA significantly inhibited miR-29b expression in CFs, which implies that Smad3 signaling promotes miR-29b expression on CFs. CONCLUSIONS: TSN exerts antifibrotic effects in postinfarct cardiac fibrosis by upregulating the expression of miR-29b, which is mediated by the TGF-ß-Smad3 signaling pathway.
Assuntos
Abietanos/farmacologia , MicroRNAs/metabolismo , Infarto do Miocárdio/tratamento farmacológico , Miocárdio/metabolismo , Remodelação Ventricular/efeitos dos fármacos , Animais , Células Cultivadas , Colágeno/metabolismo , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Fibroblastos/efeitos dos fármacos , Fibroblastos/metabolismo , Fibroblastos/patologia , Fibrose , Masculino , MicroRNAs/genética , Infarto do Miocárdio/genética , Infarto do Miocárdio/metabolismo , Infarto do Miocárdio/patologia , Infarto do Miocárdio/fisiopatologia , Miocárdio/patologia , Interferência de RNA , Ratos Sprague-Dawley , Recuperação de Função Fisiológica , Proteína Smad3/genética , Proteína Smad3/metabolismo , Transfecção , Fator de Crescimento Transformador beta1/metabolismo , Regulação para Cima , Função Ventricular Esquerda/efeitos dos fármacosAssuntos
Azoospermia/diagnóstico , Azoospermia/genética , Proteínas de Ligação a DNA/genética , Mutação , Insuficiência Ovariana Primária/diagnóstico , Insuficiência Ovariana Primária/genética , Biópsia , Análise Mutacional de DNA , Feminino , Estudos de Associação Genética , Predisposição Genética para Doença , Humanos , MasculinoRESUMO
PURPOSE: This study was designed to investigate the potential effect of bergapten on lipopolysaccharide (LPS)-mediated osteoclast formation, bone resorption and osteoclast survival in vitro. METHODS: After osteoclast precursor RAW264.7 cells were treated with bergapten (5, 20, 40 µmol/L) for 72 hours in the presence of LPS (100 ng/ml), osteoclastogenesis was identified by tartrate-resistant acid phosphatase (TRAP) staining, and the number of TRAP-positive multinucleated cells [TRAP(+)MNCs] per well were counted. To investigate the effect of bergapten on osteoclastic bone resorption, RAW264.7 cells were treated with bergapten for six days in the presence of LPS, and the area of bone resorption was analyzed with Image Pro-Plus. Next, we examined apoptosis of RAW264.7 cells after bergapten incubation for 48 hours by flow cytometer using annexin V/propidium iodide (PI) double labeling. Finally, osteoclast survival was observed by Hoechst 33342 labeling and Western blotting after bergapten treatment for 24 hours. RESULTS: Data showed that bergapten (5-40 µmol/L) dose-dependently inhibited LPS-induced osteoclast formation and bone resorption. Treatment with bergapten triggered apoptotic death of osteoclast precursor RAW264.7 cells in a dose-dependent manner. Furthermore, bergapten significantly reduced the survival of mature osteoclast, as demonstrated by emergence of apoptotic nuclei and activation of apoptotic protein caspase 3/9. CONCLUSIONS: These findings suggest that bergapten effectively prevents LPS-induced osteoclastogenesis, bone resorption and survival via apoptotic response of osteoclasts and their precursors. The study identifies bergapten as an inhibitor of osteoclast formation and bone resorption and provides evidence that bergapten might be beneficial as an alternative for prevention and treatment of inflammatory bone loss.