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1.
World J Surg Oncol ; 19(1): 262, 2021 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-34470640

RESUMO

BACKGROUND: This study aimed to investigate the correlation between miRNA-216b expression in patients with non-small cell lung cancer (NSCLC) and 18F-fluorodeoxyglucose (FDG) uptake by PET/CT and to explore the clinical application value of 18F-FDG PET/CT in miRNA-216b based on therapy for NSCLC. METHODS: Eighty patients with NSCLC and 40 healthy subjects were enrolled in our study. The SUVmax of the lesion area by PET/CT imaging was calculated. SUVmax represented the highest concentration of 18F-FDG in the lesion. The expression of miRNA-216b in the plasma and fiber bronchoscopic puncture of NSCLC patients was detected by RT qPCR. Then Pearson correlation analysis was used to analyze the correlation between miRNA-216b expression and 18F-FDG uptake in patients with different types of NSCLC. RESULTS: Compared with healthy subjects, SUVmax of early adenocarcinoma and advanced adenocarcinoma were increased. Compared with healthy subjects, SUVmax of early squamous and advanced squamous were increased. And the SUVmax content of advanced adenocarcinoma and squamous cell carcinoma was higher than that of early adenocarcinoma and squamous cell carcinoma. Compared with healthy subjects, the expression of miRNA-216b in the plasma of patients with early and advanced adenocarcinoma was reduced, and the expression of miRNA-216b in the plasma of patients with early and advanced squamous cell carcinoma was reduced. Compared with adjacent tissues, the expression of miRNA-216b in early adenocarcinoma tissues and advanced adenocarcinoma tissues was reduced, and the expression in early squamous cell carcinoma and advanced squamous cell carcinoma was reduced. Pearson correlation analysis showed a negative correlation between SUVmax and miRNA-216b (plasma and tissue) in patients with four types of NSCLC. CONCLUSION: miRNA-216b expression was negatively correlated with 18F-FDG uptake in NSCLC. miRNA-216b could be used for the classification and staging of non-small cell lung cancer. 18F-FDG PET/CT may be used to evaluate the therapeutic response in application of miRNA-216b-based cancer treatment.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Fluordesoxiglucose F18/farmacocinética , Neoplasias Pulmonares , MicroRNAs , Carcinoma Pulmonar de Células não Pequenas/diagnóstico por imagem , Carcinoma Pulmonar de Células não Pequenas/genética , Humanos , Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/genética , MicroRNAs/genética , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Tomografia por Emissão de Pósitrons , Prognóstico , Compostos Radiofarmacêuticos
2.
Mol Pharm ; 2021 Sep 27.
Artigo em Inglês | MEDLINE | ID: mdl-34579532

RESUMO

Stemness and metastasis are the two main challenges in cancer therapy and are related to disease relapse post-treatment. They both have a strong correlation with chemoresistance and poor prognosis, ultimately leading to treatment failure. It has been reported that chemotherapy can induce stemness and metastasis in many cancer types, especially treatment with the chemotherapeutic agent doxorubicin (DOX) in breast cancer. A combination treatment is an efficient and elegant approach in cancer therapy through simultaneous delivery of two or more drugs with a delivery system for its synergistic effect, which is not an additive of two individual drugs. Herein, we report a combinatorial system with DOX and all-trans retinoic acid (ATRA) to address both of the above issues. As a common critical regulatory factor for oncogenic signal transduction pathways, Pin1 is a specific isomerase highly expressed within various tumor cells. ATRA, a newly identified Pin1 inhibitor, can abolish several oncogenic pathways by effectively inhibiting and degrading overexpressed Pin1. We successfully developed a folic acid (FA)-modified chitosan (CSO)-derived polymer (FA-CSOSA) and obtained FA-CSOSA/DOX and FA-CSOSA/ATRA drug-loaded micelles. FA modification can improve the uptake of the nanoparticles in tumor cells and tumor sites via folate receptor-mediated cell internalization. Compared to treatment with DOX alone, the combined treatment induced 4T1 cell apoptosis in a synergistic manner. Reduced stemness-related protein expression and inhibited metastasis were observed during treatment with FA-CSOSA/DOX and FA-CSOSA/ATRA and were found to be associated with Pin1. Further in vivo experiments showed that treatment with FA-CSOSA/DOX and FA-CSOSA/ATRA resulted in 85.5% tumor inhibition, which was 2.5-fold greater than that of cells treated with DOX·HCl alone. This work presents a new paradigm for addressing chemotherapy-induced side effects via degradation of Pin1 induced by tumor-targeted delivery of DOX and ATRA.

3.
J Healthc Eng ; 2021: 5526977, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33728032

RESUMO

The emergence of energy spectrum CT provides greater diagnostic value for clinical practice. Its advantage is that it can provide more functional imaging parameters and accurate image information for clinical practice, which represents a mainstream direction of CT technology development at present. This paper mainly studies the clinical trial of CAMPO Precision128 Max ENERGY spectrum CT combined with multiple parameters to evaluate the benign and malignant pleural effusion. This paper analyzes the principle and key performance parameters of energy spectrum CT imaging, the etiology of pleural effusion, and its conventional diagnostic methods and uses energy spectrum CT to detect the benign and malignant pleural effusion. In this paper, two groups of patients with different types of pleural effusions were scanned by line spectrum chest CT scans, and energy spectrum analysis software was used to measure and calculate the CT values of conventional mixed energy values of ROI of patients with pleural effusions. For the CT value and energy curve slope measurement value of different single energy keV, independent sample t-test was used to analyze and compare the two sets of data, and finally it has been found out that the two sets of data were similar. According to the experimental results, the curves of energy spectrum of the two groups of data are similar in the descending curve of bow-back. The slope of energy spectrum curve in the leakage group was lower than that in the exudate group, showing statistical significance (P < 0.05). The slope of energy spectrum curve K in the malignant pleural effusion group was significantly higher than that in the benign pleural effusion group, and the difference was statistically significant (P < 0.05). The trend of energy spectrum curves of the two is roughly the same, while at the high energy level, part of the energy spectrum curves of the two are overlapped. The above conclusion indicates that energy spectrum CT plays a certain role in the differential diagnosis of pleural effusion. At the same time, energy spectrum CT also provides a noninvasive and rapid examination method for clinical differentiation of pleural effusion, which has certain clinical application value and prospect.


Assuntos
Derrame Pleural Maligno , Derrame Pleural , Diagnóstico Diferencial , Humanos , Derrame Pleural/diagnóstico por imagem , Derrame Pleural Maligno/diagnóstico por imagem , Sensibilidade e Especificidade , Tomografia Computadorizada por Raios X
5.
Exp Ther Med ; 20(6): 221, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33193836

RESUMO

Rupture of abdominal aortic aneurysm (AAA) is a devastating event that can be prevented by inhibiting the growth of small aneurysms. Therapeutic strategies targeting certain events that promote the development of AAA must be developed, in order to alter the course of AAA. Chronic inflammation of the aortic mural is a major characteristic of AAA and is related to AAA formation, development and rupture. Daphnetin (DAP) is a coumarin derivative with anti-inflammatory properties that is extracted from Daphne odora var. However, the effect of DAP on AAA development remains unclear. The present study investigated the effect of DAP on the formation and development of experimental AAAs and its potential underlying mechanisms. A mice AAA model was established by intra-aortic infusion of porcine pancreatic elastase (PPE), and mice were intraperitoneally injected with DAP immediately after PPE infusion. The maximum diameter of the abdominal aorta was measured by ultrasound system, and aortic mural changes were investigated by Elastica van Gieson (EVG) staining and immunohistochemical staining. The results demonstrated that DAP significantly suppressed PPE-induced AAA formation and attenuated the depletion of aortic medial elastin and smooth muscle cells in the media of the aorta. Furthermore, the density of mural macrophages, T cells and B cells were significantly attenuated in DAP-treated AAA mice. In addition, treatment with DAP resulted in a significant reduction in mural neovessels. These findings indicated that DAP may limit the formation and progression of experimental aneurysms by inhibiting mural inflammation and angiogenesis. These data confirmed the translational potential of DAP inclinical AAA inhibition strategies.

6.
Artigo em Inglês | MEDLINE | ID: mdl-33246351

RESUMO

INTRODUCTION: Intrahepatic cholestasis of pregnancy (ICP) is associated with an increased risk of adverse pregnancy outcomes in mothers and infants. The aim was to evaluate the sensitivity and specificity of biochemical detection of ICP by ROC curve and to determine the threshold of more reliable experimental indicators. MATERIALS AND METHODS: 305 patients and 305 healthy pregnant women were enrolled in the study. RESULTS: The average levels of TBA, ALT, and AST in the ICP group were much higher than those in the control group (P<0. 001); the area of both CG and TBA under ROC curve was up to 0.99, the sensitivity was 97.7%, and the specificity was 99.3%. CONCLUSIONS: This study did not find any single specificity and sensitivity markers that could be used to reliably diagnose ICP. In the future, we will pay more attention to the correlation between sensitive biochemical indicators and adverse pregnancy outcomes.

7.
Int J Nanomedicine ; 15: 6531-6543, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32982216

RESUMO

Background: Photoactivity "on-off" switchable nano-agents could shield phototoxicity until reaching target region, which immensely promoted photodynamic therapy. However, the masking ratio of nano-agents in vivo was dynamic and positively correlated with the phototoxicity induced by laser irradiation, in which case the timing of laser irradiation was unpredictable to maximize antitumor efficacy. Methods: Herein, low molecular weight chitosan and hydrophobic polymethylacrylamide derivatives were linked via GSH cleavable 3, 3'-dithiodipropionic acid to construct polymeric micelles (Ce6-CSPD). The doxorubicin loading nano-agent (Ce6-CSPD/DOX) could quench both photoactivity and fluorescence of photosensitizer chlorin e6 (Ce6) and doxorubicin (DOX) under physiological condition by homo-fluorescence resonance energy transfer (homoFRET). Results: Once internalized by tumor cells, the photoactivity as well as fluorescence of Ce6 was recovered rapidly when motivated by intracellular high GSH. Specifically, the fluorescence intensity and photoactivity of Ce6 were proven to be positive linear correlated, upon which appropriate timing of laser irradiation could be determined by referring to the dynamic fluorescence intensity in vivo. In addition, the theranostic nano-agents also possessed the capacity of monitoring the DOX release process. Accordingly, under the guidance of fluorescence intensity, the experimental group subjected to laser irradiation at 18 h postadministration acquired the highest antitumor inhibition efficacy compared to that at four hours and 48 h, which held great potential for maximizing chemo-photodynamic therapy and avoiding nonspecific phototoxicity precisely to normal organs. Conclusion: In summary, we prepared homoFRET-based theranostic nano-agent (Ce6-CSPD/DOX) for monitoring PDT precisely and decreasing phototoxicity to normal organs before reaching target region. Under the guidance of dynamic fluorescence intensity, the appropriate laser irradiation timing could be monitored to maximize antitumor therapy efficacy, which offered opportunities for monitoring efficiency of chemo-photodynamic therapy in a timely and accurate manner.


Assuntos
Sistemas de Liberação de Medicamentos/métodos , Fotoquimioterapia/métodos , Fármacos Fotossensibilizantes/administração & dosagem , Polímeros/química , Animais , Neoplasias da Mama/tratamento farmacológico , Linhagem Celular Tumoral , Quitosana/química , Doxorrubicina/química , Doxorrubicina/farmacologia , Liberação Controlada de Fármacos , Feminino , Humanos , Lasers , Camundongos Endogâmicos BALB C , Micelas , Nanoestruturas/administração & dosagem , Nanoestruturas/química , Fármacos Fotossensibilizantes/química , Polímeros/síntese química , Porfirinas/administração & dosagem , Porfirinas/química , Medicina de Precisão , Coelhos , Espectrometria de Fluorescência
8.
Glob Chang Biol ; 26(12): 6644-6656, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32969121

RESUMO

Alpine regions are changing rapidly due to loss of snow and ice in response to ongoing climate change. While studies have documented ecological responses in alpine lakes and streams to these changes, our ability to predict such outcomes is limited. We propose that the application of fundamental rules of life can help develop necessary predictive frameworks. We focus on four key rules of life and their interactions: the temperature dependence of biotic processes from enzymes to evolution; the wavelength dependence of the effects of solar radiation on biological and ecological processes; the ramifications of the non-arbitrary elemental stoichiometry of life; and maximization of limiting resource use efficiency across scales. As the cryosphere melts and thaws, alpine lakes and streams will experience major changes in temperature regimes, absolute and relative inputs of solar radiation in ultraviolet and photosynthetically active radiation, and relative supplies of resources (e.g., carbon, nitrogen, and phosphorus), leading to nonlinear and interactive effects on particular biota, as well as on community and ecosystem properties. We propose that applying these key rules of life to cryosphere-influenced ecosystems will reduce uncertainties about the impacts of global change and help develop an integrated global view of rapidly changing alpine environments. However, doing so will require intensive interdisciplinary collaboration and international cooperation. More broadly, the alpine cryosphere is an example of a system where improving our understanding of mechanistic underpinnings of living systems might transform our ability to predict and mitigate the impacts of ongoing global change across the daunting scope of diversity in Earth's biota and environments.


Assuntos
Lagos , Rios , Mudança Climática , Ecossistema , Neve
9.
Mol Genet Genomic Med ; 8(8): e1339, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32543126

RESUMO

BACKGROUND: Noninvasive prenatal testing (NIPT) is commonly used to screen for fetal genetic abnormalities. However, the ability of NIPT to detect copy number variations (CNVs) has not been reported. Accordingly, in this study, we analyzed the efficiency of NIPT for the detection of fetal autosomal CNVs. METHODS: Patients who were positive for autosomal CNVs by NIPT and underwent diagnostic studies by karyotype analysis and chromosomal microarray (CMA) were evaluated. Samples were divided into groups according to age, in vitro fertilization, fetal-free DNA concentration, uniquely mapped reads number, CNV size, and CNV type. RESULTS: Chromosomal microarray showed that the positive predictive value (PPV) of autosomal CNVs detected by NIPT was 14.89%. Increasing fetal DNA concentrations and uniquely mapped read numbers did not affect the PPV of CNVs detected by NIPT. There were no differences between microduplication and microdeletion PPVs detected by NIPT. The PPV of CNVs less than 10 Mb was significantly higher than that of CNVs greater than 10 Mb detected by NIPT. CONCLUSION: The accuracy of NIPT for autosomal CNVs needs to be improved.


Assuntos
Deleção Cromossômica , Transtornos Cromossômicos/genética , Duplicação Cromossômica , Cariotipagem/normas , Teste Pré-Natal não Invasivo/normas , Adulto , Transtornos Cromossômicos/diagnóstico , Variações do Número de Cópias de DNA , Feminino , Humanos , Cariotipagem/métodos , Teste Pré-Natal não Invasivo/métodos , Sensibilidade e Especificidade
10.
Nanomedicine ; 28: 102218, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32413510

RESUMO

Vascular endothelial growth factor (VEGF) has been implicated as the key regulator of tumor neovascularization. RNAi interference plays a critical role on down-regulation of VEGF, while single VEGF inhibition could not completely suppress angiogenesis and tumor growth; the effect of siRNA is temporary. To improve glioma therapy efficacy, an angiopep-2 (Ap) modified redox-responsive glycolipid-like copolymer co-delivering siVEGF and paclitaxel (PTX), termed as Ap-CSssSA/P/R complexes, was developed in this study. Ap modification significantly enhanced the distribution of Ap-CSssSA in glioma cells both in vitro and in vivo. Ap-CSssSA/P/R complexes could simultaneously deliver siVEGF and PTX into tumor cells, exhibiting great superiority in glioma growth suppression via receptor-mediated targeting delivery and cell apoptosis, accompanied with an obvious inhibition of neovascularization induced by VEGF gene silencing. The present study indicated that the combination delivery of siVEGF and PTX via Ap-modified copolymeric micelles presented a promising and safe platform for glioma targeted therapeutics.

11.
Int J Nanomedicine ; 15: 2717-2732, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32368051

RESUMO

Background: Phototherapy is a potential new candidate for glioblastoma (GBM) treatment. However inadequate phototherapy due to stability of the photosensitizer and low target specificity induces the proliferation of neovascular endothelial cells for angiogenesis and causes poor prognosis. Methods: In this study, we constructed c(RGDfk)-modified glycolipid-like micelles (cRGD-CSOSA) encapsulating indocyanine green (ICG) for dual-targeting neovascular endothelial cells and tumor cells, and cRGD-CSOSA/ICG mediated dual effect of PDT/PTT with NIR irradiation. Results: In vitro, cRGD-CSOSA/ICG inhibited cell proliferation and blocked angiogenesis with NIR irradiation. In vivo, cRGD-CSOSA/ICG exhibited increased accumulation in neovascular endothelial cells and tumor cells. Compared with that of CSOSA, the accumulation of cRGD-CSOSA in tumor tissue was further improved after dual-targeted phototherapy pretreatment. With NIR irradiation, the tumor-inhibition rate of cRGD-CSOSA/ICG was 80.00%, significantly higher than that of ICG (9.08%) and CSOSA/ICG (42.42%). Histological evaluation showed that the tumor vessels were reduced and that the apoptosis of tumor cells increased in the cRGD-CSOSA/ICG group with NIR irradiation. Conclusion: The cRGD-CSOSA/ICG nanoparticle-mediated dual-targeting phototherapy could enhance drug delivery to neovascular endothelial cells and tumor cells for anti-angiogenesis and improve the phototherapy effect of glioblastoma, providing a new strategy for glioblastoma treatment.


Assuntos
Sistemas de Liberação de Medicamentos/métodos , Glioblastoma/terapia , Verde de Indocianina/administração & dosagem , Nanopartículas/administração & dosagem , Neovascularização Patológica/tratamento farmacológico , Fototerapia/métodos , Inibidores da Angiogênese/administração & dosagem , Inibidores da Angiogênese/farmacologia , Animais , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Células Endoteliais/efeitos dos fármacos , Glioblastoma/patologia , Glicolipídeos/química , Humanos , Verde de Indocianina/química , Camundongos Nus , Micelas , Nanopartículas/química , Oligopeptídeos/química , Fármacos Fotossensibilizantes/administração & dosagem , Fármacos Fotossensibilizantes/farmacologia , Distribuição Tecidual , Ensaios Antitumorais Modelo de Xenoenxerto
12.
Arch Iran Med ; 23(4): 268-271, 2020 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-32271601

RESUMO

Since December 2019, there has been an outbreak of a novel coronavirus (COVID-19) infection in Wuhan, China. Meanwhile, the outbreak also drew attention and concern from the World Health Organization (WHO). COVID-19 is another human infectious disease caused by coronavirus. The transmission of COVID-19 is potent and the infection rate is fast. Since there is no specific drug for COVID-19, the treatment is mainly symptomatic supportive therapy. In addition, it should be pointed out that patients with severe illness need more aggressive treatment and meticulous care. Recently, accurate RNA detection has been decisive for the diagnosis of COVID-19. The development of highly sensitive RT-PCR has facilitated epidemiological studies that provide insight into the prevalence, seasonality, clinical manifestations and course of COVID-19 infection. In this review, we summarize the epidemiology and characteristics of COVID-19.


Assuntos
Betacoronavirus , Infecções por Coronavirus , Suscetibilidade a Doenças , Pandemias , Pneumonia Viral , Adolescente , Adulto , Idoso , Betacoronavirus/patogenicidade , COVID-19 , Teste para COVID-19 , Criança , Pré-Escolar , China/epidemiologia , Técnicas de Laboratório Clínico , Infecções por Coronavirus/complicações , Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/epidemiologia , Tosse/etiologia , Surtos de Doenças , Feminino , Febre/etiologia , Humanos , Lactente , Pessoa de Meia-Idade , Pneumonia Viral/complicações , Pneumonia Viral/diagnóstico , Pneumonia Viral/epidemiologia , Pneumonia Viral/etiologia , Gravidez , SARS-CoV-2 , Estudos Soroepidemiológicos , Adulto Jovem
13.
Biomaterials ; 237: 119793, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-32044521

RESUMO

Glioblastoma (GBM) is one of the malignant tumors with high mortality, and the presence of the blood brain barrier (BBB) severely limits the penetration and tissue accumulation of therapeutic agents in the lesion of GBM. Active targeting nanotechnologies can achieve efficient drug delivery in the brain, while still have a very low success rate. Here we revealed a previously unexplored phenomenon that chemotherapy with active targeting nanotechnologies causes pathological BBB functional recovery through VEGF-PI3K-AKT signaling pathway inhibition, accompanied with up-regulated expression of Claudin-5 and Occludin. Seriously, pathological BBB functional recovery induces a significant decrease of intracerebral active targeting nanotechnologies transport during GBM multiple administration, leading to chemotherapy failure in GBM therapeutics. To address this issue, we chose AKT agonist SC79 to transiently re-open functional recovering pathological BBB for continuously intracerebral delivery of brain targeted nanotherapeutics, finally producing an observable anti-GBM effect in vivo, which may offer new sight for other CNS disease treatment.


Assuntos
Neoplasias Encefálicas , Glioblastoma , Nanopartículas , Barreira Hematoencefálica , Neoplasias Encefálicas/tratamento farmacológico , Linhagem Celular Tumoral , Glioblastoma/tratamento farmacológico , Humanos , Fosfatidilinositol 3-Quinases , Proteínas Proto-Oncogênicas c-akt
14.
J Cell Mol Med ; 24(1): 227-237, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31675172

RESUMO

Previous studies have implicated the attractive and promising role of miR-590-3p to restore the cardiac function following myocardial infarction (MI). However, the molecular mechanisms for how miR-590-3p involves in cardiac fibrosis remain largely unexplored. Using human cardiac fibroblasts (HCFs) as the cellular model, luciferase report assay, mutation, EdU assay and transwell migration assay were applied to investigate the biological effects of miR-590-3p on the proliferation, differentiation, migration and collagen synthesis of cardiac fibroblasts. We found that miR-590-3p significantly suppressed cell proliferation and migration of HCFs. The mRNA and protein expression levels of α-SMA, Col1A1 and Col3A were significantly decreased by miR-590-3p. Moreover, miR-590-3p directly targeted at the 3'UTR of ZEB1 to repress the translation of ZEB1. Interfering with the expression of ZEB1 significantly decreased the cell proliferation, migration activity, mRNA and protein expressions of α-SMA, Col1A1 and Col3A. Furthermore, the expressions of miR-590-3p and ZEB1 were identified in infarct area of MI model in pigs. Collectively, miR-590-3p suppresses the cell proliferation, differentiation, migration and collagen synthesis of cardiac fibroblasts by targeting ZEB1. These works will provide useful biological information for future studies on potential roles of miR-590-3p as the therapeutic target to recover cardiac function following MI.


Assuntos
Movimento Celular , Proliferação de Células , Colágeno Tipo III/metabolismo , Colágeno Tipo I/metabolismo , Fibroblastos/patologia , MicroRNAs/genética , Infarto do Miocárdio/patologia , Homeobox 1 de Ligação a E-box em Dedo de Zinco/metabolismo , Animais , Diferenciação Celular , Colágeno Tipo I/genética , Colágeno Tipo III/genética , Modelos Animais de Doenças , Fibroblastos/metabolismo , Regulação da Expressão Gênica , Humanos , Masculino , Infarto do Miocárdio/genética , Infarto do Miocárdio/metabolismo , Suínos , Homeobox 1 de Ligação a E-box em Dedo de Zinco/genética
15.
Int J Nanomedicine ; 14: 9453-9467, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31819443

RESUMO

Background: Ovarian cancer is a common malignancy in the female reproductive system with a high mortality rate. The most important reason is multidrug resistance (MDR) of cancer chemotherapy. To reduce side effects, reverse resistance and improve efficacy for the treatment of ovarian cancer, a "core-shell" polymeric nanoparticle-mediated curcumin and paclitaxel co-delivery platform was designed. Methods: Nuclear magnetic resonance confirmed the successful grafting of polyethylenimine (PEI) and stearic acid (SA) (PEI-SA), which is designed as a mother core for transport carrier. Then, PEI-SA was modified with hyaluronic acid (HA) and physicochemical properties were examined. To understand the regulatory mechanism of resistance and measure the anti-tumor efficacy of the treatments, cytotoxicity assay, cellular uptake, P-glycoprotein (P-gp) expression and migration experiment of ovarian cancer cells were performed. In addition, adverse reactions of nanoformulation to the reproductive system were examined. Results: HA-modified drug-loaded PEI-SA had a narrow size of about 189 nm in diameters, and the particle size was suitable for endocytosis. The nanocarrier could target specifically to CD44 receptor on the ovarian cancer cell membrane. Co-delivery of curcumin and paclitaxel by the nanocarriers exerts synergistic anti-ovarian cancer effects on chemosensitive human ovarian cancer cells (SKOV3) and multi-drug resistant variant (SKOV3-TR30) in vitro, and it also shows a good anti-tumor effect in ovarian tumor-bearing nude mice. The mechanism of reversing drug resistance may be that the nanoparticles inhibit the efflux of P-gp, inhibit the migration of tumor cells, and curcumin synergistically reverses the resistance of PTX to increase antitumor activity. It is worth noting that the treatment did not cause significant toxicity to the uterus and ovaries with the observation of macroscopic and microscopic. Conclusion: This special structure of targeting nanoparticles co-delivery with the curcumin and paclitaxel can increase the anti-tumor efficacy without increasing the adverse reactions as a promising strategy for therapy ovarian cancer.


Assuntos
Curcumina/uso terapêutico , Resistencia a Medicamentos Antineoplásicos , Neoplasias Ovarianas/tratamento farmacológico , Paclitaxel/uso terapêutico , Polímeros/química , Membro 1 da Subfamília B de Cassetes de Ligação de ATP/metabolismo , Animais , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Curcumina/farmacologia , Resistência a Múltiplos Medicamentos/efeitos dos fármacos , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Feminino , Humanos , Ácido Hialurônico/química , Concentração Inibidora 50 , Camundongos Endogâmicos BALB C , Camundongos Nus , Micelas , Nanopartículas/química , Nanopartículas/ultraestrutura , Neoplasias Ovarianas/patologia , Paclitaxel/farmacologia , Polietilenoimina/química , Ácidos Esteáricos/química , Distribuição Tecidual , Resultado do Tratamento
16.
Front Cell Dev Biol ; 7: 249, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31737623

RESUMO

Myocardial infarction (MI) may cause heart failure and seriously harm human health. During the genesis of cardiac fibrosis after MI, the proliferation and migration of cardiac fibroblasts contribute to secretion and maintenance of extracellular matrix (ECM) components. Many miRNAs have been highly implicated in the processes of cardiac fibrosis after MI. However, the molecular mechanisms for how miRNAs involve in cardiac fibrosis remain largely unexplored. Based on MI model in miniature pigs, the potential miRNAs involved in MI were identified by using small RNA sequencing. Using human cardiac fibroblasts (HCFs) as a cellular model, EdU, Transwell, and the expression of ECM-related proteins were applied to investigate the cell proliferation, migration and collagen synthesis. In this study, using MI model based on miniature pigs, 84 miRNAs were identified as the differentially expressed miRNAs between MI and control group, and miR-144-3p, one of differentially expressed miRNAs, was identified to be higher expressed in infarct area. The cell proliferation, migration activity, and the mRNA and protein levels of the ECM-related genes were significantly increased by miR-144-3p mimic but significantly decreased by miR-144-3p inhibitor in cardiac fibroblasts. Furthermore, miR-144-3p was observed to repress transcription and translation of PTEN, and interfering with the expression of PTEN up-regulated the mRNAs and proteins levels of α-SMA, Col1A1, and Col3A1, and promoted the proliferation and migration of cardiac fibroblasts, which was in line with that of miR-144-3p mimics, but this observation could be reversed by miR-144-3p inhibitor. Collectively, miR-144-3p promotes cell proliferation, migration, and collagen production by targeting PTEN in cardiac fibroblasts, suggesting that miR-144-3p-mediated-PTEN regulation might be a novel therapeutic target for cardiac fibrosis after MI.

17.
J Geophys Res Atmos ; 124(6): 3143-3167, 2019 Mar 27.
Artigo em Inglês | MEDLINE | ID: mdl-31218151

RESUMO

The ability of FLake, WRF-Lake, and CoLM-Lake models in simulating the thermal features of Lake Nam Co in Central Tibetan Plateau has been evaluated in this study. All the three models with default settings exhibited distinct errors in the simulated vertical temperature profile. Then model calibration was conducted by adjusting three (four) key parameters within FLake and CoLM-Lake (WRF-Lake) in a series of sensitive experiments. Results showed that each model's performance is sensitive to the key parameters and becomes much better when adjusting all the key parameters relative to tuning single parameter. Overall, setting the temperature of maximum water density to 1.1 °C instead of 4 °C in the three models consistently leads to improved vertical thermal structure simulation during cold seasons; reducing the light extinction coefficient in FLake results in much deeper mixed layer and warmer thermocline during warm seasons in better agreement with the observation. The vertical thermal structure can be clearly improved by decreasing the light extinction coefficient and increasing the turbulent mixing in WRF-Lake and CoLM-Lake during warm seasons. Meanwhile, the modeled water temperature profile in warm seasons can be significantly improved by further replacing the constant surface roughness lengths by a parameterized scheme in WRF-Lake. Further intercomparison indicates that among the three calibrated models, FLake (WRF-Lake) performs the best to simulate the temporal evolution and intensity of temperature in the layers shallower (deeper) than 10 m, while WRF-Lake is the best at simulating the amplitude and pattern of the temperature variability at all depths.

18.
Sci Data ; 6(1): 48, 2019 05 02.
Artigo em Inglês | MEDLINE | ID: mdl-31048686

RESUMO

Lake surface water temperature (LSWT) is of vital importance for hydrological and meteorological studies. The LSWT ground measurements in the Tibetan Plateau (TP) were quite scarce because of its harsh environment. Thermal infrared remote sensing is a reliable way to calculate historical LSWT. In this study, we present the first and longest 35-year (1981-2015) daytime lake-averaged LSWT data of 97 large lakes (>80 km2 each) in the TP using the 4-km Advanced Very High Resolution Radiometer (AVHRR) Global Area Coverage (GAC) data. The LSWT dataset, taking advantage of observations from NOAA's afternoon satellites, includes three time scales, i.e., daily, 8-day-averaged, and monthly-averaged. The AVHRR-derived LSWT has a similar accuracy (RMSE = 1.7 °C) to that from other data products such as MODIS (RMSE = 1.7 °C) and ARC-Lake (RMSE = 2.0 °C). An inter-comparison of different sensors indicates that for studies such as those considering long-term climate change, the relative bias of different AVHRR sensors cannot be ignored. The proposed dataset should be, to some extent, a valuable asset for better understanding the hydrologic/climatic property and its changes over the TP.

19.
Theranostics ; 9(3): 691-707, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30809302

RESUMO

Responsive drug release in tumor mitochondria is a pre-requisite for mitochondria-targeted drug delivery systems to improve the efficacy of this promising therapeutic modality. To this end, a photothermal stimulation strategy for mitochondria-responsive drug release along with heat shock is developed to maximize the antitumor effects with minimal side effects. Methods: This strategy relies on mitochondrial-targeted delivery of doxorubicin (DOX) through a photothermal and lipophilic agent IR-780 iodide (IR780)-modified glycolipid conjugates (CSOSA), which can synergistically triggers high-level reactive oxygen species (ROS) to kill tumor cells. Results: Specifically, upon laser irradiation, the photothermal conversion by IR780-CSOSA can not only weaken the hydrophobic interaction between the core of micelles and DOX and trigger unexpected micelle swelling to release DOX in mitochondria for the amplification of ROS, but also induce mitochondria-specific heat shock to promote the fast evolution of ROS at the same locus to eradicate cancer cells in a more effective way. Furthermore, IR780-CSOSA micelles may independently realize the real-time diagnosis and imaging on multiple tumor models. Deep penetration into tumors by IR780-CSOSA/DOX micelles can be manipulated under laser irradiation. Conclusion: Such multifunctional IR780-CSOSA/DOX micelles with integration of mitochondria-responsive drug release and heat shock are demonstrated to be superior to the non-mitochondria-responsive therapy. This study opens up new avenues for the future cancer diagnosis and treatment.


Assuntos
Antibióticos Antineoplásicos/administração & dosagem , Doxorrubicina/administração & dosagem , Liberação Controlada de Fármacos , Resposta ao Choque Térmico , Indóis/uso terapêutico , Mitocôndrias/efeitos dos fármacos , Fototerapia , Animais , Antibióticos Antineoplásicos/uso terapêutico , Linhagem Celular Tumoral , Doxorrubicina/uso terapêutico , Feminino , Glicolipídeos/administração & dosagem , Glicolipídeos/uso terapêutico , Humanos , Indóis/administração & dosagem , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Micelas , Espécies Reativas de Oxigênio/metabolismo
20.
Colloids Surf B Biointerfaces ; 175: 392-402, 2019 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-30554018

RESUMO

The development of advanced gene delivery carriers with stimuli-responsive release manner for tumor therapeutics is desirable, since they can exclusively release the therapeutic gene via their structural changes in response to the specific stimuli of the target site. Moreover, interactions between macrophages and drug delivery systems (DDSs) seriously impair the treatment efficiency of DDSs, thus macrophages uptake inhibition would to some extent improve the intracellular uptake of DDSs in tumor cells. Herein, a PEGylated redox-responsive gene delivery system was developed for effective cancer therapy. PEG modified glycolipid-like polymer (P-CSSO) was electrostatic interacted with p53 to form P-CSSO/p53 complexes, which exhibited an enhanced redox sensitivity in that the disulfide bond was degraded and the rate the plasmid released from P-CSSO was 2.29-fold that of nonresponsive platform (P-CSO-SA) in 10 mM levels of glutathione (GSH). PEGylation could significantly weaken macrophages uptake, while enhance the accumulation of P-CSSO in tumor cells both in vitro and in vivo. Compared with nonresponsive complexes (P-CSO-SA/p53) (59.2%) and Lipofectamine™ 2000/p53 complexes (52.0%), the tumor inhibition rate of P-CSSO/p53 complexes (77.1%) significantly increased, which was higher than CSSO/p53 complexes (69.9%). The present study indicates that tumor microenvironment sensitive and macrophages uptake suppressive P-CSSO/p53 is a powerful in vivo gene delivery system for enhanced anticancer therapy.


Assuntos
Carcinoma Hepatocelular/tratamento farmacológico , Portadores de Fármacos/química , Técnicas de Transferência de Genes , Neoplasias Hepáticas/tratamento farmacológico , Macrófagos/metabolismo , Polímeros/administração & dosagem , Proteína Supressora de Tumor p53/administração & dosagem , Animais , Apoptose , Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/patologia , Ciclo Celular , Proliferação de Células , Quitosana/química , Feminino , Glutationa/química , Glicolipídeos/química , Humanos , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/patologia , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Micelas , Oxirredução , Polímeros/química , Células Tumorais Cultivadas , Proteína Supressora de Tumor p53/genética , Ensaios Antitumorais Modelo de Xenoenxerto
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