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1.
Technol Health Care ; 2021 Feb 26.
Artigo em Inglês | MEDLINE | ID: mdl-33682766

RESUMO

BACKGROUND: Computed tomography (CT) imaging combined with artificial intelligence is important in the diagnosis and prognosis of lung diseases. OBJECTIVE: This study aimed to investigate temporal changes of quantitative CT findings in patients with COVID-19 in three clinic types, including moderate, severe, and non-survivors, and to predict severe cases in the early stage from the results. METHODS: One hundred and two patients with confirmed COVID-19 were included in this study. Based on the time interval between onset of symptoms and the CT scan, four stages were defined in this study: Stage-1 (0 ∼7 days); Stage-2 (8 ∼ 14 days); Stage-3 (15 ∼ 21days); Stage-4 (> 21 days). Eight parameters, the infection volume and percentage of the whole lung in four different Hounsfield (HU) ranges, ((-, -750), [-750, -300), [-300, 50) and [50, +)), were calculated and compared between different groups. RESULTS: The infection volume and percentage of four HU ranges peaked in Stage-2. The highest proportion of HU [-750, 50) was found in the infected regions in non-survivors among three groups. CONCLUSIONS: The findings indicate rapid deterioration in the first week since the onset of symptoms in non-survivors. Higher proportions of HU [-750, 50) in e lesion area might be a potential bio-marker for poor prognosis in patients with COVID-19.

2.
Phytomedicine ; : 153498, 2021 Feb 12.
Artigo em Inglês | MEDLINE | ID: mdl-33640247

RESUMO

BACKGROUND: The incidence of nonalcoholic fatty liver disease (NAFLD), especially nonalcoholic steatohepatitis (NASH), has significantly increased in recent years and has become an important public health issue. However, no U.S. Food and Drug Administration (FDA)-approved first-line drug is currently available for the treatment of NAFLD and NASH; therefore, research on new drugs is currently a hot topic. Oroxylum indicum (Linn.) Kurz is extensively distributed in South China and South Asia and has many biological activities. However, its effects on NAFLD or even NASH and the corresponding mechanisms are still not clear. PURPOSE: To investigate the effect and mechanism of O. indicum seed extract (OISE) on preventing anti-inflammatory action in the progression from simple nonalcoholic fatty liver (NAFL) to NASH. METHODS: A network pharmacology method to construct ingredient-target networks and the protein-protein interaction (PPI) network of OISE in NASH were constructed for topological analyses and hub-target screening. Enrichment analyses were performed to identify the critical biological processes and signaling pathways. Simultaneously, in vitro and in vivo experiments investigated the effect and mechanism of OISE, baicalein, and chrysin on inflammation by biochemical indicator detection, luciferase reporters, pathological staining, and immunoblotting in oleic acid-stimulated HepG2 cells or in high-fat diet-fed rats. RESULTS: The network pharmacology showed that OISE prevented the development and progression of NAFL into NASH through various pathways and targets and that the nuclear factor NF-κB (NF-κB) pathway regulated by baicalein and chrysin played an important role in the treatment of NASH. In in vitro experiments, we further showed that OISE and its ingredients, namely, baicalein and chrysin, all improved the inflammatory status in oleic acid-stimulated HepG2 cells, inhibited the nuclear transcriptional activities of NF-κB, increased the IκB level, and decreased the phosphorylation level of NF-κB. Furthermore, in a high-fat diet-induced NASH model in rats, we also showed that OISE prevented the development and progression of NASH by inhibiting the nuclear transcriptional activity of NF-κB. CONCLUSION: OISE suppressed inflammatory responses and prevented the development and progression of NAFL into NASH through inhibition of the nuclear transcriptional activity of NF-κB. OISE may be used to treat NAFLD through many functions, including an increase in insulin sensitivity, a decrease in lipid accumulation in the liver, suppression of inflammation, and clearance of free radicals.

3.
Arthritis Res Ther ; 23(1): 24, 2021 01 13.
Artigo em Inglês | MEDLINE | ID: mdl-33436040

RESUMO

BACKGROUND: Lupus nephritis (LN) is one of the most severe complications of systemic lupus erythematosus (SLE). Circular RNAs (circRNAs) can act as competitive endogenous RNAs (ceRNAs) to regulate gene transcription, which is involved in mechanism of many diseases. However, the role of circRNA in lupus nephritis has been rarely reported. In this study, we aim to investigate the clinical value of circRNAs and explore the mechanism of circRNA involvement in the pathogenesis of LN. METHODS: Renal tissues from three untreated LN patients and three normal controls (NCs) were used to identify differently expressed circRNAs by next-generation sequencing (NGS). Validated assays were used by quantitative reverse transcription polymerase chain reaction (qRT-PCR). The interactions between circRNA and miRNA, or miRNA and mRNA were further determined by luciferase reporter assay. The extent of renal fibrosis between the two groups was assessed by Masson-trichome staining and immunohistochemistry (IHC) staining. RESULTS: 159 circRNAs were significantly dysregulated in LN patients compared with NCs. The expression of hsa_circ_0123190 was significantly decreased in the renal tissues of patients with LN (P = 0.014). Bio-informatics analysis and luciferase reporter assay illustrated that hsa_circ_0123190 can act as a sponge for hsa-miR-483-3p, which was also validated to interact with APLNR. APLNR mRNA expression was related with chronicity index (CI) of LN (P = 0.033, R2 = 0.452). Moreover, the fibrotic-related protein, transforming growth factor-ß1 (TGF-ß1), which was regulated by APLNR, was more pronounced in the LN group (P = 0.018). CONCLUSION: Hsa_circ_0123190 may function as a ceRNA to regulate APLNR expression by sponging hsa-miR-483-3p in LN.

4.
Mol Oncol ; 2021 Jan 28.
Artigo em Inglês | MEDLINE | ID: mdl-33508878

RESUMO

Chemotherapeutic resistance is a major obstacle in the control of advanced breast cancer (BCa). We have previously shown that small extracellular vesicles (sEVs) can transmit adriamycin resistance between BCa cells. Here, we describe that sEV-mediated TGF-ß1 intercellular transfer is involved in the drug-resistant transmission. sEVs were isolated and characterized from both sensitive and resistant cells. sEVs derived from the resistant cells were incubated with the sensitive cells and resulted in transmitting the resistant phenotype to the recipient cells. Cytokine antibody microarray revealed that most metastasis-associated cytokines present at the high levels in sEVs from the resistant cells compared with their levels in sEVs from the sensitive cells, particularly TGF-ß1 is enriched in sEVs from the resistant cells. The sEV-mediated TGF-ß1 intercellular transfer led to increasing Smad2 phosphorylation and improving cell survival by suppressing apoptosis and enhancing cell mobility. Furthermore, sEV-mediated drug-resistant transmission by delivering TGF-ß1 was validated using a zebrafish xenograft tumor model. These results elaborated that sEV-mediated TGF-ß1 intercellular transfer contributes to adriamycin resistance in BCa.

5.
Free Radic Biol Med ; 164: 85-95, 2021 Feb 20.
Artigo em Inglês | MEDLINE | ID: mdl-33418113

RESUMO

Adriamycin (ADR) resistance poses a significant challenge for successfully treating breast cancer (BCa). The mechanism underlying intrinsically acquisition of the resistance remains to be fully elucidated. Here, we describe that small extracellular vesicles (sEVs) mediated Hsp70 transfer is implicated in ADR resistance. The resistant cells derived sEVs were incubated with sensitive cells, thereby transmitting the resistant phenotype to the recipient cells. The internalization of the sEVs in the recipient cells and sEV-mediated Hsp70 transfer into mitochondria were examined by confocal microscope and transmission electron microscopy (TEM). Oxygen consumption rate (OCR) incorporated with extracellular acidification rate (ECAR) was quantified by Seahorse XF Analyzer. Mechanistically, sEVs transported Hsp70, leading to increased reactive oxygen species (ROS) and impaired mitochondria in the recipient cells, thereby inhibiting respiration but promoting glycolysis. The sEVs effect on the metabolism of the recipient cells was alleviated by silencing Hsp70 in sEVs donor cells. The aspect of sEV-Hsp70 on drug-resistant transmission was further validated by tumor zebrafish xenografts. The finding from this work suggests that sEV-mediated Hsp70 intercellular delivery enhances ADR resistance mainly through reprogramming the recipient cell energy metabolism.

6.
Sensors (Basel) ; 21(3)2021 Jan 20.
Artigo em Inglês | MEDLINE | ID: mdl-33498358

RESUMO

Semantic segmentation is one of the most widely studied problems in computer vision communities, which makes a great contribution to a variety of applications. A lot of learning-based approaches, such as Convolutional Neural Network (CNN), have made a vast contribution to this problem. While rich context information of the input images can be learned from multi-scale receptive fields by convolutions with deep layers, traditional CNNs have great difficulty in learning the geometrical relationship and distribution of objects in the RGB image due to the lack of depth information, which may lead to an inferior segmentation quality. To solve this problem, we propose a method that improves segmentation quality with depth estimation on RGB images. Specifically, we estimate depth information on RGB images via a depth estimation network, and then feed the depth map into the CNN which is able to guide the semantic segmentation. Furthermore, in order to parse the depth map and RGB images simultaneously, we construct a multi-branch encoder-decoder network and fuse the RGB and depth features step by step. Extensive experimental evaluation on four baseline networks demonstrates that our proposed method can enhance the segmentation quality considerably and obtain better performance compared to other segmentation networks.

7.
Sci Total Environ ; 761: 144192, 2021 Mar 20.
Artigo em Inglês | MEDLINE | ID: mdl-33352340

RESUMO

The catalytic boron­hydrogen bond break is usually regarded as an important reaction both in the area of environment treatment and hydrogen energy, attracting increasing attention in the past decades. Due to the limitation of conventional noble metal-based catalyst, cost-effective transition metal-based catalysts with high activity have been recently developed to become the promising candidates. Herein, the coffee ground waste was utilized as the biochar substrate loaded with ultrafine NiCoO2 nanoparticles. The abundant function groups on the biochar substrate efficiently adsorbed the metal ions and confined the crystal growth spatially, making the NiCoO2 nanoparticles highly dispersed on the surface. Moreover, the oxygen vacancies were further created in the catalysts by a vacuum-calcination strategy to boost their catalytic activity towards boron­hydrogen bond break both in the systems of 4-nitrophenol reduction by NaBH4 and hydrogen release from NH3BH3. The results indicated that the moderate presence of oxygen vacancies could effectively accelerate the boron­hydrogen bond break and the catalytic activity performed a satisfied stability during several recycles. The theoretical calculation method was adopted to analysis and discuss the mechanism within this process. This design strategy on active catalysts not only offered a novel solution of biowaste resource reuse but also demonstrated the significant role of oxygen vacancies in energy and environmental catalysis.


Assuntos
Boro , Nanopartículas , Carvão Vegetal , Café , Ligação de Hidrogênio
8.
Appl Soft Comput ; : 106897, 2020 Nov 10.
Artigo em Inglês | MEDLINE | ID: mdl-33199977

RESUMO

The sudden outbreak of novel coronavirus 2019 (COVID-19) increased the diagnostic burden of radiologists. In the time of an epidemic crisis, we hope artificial intelligence (AI) to reduce physician workload in regions with the outbreak, and improve the diagnosis accuracy for physicians before they could acquire enough experience with the new disease. In this paper, we present our experience in building and deploying an AI system that automatically analyzes CT images and provides the probability of infection to rapidly detect COVID-19 pneumonia. The proposed system which consists of classification and segmentation will save about 30%-40% of the detection time for physicians and promote the performance of COVID-19 detection. Specifically, working in an interdisciplinary team of over 30 people with medical and/or AI background, geographically distributed in Beijing and Wuhan, we are able to overcome a series of challenges (e.g. data discrepancy, testing time-effectiveness of model, data security, etc.) in this particular situation and deploy the system in four weeks. In addition, since the proposed AI system provides the priority of each CT image with probability of infection, the physicians can confirm and segregate the infected patients in time. Using 1,136 training cases (723 positives for COVID-19) from five hospitals, we are able to achieve a sensitivity of 0.974 and specificity of 0.922 on the test dataset, which included a variety of pulmonary diseases.

10.
IEEE J Biomed Health Inform ; 24(10): 2787-2797, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32816680

RESUMO

Coronavirus Disease 2019 (COVID-19) has rapidly spread worldwide since first reported. Timely diagnosis of COVID-19 is crucial both for disease control and patient care. Non-contrast thoracic computed tomography (CT) has been identified as an effective tool for the diagnosis, yet the disease outbreak has placed tremendous pressure on radiologists for reading the exams and may potentially lead to fatigue-related mis-diagnosis. Reliable automatic classification algorithms can be really helpful; however, they usually require a considerable number of COVID-19 cases for training, which is difficult to acquire in a timely manner. Meanwhile, how to effectively utilize the existing archive of non-COVID-19 data (the negative samples) in the presence of severe class imbalance is another challenge. In addition, the sudden disease outbreak necessitates fast algorithm development. In this work, we propose a novel approach for effective and efficient training of COVID-19 classification networks using a small number of COVID-19 CT exams and an archive of negative samples. Concretely, a novel self-supervised learning method is proposed to extract features from the COVID-19 and negative samples. Then, two kinds of soft-labels ('difficulty' and 'diversity') are generated for the negative samples by computing the earth mover's distances between the features of the negative and COVID-19 samples, from which data 'values' of the negative samples can be assessed. A pre-set number of negative samples are selected accordingly and fed to the neural network for training. Experimental results show that our approach can achieve superior performance using about half of the negative samples, substantially reducing model training time.


Assuntos
Betacoronavirus , Técnicas de Laboratório Clínico/estatística & dados numéricos , Infecções por Coronavirus/diagnóstico por imagem , Infecções por Coronavirus/diagnóstico , Pandemias , Pneumonia Viral/diagnóstico por imagem , Pneumonia Viral/diagnóstico , Interpretação de Imagem Radiográfica Assistida por Computador/estatística & dados numéricos , Aprendizado de Máquina Supervisionado , Tomografia Computadorizada por Raios X/estatística & dados numéricos , Algoritmos , Estudos de Coortes , Biologia Computacional , Infecções por Coronavirus/classificação , Aprendizado Profundo , Erros de Diagnóstico/estatística & dados numéricos , Humanos , Redes Neurais de Computação , Pandemias/classificação , Pneumonia Viral/classificação , Estudos Retrospectivos
11.
Cell Commun Signal ; 18(1): 128, 2020 Aug 17.
Artigo em Inglês | MEDLINE | ID: mdl-32807176

RESUMO

BACKGROUND: The activation of the NF-κB pathway plays a crucial role in the progression of breast cancer (BCa) and also involved in endocrine therapy resistance. On the contrary to the canonical NF-κB pathway, the effect of the noncanonical NF-κB pathway in BCa progression remains elusive. METHODS: BCa tumor tissues and the corresponding cell lines were examined to determine the correlation between RelB and the aggressiveness of BCa. RelB was manipulated in BCa cells to examine whether RelB promotes cell proliferation and motility by quantitation of apoptosis, cell cycle, migration, and invasion. RNA-Seq was performed to identify the critical RelB-regulated genes involved in BCa metastasis. Particularly, RelB-regulated MMP1 transcription was verified using luciferase reporter and ChIP assay. Subsequently, the effect of RelB on BCa progression was further validated using BCa mice xenograft models. RESULTS: RelB uniquely expresses at a high level in aggressive BCa tissues, particularly in triple-negative breast cancer (TNBC). RelB promotes BCa cell proliferation through increasing G1/S transition and/or decreasing apoptosis by upregulation of Cyclin D1 and Bcl-2. Additionally, RelB enhances cell mobility by activating EMT. Importantly, RelB upregulates bone metastatic protein MMP1 expression through binding to an NF-κB enhancer element located at the 5'-flanking region. Accordingly, in vivo functional validation confirmed that RelB deficiency impairs tumor growth in nude mice and inhibits lung metastasis in SCID mice. Video abstract.

12.
Clin Infect Dis ; 2020 Jul 28.
Artigo em Inglês | MEDLINE | ID: mdl-32720678

RESUMO

BACKGROUND: SARS-CoV-2 has spread worldwide and has the ability to damage multiple organs. However, information on serum SARS-CoV-2 nucleic acid(RNAemia) in patients affected by COVID-19 is limited. METHODS: Patients who admitted to Zhongnan Hospital of Wuhan University with laboratory-confirmed COVID-19, were tested SARS-COV-2 RNA in serum from January 28, 2020, to February 9, 2020. Demographic data, laboratory findings, radiological, comorbidities and outcomes data were collected and analyzed. RESULTS: 85 patients were included in the analysis. The viral load of throat swabs was significantly higher than serum samples. The highest detection of SARS-CoV-2 RNA in serum samples was between 11 to 15 days after the symptom onset. Analysis to compare with and without RNAemia provided evidence that CT and some laboratory biomarkers(total protein, BUN, LDH, hypersensitive troponin I and D-dimer) were abnormal, and that the extent of these abnormalities was generally higher in RNAemia than in non-RNAemia. Organ damages(respiratory failure, cardiac damage, renal damage and coagulopathy) were more common in RNAemia than non-RNAemia. Patients with vs without RNAemia had shorter durations from serum testing SARS-CoV-2 RNA. The mortality rate was higher among patients with vs without RNAemia. CONCLUSIONS: This study provides evidence to support that SARS-CoV-2 may have an important role in multiple organ damage, such as respiratory failure, cardiac damage, renal damage and coagulopathy. We did not find strong evidence that SARS-CoV-2 plays a role in damage of liver and the central nervous system. And our evidence suggests that RNAemia has a significant association with a higher risk of in-hospital mortality.

13.
Int J Mol Med ; 46(2): 889-897, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32626926

RESUMO

The thioredoxin interaction protein (TXNIP) has been reported to be closely related to cell oxidative stress, apoptosis and inflammation. TXNIP is involved in the regulation of oxidative stress in lung and renal injury. However, it is unclear as to whether it participates in the protective effects of sevoflurane preconditioning in cardiomyocyte injury caused by oxidative stress in ischemia. In the present study, H9c2 cardiomyocytes were cultured with 0, 1.5, 2, 3.5, 5 or 6% sevoflurane for 3 h, followed by exposure to oxygen and glucose deprivation. The results demonstrated that oxygen and glucose deprivation induced an increase in TXNIP expression, lactate dehydrogenase (LDH) release, caspase­3 activity, reactive oxygen species and malondialdehyde production. Preconditioning of the H9c2 cells with 3.5% sevoflurane suppressed TXNIP expression, LDH leakage, caspase­3 activity, reactive oxygen species and malondialdehyde production, and it promoted cell viability. TXNIP overexpression reversed the effects of 3.5% sevoflurane preconditioning on caspase­3 activity, reactive oxygen production and cell viability. Furthermore, TXNIP modulated p27 expression via PKB (protein kinase B/AKT) phosphorylation following preconditioning with 3.5% sevoflurane, and oxygen and glucose deprivation. On the whole these findings indicated that sevoflurane preconditioning protected the H9c2 cells against injury induced by oxygen and glucose deprivation by modulating TXNIP, AKT activation and p27 signaling.

14.
Rheumatol Int ; 2020 Jul 16.
Artigo em Inglês | MEDLINE | ID: mdl-32676898

RESUMO

Nervous system involvement is a rare and serious complication of Behcet's disease (BD), and the peripheral type is rarer. This article aimed to describe a case of BD with the peripheral nervous system (PNS) involvement and present a comprehensive literature review. One case of BD with PNS involvement was reported and related literature was retrospectively reviewed via PubMed/MEDLINE and Scopus database. The patient was resistant to traditional treatments, such as glucocorticoids and immunosuppressants, but had rapid quiescence after using golimumab. Our literature review suggests that the involved peripheral nerves in BD were diverse, the most common were the tibial nerves and peroneal nerves, vasculitis might be the main cause, and prednisone was still the cornerstone of treatment. TNF-α inhibitors have been increasingly used for refractory BD in recent years. This well-illustrated case demonstrates the potential benefit of golimumab to the patient with PNS involvement. Given the diversity and complexity of PNS involvement, we recommend golimumab as a new trial treatment in clinical practice.

15.
Int J Oncol ; 56(5): 1064-1074, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32319568

RESUMO

Prostate cancer (PCa) and breast cancer (BCa) are two common sex hormone­related cancer types with high rates of morbidity, and are leading causes of cancer death globally in men and women, respectively. The biological function of androgen or estrogen is a key factor for PCa or BCa tumorigenesis, respectively. Nevertheless, after hormone deprivation therapy, the majority of patients ultimately develop hormone­independent malignancies that are resistant to endocrinotherapy. It is widely recognized, therefore, that understanding of the mechanisms underlying the process from hormone dependence towards hormone independence is critical to discover molecular targets for the control of advanced PCa and BCa. This review aimed to dissect the important mechanisms involved in the therapeutic resistance of PCa and BCa. It was concluded that activation of the NF­κB pathway is an important common mechanism for metastasis and therapeutic resistance of the two types of cancer; in particular, the RelB­activated noncanonical NF­κB pathway appears to be able to lengthen and strengthen NF­κB activity, which has been a focus of recent investigations.

17.
J Virol Methods ; 282: 113774, 2019 Nov 11.
Artigo em Inglês | MEDLINE | ID: mdl-31726113

RESUMO

Porcine Reproductive and Respiratory Syndrome (PRRS), an acute infectious disease caused by the porcine reproductive and respiratory syndrome virus (PRRSV), is one of the most devastating diseases affecting the global swine industry. In order to establish a multiplex real-time PCR method for the simultaneous detection of the classical PRRSV (C-PRRSV) strain, the highly pathogenic PRRSV (HP-PRRSV) strain and NADC30-like PRRSV (NL-PRRSV) strain, we designed specific primers and TaqMan fluorescent probes based on the Nsp2 target gene sequence of these three different PRRSV strains, and designed American-type PRRSV (PRRSV-U) special primers and probes based on the relatively conserved target gene sequence of ORF7. The method established in this study can quickly and accurately detect and differentiate three types of strains of clinical tissue samples, respectively. This method plays a key role in the rapid diagnosis and determination of PRRSV.

18.
Sci Adv ; 5(11): eaay4275, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31723607

RESUMO

In the process of finding high-performance materials for organic photovoltaics (OPVs), it is meaningful if one can establish the relationship between chemical structures and photovoltaic properties even before synthesizing them. Here, we first establish a database containing over 1700 donor materials reported in the literature. Through supervised learning, our machine learning (ML) models can build up the structure-property relationship and, thus, implement fast screening of OPV materials. We explore several expressions for molecule structures, i.e., images, ASCII strings, descriptors, and fingerprints, as inputs for various ML algorithms. It is found that fingerprints with length over 1000 bits can obtain high prediction accuracy. The reliability of our approach is further verified by screening 10 newly designed donor materials. Good consistency between model predictions and experimental outcomes is obtained. The result indicates that ML is a powerful tool to prescreen new OPV materials, thus accelerating the development of the OPV field.

19.
World Neurosurg ; 132: e21-e27, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31521754

RESUMO

BACKGROUND: To investigate role of Low-dose, Early Fresh frozen plasma Transfusion (LEFT) therapy in preventing perioperative coagulopathy and improving long-term outcome after severe traumatic brain injury (TBI). METHODS: A prospective, single-center, parallel-group, randomized trial was designed. Patients with severe TBI were eligible. We used a computer-generated randomization list and closed opaque envelops to randomly allocate patients to treatment with fresh frozen plasma (5 mL/kg body weight; LEFT group) or normal saline (5 mL/kg body weight; NO LEFT group) after admission in the operating room. RESULTS: Between January 1, 2018, and November 31, 2018, 63 patients were included and randomly allocated to LEFT (n = 28) and NO LEFT (n = 35) groups. The final interim analysis included 20 patients in the LEFT group and 32 patients in the NO LEFT group. The study was terminated early for futility and safety reasons because a high proportion of patients (7 of 20; 35.0%) in the LEFT group developed new delayed traumatic intracranial hematoma after surgery compared with the NO LEFT group (3 of 32; 9.4%) (relative risk, 5.205; 95% confidence interval, 1.159-23.384; P = 0.023). Demographic characteristics and indexes of severity of brain injury were similar at baseline. CONCLUSIONS: LEFT therapy was associated with a higher incidence of delayed traumatic intracranial hematoma than normal fresh frozen plasma transfusion in patients with severe TBI. A restricted fresh frozen plasma transfusion protocol, in the right clinical setting, may be more appropriate in patients with TBIs.


Assuntos
Transfusão de Sangue/métodos , Lesões Encefálicas Traumáticas/terapia , Plasma , Idoso , Lesões Encefálicas Traumáticas/complicações , Lesões Encefálicas Traumáticas/cirurgia , Craniotomia , Método Duplo-Cego , Feminino , Hematoma Subdural Agudo/cirurgia , Hematoma Subdural Agudo/terapia , Humanos , Hemorragia Intracraniana Traumática/complicações , Hemorragias Intracranianas/etiologia , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Prevenção Secundária , Resultado do Tratamento
20.
Cancer Manag Res ; 11: 6829-6840, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31440081

RESUMO

Background: The presence of glioma stem cells (GSCs) is thought to be a key factor responsible for development of the incurable glioblastoma multiforme (GBM). GSCs are often displayed during chemotherapy resistance, except for demethoxycurcumin (DMC), a component of curcumin, which has been previously confirmed to inhibit GSCs proliferation and induce apoptosis. Purpose: The objective of this study was to identify the main mechanism underlying anti-GSCs resistance by DMC. Patients and methods: qRT-PCR was used to determine the expression of miR-145 in glioma patients and GSCs, and GSCs were transfected with miR-145 overexpressed vectors. Then, functional analyses (in vitro and in vivo) were performed to confirm the role of miR-145 and DMC in GSCs. Finally, related proteins were tested by immunohistochemistry and Western blot. Results: miR-145 was atypically low-expressed miRNA in GSCs, and could enhance GSC chemosensitivity to DMC both in vitro and in vivo. Upregulation of miR-145 in GSCs resulted in increased cell growth inhibition and apoptosis to DMC. Further research on the mechanism demonstrated that the combined effects of miR-145 and DMC were involved in the miR-145/SOX2-Wnt/ß-catenin pathway. Overexpression of SOX2 reduced GSC resistance to growth inhibition by miR-145+ DMC treatment. Conclusion: Our data strongly support an important role for miR-145 in enhancing GSC chemosensitivity to DMC by targeting the SOX2-Wnt/ß-catenin axis.

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