Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 52
Filtrar
1.
Artigo em Inglês | MEDLINE | ID: mdl-34508561

RESUMO

OBJECTIVES: To explore the efficacy of plasma exchange (PE) therapy in refractory idiopathic inflammatory myopathy (IIM) patients with positive anti-signal recognition particle (SRP) antibody. METHODS: Nine refractory IIM patients with positive anti-SRP antibody were enrolled, who received PE therapy at Ruijin Hospital from Octobor 2017 to December 2020. The clinical manifestations, laboratory tests, chest CT and lower extremity MRI images before and after PE therapy were compared. The treatment response was evaluated by the 2016 American College of Rheumatology (ACR)/European League Against Rheumatism (EULAR) myositis response criteria. RESULTS: 88.9% (8/9) subjects had achieved improvement by 3 weeks after PE therapy, with 55.6% (5/9) minimal improvement and 33.3% (3/9) moderate improvement. There were statistically significant improvements between baseline and after PE therapy at 3 weeks on the core set measures: physician global activity, patient global activity, Health Assessment Questionnaire (HAQ), manual muscle testing (MMT), extramuscular disease activity, and muscle enzymes activity including creatine kinase (CK), lactate dehydrogenase (LDH), aspartate transaminase (AST), except for alanine transaminase (ALT). Moreover, the chest CT showed regression of ground glass opacities and irregular linear opacities after PE therapy in four patients with interstitial lung disease. The MRI images of lower extremity in four patients showed reduction of muscle oedema after the therapy. CONCLUSION: PE therapy is effective for refractory IIM patients with positive anti-SRP antibody. It should be considered as an alternative treatment for those patients who are resistant to the combined therapy of glucocorticoids and immunosuppressive agents.

2.
Rheumatol Int ; 2021 Sep 09.
Artigo em Inglês | MEDLINE | ID: mdl-34499196

RESUMO

In view of the possible involvement of vascular endothelial growth factor-C (VEGF-C) in pathogenesis of adult-onset Still's disease (AOSD) based on our previous genome-wide association study (GWAS) results, the primary objective of this study, therefore, was to investigate the correlations between the content of VEGF-C in serum and clinical and biochemical markers of AOSD. Blood samples were collected from 80 patients with AOSD, 26 with rheumatoid arthritis (RA), 30 with systemic lupus erythematosus (SLE) and 31 healthy control subjects. The serum VEGF-C levels were determined using an enzyme-linked immunosorbent assay (ELISA). Statistical analysis and comparisons were conducted. A significantly higher serum VEGF-C level was observed in patients with AOSD than in HC. Serum VEGF-C levels had high AUC value of 0.8145 for distinguishing AOSD group from healthy group with sensitivity of 0.7097 and specificity of 0.8250. It also showed good diagnostic value to differentiate AOSD from other autoinflammatory diseases with sensitivity of 0.7500 and specificity of 0.5500. AOSD patients with fever, arthralgia, skin rash, sore throat, lymphadenopathy, splenomegaly hepatomegaly and pleuritis, had a higher level than those who did not have these symptoms (p = 0.0012, p = 0.0092, p = 0.0056, p = 0.0123, p = 0.0068, p = 0.0030, p = 0.0020, and p = 0.0018, respectively). The serum VEGF-C levels were also positively correlated with laboratory features and several cytokines related to AOSD disease activity. In conclusion, our study unveiled a close association between serum VEGF-C levels and AOSD including disease activity and clinical hematological manifestations, suggesting the potential utility of VEGF-C as a candidate biomarker to assess disease activity in AOSD.

3.
Front Immunol ; 12: 702425, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34489952

RESUMO

Antiphospholipid syndrome (APS) is a multisystem disorder characterized by thrombosis and/or recurrent fetal loss. This clinical phenotype heterogeneity may result in differences in response to treatment and prognosis. In this study, we aimed to identify primary thrombotic APS (TAPS) from primary obstetric APS (OAPS) using urine proteomics as a non-invasive method. Only patients with primary APS were enrolled in this study from 2016 to 2018 at a single clinical center in Shanghai. Urine samples from 15 patients with TAPS, 9 patients with OAPS, and 15 healthy controls (HCs) were collected and analyzed using isobaric tags for relative and absolute quantification (iTRAQ) labeling combined with liquid chromatography-tandem mass spectrometry analysis to identify differentially expressed proteins. Cluster analysis of urine proteomics identified differentiated proteins among the TAPS, OAPS, and HC groups. Urinary proteins were enriched in cytokine and cytokine receptor pathways. Representative secreted cytokines screened out (fold change >1.20, or <0.83, p<0.05) in these differentiated proteins were measured by enzyme-linked immunosorbent assay in a validation cohort. The results showed that the levels of C-X-C motif chemokine ligand 12 (CXCL12) were higher in the urine of patients with TAPS than in those with OAPS (p=0.035), while the levels of platelet-derived growth factor subunit B (PDGFB) were lower in patients with TAPS than in those with OAPS (p=0.041). In addition, correlation analysis showed that CXCL12 levels were positively correlated with immunoglobulin G anti-ß2-glycoprotein I antibody (r=0.617, p=0.016). Our results demonstrated that urinary CXCL12 and PDGFB might serve as potential non-invasive markers to differentiate primary TAPS from primary OAPS.

4.
Front Public Health ; 9: 663093, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34485213

RESUMO

Introduction: Pneumocystis pneumonia (PCP) is one of the most common opportunistic infections in HIV-infected patients. However, coinfection with Tropheryma whipplei is infrequent in AIDS patients with PCP. Case Presentation: We report a 28-year-old male AIDS patient coinfected with T. whipplei and Pneumocystis jirovecii diagnosed in the bronchoalveolar lavage. After sulfamethoxazole-trimethoprim and meropenem treatment, the patient showed clinical improvement in 2 weeks. Conclusion: Clinicians need to be alert to the occurrence of T. whipplei infection in AIDS patients with PCP and timely diagnosis and antibacterial treatments are essential. This case may help clinicians for timely diagnosis of the coinfection of T. whipplei and P. jirovecii in AIDS patients.


Assuntos
Síndrome de Imunodeficiência Adquirida , Pneumocystis carinii , Pneumonia por Pneumocystis , Síndrome de Imunodeficiência Adquirida/complicações , Adulto , Humanos , Masculino , Pneumonia por Pneumocystis/complicações , Combinação Trimetoprima e Sulfametoxazol/uso terapêutico , Tropheryma/genética
5.
Exp Cell Res ; 408(1): 112834, 2021 Sep 16.
Artigo em Inglês | MEDLINE | ID: mdl-34537206

RESUMO

Aberrant activity of bone resorbing osteoclasts plays a key role in the development of osteoporosis and cancer bone metastasis. The identification of novel and specific targets will be helpful for the development of new therapeutic strategies for bone metastasis in lung cancer. Herein, we examined microRNAs in tumor cell-derived exosomes to investigate the communication between the bone environment and tumor cells. TCGA database analysis showed that the level of miR-17-5p increased in non-small cell lung cancer tissues compared with non-tumor tissues. To investigate the function of exosomes in inducing osteoclastogenesis, osteoclast precursors were incubated with exosomes isolated from non-small cell lung cancer cell line, as well as receptor activator of NF-KB ligand and M-CSF to induce osteoclastogenesis. We found that exosomal miR-17-5p is upregulated in a non-small cell lung cancer cell line with bone metastasis compared with the original cell line. Overexpression of miR-17-5p enhanced the osteoclastogenesis of RAW264.7 cells. PTEN was identified as a direct target of miR-17-5p and showed negative effects on osteoclastogenesis. Importantly, treatment of LY294002 (an inhibitor of the PI3K/Akt pathway) attenuated miR-17-5p-mediated osteoclastogenesis effects. Taken together, our findings demonstrated that miR-17-5p promotes osteoclastogenesis through the PI3K/Akt pathway via targeting PTEN in lung cancer.

6.
BMC Infect Dis ; 21(1): 774, 2021 Aug 09.
Artigo em Inglês | MEDLINE | ID: mdl-34372792

RESUMO

BACKGROUND: The severity of COVID-19 associates with the clinical decision making and the prognosis of COVID-19 patients, therefore, early identification of patients who are likely to develop severe or critical COVID-19 is critical in clinical practice. The aim of this study was to screen severity-associated markers and construct an assessment model for predicting the severity of COVID-19. METHODS: 172 confirmed COVID-19 patients were enrolled from two designated hospitals in Hangzhou, China. Ordinal logistic regression was used to screen severity-associated markers. Least Absolute Shrinkage and Selection Operator (LASSO) regression was performed for further feature selection. Assessment models were constructed using logistic regression, ridge regression, support vector machine and random forest. The area under the receiver operator characteristic curve (AUROC) was used to evaluate the performance of different models. Internal validation was performed by using bootstrap with 500 re-sampling in the training set, and external validation was performed in the validation set for the four models, respectively. RESULTS: Age, comorbidity, fever, and 18 laboratory markers were associated with the severity of COVID-19 (all P values < 0.05). By LASSO regression, eight markers were included for the assessment model construction. The ridge regression model had the best performance with AUROCs of 0.930 (95% CI, 0.914-0.943) and 0.827 (95% CI, 0.716-0.921) in the internal and external validations, respectively. A risk score, established based on the ridge regression model, had good discrimination in all patients with an AUROC of 0.897 (95% CI 0.845-0.940), and a well-fitted calibration curve. Using the optimal cutoff value of 71, the sensitivity and specificity were 87.1% and 78.1%, respectively. A web-based assessment system was developed based on the risk score. CONCLUSIONS: Eight clinical markers of lactate dehydrogenase, C-reactive protein, albumin, comorbidity, electrolyte disturbance, coagulation function, eosinophil and lymphocyte counts were associated with the severity of COVID-19. An assessment model constructed with these eight markers would help the clinician to evaluate the likelihood of developing severity of COVID-19 at admission and early take measures on clinical treatment.


Assuntos
COVID-19 , Biomarcadores , China/epidemiologia , Humanos , Estudos Retrospectivos , Medição de Risco , SARS-CoV-2
7.
Rheumatology (Oxford) ; 60(9): 3986-4000, 2021 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-34117886

RESUMO

Adult-onset Still's disease (AOSD) is a rare, but characteristic non-familial, multi-genic systemic auto-inflammatory disorder, characterized by high spiking fever, salmon-like evanescent skin rash, polyarthritis, sore throat, hyperferritinemia and leucocytosis. The hallmark of AOSD is a cytokine storm triggered by dysregulation of inflammation. Nowadays, with advances in anti-cytokine biologic agents, the treatment of AOSD is no longer limited to NSAIDs, glucocorticoids or conventional synthetic DMARDs. In this review, we focussed on the roles of these cytokines in the pathogenesis of AOSD and summarized the current and emerging biological therapy.


Assuntos
Terapia Biológica/métodos , Doença de Still de Início Tardio/terapia , Síndrome da Liberação de Citocina/imunologia , Síndrome da Liberação de Citocina/terapia , Humanos , Doença de Still de Início Tardio/imunologia
8.
Nanomicro Lett ; 13(1): 124, 2021 May 11.
Artigo em Inglês | MEDLINE | ID: mdl-34138351

RESUMO

HIGHLIGHTS: Shape memory self-soldering tape used as conductive interconnecting material. Perfect shape and conductivity memory performance and anti-fatigue performance. Reversible strong-to-weak adhesion switched by temperature. With practical interest in the future applications of next-generation electronic devices, it is imperative to develop new conductive interconnecting materials appropriate for modern electronic devices to replace traditional rigid solder tin and silver paste of high melting temperature or corrosive solvent requirements. Herein, we design highly stretchable shape memory self-soldering conductive (SMSC) tape with reversible adhesion switched by temperature, which is composed of silver particles encapsulated by shape memory polymer. SMSC tape has perfect shape and conductivity memory property and anti-fatigue ability even under the strain of 90%. It also exhibits an initial conductivity of 2772 S cm-1 and a maximum tensile strain of ~ 100%. The maximum conductivity could be increased to 5446 S cm-1 by decreasing the strain to 17%. Meanwhile, SMSC tape can easily realize a heating induced reversible strong-to-weak adhesion transition for self-soldering circuit. The combination of stable conductivity, excellent shape memory performance, and temperature-switching reversible adhesion enables SMSC tape to serve two functions of electrode and solder simultaneously. This provides a new way for conductive interconnecting materials to meet requirements of modern electronic devices in the future.

9.
Scand J Clin Lab Invest ; 81(4): 276-281, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-33999736

RESUMO

Circulating tumor DNA (ctDNA), a fraction of cell-free DNA (cfDNA) in the circulatory system, is released from tumor cells and thus carries tumor-specific genetic signatures. Using blood-derived ctDNA to detect somatic mutations has shown great value in guiding cancer targeted therapy. Isolation and detection efficiencies are the key factors affecting the performance of ctDNA detection. To optimize and standardize our clinical practice, in this study, we analyzed the isolation efficiency of four commercial cfDNA purification kits: QIAamp circulating nucleic acid kit, AmoyDx® Circulating DNA kits, Microdiag® circulating DNA isolation kit, and MagMAX cell-free DNA isolation kit; and the detection efficiency of two mainstream domestic EGFR gene mutation detection kits: MicroDiag EGFR gene mutation detection kit and Fluorometric real-time PCR Detection Kit for the analysis of EGFR gene mutations. Reference materials and plasma samples collected from lung cancer patients and healthy volunteers were used for the analysis. Our results showed that QIAamp circulating nucleic acid kit and Microdiag® circulating DNA kit had the highest recovery rate (up to 21.25 ng/mL) for short DNA fragments of about 173 bp which is the peak length of ctDNA. For ctDNA detection, the MicroDiag® EGFR gene mutation detection kit showed the highest detection rate and sensitivity for detecting EGFR mutations at a mutant frequency of 0.5%. This work provides a reliable choice of commercial kits for the clinical application of ctDNA.

10.
J Drug Target ; 29(6): 576-591, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-33554661

RESUMO

Mitophagy is a selective form of macroautophagy in which dysfunctional and damaged mitochondria can be efficiently degraded, removed and recycled through autophagy. Selective removal of damaged or fragmented mitochondria is critical to the functional integrity of the entire mitochondrial network and cells. In past decades, numerous studies have shown that mitophagy is involved in various diseases; however, since the dual role of mitophagy in tumour development, mitophagy role in tumour is controversial, and further elucidation is needed. That is, although mitophagy has been demonstrated to contribute to carcinogenesis, cell migration, ferroptosis inhibition, cancer stemness maintenance, tumour immune escape, drug resistance, etc. during cancer progression, many research also shows that to promote cancer cell death, mitophagy can be induced physiologically or pharmacologically to maintain normal cellular metabolism and prevent cell stress responses and genome damage by diminishing mitochondrial damage, thus suppressing tumour development accompanying these changes. Signalling pathway-specific molecular mechanisms are currently of great biological significance in the identification of potential therapeutic targets. Here, we review recent progress of molecular pathways mediating mitophagy including both canonical pathways (Parkin/PINK1- and FUNDC1-mediated mitophagy) and noncanonical pathways (FKBP8-, Nrf2-, and DRP1-mediated mitophagy); and the regulation of these pathways, and abovementioned pro-cancer and pro-death roles of mitophagy. Finally, we summarise the role of mitophagy in cancer therapy. Mitophagy can potentially be acted as the target for cancer therapy by promotion or inhibition.

11.
Nano Lett ; 2021 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-33404256

RESUMO

Thermoelectric (TE) technology provides a new way to directly harvest and convert the heat continuously released from the human body. The greatest challenge for TE materials applied in wearable TE generators is compatible with the constantly changing morphology of the human body while offering a continuous and stable power output. Here, a stretchable carboxylic single-walled carbon nanotube (SWNT)-based TE fiber is prepared by an improved wet-spinning method. The stable Seebeck coefficient of the annealed carboxylic SWNT-based TE fiber is 44 µV/K even under the tensile strain of ∼30%. Experimental results show that the fiber can continue to generate constant TE potential when it is changed to various shapes. The new stretchable TE fiber has a larger Seebeck coefficient and more stretchability than existing TE fibers based on the Seebeck effect, opening a path to using the technology for a variety of practical applications.

12.
Rheumatology (Oxford) ; 60(10): 4520-4529, 2021 Oct 02.
Artigo em Inglês | MEDLINE | ID: mdl-33493278

RESUMO

OBJECTIVES: To describe the detailed characteristics and explore the potential risk factors of relapses in patients with adult-onset Still's disease (AOSD). METHODS: We enrolled patients with AOSD admitted to the Department of Rheumatology and Immunology, Ruijin Hospital from August 2016 to September 2019. Kaplan-Meier curves and the log rank test were used to estimate the cumulative relapse probability and persistent remission rate before the first occurrence of relapse. The multivariate Cox proportional hazard method was utilized to identify risk factors associated with relapses of AOSD. RESULTS: A total of 122 patients with AOSD were enrolled with a median follow-up of 12.6 months. Among them, 26 (21.3%) patients had at least one relapse. The cumulative relapse rates of AOSD patients were 14.42%, 21.79%, 24.81% and 28.57% at 6, 12, 18 and 36 months, respectively. According to the multivariate analysis, intensive treatment (odds ratio: 6.848; 95% CI: 2.441, 19.211) and macrophage activation syndrome (odds ratio: 4.020, 95% CI: 1.564, 10.322) were associated with increased risk of relapse. CONCLUSION: Our study indicated that relapses occurred in at least one-fifth of patients with AOSD, and patients with high disease severity at initial attack may have an increased risk of relapse, which needs more intensive therapy and close follow-up.

13.
Biomed Pharmacother ; 133: 110956, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33189066

RESUMO

Breast cancer is the most commonly diagnosed cancer among women. Although routine and targeted therapies have improved the survival rate, there are still considerable challenges in the treatment of breast cancer. Metastasis is the leading cause of death in patients diagnosed with breast cancer. Yes-associated protein (YAP) and/or PDZ binding motif (TAZ) are usually abnormally activated in breast cancer leading to a variety of effects on tumour promotion, such as epithelial-mesenchymal transition, cancer stem cell production and drug-resistance. The abnormal activation of YAP/TAZ can affect metastasis-related processes and promote cancer progression and metastasis by interacting with some metastasis-related factors and pathways. In this article, we summarise the evidence that YAP/TAZ regulates breast cancer metastasis, its post-translational modification mechanisms, and the latest advances in the treatment of YAP/TAZ-related breast cancer metastasis, besides providing a new strategy of YAP/TAZ-based treatment of human breast cancer.


Assuntos
Antineoplásicos/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Processamento de Proteína Pós-Traducional/efeitos dos fármacos , Proteínas Proto-Oncogênicas c-yes/metabolismo , Transativadores/metabolismo , Animais , Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Feminino , Humanos , Terapia de Alvo Molecular , Metástase Neoplásica , Domínios Proteicos , Proteínas Proto-Oncogênicas c-yes/química , Transdução de Sinais , Relação Estrutura-Atividade , Transativadores/química
14.
Rheumatology (Oxford) ; 60(1): 304-315, 2021 01 05.
Artigo em Inglês | MEDLINE | ID: mdl-32766690

RESUMO

OBJECTIVE: Liver damage is a common manifestation and can be life-threatening in adult-onset Still's disease (AOSD), an autoinflammatory disease. The hallmark of AOSD is activation of neutrophils, whose infiltration in liver is suspected to promote tissue injury. Here we aimed to identify a candidate biomarker and to validate its association with liver damage in AOSD. METHODS: Transcriptome analysis of neutrophils from treatment-naïve active AOSD patients and healthy donors was performed. Lipocalin-2 (LCN2) expression was assessed in neutrophils, plasma and liver biopsies of AOSD. The correlations of LCN2 with different variables and its ability to identify liver damage from AOSD patients were analysed. RESULTS: LCN2, a novel biomarker in hepatic inflammation, was found to be upregulated in AOSD neutrophils by RNA sequencing and confirmed at the mRNA and protein levels. Plasma levels of LCN2 were significantly higher in AOSD patients than healthy controls, RA and SLE patients. Plasma LCN2 levels were closely correlated with inflammatory markers, systemic score, HScore and cytokines. Moreover, LCN2 levels were increased in active AOSD with liver involvement and independently associated with liver dysfunction. Enhanced expression of LCN2 was detected in liver biopsies from three patients with ongoing liver injury. Furthermore, the area under the curve value of LCN2 for identifying AOSD with liver injury from other liver diseases was 0.9694. CONCLUSION: Our results reveal that neutrophils-derived LCN2 is higher in plasma and liver tissue in AOSD patients than in healthy controls, and it could serve as a potent biomarker for identifying AOSD with systemic inflammation, especially liver damage caused by hyperinflammation.


Assuntos
Lipocalina-2/metabolismo , Fígado/metabolismo , Doença de Still de Início Tardio/metabolismo , Adulto , Biomarcadores/metabolismo , Feminino , Humanos , Inflamação/metabolismo , Inflamação/patologia , Lipocalina-2/sangue , Fígado/patologia , Masculino , Pessoa de Meia-Idade , Neutrófilos/metabolismo , Índice de Gravidade de Doença , Doença de Still de Início Tardio/sangue , Doença de Still de Início Tardio/diagnóstico , Doença de Still de Início Tardio/patologia
15.
Arthritis Rheumatol ; 73(6): 1033-1043, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-33381895

RESUMO

OBJECTIVE: Adult-onset Still's disease (AOSD) is a severe autoinflammatory disease. Neutrophil activation with enhanced neutrophil extracellular trap (NET) formation is involved in the pathogenesis of AOSD. Functional leukocyte immunoglobulin-like receptor A3 (LIR-A3; gene name LILRA3) has been reported to be associated with many autoimmune diseases. We aimed to investigate the association of LILRA3 with disease susceptibility and neutrophil activation in AOSD. METHODS: The LILRA3 deletion polymorphism and its tagging single-nucleotide polymorphism rs103294 were genotyped in 164 patients with AOSD and 305 healthy controls. The impact of LILRA3 on clinical features and messenger RNA expression was evaluated. Plasma levels of LIR-A3 were detected using enzyme-linked immunosorbent assay (ELISA), and the correlation between LIR-A3 plasma levels and disease activity and levels of circulating NET-DNA was investigated. LIR-A3-induced NETs were determined using PicoGreen double-stranded DNA dye and immunofluorescence analysis in human neutrophils and a neutrophil-like differentiated NB4 cell line transfected with LIR-B2 small interfering RNA. RESULTS: The findings from genotyping demonstrated that functional LILRA3 was a risk factor for AOSD (11% in AOSD patients versus 5.6% in healthy controls; odds ratio 2.089 [95% confidence interval 1.030-4.291], P = 0.034), and associated with leukocytosis (P = 0.039) and increased levels of circulating neutrophils (P = 0.027). Functional LILRA3 messenger RNA expression was higher in the peripheral blood mononuclear cells (P < 0.0001) and neutrophils (P < 0.001) of LILRA3+/+ patients. Plasma levels of LIR-A3 were elevated in patients with AOSD (P < 0.0001) and correlated with disease activity indicators and levels of circulating NET-DNA complexes. Finally, enhanced NET formation was identified in neutrophils from healthy controls and patients with inactive AOSD after stimulation of the neutrophils with LIR-A3. Moreover, NET formation was impaired in NB4 cells after knockdown of LILRB2 gene expression. CONCLUSION: Our study provides the first evidence that functional LILRA3 is a novel genetic risk factor for the development of AOSD and that functional LIR-A3 may play a pathogenic role by inducing formation of NETs.


Assuntos
Armadilhas Extracelulares/genética , Ativação de Neutrófilo/genética , Receptores Imunológicos/genética , Doença de Still de Início Tardio/genética , Adulto , Estudos de Casos e Controles , Armadilhas Extracelulares/metabolismo , Feminino , Predisposição Genética para Doença , Humanos , Leucocitose , Masculino , Neutrófilos , Polimorfismo de Nucleotídeo Único , RNA Mensageiro/metabolismo , Receptores Imunológicos/metabolismo , Doença de Still de Início Tardio/metabolismo
16.
Int J Nanomedicine ; 15: 9447-9467, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33268987

RESUMO

Nanomedicines (NMs) have played an increasing role in cancer therapy as carriers to efficiently deliver therapeutics into tumor cells. For this application, the uptake of NMs by tumor cells is usually a prerequisite to deliver the cargo to intracellular locations, which mainly relies on endocytosis. NMs can enter cells through a variety of endocytosis pathways. Different endocytosis pathways exhibit different intracellular trafficking routes and diverse subcellular localizations. Therefore, a comprehensive understanding of endocytosis mechanisms is necessary for increasing cellular entry efficiency and to trace the fate of NMs after internalization. This review focuses on endocytosis pathways of NMs in tumor cells, mainly including clathrin- and caveolae-mediated endocytosis pathways, involving effector molecules, expression difference of those molecules between normal and tumor cells, as well as the intracellular trafficking route of corresponding endocytosis vesicles. Then, the latest strategies for NMs to actively employ endocytosis are described, including improving tumor cellular uptake of NMs by receptor-mediated endocytosis, transporter-mediated endocytosis and enabling drug activity by changing intracellular routes. Finally, active targeting strategies towards intracellular organelles are also mentioned. This review will be helpful not only in explicating endocytosis and the trafficking process of NMs and elucidating anti-tumor mechanisms inside the cell but also in rendering new ideas for the design of highly efficacious and cancer-targeted NMs.


Assuntos
Endocitose , Nanomedicina , Neoplasias/patologia , Neoplasias/terapia , Organelas/metabolismo , Animais , Cavéolas/metabolismo , Clatrina/metabolismo , Humanos
18.
Front Immunol ; 11: 563335, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33240258

RESUMO

Adult-onset Still's disease (AOSD) is an autoinflammatory disease with multisystem involvement. Early identification of patients with severe complications and those refractory to glucocorticoid is crucial to improve therapeutic strategy in AOSD. Exaggerated neutrophil activation and enhanced formation of neutrophil extracellular traps (NETs) in patients with AOSD were found to be closely associated with etiopathogenesis. In this study, we aim to investigate, to our knowledge for the first time, the clinical value of circulating NETs by machine learning to distinguish AOSD patients with organ involvement and refractory to glucocorticoid. Plasma samples were used to measure cell-free DNA, NE-DNA, MPO-DNA, and citH3-DNA complexes from training and validation sets. The training set included 40 AOSD patients and 24 healthy controls (HCs), and the validation set included 26 AOSD patients and 16 HCs. Support vector machines (SVM) were used for modeling and validation of circulating NETs signature for the diagnosis of AOSD and identifying patients refractory to low-dose glucocorticoid treatment. The training set was used to build a model, and the validation set was used to test the predictive capacity of the model. A total of four circulating NETs showed similar trends in different individuals and could distinguish patients with AOSD from HCs by SVM (AUC value: 0.88). Circulating NETs in plasma were closely correlated with systemic score, laboratory tests, and cytokines. Moreover, circulating NETs had the potential to distinguish patients with liver and cardiopulmonary system involvement. Furthermore, the AUC value of combined NETs to identify patients who were refractory to low-dose glucocorticoid was 0.917. In conclusion, circulating NETs signature provide added clinical value in monitoring AOSD patients. It may provide evidence to predict who is prone to be refractory to low-dose glucocorticoid and help to make efficient therapeutic strategy.


Assuntos
Armadilhas Extracelulares/metabolismo , Glucocorticoides/administração & dosagem , Doença de Still de Início Tardio/diagnóstico , Doença de Still de Início Tardio/tratamento farmacológico , Máquina de Vetores de Suporte , Adulto , Estudos de Casos e Controles , Ácidos Nucleicos Livres , Citocinas/sangue , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Doença de Still de Início Tardio/sangue , Doença de Still de Início Tardio/imunologia , Resultado do Tratamento , Adulto Jovem
19.
Front Neurol ; 11: 577128, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33224091

RESUMO

Introduction: Autonomic dysfunction is a common and disabling non-motor symptom of Parkinson's disease (PD). We aimed to understand autonomic dysfunction in PD motor subtypes, the pattern of sympathetic skin response (SSR) to motor asymmetry, and the association of SSR with autonomic and motor dysfunctions. Methods: A total of 101 PD patients of Han Chinese were included. Unified PD rating scale (UPDRS), scales for outcomes in PD-autonomic symptoms (SCOPA-AUT), orthostatic hypotension, and SSR were evaluated. Results: SCOPA-AUT and incidences of orthostatic hypotension and absent SSR were worse in the subtype of postural instability gait disorder (PIGD) than the subtypes of tremor dominant and intermediate. SSR latency and amplitude were asymmetrical corresponding to the accentuation of motor severity. Patients with absent SSR had worse UPDRS and SCOPA-AUT scores. SSR parameters of the severe side in patients with SSR showed no independent association with the scores. Conclusion: Our results support that autonomic dysfunction is more severe in the PIGD than other subtypes and demonstrate an asymmetry of SSR in PD patients. Absent SSR may indicate worse autonomic and motor symptoms, but SSR parameters are not sufficient to evaluate the severity of the dysfunctions.

20.
J Neurovirol ; 26(6): 952-956, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-32839952

RESUMO

Progressive multifocal leukoencephalopathy (PML) is a rare demyelinating disease of the central nervous system caused by JC virus (JCV) and is difficult to diagnose. We report on a male HIV-positive patient with PML finally diagnosed by 3 times lumbar punctures and 2 times brain biopsies. Negative results of JCV-PCR in cerebrospinal fluid (CSF) do not rule out the diagnosis of PML when clinical manifestations and neuroimaging features suspected PML. It is necessary to obtain new CSF and make repeat tests and even perform brain biopsy.

SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...