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1.
J Pathol Clin Res ; 2021 Sep 04.
Artigo em Inglês | MEDLINE | ID: mdl-34480529

RESUMO

Myeloproliferative neoplasms (MPNs) are characterized by upregulation of proinflammatory cytokines and immune dysregulation, which provide a reasonable basis for immunotherapy in patients. Megakaryocytes are crucial in the pathogenesis of primary myelofibrosis (PMF), the most clinically aggressive subtype of MPN. In this study, we aimed to explore PD-L1 (programmed death-ligand 1) expression in megakaryocytes and its clinical implications in PMF. We analyzed PD-L1 expression on megakaryocytes in PMF patients by immunohistochemistry and correlated the results with clinicopathological features and molecular aberrations. We employed a two-tier grading system considering both the proportion of cells positively stained and the intensity of staining. Among the 85 PMF patients, 41 (48%) showed positive PD-L1 expression on megakaryocytes with the immune-reactive score ranging from 1 to 12. PD-L1 expression correlated closely with higher white blood cell count (p = 0.045), overt myelofibrosis (p = 0.010), JAK2V617F mutation (p = 0.011), and high-molecular risk mutations (p = 0.045), leading to less favorable overall survival in these patients (hazard ratio 0.341, 95% CI 0.135-0.863, p = 0.023). Our study provides unique insights into the interaction between immunologic and molecular phenotypes in PMF patients. Future work to explore the translational potential of PD-L1 in the clinical setting is needed.

2.
ACS Nano ; 2020 Oct 07.
Artigo em Inglês | MEDLINE | ID: mdl-33025785

RESUMO

Modern development of flexible electronics has made use of bioelectronic materials as artificial tissue in vivo. As hydrogels are more similar to nerve tissue, functional hydrogels have become a promising candidate for bioelectronics. Meanwhile, interfacing functional hydrogels and living tissues is at the forefront of bioelectronics. The peripheral nerve injury often leads to paralysis, chronic pain, neurologic disorders, and even disability, because it has affected the bioelectrical signal transmission between the brain and the rest of body. Here, a kind of light-stimuli-responsive and stretchable conducting polymer hydrogel (CPH) is developed to explore artificial nerve. The conductivity of CPH can be enhanced when illuminated by near-infrared light, which can promote the conduction of the bioelectrical signal. When CPH is mechanically elongated, it still has high durability of conductivity and, thus, can accommodate unexpected strain of nerve tissues in motion. Thereby, CPH can better serve as an implant of the serious peripheral nerve injury in vivo, especially in the case that the length of the missing nerve exceeds 10 mm.

3.
Nat Commun ; 11(1): 5033, 2020 10 06.
Artigo em Inglês | MEDLINE | ID: mdl-33024092

RESUMO

Soaring cases of coronavirus disease (COVID-19) are pummeling the global health system. Overwhelmed health facilities have endeavored to mitigate the pandemic, but mortality of COVID-19 continues to increase. Here, we present a mortality risk prediction model for COVID-19 (MRPMC) that uses patients' clinical data on admission to stratify patients by mortality risk, which enables prediction of physiological deterioration and death up to 20 days in advance. This ensemble model is built using four machine learning methods including Logistic Regression, Support Vector Machine, Gradient Boosted Decision Tree, and Neural Network. We validate MRPMC in an internal validation cohort and two external validation cohorts, where it achieves an AUC of 0.9621 (95% CI: 0.9464-0.9778), 0.9760 (0.9613-0.9906), and 0.9246 (0.8763-0.9729), respectively. This model enables expeditious and accurate mortality risk stratification of patients with COVID-19, and potentially facilitates more responsive health systems that are conducive to high risk COVID-19 patients.


Assuntos
Infecções por Coronavirus/mortalidade , Aprendizado de Máquina , Pandemias , Pneumonia Viral/mortalidade , Idoso , Betacoronavirus , COVID-19 , China/epidemiologia , Feminino , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Redes Neurais de Computação , Medição de Risco , SARS-CoV-2 , Máquina de Vetores de Suporte
4.
Adv Mater ; 32(43): e2003800, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32924217

RESUMO

The degeneration of dopaminergic neurons is a major contributor to the pathogenesis of mid-brain disorders. Clinically, cell therapeutic solutions, by increasing the neurotransmitter dopamine levels in the patients, are hindered by low efficiency and/or side effects. Here, a strategy using electromagnetized nanoparticles to modulate neural plasticity and recover degenerative dopamine neurons in vivo is reported. Remarkably, electromagnetic fields generated by the nanoparticles under ultrasound stimulation modulate intracellular calcium signaling to influence synaptic plasticity and control neural behavior. Dopaminergic neuronal functions are reversed by upregulating the expression tyrosine hydroxylase, thus resulting in ameliorating the neural behavioral disorders in zebrafish. This wireless tool can serve as a viable and safe strategy for the regenerative therapy of the neurodegenerative disorders.


Assuntos
Materiais Biocompatíveis/química , Materiais Biocompatíveis/farmacologia , Encéfalo/citologia , Neurônios Dopaminérgicos/citologia , Neurônios Dopaminérgicos/efeitos dos fármacos , Fenômenos Eletromagnéticos , Plasticidade Neuronal/efeitos dos fármacos , Animais , Sinalização do Cálcio/efeitos dos fármacos , Neurônios Dopaminérgicos/patologia , Regulação Enzimológica da Expressão Gênica/efeitos dos fármacos , Espaço Intracelular/efeitos dos fármacos , Espaço Intracelular/metabolismo , Nanopartículas/química , Tirosina 3-Mono-Oxigenase/metabolismo , Ondas Ultrassônicas , Tecnologia sem Fio , Peixe-Zebra
5.
ACS Appl Mater Interfaces ; 12(25): 28759-28767, 2020 Jun 24.
Artigo em Inglês | MEDLINE | ID: mdl-32478503

RESUMO

A high-optical-resolution artificial retina system that accurately communicates with the optic nerve is the main challenge in the modern biological science and bionic field. Here, we developed a bionic artificial retina possessing phototransduction "cells" with measurements even smaller than that of the neural cells. Using the technique of micrometer processing, we constructed a pyramid-shape periodic microarray of a photoreceptor. Each "sensing cell" took advantage of polythiophene derivative/fullerene derivative (PCBM) as a photoelectric converter. Because folic acid played an essential role in eye growth, we particularly modified the polythiophene derivatives with folic acid tags. Therefore, the artificial retina could enlarge the contact area and even recognize the nerve cells to improve the consequence of nerve stimulation. We implanted the artificial retina into blinded rats' eyes. Electrophysiological analysis revealed its recovery of photosensitive function 3 months after surgery. Our work provides an innovative idea for fabricating a high-resolution bionic artificial retina system. It shows great potential in artificial intelligence and biomedicine.


Assuntos
Biônica , Polímeros/química , Retina , Animais , Ácido Fólico/química , Próteses e Implantes , Ratos , Tiofenos/química
6.
Small ; 15(17): e1900212, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30941900

RESUMO

A multimodal cancer therapeutic nanoplatform is reported. It demonstrates a promising approach to synergistically regulating the tumor microenvironment. The combination of intracellular reactive oxygen species (ROS) generated by irradiation of photosensitizer and endoplasmic reticulum (ER) stress induced by 2-deoxy-glucose (2-DG) has a profound effect on necrotic or apoptotic cell death. Especially, targeting metabolic pathway by 2-DG is a promising strategy to promote the effect of photodynamic therapy and chemotherapy. The nanoplatform can readily release its cargoes inside cancer cells and combines the advantages of ROS-sensitive releasing chemotherapeutic drugs, upregulating apoptosis pathways under ER stress, light-induced generation of cytotoxic ROS, achieving tumor accumulation, and in vivo fluorescence imaging capability. This work highlights the importance of considering multiple intracellular stresses as design parameters for nanoscale functional materials in cell biology, immune response, as well as medical treatments of cancer, Alzheimer's disease, etc.


Assuntos
Antineoplásicos/farmacologia , Desoxiglucose/farmacologia , Estresse do Retículo Endoplasmático , Luz , Microambiente Tumoral/efeitos dos fármacos , Apoptose , Terapia Combinada , Humanos , Cinética , Células MCF-7 , Nanomedicina , Necrose , Fagocitose , Fotoquimioterapia , Fármacos Fotossensibilizantes/farmacologia , Espécies Reativas de Oxigênio
7.
Bull Environ Contam Toxicol ; 98(5): 612-618, 2017 May.
Artigo em Inglês | MEDLINE | ID: mdl-28315003

RESUMO

The aim of the present study was to identify whether the responses of oxidative stress in zebrafish liver are similar to those in mammalians upon low doses of Cd2+ exposure in short durations. Fish were exposed to 1.78 µM Cd2+ (treatment) and 0.0 µM Cd2+ (control) for 0, 1, 3, and 6 h. The reactive oxygen species (ROS) and lipid peroxidation (LPO) of hepatic tissues significantly increased after 3 and 6 h of Cd2+ exposure, respectively. Antioxidants glutathione peroxidase (gpx1a), superoxide dismutase (sod), and catalase (cat) were up regulated after 1-3 h, and metallothionein isoforms (smtB and mt2) increased after 3-6 h of Cd2+ exposure. The caspase-3 and p53 mRNA expressions significantly increased threefolds after 1 h of Cd2+ exposure. Results confirmed that oxidative stress in the hepatic tissue was induced by Cd2+ within 3 h. However, anti-oxidative functions immediately up regulated, causing cell apoptosis levels to decrease after 6 h of Cd2+ exposure.


Assuntos
Antioxidantes/metabolismo , Cádmio/toxicidade , Fígado/metabolismo , Peixe-Zebra/metabolismo , Animais , Apoptose/efeitos dos fármacos , Peroxidação de Lipídeos/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Espécies Reativas de Oxigênio/metabolismo
8.
Adv Mater ; 28(48): 10684-10691, 2016 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-27731536

RESUMO

A bioinspired photodetector with signal transmissible to neuron cells is fabricated. Photoisomerization of the dye molecules embedded in the ferroelectric polymer membrane achieves electric polarization change under visible light. The photodetector realizes high sensitivity, color recognition, transient response, and 3D visual detection with resolution of 25 000 PPI, and, impressively, directly transduces the signal to neuron cells.


Assuntos
Materiais Biomiméticos/química , Materiais Biomiméticos/efeitos da radiação , Neurônios/citologia , Neurônios/efeitos da radiação , Polímeros/química , Polímeros/efeitos da radiação , Transdução de Sinais/efeitos da radiação , Animais , Cor , Corantes/química , Corantes/efeitos da radiação , Eletricidade , Isomerismo , Luz , Células PC12 , Ratos
9.
Fish Physiol Biochem ; 42(6): 1709-1720, 2016 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-27329524

RESUMO

There were not any past studies about metallothionein isoforms (smtB and mt2) having anti-oxidative functions on zebrafish after Cd2+ exposure. On the other hand, the anti-oxidative enzymatic factors such as superoxide dismutase (sod), glutathione peroxidase (gpx1a), and catalase (cat) are used as references to investigate whether the smtB and mt2 have anti-oxidative responses on the gills and brain of zebrafish after 1-6 h of 0 and 1.78 µM Cd2+ exposure. The anti-oxidative system such as sod, cat, and gpx1a mRNA expressions demonstrated a cascade response upon Cd2+-induced oxidative stress in the present study. Interestingly, the smtB mRNA expression levels increased by 3.2- to 6.1-fold, and mt2 raised by 4.1- to 11.3-fold in gills at 1 and 3 h after exposure to Cd2+, respectively. On the other hand, the smtB mRNA levels increased by 10.6- to 58.6-fold, but mt2 mRNA levels increased by 2.3- to 11.1-fold in brain at 1 and 3 h after exposure to Cd2+, respectively. In addition, both tissues showed increased apoptosis levels at 3 h, and recovery after 6 h of Cd2+ exposure. From the results, we suggest that both mt2 and smtB play a role in anti-oxidation responses within 6 h after exposure to Cd2+. In conclusion, the smtB mRNA levels have a higher response than mt2 in the brain, but both mRNA expressions appear to have a similar pattern in the gill. We suggest that smtB plays an important role to defend oxidative stress in the brain of adult zebrafish upon acute Cd2+ exposure.


Assuntos
Encéfalo/efeitos dos fármacos , Cádmio/toxicidade , Brânquias/efeitos dos fármacos , Metalotioneína/genética , Proteínas de Peixe-Zebra/genética , Peixe-Zebra/genética , Animais , Apoptose/efeitos dos fármacos , Encéfalo/metabolismo , Catalase/genética , Expressão Gênica , Brânquias/metabolismo , Glutationa Peroxidase/genética , Masculino , Isoformas de Proteínas/genética , RNA Mensageiro/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Superóxido Dismutase/genética , Poluentes Químicos da Água/toxicidade , Peixe-Zebra/metabolismo , Proteínas de Peixe-Zebra/metabolismo
10.
Artigo em Inglês | MEDLINE | ID: mdl-26025641

RESUMO

The present study seeks to detect oxidative damage and to compare anti-oxidative responses among liver, gills and brain of adult zebrafish that were cooled from 28 °C (control) to 12 °C (treatment) for 0-24 h. The lipid peroxidation of liver, gill and brain tissues significantly increased at 1h after transfer, but reactive oxygen species in the treatment group increased significantly after 24 h as compared to the control. The fish were found to develop a cascading anti-oxidative mechanism beginning with an increase in Cu/Zn-SOD levels, followed by increased CAT and GPx mRNA expressions in the three tissue types. Both smtB and mt2 mRNAs increased in the hepatic and brain tissues following 1h of cold stress, but only smtB exhibited a significant increase in the gills at 1 h and 6 h after transfer to 12 °C. Furthermore, cellular apoptosis in the brain was not evident after cold shock, but liver and gills showed cellular apoptosis at 1-3 h, with another peak in the liver at 6 h after cold shock. The results suggest that the cold shock induced oxidative stress, and the enzymatic (SOD, GPx and CAT) and non-enzymatic (mt-2 and smt-B) mRNA expressions all play a role in the resulting anti-oxidation within 1-6 h of cold shock. A functional comparison showed that the brain had the most powerful antioxidant defense system of the three tissue types since it had the highest smtB mRNA expression and a lower level of cell apoptosis than the liver and gills after exposure to cold stress.


Assuntos
Antioxidantes/metabolismo , Encéfalo/fisiologia , Temperatura Baixa , Brânquias/fisiologia , Fígado/fisiologia , Estresse Fisiológico , Peixe-Zebra/fisiologia , Animais , Apoptose , Peroxidação de Lipídeos , Espécies Reativas de Oxigênio/metabolismo
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