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1.
Int J Nanomedicine ; 19: 4279-4295, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38766658

RESUMO

Ischemic stroke, being a prominent contributor to global disability and mortality, lacks an efficacious therapeutic approach in current clinical settings. Neural stem cells (NSCs) are a type of stem cell that are only found inside the nervous system. These cells can differentiate into various kinds of cells, potentially regenerating or restoring neural networks within areas of the brain that have been destroyed. This review begins by providing an introduction to the existing therapeutic approaches for ischemic stroke, followed by an examination of the promise and limits associated with the utilization of NSCs for the treatment of ischemic stroke. Subsequently, a comprehensive overview was conducted to synthesize the existing literature on the underlying processes of neural stem cell-derived small extracellular vesicles (NSC-sEVs) transplantation therapy in the context of ischemic stroke. These mechanisms encompass neuroprotection, inflammatory response suppression, and endogenous nerve and vascular regeneration facilitation. Nevertheless, the clinical translation of NSC-sEVs is hindered by challenges such as inadequate targeting efficacy and insufficient content loading. In light of these limitations, we have compiled an overview of the advancements in utilizing modified NSC-sEVs for treating ischemic stroke based on current methods of extracellular vesicle modification. In conclusion, examining NSC-sEVs-based therapeutic approaches is anticipated to be prominent in both fundamental and applied investigations about ischemic stroke.


Assuntos
Vesículas Extracelulares , AVC Isquêmico , Células-Tronco Neurais , Humanos , AVC Isquêmico/terapia , Animais , Transplante de Células-Tronco/métodos
2.
Int J Nanomedicine ; 19: 3715-3735, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38681090

RESUMO

Liposomes, noted for their tunable particle size, surface customization, and varied drug delivery capacities, are increasingly acknowledged in therapeutic applications. These vesicles exhibit surface flexibility, enabling the incorporation of targeting moieties or peptides to achieve specific targeting and avoid lysosomal entrapment. Internally, their adaptable architecture permits the inclusion of a broad spectrum of drugs, contingent on their solubility characteristics. This study thoroughly reviews liposome fabrication, surface modifications, and drug release mechanisms post-systemic administration, with a particular emphasis on drugs crossing the blood-brain barrier (BBB) to address lesions. Additionally, the review delves into recent developments in the use of liposomes in ischemic stroke models, offering a comparative evaluation with other nanocarriers like exosomes and nano-micelles, thereby facilitating their clinical advancement.


Assuntos
Barreira Hematoencefálica , Portadores de Fármacos , AVC Isquêmico , Lipossomos , Lipossomos/química , Humanos , Barreira Hematoencefálica/metabolismo , Barreira Hematoencefálica/efeitos dos fármacos , AVC Isquêmico/tratamento farmacológico , Portadores de Fármacos/química , Portadores de Fármacos/farmacocinética , Animais , Sistemas de Liberação de Medicamentos/métodos , Liberação Controlada de Fármacos , Tamanho da Partícula
4.
Int Immunopharmacol ; 125(Pt A): 111164, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37925947

RESUMO

INTRODUCTION: The treatment of burn wounds, especially deep burn wounds, remains a major clinical challenge. Growth factors such as basic fibroblast growth factor (bFGF) and vascular endothelial growth factor A (VEGFA) show great potential in promoting the healing of damaged tissues. This study explored wound healing following targeted delivery of bFGF and VEGFA genes into deep burn wounds through a novel platelet membrane-coated nanoparticle (PM@gene-NP) complex delivery system. METHODS: First, bFGF and VEGFA genes were inserted into plasmid (pEGFP-N1) vectors. Subsequently, the assembled plasmids were loaded onto nanoparticles to form gene-loaded nanoparticle complexes, which were then wrapped with extracted platelet membrane, fully simulating the characteristics of platelets, in order to actively target sites of inflammatory damage. After administration of PM@gene-NP complexes through the tail vein of rats, a series of experiments were conducted to evaluate wound healing. RESULTS: The PM@gene-NP complexes effectively targeted the burn sites. After the administration of the PM@gene-NP complexes, the rats exhibited increased blood flow in the burn wounds, which also healed faster than control groups. Histological results showed fewer inflammatory cells in the burned skin tissue after treatment. After the wounds healed, the production of hair follicles, sebaceous glands and other skin accessories in the skin tissue increased. CONCLUSION: Our results showed that the PM@gene-NP complexes can effectively deliver gene therapy to the injured area, and this delivery system should be considered as a potential method for treating deep burns.


Assuntos
Queimaduras , Nanopartículas , Ratos , Animais , Fator A de Crescimento do Endotélio Vascular/genética , Fator A de Crescimento do Endotélio Vascular/metabolismo , Fator 2 de Crescimento de Fibroblastos/genética , Biomimética , Cicatrização/genética , Queimaduras/genética , Queimaduras/terapia , Queimaduras/patologia
5.
Sci Transl Med ; 15(716): eadh4181, 2023 10 04.
Artigo em Inglês | MEDLINE | ID: mdl-37792958

RESUMO

Clonal evolution drives cancer progression and therapeutic resistance. Recent studies have revealed divergent longitudinal trajectories in gliomas, but early molecular features steering posttreatment cancer evolution remain unclear. Here, we collected sequencing and clinical data of initial-recurrent tumor pairs from 544 adult diffuse gliomas and performed multivariate analysis to identify early molecular predictors of tumor evolution in three diffuse glioma subtypes. We found that CDKN2A deletion at initial diagnosis preceded tumor necrosis and microvascular proliferation that occur at later stages of IDH-mutant glioma. Ki67 expression at diagnosis was positively correlated with acquiring hypermutation at recurrence in the IDH-wild-type glioma. In all glioma subtypes, MYC gain or MYC-target activation at diagnosis was associated with treatment-induced hypermutation at recurrence. To predict glioma evolution, we constructed CELLO2 (Cancer EvoLution for LOngitudinal data version 2), a machine learning model integrating features at diagnosis to forecast hypermutation and progression after treatment. CELLO2 successfully stratified patients into subgroups with distinct prognoses and identified a high-risk patient group featured by MYC gain with worse post-progression survival, from the low-grade IDH-mutant-noncodel subtype. We then performed chronic temozolomide-induction experiments in glioma cell lines and isogenic patient-derived gliomaspheres and demonstrated that MYC drives temozolomide resistance by promoting hypermutation. Mechanistically, we demonstrated that, by binding to open chromatin and transcriptionally active genomic regions, c-MYC increases the vulnerability of key mismatch repair genes to treatment-induced mutagenesis, thus triggering hypermutation. This study reveals early predictors of cancer evolution under therapy and provides a resource for precision oncology targeting cancer dynamics in diffuse gliomas.


Assuntos
Neoplasias Encefálicas , Glioma , Adulto , Humanos , Neoplasias Encefálicas/terapia , Temozolomida/farmacologia , Temozolomida/uso terapêutico , Mutação/genética , Medicina de Precisão , Recidiva Local de Neoplasia/tratamento farmacológico , Glioma/tratamento farmacológico
6.
Cell Rep Med ; 4(9): 101177, 2023 09 19.
Artigo em Inglês | MEDLINE | ID: mdl-37652019

RESUMO

The role of brain immune compartments in glioma evolution remains elusive. We profile immune cells in glioma microenvironment and the matched peripheral blood from 11 patients. Glioblastoma exhibits specific infiltration of blood-originated monocytes expressing epidermal growth factor receptor (EGFR) ligands EREG and AREG, coined as tumor-associated monocytes (TAMo). TAMo infiltration is mutually exclusive with EGFR alterations (p = 0.019), while co-occurring with mesenchymal subtype (p = 4.7 × 10-7) and marking worse prognosis (p = 0.004 and 0.032 in two cohorts). Evolutionary analysis of initial-recurrent glioma pairs and single-cell study of a multi-centric glioblastoma reveal association between elevated TAMo and glioma mesenchymal transformation. Further analyses identify FOSL2 as a TAMo master regulator and demonstrates that FOSL2-EREG/AREG-EGFR signaling axis promotes glioma invasion in vitro. Collectively, we identify TAMo in tumor microenvironment and reveal its driving role in activating EGFR signaling to shape glioma evolution.


Assuntos
Glioblastoma , Glioma , Humanos , Glioblastoma/genética , Monócitos , Glioma/genética , Receptores ErbB/genética , Encéfalo , Microambiente Tumoral/genética
7.
Eur J Pharm Biopharm ; 190: 58-72, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37437667

RESUMO

BACKGROUND: Subcutaneous injection of biopharmaceutical agents or microparticles is challenging due to issues with low injection efficiency and high residual amounts. OBJECTIVE: This study aimed to determine the important factors affecting the injectability of microparticle delivery systems, establish a suitable injection system with lower injection force and higher discharge rate, and eventually develop a reliable injectability evaluation system for injectable microparticle delivery systems in vitro and in vivo. METHODS: The effects of various parameters, including particle size, injection speed, concentration of microspheres suspension, vehicle viscosity, needle length and gauge were evaluated by measuring the injection force and discharge rate. The characteristics of microparticles and rheological measurement of the suspension systems were studied. A design of experiment approach was utilized to evaluate the interaction between the microsphere suspension, vehicle viscosity and needle gauges. Both in vitro sieve tests and in vivo tests in rats were conducted to evaluate injectability. RESULTS: The in vitro test results showed that the vehicle viscosity and injection speed have varying effects on discharge rate and injection force, respectively. Particle size and needle gauge have substantial influence on injectability, larger particle size and smaller needle gauges resulting in poor injectability, while the needle gauge was found to have the greatest influence on injectability. Levonorgestrel (LNG) microsphere and glass bead were relatively uniform spherical, the glass bead had extremely smooth surface; while mesoporous silica had irregular shape. The settling rate of glass bead was the fastest, which was about 18 times faster than the LNG microsphere. The CMC-Na had a poor interaction with the LNG microspheres, glass bead and mesoporous silica and showed basically Newtonian behavior in the shear rate range of 0.1 s-1-100 s-1. When shear rate increased to more than 100 s-1, no obvious shear thinning behavior was observed. CMC-Na formed a nodule structure with whether LNG microspheres or the glass beads, which were much lower than that with the mesoporous silica in static state, among which the glass beads were the weakest. The viscosity of the suspension increased with the rising of the volume fraction of particles. Fundamentals of hydrodynamics in capillaries were referenced, such as Navier-Stokes Law equation, Krieger-Dougherty (K-D) equation, Hagen-Poiseuille equation. The best results achieved was using a suspension concentration of 120-240 mg /mL and a viscosity of 60 cP at 20 °C with 23-gauge needles. The optimized conditions were verified in vivo tests. It was proven that the LNG microsphere suspension had a good injectability when injected into subcutaneous tissue of rats. CONCLUSION: The injection system of injectable microparticle delivery system with lower injection force and higher discharge rate was established and the evaluation method was suitable for the injectability evaluation both in vivo and in vitro. Improved injectability would promote the clinical translation of microparticle delivery systems.


Assuntos
Fenômenos Mecânicos , Alta do Paciente , Humanos , Animais , Ratos , Injeções Subcutâneas , Suspensões , Microesferas , Viscosidade
8.
Phys Rev Lett ; 130(15): 153803, 2023 Apr 14.
Artigo em Inglês | MEDLINE | ID: mdl-37115865

RESUMO

Orbital angular momentum (OAM) conservation plays an important role in shaping and controlling structured light with nonlinear optics. The OAM of a beam originating from three-wave mixing should be the sum or difference of the other two inputs because no light-matter OAM exchange occurs in parametric nonlinear interactions. Here, we report anomalous OAM transfer in parametric upconversion, in which a Hermite-Gauss mode signal interacts with a specially engineered pump capable of astigmatic transformation, resulting in Laguerre-Gaussian mode sum-frequency generation (SFG). The anomaly here refers to the fact that the pump and signal both carry no net OAM, while their SFG does. We reveal experimentally that there is also an OAM inflow to the residual pump, having the same amount of that to the SFG but with the opposite sign, and thus holds system OAM conservation. This unexpected OAM selection rule improves our understanding of OAM transfer among interacting waves and may inspire new ideas for controlling OAM states via nonlinear optics.

9.
Genome Med ; 15(1): 16, 2023 03 13.
Artigo em Inglês | MEDLINE | ID: mdl-36915208

RESUMO

BACKGROUND: Although temozolomide (TMZ) has been used as a standard adjuvant chemotherapeutic agent for primary glioblastoma (GBM), treating isocitrate dehydrogenase wild-type (IDH-wt) cases remains challenging due to intrinsic and acquired drug resistance. Therefore, elucidation of the molecular mechanisms of TMZ resistance is critical for its precision application. METHODS: We stratified 69 primary IDH-wt GBM patients into TMZ-resistant (n = 29) and sensitive (n = 40) groups, using TMZ screening of the corresponding patient-derived glioma stem-like cells (GSCs). Genomic and transcriptomic features were then examined to identify TMZ-associated molecular alterations. Subsequently, we developed a machine learning (ML) model to predict TMZ response from combined signatures. Moreover, TMZ response in multisector samples (52 tumor sectors from 18 cases) was evaluated to validate findings and investigate the impact of intra-tumoral heterogeneity on TMZ efficacy. RESULTS: In vitro TMZ sensitivity of patient-derived GSCs classified patients into groups with different survival outcomes (P = 1.12e-4 for progression-free survival (PFS) and 3.63e-4 for overall survival (OS)). Moreover, we found that elevated gene expression of EGR4, PAPPA, LRRC3, and ANXA3 was associated to intrinsic TMZ resistance. In addition, other features such as 5-aminolevulinic acid negative, mesenchymal/proneural expression subtypes, and hypermutation phenomena were prone to promote TMZ resistance. In contrast, concurrent copy-number-alteration in PTEN, EGFR, and CDKN2A/B was more frequent in TMZ-sensitive samples (Fisher's exact P = 0.0102), subsequently consolidated by multi-sector sequencing analyses. Integrating all features, we trained a ML tool to segregate TMZ-resistant and sensitive groups. Notably, our method segregated IDH-wt GBM patients from The Cancer Genome Atlas (TCGA) into two groups with divergent survival outcomes (P = 4.58e-4 for PFS and 3.66e-4 for OS). Furthermore, we showed a highly heterogeneous TMZ-response pattern within each GBM patient using in vitro TMZ screening and genomic characterization of multisector GSCs. Lastly, the prediction model that evaluates the TMZ efficacy for primary IDH-wt GBMs was developed into a webserver for public usage ( http://www.wang-lab-hkust.com:3838/TMZEP ). CONCLUSIONS: We identified molecular characteristics associated to TMZ sensitivity, and illustrate the potential clinical value of a ML model trained from pharmacogenomic profiling of patient-derived GSC against IDH-wt GBMs.


Assuntos
Neoplasias Encefálicas , Glioblastoma , Glioma , Humanos , Glioblastoma/tratamento farmacológico , Glioblastoma/genética , Glioblastoma/metabolismo , Farmacogenética , Neoplasias Encefálicas/tratamento farmacológico , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/metabolismo , Temozolomida/farmacologia , Temozolomida/uso terapêutico , Glioma/genética , Resistencia a Medicamentos Antineoplásicos/genética , Fatores de Transcrição de Resposta de Crescimento Precoce
10.
Int Wound J ; 20(1): 8-17, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-35560869

RESUMO

A meta-analysis was performed to evaluate the effect of stem cells treatment in managing burn wounds. A systematic literature search up to March 2022 incorporated 24 studies reported between 2013 and 2021 including 400 animals with burn wounds at the beginning of the study; 211 were using stem cells treatment, and 189 controlled. Statistical tools like the contentious method were used within a random or fixed-influence model to establish the mean difference (MD) with 95% confidence intervals (CIs) to evaluate the influence of stem cells treatment in managing burn wounds. Stem cells treatment had a significantly higher burn wound healing rate (MD, 15.18; 95% CI, 11.29-19.07, P < .001), higher blood vessel number (MD, 12.28; 95% CI, 10.06-14.51, P < .001), higher vascular endothelial growth factor (MD, 10.24; 95% CI, 7.19-13.29, P < .001), lower interleukin-1 level (MD, -98.48; 95% CI, -155.33 to -41.63, P < .001), and lower tumour necrosis factor α level (MD, -28.71; 95% CI, -46.65 to -10.76, P < .002) compared with control in animals' models with burn wounds. Stem cells treatment had a significantly higher burn wound healing rate, higher blood vessel number, higher vascular endothelial growth factor, lower interleukin-1 level, and lower tumour necrosis factor α level compared with control in animals' models with burn wounds. Further studies are required to validate these findings.


Assuntos
Queimaduras , Fator de Necrose Tumoral alfa , Animais , Fator A de Crescimento do Endotélio Vascular , Queimaduras/terapia , Células-Tronco , Interleucina-1
11.
Neural Regen Res ; 18(2): 404-409, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-35900437

RESUMO

Our previous study demonstrated the potential therapeutic role of human neural stem cell-derived exosomes (hNSC-Exo) in ischemic stroke. Here, we loaded brain-derived neurotrophic factor (BDNF) into exosomes derived from NSCs to construct engineered exosomes (BDNF-hNSC-Exo) and compared their effects with those of hNSC-Exo on ischemic stroke both in vitro and in vivo. In a model of H2O2-induced oxidative stress in NSCs, BDNF-hNSC-Exo markedly enhanced cell survival. In a rat middle cerebral artery occlusion model, BDNF-hNSC-Exo not only inhibited the activation of microglia, but also promoted the differentiation of endogenous NSCs into neurons. These results suggest that BDNF can improve the function of NSC-derived exosomes in the treatment of ischemic stroke. Our research may support the clinical use of other neurotrophic factors for central nervous system diseases.

12.
Front Bioeng Biotechnol ; 10: 1025546, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36394011

RESUMO

Background: Keloid, also known as connective tissue hyperplasia, is a benign proliferative disorder with a global distribution. The available therapeutic interventions are steroid injections, surgical removal of keloids, radiotherapy, compression therapy, the application of cryosurgery, and many other methods. Objectives: Existing treatments or approaches for keloids may lead to similar or even larger lesions at the site of keloid excision, leading to a high recurrence rate. Therefore, this study aims at identifying a new gene-based therapy for the treatment of keloids. Methods: An ASPN-siRNA/nanoparticle combination (si-ASPN) and a negative siRNA/nanoparticle complex (NC) was developed on the basis of bioinformatics studies and used in vitro and in vivo experiments. Results: The results showed a strong correlation between the development of keloids and high expression of ASPN protein. With the expression of ASPN protein greatly reduced in keloid fibroblasts and nude mice allografts after treatment with si-ASPN, the collagen and fibroblasts were also uniform, thinner, parallel and regular. Conclusion: All the above experimental results suggest that keloid and ASPN are closely related and both fibroblast growth and metabolism of keloid are inhibited after silencing ASPN. Therefore, ASPN-siRNA delivered via nanoparticles can serve as a novel intervention therapy for the treatment of keloids.

13.
Front Cell Dev Biol ; 9: 703989, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34307384

RESUMO

Acute spinal cord injury (SCI) is a serious traumatic event to the spinal cord with considerable morbidity and mortality. This injury leads to short- and long-term variations in the spinal cord, and can have a serious effect on the patient's sensory, motor, or autonomic functions. Due to the complicated pathological process of SCI, there is currently no successful clinical treatment strategy. Exosomes, extracellular vesicles (EVs) with a double-layer membrane structure of 30-150 nm diameter, have recently been considered as critical mediators for communication between cells and tissues by transferring proteins, lipids, and nucleic acids. Further studies verified that exosomes participate in the pathophysiological process of several diseases, including cancer, neurodegenerative diseases, and cardiovascular diseases, and could have a significant impact in their treatment. As natural carriers of biologically active cargos, exosomes have emerged as pathological mediators of SCI. In this review article, we critically discuss the functions of exosomes as intracellular mediators and potential treatments in SCI and provide an outlook on future research.

14.
Mol Ther Nucleic Acids ; 22: 657-672, 2020 Dec 04.
Artigo em Inglês | MEDLINE | ID: mdl-33230464

RESUMO

The aim of the present study was to investigate the neuroprotective roles and mechanisms of the circular RNA circSHOC2 in ischemic-preconditioned astrocyte-derived exosomes (IPAS-EXOs) against ischemic stroke. We established an ischemia model based on oxygen glucose deprivation (OGD) in vitro and isolated resultant exosomes from astrocytes. Neuronal viability and apoptosis were determined by Cell Counting Kit-8 (CCK-8) assays and TUNEL (terminal deoxynucleotidyltransferase-mediated deoxyuridine triphosphate nick end labeling) staining, respectively. Autophagy-related proteins were analyzed by western blotting. We found that exosomes derived from IPAS-preconditioned medium (IPAS-CM) exerted neuroprotection. Furthermore, circSHOC2 expression was significantly upregulated in exosomes released from IPAS-CM. Overexpression of circSHOC2 in neurons yielded the same protective effects as those from IPAS-EXOs in vitro, and similar results were also observed in the middle cerebral artery occlusion (MCAO) mouse model. Mechanistically, circSHOC2 reduced neuronal apoptosis via regulating autophagy. Furthermore, circSHOC2 was found to sponge miR-7670-3p, which regulated SIRT1 expression. Transfection with an miR-7670-3p small interfering RNA (siRNA) (siRNA-7670-3p) and incubation with circSHOC2 extracellular vesicles attenuated ischemia-induced neuronal apoptosis in vivo and in vitro, while silencing of SIRT1 reversed the protective effects of exosomal circSHOC2 on hypoxic cerebral neurons. Taken together, our findings indicate that circSHOC2 in IPAS-EXOs suppressed neuronal apoptosis and ameliorated neuronal damage by regulating autophagy and acting on the miR-7670-3p/SIRT1 axis, which might contribute to a therapeutic strategy for ischemic stroke treatment.

15.
J Cell Mol Med ; 24(20): 11755-11767, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32918360

RESUMO

Our objective was to determine the molecular mechanisms by which lncRNA HOXA-AS3 regulates the biological behaviour of glioblastoma multiforme (GBM). We used an lncRNA microarray assay to identify GBM-related lncRNA expression profiles. Qrt-PCR was used to survey the levels of expression of long non-coding RNA (lncRNA) HOXA-AS3 and the target gene. Dual-luciferase reporter assays were used to investigate the interaction of lncRNA HOXA-AS3, the target gene and miRNA. Western blot analysis was used to examine the expression of USP3 and epithelial-mesenchymal transition (EMT) genes. The MTT assay, transwell assay and wound healing assay were used to analyse the effects of lncRNA HOXA-AS3 on GBM cell viability, mobility and invasiveness, respectively. Our results showed that lncRNA HOXA-AS3 was significantly up-regulated in GBM cells and could promote GBM cell proliferation, invasion and migration in vitro and in vivo. HOXA-AS was found to be associated with poor survival prognosis in glioma patients. The dual-luciferase reporter assay also revealed that lncRNA HOXA-AS3 acts as a mir-455-5p sponge by up-regulating USP3 expression to promote GBM progression. Western blot analysis showed that lncRNA HOXA-AS3 could up-regulate EMT-related gene expression in GBM. Experiments showed mir-455-5p could rescue the effect of lncRNA HOXA-AS3 on cell proliferation and invasion. The newly identified HOXA-AS3/mir-455-5p/USP3 pathway offers important clues to understanding the key mechanisms underlying the action of lncRNA HOXA-AS3 in glioblastoma.


Assuntos
Neoplasias Encefálicas/genética , Neoplasias Encefálicas/patologia , Regulação Neoplásica da Expressão Gênica , Glioblastoma/genética , Glioblastoma/patologia , MicroRNAs/genética , RNA Longo não Codificante/metabolismo , Proteases Específicas de Ubiquitina/genética , Animais , Sequência de Bases , Carcinogênese/genética , Carcinogênese/patologia , Linhagem Celular Tumoral , Proliferação de Células/genética , Transição Epitelial-Mesenquimal/genética , Humanos , Camundongos Nus , MicroRNAs/metabolismo , Invasividade Neoplásica , RNA Longo não Codificante/genética , Proteases Específicas de Ubiquitina/metabolismo , Regulação para Cima/genética , Ensaios Antitumorais Modelo de Xenoenxerto
16.
J Biomed Nanotechnol ; 16(4): 399-418, 2020 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-32970974

RESUMO

Exosomes are small extracellular vesicles of 30-150 nm diameter secreted by almost all cells. In recent years, with continuous deeper understanding of exosomes physiological functions, different reports have proven that exosomes can facilitate cell-to-cell communication by binding to target cells and transferring their contents, together with RNAs, DNAs, proteins, and lipids between cells and tissues. With advantages that exosomes can be involved in various types of physiological processes, such as blood coagulation, cellular homeostasis, inflammation, immune surveillance, stem cell differentiation, neuroprotection, and tissue regeneration and angiogenesis. Exosomes have been demonstrated that they can be applied in identification and treatment of multiple disorders such as cancers, cerebral ischemia, and respiratory infectious diseases. Importantly, researchers utilize application of exosomes in the treatment of various respiratory infectious diseases that have made some breakthrough progress. However, with the global pandemic of Coronavirus Disease 2019 (COVID-19), we have focused on applications of exosomes in respiratory infectious diseases and their serious complications, including influenza, TB, ARDS and sepsis. In this review, we explain the use of exosomes in various respiratory infectious diseases and their serious complications, and hope to provide new ideas for the treatment of new coronavirus infections.


Assuntos
Infecções por Coronavirus/terapia , Exossomos , Pneumonia Viral/terapia , Infecções Respiratórias/terapia , Betacoronavirus , COVID-19 , Comunicação Celular , Humanos , Pandemias , SARS-CoV-2
17.
Opt Lett ; 45(11): 3034-3037, 2020 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-32479452

RESUMO

The Ince-Gaussian (IG) mode, a recently discovered type of structured Gaussian beam, corresponds to eigenfunctions of the paraxial wave equation in elliptical coordinates. This propagation-invariant mode is of significance in various domains, in particular, its nonlinear transformation; however, there have been few relevant studies to date. In this Letter, we report the parametric upconversion of IG modes and associated full-field selection rule for the first time, to the best of our knowledge. We demonstrate that IG signals can be perfectly upconverted by a flattop-beam pump; in contrast, significant mode distortion occurred when using the most common Gaussian pump. Particular attention was given to the origin of the distortion, i.e., radial-mode degeneration induced by the sum-frequency generation excited by a Gaussian pump. This proof-of-principle demonstration has great significance in relevant areas, such as high-dimensional quantum frequency interfacing and upconversion imaging.

18.
J Adv Res ; 24: 435-445, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32551140

RESUMO

Transplanted neural stem cells promote neural tissue regeneration and functional recovery primarily by releasing paracrine factors. Exosomes act as important secreted paracrine molecules to deliver therapeutic agents involved in cellular functions. Here, we focused on the role of exosomes (hNSC-Exo) derived from human neural stem cells (hNSCs). We utilized the pro-inflammatory factor interferon gamma (IFN-γ) to induce the generation of altered exosomes (IFN-γ-hNSC-Exo), and compared their roles with those of hNSC-Exo and explored the potential mechanism. Importantly, IFN-γ preconditioning did not affect the secretion, but significantly altered the ability of exosomes derived from hNSCs. Moreover, IFN-γ-hNSC-Exo was functionally superior to hNSC-Exo; showed increased cell proliferation and cell survival and decreased cell apoptosis in vitro. Furthermore, IFN-γ-hNSC-Exo further exerted therapeutic effects (showed better behavioral and structural outcomes) compared to those of hNSCs-Exo in an ischemic stroke rat model. Next-generation sequencing (NGS) revealed specific exosomal miRNAs (hsa-miR-206, hsa-miR-133a-3p and hsa-miR-3656) in IFN-γ-hNSC-Exo with important roles in cell survival. Thus, our findings demonstrate that the inflammatory factor IFN-γ can regulate the functions of exosomes and highlight its role in regulating the application of neural stem cell-derived exosomes.

19.
Sci Rep ; 10(1): 199, 2020 Jan 13.
Artigo em Inglês | MEDLINE | ID: mdl-31932711

RESUMO

It is well known that when a laser is reflected from a rough surface or transmitted through a diffusive medium, a speckle pattern will be formed at a given observation plane. An important parameter of speckle is its size, which for the case of homogeneous illumination, well-known relations for its computation have been derived. This is not the case for structured light beams of non-homogeneous intensity and phase distribution. Here, we propose and demonstrate, using Hermite- and Laguerre-Gaussian light modes, that the mean size of the speckle generated by these structured light beams can be measured assuming a homogeneous illumination. We further provide with mathematical expressions that relate the speckle size to the generalised definition of "spot size". To reinforce our assessment, we compare the mean speckle size generated by structured light modes with that generated by wave fronts of constant phase and amplitude and show that in both cases the mean speckle size is almost identical. Our findings reveal a fundamental property of speckle, which will be of great relevance in many speckle-based applications and will pave the way towards the development of novel applications.

20.
Opt Express ; 27(21): 31087-31093, 2019 Oct 14.
Artigo em Inglês | MEDLINE | ID: mdl-31684348

RESUMO

Stokes polarimetry (SP) is a powerful technique that enables spatial reconstruction of the state of polarization (SoP) of a light beam using only intensity measurements. A given SoP is reconstructed from a set of four Stokes parameters, which are computed through four intensity measurements. Since all intensities must be performed on the same beam, it is common to record each intensity individually, one after the other, limiting its performance to light beams with static SoP. Here, we put forward a novel technique to extend SP to a broader set of light beams with dynamic SoP. This technique relies on the superposition principle, which enables the splitting of the input beam into identical copies, allowing the simultaneous measurement of all intensities. For this, the input beam is passed through a multiplexed digital hologram displayed on a polarization-insensitive Digital Micromirror Device (DMD) that grants independent and rapid (20 kHz) manipulation of each beam. We are able to reliably reconstruct the SoP with high fidelity and at speeds of up to 27 Hz, paving the way for real-time polarimetry of structured light.

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