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1.
J Am Chem Soc ; 146(27): 18418-18426, 2024 Jul 10.
Artigo em Inglês | MEDLINE | ID: mdl-38812275

RESUMO

Zeolite nanosheets with an extremely thin thickness featuring both unique pore systems and low diffusion resistance have the potential to achieve enhanced catalytic performance in the conversion of bulky molecular biomass. The preparation of unit-cell level nanosheets generally requires complex and costly multifunctional surfactants or an organic structure-directing agent (OSDA). Commercially available and environmentally friendly ionic liquids can also direct the structure of zeolite nanosheets by π-π stacking when these kinds of OSDA are used in large amount. Herein, we first report unit-cell-sized silicogermanate nanosheets of NS-IM-20 (UWY topology), 5 nm in thickness, which were synthesized at a relatively low ionic liquid concentration with the assistance of halide ion (Cl-). The Pd-loaded NS-IM-20 nanosheets with a hierarchical porosity and moderate acidity act as promising bifunctional catalysts for selective biomass conversion.

2.
Small ; 20(16): e2304318, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38018305

RESUMO

The long-term inflammatory microenvironment is one of the main obstacles to inhibit acute spinal cord injury (SCI) repair. The natural adipose tissue-derived extracellular matrix hydrogel shows effective anti-inflammatory regulation because of its unique protein components. However, the rapid degradation rate and removal of functional proteins during the decellularization process impair the lasting anti-inflammation function of the adipose tissue-derived hydrogel. To address this problem, adipose tissue lysate provides an effective way for SCI repair due to its abundance of anti-inflammatory and nerve regeneration-related proteins. Thereby, human adipose tissue lysate-based hydrogel (HATLH) with an appropriate degradation rate is developed, which aims to in situ long-term recruit and induce anti-inflammatory M2 macrophages through sustainedly released proteins. HATLH can recruit and polarize M2 macrophages while inhibiting pro-inflammatory M1 macrophages regardless of human or mouse-originated. The axonal growth of neuronal cells also can be effectively improved by HATLH and HATLH-induced M2 macrophages. In vivo experiments reveal that HATLH promotes endogenous M2 macrophages infiltration in large numbers (3.5 × 105/100 µL hydrogel) and maintains a long duration for over a month. In a mouse SCI model, HATLH significantly inhibits local inflammatory response, improves neuron and oligodendrocyte differentiation, enhances axonal growth and remyelination, as well as accelerates neurological function restoration.


Assuntos
Hidrogéis , Traumatismos da Medula Espinal , Humanos , Camundongos , Animais , Hidrogéis/farmacologia , Traumatismos da Medula Espinal/tratamento farmacológico , Neurônios/metabolismo , Macrófagos/metabolismo , Anti-Inflamatórios/uso terapêutico
3.
Ann Surg Oncol ; 31(5): 3086, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38319517

RESUMO

BACKGROUND: Hepatectomy combined with hepatic artery reconstruction in the operation for hilar cholangiocarcinoma (Klatskin tumor) is a challenging procedure. We present a video of left hepatectomy combined with right hepatic artery reconstruction for hilar cholangiocarcinoma. PATIENT AND METHODS: The patient was a 60-year-old male who presented with obstructive jaundice. The imaging examination showed that the confluence of left and right hepatic ducts and the wall of common hepatic duct were thickened, the local lumen was narrowed, the intrahepatic bile duct was dilated, and the right hepatic artery was invaded by tumors nearly 2.3 centimeters. Left hepatectomy with total caudate lobectomy, resection with reconstruction of right hepatic artery, hilar lymphadenectomy, and Roux-en-Y hepaticojejunostomy were performed. RESULTS: The operation time was 345 min, and the amount of bleeding was about 400 ml. There was no blood transfusion. The pathology showed poorly differentiated adenocarcinoma, with negative margins of common bile duct and right hepatic duct, and negative results of all lymph nodes. The patient's recovery was uneventful and he was discharged on postoperative day 14. The patient was disease free at 12-month follow-up evaluation. CONCLUSIONS: Hepatic artery resection and reconstruction procedure is safe and feasible for hilar cholangiocarcinoma in a highly tertiary hepatobiliary center.


Assuntos
Neoplasias dos Ductos Biliares , Colangiocarcinoma , Tumor de Klatskin , Masculino , Humanos , Pessoa de Meia-Idade , Tumor de Klatskin/cirurgia , Tumor de Klatskin/patologia , Hepatectomia/métodos , Artéria Hepática/cirurgia , Artéria Hepática/patologia , Fígado/cirurgia , Neoplasias dos Ductos Biliares/cirurgia , Neoplasias dos Ductos Biliares/patologia , Colangiocarcinoma/cirurgia
4.
Cancer Cell Int ; 24(1): 242, 2024 Jul 11.
Artigo em Inglês | MEDLINE | ID: mdl-38992667

RESUMO

As one of the significant challenges to human health, cancer has long been a focal point in medical treatment. With ongoing advancements in the field of medicine, numerous methodologies for cancer therapy have emerged, among which oncolytic virus therapy has gained considerable attention. However, oncolytic viruses still exhibit limitations. Combining them with various therapies can further enhance the efficacy of cancer treatment, offering renewed hope for patients. In recent research, scientists have recognized the promising prospect of amalgamating oncolytic virus therapy with diverse treatments, potentially surmounting the restrictions of singular approaches. The central concept of this combined therapy revolves around leveraging oncolytic virus to incite localized tumor inflammation, augmenting the immune response for immunotherapeutic efficacy. Through this approach, the patient's immune system can better recognize and eliminate cancer cells, simultaneously reducing tumor evasion mechanisms against the immune system. This review delves deeply into the latest research progress concerning the integration of oncolytic virus with diverse treatments and its role in various types of cancer therapy. We aim to analyze the mechanisms, advantages, potential challenges, and future research directions of this combination therapy. By extensively exploring this field, we aim to instill renewed hope in the fight against cancer.

5.
J Nanobiotechnology ; 22(1): 103, 2024 Mar 11.
Artigo em Inglês | MEDLINE | ID: mdl-38468261

RESUMO

BACKGROUND: Rheumatoid arthritis (RA) is a prevalent inflammatory autoimmune disease characterised by persistent inflammation and joint damage with elevated levels of reactive oxygen species (ROS). Current treatment modalities for RA have significant limitations, including poor bioavailability, severe side effects, and inadequate targeting of inflamed joints. Herein, we synthesised cerium/manganese oxide nanoparticles (NPs) as efficient drug carriers with antioxidant and catalytic-like functions that can eliminate ROS to facilitate the polarization of macrophages phenotype from M1 to M2 and alleviate inflammation. Methotrexate (MTX), a first-line RA medication, was loaded into the NPs, which were further modified with bovine serum albumin (BSA) and integrated into dissolving hyaluronic acid-based microneedles (MNs) for transdermal delivery. RESULT: This innovative approach significantly enhanced drug delivery efficiency, reduced RA inflammation, and successfully modulated macrophage polarization toward an anti-inflammatory phenotype. CONCLUSION: This research not only presents a promising drug delivery strategy for RA but also contributes broadly to the field of immune disease treatment by offering an advanced approach for macrophage phenotypic reprogramming.


Assuntos
Artrite Reumatoide , Cério , Compostos de Manganês , Nanopartículas , Óxidos , Humanos , Manganês/farmacologia , Espécies Reativas de Oxigênio/farmacologia , Artrite Reumatoide/tratamento farmacológico , Macrófagos , Inflamação , Cério/farmacologia
6.
J Nanobiotechnology ; 22(1): 201, 2024 Apr 24.
Artigo em Inglês | MEDLINE | ID: mdl-38659058

RESUMO

The utilization of extracellular vesicles (EV) in immunotherapy, aiming at suppressing peripheral immune cells responsible for inflammation, has demonstrated significant efficacy in treating various inflammatory diseases. However, the clinical application of EV has faced challenges due to their inadequate targeting ability. In addition, most of the circulating EV would be cleared by the liver, resulting in a short biological half-life after systemic administration. Inspired by the natural microvesicles (MV, as a subset of large size EV) are originated and shed from the plasma membrane, we developed the immunosuppressive MV-mimetic (MVM) from endotoxin tolerant dendritic cells (DC) by a straightforward and effective extrusion approach, in which DC surface proteins were inherited for providing the homing ability to the spleen, while αCD3 antibodies were conjugated to the MVM membranes for specific targeting of T cells. The engineered MVM carried a large number of bioactive cargos from the parental cells, which exhibited a remarkable ability to promote the induction of regulatory T cells (Treg) and polarization of anti-inflammatory M2 macrophages. Mechanistically, the elevated Treg level by MVM was mediated due to the upregulation of miR-155-3p. Furthermore, it was observed that systemic and local immunosuppression was induced by MVM in models of sepsis and rheumatoid arthritis through the improvement of Treg and M2 macrophages. These findings reveal a promising cell-free strategy for managing inflammatory responses to infections or tissue injury, thereby maintaining immune homeostasis.


Assuntos
Micropartículas Derivadas de Células , Células Dendríticas , Inflamação , Células Dendríticas/efeitos dos fármacos , Células Dendríticas/imunologia , Células Dendríticas/metabolismo , Animais , Camundongos , Inflamação/tratamento farmacológico , Micropartículas Derivadas de Células/metabolismo , Camundongos Endogâmicos C57BL , Linfócitos T Reguladores/imunologia , Linfócitos T Reguladores/efeitos dos fármacos , Vesículas Extracelulares , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Macrófagos/imunologia , Sepse/imunologia , Sepse/tratamento farmacológico , Artrite Reumatoide/tratamento farmacológico , Artrite Reumatoide/imunologia , Linfócitos T/imunologia , Linfócitos T/efeitos dos fármacos , Humanos , Imunoterapia/métodos
7.
Angew Chem Int Ed Engl ; 63(10): e202318298, 2024 Mar 04.
Artigo em Inglês | MEDLINE | ID: mdl-38240576

RESUMO

A multidimensional extra-large pore zeolite with highly hydrothermal stability, denoted as -IRT-HS, has been developed successfully, starting from Ge-rich germanosilicate precursor hydrothermally directed by a small and commercially available piperidinium-type organic structure-directing agent (OSDA). -IRT-HS, with the supermicropores, is structurally analogues to 28-membered ring -IRT topology as confirmed by various spectroscopic techniques. And it is the high-silica (Si/Ge=58) zeolite with the largest pore size as well. Notably, using acid-washed as-made Ge-rich -IRT precursor as the silicon source is crucial to restore partially collapsed structure into a stable framework by OSDA-assisted recrystallization. The calcined -IRT-HS maintains a high crystallinity, even when stored in a humid environment for extended periods or directly exposed to water. Additionally, high silica Al-containing analogue is also readily synthesized, serving as an active solid-acid catalyst in 1,3,5-triisopropylbenzene cracking reaction, yielding an impressive initial conversion up to 76.1 % much higher than conventional large-pore Beta zeolite (30.4 %). This work will pave the way for the designed synthesis of targeted high-silica zeolites with stable and extra-large pore frameworks, mimicking the structures of existing Ge-rich counterparts.

8.
J Nanobiotechnology ; 21(1): 486, 2023 Dec 18.
Artigo em Inglês | MEDLINE | ID: mdl-38105181

RESUMO

Osteoarthritis (OA) is a common degenerative joint disease characterized by progressive cartilage degradation and inflammation. In recent years, mesenchymal stem cells (MSCs) derived exosomes (MSCs-Exo) have attracted widespread attention for their potential role in modulating OA pathology. However, the unpredictable therapeutic effects of exosomes have been a significant barrier to their extensive clinical application. In this study, we investigated whether fucoidan-pretreated MSC-derived exosomes (F-MSCs-Exo) could better protect chondrocytes in osteoarthritic joints and elucidate its underlying mechanisms. In order to evaluate the role of F-MSCs-Exo in osteoarthritis, both in vitro and in vivo studies were conducted. MiRNA sequencing was employed to analyze MSCs-Exo and F-MSCs-Exo, enabling the identification of differentially expressed genes and the exploration of the underlying mechanisms behind the protective effects of F-MSCs-Exo in osteoarthritis. Compared to MSCs-Exo, F-MSCs-Exo demonstrated superior effectiveness in inhibiting inflammatory responses and extracellular matrix degradation in rat chondrocytes. Moreover, F-MSCs-Exo exhibited enhanced activation of autophagy in chondrocytes. MiRNA sequencing of both MSCs-Exo and F-MSCs-Exo revealed that miR-146b-5p emerged as a promising candidate mediator for the chondroprotective function of F-MSCs-Exo, with TRAF6 identified as its downstream target. In conclusion, our research results demonstrate that miR-146b-5p encapsulated in F-MSCs-Exo effectively inhibits TRAF6 activation, thereby suppressing inflammatory responses and extracellular matrix degradation, while promoting chondrocyte autophagy for the protection of osteoarthritic cartilage cells. Consequently, the development of a therapeutic approach combining fucoidan with MSC-derived exosomes provides a promising strategy for the clinical treatment of osteoarthritis.


Assuntos
Condrócitos , Exossomos , Células-Tronco Mesenquimais , MicroRNAs , Osteoartrite , Animais , Ratos , Condrócitos/metabolismo , Exossomos/metabolismo , MicroRNAs/metabolismo , Osteoartrite/metabolismo , Fator 6 Associado a Receptor de TNF/metabolismo , Fator 6 Associado a Receptor de TNF/farmacologia
9.
Sex Health ; 20(4): 323-329, 2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-37088545

RESUMO

BACKGROUND: This study responds to the increasing rate of HIV/AIDS and unplanned pregnancies among Chinese college students from a sociocultural perspective, and investigates the influences of sociocultural factors in shaping sex-related beliefs and acts among Chinese college students. METHODS: An online survey was conducted on a purposive sample of 1286 female college students in four cities in east and west China. RESULTS: Significant east-west disparities have emerged in the rate of sexual intercourse experience, rate of safer sex, conservative sexual values, authority sex education, unofficial sex knowledge access and HIV knowledge. A higher rate of sexual activity, but lower rate of safer sex, were found among the students in the west relative to those in the east. CONCLUSIONS: This study demonstrates that in a large country, such as China, regional disparities in economy, social development and sexual norms are salient to affect individuals' sexual behaviours.


Assuntos
Síndrome da Imunodeficiência Adquirida , Sexo Seguro , Gravidez , Humanos , Feminino , Comportamento Sexual , Coito , Estudantes , China/epidemiologia , Inquéritos e Questionários , Conhecimentos, Atitudes e Prática em Saúde
10.
Molecules ; 28(6)2023 Mar 14.
Artigo em Inglês | MEDLINE | ID: mdl-36985606

RESUMO

The key challenge in the practical application of electrochromic energy storage devices (EESDs) is the fabrication of high-performance electrode materials. Herein, we deposited K7[La(H2O)x(α2-P2W17O61)] (P2W17La) onto TiO2 nanowires (NW) to construct an NW-P2W17La nanocomposite using a layer-by-layer self-assembly method. In contrast to the pure P2W17La films, the nanocomposite exhibits enhanced electrochromic and electrochemical performance owing to the 3D sea-cucumber-like microstructure. An EESD using the NW-P2W17La film as the cathode exhibited outstanding electrochromic and energy storage properties, with high optical modulation (48.6% at 605 nm), high switching speeds (tcoloring = 15 s, tbleaching = 4 s), and high area capacitance (5.72 mF cm-2 at 0.15 mA cm-2). The device can reversibly switch between transparent and dark blue during the charge/discharge process, indicating that electrochromic contrast can be used as a quantitative indicator of the energy storage status.

11.
Angew Chem Int Ed Engl ; 62(25): e202304734, 2023 Jun 19.
Artigo em Inglês | MEDLINE | ID: mdl-37118980

RESUMO

Membrane separation is an energy-efficient and environmentally friendly process. Two-dimensional (2D) molecular sieving membranes featuring unique nanopores and low transport resistance have the potential to achieve highly permeable and selective mixture separation with low energy consumption. High-aspect-ratio zeolite nanosheets with intrinsic molecular-sieving pores perpendicular to the layers are desirable building blocks for fabricating high-performance 2D zeolite membrane. However, a wider application of 2D zeolitic membranes is restricted by the limited number of recognized zeolite nanosheets. Herein, we report a swollen layered zeolite, ECNU-28, with SZR topology and eight-member ring (8-MR, 3.0 Å×4.8 Å) pores normal to the nanosheets. It can be easily exfoliated to construct 2D membrane, which shows a high hydrogen selectivity up to 130 from natural gas and is promising for hydrogen purification and greenhouse gas capture.


Assuntos
Nanoporos , Zeolitas , Cromatografia Líquida , Hidrogênio
12.
Small ; 18(44): e2203114, 2022 11.
Artigo em Inglês | MEDLINE | ID: mdl-36148846

RESUMO

Although enormous success has been obtained for dendritic cells (DCs)-mediated antigen-specific T cells anticancer immunotherapy in the clinic, it still faces major challenging problems: insufficient DCs in tumor tissue and low response rate for tumor cells lacking antigen expression, especially in low immunogenic tumors such as pancreatic cancer. Here, these challenges are tackled through tumor microenvironment responsive nanogels with prominent tumor-targeting capability by Panc02 cell membranes coating and inhibition of tumor-derived prostaglandin E2 (PGE2), aimed at improving natural killer (NK) cells activation and inducing activated NK cells-dependent DCs recruitment. The engineered nanogels can on-demand release acetaminophen to inhibit PGE2 secretion, thus promoting the activity of NK cells for non-antigen-specific tumor elimination. Furthermore, activated NK cells can secrete chemokines as CC motif chemokine ligand 5 and X-C motif chemokine ligand 1 to recruit immature DCs, and then promote DCs maturation and induce antigen-dependent CD8+ T cells proliferation for enhancing antigen-specific immunotherapy. Notably, these responsive nanogels show excellent therapeutic effect on Panc02 pancreatic tumor growth and postsurgical recurrence, especially combination of the programmed cell death-ligand 1 checkpoint-blockade immunotherapy. Therefore, this study provides a simple strategy for enhancing low immunogenic tumors immunotherapy through an antigen-independent way and antigen-dependent way synergetically.


Assuntos
Linfócitos T CD8-Positivos , Neoplasias Pancreáticas , Humanos , Nanogéis , Células Dendríticas/metabolismo , Dinoprostona/metabolismo , Dinoprostona/farmacologia , Ligantes , Células Matadoras Naturais , Imunoterapia , Quimiocinas/metabolismo , Neoplasias Pancreáticas/terapia , Microambiente Tumoral
13.
J Nanobiotechnology ; 20(1): 404, 2022 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-36064365

RESUMO

BACKGROUND: Ulcerative colitis (UC) is a major type of inflammatory bowel disease (IBD), which could induce bloody stool, diarrhea, colon atrophy and eventually lead to colorectal cancer. The conventional daily oral administration of drugs only relieve the inflammatory response of colon in the short term, Biological agents such as antibody drugs has proven its efficiency in inhibiting colitis, while the low drug bioavailability means that large doses of antibodies are required, ultimately causing systemic toxicity. Small interfering RNA (siRNA) has significant advantages over antibody drugs in terms of safety and efficacy, and it have been widely applied as potential candidates for a variety of inflammation-related diseases. However, oral delivery of siRNA fails to overcome the degradation of the gastrointestinal environment to produce a significant therapeutic effect in ulcerative colitis. Herein, we design the hybrid delivery system that the siRNA loaded MOF encapsulated in the sodium alginate particles to overcome the barriers in the oral process. RESULTS: The hybrid delivery system (SA@MOF-siRNATNFα) was successfully constructed, and it could not only survive the low pH environment in the stomach and small intestine, but also taken up more by inflammatory macrophages, as well as released much more MOF-siRNATNFα. Moreover, SA@MOF-siRNATNFα tended to enriched and infiltrated into local colon tissues. As a result, SA@MOF-siRNATNFα significantly reduced the progression of colitis, of which the treated mice did not experience significant weight loss, bloody stools and diarrhea. CONCLUSION: We confirmed that the formulation of hydrogel-metal-organic framework hybrids could improve the protection of incorporated payload in the gastric and early small intestine, enhancing the delivery of MOF-siRNA to colon.


Assuntos
Colite Ulcerativa , Colite , Estruturas Metalorgânicas , Animais , Colite/tratamento farmacológico , Colite Ulcerativa/tratamento farmacológico , Diarreia , Hidrogéis , Camundongos , RNA Interferente Pequeno , Fator de Necrose Tumoral alfa/metabolismo
14.
J Environ Manage ; 317: 115374, 2022 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-35751234

RESUMO

Increasing both carbon (C) sequestration and food production is essential for a sustainable future. However, increasing soil C sequestration or graining yield/quality in rice (Oryza sativa L.) systems has been a tradeoff in that pursuing one goal may compromise the other goal. Field experiments were designed to evaluate methane emission and grain yield in two rice systems in southern China, including the traditional double rice with a seedling transplanting system and innovative ratoon rice with a direct seeding system. Grain yield, grain quality, methane (CH4) emission, and total organic carbon (TOC) loss rate were investigated, and yield-scaled CH4 gas emission was assessed. It is found that double rice has a higher grain yield than ratoon rice. However, the grain quality (processing, appearance of chalkiness degree and chalky grain percentage, and nutritional quality) of ratoon rice is superior to double rice, especially the ratoon crop. The yield-scaled CH4 emission of ratoon rice (0.06 kg kg-1) decreased by 49.29% than double rice (0.12 kg kg-1) throughout the growth period. Compared with the TOC loss rate of double rice (2.95 g kg-1), the rate of ratoon rice was lower (1.97 g kg-1). As a result, ratoon rice with direct seeding can not only improve grain quality but also mitigate yield-scaled CH4 gas emission and TOC loss rate of rice fields. Therefore, we suggest to use ratoon rice with a direct seeding technique to promote agricultural C sequestration.


Assuntos
Oryza , Agricultura/métodos , Carbono , Sequestro de Carbono , China , Grão Comestível , Metano/análise , Óxido Nitroso/análise , Solo
15.
J Am Chem Soc ; 143(49): 20569-20573, 2021 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-34812621

RESUMO

Nonasil (NON-type framework) zeolite, having inner large cages but only 6-ring (R) apertures, is recognized as a nonporous material without practical application values as catalysts or adsorbents. A novel bottom-up structural construction strategy assisted with well-designed Gemini-type surfactant is proposed to "open" the non cages, constructing two novel NON-related structures with accessible and stable acid sites. The obtained derivant (named as ECNU-27) possessed hierarchical porosity with short-range ordered 8-R micropores and abundant intercrystal mesopores, serving as a promising catalyst for the 1-butene cracking to lower alkenes.

16.
Clin Sci (Lond) ; 135(7): 847-864, 2021 04 16.
Artigo em Inglês | MEDLINE | ID: mdl-33755094

RESUMO

Metastasis is the main cause of poor postoperative survival of hepatocellular carcinoma (HCC) patients. Cytoskeleton rearrangement is a key event in cancer metastasis. However, the significance of microtubule (MT), one of the core components of cytoskeleton, in this process is only beginning to be revealed. Here, we find that the MT dynamics regulator end-binding protein 2 (EB2) is highly expressed in HCC and predicts poor prognosis of HCC patients. Functional studies show that EB2 overexpression promotes HCC proliferation, invasion and metastasis in vitro and in vivo, while EB2 knockdown has opposite results. Mechanistically, EB2 mediates MTs destabilization, increases Src (Src proto-oncogene non-receptor tyrosine kinase) activity, and thus facilitates extracellular signal-regulated kinase (ERK) signaling activation, which could in turn promote EB2 expression in HCC, eventually resulting in enhanced HCC proliferation, invasion and metastasis. Furthermore, U0126, a specific ERK inhibitor, could effectively inhibit EB2-mediated HCC proliferation and metastasis in vitro and in vivo. In conclusion, EB2 coordinates MT cytoskeleton and intracellular signal transduction, forming an EB2-MT-ERK positive feedback loop, to facilitate HCC proliferation, invasion and metastasis. EB2 could serve as a promising prognostic biomarker and potential therapeutic target for HCC; HCC patients with high EB2 expression may benefit from treatment with ERK inhibitors.


Assuntos
Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/patologia , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/patologia , Sistema de Sinalização das MAP Quinases , Microtúbulos/metabolismo , Animais , Carcinoma Hepatocelular/genética , Linhagem Celular , Linhagem Celular Tumoral , Proliferação de Células , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Neoplasias Hepáticas/genética , Masculino , Camundongos , Camundongos Nus , Proteínas Associadas aos Microtúbulos/metabolismo , Pessoa de Meia-Idade , Metástase Neoplásica , Proto-Oncogene Mas , Transdução de Sinais
17.
Nanotechnology ; 32(9): 095107, 2021 Feb 26.
Artigo em Inglês | MEDLINE | ID: mdl-33238258

RESUMO

In the past two decades, protein drugs have evolved to become the most successful and important strategy in cancer therapy. However, systematical administration of protein drugs may cause serious side effects. In order to prepare a new promising hydrophilic drugs carrier, we constructed a PEGylated hyaluronic acid nanogel (NI-MAHA-PEG nanogel) with hypoxia and enzymatic responsiveness, which can selectively release hydrophilic drugs interleukin-12 (IL-12) on demand in a tumor microenvironment. We observed that release of IL-12 from nanogels by hypoxia-responsive stimulation, nanogels have anti-tumor effects on melanoma. Compared with physiological conditions, the IL-12 release rate has achieved remarkable growth under hypoxic conditions. Similarly, the drug release rate increased significantly with the addition of 500 U ml-1 hyaluronidase. We provide a novel strategy to allow efficient delivery, on-demand release, and enhanced access of proteins to hypoxic tumor regions. The rational design of this nanogels drug delivery system can further explore the use of various drugs to treat many cancers.


Assuntos
Ácido Hialurônico/química , Interleucina-12/administração & dosagem , Melanoma Experimental/tratamento farmacológico , Neoplasias Cutâneas/tratamento farmacológico , Animais , Hipóxia Celular , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Feminino , Interleucina-12/química , Interleucina-12/farmacologia , Camundongos , Nanogéis , Polietilenoglicóis/química , Ensaios Antitumorais Modelo de Xenoenxerto
18.
World J Surg Oncol ; 19(1): 95, 2021 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-33785022

RESUMO

BACKGROUND: The feasibility of association liver partition and portal vein ligation for staged hepatectomy (ALPPS) for solitary huge hepatocellular carcinoma (HCC, maximal diameter ≥ 10 cm) remains uncertain. This study aims to evaluate the safety and the efficacy of ALPPS for patients with solitary huge HCC. METHODS: Twenty patients with solitary huge HCC who received ALPPS during January 2017 and December 2019 were retrospectively analyzed. The oncological characteristics of contemporaneous patients who underwent one-stage resection and transcatheter arterial chemoembolization (TACE) were compared using propensity score matching (PSM). RESULTS: All patients underwent complete two-staged ALPPS. The median future liver remnant from the ALPPS-I stage to the ALPPS-II stage increased by 64.5% (range = 22.3-221.9%) with a median interval of 18 days (range = 10-54 days). The 90-day mortality rate after the ALPPS-II stage was 5%. The 1- and 3-year overall survival (OS) rates were 70.0% and 57.4%, respectively, whereas the 1- and 3-year progression-free survival (PFS) rates were 60.0% and 43.0%, respectively. In the one-to-one PSM analysis, the long-term survival of patients who received ALPPS was significantly better than those who received TACE (OS, P = 0.007; PFS, P = 0.011) but comparable with those who underwent one-stage resection (OS, P = 0.463; PFS, P = 0.786). CONCLUSION: The surgical outcomes of ALPPS were superior to those of TACE and similar to those of one-stage resection. ALPPS is a safe and effective treatment strategy for patients with unresectable solitary huge HCC.


Assuntos
Carcinoma Hepatocelular , Quimioembolização Terapêutica , Neoplasias Hepáticas , Carcinoma Hepatocelular/cirurgia , Hepatectomia , Humanos , Ligadura , Neoplasias Hepáticas/cirurgia , Veia Porta/cirurgia , Prognóstico , Estudos Retrospectivos , Resultado do Tratamento
19.
Clin Sci (Lond) ; 133(14): 1645-1662, 2019 07 31.
Artigo em Inglês | MEDLINE | ID: mdl-31278131

RESUMO

Heart development protein with EGF-like domains 1 (HEG1) plays critical roles in embryo development and angiogenesis, which are closely related to tumor progression. However, the role of HEG1 in hepatocellular carcinoma (HCC) remains unknown. In the present study, we explored the clinical significance, biological function and regulatory mechanisms of HEG1 in HCC and found that HEG1 is significantly up-regulated in HCC cell lines and primary tumor samples. Additionally, high HEG1 expression is correlated with aggressive clinicopathological features. Patients with high HEG1 expression had shorter overall survival (OS) and disease-free survival (DFS) than those with low HEG1 expression, which indicated that HEG1 is an independent factor for poor prognosis. Lentivirus-mediated HEG1 overexpression significantly promotes HCC cell migration, invasion and epithelial-mesenchymal transition (EMT) in vitro and promotes intrahepatic metastasis, lung metastasis and EMT in vivo Opposing results are observed when HEG1 is silenced. Mechanistically, HEG1 promotes ß-catenin expression and maintains its stability, leading to intracellular ß-catenin accumulation, ß-catenin nuclear translocation and Wnt signaling activation. Loss- and gain-of-function assays further confirmed that ß-catenin is essential for HEG1-mediated promotion of HCC invasion, metastasis and EMT. In conclusion, HEG1 indicates poor prognosis; plays important roles in HCC invasion, metastasis and EMT by activating Wnt/ß-catenin signaling; and can serve as a potentially valuable prognostic biomarker and therapeutic target for HCC.


Assuntos
Carcinoma Hepatocelular/metabolismo , Transição Epitelial-Mesenquimal , Neoplasias Hepáticas/metabolismo , Proteínas de Membrana/metabolismo , beta Catenina/metabolismo , Adulto , Idoso , Animais , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/patologia , Carcinoma Hepatocelular/fisiopatologia , Linhagem Celular Tumoral , Estudos de Coortes , Intervalo Livre de Doença , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/fisiopatologia , Masculino , Proteínas de Membrana/genética , Camundongos , Camundongos Endogâmicos BALB C , Pessoa de Meia-Idade , Invasividade Neoplásica , Metástase Neoplásica , Prognóstico , Via de Sinalização Wnt , beta Catenina/genética
20.
Sensors (Basel) ; 19(12)2019 Jun 14.
Artigo em Inglês | MEDLINE | ID: mdl-31207972

RESUMO

Mobile crowdsourcing has been exploited to collect enough fingerprints for fingerprinting-based localization. Since the construction of a fingerprint database is time consuming, mobile users should be well motivated to participate in fingerprint collection task. To this end, a Walrasian equilibrium-based incentive mechanism is proposed in this paper to motivate mobile users. The proposed mechanism can eliminate the monopoly of the crowdsourcer, balance the supply and demand of fingerprint data, and maximize the benefit of all participators. In order to reach the Walrasian equilibrium, firstly, the social welfare maximization problem is constructed. To solve the original optimization problem, a dual decomposition method is employed. The maximization of social welfare is decomposed into the triple benefit optimization among the crowdsourcer, mobile users, and the whole system. Accordingly, a distributed iterative algorithm is designed. Through the simulation, the performance of the proposed incentive scheme is verified and analyzed. Simulation results demonstrated that the proposed iterative algorithm satisfies the convergence and optimality. Moreover, the self-reconstruction ability of the proposed incentive scheme was also verified, indicating that the system has strong robustness and scalability.

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