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1.
J Neuroinflammation ; 21(1): 43, 2024 Feb 05.
Artículo en Inglés | MEDLINE | ID: mdl-38317227

RESUMEN

Glaucoma is a complex neurodegenerative disorder characterized by the progressive loss of retinal ganglion cells (RGC) and optic nerve axons, leading to irreversible visual impairment. Despite its clinical significance, the underlying mechanisms of glaucoma pathogenesis remain poorly understood. In this study, we aimed to unravel the multifaceted nature of glaucoma by investigating the interaction between T cells and retinas. By utilizing clinical samples, murine glaucoma models, and T cell transfer models, we made several key findings. Firstly, we observed that CD4+ T cells from glaucoma patients displayed enhanced activation and a bias towards T helper (Th) 1 responses, which correlated with visual impairment. Secondly, we identified the infiltration of Th1 cells into the retina, where they targeted RGC and integrated into the pro-inflammatory glial network, contributing to progressive RGC loss. Thirdly, we discovered that circulating Th1 cells upregulated vascular cell adhesion protein 1 (VCAM-1) on retinal microvessels, facilitating their entry into the neural retina. Lastly, we found that Th1 cells underwent functional reprogramming before reaching the retina, acquiring a phenotype associated with lymphocyte migration and neurodegenerative diseases. Our study provides novel insights into the role of peripheral CD4+ T cells in glaucoma pathogenesis, shedding light on the mechanisms underlying their infiltration into the retina and offering potential avenues for innovative therapeutic interventions in this sight-threatening disease.


Asunto(s)
Glaucoma , Células Ganglionares de la Retina , Humanos , Ratones , Animales , Células Ganglionares de la Retina/patología , Molécula 1 de Adhesión Celular Vascular/metabolismo , Células TH1/patología , Glaucoma/metabolismo , Retina/patología , Trastornos de la Visión/patología , Modelos Animales de Enfermedad
2.
Phys Chem Chem Phys ; 26(3): 1722-1728, 2024 Jan 17.
Artículo en Inglés | MEDLINE | ID: mdl-38164760

RESUMEN

The framework material Eu[Ag(CN)2]3·3H2O exhibits a negative linear compressibility (NLC) of -4.2(1) TPa-1 over the largest pressure range yet observed (0-8.2 GPa). High-pressure single-crystal X-ray diffraction data show that the rapid contraction of the Kagome silver layers under compression causes the wine-rack lattice to expand along the c-axis. The hydrogen bonds between the water molecules and the main frameworks constrain the structural deformation under pressure and eventually a weak NLC effect generated. Furthermore, we found that the pressure-induced emission intensity increases almost 800-fold at 4.0 GPa, followed by a gradual decrease and disappearance at 8.1 GPa. Under compression, high pressure significantly tunes the triplet level positions near the Eu3+ ions, and horizontal displacement between a quenching excited state and the excited levels of Eu3+ facilitates the energy transfer process to the 5D0 excited state and limits the nonradiative corssover at elevated pressures, thus increasing the emission intensity. In addition, we observe a gradual band gap reduction with increasing pressure, and the sample could not be returned to the initial state after the pressure was completely released. By controlling the structural flexibility, we observe a coupled NLC and pressure-induced strong enhancement of the emission properties of Eu[Ag(CN)2]3·3H2O, which provides a new route for the design of new optical devices with intriguing luminescence properties under extreme environments.

3.
BMC Med Ethics ; 25(1): 13, 2024 02 04.
Artículo en Inglés | MEDLINE | ID: mdl-38311761

RESUMEN

BACKGROUND: The underrepresentation of scholarly works from low- and middle-income countries (LMICs) in academic literature is a documented concern, attributed partly to editorial biases. This trend, prevalent across various disciplines, has been less explored in the context of medical ethics journals. This study aimed to examine the composition of editorial board members (EBM) in high-impact medical ethics journals and to evaluate the extent of international diversity within these editorial teams. METHODS: This study incorporated an analysis of 16 high-impact medical ethics journals. Information regarding the EBM of these journals was systematically gathered and categorized based on the World Bank's country income classifications. An in-depth examination of the editorial board compositions was then conducted. RESULTS: The study identified 669 EBM across the selected journals. A predominant 89.84% (601) of these members were from high-income countries (HICs), with upper-middle-income countries contributing 7.47% (50) and lower-middle-income countries 2.69% (18). No EBM were associated with low-income countries. A regional breakdown indicated that North America was the most represented area, accounting for 48.88% (327), followed by Europe & Central Asia (27.50%, 184), East Asia & Pacific (13.45%, 90), Latin America & Caribbean (4.63%, 31), Sub-Saharan Africa (4.19%, 28), Middle East & North Africa (0.75%, 5), and South Asia (0.60%, 4). In total, these EBMs hailed from 46 different countries, with the United States representing the largest proportion (43.80%, 293), followed by the United Kingdom (13.15%, 88), Australia (7.92%, 53), Germany (6.73%, 45), and Canada (5.08%, 34). CONCLUSIONS: There is a significant lack of international representation within the EBM of high-impact medical ethics journals. The majority of editors in this field are affiliated with HICs, leading to a severe underrepresentation of LMICs within the editorial boards.


Asunto(s)
Publicaciones Periódicas como Asunto , Humanos , Estados Unidos , Europa (Continente) , Reino Unido , Ética Médica , Canadá
4.
Zhongguo Zhong Yao Za Zhi ; 49(2): 565-568, 2024 Jan.
Artículo en Zh | MEDLINE | ID: mdl-38403331

RESUMEN

Traditional Chinese medicine(TCM) preparations in medical institutions, as a unique and important form of preparations in China, have a long history of human use and serve as a bridge between clinical experience prescriptions and new Chinese medicine preparations. The state encourages medical institutions to transform their preparations into new traditional Chinese medicines, emphasizing their role as "incubators". Since the proposal of the traditional Chinese medicine registration and evaluation evidence system with the integration of TCM theory, human use experience(HUE), and clinical experience, the idea of transforming preparations used in medical institutions into new drugs based on HUE has been increasingly valued by drug research and development organizations. In the transformation process, pharmaceutical changes should be concerned from multiple aspects. This paper discusses the pharmaceutical changes and countermeasures based on the transformation of traditional Chinese medicine preparations in medical institutions into new drugs based on HUE from the aspects of excipients, dosage forms, production technology, production scale, packaging materials and containers, production sites, and registration standards. It is emphasized that scientific decisions should be made according to the characteristics and clinical needs of drugs to ensure the stability of drug quality. The impacts of pharmaceutical changes on drug quality should be objectively assessed based on appropriate evaluation indexes and detection methods. The layout should be carried out in advance, and the key pharmaceutical information of the preparations should be kept stable, so as to underpin the transformation of traditional Chinese medicine preparations in medical institutions into new drugs based on HUE.


Asunto(s)
Medicamentos Herbarios Chinos , Medicina Tradicional China , Humanos , Medicamentos Herbarios Chinos/uso terapéutico , Estándares de Referencia , Control de Calidad , Composición de Medicamentos , Preparaciones Farmacéuticas
5.
Zhongguo Zhong Yao Za Zhi ; 49(3): 849-852, 2024 Feb.
Artículo en Zh | MEDLINE | ID: mdl-38621889

RESUMEN

Chinese drug registration laws and regulations have always reserved a place for the new traditional Chinese medicine(TCM) drugs for syndromes, but so far no such new drugs have been approved for registration. This paper expounded on the relevant policies, regulations, and technologies of new TCM drugs for syndromes in China and pointed out that the application of the animal model of TCM syndromes to carry out pharmacodynamics research and clinical efficacy evaluation criteria of TCM syndromes were the main technical difficulties in the research and development of new TCM drugs for syndromes. Not all syndromes are suitable for developing new drugs, and the indications for new TCM drugs should be constant syndromes. Among the three research and development models of simple syndrome, syndrome-unified disease, and combined disease and syndrome, the research and development model of combined disease and syndrome is recommended. Clinical positioning is the key to new TCM drugs for syndromes. It is encouraged to conduct high-quality human use experience studies to determine the clinical positioning of new TCM drugs for syndromes, as well as the target population, dose, course of treatment, and initial therapeutic and safety, and apply for exemption from non-clinical effectiveness studies. Clinical trials of new TCM drugs for syndromes should take the target symptoms or signs as the main efficacy index and the efficacy of TCM syndromes as the secondary efficacy index. Clinical research program design should implement the "patient-centered" concept and introduce clinical outcome evaluation indicators. In the clinical safety evaluation, special conditions such as characteristic syndromes and changes should be considered. With the construction of the human use experience technology system and the promotion of the TCM registration and evaluation evidence system featuring the "combination of TCM theory, human use experience, and clinical trials", it is believed that many high-quality new TCM drugs for syndromes will be developed in the future.


Asunto(s)
Medicamentos Herbarios Chinos , Medicina Tradicional China , Humanos , Investigación , Síndrome , China , Medicamentos Herbarios Chinos/uso terapéutico
6.
Acta Pharmacol Sin ; 44(5): 999-1013, 2023 May.
Artículo en Inglés | MEDLINE | ID: mdl-36347996

RESUMEN

Non-healing diabetic wounds (DW) are a serious clinical problem that remained poorly understood. We recently found that topical application of growth differentiation factor 11 (GDF11) accelerated skin wound healing in both Type 1 DM (T1DM) and genetically engineered Type 2 diabetic db/db (T2DM) mice. In the present study, we elucidated the cellular and molecular mechanisms underlying the action of GDF11 on healing of small skin wound. Single round-shape full-thickness wound of 5-mm diameter with muscle and bone exposed was made on mouse dorsum using a sterile punch biopsy 7 days following the onset of DM. Recombinant human GDF11 (rGDF11, 50 ng/mL, 10 µL) was topically applied onto the wound area twice a day until epidermal closure (maximum 14 days). Digital images of wound were obtained once a day from D0 to D14 post-wounding. We showed that topical application of GDF11 accelerated the healing of full-thickness skin wounds in both type 1 and type 2 diabetic mice, even after GDF8 (a muscle growth factor) had been silenced. At the cellular level, GDF11 significantly facilitated neovascularization to enhance regeneration of skin tissues by stimulating mobilization, migration and homing of endothelial progenitor cells (EPCs) to the wounded area. At the molecular level, GDF11 greatly increased HIF-1ɑ expression to enhance the activities of VEGF and SDF-1ɑ, thereby neovascularization. We found that endogenous GDF11 level was robustly decreased in skin tissue of diabetic wounds. The specific antibody against GDF11 or silence of GDF11 by siRNA in healthy mice mimicked the non-healing property of diabetic wound. Thus, we demonstrate that GDF11 promotes diabetic wound healing via stimulating endothelial progenitor cells mobilization and neovascularization mediated by HIF-1ɑ-VEGF/SDF-1ɑ pathway. Our results support the potential of GDF11 as a therapeutic agent for non-healing DW.


Asunto(s)
Diabetes Mellitus Experimental , Células Progenitoras Endoteliales , Factores de Diferenciación de Crecimiento , Cicatrización de Heridas , Animales , Humanos , Ratones , Proteínas Morfogenéticas Óseas/metabolismo , Quimiocina CXCL12/efectos de los fármacos , Quimiocina CXCL12/metabolismo , Diabetes Mellitus Experimental/complicaciones , Diabetes Mellitus Experimental/tratamiento farmacológico , Diabetes Mellitus Experimental/metabolismo , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Diabetes Mellitus Tipo 2/metabolismo , Células Progenitoras Endoteliales/metabolismo , Células Progenitoras Endoteliales/patología , Factores de Diferenciación de Crecimiento/uso terapéutico , Factores de Diferenciación de Crecimiento/metabolismo , Neovascularización Fisiológica , Factor A de Crecimiento Endotelial Vascular/efectos de los fármacos , Factor A de Crecimiento Endotelial Vascular/metabolismo , Cicatrización de Heridas/efectos de los fármacos , Proteínas Recombinantes/metabolismo , Proteínas Recombinantes/uso terapéutico , Subunidad alfa del Factor 1 Inducible por Hipoxia/efectos de los fármacos , Subunidad alfa del Factor 1 Inducible por Hipoxia/metabolismo
7.
J Cell Mol Med ; 26(1): 202-215, 2022 01.
Artículo en Inglés | MEDLINE | ID: mdl-34859578

RESUMEN

This study explored the role played by combined ICA and bone mesenchymal stem cells (BMSCs) in repairing rabbit knee cartilage defects. Firstly, rabbit BMSCs were isolated and used to construct an in vitro cellular model of oxygen-glucose deprivation/reoxygenation (OGD/R). Subsequently, ICA processing, Alcian blue staining, immunofluorescence and Western blot studies were performed to evaluate the ability of BMSCs to display signs of chondrogenic differentiation. Furthermore, a rabbit knee cartilage injury model was established in vivo. International Cartilage Repair Society (ICRS) macroscopic evaluations, H&E, Alcian blue and EdU staining, as well as immunohistochemistry, were analysed cartilage repair and pathological condition of the knee cartilage tissue. Our in vitro results showed that ICA promoted the chondrogenic differentiation of BMSCs, as well as aggrecan (AGR), bone morphogenetic protein 2 (BMP2) and COL2A1 protein expression in BMSCs. In vivo experiments showed that rabbits in the BMSCs or ICA treatment group had higher ICRS scores and displayed a better restoration of cartilage-like tissue and chondrocyte expression on the surface of their cartilage defects. In conclusion, ICA or BMSCs alone could repair rabbit knee cartilage damage, and combined treatment with ICA and BMSCs showed a better ability to repair rabbit knee cartilage damage.


Asunto(s)
Cartílago Articular , Células Madre Mesenquimatosas , Animales , Células de la Médula Ósea/metabolismo , Cartílago Articular/patología , Diferenciación Celular , Células Cultivadas , Condrogénesis/genética , Flavonoides , Glucosa/metabolismo , Células Madre Mesenquimatosas/metabolismo , Oxígeno/metabolismo , Oxígeno/farmacología , Conejos
8.
Acc Chem Res ; 54(4): 1011-1022, 2021 Feb 16.
Artículo en Inglés | MEDLINE | ID: mdl-33535000

RESUMEN

ConspectusSince the rise of two-dimensional (2D) materials, synthetic methods including mechanical exfoliation, solution synthesis, and chemical vapor deposition (CVD) have been developed. Mechanical exfoliation prepares randomly shaped materials with small size. Solution synthesis introduces impurities that degrade the performances. CVD is the most successful one for low-cost scalable preparation. However, when it comes to practical applications, disadvantages such as high operating temperature (∼1000 °C), probable usage of metal catalysts, contamination, defects, and interstices introduced by postgrowth transfer are not negligible. These are the reasons why plasma-enhanced CVD (PECVD), a method that enables catalyst-free in situ preparation at low temperature, is imperatively desirable.In this Account, we summarize our recent progress on controllable preparation of 2D materials by PECVD and their applications. We found that there was a competition between etching and nucleation and deposition in PECVD, making it highly controllable to obtain desired materials. Under different equilibrium states of the competition, various 2D materials with diverse morphologies and properties were prepared including pristine or nitrogen-doped graphene crystals, graphene quantum dots, graphene nanowalls, hexagonal boron nitride (h-BN), B-C-N ternary materials (BCxN), etc. We also used mild plasma to modify or treat 2D materials (e.g., WSe2) for desired properties.PECVD has advantages such as low temperature, transfer-free process, and industrial compatibility, which enable facile, scalable, and low-cost preparation of 2D materials with clean surfaces and interfaces directly on noncatalytic substrates. These merits significantly benefit the as-prepared materials in the applications. Field-effect transistors with high motilities were directly fabricated on graphene and nitrogen-doped graphene. By use of h-BN as the dielectric interfacial layer, both mobilities and saturated power densities of the devices were improved owing to the clean, closely contacted interface and enhanced interfacial thermal dissipation. High-quality materials and interfaces also enabled promising applications of these materials in photodetectors, pressure sensors, biochemical sensors, electronic skins, Raman enhancement, etc. To demonstrate the commercial applications, several prototypical devices were studied such as distributed pressure sensor arrays, touching module on a robot hand for braille recognition, and smart gloves for recording sign language. Finally, we discuss opportunities and challenges of PECVD as a comprehensive preparation methodology of 2D materials for future applications beyond traditional CVD.

9.
World J Surg Oncol ; 20(1): 212, 2022 Jun 22.
Artículo en Inglés | MEDLINE | ID: mdl-35729577

RESUMEN

BACKGROUND: The link between glutathione S-transferase P1 (GSTP1) c.313A > G polymorphism and chemotherapy-related adverse events remains controversial. The goal of this study was to assess how this variant affected the toxicity of anthracycline-/paclitaxel-based chemotherapy in patients with breast cancer. METHODS: This study retrospectively investigated pharmacogenetic associations of GSTP1 c.313A > G with chemotherapy-related adverse events in 142 breast cancer patients who received anthracycline and/or paclitaxel chemotherapy. RESULTS: There were 61 (43.0%), 81 (57.0%), 43 (30.3%), and 99 (69.7%) patients in the T0-T2, T3-T4, N0-N1, and N2-N3 stages, respectively. There were 108 (76.1%) patients in clinical stages I-III and 34 (23.9%) patients in clinical stage IV. The numbers of patients with luminal A, luminal B, HER2 + , and triple-negative breast cancer (TNBC) were 10 (7.0%), 77 (54.2%), 33 (23.2%), and 22 (15.5%), respectively. The numbers of patients who carried GSTP1 c.313A > G A/A, A/G, and G/G genotypes were 94 (66.2%), 45 (31.7%), and 3 (2.1%), respectively. There were no statistically significant differences in the proportion of certain toxicities in patients with A/G, G/G, and A/G + G/G genotypes, except for neutropenia, in which the proportion of patients with A/G + G/G (χ2 = 6.586, P = 0.035) genotypes was significantly higher than that with the AA genotype. The logistic regression analysis indicated that GSTP1 c.313A > G mutation (A/G + G/G vs. A/A genotype) (adjusted OR 4.273, 95% CI 1.141-16.000, P = 0.031) was an independent variable associated with neutropenia. CONCLUSIONS: The findings of this study indicate that the GSTP1 c.313A > G mutation is an independent risk factor for neutropenia hematotoxicity in breast cancer patients induced by anthracycline-/paclitaxel-based chemotherapy.


Asunto(s)
Neoplasias de la Mama , Neutropenia , Antraciclinas/efectos adversos , Antibióticos Antineoplásicos/uso terapéutico , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/genética , Femenino , Genotipo , Gutatión-S-Transferasa pi/genética , Glutatión Transferasa/genética , Glutatión Transferasa/uso terapéutico , Humanos , Mutación , Neutropenia/inducido químicamente , Neutropenia/genética , Paclitaxel/efectos adversos , Estudios Retrospectivos , Factores de Riesgo
10.
Pharm Biol ; 60(1): 1303-1316, 2022 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-35801991

RESUMEN

CONTEXT: Morinda officinalis F.C. How. (MO) (Rubiaceae) can strengthen bone function. OBJECTIVE: To examine the functional mechanism and effect of MO polysaccharides (MOPs) in rats with glucocorticoid-induced osteoporosis (GIOP). MATERIALS AND METHODS: Rats with GIOP were treated with 5, 15 or 45 mL/kg of MOP [n = 15 for each dose, intraperitoneal (i.p.) injection every other day for 8 weeks]. The body weight of rats and histomorphology of bone tissues were examined. Bone marrow mesenchymal stem cells (BMSCs)-derived exosomes (Exo) were collected and identified. Bone marrow-derived macrophages (BMMs) were induced to differentiate into osteoclasts and treated with BMSC-Exo for in vitro studies. RESULTS: MOP reduced the body weight (5, 15, or 45 mg/kg MOP vs. phosphate-buffered saline: 8%, 15% and 25%, p < 0.01), elevated the bone volume to tissue volume (BV/TV), mean trabecular thickness (Tb.Th), mean trabecular number (Tb.N) and mean connectivity density (Conn.D) (40-86%, p < 0.01), decreased the mean trabecular separation/spacing (Tb.Sp) (22-37%, p < 0.01), increased the cortical bone continuity (35-90%, p < 0.01) and elevated RUNX family transcription factor 2 and RANK levels (5-12%, p < 0.01), but suppressed matrix metallopeptidase 9 and cathepsin K levels (9-20%, p < 0.01) in femur tissues. BMSC-Exo from MOP-treated rats (MOP-Exo) suppressed osteoclastic differentiation and proliferation of BMMs. The downregulation of microRNA-101-3p (miR-101-3p) or the upregulation of prostaglandin-endoperoxide synthase 2 (PTGS2) blocked the functions of MOP-Exo. DISCUSSION AND CONCLUSIONS: MOP inhibits osteoclastic differentiation and could potentially be used for osteoporosis management. This suppression may be enhanced by the upregulation of miR-101-3p or the inhibition of PTGS2.


Asunto(s)
Exosomas , Células Madre Mesenquimatosas , MicroARNs , Morinda , Osteoporosis , Animales , Peso Corporal , Ciclooxigenasa 2 , Osteoporosis/inducido químicamente , Osteoporosis/tratamiento farmacológico , Polisacáridos/farmacología , Ratas , Ratas Sprague-Dawley
11.
Microb Pathog ; 150: 104701, 2021 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-33340654

RESUMEN

BACKGROUND: Yeast form of T.marneffei can produce DOPA-melanin which perform an important role in the pathogen surviving in macrophage. So far, the proteomic associated with melanin synthesis remain unclearly in T.marneffei. METHODS: The whole yeast cell proteins were extracted from T.marneffei cultured with or without l-DOPA. Using two-dimensional gel electrophoresis combined with MALDI-TOF mass spectrometry, distinguished proteins were identified between T.marneffei cultured with or without l-DOPA. Furthermore, geldanamycin were used to assess the inhibition effect on T.marneffei melanin production in vitro. RESULTS: 16 distinguished proteins were identified in DOPA-melanized yeast cells, as well as 15 triple-up-expressed proteins and 7 triple-down-expressed proteins in comparison with non DOPA-melanized yeast cells. Of note, proteins differentially expressed proteins were predominantly heat shock proteins. HSP90/60/70 genes expressions increased significantly demonstrated by q-RT-PCR, which was consistent with the proteomics changes. GO analysis showed that the majority of differentially expressed proteins including HSPs(especially HSP90) were found enriched in stress response, cellular process, protein folding, stimuli response and biological process. KEGG pathway analysis showed that proteins were enriched predominantly in phagosome. HSP90 inhibitor(Geldanamycin) inhibited the brown-black pigment production of T.marneffei yeast grown on brain heart infusion agar, as well as the inhibition effect was observed by transmission electron microscope. CONCLUSIONS: The results demonstrates that HSP90 palys an essential role in T.marneffei DOPA-melanin synthesis pathway.


Asunto(s)
Talaromyces , Dihidroxifenilalanina/análogos & derivados , Proteómica
12.
Australas J Dermatol ; 62(2): 217-220, 2021 May.
Artículo en Inglés | MEDLINE | ID: mdl-33742458

RESUMEN

Blau syndrome (BS) is a rare monogenic disease caused by mutation of NOD2/CARD15 gene. A case of Blau syndrome in a 4-year-old Chinese boy c.1001G > A(p.R334Q) mutation in the NOD2 genes reported. Imaging revealed a nodule at the tip of the right lung.


Asunto(s)
Artritis/diagnóstico , Sarcoidosis/diagnóstico , Nódulo Pulmonar Solitario/diagnóstico por imagen , Sinovitis/diagnóstico , Uveítis/diagnóstico , Artritis/genética , Pueblo Asiatico , Biopsia , Preescolar , China , Humanos , Masculino , Mutación , Proteína Adaptadora de Señalización NOD2/genética , Sarcoidosis/genética , Piel/patología , Sinovitis/genética , Tomografía Computarizada por Rayos X , Uveítis/genética
13.
J Environ Manage ; 254: 109789, 2020 Jan 15.
Artículo en Inglés | MEDLINE | ID: mdl-31731029

RESUMEN

We use "China's sulfur dioxide (SO2) emissions trading program" as a quasi-natural experiment to identify the causal effect of this market-based environmental regulation on firm's labor demand. Based on the difference-in-differences (DID) method and a series of robustness tests, we observe robust evidence that the emissions trading program significantly increases the labor demand of regulated firms, and that this positive employment effect is driven by the expansion of firm's production scale. The observable evidence leads us to cautiously conclude that the market-based environmental regulations in even developing countries could achieve the double dividend of coexistence of environmental protection and employment growth.


Asunto(s)
Industria Manufacturera , Dióxido de Azufre , China
14.
Cell Tissue Bank ; 20(2): 209-220, 2019 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-30854603

RESUMEN

The treatment of articular cartilage defects has become a major clinical concern. Currently, additional efforts are necessary to develop effective methods to cure this disease. In this work, we combined gene therapy with tissue engineering methods to test their effect on cartilage repair. In in vitro experiments, we obtained C-type natriuretic peptide (CNP) gene-modified bone marrow-derived mesenchymal stem cells (BMSCs) by transfection with recombinant adenovirus containing the CNP gene and revealed that CNP gene-modified BMSCs had good chondrogenic differentiation ability. By the freeze-drying method, we successfully synthesized a chitosan/silk fibroin (CS/SF) porous scaffold, which had a suitable aperture size for chondrogenesis. Then, we loaded CNP gene-modified BMSCs onto CS/SF scaffolds and tested their effect on repairing full-thickness cartilage defects in rat joints. The gross morphology and histology examination results showed that the composite of the CNP gene-modified BMSCs and CS/SF scaffolds had better repair effects than those of the other three groups at each time point. Additionally, compared to the group with BMSCs and scaffolds, we found that there was more cartilage matrix in the CNP gene-modified BMSCs and CS/SF scaffolds group. Data obtained in the present study suggest that the composite of CNP gene-modified BMSCs and CS/SF scaffolds represent promising strategies for repairing focal cartilage lesions.


Asunto(s)
Cartílago Articular/citología , Regeneración Tisular Dirigida/métodos , Células Madre Mesenquimatosas/citología , Péptido Natriurético Tipo-C/genética , Ingeniería de Tejidos/métodos , Andamios del Tejido/química , Adenoviridae/genética , Animales , Células de la Médula Ósea/citología , Células de la Médula Ósea/metabolismo , Cartílago Articular/crecimiento & desarrollo , Células Cultivadas , Quitosano/química , Fibroínas/química , Terapia Genética/métodos , Masculino , Células Madre Mesenquimatosas/metabolismo , Ratas , Ratas Sprague-Dawley , Transfección
15.
Int Wound J ; 16(3): 724-729, 2019 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-30784197

RESUMEN

In this study, the mechanism of TDP-43 gene expression on inflammatory factors and Jun N-terminal kinase (JNK) and p38 mitogen-activated protein kinase (MAPK) signalling pathways in ischaemic hypoxic stress dependence was investigated. Sixty SD rats were selected and divided into the control group, the osteoarthritis (OA) model group, and the TDP-43-mMSCs+OA group. In the OA model group and the TDP-43-mMSCs+OA group, OA was established by collagenase injection. Western blotting assays were used to detect the expression of TDP-43 in cartilage tissues of each rat. The secretion of tumour necrosis factor-α (TNF-α) and interleukin-1ß (IL-1ß) in the serum of rats was determined by enzyme-linked immunosorbent assay (ELISA). The formation of cytoplasmic stress granules (SGs) and the expression of receptor for activated c-kinase 1 (RACK1) were detected by Western blotting assays in each group of rats. The expression of MTK1 and MAPKKK phosphorylation and changes in the JNK and p38 MAPK signalling pathways were detected by Western blotting assays. Compared with the control group, the expression of TDP-43 in the cartilage tissue of rats in the OA model group was significantly decreased. The expression of TDP-43 in the cartilage tissue of rats in the TDP-43-mMSCs+OA group was significantly higher than that of the control group and the OA model group, which indicates that TDP-43-mMSC transplantation was successful. Enzyme-linked immunosorbent assay results showed that the plasma TNF-α and IL-1ß levels in the OA model group were significantly increased (P < 0.01) when compared with the control group. However, the secretion of TNF-α and IL-1ß in the serum of the TDP-43-mMSCs+OA group was significantly lower than that of the model group (P < 0.01) but still higher than the control group. This indicates that overexpression of TDP-43 reduces the inflammatory response induced by OA. Western blotting assays showed that the amount of cytoplasmic SGs in the cartilage tissue of rats in the OA model group was significantly decreased when compared with the control group. The amount of SGs in the cartilage of rats in the TDP-43-mMSCs+OA group was significantly higher than that of the model group. The expression of RACK1 in the cartilage tissue of rats in the OA model group was significantly higher than that of the control group. Overexpression of the TDP-43 gene can interfere with the secretion of inflammatory factors and inhibit the activation of the JNK and p38 MAPK signalling pathways by ischaemic hypoxia stress. Thus, the molecular mechanism of chondrocytopathic lesions was reversed, which provided a new theoretical basis for the treatment of OA.


Asunto(s)
Proteínas Adaptadoras Transductoras de Señales/metabolismo , Proteínas de Unión al ADN/metabolismo , Hipoxia/fisiopatología , Inflamación/genética , Inflamación/fisiopatología , Osteoartritis/genética , Osteoartritis/fisiopatología , Proteínas Quinasas p38 Activadas por Mitógenos/metabolismo , Proteínas Adaptadoras Transductoras de Señales/genética , Animales , Proteínas de Unión al ADN/genética , Modelos Animales de Enfermedad , Regulación de la Expresión Génica , Hipoxia/genética , Masculino , Ratas , Ratas Sprague-Dawley , Proteínas Quinasas p38 Activadas por Mitógenos/genética
16.
Analyst ; 142(15): 2805-2811, 2017 Jul 24.
Artículo en Inglés | MEDLINE | ID: mdl-28686255

RESUMEN

As a recently developed detection technique, photoelectrochemical (PEC) measurement has received extensive attention. However, owing to the lack of a comprehensive approach to engineer the photo-generated carriers, the performance is still limited. As an example, a significant use of PEC measurement might be in understanding the roles of glutathione in physiological and pathological processes. Here, we developed a new approach for engineering the photo-generated carriers with the aid of the synergic effect of self-doping, surface plasmon resonance, electrical field amplification effect, etc. Thus, a highly sensitive multicomponent PEC platform has been developed, in which Au nanorods are decorated on the surface of self-doped TiO2 nanowires, followed by surface receptor functionalization with hemin for capturing glutathione. The synergic effect effectively increases generation, separation and transfer kinetics of the photo-generated carriers, which can be further increased by using a mixture of Au nanorods with different aspect ratios to tune the absorption wavelength to the entire UV-visible region. As a result, this system exhibits a broad linear range from 10 nM to 17.5 µM and low detection limit down to 8.6 nM for detecting glutathione, about 1-2 orders of magnitude lower than most existing PEC sensors.

18.
Phys Rev Lett ; 116(12): 126101, 2016 Mar 25.
Artículo en Inglés | MEDLINE | ID: mdl-27058087

RESUMEN

In this Letter, we report the observation of thermally induced rotation of graphene on hexagonal boron nitride (h-BN). After the rotation, two thermally stable configurations of graphene on h-BN with a relative lattice twisting angle of 0° (most stable) and 30° (metastable), respectively, were found. Graphene on h-BN with a twisting angle below (above) a critical angle of ∼12±2° tends to rotate towards 0° (30°) at a temperature of >100 °C, which is in line with our theoretical simulations. In addition, by manipulating the annealing temperature and the flake sizes of graphene, moiré superlattices with large spatial periods of graphene on h-BN are achieved. Our studies provide a detailed understanding of the thermodynamic properties of graphene on h-BN and a feasible approach to obtaining van der Waals heterostructures with aligned lattices.

19.
Nanotechnology ; 27(50): 505603, 2016 Dec 16.
Artículo en Inglés | MEDLINE | ID: mdl-27861166

RESUMEN

Graphene has attracted tremendous research interest owing to its widespread potential applications. However, these applications are partially hampered by the lack of a general method to produce high-quality graphene at low cost. Here, to the best of our knowledge, we use low-cost solid carbon allotropes as the precursor in plasma-enhanced chemical vapor deposition (PECVD) for the first time, and find that the hydrogen plasma and reaction temperature play a crucial role in the process. Hydrogen plasma etches carbon black, and produces graphene crystals in a high-temperature zone. Based on this finding, a modified PECVD technology is developed, which produces transparent conductive nanographene films directly on various substrates at a temperature as low as 600 °C. For application, the closely packed structure of the nanographene film enables a remarkable temperature-dependent behavior of the resistance with a ratio higher than that previously reported, indicating its great potential for usage in highly sensitive temperature detectors.

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