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1.
J Vasc Res ; 61(2): 89-98, 2024.
Artigo em Francês | MEDLINE | ID: mdl-38368869

RESUMO

INTRODUCTION: Vascular prosthetic grafts are widely used in vascular surgery; however, graft infection remains a major concern. Silver-coated vascular grafts have demonstrated anti-infection properties in clinical settings; however, whether the silver irons influence foreign body reaction or neointimal hyperplasia remains unclear. METHODS: Sodium alginate and hyaluronic acid (SA/HA) hydrogel patches loaded with rhodamine, with or without silver, were fabricated. Patches were implanted in the subcutaneous or abdominal cavity and inferior vena cava of rats. Samples were harvested on day 14 and examined via immunohistochemical and immunofluorescence analyses. RESULTS: Silver hydrogel was found to decrease the foreign body reaction; after subcutaneous and abdominal cavity implantation in rats, the capsule was found to be thinner in the silver hydrogel group than in the control hydrogel group. The silver hydrogel group had fewer CD68-positive cells and proliferating cell nuclear antigen and interleukin-33 (IL-33) dual-positive cells than the control hydrogel group. Additionally, the silver hydrogel patch reduced the neointimal thickness after patch venoplasty in rats, and the number of IL-33- and IL-1ß-positive cells was lower than that in the control patch. CONCLUSION: Silver-loaded SA/HA hydrogel patches decreased the foreign body reaction and venous neointimal hyperplasia in rats by the inhibition of IL-33 expression.


Assuntos
Interleucina-33 , Prata , Ratos , Animais , Hiperplasia , Neointima , Reação a Corpo Estranho/etiologia , Reação a Corpo Estranho/prevenção & controle , Hidrogéis
2.
Inorg Chem ; 63(21): 9864-9876, 2024 May 27.
Artigo em Inglês | MEDLINE | ID: mdl-38756060

RESUMO

Rechargeable aqueous zinc-ion batteries (RAZIBs) have received extensive attention because of their advantages of low cost, high safety, and nontoxicity. However, problems such as dissolution of the active cathode material, dendrites/passivation of the zinc anode, and slow reaction kinetics hindered their further applications. In this work, a crystalline/amorphous composite-type material composed of crystalline MnCO3 and amorphous MnOx was prepared and used as the cathode material for RAZIBs. The MnCO3@amorphous MnOx (MnCO3@A-MnOx) composite possesses the merits of both the pure crystalline phase of MnCO3 and the amorphous phase of MnOx, which can deliver better electrochemical performance than the corresponding single component in repeated cycles. In addition, crystalline MnCO3 undergoes a complex phase transition to the active MnO2 during the first charge process, providing the composite with a stable structure and additional electrochemical capacity. The electrochemical measurement results indicate that the MnCO3@A-MnOx electrode can display high reversible discharge capacity at 0.1 A g-1, excellent rate performance at 5.0 A g-1, and long cycling stability over 2000 cycles, showing great potential as a cathode material for high-performance RAZIBs.

3.
Mol Med ; 29(1): 39, 2023 03 28.
Artigo em Inglês | MEDLINE | ID: mdl-36977984

RESUMO

BACKGROUND: Diabetes-related limb ischemia is a challenge for lower extremity amputation. Aurora Kinase A (AURKA) is an essential serine/threonine kinase for mitosis, while its role in limb ischemia remains unclear. METHOD: Human microvascular endothelial cells (HMEC-1) were cultured in high glucose (HG, 25 mmol/L D-glucose) and no additional growth factors (ND) medium to mimic diabetes and low growth factors deprivation as in vitro model. Diabetic C57BL/6 mice were induced by streptozotocin (STZ) administration. After seven days, ischemia was surgically performed by left unilateral femoral artery ligation on diabetic mice. The vector of adenovirus was utilized to overexpress AURKA in vitro and in vivo. RESULTS: In our study, HG and ND-mediated downregulation of AURKA impaired the cell cycle progression, proliferation, migration, and tube formation ability of HMEC-1, which were rescued by overexpressed AURKA. Increased expression of vascular endothelial growth factor A (VEGFA) induced by overexpressed AURKA were likely regulatory molecules that coordinate these events. Mice with AURKA overexpression exhibited improved angiogenesis in response to VEGF in Matrigel plug assay, with increased capillary density and hemoglobin content. In diabetic limb ischemia mice, AURKA overexpression rescued blood perfusion and motor deficits, accompanied by the recovery of gastrocnemius muscles observed by H&E staining and positive Desmin staining. Moreover, AURKA overexpression rescued diabetes-related impairment of angiogenesis, arteriogenesis, and functional recovery in the ischemic limb. Signal pathway results revealed that VEGFR2/PI3K/AKT pathway might be involved in AURKA triggered angiogenesis procedure. In addition, AURKA overexpression impeded oxidative stress and subsequent following lipid peroxidation both in vitro and in vivo, indicating another protective mechanism of AURKA function in diabetic limb ischemia. The changes in lipid peroxidation biomarkers (lipid ROS, GPX4, SLC7A11, ALOX5, and ASLC4) in in vitro and in vivo were suggestive of the possible involvement of ferroptosis and interaction between AUKRA and ferroptosis in diabetic limb ischemia, which need further investigation. CONCLUSIONS: These results implicated a potent role of AURKA in diabetes-related impairment of ischemia-mediated angiogenesis and implied a potential therapeutic target for ischemic diseases of diabetes.


Assuntos
Diabetes Mellitus Experimental , Fator A de Crescimento do Endotélio Vascular , Humanos , Camundongos , Animais , Fator A de Crescimento do Endotélio Vascular/metabolismo , Aurora Quinase A/metabolismo , Aurora Quinase A/uso terapêutico , Diabetes Mellitus Experimental/metabolismo , Células Endoteliais/metabolismo , Neovascularização Fisiológica , Fosfatidilinositol 3-Quinases/metabolismo , Membro Posterior , Camundongos Endogâmicos C57BL , Isquemia , Músculo Esquelético/metabolismo
4.
BMC Med Educ ; 23(1): 812, 2023 Oct 27.
Artigo em Inglês | MEDLINE | ID: mdl-37891526

RESUMO

BACKGROUND: The simulated three-dimensional (3D) printed anatomical model of the aorta, which has become the norm in medical education, has poor authenticity, tactility, feasibility, and interactivity. Therefore, this study explored the educational value and effect of mixed reality (MR) combined with a 3D printed model of aortic disease in training surgical residents. METHOD: Fifty-one resident physicians who rotated in vascular surgery were selected and divided into traditional (27) and experimental (24) teaching groups using the random number table method. After undergoing the experimental and traditional training routines on aortic disease, both the groups took a theoretical test on aortic disease and an assessment of the simulation based on the Michigan Standard Simulation Experience Scale (MiSSES) template. Their scores and assessment results were compared. The study was conducted at the Department of Vascular Surgery of Peking University People's Hospital, Beijing, China. RESULTS: In the theoretical test on aortic disease, the experimental teaching group obtained higher mean total scores (79.0 ± 9.1 vs. 72.6 ± 7.5, P = 0.013) and higher scores in anatomy/ pathophysiology (30.8 ± 5.4 vs. 24.8 ± 5.8; P < 0.001) than the traditional teaching group. The differences in their scores in the differential diagnosis (25.8 ± 3.0 vs. 23.3 ± 4.9; P = 0.078) and treatment (22.5 ± 11.8 vs. 24.5 ± 8.2; P = 0.603) sessions were insignificant. The MR-assisted teaching stratified the vascular residents through the MiSSES survey. Overall, 95.8% residents (23/24) strongly or somewhat agreed that the MR was adequately realistic and the curriculum helped improve the ability to understanding aortic diseases. Further, 91.7% residents (22/24) strongly or somewhat agreed that the MR-assisted teaching was a good training tool for knowledge on aortic diseases. All residents responded with "Good" or "Outstanding" on the overall rating of the MR experience. CONCLUSIONS: MR combined with the 3D printed model helped residents understand and master aortic disease, particularly regarding anatomy and pathophysiology. Additionally, the realistic 3D printing and MR models improved the self-efficacy of residents in studying aortic diseases, thus greatly stimulating their enthusiasm and initiative to study.


Assuntos
Doenças da Aorta , Realidade Aumentada , Internato e Residência , Humanos , Estudos de Casos e Controles , Procedimentos Cirúrgicos Vasculares , Impressão Tridimensional , Competência Clínica
5.
Nano Lett ; 22(6): 2444-2449, 2022 Mar 23.
Artigo em Inglês | MEDLINE | ID: mdl-35230850

RESUMO

Materials with crystalline structures of circular symmetry are rare in nature; however, they are highly desired in optical applications with structured lights, whose characteristics are of cylindrical symmetry. In this work, using a naturally existing circular anisotropy from a spherulite formed by molecular self-assembly, we obtain a cylindrical vector optical vortex beam generation transformed from the spin angular momentum in the wide visible range. The proposed strategy provides promising and broad opportunities for the applications of spherulites in the generation of structured lights and modulations of both the polarization and the angular momentum.

6.
Ann Vasc Surg ; 79: 139-144, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-34644658

RESUMO

OBJECTIVE: Peripheral artery disease (PAD) is often caused by atherosclerosis. However, causes other than atherosclerosis is often overlooked. Popliteal artery entrapment syndrome (PAES) and popliteal artery adventitial cystic disease (PACD) are two common nonatheromatous causes of claudication and critical limb ischemia. The purpose of this study is to present early results of treatment of PAES and PACD involving the lower limbs. METHODS: From December 2019 to February 2021, 10 patients with PAES underwent surgeries, and 1 patient with PAES received conservative treatment. 2 patients with PACD underwent surgery. Patient data including age, gender, etiology of vascular pathology, diseased vessel, surgical method, and hemodynamic status were collected retrospectively. RESULTS: The mean follow-up duration was 5.64 ± 3.72 months (range, 1-12 months). All patients had their symptoms improved or resolved. The success rate of surgery was 100%, the rate of freedom from reintervention for any reason was 100%. There were no death, bleeding, embolism, or skin ulcers during late follow-up. CONCLUSIONS: PAES and PACD require early diagnosis and intervention, and early surgery may lead to good early- and mid-term results.


Assuntos
Tratamento Conservador , Doença Arterial Periférica/terapia , Síndrome do Aprisionamento da Artéria Poplítea/terapia , Artéria Poplítea/cirurgia , Procedimentos Cirúrgicos Vasculares , Adolescente , Adulto , China , Tratamento Conservador/efeitos adversos , Feminino , Hemodinâmica , Humanos , Masculino , Pessoa de Meia-Idade , Doença Arterial Periférica/diagnóstico por imagem , Doença Arterial Periférica/fisiopatologia , Artéria Poplítea/diagnóstico por imagem , Artéria Poplítea/fisiopatologia , Síndrome do Aprisionamento da Artéria Poplítea/diagnóstico por imagem , Síndrome do Aprisionamento da Artéria Poplítea/fisiopatologia , Estudos Retrospectivos , Fatores de Tempo , Resultado do Tratamento , Procedimentos Cirúrgicos Vasculares/efeitos adversos
7.
Ann Vasc Surg ; 85: 383-394, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-35461996

RESUMO

BACKGROUND: This study explored seasonal and monthly variations of the incidence of acute aortic dissection (AAD). METHODS: MEDLINE, EMBASE, and the Cochrane Library databases were searched up to July 2021. Temporal variation in the incidence of AAD was analyzed including all studies analyzing seasonal and monthly aggregations. Then, we performed subgroup analyses according to the type of AAD. Two authors independently reviewed and extracted data. RESULTS: Twenty-seven studies for a total of 128,101 patients were included. Our results showed that the incidence of AAD was highest in winter and lowest in summer. Regardless of type A or type B, the incidence of AAD was significantly higher in winter than in summer and autumn. Nonetheless, there was no significant difference between spring and winter, and between summer and autumn. Results may be limited by the quality of the included articles. However, in the sensitivity analysis that excluded low-quality studies, results did not change significantly. In addition, the pooled incidence was highest in January and lowest in August. CONCLUSIONS: Our data strongly support the presence of distribution patterns in the incidence of AAD, characterized by significantly higher risk in winter and in January. These distribution patterns of AAD incidence may help to develop better prevention strategies.


Assuntos
Dissecção Aórtica , Dissecção Aórtica/diagnóstico por imagem , Dissecção Aórtica/epidemiologia , Humanos , Incidência , Estações do Ano , Resultado do Tratamento
8.
Ann Vasc Surg ; 81: 324-332, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-34775019

RESUMO

BACKGROUND: Spiral saphenous vein grafts (SSVG) or paneled vein grafts (PVG) can be used when the diameter of the autologous great saphenous vein does not match the vessel that needs to be repaired. This study aimed to present early results of complex vascular reconstruction with SSVGs and PVGs in the lower extremities. METHODS: From May 2019 through January 2021, 6 SSVGs and 3 PVGs were used for vascular reconstruction in 9 patients. Patient data were collected retrospectively, including age, gender, cause of vascular pathology, target vessels, concomitant injury, surgical method, additional surgical methods, and hemodynamic status. The Kaplan-Meier method was used to calculate the rate of freedom from reintervention. RESULTS: Among these patients, 7 had trauma, 1 had graft infection, and 1 had vascular reconstruction after tumor excision. The mean duration of follow-up was 6 ± 6.6 months (range 1-19 months). The rate of freedom from reintervention for any reason was 77.8% at 1 year. Two patients underwent amputation after vascular reconstruction with patent vascular reconstructions. One of the 2 amputations was performed because of infection, and the other was due to ischemia >24 hr. The success rate of reconstruction was 100%, and the primary patency rate was 100%. The rate of limb salvage was 77.8%. There was no death, bleeding, embolism, skin ulcers, graft-related complication, or aneurysmal dilation during follow-up. CONCLUSIONS: SSVG and PVG were associated with low infection rates and satisfactory short-term patency rates. Both 2 grafts may be good choices when there is a diameter mismatch in vascular reconstructions.


Assuntos
Extremidade Inferior , Veia Safena , Amputação Cirúrgica/efeitos adversos , Oclusão de Enxerto Vascular/etiologia , Oclusão de Enxerto Vascular/cirurgia , Humanos , Salvamento de Membro/efeitos adversos , Extremidade Inferior/irrigação sanguínea , Estudos Retrospectivos , Veia Safena/transplante , Resultado do Tratamento , Grau de Desobstrução Vascular
9.
Ecotoxicol Environ Saf ; 208: 111450, 2021 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-33039871

RESUMO

Despite of growing evidence linking PM2.5 exposure to autophagic activity in various human cells, the functional significance of PM2.5 exposure affecting autophagy in the pathogenesis of human cardiovascular disease and the underlying molecular mechanisms remain unclear. In this study, the effects of ambient PM2.5 (with final concentration 0, 1, 5, 25 µg/mL) on the autophagic activity in human umbilical vein endothelial cells (HUVECs) were systematically studied. The results showed that the internalized PM2.5 mainly localized in the membrane-surrounded vacuoles in the cytoplasm. Compared with the negative control, dose-dependent increase of autophagosomes, puncta and protein levels of LC3-II and p62, and both dose- and time-dependent increase of AKT phosphorylation, with inversely time-dependent reduction of Beclin 1, ATG3 and ATG5 proteins, were presented in the PM2.5-treated HUVECs, indicating a clear impairment of autophagic degradation in the PM2.5-exposed HUVECs. Meanwhile, increase in lysosomes, LAMP1, proteases of CTSB and CTSD, and protein phosphorylation of ERK1/2 and TFEB was identified in the PM2.5-treated HUVECs, showing a PM2.5-mediated enhancement in lysosomal activity. A novel finding in this study is that both Sntaxin-17 and LAMP2, two key proteins involved in the control of membrane fusion between autophagosome and lysosome, were significantly decreased in the PM2.5-exposed HUVECs, suggesting that the fusion of autophagosome-lysosome was blocked up. Collectively, ambient PM2.5 exposure may block up the autophagic flux in HUVECs through inhibiting the expression of Sntaxin-17 and LAMP2. Autophagic activity in HUVECs is a useful biomarker for assessing risks of environmental factors to human cardiovascular health.


Assuntos
Poluentes Atmosféricos/toxicidade , Proteína 2 de Membrana Associada ao Lisossomo/metabolismo , Material Particulado/toxicidade , Autofagossomos/efeitos dos fármacos , Autofagia/efeitos dos fármacos , Proteína Beclina-1/metabolismo , Células Endoteliais da Veia Umbilical Humana/efeitos dos fármacos , Células Endoteliais da Veia Umbilical Humana/metabolismo , Células Endoteliais da Veia Umbilical Humana/fisiologia , Humanos , Proteína 2 de Membrana Associada ao Lisossomo/antagonistas & inibidores , Lisossomos/efeitos dos fármacos , Fosforilação
10.
Water Sci Technol ; 82(10): 2051-2061, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-33263583

RESUMO

Sludge dewatering is an important step for wastewater treatment. Composite degradable flocculant (CDF) was prepared by cationic polyacrylamide (PAM) grafting onto modified starch with a novel initiator, and characterized by Fourier transform infrared spectroscopy. The microstructure of flocculated sludge was characterized by scanning electron microscopy. The study investigated the properties of CDF compared to PAM, which showed that the prepared CDF exhibited a highly effective flocculation on sludge dewatering, a higher transmittance and chemical oxygen demand removal rate, and a lower value of effluent ammonia nitrogen and total phosphorus. The fermentation process was also analyzed by testing the performance of dewatered sludge (temperature, pH, ammonia nitrogen, E4/E6 (humic acid absorbance at 465 nm (E4) and 665 nm (E6))). The dehydrated sludge with CDF could be easily compressed into cakes by belt-filter for easy transportation and storage. With the continuous addition of CDF and PAM, the corresponding index of capillary suction time (CST) increased. Moreover, the total value of CST with CDF was low, showing a good dewaterability. In addition, the sludge index of pumping time and moisture content with CDF were low in contrast with PAM. Fermentation experiments demonstrated that sludge with CDF had a comparatively high temperature and low value of E4/E6. Such novel CDF shows enormous potential in wastewater treatment and sludge fermentation.


Assuntos
Esgotos , Amido , Floculação , Espectroscopia de Infravermelho com Transformada de Fourier , Eliminação de Resíduos Líquidos
11.
Environ Toxicol ; 34(11): 1199-1207, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31294929

RESUMO

Despite intensive research activities, there are still many major knowledge gaps over the potential adverse effects of titanium dioxide nanoparticles (TiO2 -NPs), one of the most widely produced and used nanoparticles, on human cardiovascular health and the underlying mechanisms. In the present study, alkaline comet assay and cytokinesis-block micronucleus test were employed to determine the genotoxic potentials of four sizes (100, 50, 30, and 10 nm) of anatase TiO2 -NPs to human umbilical vein endothelial cells (HUVECs) in culture. Also, the intracellular redox statuses were explored through the measurement of the levels of reactive oxygen species (ROS) and reduced glutathione (GSH) with kits, respectively. Meanwhile, the protein levels of nuclear factor erythroid 2-related factor 2 (Nrf2) were also detected by western blot. The results showed that at the exposed levels (1, 5, and 25 µg/mL), all the four sizes of TiO2 -NPs could elicit an increase of both DNA damage and MN frequency in HUVECs in culture, with a positive dose-dependent and negative size-dependent effect relationship (T100 < T50 < T30 < T10). Also, increased levels of intracellular ROS, but decreased levels of GSH, were found in all the TiO2 -NP-treated groups. Intriguingly, a very similar manner of dose-dependent and size-dependent effect relationship was observed between the ROS test and both comet assay and MN test, but contrary to that of GSH assay. Correspondingly, the levels of Nrf2 protein were also elevated in the TiO2 -NP-exposed HUVECs, with an inversely size-dependent effect relationship. These findings indicated that induction of oxidative stress and subsequent genotoxicity might be an important biological mechanism by which TiO2 -NP exposure would cause detrimental effects to human cardiovascular health.


Assuntos
Dano ao DNA/efeitos dos fármacos , Nanopartículas Metálicas/toxicidade , Titânio/química , Núcleo Celular/efeitos dos fármacos , Núcleo Celular/metabolismo , Glutationa/metabolismo , Células Endoteliais da Veia Umbilical Humana , Humanos , Nanopartículas Metálicas/química , Fator 2 Relacionado a NF-E2/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Tamanho da Partícula , Espécies Reativas de Oxigênio/metabolismo , Regulação para Cima/efeitos dos fármacos
12.
Environ Toxicol ; 33(12): 1221-1228, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30126039

RESUMO

Concerns over the health risk of the widely distributed, commonly used titanium dioxide nanoparticles (nano-TiO2 ) are increasing worldwide. Yet, up-to-now, our understanding in their potential effects on the cardiovascular system is very limited and the toxicological mechanisms are still unclear. In the present study, the CCK-8 assay was performed to determine the cytotoxicity of four sizes (10, 30, 50, and 100 nm) of anatase nano-TiO2 on human umbilical vein endothelial cells (HUVECs) in culture, and the flow cytometry was employed to investigate the potential of these nano-TiO2 to induce the apoptosis of HUVECs. The apoptotic pathway was also probed through the determination of the protein expression and activation of p53, Bax, Bcl-2, caspases-9, -7, -3, and PARP by western blot. The results showed that at the administrative levels (1, 5, 25 µg/mL), all the four sizes of nano-TiO2 could significantly inhibit the viability of HUVECs and elicit significant apoptosis in them, compared with the negative control (P < .05, P < .01). Moreover, the apoptotic rates of HUVECs were increased respectively with the elevating levels and decreasing sizes of the administrative nano-TiO2 , showing a clear dose- and size-dependent effect relationships. Interestingly, the increasing phosphorylation of p53, decreasing ratio of Bcl-2/Bax, and enhancing activation of the downstream proteins caspase-9, -7, -3, and PARP, were also observed with the decreasing sizes of the administrative nano-TiO2 in the western blot, indicating that the intracellular approach of apoptosis, the p53-caspase pathway, is the major way of the nano-TiO2 -mediated apoptosis in HUVECs in culture and that the size is an important parameter that may determine the potential of nano-TiO2 to induce cellular response. In conclusion, these results suggested that high levels of nano-TiO2 exposure may pose potential risks to human cardiovascular health by inducing cardiovascular EC apoptosis.


Assuntos
Apoptose/efeitos dos fármacos , Células Endoteliais da Veia Umbilical Humana/efeitos dos fármacos , Nanopartículas/toxicidade , Titânio/toxicidade , Caspase 9/metabolismo , Caspases/metabolismo , Células Cultivadas , Citoplasma/metabolismo , Células Endoteliais da Veia Umbilical Humana/fisiologia , Humanos , Tamanho da Partícula , Fosforilação , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Transdução de Sinais/efeitos dos fármacos , Titânio/química
13.
Development ; 140(4): 780-8, 2013 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-23362346

RESUMO

Thymic epithelial cells (TECs) are the main component of the thymic stroma, which supports T-cell proliferation and repertoire selection. Here, we demonstrate that Cbx4, a Polycomb protein that is highly expressed in the thymic epithelium, has an essential and non-redundant role in thymic organogenesis. Targeted disruption of Cbx4 causes severe hypoplasia of the fetal thymus as a result of reduced thymocyte proliferation. Cell-specific deletion of Cbx4 shows that the compromised thymopoiesis is rooted in a defective epithelial compartment. Cbx4-deficient TECs exhibit impaired proliferative capacity, and the limited thymic epithelial architecture quickly deteriorates in postnatal mutant mice, leading to an almost complete blockade of T-cell development shortly after birth and markedly reduced peripheral T-cell populations in adult mice. Furthermore, we show that Cbx4 physically interacts and functionally correlates with p63, which is a transcriptional regulator that is proposed to be important for the maintenance of the stemness of epithelial progenitors. Together, these data establish Cbx4 as a crucial regulator for the generation and maintenance of the thymic epithelium and, hence, for thymocyte development.


Assuntos
Proliferação de Células , Células Epiteliais/fisiologia , Regulação da Expressão Gênica no Desenvolvimento/fisiologia , Organogênese/fisiologia , Complexo Repressor Polycomb 1/metabolismo , Timo/embriologia , Ubiquitina-Proteína Ligases/metabolismo , Animais , Bromodesoxiuridina , Células Epiteliais/metabolismo , Citometria de Fluxo , Regulação da Expressão Gênica no Desenvolvimento/genética , Marcação de Genes , Técnicas Histológicas , Imunoprecipitação , Ligases , Camundongos , Microscopia de Fluorescência , Fosfoproteínas/metabolismo , Reação em Cadeia da Polimerase em Tempo Real , Linfócitos T/citologia , Timo/citologia , Transativadores/metabolismo
14.
J Immunol ; 193(2): 663-672, 2014 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-24920844

RESUMO

T regulatory (Treg) cells play crucial roles in the regulation of cellular immunity. The development of Treg cells depends on signals from TCRs and IL-2Rs and is influenced by a variety of transcription factors. The basic helix-loop-helix proteins are known to influence TCR signaling thresholds. Whether this property impacts Treg differentiation is not understood. In this study, we interrogated the role of basic helix-loop-helix proteins in the production of Treg cells using the CD4 promoter-driven Id1 transgene. We found that Treg cells continued to accumulate as Id1 transgenic mice aged, resulting in a significant increase in Treg cell counts in the thymus as well as in the periphery compared with wild-type controls. Data from mixed bone marrow assays suggest that Id1 acts intrinsically on developing Treg cells. We made a connection between Id1 expression and CD28 costimulatory signaling because Id1 transgene expression facilitated the formation of Treg precursors in CD28(-/-) mice and the in vitro differentiation of Treg cells on thymic dendritic cells despite the blockade of costimulation by anti-CD80/CD86. Id1 expression also allowed in vitro Treg differentiation without anti-CD28 costimulation, which was at least in part due to enhanced production of IL-2. Notably, with full strength of costimulatory signals, however, Id1 expression caused modest but significant suppression of Treg induction. Finally, we demonstrate that Id1 transgenic mice were less susceptible to the induction of experimental autoimmune encephalomyelitis, thus illustrating the impact of Id1-mediated augmentation of Treg cell levels on cellular immunity.


Assuntos
Diferenciação Celular/imunologia , Proteína 1 Inibidora de Diferenciação/imunologia , Receptores de Antígenos de Linfócitos T/imunologia , Linfócitos T Reguladores/imunologia , Animais , Antígeno B7-1/imunologia , Antígeno B7-1/metabolismo , Antígeno B7-2/imunologia , Antígeno B7-2/metabolismo , Antígenos CD28/genética , Antígenos CD28/imunologia , Antígenos CD28/metabolismo , Diferenciação Celular/genética , Células Cultivadas , Células Dendríticas/imunologia , Células Dendríticas/metabolismo , Encefalomielite Autoimune Experimental/genética , Encefalomielite Autoimune Experimental/imunologia , Encefalomielite Autoimune Experimental/metabolismo , Citometria de Fluxo , Fatores de Transcrição Forkhead/imunologia , Fatores de Transcrição Forkhead/metabolismo , Proteína 1 Inibidora de Diferenciação/genética , Proteína 1 Inibidora de Diferenciação/metabolismo , Interleucina-2/imunologia , Interleucina-2/metabolismo , Contagem de Linfócitos , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Camundongos Transgênicos , Receptores de Antígenos de Linfócitos T/metabolismo , Transdução de Sinais/genética , Transdução de Sinais/imunologia , Linfócitos T Reguladores/metabolismo , Timo/imunologia , Timo/metabolismo
15.
ACS Omega ; 9(16): 18083-18098, 2024 Apr 23.
Artigo em Inglês | MEDLINE | ID: mdl-38680308

RESUMO

Cardiovascular diseases (CVDs) are significant causes of morbidity and mortality worldwide, and pathological cardiac hypertrophy (PCH) is an essential predictor of many heart diseases. Guanxinshutong capsule (GXST) is a Chinese patent medicine widely used in the clinical treatment of CVD, In our previous research, we identified 111 compounds of GXST. In order to reveal the potential molecular mechanisms by which GXST treats PCH, this study employed network pharmacology methods to screen for the active ingredients of GXST in treating PCH and predicted the potential targets. The results identified 26 active ingredients of GXST and 110 potential targets for PCH. Through a protein-protein interaction (PPI) network, gene ontology (GO), and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis, we confirmed AKT1, MAPK1, and MAPK3 as the core proteins in GXST treatment of PCH, thus establishing the PI3K/AKT and MAPK signaling pathways as the significant mechanisms of GXST in treating PCH. The results of molecular docking (MD) demonstrate that flavonoid naringenin and diterpenoid tanshinone iia have the highest binding affinity with the core protein. Before performing molecular dynamics simulations (MDSs), the geometric structure of naringenin and tanshinone iia was optimized using density functional theory (DFT) at the B97-3c level, and RESP2 atomic charge calculations were carried out at the B3LYP-D3(BJ)/def2-TZVP level. Further MDS results demonstrated that in the human body environment, the complex of naringenin and tanshinone iii with core proteins exhibited high stability, flexibility, and low binding free energy. Additionally, naringenin and tanshinone iia showed favorable absorption, distribution, metabolism, excretion, and toxicity (ADMET) characteristics and passed the drug similarity (DS) assessment. Ultrasound cardiograms and cardiac morphometric measurements in animal experiments demonstrate that GXST can improve the PCH induced by isoproterenol (ISO). Protein immunoblotting results indicate that GXST increases the expression of P-eNOS and eNOS by activating the PI3K/AKT signaling pathway and the MAPK signaling pathway, further elucidating the mechanism of action of GXST in treating PCH. This study contributes to the elucidation of the key ingredients and molecular mechanisms of GXST in treating PCH.

16.
J Am Chem Soc ; 135(20): 7486-95, 2013 May 22.
Artigo em Inglês | MEDLINE | ID: mdl-23607819

RESUMO

The thermopower (S) and electrical conductivity (σ) in conventional semiconductors are coupled adversely through the carriers' density (n) making it difficult to achieve meaningful simultaneous improvements in both electronic properties through doping and/or substitutional chemistry. Here, we demonstrate the effectiveness of coherently embedded full-Heusler (FH) quantum dots (QDs) in tailoring the density, mobility, and effective mass of charge carriers in the n-type Ti(0.1)Zr(0.9)NiSn half-Heusler matrix. We propose that the embedded FH QD forms a potential barrier at the interface with the matrix due to the offset of their conduction band minima. This potential barrier discriminates existing charge carriers from the conduction band of the matrix with respect to their relative energy leading to simultaneous large enhancements of the thermopower (up to 200%) and carrier mobility (up to 43%) of the resulting Ti(0.1)Zr(0.9)Ni(1+x)Sn nanocomposites. The improvement in S with increasing mole fraction of the FH-QDs arises from a drastic reduction (up to 250%) in the effective carrier density coupled with an increase in the carrier's effective mass (m*), whereas the surprising enhancement in the mobility (µ) is attributed to an increase in the carrier's relaxation time (τ). This strategy to manipulate the transport behavior of existing ensembles of charge carriers within a bulk semiconductor using QDs is very promising and could pave the way to a new generation of high figure of merit thermoelectric materials.


Assuntos
Pontos Quânticos , Temperatura , Tamanho da Partícula , Semicondutores , Propriedades de Superfície
17.
Biochem Biophys Res Commun ; 436(1): 47-52, 2013 Jun 21.
Artigo em Inglês | MEDLINE | ID: mdl-23707719

RESUMO

Although the role of E proteins in the thymocyte development is well documented, much less is known about their function in peripheral T cells. Here we demonstrated that CD4 promoter-driven transgenic expression of Id1, a naturally occurring dominant-negative inhibitor of E proteins, can substitute for the co-stimulatory signal delivered by CD28 to facilitate the proliferation and survival of naïve CD4+ cells upon anti-CD3 stimulation. We next discovered that IL-2 production and NF-κB activity after anti-CD3 stimulation were significantly elevated in Id1-expressing cells, which may be, at least in part, responsible for the augmentation of their proliferation and survival. Taken together, results from this study suggest an important role of E and Id proteins in peripheral T cell activation. The ability of Id proteins to by-pass co-stimulatory signals to enable T cell activation has significant implications in regulating T cell immunity.


Assuntos
Linfócitos T CD4-Positivos/citologia , Regulação da Expressão Gênica , Proteína 1 Inibidora de Diferenciação/biossíntese , Receptores de Antígenos de Linfócitos T/metabolismo , Animais , Antígenos CD28/metabolismo , Complexo CD3/metabolismo , Proliferação de Células , Separação Celular , Sobrevivência Celular , Relação Dose-Resposta a Droga , Citometria de Fluxo , Interleucina-2/metabolismo , Ativação Linfocitária , Camundongos , Camundongos Transgênicos , NF-kappa B/metabolismo
18.
Clin Dev Immunol ; 2013: 462152, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-24369474

RESUMO

Netrin-1, a known axon guidance molecule, being a secreted laminin-related molecule, has been suggested to be involved in multiple physiological and pathological conditions, such as organogenesis, angiogenesis, tumorigenesis, and inflammation-mediated tissue injury. However, its function in thymocyte development is still unknown. Here, we demonstrate that Netrin-1 is expressed in mouse thymus tissue and is primarily expressed in thymic stromal cells, and the expression of Netrin-1 in thymocytes can be induced by anti-CD3 antibody or IL-7 treatment. Importantly, Netrin-1 mediates the adhesion of thymocytes, and this effect is comparable to or greater than that of fibronectin. Furthermore, Netrin-1 specifically promotes the chemotaxis of CXCL12. These suggest that Netrin-1 may play an important role in thymocyte development.


Assuntos
Movimento Celular/genética , Expressão Gênica , Fatores de Crescimento Neural/genética , Timócitos/metabolismo , Timo/metabolismo , Proteínas Supressoras de Tumor/genética , Animais , Adesão Celular/genética , Adesão Celular/imunologia , Movimento Celular/imunologia , Quimiocina CXCL12/farmacologia , Regulação da Expressão Gênica/efeitos dos fármacos , Interleucina-7/farmacologia , Camundongos , Fatores de Crescimento Neural/metabolismo , Receptores de Netrina , Netrina-1 , Receptores de Superfície Celular/genética , Receptores de Superfície Celular/metabolismo , Timócitos/imunologia , Timo/imunologia , Proteínas Supressoras de Tumor/metabolismo
19.
Zhongguo Zhong Xi Yi Jie He Za Zhi ; 33(6): 795-9, 2013 Jun.
Artigo em Chinês | MEDLINE | ID: mdl-23980361

RESUMO

OBJECTIVE: To explore the effect of Chinese herbs for Shen invigorating and blood activating (CHSIBA) on the number of endothelial progenitor cells (EPCs) in the bone marrow and the peripheral blood and the signaling pathway of bone marrow matrix metalloproteinase 9 (MMP-9) of the myocardial infarction (MI) model rats. METHODS: The MI rat model was established by ligation. Thirty successfully modeled rats were randomly divided into the high dose CHSIBA group, the low dose CHSIBA group, and the model group, 10 in each group. Besides, another 10 normal rats were recruited as the blank group. Rats in the high dose CHSIBA group and the low dose CHSIBA group were administered with CHSIBA at 3 g/kg and 1.5 g/kg body weight by gastrogavage (by adding them in 4 mL physiological saline), once daily. Rats in the model group and the blank group were administered with 4 mL physiological saline once daily. The EPCs were collected from the bone marrow and the peripheral blood 4 weeks later. Seven days later the CD34/CD133 phenotype was identified in collected sticking wall cells using flow cytometry. The MMP-9 and water soluble Kit ligand (sKitL) were detected using Western blot. The expressions of vascular endothelial growth factor (VEGF) and stromal cell-derived factor-1alpha (SDF-1alpha) were detected using ELISA. RESULTS: The CD34/CD133 positive rate and the EPC quantity in the bone marrow and the peripheral blood were higher in the high dose CHSIBA group and the low dose CHSIBA group than in the model group (P < 0.05, P < 0.01). Besides, the expressions of VEGF, SDF-1alpha, MMP-9, and sKitL in the bone marrow and the peripheral blood were also higher in the high dose CHSIBA group and the low dose CHSIBA group than in the model group (P < 0.05, P < 0.01). CONCLUSION: CHSIBA could activate MMP-9 signaling pathway, increase its upstream and downstream signal expression levels, and mobilize EPCs in the bone marrow to enter the blood circulation.


Assuntos
Células da Medula Óssea/efeitos dos fármacos , Medicamentos de Ervas Chinesas/farmacologia , Metaloproteinase 9 da Matriz/metabolismo , Infarto do Miocárdio/metabolismo , Transdução de Sinais , Animais , Células da Medula Óssea/metabolismo , Células Endoteliais/efeitos dos fármacos , Células Endoteliais/metabolismo , Masculino , Ratos , Ratos Sprague-Dawley , Células-Tronco/efeitos dos fármacos , Células-Tronco/metabolismo
20.
J Colloid Interface Sci ; 636: 305-316, 2023 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-36638570

RESUMO

High-efficiency oxygen reduction reaction (ORR) electrocatalyst in microbial fuel cells (MFCs) is important to boost the power production efficiency and reduce overall cost. Herein, we demonstrate a novel nitrogen (N)-doped carbon nanofiber (N-CNF) supported metal and metal compound heterostructure derived from metal-organic frameworks (MOFs), which endows superior electrocatalytic activity by optimizing the coupling modulation effect. The resulting cobalt/cobalt phosphide and cobalt/cobalt sulfide nanoparticles embedded in N-doped carbon nanofiber (Co/CoP/Co2P@N-CNF, Co/CoS2@N-CNF) present superior ORR activity and methanol tolerance. Moreover, the assembled MFCs modified with Co/CoP/Co2P@N-CNF and Co/CoS2@N-CNF composite also achieve higher power density (375.16 and 400.06 mW m-2) as well as coulombic efficiency (11.2 %, 12.4 %), superior than that of Pt/C electrode (333.70 mW m-2, 10.4 %). Impressively, the Co/CoS2@N-CNF electrode exhibits long-term stability and durability in dual-chamber MFCs. A high-performance heterostructure cathode with an effective strategy for bridging nanocatalysis and practical MFCs is reported and presented.

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