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1.
Front Oncol ; 11: 737989, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34745959

RESUMO

Purpose: To compare the diagnostic performance of 68Ga-PSMA-11 PET/CT and mpMRI for pelvic lymph node staging prior to radical prostatectomy in prostate cancer (PCa) patients based on per patient data. Methods: PubMed and Embase databases were searched until October 2020 for eligible studies evaluating head-to-head comparison of 68Ga-PSMA-PET/CT and mpMRI for the detection of pelvic lymph node metastases (PLNMs) using pelvic lymph node dissection (PLND) as gold standard. The pooled sensitivity, specificity, and area under the summary receiver-operating characteristics curve (AUC) were determined for the two imaging modalities. Results: Nine studies with 640 patients were included. The pooled sensitivity, specificity, and AUC for 68Ga-PSMA-11 PET/CT vs. mpMRI were 0.71 (95% CI: 0.48-0.86) vs. 0.40 (95% CI: 0.16-0.71), 0.92 (95% CI: 0.88-0.95) vs. 0.92 (95% CI: 0.80-0.97), and 0.92 (95% CI: 0.88-0.95) vs. 0.82 (95% CI: 0.79-0.86), respectively. There was substantial heterogeneity for both imaging modalities, and meta-regression analysis revealed that the number of patients, prevalence of PLNMs, PSA level, reference standard, and risk classification might be the potential causes of heterogeneity. Conclusion: This meta-analysis of head-to-head comparison studies confirms that there is a trend toward a higher sensitivity and diagnostic accuracy of 68Ga-PSMA-11 PET/CT compared to mpMRI for the detection of PLNMs in PCa patients. Nevertheless, according to current guidelines, PLND still needs to be recommended in case of negative results from 68Ga-PSMA-11 PET/CT due to significant risk of malignancy.

3.
Nature ; 597(7877): 503-510, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34552257

RESUMO

Large, distributed collections of miniaturized, wireless electronic devices1,2 may form the basis of future systems for environmental monitoring3, population surveillance4, disease management5 and other applications that demand coverage over expansive spatial scales. Aerial schemes to distribute the components for such networks are required, and-inspired by wind-dispersed seeds6-we examined passive structures designed for controlled, unpowered flight across natural environments or city settings. Techniques in mechanically guided assembly of three-dimensional (3D) mesostructures7-9 provide access to miniature, 3D fliers optimized for such purposes, in processes that align with the most sophisticated production techniques for electronic, optoelectronic, microfluidic and microelectromechanical technologies. Here we demonstrate a range of 3D macro-, meso- and microscale fliers produced in this manner, including those that incorporate active electronic and colorimetric payloads. Analytical, computational and experimental studies of the aerodynamics of high-performance structures of this type establish a set of fundamental considerations in bio-inspired design, with a focus on 3D fliers that exhibit controlled rotational kinematics and low terminal velocities. An approach that represents these complex 3D structures as discrete numbers of blades captures the essential physics in simple, analytical scaling forms, validated by computational and experimental results. Battery-free, wireless devices and colorimetric sensors for environmental measurements provide simple examples of a wide spectrum of applications of these unusual concepts.

4.
Prenat Diagn ; 41(12): 1518-1523, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34480362

RESUMO

OBJECTIVE: To clarify the relationships between placental characteristics and birthweight discordance in three types of selective intrauterine growth restriction (sIUGR) in monochorionic diamniotic twins. METHODS: A retrospective cohort study was conducted between april 2013 and april 2020. Associations between placental characteristics and birthweight discordance were evaluated through multiple linear regression analyses with two models for each sIUGR type. Model A was adjusted for gestational age, Model B additionally adjusted for the impact of placental characteristics interacted. RESULTS: In cases of type I sIUGR, birthweight discordance ratio was positively associated with placental territory discordance ratio [(ß = 0.181,95%CI(0.072,0.290), p < 0.05), (ß = 0.239,95%CI(0.125, 0.353), p < 0.05)] under both Model A and Model B. In-type II sIUGR [(ß = -0.012,95%CI(-0.020, -0.004), p < 0.05) (ß = -0.010,95%CI (-0.018, -0.002), p < 0.05)] and type III sIUGR [(ß = -0.011,95%CI (-0.021, -0.001), p < 0.05), (ß = -0.012,95%CI(-0.022, -0.003), p < 0.05)], birthweight discordance ratio was negatively associated with the total diameter of all the anastomoses as calculated with both Model A and Model B. CONCLUSION: Birthweight discordance is primarily related to placental territory discordance in type I sIUGR, whereas vascular anastomoses play important roles for growth-restricted fetal compensation in type II and III sIUGR.

5.
Mater Horiz ; 8(12): 3324-3333, 2021 Nov 29.
Artigo em Inglês | MEDLINE | ID: mdl-34528049

RESUMO

Origami-inspired multistable structures are gaining increasing interest because of their potential applications in fields ranging from deployable structures to reconfigurable microelectronics. The multistability of such structures is critical for their applications but is challenging to manipulate due to the highly nonlinear deformations and complex configurations of the structures. Here, a comprehensive experimental and computational study is reported to tailor the multistable states of origami-inspired, buckled ferromagnetic structures and their reconfiguration paths. Using ribbon structures as an example, a design phase diagram is constructed as a function of the crease number and compressive strain. As the crease number increases from 0 to 7, the number of distinct stable states first increases and then decreases. The multistability is also shown to be actively tuned by varying the strain from 0% to 40%. Furthermore, analyzing energy barriers for reconfiguration among the stable states reveals dynamic changes in reconfiguration paths with increasing strains. Guided by studies above, diverse examples are designed and demonstrated, from programmable structure arrays to a soft robot. These studies lay out the foundation for the rational design of functional, multistable structures.

6.
ACS Appl Mater Interfaces ; 13(28): 33464-33476, 2021 Jul 21.
Artigo em Inglês | MEDLINE | ID: mdl-34241991

RESUMO

Encapsulation materials play an important role in many applications including wearable electronics, medical devices, underwater robotics, marine skin tagging system, food packaging, and energy conversation and storage devices. To date, all the encapsulation materials, including polymer layers and inorganic materials, are solid materials. These solid materials suffer from limited barrier lifetimes due to pinholes, cracks, and nanopores or from complicated fabrication processes and limited stretchability for interfacing with complex 3D surfaces. This paper reports a solution to this material challenge by demonstrating bioinspired oil-infused slippery surfaces with excellent waterproof property for the first time. A water vapor transmission test shows that locking a thin layer of oil on the silicone elastomer improves the water vapor barrier performance by three orders of magnitude. Accelerated lifetime tests suggest robust water barrier characteristics that approach 226 days at 37 °C even under severe mechanical damage. A combination of temperature- and thickness-dependent experimental measurements and reaction-diffusion modeling reveals the key waterproof property. In addition to serving as a barrier to water, the oil-infused surface demonstrates an attractive ion barrier property. All these exceptional properties suggest the potential applications of slippery surfaces as encapsulation materials for medical devices, underwater electronics, and many others.


Assuntos
Fluorcarbonetos/química , Óleos/química , Elastômeros de Silicone/química , Interações Hidrofóbicas e Hidrofílicas , Teste de Materiais , Permeabilidade , Óleos de Silicone/química , Vapor , Propriedades de Superfície , Água/química
7.
Acta Obstet Gynecol Scand ; 100(9): 1688-1693, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34075586

RESUMO

INTRODUCTION: This study aimed to explore the differences in placental characteristics among three types of selective fetal growth restriction (sFGR) in monochorionic diamniotic twin pregnancies. MATERIAL AND METHODS: A total of 123 placentas with sFGR between April 2013 and October 2019 were retrospectively analyzed after dye injection. Placental characteristics were compared among the three types. RESULTS: The gestational age at diagnosis and delivery was less in sFGR II and III than in sFGR I (22.9 [21.7-33.6], 23.3 [20.0-26.1] and 25.7 [19.0-35.0] weeks, p < 0.001; 32.3 [31.6-35.1], 34.1 [29.9-34.7] and 35.5 [34.0-37.0] weeks, p < 0.001). The birthweight discordance ratio was less in sFGR I than in sFGR II (0.28 [0.14-0.43] and 0.30 [0.23-0.37], p < 0.001). The prevalence of a thick artery-artery anastomosis was higher in sFGR III than in sFGR I or II (81.8%, 44.9% and 48.6%, p = 0.010). The placental territory discordance ratio was higher in sFGR II and III than in sFGR I (0.60 [0.17-0.88], 0.60 [0.01-0.80] and 0.50 [0.01-0.71], p = 0.001). CONCLUSIONS: Compared with sFGR I, the earlier onset time of sFGR II and III might be due to their higher placental territory discordance. The prevalence of thick artery-artery anastomoses was expected to be higher in sFGR III than in sFGR I or II.


Assuntos
Retardo do Crescimento Fetal/diagnóstico por imagem , Placenta/fisiopatologia , Gravidez de Gêmeos , Gêmeos Monozigóticos , Ultrassonografia Pré-Natal , Artérias Umbilicais/fisiologia , Adulto , Velocidade do Fluxo Sanguíneo , Estudos de Coortes , Feminino , Idade Gestacional , Humanos , Gravidez , Fluxo Pulsátil , Estudos Retrospectivos , Adulto Jovem
8.
ACS Appl Mater Interfaces ; 13(7): 8929-8939, 2021 Feb 24.
Artigo em Inglês | MEDLINE | ID: mdl-33577299

RESUMO

Three-dimensional (3D) mesostructures are gaining rapidly growing interest due to their potential applications in a broad range of areas. Despite intensive studies, remotely controlled, reversible, on-demand assembly and reconfiguration of 3D mesostructures, which are desired for many applications, including robotics, minimally invasive biomedical devices, and deployable systems, remain a challenge. Here, we introduce a facile strategy to utilize liquid crystal elastomers (LCEs), a soft polymer capable of large, reversible shape changes, as a platform for reversible assembly and programming of 3D mesostructures via compressive buckling of two-dimensional (2D) precursors in a remote and on-demand fashion. The highly stretchable, reversible shape-switching behavior of the LCE substrate, resulting from the soft elasticity of the material and the reversible nematic-isotropic transition of liquid crystal (LC) molecules upon remote thermal stimuli, provides deterministic thermal-mechanical control over the reversible assembly and reconfiguration processes. Demonstrations include experimental results and finite element simulations of 3D mesostructures with diverse geometries and material compositions, showing the versatility and reliability of the approach. Furthermore, a reconfigurable light-emitting system is assembled and morphed between its "on" and "off" status via the LCE platform. These results provide many exciting opportunities for areas from remotely programmable 3D mesostructures to tunable electronic systems.

9.
Nucl Med Commun ; 42(5): 523-527, 2021 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-33481505

RESUMO

OBJECTIVE: To investigate the diagnostic performance of 18F-FDG PET/computed tomography (CT) for the detection of occult primary tumors in patients with squamous cell carcinoma of unknown primary (SCCUP) in the head and neck. PATIENTS: From March 2016 to January 2020, 37 patients diagnosed as SCCUP before PET/CT were retrospectively reviewed. The diagnosis of SCCUP was made when an overt primary tumor location could not be found for histologically proven squamous cell cervical lymphadenopathy after a complete diagnostic workup which includes full medical history, physical examinations, flexible rhinolaryngoscopy and CT or MRI. The PET/CT images were visually assessed by two nuclear medicine radiologists. Histopathological investigations after the PET scan served as the reference standard. RESULTS: The sensitivity, specificity, positive predictive value, negative predictive value and accuracy of PET/CT for SCCUP were 71.4, 43.8, 62.5, 53.9 and 59.5%, respectively. PET/CT allowed identification of previously undetected lesions in 40.5% of the SCCUP patients. A total of 24 PET/CT scans indicated a positive result. Among them, nine were categorized into false-positive because of negative results from subsequent targeted and random biopsies. There were 13 PET/CT scans with a negative result, six of which, however, were revealed to have a primary site by subsequent random biopsies. CONCLUSION: 18F-FDG PET/CT was shown to be useful in detecting a primary tumor for SCCUP, but had limitations in terms of both false-positive cases and false-negative cases. Therefore, histopathological investigations such as targeted and random biopsy should be viewed as necessary practice irrespective of PET/CT results.


Assuntos
Carcinoma de Células Escamosas/diagnóstico por imagem , Fluordesoxiglucose F18 , Neoplasias de Cabeça e Pescoço/diagnóstico por imagem , Neoplasias Primárias Desconhecidas/diagnóstico por imagem , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Adulto , Idoso , Carcinoma de Células Escamosas/patologia , Neoplasias de Cabeça e Pescoço/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias Primárias Desconhecidas/patologia , Estudos Retrospectivos , Sensibilidade e Especificidade
10.
Placenta ; 103: 10-15, 2021 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-33068961

RESUMO

INTRODUCTION: To investigate the correlation between placental superficial anastomoses, placental territory and the umbilical cord attachment site with the time of onset of twin-to-twin transfusion syndrome (TTTS), and to explore the influence of placental characteristics on the time of onset of TTTS. METHODS: A retrospective analysis was performed on 48 cases of TTTS managed conservatively at the Obstetrics Department of Peking University Third Hospital from April 2014 to April 2019. Placental superficial anastomoses, placental territory, the distance between the insertion points of the umbilical cord were measured after placental dye injection. Correlation analysis was conducted between placental characteristics and the time of onset of TTTS. RESULTS: (1) The incidence of AA anastomoses was 33.3% (16/48) with a mean total diameter of 2.3 ± 1.4 mm, that of AV anastomoses was 95.8% (46/48) with a mean total diameter of 1.2 ± 0.4 mm, and that of VV anastomoses 22.9% (11/48) with a mean total diameter of 2.3 ± 1.1 mm (2) The time of onset of TTTS was positively correlated with the umbilical insertion ratio (Spearman correlation coefficient = 0.404, P = 0.004), but not correlated with the total diameter of anastomoses in the three different types, or with placental territory discordance. DISCUSSION: The time of onset of TTTS was positively correlated with the umbilical insertion ratio, which suggest that the distance between umbilical cord insertion sites may affect the time of onset of TTTS. The smaller the distance between the umbilical cord insertion sites, the earlier the time of onset of TTTS is likely to be.

11.
Acta Obstet Gynecol Scand ; 100(2): 229-234, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-32897576

RESUMO

INTRODUCTION: The aim of the study was to investigate the placental characteristics in spontaneous twin anemia polycythemia sequence. MATERIAL AND METHODS: A retrospective case-control study of spontaneous twin anemia polycythemia sequence, twin-to-twin transfusion syndrome and normal monochorionic diamniotic twin pregnancies was performed. The primary outcome was placental characteristics. RESULTS: The prevalence of artery-artery anastomoses in spontaneous twin anemia polycythemia sequence and twin-to-twin transfusion syndrome groups was significantly lower than in the normal monochorionic diamniotic twin group (40.0% vs 33.3% vs 88.8%, respectively, P < .001). The total number of vascular anastomoses in the spontaneous twin anemia polycythemia sequence group (with range given in parentheses) was significantly lower than in the two control groups (3 [1-6] vs 5 [1-14] vs 6 [1-20], P = .001/<.001/.794). The number of artery-vein anastomoses in the spontaneous twin anemia polycythemia sequence was significantly lower than in the two control groups (2 [1-5] vs 4 [1-13] vs 5 [1-19], P = .011/.001/1.000). The total diameter of all vascular anastomoses was significantly smaller in the spontaneous twin anemia polycythemia sequence than in the two control groups (0.9 mm [0.3-4.7] vs 5.2 mm [0.8-24.6] vs 7.3 mm [1.0-25.1], P < .001/<.001/.104), as was the total diameter of artery-to-artery anastomoses (0.5 mm [0.3-1.3] vs 2.0 mm [0.5-11.8] vs 2.3 mm [0.7-9.7], P = .003/<.001/1.000) and the total diameter of artery-to-vein anastomoses (0.8 mm [0.3-2.1] vs 4.6 mm [0.8-15.3] vs 4.0 mm [0.2-21.8], P < .001/<.001/1.000). The ratio between the distance of the two umbilical cords insertion points and the placental maximum diameter in the spontaneous twin anemia polycythemia sequence group was significantly larger than in the two control groups (0.78 [0.49-0.99] vs 0.64 [0.32-1.00] vs 0.55 [0.05-1.00], P = .033/<.001/.138). CONCLUSIONS: In spontaneous twin anemia polycythemia sequence placentas, the number of superficial vascular anastomoses is lower, their diameter is smaller and the distance between the two umbilical cord insertion points is longer.


Assuntos
Doenças em Gêmeos/complicações , Transfusão Feto-Fetal/complicações , Policitemia/complicações , Cordão Umbilical/anatomia & histologia , Adulto , Estudos de Casos e Controles , Corantes , Feminino , Humanos , Processamento de Imagem Assistida por Computador , Fotografação , Placenta/anatomia & histologia , Gravidez , Estudos Retrospectivos , Gêmeos Monozigóticos , Adulto Jovem
12.
Placenta ; 104: 89-93, 2021 01 15.
Artigo em Inglês | MEDLINE | ID: mdl-33296736

RESUMO

INTRODUCTION: To investigate differences in the pregnancy outcomes and placental characteristics of selective intrauterine growth restriction (sIUGR) with or without twin anemia polythemia sequence (TAPS). METHODS: sIUGR patients were assigned into two groups based on the occurrence of TAPS. The pregnancy outcomes and placental characteristics were compared. A diameter of ≥2 mm was defined as thick anastomosis. RESULTS: The prevalence of artery-to-artery (AA) (45.5% vs 88.6%, P = 0.002) and thick AA (0% vs 53.5%) in TAPS group were lower than non-TAPS group. The overall diameter of AA (0.5 (0.4-1.3) vs 2.5 (0.3-7.1) mm, P = 0.001) in TAPS group was smaller than non-TAPS group. The prevalence of thick artery-to-vein (AV) (0% vs 36.0%) in TAPS group was lower than non-TAPS group. Also, the overall diameter of AV (0.9 (0.6-2.1) vs 4.8 (0.3-17.8) mm, P < 0.001) in TAPS group was smaller than non-TAPS group. The total quantity (2 (1-6) vs 6 (1-16), P = 0.001), and the overall diameter of anastomoses (1.1 (0.6-4.7) vs 7.5 (0.5-22.4) mm, P < 0.001) were smaller in TAPS group than non-TAPS group. The placental territory discordance ratio of TAPS group was smaller than non-TAPS group (0.39 (0.13-0.56) vs 0.56 (0.01-0.88), P = 0.008). The umbilical cord insertion distance ratio in TAPS group was higher than non-TAPS group (0.81 ± 0.12 vs 0.57 ± 0.20, P < 0.001). DISCUSSION: The placental anastomoses of sIUGR with TAPS were small. sIUGR with TAPS had smaller differences in placental share and larger distances between umbilical cord insertions.

13.
J Matern Fetal Neonatal Med ; : 1-7, 2020 Nov 17.
Artigo em Inglês | MEDLINE | ID: mdl-33203261

RESUMO

OBJECTIVE: To explore differences among placental anastomoses, territory discordance, and umbilical cord insertion of twin-to-twin transfusion syndrome (TTTS) with and without selective intrauterine growth restriction (sIUGR). METHODS: This study retrospectively analyzed 57 patients with TTTS who received conservative treatment and finally delivered at the Department of Obstetrics and Gynecology of Peking University Third Hospital from April 2014 to April 2019. Nine of the patient's placentas were too broken to finish the perfusion, and 48 were kept for graph analysis after perfusion. Among the 48 placentas, there were 17 in the TTTS with sIUGR group and 31 in the TTTS without sIUGR group. Differences in the placentas were compared between groups. RESULTS: The birth weight discordance ratio in the sIUGR group was significantly higher than that in the non-sIUGR group (0.41 ± 0.20 vs 0.24 ± 0.15, p = .001). The prevalence of thick artery-artery (AA) anastomoses in the sIUGR group was significantly higher than that in the non-sIUGR group (35.3% vs 6.5%, p = .017). The placental territory discordance ratio in the sIUGR group was significantly higher than that in the non-sIUGR group (0.40 [0.05, 0.86] vs 0.25 [0.02, 0.67], p = .024). The prevalence of velamentous cord insertion in the sIUGR group was significantly higher than that in the non sIUGR group (35.3% and 6.5%, p = .017). CONCLUSIONS: Placental territory discordance and velamentous umbilical cord insertion may be causes of TTTS with sIUGR. Compared with TTTS without sIUGR, TTTS with sIUGR had a higher prevalence of protective AA anastomoses in the placenta.

14.
Mol Med ; 26(1): 37, 2020 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-32357834

RESUMO

BACKGROUND: Selective intrauterine fetal growth restriction (sIUGR) in monochorionic diamniotic twins, especially types 2&3 with abnormal umbilical artery Doppler, results in increased risk of fetal/perinatal mortality and postnatal disability. We investigate whether the hair metabolome profiles of neonates were associated with the pathophysiological differences across the different clinical forms of sIUGR in twins. METHODS: Hair samples were collected at delivery from 10 pairs of type 1 sIUGR twins, 8 pairs of types 2&3 sIUGR twins, and 11 pairs of twins without sIUGR. The hair metabolome was characterized using gas chromatography-mass spectrometry. RESULTS: Our results demonstrated that the hair metabolite profiles of the different sIUGR subclinical forms were associated with the averaged fetal growth rate after 28 weeks of gestation but not with birthweight. The hair profiles were capable of discriminating type2&3 sIUGR twins from twins without sIUGR. In particular, the metabolites 2-aminobutyric acid, cysteine, alanine, and tyrosine all displayed areas under the receiver operating characteristic curve were above 0.9. The metabolic pathway analysis highlighted the associations of sIUGR twins with abnormal umbilical artery flow with increased metabolites from a nutrient depletion pathway, glutathione metabolism, and nerve development. CONCLUSION: This study offers novel insight into the severity of intrauterine ischemia and hypoxia for T2&3 sIUGR twins, through evaluation of the neonatal hair metabolome.


Assuntos
Metabolismo Energético , Retardo do Crescimento Fetal/metabolismo , Cabelo/metabolismo , Fenótipo , Gêmeos Monozigóticos , Artérias Umbilicais/fisiopatologia , Estudos de Casos e Controles , Biologia Computacional , Feminino , Retardo do Crescimento Fetal/diagnóstico , Cromatografia Gasosa-Espectrometria de Massas , Idade Gestacional , Humanos , Recém-Nascido , Metaboloma , Metabolômica/métodos , Gravidez , Curva ROC , Fluxo Sanguíneo Regional , Ultrassonografia Pré-Natal
15.
J Viral Hepat ; 27(9): 948-950, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32281709

RESUMO

Diffuse large B-cell lymphoma (DLBCL) has been reported to have a significant association with the hepatitis B virus (HBV) infection. However, there has been no experimental evidence to determine whether the components of the hepatitis B virus are expressed in lymphoid cells. In this study, we used immunohistochemical methods to explore whether the antigens of hepatitis B virus are expressed in DLBCL lymphoma cells in HBsAg-positive DLBCL patients (HBsAg + DLBCL). HBx antigen was detected in 48.9% of HBsAg + DLBCL patients, and the expression rate of the Pre-S2 antigen was 57.2%. HBx expression was significantly associated with high-level expression of c-Myc, while the Pre-S2 antigen was not. In this study, we demonstrated that HBx antigen and Pre-S2 antigen could be detected in lymphoma cells, and HBx expression was related to c-Myc expression. Our findings provide a strong basis for further study of the HBV-infected DLBCL and molecular mechanism underlying the lymphomagenesis.


Assuntos
Antígenos de Superfície da Hepatite B/análise , Hepatite B , Linfoma Difuso de Grandes Células B , Transativadores/análise , Proteínas Virais Reguladoras e Acessórias/análise , Hepatite B/complicações , Vírus da Hepatite B , Humanos , Linfoma Difuso de Grandes Células B/virologia
16.
Pharm Biol ; 57(1): 717-728, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31622116

RESUMO

Context: Hyaluronic acid (HA) plays critical roles in the structural skeleton, joint lubrication, renal function and cell signaling. We previously showed that partially N-butyrylated, low molecular weight, hyaluronic acid (BHA) exhibited an anti-inflammatory effect in cultured human macrophage, where inflammation was induced either by a TL-4 agonist or the low molecular weight HA itself, in dose-dependent fashion. Objectives: To investigate the anti-inflammatory, antioxidative, and antihyperuricemic effects of BHA using animal models of acute gouty arthritis and hyperuricemia. Materials and methods: The anti-inflammatory effect of articular BHA (10 and 50 µg) injections was evaluated by measuring joint swelling and the serum levels of inflammatory cytokines in a model of acute gouty arthritis induced by intra-articular injection of monosodium urate crystals in Wistar rats (n = 10/group), in comparison to the control group with saline injection. Antioxidative and antihyperuricemic activities were investigated using intraperitoneal injections of oteracil potassium and yeast extract hyperuricemic Balb/C mice, which were treated with intraperitoneal injection of BHA at day 6-8 in the model. Results: In the gouty arthritis rat model, BHA at a higher dosage (50 µg) demonstrated a strong anti-inflammatory effect by reducing the degree of articular swelling and the serum levels of IL-1ß, IL-8, IFN-γ, and MCP-1 by 5.56%, 6.55%, 15.58% and 33.18%. In the hyperuricemic mouse model, lower dosage BHA (10 µg) was sufficient to provide antioxidative activities by significantly decreasing the ROS levels in both serum and liver by 14.87% and 8.04%, while improving liver SOD by 12.77%. Intraperitoneal injection of BHA suppressed uric acid production through reducing liver XO activity by 19.78% and decreased the serum uric acid level in hyperuricemic mice by 30.41%. Conclusions: This study demonstrated for the first time that BHA exhibits anti-inflammatory, antioxidative and antihyperuricemic effects in vivo, suggesting a potential therapeutic application of BHA in gouty arthritis and hyperuricemia.


Assuntos
Anti-Inflamatórios/farmacologia , Artrite Gotosa/tratamento farmacológico , Ácido Hialurônico/farmacologia , Hiperuricemia/tratamento farmacológico , Animais , Anti-Inflamatórios/administração & dosagem , Anti-Inflamatórios/química , Antioxidantes/administração & dosagem , Antioxidantes/química , Antioxidantes/farmacologia , Artrite Gotosa/patologia , Butiratos/química , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Ácido Hialurônico/administração & dosagem , Ácido Hialurônico/química , Hiperuricemia/patologia , Inflamação/tratamento farmacológico , Inflamação/patologia , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Ratos , Ratos Wistar , Ácido Úrico/sangue
17.
Proc Natl Acad Sci U S A ; 116(43): 21427-21437, 2019 10 22.
Artigo em Inglês | MEDLINE | ID: mdl-31601737

RESUMO

Pharmacology and optogenetics are widely used in neuroscience research to study the central and peripheral nervous systems. While both approaches allow for sophisticated studies of neural circuitry, continued advances are, in part, hampered by technology limitations associated with requirements for physical tethers that connect external equipment to rigid probes inserted into delicate regions of the brain. The results can lead to tissue damage and alterations in behavioral tasks and natural movements, with additional difficulties in use for studies that involve social interactions and/or motions in complex 3-dimensional environments. These disadvantages are particularly pronounced in research that demands combined optogenetic and pharmacological functions in a single experiment. Here, we present a lightweight, wireless, battery-free injectable microsystem that combines soft microfluidic and microscale inorganic light-emitting diode probes for programmable pharmacology and optogenetics, designed to offer the features of drug refillability and adjustable flow rates, together with programmable control over the temporal profiles. The technology has potential for large-scale manufacturing and broad distribution to the neuroscience community, with capabilities in targeting specific neuronal populations in freely moving animals. In addition, the same platform can easily be adapted for a wide range of other types of passive or active electronic functions, including electrical stimulation.


Assuntos
Optogenética/métodos , Farmacologia/métodos , Animais , Encéfalo/metabolismo , Química Encefálica , Channelrhodopsins/metabolismo , Estimulação Elétrica , Feminino , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Optogenética/instrumentação , Farmacologia/instrumentação , Próteses e Implantes , Tecnologia sem Fio/instrumentação
18.
Cancer Sci ; 110(11): 3442-3452, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31432592

RESUMO

Functional E-cadherin loss, a hallmark of epithelial-mesenchymal transition (EMT), is important for metastasis. However, the mechanism of Snail2 in hepatocellular carcinoma (HCC) EMT and metastasis remains unclear. Here, we showed that Snail2 was upregulated in primary HCC, and significantly increased during transforming growth factor-ß-induced liver cell EMT. Snail2-overexpressing and knockdown cell lines have been established to determine its function in EMT in HCC. H3K9 methylation was upregulated and H3K4 and H3K56 acetylation were downregulated at the E-cadherin promoter in Snail2-overexpressing cancer cells. Furthermore, Snail2 interacted with G9a and histone deacetylases (HDACs) to form a complex to suppress E-cadherin transcription. Snail2 overexpression enhanced migration and invasion in HCC cells, whereas G9a and HDAC inhibition significantly reversed this effect. Moreover, Snail2 overexpression in cancer cells increased tumor metastasis and shortened survival time in mice, whereas G9a and HDAC inhibitors extended survival. Our study not only reveals a critical mechanism underlying the epigenetic regulation of EMT but also suggests novel treatment strategies for HCC.


Assuntos
Caderinas/metabolismo , Carcinoma Hepatocelular/metabolismo , Epigênese Genética , Transição Epitelial-Mesenquimal/genética , Antígenos de Histocompatibilidade/metabolismo , Histona Desacetilases/metabolismo , Histona-Lisina N-Metiltransferase/metabolismo , Neoplasias Hepáticas/metabolismo , Fatores de Transcrição da Família Snail/metabolismo , Acetilação , Animais , Azepinas/uso terapêutico , Carcinoma Hepatocelular/secundário , Movimento Celular , Progressão da Doença , Regulação para Baixo , Feminino , Inibidores de Histona Desacetilases/uso terapêutico , Humanos , Ácidos Hidroxâmicos/uso terapêutico , Fígado/efeitos dos fármacos , Fígado/metabolismo , Neoplasias Hepáticas/patologia , Metilação , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Invasividade Neoplásica , Metástase Neoplásica , Quinazolinas/uso terapêutico , Transcrição Genética , Fator de Crescimento Transformador beta/farmacologia
19.
Sci Adv ; 5(7): eaaw5296, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-31281895

RESUMO

Studies of the peripheral nervous system rely on controlled manipulation of neuronal function with pharmacologic and/or optogenetic techniques. Traditional hardware for these purposes can cause notable damage to fragile nerve tissues, create irritation at the biotic/abiotic interface, and alter the natural behaviors of animals. Here, we present a wireless, battery-free device that integrates a microscale inorganic light-emitting diode and an ultralow-power microfluidic system with an electrochemical pumping mechanism in a soft platform that can be mounted onto target peripheral nerves for programmed delivery of light and/or pharmacological agents in freely moving animals. Biocompliant designs lead to minimal effects on overall nerve health and function, even with chronic use in vivo. The small size and light weight construction allow for deployment as fully implantable devices in mice. These features create opportunities for studies of the peripheral nervous system outside of the scope of those possible with existing technologies.


Assuntos
Encéfalo/fisiopatologia , Optogenética/métodos , Nervos Periféricos , Tecnologia sem Fio , Animais , Humanos , Camundongos , Neurotransmissores/farmacologia , Próteses e Implantes
20.
Proc Natl Acad Sci U S A ; 116(31): 15368-15377, 2019 07 30.
Artigo em Inglês | MEDLINE | ID: mdl-31315983

RESUMO

Techniques for forming sophisticated, 3D mesostructures in advanced, functional materials are of rapidly growing interest, owing to their potential uses across a broad range of fundamental and applied areas of application. Recently developed approaches to 3D assembly that rely on controlled buckling mechanics serve as versatile routes to 3D mesostructures in a diverse range of high-quality materials and length scales of relevance for 3D microsystems with unusual function and/or enhanced performance. Nonlinear buckling and delamination behaviors in materials that combine both weak and strong interfaces are foundational to the assembly process, but they can be difficult to control, especially for complex geometries. This paper presents theoretical and experimental studies of the fundamental aspects of adhesion and delamination in this context. By quantifying the effects of various essential parameters on these processes, we establish general design diagrams for different material systems, taking into account 4 dominant delamination states (wrinkling, partial delamination of the weak interface, full delamination of the weak interface, and partial delamination of the strong interface). These diagrams provide guidelines for the selection of engineering parameters that avoid interface-related failure, as demonstrated by a series of examples in 3D helical mesostructures and mesostructures that are reconfigurable based on the control of loading-path trajectories. Three-dimensional micromechanical resonators with frequencies that can be selected between 2 distinct values serve as demonstrative examples.

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