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1.
BMC Public Health ; 24(1): 119, 2024 01 08.
Artigo em Inglês | MEDLINE | ID: mdl-38191342

RESUMO

BACKGROUND: Medical service prices play a crucial role in cost containment in China. This study aimed to assess the change in medical service price levels at the macro level and the relationship with relevant macroeconomic factors. METHODS: Data from the 2022 China Statistics Yearbook, the 2022 China Health Statistics Yearbook, and the 2020 China National Health Accounts Report were used. Time trends of health price levels, utilization, and health expenditure were examined. A time-series regression model was employed to measure the impact of service utilization and medical service prices on total medical service expenditure growth from 2000 to 2021. The Johansen cointegration test was conducted to test the cointegrating relationship between medical service price levels and total medical service expenditure, average wage of employees and CPI. The Granger causality test was performed to observe the direction of causality. RESULTS: Descriptive analyses showed consistent growth in utilization and medical service price levels from 2000 to 2021. The time-series model indicated that medical service expenditure was influenced by the rise in inpatient admissions and price levels of medical service and medicine. The Johansen cointegration test identified a long-term equilibrium relationship between medical service price levels and total medical service expenditure, average wage and CPI. The change in medical service price levels was the Granger cause of the change in medical service expenditure, but it had no impact on average wage and CPI. However, the change in medical service price levels was influenced by these three macroeconomic factors. CONCLUSIONS: The growth of medical service expenditure in China was driven by inpatient use and price level. There was a long-term equilibrium relationship between medical service price levels and relevant macroeconomic factors. However, medical service price levels only affected medical service expenditure and have no impact on average wage and CPI. It is necessary to improve the value transmission mechanism of medical service prices.


Assuntos
Gastos em Saúde , Nível de Saúde , Humanos , China , Hospitalização , Pacientes Internados
2.
Proc Natl Acad Sci U S A ; 115(52): 13234-13239, 2018 12 26.
Artigo em Inglês | MEDLINE | ID: mdl-30538196

RESUMO

Amyloid fibrils are cross-ß-rich aggregates that are exceptionally stable forms of protein assembly. Accumulation of tau amyloid fibrils is involved in many neurodegenerative diseases, including Alzheimer's disease (AD). Heparin-induced aggregates have been widely used and assumed to be a good tau amyloid fibril model for most biophysical studies. Here we show that mature fibrils made of 4R tau variants, prepared with heparin or RNA, spontaneously depolymerize and release monomers when their cofactors are removed. We demonstrate that the cross-ß-sheet assembly formed in vitro with polyanion addition is unstable at room temperature. We furthermore demonstrate high seeding capacity with transgenic AD mouse brain-extracted tau fibrils in vitro that, however, is exhausted after one generation, while supplementation with RNA cofactors resulted in sustained seeding over multiple generations. We suggest that tau fibrils formed in brains are supported by unknown cofactors and inhere higher-quality packing, as reflected in a more distinct conformational arrangement in the mouse fibril-seeded, compared with heparin-induced, tau fibrils. Our study suggests that the role of cofactors in tauopathies is a worthy focus of future studies, as they may be viable targets for diagnosis and therapeutics.


Assuntos
Doença de Alzheimer/patologia , Amiloide/química , Encéfalo/patologia , Heparina/química , RNA/química , Proteínas Recombinantes/química , Proteínas tau/química , Doença de Alzheimer/metabolismo , Amiloide/metabolismo , Animais , Encéfalo/metabolismo , Heparina/metabolismo , Camundongos , Camundongos Transgênicos , Conformação Proteica , RNA/metabolismo , Proteínas Recombinantes/metabolismo , Proteínas tau/metabolismo
3.
J Craniofac Surg ; 32(8): 2784-2787, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34727480

RESUMO

ABSTRACT: Mandibular angle osteotomy with outer cortex grinding has become the preferred cosmetic procedure for correcting square faces. After surgery, bone hyperplasia at the mandibular angle affects the operation result. This study evaluated the effect of the masticatory muscles on bone repair. From January 2016 to January 2019, patients who underwent mandibular angle osteotomy with outer cortex grinding were retrospectively reviewed. Computed tomography data of these patients were collected, and the bone volume of the mandibular angle changes and its correlation with masticatory muscle morphology were analyzed. Computed tomography data measurement results showed that a large amount of bone in the mandibular angle area was removed by the operation; however, the long-term follow-up results showed that there was bone hyperplasia in the mandibular angle areas. Compared with the immediate postoperative bone volume, the difference was statistically significant (P < 0.01). The thickness and cross-sectional area of the masseter muscle were significantly related to bone regeneration (P < 0.01). This study suggests that mandibular angle osteotomy with outer cortex grinding could ablate the symptoms of a prominent mandibular angle; however, muscle-related bone hyperplasia in the mandibular angle area after surgery was a non-negligible event, which may significantly compromise surgical outcomes.


Assuntos
Músculo Masseter , Osteotomia , Regeneração Óssea , Humanos , Mandíbula/diagnóstico por imagem , Mandíbula/cirurgia , Músculos da Mastigação/diagnóstico por imagem , Estudos Retrospectivos
4.
J Craniofac Surg ; 32(7): 2305-2309, 2021 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-34705378

RESUMO

ABSTRACT: This study evaluated age-associated morphology changes in the cranial base, facial development, and upper airway of patients with Treacher Collins syndrome (TCS). A total of 33 preoperative computed tomographic images (TCS, n = 14; control, n = 19) were included in the study and divided into three age-related subgroups (2-6 years, 7-18 years, and older than 18 years). Linear, angular cephalometric measurements and upper airway volumes were collected. All measurements were analyzed using ProPlan CMF software (version 3.0; Materialize, Leuven, Belgium). The association between aging and upper airway morphology was analyzed. Compared to control subjects, TCS patients had a smaller cranial base, maxilla, and nose; they also had reduced upper airway volume compared to control subjects. The observed differences were most significant in patients between the ages of 7 and 18 years. This study used computed tomography-based three-dimensional analyses to provide a detailed description of age-related changes that occur in craniofacial measurements and upper airway volumes in children, adolescents, and young adult patients with TCS in China. These data can be used to evaluate individual patients with TCS and to select treatment to improve the growth of the craniofacial region.


Assuntos
Disostose Mandibulofacial , Adolescente , Cefalometria , Criança , Humanos , Mandíbula , Disostose Mandibulofacial/diagnóstico por imagem , Maxila , Base do Crânio
5.
PLoS Biol ; 15(7): e2002183, 2017 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-28683104

RESUMO

Nonmembrane-bound organelles that behave like liquid droplets are widespread among eukaryotic cells. Their dysregulation appears to be a critical step in several neurodegenerative conditions. Here, we report that tau protein, the primary constituent of Alzheimer neurofibrillary tangles, can form liquid droplets and therefore has the necessary biophysical properties to undergo liquid-liquid phase separation (LLPS) in cells. Consonant with the factors that induce LLPS, tau is an intrinsically disordered protein that complexes with RNA to form droplets. Uniquely, the pool of RNAs to which tau binds in living cells are tRNAs. This phase state of tau is held in an approximately 1:1 charge balance across the protein and the nucleic acid constituents, and can thus be maximal at different RNA:tau mass ratios, depending on the biopolymer constituents involved. This feature is characteristic of complex coacervation. We furthermore show that the LLPS process is directly and sensitively tuned by salt concentration and temperature, implying it is modulated by both electrostatic interactions between the involved protein and nucleic acid constituents, as well as net changes in entropy. Despite the high protein concentration within the complex coacervate phase, tau is locally freely tumbling and capable of diffusing through the droplet interior. In fact, tau in the condensed phase state does not reveal any immediate changes in local protein packing, local conformations and local protein dynamics from that of tau in the dilute solution state. In contrast, the population of aggregation-prone tau as induced by the complexation with heparin is accompanied by large changes in local tau conformations and irreversible aggregation. However, prolonged residency within the droplet state eventually results in the emergence of detectable ß-sheet structures according to thioflavin-T assay. These findings suggest that the droplet state can incubate tau and predispose the protein toward the formation of insoluble fibrils.


Assuntos
Agregação Patológica de Proteínas , RNA/metabolismo , Proteínas tau/metabolismo , Células Cultivadas , Humanos , Temperatura
6.
Methods Mol Biol ; 2754: 185-192, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38512667

RESUMO

Protein liquid-liquid phase separation (LLPS) has been associated with protein amyloid aggregation. Amyloid aggregation of tau is a hallmark of Alzheimer's disease and other neurodegenerative diseases. This protocol provides steps to prepare tau condensates via LLPS, so that researchers can further study its driving forces and its relationship with tau amyloid aggregation.


Assuntos
Doença de Alzheimer , Proteínas tau , Humanos , Proteínas tau/metabolismo , Separação de Fases , Doença de Alzheimer/metabolismo , Amiloide/metabolismo , Proteínas Amiloidogênicas
7.
Methods Mol Biol ; 2551: 269-284, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36310209

RESUMO

Protein liquid-liquid phase separation (LLPS) has been associated with biological functions and pathological aggregation. Mapping the phase separation conditions is the first step to identify and quantify the driving forces of LLPS. Here, we describe the protocols to draw the phase diagram of tau-RNA LLPS and use the mapped diagram to guide experimental conditions for LLPS-cell coculturing, electron resonance spectroscopy in particular double electron-electron resonance spectroscopy, crosslinking immunoprecipitation, and isothermal titration calorimetry.


Assuntos
RNA , RNA/metabolismo
8.
J Diabetes Investig ; 13(6): 1062-1072, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35119212

RESUMO

AIMS/INTRODUCTION: To assess the relationship between type 2 diabetes mellitus onset age and vascular complications in China. MATERIALS AND METHODS: A retrospective review of 3,568 patients with type 2 diabetes mellitus using a propensity score-matched (PSM) cohort analysis was carried out in two different age of onset groups (age 40 and 60 years). These groups were then subdivided into two groups, early-onset diabetes (EOD40 and EOD60; the onset age before 40 and 60 years, respectively) and late-onset diabetes (LOD40 and LOD60: the onset age after 40 and 60 years, respectively). Macrovascular and microvascular complications were analyzed before and after PSM. RESULTS: Patients categorized in both the early-onset disease (EOD) groups had a higher risk of developing macro- and microvascular complications before PSM. After PSM, no differences existed between the EOD and late-onset disease groups in the risk of macrovascular complications. Compared with the late-onset disease group, the odds ratio of having a microvascular complication of diabetic retinopathy, chronic kidney disease and diabetic peripheral neuropathy in the 40-year-old EOD group increased to 2.906, 1.967 and 1.672 (P < 0.05), respectively. The odds ratio of diabetic retinopathy and diabetic peripheral neuropathy in the 60-year-old EOD group was 1.763 and 1.675 (P < 0.05), respectively. CONCLUSIONS: The earlier the onset of type 2 diabetes mellitus, the higher risk of microvascular, but not necessarily macrovascular, complications. It is not too late to prevent diabetes at any age. Pre-emptive microvascular treatment or preventative measures in EOD patients who do not yet show symptoms, might be beneficial.


Assuntos
Doenças Cardiovasculares , Diabetes Mellitus Tipo 2 , Nefropatias Diabéticas , Neuropatias Diabéticas , Retinopatia Diabética , Adulto , Idade de Início , Doenças Cardiovasculares/complicações , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/diagnóstico , Diabetes Mellitus Tipo 2/epidemiologia , Nefropatias Diabéticas/complicações , Nefropatias Diabéticas/etiologia , Neuropatias Diabéticas/complicações , Neuropatias Diabéticas/etiologia , Retinopatia Diabética/complicações , Retinopatia Diabética/etiologia , Humanos , Pessoa de Meia-Idade , Pontuação de Propensão , Fatores de Risco
9.
Zhongguo Xiu Fu Chong Jian Wai Ke Za Zhi ; 35(5): 611-619, 2021 May 15.
Artigo em Chinês | MEDLINE | ID: mdl-33998216

RESUMO

OBJECTIVE: To investigate the effect of silk fibroin-poly- L-lactic acid (SF-PLLA) microcarriers on the expansion and differentiation of adipose-derived stem cells (ADSCs). METHODS: ADSCs were extracted from adipose tissue donated voluntarily by patients undergoing liposuction by enzymatic digestion. The 3rd generation ADSCs were inoculated on CultiSpher G and SF-PLLA microcarriers (set up as groups A and B, respectively), and cultured in the rotary cell culture system. ADSCs cultured in normal two-dimensional plane were used as the control group (group C). Scanning electron microscope was used to observe the microcarriers structure and cell growth. Live/Dead staining and confocal fluorescence microscope was used to observe the distribution and survival condition of cells on two microcarriers. DNA quantification was used to assess cell proliferation on two microcarriers. Real-time fluorescence quantitative PCR (qRT-PCR) was used to detect chondrogenesis, osteogenesis, and adipogenesis related gene expression of ADSCs in 3 groups cultured for 18 days. Flow cytometry was used to identify the MSCs surface markers of ADSCs in 3 groups cultured for 18 days, and differential experiments were made to identify differentiation ability of the harvested cells. RESULTS: ADSCs could be adhered to and efficiently amplified on the two microcarriers. After 18 days of cultivation, the total increment of ADSCs of the two microcarriers were similar ( P>0.05). qRT-PCR results showed that chondrogenesis related genes (aggrecan, cartilage oligomeric matrix protein, SOX9) were significantly up-regulated for ADSCs on SF-PLLA microcarriers and adipogenesis related genes (peroxisome proliferator-activated receptor γ, lipoprotein lipase, ADIPOQ) were significantly up-regulated for ADSCs on CultiSpher G microcarriers, all showing significant differences ( P<0.05). Flow cytometry and differentiation identification proved that the harvested cells of the two groups were still ADSCs. CONCLUSION: The ADSCs can be amplified by SF-PLLA microcarriers, and the chondrogenic differential ability of harvested cells was up-regulated while the adipogenic differential was down-regulated.


Assuntos
Tecido Adiposo/citologia , Fibroínas , Ácido Láctico , Células-Tronco/citologia , Diferenciação Celular , Células Cultivadas , Humanos
10.
Zhongguo Xiu Fu Chong Jian Wai Ke Za Zhi ; 35(7): 896-903, 2021 Jul 15.
Artigo em Chinês | MEDLINE | ID: mdl-34308600

RESUMO

OBJECTIVE: To explore the feasibility of three-dimensional (3D) bioprinted adipose-derived stem cells (ADSCs) combined with gelatin methacryloyl (GelMA) to construct tissue engineered cartilage. METHODS: Adipose tissue voluntarily donated by liposuction patients was collected to isolate and culture human ADSCs (hADSCs). The third generation cells were mixed with GelMA hydrogel and photoinitiator to make biological ink. The hADSCs-GelMA composite scaffold was prepared by 3D bioprinting technology, and it was observed in general, and observed by scanning electron microscope after cultured for 1 day and chondrogenic induction culture for 14 days. After cultured for 1, 4, and 7 days, the composite scaffolds were taken for live/dead cell staining to observe cell survival rate; and cell counting kit 8 (CCK-8) method was used to detect cell proliferation. The composite scaffold samples cultured in cartilage induction for 14 days were taken as the experimental group, and the composite scaffolds cultured in complete medium for 14 days were used as the control group. Real-time fluorescent quantitative PCR (qRT-PCR) was performed to detect cartilage formation. The relative expression levels of the mRNA of cartilage matrix gene [(aggrecan, ACAN)], chondrogenic regulatory factor (SOX9), cartilage-specific gene [collagen type Ⅱ A1 (COLⅡA1)], and cartilage hypertrophy marker gene [collagen type ⅩA1 (COLⅩA1)] were detected. The 3D bioprinted hADSCs-GelMA composite scaffold (experimental group) and the blank GelMA hydrogel scaffold without cells (control group) cultured for 14 days of chondrogenesis were implanted into the subcutaneous pockets of the back of nude mice respectively, and the materials were taken after 4 weeks, and gross observation, Safranin O staining, Alcian blue staining, and collagen type Ⅱ immunohistochemical staining were performed to observe the cartilage formation in the composite scaffold. RESULTS: Macroscope and scanning electron microscope observations showed that the hADSCs-GelMA composite scaffolds had a stable and regular structure. The cell viability could be maintained at 80%-90% at 1, 4, and 7 days after printing, and the differences between different time points were significant ( P<0.05). The results of CCK-8 experiment showed that the cells in the scaffold showed continuous proliferation after printing. After 14 days of chondrogenic induction and culture on the composite scaffold, the expressions of ACAN, SOX9, and COLⅡA1 were significantly up-regulated ( P<0.05), the expression of COLⅩA1 was significantly down-regulated ( P<0.05). The scaffold was taken out at 4 weeks after implantation. The structure of the scaffold was complete and clear. Histological and immunohistochemical results showed that cartilage matrix and collagen type Ⅱ were deposited, and there was cartilage lacuna formation, which confirmed the formation of cartilage tissue. CONCLUSION: The 3D bioprinted hADSCs-GelMA composite scaffold has a stable 3D structure and high cell viability, and can be induced differentiation into cartilage tissue, which can be used to construct tissue engineered cartilage in vivo and in vitro.


Assuntos
Gelatina , Engenharia Tecidual , Tecido Adiposo , Animais , Cartilagem , Diferenciação Celular , Células Cultivadas , Humanos , Camundongos , Camundongos Nus , Células-Tronco , Alicerces Teciduais
11.
Zhongguo Xiu Fu Chong Jian Wai Ke Za Zhi ; 35(1): 86-94, 2021 Jan 15.
Artigo em Chinês | MEDLINE | ID: mdl-33448205

RESUMO

OBJECTIVE: To three-dimensionally calculate the craniofacial parameters of midface of patients with Treacher Collins syndrome (TCS) in China, in order to understand the changes in the spatial position relationship between the various anatomical structures of the midface. METHODS: CT imaging data of TCS patients and age- and gender-matched normal populations between January 2013 and July 2020 was retrospectively analyzed. A total of 33 cases met the selection criteria for inclusion in the study, including 14 cases in the TCS group and 19 cases in the control group. ProPlan CMF 3.0 software was used to perform three-dimensional digital reconstruction of the craniofacial bone, measure the anatomical parameters of the midface, and analyze its morphological structure; at the same time perform three-dimensional digital reconstruction of the upper airway for morphological analysis (measure upper airway volume). RESULTS: CT images analysis revealed that all 14 patients with TCS presented the typical features with downward slanting of the palpebral fissures and different degrees of zygomatico-orbital complex dysplasia. Cephalometric and morphological analysis of the midface revealed that, multiple transverse diameters of the midface of TCS patients were significantly decreased when compared with the control group ( P<0.05), such as the width of the maxillary base, the length of the maxillary complex, and some distances related to the nasal morphology; but the distance between bilateral orbitales increased in TCS group ( P<0.05). Several anteroposterior distances in TCS group were decreased significantly when compared to control group and the distance between the skull base point and the posterior nasal spine was the most shortened ( P<0.05). But there was no significant difference of the distance between nasion and anterior nasal spine, which represented anterior midface height, between groups ( P>0.05). The skull base angle and SNB angle (the angle between the sella point-nose root point-inferior alveolar seat point) of the TCS group both decreased when compared with the control group ( P<0.05), but there was no significant difference in SNA angle (the angle between the sella point-nose root point-upper alveolar seat point) between the two groups ( P>0.05). The total volume of the upper airway was (24 621.07±8 476.63) mm 3 in the TCS group, which was significantly lower than that of the control group [(32 864.21±13 148.74) mm 3] ( t=2.185, P=0.037). CONCLUSION: The transverse distances, anteroposterior distances, and multiple craniofacial angles measurement of TCS patients were significantly decreased when compared to the control group, presented with different degrees of zygomatico-orbital complex dysplasia, nasal and maxillary dysplasia, but there was no obvious restriction in face height development. Reduced internal diameters of the upper airway maybe responsible for the decreased upper airway volume of patients with TCS.


Assuntos
Disostose Mandibulofacial , Cefalometria , China , Humanos , Imageamento Tridimensional , Disostose Mandibulofacial/diagnóstico por imagem , Estudos Retrospectivos , Síndrome
12.
J Mol Biol ; 433(2): 166731, 2021 01 22.
Artigo em Inglês | MEDLINE | ID: mdl-33279579

RESUMO

Amyloid aggregation of tau protein is implicated in neurodegenerative diseases, yet its facilitating factors are poorly understood. Recently, tau has been shown to undergo liquid liquid phase separation (LLPS) both in vivo and in vitro. LLPS was shown to facilitate tau amyloid aggregation in certain cases, while being independent of aggregation in other cases. It is therefore important to understand the differentiating properties that resolve this apparent conflict. We report on a model system of hydrophobically driven LLPS induced by high salt concentration (LLPS-HS), and compare it to electrostatically driven LLPS represented by tau-RNA/heparin complex coacervation (LLPS-ED). We show that LLPS-HS promotes tau protein dehydration, undergoes maturation and directly leads to canonical tau fibrils, while LLPS-ED is reversible, remains hydrated and does not promote amyloid aggregation. We show that the nature of the interaction driving tau condensation is a differentiating factor between aggregation-prone and aggregation-independent LLPS.


Assuntos
Amiloide/química , Interações Hidrofóbicas e Hidrofílicas , Extração Líquido-Líquido , Proteínas tau/química , Proteínas tau/isolamento & purificação , Amiloide/metabolismo , Amiloide/ultraestrutura , Humanos , Extração Líquido-Líquido/métodos , Agregados Proteicos , Agregação Patológica de Proteínas , Análise Espectral , Proteínas tau/metabolismo
13.
Protein Sci ; 30(7): 1393-1407, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-33955104

RESUMO

The liquid-liquid phase separation (LLPS) of Tau has been postulated to play a role in modulating the aggregation property of Tau, a process known to be critically associated with the pathology of a broad range of neurodegenerative diseases including Alzheimer's Disease. Tau can undergo LLPS by homotypic interaction through self-coacervation (SC) or by heterotypic association through complex-coacervation (CC) between Tau and binding partners such as RNA. What is unclear is in what way the formation mechanisms for self and complex coacervation of Tau are similar or different, and the addition of a binding partner to Tau alters the properties of LLPS and Tau. A combination of in vitro experimental and computational study reveals that the primary driving force for both Tau CC and SC is electrostatic interactions between Tau-RNA or Tau-Tau macromolecules. The liquid condensates formed by the complex coacervation of Tau and RNA have distinctly higher micro-viscosity and greater thermal stability than that formed by the SC of Tau. Our study shows that subtle changes in solution conditions, including molecular crowding and the presence of binding partners, can lead to the formation of different types of Tau condensates with distinct micro-viscosity that can coexist as persistent and immiscible entities in solution. We speculate that the formation, rheological properties and stability of Tau droplets can be readily tuned by cellular factors, and that liquid condensation of Tau can alter the conformational equilibrium of Tau.


Assuntos
Simulação por Computador , Modelos Químicos , Agregados Proteicos , Proteínas tau/química , Humanos
14.
ACS Chem Neurosci ; 11(4): 615-627, 2020 02 19.
Artigo em Inglês | MEDLINE | ID: mdl-31971365

RESUMO

Amyloid aggregation of the microtubule binding protein tau is a hallmark of many neurodegenerative diseases. Recently, tau has been found to undergo liquid-liquid phase separation (LLPS) by an electrostatically driven complex coacervation (CC) mechanism near physiological conditions. Although LLPS and aggregation have been shown to simultaneously occur under certain common conditions, it is unclear whether LLPS promotes aggregation of tau, or whether they are two independent processes. In this study, we address this question by combining multiple biochemical and biophysical assays in vitro. We investigate the impacts of LLPS-CC on cofactor-induced tau aggregation by evaluating the conformation of tau, kinetics of aggregation, and fibril quantity. We showed that none of these properties are influenced directly by LLPS-CC and that LLPS-CC and cofactor-induced aggregation of tau merely occur under overlapping conditions of enhanced intermolecular interactions and localization but are two independent processes. We furthermore showed that tau LLPS can be driven by nonelectrostatic interaction using high-salt concentrations. Under these conditions, LLPS strongly correlated with increased aggregation propensity. Whether LLPS of tau formed under different conditions or of different constituents may actively promote aggregation of tau remains an open question, but this study shows that the readily accessible electrostatically driven condensation of tau into LLPS in and of itself is not sufficient to promote aggregation.


Assuntos
Amiloide/metabolismo , Amiloidose/metabolismo , Agregação Patológica de Proteínas/metabolismo , Proteínas tau/metabolismo , Proteínas Amiloidogênicas/metabolismo , Humanos , Microtúbulos/metabolismo , Doenças Neurodegenerativas/metabolismo
15.
Commun Chem ; 3(1): 83, 2020 Jun 26.
Artigo em Inglês | MEDLINE | ID: mdl-36703474

RESUMO

Complex coacervation driven liquid-liquid phase separation (LLPS) of biopolymers has been attracting attention as a novel phase in living cells. Studies of LLPS in this context are typically of proteins harboring chemical and structural complexity, leaving unclear which properties are fundamental to complex coacervation versus protein-specific. This study focuses on the role of polyethylene glycol (PEG)-a widely used molecular crowder-in LLPS. Significantly, entropy-driven LLPS is recapitulated with charged polymers lacking hydrophobicity and sequence complexity, and its propensity dramatically enhanced by PEG. Experimental and field-theoretic simulation results are consistent with PEG driving LLPS by dehydration of polymers, and show that PEG exerts its effect without partitioning into the dense coacervate phase. It is then up to biology to impose additional variations of functional significance to the LLPS of biological systems.

16.
Zhongguo Xiu Fu Chong Jian Wai Ke Za Zhi ; 33(12): 1578-1583, 2019 Dec 15.
Artigo em Chinês | MEDLINE | ID: mdl-31823562

RESUMO

OBJECTIVE: To summarize the progress of diagnosis and treatment of upper respiratory obstruction in patients with Treacher Collins syndrome (TCS). METHODS: The domestic and abroad literature about the diagnosis and treatment of upper respiratory obstruction in patients with TCS was extensively reviewed and analyzed. RESULTS: TCS is an autosomal-dominant craniofacial developmental syndrome. It is often accompanied by midface and/or mandibular hypoplasia, soft tissue hypertrophy, and other respiratory tissue developmental abnormalities, which can lead to different degrees of upper respiratory obstruction symptoms. Respiratory obstruction in patients with TCS is affected by many factors, and the obstructive degree are different. Early detection of the causes and obstructive sites and adopted targeted treatments can relieve the symptoms of respiratory obstruction and avoid severe complications. CONCLUSION: Due to the low incidence of TCS, there is still a lack of high-quality research evidence to guide clinical treatment. Large-scale and prospective clinical studies are needed to provide new ideas for the treatment and prevention of upper respiratory obstruction.


Assuntos
Disostose Mandibulofacial , Doenças Respiratórias , Face , Ossos Faciais , Humanos , Disostose Mandibulofacial/complicações , Disostose Mandibulofacial/diagnóstico , Disostose Mandibulofacial/terapia , Estudos Prospectivos , Doenças Respiratórias/diagnóstico , Doenças Respiratórias/etiologia , Doenças Respiratórias/terapia
17.
Elife ; 82019 04 05.
Artigo em Inglês | MEDLINE | ID: mdl-30950394

RESUMO

The mechanism that leads to liquid-liquid phase separation (LLPS) of the tau protein, whose pathological aggregation is implicated in neurodegenerative disorders, is not well understood. Establishing a phase diagram that delineates the boundaries of phase co-existence is key to understanding whether LLPS is an equilibrium or intermediate state. We demonstrate that tau and RNA reversibly form complex coacervates. While the equilibrium phase diagram can be fit to an analytical theory, a more advanced model is investigated through field theoretic simulations (FTS) that provided direct insight into the thermodynamic driving forces of tau LLPS. Together, experiment and simulation reveal that tau-RNA LLPS is stable within a narrow equilibrium window near physiological conditions over experimentally tunable parameters including temperature, salt and tau concentrations, and is entropy-driven. Guided by our phase diagram, we show that tau can be driven toward LLPS under live cell coculturing conditions with rationally chosen experimental parameters.


Assuntos
RNA/metabolismo , Proteínas tau/metabolismo , Coloides , Interações Hidrofóbicas e Hidrofílicas , Concentração Osmolar , Ligação Proteica , RNA/química , Temperatura , Proteínas tau/química
18.
Zhongguo Xiu Fu Chong Jian Wai Ke Za Zhi ; 32(1): 118-124, 2018 01 15.
Artigo em Chinês | MEDLINE | ID: mdl-29806376

RESUMO

Objective: To summarize the monitoring methods and preventions of the disorder of blood supplying of expanded flaps, so as to provide some references for improving the survival of expanded flaps. Methods: The domestic and abroad related literature about the disorder of blood supplying of expanded flaps was reviewed and analyzed. Results: Handheld Doppler, digital subtraction angiography, computer tomographic angiography, magnetic resonance angiography, and fluorescein angiography can be used as reliable preoperative imaging methods in designing expanded flaps with rich blood supply. Several techniques can be used for monitoring the blood supply of expanded flaps during the early postoperative period including traditional monitoring via physical examination, monitoring via dynamic infrared thermography, near-infrared spectroscopy tissue oximeter, external and implantable Doppler, and more recently developed diffuse correlation spectroscopy. Surgical delay, bloodletting, leech therapy, hyperbaric oxygen, and so on can decrease the risk of necrosis in expanded flaps. Conclusion: The survival of expanded flap is influenced by many factors. Preoperative design by using handheld Doppler and new imaging technology and postoperative early detection of blood supply can provide references of timely intervention, so that ischemic necrosis of the flaps can be reduced, and the success rate of surgery can be improved.


Assuntos
Necrose/prevenção & controle , Exame Físico/métodos , Cuidados Pré-Operatórios , Retalhos Cirúrgicos/irrigação sanguínea , Ultrassonografia Doppler/métodos , Humanos , Oximetria/métodos , Cuidados Pós-Operatórios/métodos , Período Pós-Operatório , Próteses e Implantes , Espectroscopia de Luz Próxima ao Infravermelho/métodos , Retalhos Cirúrgicos/patologia
19.
Adv Colloid Interface Sci ; 239: 61-73, 2017 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-27499328

RESUMO

Complex coacervate refers to a phase-separated fluid, typically of two oppositely charged polyelectrolytes in solution, representing a complex fluid system that has been shown to be of essential interest to biological systems, as well as for soft materials processing owing to the expectation of superior underwater coating or adhesion properties. The significance and interest in complex coacervate fluids critically rely on its low interfacial tension with respect to water that, in turn, facilitates the wetting of macromolecular or material surfaces under aqueous conditions, provided there is attractive interaction between the polyelectrolyte constituents and the surface. However, the molecular and structural bases of these properties remain unclear. Recent studies propose that the formation of water-filled and bifluidic sponge-like nanostructured network, driven by the tuning of electrostatic interactions between the polyelectrolyte constituents or their complexes may be a common feature of complex coacervate fluids that display low fluid viscosity and low interfacial tension, but more studies are needed to verify the generality of these observations. In this review, we summarize representative studies of interfacial tension and ultrastructures of complex coacervate fluids. We highlight that a consensus property of the complex coacervate fluid is the observation of high or even bulk-like water dynamics within the dense complex coacervate phase that is consistent with a low cohesive energy fluid. Our own studies on this subject are enabled by the application of magnetic resonance relaxometry methods relying on spin labels tethered to polyelectrolyte constituents or added as spin labeled probe molecules that partition into the dense versus the equilibrium coacervate phase, permitting the extraction of information on local polymer dynamics, polymer packing and local water dynamics. We conclude with a snapshot of our current perspective on the molecular and structural bases of the low interfacial tension of complex coacervate fluids.

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