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1.
Archit Intell ; 1(1): 17, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36439646

RESUMO

In the field of digital design, a recent hot topic is the study of the interaction between spatial environment design and human factors. Electroencephalogram (EEG) and eye tracking can be used as quantitative analysis methods for architectural space evaluation; however, conclusions from existing studies on improving the quality of spatial environments based on human factors tend to remain qualitative. In order to realise the quantitative optimisation design of spatial elements from human physiological data, this research used the digital space optimisation method and perceptual evaluation research. In this way, it established an optimisation method for built space elements in real-time using human psychological indicators. Firstly, this method used the specific indicators of the Meditation value and Attention value in the human EEG signal, taking the ThinkGear AM (TGAM) module as the optimisation objective, the architectural space colour and the window size as the optimisation object, and the multi-objective genetic algorithm as the optimisation tool. Secondly, this research combined virtual reality scenarios and parametric linkage models to realise this optimisation method to establish a tool platform and workflow. Thirdly, this study took the optimisation of a typical living space as an example and recruited 50 volunteers to participate in an optimisation experiment. The results indicated that with the iterative optimisation of the multi-objective genetic algorithm, the specific EEG index decreases significantly and the standard deviation of the in-dex fluctuates and decreases during the iterative process, which further indicates that the optimisation method established in this study with the specific EEG index as the optimisation objective is effective and feasible. In addition, this study laid the foundation for more EEG indicators and more complex spatial element opti-misation research in the future.

2.
Artigo em Inglês | MEDLINE | ID: mdl-35954788

RESUMO

The accessibility of medical service facilities is a vital influence on elderly people choosing medical treatment. Encouraging residents to seek nearby medical treatment can facilitate the rational layout and diversion of urban medical facilities and reduce health resource waste. However, due to accessibility factors, elderly people may not choose the nearest hospital. In order to investigate such factors, we conducted a questionnaire survey among the elderly from 10 tertiary general hospitals in Hefei, China. On the basis of the origin-destination (OD) cost matrix analysis and statistical analysis of 830 valid questionnaires, this paper analyzed the elders' selection rules when choosing medical facilities and the factors considered when making a choice. The study found that although 85% of elderly participants valued a short distance to tertiary hospitals, only 31% of them attended the closest hospitals in reality, which correlated with regularity according to their education level, travel activity status, and place of residence. The elderly highlighted road congestion, convenience of public transport stations, and number of transfers as critical in determining whether they sought nearby medical treatment. According to the results, effective ways to encourage the elderly to attend their nearest hospital, from the perspective of accessibility, include easing road congestion, improving the layout of public transport stations, and optimizing urban public transport routes. In particular, when planning future medical facilities, attention should be paid to the elderly with primary school education or below, who cannot travel independently, and those who live far from the city center.


Assuntos
Instalações de Saúde , Hospitais Gerais , Idoso , China , Acesso aos Serviços de Saúde , Humanos , Inquéritos e Questionários , Centros de Atenção Terciária
3.
Front Public Health ; 10: 855857, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35372251

RESUMO

Objective: To investigate the effect of hospital outdoor rest space on the eye movement measures and self-rating restoration of staff. Background: Relieving the pressure of hospital staff through exposure to hospital outdoor rest space is essential, but there is a scarcity of research on the impact of hospital outdoor rest space on the eye movement measures and self-rating restoration of staff, especially for large Chinese hospitals. Methods: Cross-analysis was conducted based on the eye movement measures of 76 staff members obtained by eye movement tracking equipment in combination with the self-rating restoration scale and hospital outdoor rest space picture attributes (element proportion and position, brightness and saturation). Results: The differences in eye movement measures of different staff attributes (occupation, age, and gender) were identified, and the effects of hospital outdoor rest space picture attributes on the eye movement measures and self-rating restoration scale of staff were summarized. A number of proposals were also formulated: hospital outdoor rest space should be set up close to the working area of the group of medical staff; attention should be paid to the actual needs of senior staff members and the work pressure of junior nurses; the exposure to natural environment should be increased and the proportion of hard artificial elements should be reduced; the natural environment should be placed in the visual center; the saturation and brightness of hospital outdoor rest space should be increased; and staff members should have access to the sky environment in a variety of ways. Conclusion: The present study is an empirical study of evidence-based design on hospital outdoor rest space in China, and the results reveal the effects of hospital outdoor rest space on the eye movement measures and self-rating restoration of staff.


Assuntos
Meio Ambiente , Movimentos Oculares , Estresse Ocupacional , Recursos Humanos em Hospital , China , Hospitais , Humanos , Estresse Ocupacional/prevenção & controle , Descanso
4.
Heliyon ; 8(12): e12627, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36619408

RESUMO

Heritage value is a prerequisite for protecting and utilising traditional villages. In response to the unclear definition of heritage value, this study develops a conceptual model and an indicator system of traditional village heritage value based on cultural ecology. Additionally, the study analyses heritage value using a three-dimensional matrix model and cluster analysis. The results show significant differences in the heritage value of Huizhou traditional villages. High heritage values are mainly distributed in Yi County and She County, while low heritage values are mainly distributed at the edges of the region. Among the diversity, continuity and integrity differences, the integrity difference is the highest, and is reflected in the quality of heritage ontology and the relationship between heritage ontology and the surrounding environment. In addition, four types of Huizhou traditional villages are identified: resource single type, inheritance dilemma type, quality dilemma type, and heritage vitality type. Utilisation strategies are proposed for the four types to guide the classified management of traditional villages.

5.
HERD ; 15(1): 239-255, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34409863

RESUMO

OBJECTIVES: To investigate the differences and relationships between different outdoor spaces of hospitals on the physiological electroencephalography (EEG) feedback (PEEGF) of staff. BACKGROUND: Relieving the pressure of hospital staff is essential, and several studies have revealed that even short-term exposure to outdoor space has a decompression effect. Yet, the focus is scarcely centered on the differences and influential relationships between the PEEGF from different outdoor spaces where the staff spend time, particularly in large-scale hospitals in China. METHODS: EEG measurement equipment was utilized to obtain the value of ß wave (vßw) that represents the stress and anxiety of staff in three different outdoor spaces: open, traffic, and rest. On the basis of EEG data, correlation analysis was conducted in accordance with the proportion of space elements. RESULTS: The proportion of natural elements, such as landscape (r = -.800** p=.005) and waterscape (r = -.782* p=.013), were negatively correlated with the vßw produced by staff, while the proportion of hard paving was positive (r = .817** p=.004) with more vßw produced by staff. In other words, the percentage of landscape and waterscape can reduce stress, while hard paving has the opposite effect. Further, there was a difference in the amount of vßw generated between nurses and administrators in the open space at the entrance of the main building (p = .043). CONCLUSIONS: The present study revealed the influence of different outdoor space elements of the hospital on the physiological feedback of staff, demonstrated the practical necessity of evidence-based design, and proposed relevant optimization suggestions.


Assuntos
Eletroencefalografia , Hospitais , Retroalimentação , Retroalimentação Fisiológica , Humanos , Recursos Humanos em Hospital
6.
Sci Rep ; 11(1): 18201, 2021 09 14.
Artigo em Inglês | MEDLINE | ID: mdl-34521875

RESUMO

Panax ginseng is one of the oldest and most generally prescribed herbs in Eastern traditional medicine to treat diseases. Several studies had documented that ginseng leaves have anti-oxidative, anti-inflammatory, and anticancer properties similar to those of ginseng root. The aim of this research was to forecast of the molecular mechanism of ginseng leaves on lung cancer by molecular docking and network pharmacology so as to decipher ginseng leaves' entire mechanism. The compounds associated with ginseng leaves were searched by TCMSP. TCMSP and Swiss Target Prediction databases were used to sort out the potential targets of the main chemical components. Targets were collected from OMIM, PharmGKB, TTD, DrugBank and GeneCards which related to immunity and lung cancer. Ginseng leaves exert its lung cancer suppressive function by regulating the several signaling proteins, such as JUN, STAT3, AKT1, TNF, MAPK1, TP53. GO and KEGG analyses indicated that the immunoreaction against lung cancer by ginseng leaves might be related to response to lipopolysaccharide, response to oxidative stress, PI3K-Akt, MAPK and TNF pathway. Molecular docking analysis demonstrated that hydrogen bonding was interaction's core forms. The results of CCK8 test and qRT-PCR showed that ginseng leaves inhibit cell proliferation and regulates AKT1 and P53 expression in A549. The present study clarifies the mechanism of Ginseng leaves against lung cancer and provides evidence to support its clinical use.


Assuntos
Antineoplásicos/farmacologia , Fatores Imunológicos/farmacologia , Neoplasias Pulmonares/metabolismo , Panax/química , Extratos Vegetais/farmacologia , Células A549 , Proliferação de Células/efeitos dos fármacos , Humanos , Proteína Quinase 1 Ativada por Mitógeno/genética , Proteína Quinase 1 Ativada por Mitógeno/metabolismo , Folhas de Planta/química , Proteínas Proto-Oncogênicas c-akt/genética , Proteínas Proto-Oncogênicas c-akt/metabolismo , Transdução de Sinais/efeitos dos fármacos , Transcriptoma/efeitos dos fármacos , Fator de Necrose Tumoral alfa/genética , Fator de Necrose Tumoral alfa/metabolismo , Proteína Supressora de Tumor p53/genética , Proteína Supressora de Tumor p53/metabolismo
7.
PLoS Genet ; 17(2): e1009066, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33571185

RESUMO

Intracellular Ca2+ level is under strict regulation through calcium channels and storage pools including the endoplasmic reticulum (ER). Mutations in certain ion channel subunits, which cause mis-regulated Ca2+ influx, induce the excitotoxic necrosis of neurons. In the nematode Caenorhabditis elegans, dominant mutations in the DEG/ENaC sodium channel subunit MEC-4 induce six mechanosensory (touch) neurons to undergo excitotoxic necrosis. These necrotic neurons are subsequently engulfed and digested by neighboring hypodermal cells. We previously reported that necrotic touch neurons actively expose phosphatidylserine (PS), an "eat-me" signal, to attract engulfing cells. However, the upstream signal that triggers PS externalization remained elusive. Here we report that a robust and transient increase of cytoplasmic Ca2+ level occurs prior to the exposure of PS on necrotic touch neurons. Inhibiting the release of Ca2+ from the ER, either pharmacologically or genetically, specifically impairs PS exposure on necrotic but not apoptotic cells. On the contrary, inhibiting the reuptake of cytoplasmic Ca2+ into the ER induces ectopic necrosis and PS exposure. Remarkably, PS exposure occurs independently of other necrosis events. Furthermore, unlike in mutants of DEG/ENaC channels, in dominant mutants of deg-3 and trp-4, which encode Ca2+ channels, PS exposure on necrotic neurons does not rely on the ER Ca2+ pool. Our findings indicate that high levels of cytoplasmic Ca2+ are necessary and sufficient for PS exposure. They further reveal two Ca2+-dependent, necrosis-specific pathways that promote PS exposure, a "two-step" pathway initiated by a modest influx of Ca2+ and further boosted by the release of Ca2+ from the ER, and another, ER-independent, pathway. Moreover, we found that ANOH-1, the worm homolog of mammalian phospholipid scramblase TMEM16F, is necessary for efficient PS exposure in thapsgargin-treated worms and trp-4 mutants, like in mec-4 mutants. We propose that both the ER-mediated and ER-independent Ca2+ pathways promote PS externalization through activating ANOH-1.


Assuntos
Caenorhabditis elegans/metabolismo , Cálcio/metabolismo , Retículo Endoplasmático/metabolismo , Neurônios/metabolismo , Fosfatidilserinas/metabolismo , Animais , Animais Geneticamente Modificados , Apoptose/genética , Caenorhabditis elegans/efeitos dos fármacos , Caenorhabditis elegans/genética , Proteínas de Caenorhabditis elegans/genética , Proteínas de Caenorhabditis elegans/metabolismo , Citoplasma/metabolismo , Dantroleno/farmacologia , Canais de Sódio Degenerina/genética , Canais de Sódio Degenerina/metabolismo , Retículo Endoplasmático/efeitos dos fármacos , Retículo Endoplasmático/genética , Inibidores Enzimáticos/farmacologia , Proteínas de Membrana/genética , Proteínas de Membrana/metabolismo , Relaxantes Musculares Centrais/farmacologia , Necrose/genética , Necrose/metabolismo , Neurônios/efeitos dos fármacos , Neurônios/patologia , Proteínas de Transferência de Fosfolipídeos/genética , Proteínas de Transferência de Fosfolipídeos/metabolismo , Canais de Sódio/genética , Canais de Sódio/metabolismo , Canais de Cátion TRPC/genética , Canais de Cátion TRPC/metabolismo , Tapsigargina/farmacologia
8.
Medicine (Baltimore) ; 99(44): e22886, 2020 Oct 30.
Artigo em Inglês | MEDLINE | ID: mdl-33126339

RESUMO

BACKGROUND: Trastuzumab emtansine (T-DM1) is an antibody-drug conjugate that retains the antitumor effects of trastuzumab while also delivering the cytotoxic antimicrotubule agent, DM1, directly to tumor cells that overexpress human epidermal growth factor receptor 2. The pharmacokinetic (PK) profile of T-DM1 has been well characterized in Western, Asian, and Japanese patients; this single-center, phase I study (NCT03153163) examined the PK of T-DM1 and safety specifically in Chinese patients. METHODS: Patients with locally advanced or metastatic breast cancer, previously treated with trastuzumab and a taxane, received open-label T-DM1 at 3.6 mg/kg every 3 weeks. Serum T-DM1 and total trastuzumab, and plasma DM1 were evaluated, and PK parameters were calculated using standard noncompartmental approaches. Adverse events (AEs) were assessed, and immunogenicity was evaluated by measuring antidrug antibodies to T-DM1. RESULTS: Among 11 Chinese patients, mean (±standard deviation) PK parameters (maximum serum concentration, 77.6 ±â€Š17.4 µg/mL; clearance 11.0 ±â€Š2.6 mL/d/kg; terminal half-life 3.8 ±â€Š1.0 days) were similar to those previously reported in Western and Japanese patients. One patient transiently developed antidrug antibodies, which did not appear to influence safety or PK. T-DM1 was generally well tolerated. Grade 3-4 AEs occurred in 7 patients (63.6%) and serious AEs occurred in 4 patients (36.4%). Platelet count decrease was the most common all-grade AE (10/11; 90.9%), grade 3-4 AE (5/11; 45.5%), and serious AE (3/11; 27.3%), but did not appear to be associated with any clinically significant bleeding events. CONCLUSIONS: T-DM1 PK in Chinese patients was consistent with those in global and Asian populations, supporting its use in patients with advanced human epidermal growth factor receptor 2-positive breast cancer following progression on trastuzumab and a taxane. The safety profile of T-DM1 was consistent with prior experience.


Assuntos
Neoplasias da Mama/tratamento farmacológico , Receptor ErbB-2/análise , Trastuzumab , Antineoplásicos Imunológicos/administração & dosagem , Antineoplásicos Imunológicos/efeitos adversos , Antineoplásicos Imunológicos/farmacocinética , Neoplasias da Mama/imunologia , Neoplasias da Mama/patologia , China , Monitoramento de Medicamentos/métodos , Feminino , Humanos , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Trastuzumab/administração & dosagem , Trastuzumab/efeitos adversos , Trastuzumab/farmacocinética , Resultado do Tratamento
9.
MAbs ; 12(1): 1699768, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31852341

RESUMO

vc-MMAE antibody-drug conjugates (ADCs) consist of a monoclonal antibody (mAb) covalently bound with a potent anti-mitotic toxin (MMAE) through a protease-labile valine-citrulline (vc) linker. The objective of this study was to characterize the pharmacokinetics (PK) and explore exposure-response relationships of eight vc-MMAE ADCs, against different targets and for diverse tumor indications, using data from eight first-in-human Phase 1 studies. PK parameters of the three analytes, namely antibody-conjugated MMAE (acMMAE), total antibody, and unconjugated MMAE, were estimated using non-compartmental approaches and compared across the eight vc-MMAE ADCs. Relationships between analytes were assessed by linear regression. Exposure-response relationships were explored with key efficacy (objective response rate) and safety (Grade 2+ peripheral neuropathy) endpoints. PK profiles of acMMAE, total antibody and unconjugated MMAE following the first dose of 2.4 mg/kg were comparable across the eight ADCs; the exposure differences between molecules were small relative to the inter-subject variability. acMMAE exposure was strongly correlated with total antibody exposure for all the eight ADCs, but such correlation was less evident between acMMAE and unconjugated MMAE exposure. For multiple ADCs evaluated, efficacy and safety endpoints appeared to correlate well with acMMAE exposure, but not with unconjugated MMAE over the doses tested. PK of vc-MMAE ADCs was well characterized and demonstrated remarkable similarity at 2.4 mg/kg across the eight ADCs. Results from analyte correlation and exposure-response relationship analyses suggest that measurement of acMMAE analyte alone might be adequate for vc-MMAE ADCs to support the clinical pharmacology strategy used during late-stage clinical development.


Assuntos
Antineoplásicos Imunológicos/farmacocinética , Imunoconjugados/farmacocinética , Imunoterapia/métodos , Neoplasias/terapia , Antimitóticos , Ensaios Clínicos Fase I como Assunto , Humanos , Neoplasias/imunologia
10.
Clin Transl Sci ; 12(5): 534-544, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31115997

RESUMO

Prediction of human pharmacokinetics (PK) based on preclinical information for antibody-drug conjugates (ADCs) provide important insight into first-in-human (FIH) study design. This retrospective analysis was conducted to identify an appropriate scaling method to predict human PK for ADCs from animal PK data in the linear range. Different methods for projecting human clearance (CL) from animal PK data for 11 ADCs exhibiting linear PK over the tested dose ranges were examined: multiple species allometric scaling (CL vs. body weight), allometric scaling with correction factors, allometric scaling based on rule of exponent, and scaling from only cynomolgus monkey PK data. Two analytes of interest for ADCs, namely total antibody and conjugate (measured as conjugated drug or conjugated antibody), were assessed. Percentage prediction errors (PEs) and residual sum of squares (RSS) were compared across methods. Human CL was best estimated using cynomolgus monkey PK data alone and an allometric scaling exponent of 1.0 for CL. This was consistently observed for both conjugate and total antibody analytes. Other scaling methods either underestimated or overestimated human CL, or produced larger average absolute PEs and RSS. Human concentration-time profiles were also reasonably predicted from the cynomolgus monkey data using species-invariant time method with a fixed exponent of 1.0 for CL and 1.0 for volume of distribution. In conclusion, results from this retrospective analysis of 11 ADCs indicate that allometric scaling of CL with an exponent of 1.0 using cynomolgus monkey PK data alone can successfully project human PK profiles of an ADC within linear range.


Assuntos
Imunoconjugados/farmacocinética , Animais , Anticorpos Monoclonais/farmacocinética , Humanos , Macaca fascicularis , Taxa de Depuração Metabólica
11.
Chinese Health Economics ; (12): 24-28, 2017.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-666655

RESUMO

The establishment of negotiation and consultation mechanism between medical insurance management agency and medical institution,could proceed the development of provider payment system reforms.This paper discussed the policy basis and the basic principle of negotiation and consultation in provider payment system reforms,and the subject,level and model,content,the carrying out and so on.

12.
Indian J Orthop ; 50(4): 421-6, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27512225

RESUMO

BACKGROUND: The diagnosis and treatment of bone nonunion have been studied extensively. Diagnosis and treatment of nonunion are mainly performed based on the interpretation of clinico-radiographic findings, which depend on the clinician's experience and the degree of bone callus formation during the fracture-healing process. However, resolution may be compromised when the bone mineral content is <25%. A feasible method of monitoring bone-healing is therefore needed. We monitored a rabbit model of bone nonunion by regular radiographic examinations, QCT detection, and biomarker concentrations. MATERIALS AND METHODS: Twenty purebred New Zealand rabbits (10 male and 10 female, 5-6 months of age, 2.5-3.0 kg) were divided into bone defect Group (I) that 10 left radius bones underwent resection of 1.5 cm of mid-radius bone and bone fracture Group (II) that another 10 left radius bones underwent only mid-radius fracture. Quantitative computed tomography detection of bone mineral density (BMD) and serum markers of bone formation (osteocalcin [OC], bone-specific alkaline phosphatase) and bone resorption (C- and N-terminal telopeptides of type I collagen (NTX) and tartrate-resistant acid phosphatase 5b) were assayed. There are twenty rabbits (10 male and 10 females). The age was 5-6 months weighing 2.5-3.0 kg). The defect was created in middle 1/3 radius in 10 rabbits and fracture was created in middle 1/3 radius of 10 rabbits. RESULTS: BMD and NTX concentrations were significantly lower at 5 weeks postoperatively compared to the preoperative values and were significantly different between the two groups. OC showed no significant difference before and after surgery. CONCLUSIONS: BMD and NTX concentrations may be useful for early detection of bone nonunion in rabbits.

13.
Worm ; 5(1): e1120400, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27073733

RESUMO

Necrosis is a type of cell death often caused by cell injury and is linked to human diseases including neuron degeneration, stroke, and cancer. Cells undergoing necrosis are engulfed and degraded by engulfing cells, their predators. The mechanisms by which necrotic cells are recognized and removed remain elusive. Here we comment on our recent findings that reveal new molecular mechanisms of necrotic-cell recognition. Through studying the C. elegans touch neurons undergoing excitotoxic necrosis, we identified a receptor/ligand pair that enables engulfing cells to recognize necrotic neurons. The phagocytic receptor CED-1 is activated through interaction with its ligand phosphatidylserine (PS), exposed on the surface of necrotic cells. Furthermore, against the common belief that necrotic cells have ruptured plasma membrane, we found that necrotic C. elegans touch neurons actively present PS on their outer surfaces while maintaining plasma membrane integrity. We further identified 2 mechanisms governing the presentation of PS, one of which is shared with cells undergoing apoptosis, a "cell suicide" event, whereas the other is unique to necrotic neurons. The influx of Ca(2+), a key necrosis-triggering factor, is implicated in activating a neuronal PS-scramblase for PS exposure. We propose that the mechanisms controlling PS-exposure and necrotic-cell recognition by engulfing cells are likely conserved from worms to humans.

14.
Exp Ther Med ; 12(6): 3595-3601, 2016 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-28105092

RESUMO

The aim of the present study was to establish an experimental animal model of fracture nonunion, and to investigate the changes in serum biomarker concentrations in fracture nonunion. A total of 20 purebred New Zealand rabbits were divided into two group: A bone defect group and a bone fracture group. In the bone defect group, a 15-mm section of bone (including the periosteum) was removed from the mid-radius, and the medullary cavities were closed with bone wax. In the bone fracture group, the mid-radius was fractured. X-rays were taken and blood samples were collected preoperatively and at 2, 3, 4, 5, 6, 7, 8, 10 and 12 weeks after the surgical procedure. The serum concentrations of osteocalcin (OC) and bone-specific alkaline phosphatase (BSAP) served as markers of bone formation, and those of C-terminal telopeptide of type I collagen (CTX), N-terminal telopeptide of type I collagen (NTX) and tartrate-resistant acid phosphatase 5b (TRACP 5b) served as markers of bone resorption. The concentration levels of the markers were measured using a biotin double-antibody sandwich enzyme-linked immunosorbent assay. In the bone defect group, bone callus was observed on X-ray at 2 weeks in three rabbits and the bone calluses stabilized at 5 weeks; however, none of the bones had healed at 8 weeks. In the bone fracture group, the fracture line was distorted at 2 weeks and bone calluses formed at 6-8 weeks. In the bone defect group, the serum BSAP and TRACP 5b concentrations increased following the surgical procedure, peaked at 4 weeks, began to decrease at 5 weeks and stabilized after 6 weeks. The serum OC concentrations did not change significantly following the surgical procedure. The serum CTX concentrations fluctuated during the first 4 weeks, peaked at 5 weeks, then decreased and stabilized after 6 weeks. The serum NTX concentrations fluctuated during the first 4 weeks, were significantly lower at 5 weeks compared with the other time points and stabilized after 6 weeks. These results suggested that a bone nonunion model can be established in New Zealand rabbits by resecting a 15-mm section of bone from the mid-radius prior to bone wax blocking. Measurement of the serum BSAP, CTX, NTX, and TRACP 5b concentrations may be useful for the early detection of bone nonunion. The serum NTX concentrations changed significantly in rabbits with bone nonunion. Further studies are required in order to determine the feasibility of using serum NTX concentrations for the early diagnosis of bone nonunion.

15.
Mol Med Rep ; 13(1): 287-94, 2016 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-26549244

RESUMO

Previous in vitro studies have demonstrated that resveratrol is able to significantly inhibit the upregulation of mucin 5AC (MUC5AC), a major component of mucus; thus indicating that resveratrol may have potential in regulating mucus overproduction. However, there have been few studies regarding the resveratrol­mediated prevention of MUC5AC overproduction in vivo, and the mechanisms by which resveratrol regulates MUC5AC expression have yet to be elucidated. In the present study, an ovalbumin (OVA)­challenged murine model of asthma was used to assess the effects of resveratrol treatment on mucus production in vivo. The results demonstrated that resveratrol significantly inhibited OVA­induced airway inflammation and mucus production. In addition, the mRNA and protein expression levels of MUC5AC were increased in the OVA­challenged mice, whereas treatment with resveratrol significantly inhibited this effect. The expression levels of murine calcium­activated chloride channel (mCLCA)3, an important key mediator of MUC5AC production, were also reduced following resveratrol treatment. Furthermore, in vitro studies demonstrated that resveratrol significantly inhibited human (h)CLCA1 and MUC5AC expression in a dose­dependent manner. These results indicated that resveratrol was effective in preventing mucus overproduction and MUC5AC expression in vivo, and its underlying mechanism may be associated with regulation of the mCLCA3/hCLCA1 signaling pathway.


Assuntos
Asma/tratamento farmacológico , Asma/metabolismo , Mucina-5AC/metabolismo , Muco/metabolismo , Estilbenos/farmacologia , Estilbenos/uso terapêutico , Animais , Asma/genética , Asma/patologia , Linhagem Celular , Modelos Animais de Doenças , Células Epiteliais/efeitos dos fármacos , Células Epiteliais/metabolismo , Feminino , Regulação da Expressão Gênica/efeitos dos fármacos , Humanos , Pulmão/efeitos dos fármacos , Pulmão/metabolismo , Pulmão/patologia , Camundongos Endogâmicos BALB C , Mucina-5AC/genética , Pneumonia/complicações , Pneumonia/tratamento farmacológico , Pneumonia/patologia , Resveratrol
17.
PLoS Genet ; 11(6): e1005285, 2015 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-26061275

RESUMO

Necrosis, a kind of cell death closely associated with pathogenesis and genetic programs, is distinct from apoptosis in both morphology and mechanism. Like apoptotic cells, necrotic cells are swiftly removed from animal bodies to prevent harmful inflammatory and autoimmune responses. In the nematode Caenorhabditis elegans, gain-of-function mutations in certain ion channel subunits result in the excitotoxic necrosis of six touch neurons and their subsequent engulfment and degradation inside engulfing cells. How necrotic cells are recognized by engulfing cells is unclear. Phosphatidylserine (PS) is an important apoptotic-cell surface signal that attracts engulfing cells. Here we observed PS exposure on the surface of necrotic touch neurons. In addition, the phagocytic receptor CED-1 clusters around necrotic cells and promotes their engulfment. The extracellular domain of CED-1 associates with PS in vitro. We further identified a necrotic cell-specific function of CED-7, a member of the ATP-binding cassette (ABC) transporter family, in promoting PS exposure. In addition to CED-7, anoctamin homolog-1 (ANOH-1), the C. elegans homolog of the mammalian Ca(2+)-dependent phospholipid scramblase TMEM16F, plays an independent role in promoting PS exposure on necrotic cells. The combined activities from CED-7 and ANOH-1 ensure efficient exposure of PS on necrotic cells to attract their phagocytes. In addition, CED-8, the C. elegans homolog of mammalian Xk-related protein 8 also makes a contribution to necrotic cell-removal at the first larval stage. Our work indicates that cells killed by different mechanisms (necrosis or apoptosis) expose a common "eat me" signal to attract their phagocytic receptor(s); furthermore, unlike what was previously believed, necrotic cells actively present PS on their outer surfaces through at least two distinct molecular mechanisms rather than leaking out PS passively.


Assuntos
Caenorhabditis elegans/metabolismo , Fagócitos/metabolismo , Fagocitose , Fosfatidilserinas/metabolismo , Transportadores de Cassetes de Ligação de ATP/metabolismo , Animais , Apoptose , Caenorhabditis elegans/imunologia , Proteínas de Caenorhabditis elegans/metabolismo , Proteínas de Membrana/metabolismo , Necrose , Proteínas de Transferência de Fosfolipídeos/metabolismo
18.
Environ Sci Pollut Res Int ; 22(3): 1697-704, 2015 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-25266058

RESUMO

The increasing levels of heavy metals in the environment generally related with the rapid industrialization and urbanization. Mercury (Hg) is a global toxin with wide concerns, and China gradually becomes the main producer, consumer, and emitter of Hg in the world. However, few historical data are available on the occurrence of Hg in Chinese urban areas. Here, we collected 35 lake surface sediment samples from 35 public parks and 1 sediment core in the Luxun Park in Shanghai, a hyper-urbanization city in China, to determine the spatial and vertical distributions of total mercury (THg) and methylmercury (MeHg) and to explore the Hg pollution history with the industrial development. Higher concentrations of Hg and MeHg and greater Hg enrichment were found in urban areas compared with suburban area with the following order: central urban core area > developed urban area > developing urban area > suburban area. The THg concentration in the sediment core showed an increasing trend from 1876 to 2000 and a decreasing trend from 2000 to 2012, coinciding with the process of industrialization and urbanization in Shanghai. However, THg fluxes unceasingly increased from 1876 to present probably attributed to coal consumption in the suburban area and transportation agglomeration in the central urban core area. Unlike THg, no significant variations for MeHg with time and the maximum value (0.17 µg/kg) appeared in 1947. The methylation ratio of MeHg to THg in the sediment is pretty low, and more studies are needed to further understand the fate of Hg in the environment.


Assuntos
Mercúrio/análise , Metais Pesados/análise , Compostos de Metilmercúrio/química , Poluentes Químicos da Água/análise , China , Cidades , Poluição Ambiental , Lagos/química , População Rural , Urbanização
19.
Ecotoxicol Environ Saf ; 102: 129-35, 2014 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-24530728

RESUMO

Rapid urbanization has caused potential pollution of heavy metal in Shanghai. A comprehensive pollution study of heavy metals (Cd, Cu, Pb, and Zn) in 35 lake surface sediments from city parks in the four different urbanized areas of Shanghai was conducted. Intensive human activities caused moderate enrichment of the four metals in highly urbanized areas, especially Cd with the significant enrichment in the central urban core area. However, the levels of the four metals in all the sediments were lower than the corresponding consensus-based Probable Effect Concentration, indicating adverse effects not to occur frequently. The integrated pollution assessments of multiple heavy metals also suggested low ecological risk and 15-29 percent probability of toxicity in most of sediments. The metal speciation analysis showed that Cd, Cu, Pb, and Zn were dominated by the non-residual fractions and thus they have high mobility and bioavailability, indicating significant anthropogenic sources. According to the Risk Assessment Code, Cd had the highest bioavailable fraction and represented high or very high risk, followed by Zn with medium or high risks in most of samples, while no or low risk was found for Cu and Pb at most sites because they were dominated by reducible and residual fractions. Correlation analysis showed that chemical fractions of heavy metals were prone to transform among each other if environmental conditions changed. Therefore, in view of anthropogenic inputs and speciation distribution, heavy metals with very high bioavailability at very low total levels and those with low bioavailability at very high total levels should not be ignored.


Assuntos
Cidades , Monitoramento Ambiental , Sedimentos Geológicos/química , Lagos , Metais Pesados/análise , Poluentes Químicos da Água/análise , China , Humanos , Metais Pesados/química , Medição de Risco
20.
Methods Mol Biol ; 1004: 183-202, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-23733578

RESUMO

The nematode Caenorhabditis elegans is an excellent model organism for studying the mechanisms -controlling cell death, including apoptosis, a cell suicide event, and necrosis, pathological cell deaths caused by environmental insults or genetic alterations. C. elegans has also been established as a model for understanding how dying cells are cleared from animal bodies. In particular, the transparent nature of worm bodies and eggshells make C. elegans particularly amenable for live-cell microscopy. Here we describe methods for identifying apoptotic and necrotic cells in living C. elegans embryos, larvae, and adults and for monitoring their clearance during development. We further discuss specific methods to distinguish engulfed from unengulfed apoptotic cells, and methods to monitor cellular and molecular events occurring during phagosome maturation. These methods are based on Differential Interference Contrast (DIC) microscopy or fluorescence microscopy using GFP-based reporters.


Assuntos
Apoptose , Caenorhabditis elegans/citologia , Técnicas Citológicas/métodos , Animais , Biomarcadores/metabolismo , Caenorhabditis elegans/embriologia , Caenorhabditis elegans/metabolismo , Proteínas de Caenorhabditis elegans/metabolismo , Contagem de Células , Embrião não Mamífero/citologia , Embrião não Mamífero/metabolismo , Proteínas de Fluorescência Verde/metabolismo , Microscopia de Interferência , Necrose , Neurônios/citologia , Fagocitose , Fagossomos/metabolismo , Imagem com Lapso de Tempo
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