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1.
Hu Li Za Zhi ; 70(2): 34-44, 2023 Apr.
Artigo em Chinês | MEDLINE | ID: mdl-36942541

RESUMO

BACKGROUND: Musculoskeletal disorders are a common occupational disease. The prevalence of musculoskeletal disorders among nurses is estimated at 65.1%-87.3%, with neck, shoulders, and lower back being most affected. PURPOSE: To explore the effectiveness of tennis ball massage therapy in alleviating muscle soreness and improving pain relief self-efficacy. METHODS: In this quasi-experimental, single-group, pre- and post-test study, 216 nurses in regional teaching hospitals were screened for neck, shoulder, and back pain. Based on the unit attributes, systematic random sampling was employed to recruit 36 nurses to participate in a four-week "fighting pain" intervention program. The "Pain Visual Scale" and "Pain Relief Self-efficacy Scale" were used as the assessment tools. One-way and two-way repeated measure analysis of variance, a signed ranks test, and the Friedman test were used to assess longitudinal change in the data. RESULTS: Shoulders were the most reported site of muscle pain (94.4%), followed by the neck (88.9%) and the upper back (55.6%). The locations of neck, shoulder, and back pain were interacted differently with the four measurement times (F = 2.69, p = .020). In the post hoc comparison, pain relief effectiveness was most significant in the third posttest, followed by the second. The pain relief was significantly different between the pre-test and the third post-test (t = 6.39, 8.68, 6.96, p < .001). There was a significant difference before and after the intervention of the pain relief self-efficacy (F = 53.49, p < .001). The post hoc comparison results revealed that self-efficacy was lowest at pretest and highest at the third posttest. Significant differences were observed between the pre-test and third post-test at the end of the intervention (t = -10.25, p < .001). CONCLUSIONS / IMPLICATIONS FOR PRACTICE: This study shows that tennis ball massage can improve neck, shoulder, and back pain in nurses and improve pain relief self-efficacy. Tennis ball massage is easy to implement, has no time and space restrictions, and requires no assistance to operate. This equipment can be used to effectively reduce muscle pain, improve the comfort of performing regular activities, and raise work efficiency, reducing the negative impact of muscle pain on work.


Assuntos
Doenças Musculoesqueléticas , Tênis , Humanos , Mialgia , Autoeficácia , Doenças Musculoesqueléticas/terapia , Dor nas Costas/terapia , Massagem/métodos
2.
MedComm (2020) ; 4(2): e229, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-36891351

RESUMO

Interleukin 37 (IL-37), a member of the IL-1 family, is considered a suppressor of innate and adaptive immunity and, hence is a regulator of tumor immunity. However, the specific molecular mechanism and role of IL-37 in skin cancer remain unclear. Here, we report that IL-37b-transgenic mice (IL-37tg) treated with the carcinogenic 7,12-dimethylbenzoanthracene (DMBA)/12-o-tetradecylphorbol-13-acetate (TPA) exhibited enhanced skin cancer and increased tumor burden in the skin by inhibiting the function of CD103+ dendritic cells (DCs). Notably, IL-37 induced rapid phosphorylation of adenosine 5'-monophosphate (AMP)-activated protein kinase (AMPK), and via single immunoglobulin IL-1-related receptor (SIGIRR), inhibited the long-term Akt activation. Specifically, by affecting the SIGIRR-AMPK-Akt signaling axis, which is related to the regulation of glycolysis in CD103+DCs, IL-37 inhibited their anti-tumor function. Our results show that a marked correlation between the CD103+DC signature (IRF8, FMS-like tyrosine kinase 3 ligand, CLEC9A, CLNK, XCR1, BATF3, and ZBTB46) and chemokines C-X-C motif chemokine ligand 9, CXCL10, and CD8A in a mouse model with DMBA/TPA-induced skin cancer. In a word, our results highlight that IL-37 as an inhibitor of tumor immune surveillance through modulating CD103+DCs and establishing an important link between metabolism and immunity as a therapeutic target for skin cancer.

3.
Hu Li Za Zhi ; 70(1): 35-47, 2023 Feb.
Artigo em Chinês | MEDLINE | ID: mdl-36647309

RESUMO

BACKGROUND: Fatigue may lead to disordered sleep. Primary caregivers of patients with cancer may suffer from higher levels of disordered sleep because of care-related fatigue. Older-adult veterans with cancer tend to be emotionally negative, which increases the challenges of care. PURPOSE: This study was designed to investigate the veteran status of patients as a possible moderator in the relationship between fatigue and disordered sleep in primary caregivers. METHODS: In this cross-sectional study, 127 primary caregivers of patients with cancer were randomly recruited from three hospitals in northern Taiwan. Data were collected using a demographics datasheet, the Taiwanese version of the Brief Fatigue Inventory, and the Chinese version of the Pittsburgh Sleep Quality Index. Descriptive statistics, independent t-tests, one-way ANOVA, Pearson correlation analyses, and hierarchical regression analyses were used to analyze the obtained data. RESULTS: Fatigue in the participants was shown to correlate significantly and positively with their sleep quality (r = .632, p < .01), with fatigue found to affect sleep quality positively (ß = .472, p < .001). The regression analyses showed the explanatory power of fatigue on sleep disorders (b = .148, p < .001) to be higher in caregivers of veteran patients than in caregivers of non-veteran patients (b = .091, p < .001). CONCLUSIONS / IMPLICATIONS FOR PRACTICE: Veteran patient status may moderate the relationship between fatigue and disordered sleep in primary caregivers. Nurses should assess caregiver fatigue status and offer appropriate resources.


Assuntos
Neoplasias , Transtornos do Sono-Vigília , Adulto , Humanos , Cuidadores/psicologia , Estudos Transversais , Neoplasias/complicações , Neoplasias/psicologia , Transtornos do Sono-Vigília/etiologia , Fadiga/etiologia , Sono
4.
Eur J Pediatr ; 182(1): 343-352, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36352243

RESUMO

Unnecessary radiation exposure (URE) during radiographic examination is an issue among infants in neonatal intensive care units (NICUs). The causes of URE have not been fully explored. This study investigated the incidence and identified the causes of URE in infants during diagnostic radiography in a NICU. This was a retrospective cohort study. We retrieved and analysed requests and radiographs taken at a tertiary NICU between September and November 2018. URE was defined as the rate of discordance between requests and images taken (DisBRI) and unnecessary radiation exposure in irrelevant regions (UREIR) during radiography. We compared the rates of URE between very low-birth-weight (VLBW, birth weight < 1500 g) infants and non-VLBW infants. A total of 306 radiographs from 88 infants were taken. The means ± standard deviations (SDs) of gestational age and birth weight were 35.7 ± 3.6 weeks and 2471 ± 816 g, respectively. Each infant underwent an average of 3.5 radiographs. The DisBRI rate was 1.3% and was mostly related to poor adherence to requests. The UREIR rates in thoraco-abdominal babygrams were 89.6% for the head, 14.8% for the elbows and 18.4% for the knee and were mainly related to improper positioning of and collimation in infants while performing radiography. The UREIR rates for the head, knee and ankle were higher in VLBW infants than in non-VLBW infants (94.6% vs. 85.6%, 27.0% vs. 11.5% and 5.4% vs. 0.7%, respectively, p < 0.05). CONCLUSIONS: URE during diagnostic radiography is common in sick infants and is mainly related to improper positioning and collimation during examinations. Adherence to protocols when performing radiographic examination or using ultrasonography may be a solution to reduce URE in infants in NICUs. WHAT IS KNOWN: • The risk of unnecessary radiation exposure (URE) during radiography has been a common and important issue in sick infants in neonatal intensive care units (NICUs). • The new point-of-care ultrasound (POCUS) technique decreases the need for chest films and prevents radiation exposure in neonates. WHAT IS NEW: • In the NICU, URE is still a common issue in critically ill infants during radiographic examinations. The causes of URE during diagnostic radiography are mainly due to improper positioning and collimation during examinations. • The incidence of URE in irrelevant regions is higher in very low-birth-weight (VLBW) infants than in non-VLBW infants.


Assuntos
Unidades de Terapia Intensiva Neonatal , Exposição à Radiação , Recém-Nascido , Lactente , Humanos , Peso ao Nascer , Estudos Retrospectivos , Recém-Nascido de muito Baixo Peso , Radiografia , Exposição à Radiação/efeitos adversos
5.
Signal Transduct Target Ther ; 7(1): 19, 2022 01 20.
Artigo em Inglês | MEDLINE | ID: mdl-35046386

RESUMO

Interleukin-37b (hereafter called IL-37) was identified as fundamental inhibitor of natural and acquired immunity. The molecular mechanism and function of IL-37 in colorectal cancer (CRC) has been elusive. Here, we found that IL-37 transgenic (IL-37tg) mice were highly susceptible to colitis-associated colorectal cancer (CAC) and suffered from dramatically increased tumor burdens in colon. Nevertheless, IL-37 is dispensable for intestinal mutagenesis, and CRC cell proliferation, apoptosis, and migration. Notably, IL-37 dampened protective cytotoxic T cell-mediated immunity in CAC and B16-OVA models. CD8+ T cell dysfunction is defined by reduced retention and activation as well as failure to proliferate and produce cytotoxic cytokines in IL-37tg mice, enabling tumor evasion of immune surveillance. The dysfunction led by IL-37 antagonizes IL-18-induced proliferation and effector function of CD8+ T cells, which was dependent on SIGIRR (single immunoglobulin interleukin-1 receptor-related protein). Finally, we observed that IL-37 levels were significantly increased in CRC patients, and positively correlated with serum CRC biomarker CEA levels, but negatively correlated with the CD8+ T cell infiltration in CRC patients. Our findings highlight the role of IL-37 in harnessing antitumor immunity by inactivation of cytotoxic T cells and establish a new defined inhibitory factor IL-37/SIGIRR in cancer-immunity cycle as therapeutic targets in CRC.


Assuntos
Carcinogênese/imunologia , Colite/imunologia , Neoplasias Colorretais/imunologia , Interleucina-1/imunologia , Proteínas de Neoplasias/imunologia , Receptores de Interleucina-1/imunologia , Linfócitos T Citotóxicos/imunologia , Animais , Carcinogênese/genética , Colite/genética , Colite/patologia , Neoplasias Colorretais/genética , Interleucina-1/genética , Camundongos , Camundongos Transgênicos , Proteínas de Neoplasias/genética , Receptores de Interleucina-1/genética
6.
Pharmgenomics Pers Med ; 14: 211-220, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33568933

RESUMO

BACKGROUND: Patients with diabetes have more calcification in atherosclerotic plaque and a higher occurrence of secondary cardiovascular events than patients without diabetes. The objective of this study was to identify crucial genes involved in the development of diabetic atherosclerotic plaque using a bioinformatics approach. METHODS: Microarray dataset GSE118481 was downloaded from the Gene Expression Omnibus (GEO) database; the dataset included 6 patients with diabetic atherosclerotic plaque (DBT) and 6 nondiabetic patients with atherosclerotic plaque (Ctrl). Differentially expressed genes (DEG) between the DBT and Ctrl groups were identified and then subjected to functional enrichment analysis. Based on the enriched pathways of DEGs, diabetic atherosclerotic plaque-related pathways were screened using the comparative toxicogenomics database (CTD). We then constructed a protein-protein interaction (PPI) network and transcription factor (TF)-miRNA-mRNA network. RESULTS: A total of 243 DEGs were obtained in the DBT group compared with the Ctrl group, including 85 up-regulated and 158 down-regulated DEGs. Functional enrichment analysis showed that up-regulated DEGs were mainly enriched in isoprenoid metabolic process, DNA-binding TF activity, and response to virus. Additionally, DEGs participating in the toll-like receptor signaling pathway were closely related to diabetes, carotid stenosis, and insulin resistance. The TF-miRNA-mRNA network showed that toll-like receptor 4 (TLR4), BCL2-like 11 (BCL2L11), and glutamate-cysteine ligase catalytic subunit (GCLC) were hub genes. Furthermore, TLR4 was regulated by TF signal transducer and activator of transcription 6 (STAT6); BCL2L11 was targeted by hsa-miR-24-3p; and GCLC was regulated by nuclear factor, erythroid 2 like 2 (NFE2L2). CONCLUSION: Identification of hub genes and pathways increased our understanding of the molecular mechanisms underlying the atherosclerotic plaque in patients with or without diabetes. These crucial genes (TLR4, BC2L11, and GCLC) might function as molecular biomarkers for diabetic atherosclerotic plaque.

7.
Connect Tissue Res ; 61(5): 435-444, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-31023105

RESUMO

PURPOSE: To investigate whether salvianolic acid B is able to enhance repair of degenerated intervertebral discs by mesenchymal stem cells (MSCs) through the promotion of MSC differentiation into nucleus pulposus cells in a nucleus-pulposus-like environment and by enhancing the trophic effect of MSCs on residual nucleus pulposus cells (mediated by transforming growth factor-ß1). MATERIALS AND METHODS: Successful intervertebral disc degeneration models, established by aspiration of the nucleus pulposus in New Zealand white rabbits, were randomly divided into eight groups: Group A was treated with MSC transplantation. Group B was treated with MSC transplantation and salvianolic acid B, with the subgroups B1, B2, B3, and B4 receiving 0.01 mg/L, 0.1 mg/L, 1 mg/L, and 10 mg/L salvianolic acid B, respectively. Groups C and D were treated with phosphate buffer saline and sham graft, respectively. Group E was the normal control group. At the end of week 8, the type II collagen, proteoglycan, transforming growth factor-ß1, and water contents in each group were examined by semi-quantitative immunohistochemistry, spectrophotometry, enzyme-linked immunosorbent assay, and magnetic resonance, respectively. RESULTS: The content of type II collagen, proteoglycan, transforming growth factor-ß1, and water in groups B3 and B4 were significantly higher than those in group A (p < 0.01). CONCLUSIONS: Salvianolic acid B (1 mg/L to 10 mg/L) plus MSC transplantation was more effective in repairing degenerated intervertebral discs than was stem cell transplantation alone.


Assuntos
Alcenos/farmacologia , Degeneração do Disco Intervertebral , Transplante de Células-Tronco Mesenquimais , Células-Tronco Mesenquimais/metabolismo , Núcleo Pulposo/fisiologia , Polifenóis/farmacologia , Regeneração , Animais , Modelos Animais de Doenças , Degeneração do Disco Intervertebral/metabolismo , Degeneração do Disco Intervertebral/terapia , Coelhos
8.
J Struct Biol ; 197(3): 322-329, 2017 03.
Artigo em Inglês | MEDLINE | ID: mdl-28017791

RESUMO

A recurrent interrogation when imaging soft biomolecules using atomic force microscopy (AFM) is the putative deformation of molecules leading to a bias in recording true topographical surfaces. Deformation of biomolecules comes from three sources: sample instability, adsorption to the imaging substrate, and crushing under tip pressure. To disentangle these causes, we measured the maximum height of a well-known biomolecule, the tobacco mosaic virus (TMV), under eight different experimental conditions positing that the maximum height value is a specific indicator of sample deformations. Six basic AFM experimental factors were tested: imaging in air (AIR) versus in liquid (LIQ), imaging with flat minerals (MICA) versus flat organic surfaces (self-assembled monolayers, SAM), and imaging forces with oscillating tapping mode (TAP) versus PeakForce tapping (PFT). The results show that the most critical parameter in accurately measuring the height of TMV in air is the substrate. In a liquid environment, regardless of the substrate, the most critical parameter is the imaging mode. Most importantly, the expected TMV height values were obtained with both imaging with the PeakForce tapping mode either in liquid or in air at the condition of using self-assembled monolayers as substrate. This study unambiguously explains previous poor results of imaging biomolecules on mica in air and suggests alternative methodologies for depositing soft biomolecules on well organized self-assembled monolayers.


Assuntos
Microscopia de Força Atômica/métodos , Vírus do Mosaico do Tabaco/ultraestrutura
9.
BMC Struct Biol ; 16(1): 18, 2016 10 27.
Artigo em Inglês | MEDLINE | ID: mdl-27788689

RESUMO

BACKGROUND: Synchrotron radiation facilities are pillars of modern structural biology. Small-Angle X-ray scattering performed at synchrotron sources is often used to characterize the shape of biological macromolecules. A major challenge with high-energy X-ray beam on such macromolecules is the perturbation of sample due to radiation damage. RESULTS: By employing atomic force microscopy, another common technique to determine the shape of biological macromolecules when deposited on flat substrates, we present a protocol to evaluate and characterize consequences of radiation damage. It requires the acquisition of images of irradiated samples at the single molecule level in a timely manner while using minimal amounts of protein. The protocol has been tested on two different molecular systems: a large globular tetremeric enzyme (ß-Amylase) and a rod-shape plant virus (tobacco mosaic virus). Radiation damage on the globular enzyme leads to an apparent increase in molecular sizes whereas the effect on the long virus is a breakage into smaller pieces resulting in a decrease of the average long-axis radius. CONCLUSIONS: These results show that radiation damage can appear in different forms and strongly support the need to check the effect of radiation damage at synchrotron sources using the presented protocol.


Assuntos
Amilases/química , Microscopia de Força Atômica , Espalhamento a Baixo Ângulo , Amilases/metabolismo , Amilases/efeitos da radiação , Ipomoea batatas/enzimologia , Níquel/química , Estrutura Quaternária de Proteína , Vírus do Mosaico do Tabaco/química , Vírus do Mosaico do Tabaco/efeitos da radiação , Difração de Raios X , Raios X
10.
J Mol Recognit ; 29(1): 51-5, 2016 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-26224520

RESUMO

Image visibility is a central issue in analyzing all kinds of microscopic images. An increase of intensity contrast helps to raise the image visibility, thereby to reveal fine image features. Accordingly, a proper evaluation of results with current imaging parameters can be used for feedback on future imaging experiments. In this work, we have applied the Laplacian function of image intensity as either an additive component (Laplacian mask) or a multiplying factor (Laplacian weight) for enhancing image contrast of high-resolution AFM images of two molecular systems, an unknown protein imaged in air, provided by AFM COST Action TD1002 (http://www.afm4nanomedbio.eu/), and tobacco mosaic virus (TMV) particles imaged in liquid. Based on both visual inspection and quantitative representation of contrast measurements, we found that the Laplacian weight is more effective than the Laplacian mask for the unknown protein, whereas for the TMV system the strengthened Laplacian mask is superior to the Laplacian weight. The present results indicate that a mathematical function, as exemplified by the Laplacian function, may yield varied processing effects with different operations. To interpret the diversity of molecular structure and topology in images, an explicit expression for processing procedures should be included in scientific reports alongside instrumental setups.


Assuntos
Microscopia de Força Atômica/métodos , Proteínas/química , Algoritmos , Processamento de Imagem Assistida por Computador/métodos , Vírus do Mosaico do Tabaco/química
11.
Int J Clin Exp Pathol ; 8(11): 14983-8, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26823832

RESUMO

OBJECTIVE: MiRNAs play crucial roles in progression of cancer. However, the underlying mechanisms of miRNAs in non small cell lung cancer are still poorly understood. The aim of this study was to investigate the expression level of microRNA-126 (miR-126) and microRNA-133b (miR-133b) and also their association with clinicopathological features in patients with non small cell lung cancer (NSCLC). METHODS: Total RNA was purified from NSCLC tissues and adjacent non-tumor tissues and then quantitative real-time PCR (qRT-PCR) was used to evaluate the expression rate of microRNAs. Furthermore, the association of miR-126 and miR-133b level with clinicopathological features and prognosis were evaluated. RESULTS: Our findings showed that expression of miR-126 was decreased in NSCLC tissues compared with adjacent non-tumor tissues. On the other hand, a lower expression of miR-133b was seen in NSCLC tissues when compared with adjacent non-tumor tissues. In term of miR-126, our results showed that miR-126 was associated with tumor stage and lymph nodes metastasis (P<0.05). In term of miR-133b, our finding indicated that decreased expression of miR-133b was correlated with advanced tumor stage and lymph nodes metastasis (P<0.05). Kaplan-Meier analysis and log-rank test indicated that patients with low expression of miR-126 and miR-133b had a shorter overall survival (log-rank test; P<0.05). Multivariate Cox proportional hazards model revealed that low expression of miR-126 and miR-133b, advanced tumor stage and lymph nodes metastasis were independent prognostic factors for overall survival of NSCLC patients. CONCLUSIONS: These findings suggested that miR-126 and miR-133b might play a key role in the progression and metastasis of NSCLC and would be applied as a novel therapeutic agent.


Assuntos
Biomarcadores Tumorais/análise , Carcinoma Pulmonar de Células não Pequenas/patologia , Neoplasias Pulmonares/patologia , Adulto , Idoso , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Progressão da Doença , Intervalo Livre de Doença , Regulação para Baixo , Feminino , Humanos , Estimativa de Kaplan-Meier , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/mortalidade , Metástase Linfática/genética , Metástase Linfática/patologia , Masculino , MicroRNAs , Pessoa de Meia-Idade , Prognóstico , Modelos de Riscos Proporcionais , Reação em Cadeia da Polimerase em Tempo Real
12.
Biosens Bioelectron ; 54: 306-10, 2014 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-24291267

RESUMO

We demonstrate a biosensor structure consisting of an IGZO (Indium-Gallium-Zinc-Oxide) TFT (thin film transistor) and an extended sensing pad. The TFT acts as the sensing and readout device, while the sensing pad ensures the isolation of biological solution from the transistor channel layer, and meanwhile increases the sensing area. The biosensor is functionalized by first applying ZnO nanorods to increase the surface area for attracting electrical charges of EGFR (epidermal growth factor receptor) antibodies. The device is able to selectively detect 36.2 fM of EGFR in the total protein solution of 0.1 ng/ml extracted from squamous cell carcinoma (SCC). Furthermore, the conjugation duration of the functionalized device with EGFR can be limited to 3 min, implying that the biosensor has the advantage for real-time detection.


Assuntos
Anticorpos Imobilizados/química , Técnicas Biossensoriais/instrumentação , Nanotubos/química , Transistores Eletrônicos , Óxido de Zinco/química , Linhagem Celular , Linhagem Celular Tumoral , Desenho de Equipamento , Gálio/química , Humanos , Índio/química , Limite de Detecção
13.
Nanoscale ; 5(22): 10877-86, 2013 Nov 21.
Artigo em Inglês | MEDLINE | ID: mdl-24056758

RESUMO

In this work, we propose "single-image analysis", as opposed to multi-image averaging, for extracting valuable information from AFM images of single bio-particles. This approach allows us to study molecular systems imaged by AFM under general circumstances without restrictions on their structural forms. As feature exhibition is a resolution correlation, we have performed AFM imaging on surfaces of tobacco mosaic virus (TMV) to demonstrate variations of structural patterns with probing resolution. Two AFM images were acquired with the same tip at different probing resolutions in terms of pixel width, i.e., 1.95 and 0.49 nm per pixel. For assessment, we have constructed an in silico topograph based on the three-dimensional crystal structure of TMV as a reference. The prominent artifacts observed in the AFM-determined shape of TMV were attributed to tip convolutions. The width of TMV rod was systematically overestimated by ~10 nm at both probing resolutions of AFM. Nevertheless, the effects of tip convolution were less severe in vertical orientation so that the estimated height of TMV by AFM imaging was in close agreement with the in silico X-ray topograph. Using dedicated image processing algorithms, we found that at low resolution (i.e., 1.95 nm per pixel), the extracted surface features of TMV can be interpreted as a partial or full helical repeat (three complete turns with ~7.0 nm in length), while individual protein subunits (~2.5 nm) were perceivable only at high resolution. The present study shows that the scales of revealed structural features in AFM images are subject to both probing resolution and processing algorithms for image analysis.


Assuntos
Microscopia de Força Atômica , Nanoestruturas/química , Vírion/isolamento & purificação , Algoritmos , Propriedades de Superfície , Vírus do Mosaico do Tabaco/química , Vírus do Mosaico do Tabaco/fisiologia
14.
Thromb Res ; 130 Suppl 1: S47-9, 2012 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-23026661

RESUMO

Over 30 thromboembolic events have been reported in factor VII (FVII) deficiency either associated with previously asymptomatic forms or bleeding diathesis. Whether this coexistence is fortuitous or not is still a mater of debate. Nevertheless, it is well admitted that (i) thrombotic events occurring in FVII-deficient patients with any apparent triggering factors are very rare, (ii) surgical procedures, replacement therapy (especially containing activated factors) but also the presence of an antiphospholipid syndrome are frequently associated with these particular thrombotic events, (iii) in the same way, R304Q and A294V FVII variants appear to be more prevalent than other FVII equally frequent mutations and finally (iv) low FVII coagulant activity levels do not protect against thrombosis. Therefore, peri-operative thrombotic prophylaxis should be relevant for these particular FVII-deficient patients. However, safety, treatment modalities and specific indications of such an antithrombotic prophylaxis remain to be established.


Assuntos
Coagulação Sanguínea , Deficiência do Fator VII/complicações , Tromboembolia/complicações , Anticoagulantes/efeitos adversos , Síndrome Antifosfolipídica/sangue , Síndrome Antifosfolipídica/complicações , Coagulação Sanguínea/efeitos dos fármacos , Coagulação Sanguínea/genética , Deficiência do Fator VII/sangue , Deficiência do Fator VII/tratamento farmacológico , Deficiência do Fator VII/genética , Fibrinolíticos/efeitos adversos , Predisposição Genética para Doença , Humanos , Mutação , Fenótipo , Prognóstico , Medição de Risco , Fatores de Risco , Procedimentos Cirúrgicos Operatórios/efeitos adversos , Tromboembolia/sangue , Tromboembolia/tratamento farmacológico
15.
Structure ; 20(1): 113-20, 2012 Jan 11.
Artigo em Inglês | MEDLINE | ID: mdl-22244760

RESUMO

Classical structural biology techniques face a great challenge to determine the structure at the atomic level of large and flexible macromolecules. We present a novel methodology that combines high-resolution AFM topographic images with atomic coordinates of proteins to assemble very large macromolecules or particles. Our method uses a two-step protocol: atomic coordinates of individual domains are docked beneath the molecular surface of the large macromolecule, and then each domain is assembled using a combinatorial search. The protocol was validated on three test cases: a simulated system of antibody structures; and two experimentally based test cases: Tobacco mosaic virus, a rod-shaped virus; and Aquaporin Z, a bacterial membrane protein. We have shown that AFM-intermediate resolution topography and partial surface data are useful constraints for building macromolecular assemblies. The protocol is applicable to multicomponent structures connected in the polypeptide chain or as disjoint molecules. The approach effectively increases the resolution of AFM beyond topographical information down to atomic-detail structures.


Assuntos
Biologia Computacional/métodos , Microscopia de Força Atômica/métodos , Modelos Moleculares , Estrutura Terciária de Proteína , Proteínas/química , Aquaporinas/química , Proteínas de Escherichia coli/química , Vírus do Mosaico do Tabaco/química
16.
Curr Med Chem ; 16(8): 953-64, 2009.
Artigo em Inglês | MEDLINE | ID: mdl-19275605

RESUMO

Interaction modes and molecular surface properties for both peptide- and protein-antibody complexes have been investigated. Datasets were constituted from the IMGT database and consisted of 37 peptide-antibody (PEPT) and 155 protein-antibody (PROT) complexes. A computer approach was developed to analyze the surface of peptides and proteins using a level set method which allows the characterization of shape complementarity using surface curvature. We found that in both datasets, the interacting surfaces of the two binding partners, exhibited a moderate degree of shape complementarity at the molecular level but not at the atomic level. We also evaluated the structural similarity between peptides bound to antibodies and the corresponding regions in the 3D structures of the cognate proteins. We found that no more than 25% of Phipsi; dihedral angles were conserved between the corresponding regions in peptides and proteins. We also superimposed the parent protein structure onto that of the bound peptides and visually looked for the presence of bumps or clashes between the cognate protein and the antibody. Except for antibodies possessing neutralizing activity and for those bound to a peptide longer than 30 residues, no superimposition in peptide-antibody complexes was found to be bump or clash-free. These findings indicate that studies restricted to continuous epitopes are unlikely to provide the information needed to design short linear peptides that could be expected to mimic satisfactorily the discontinuous epitopes of native proteins and be successful as synthetic vaccines.


Assuntos
Epitopos/química , Epitopos/imunologia , Peptídeos/química , Peptídeos/imunologia , Anticorpos/imunologia , Toxina da Cólera/química , Toxina da Cólera/imunologia , Reações Cruzadas/imunologia , Bases de Dados de Proteínas , Estrutura Secundária de Proteína , Relação Estrutura-Atividade , Vacinas de Subunidades Antigênicas/síntese química , Vacinas de Subunidades Antigênicas/química , Vacinas de Subunidades Antigênicas/imunologia , Vacinas Sintéticas/química , Vacinas Sintéticas/imunologia
17.
Proteins ; 65(1): 192-202, 2006 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-16807887

RESUMO

The key issue for disulfide bond engineering is to select the most appropriate location in the protein. By surveying the structure of experimentally engineered disulfide bonds, we found about half of them that have geometry incompatible with any native disulfide bond geometry. To improve the current prediction methods that tend to apply either ideal geometrical or energetical criteria to single three-dimensional structures, we have combined a novel computational protocol with the usage of multiple protein structures to take into account protein backbone flexibility. The multiple structures can be selected from either independently determined crystal structures for identical proteins, models of nuclear magnetic resonance experiments, or crystal structures of homology-related proteins. We have validated our approach by comparing the predictions with known disulfide bonds. The accuracy of prediction for native disulfide bonds reaches 99.6%. In a more stringent test on the reported engineered disulfide bonds, we have obtained a success rate of 93%. Our protocol also determines the oxido-reduction state of a predicted disulfide bond and the corresponding mutational cost. From the energy ranking, the user can easily choose top predicted sites for mutagenesis experiments. Our method provides information about local stability of the engineered disulfide bond surroundings.


Assuntos
Dissulfetos/química , Engenharia de Proteínas , Proteínas de Bactérias , Cristalografia por Raios X , Cistina/química , Humanos , Modelos Moleculares , Mutagênese Sítio-Dirigida , Ressonância Magnética Nuclear Biomolecular , Peptídeos/química , Proteínas de Plantas/química , Príons/química , Conformação Proteica , Ribonucleases/química , Subtilisina/química
18.
J Biol Chem ; 279(31): 32545-53, 2004 Jul 30.
Artigo em Inglês | MEDLINE | ID: mdl-15155756

RESUMO

The photosynthetic cyclic electron transfer of the purple bacterium Rubrivivax gelatinosus, involving the cytochrome bc(1) complex and the reaction center, can be carried out via two pathways. A high potential iron-sulfur protein (HiPIP) acts as the in vivo periplasmic electron donor to the reaction center (RC)-bound cytochrome when cells are grown under anaerobic conditions in the light, while cytochrome c is the soluble electron carrier for cells grown under (8)aerobic conditions in the dark. A spontaneous reversion of R. gelatinosus C244, a defective mutant in synthesis of the RC-bound cytochrome by insertion of a Km(r) cassette leading to gene disruption with a slow growth rate, restores the normal photosynthetic growth. This revertant, designated C244-P1, lost the Km(r) cassette but synthesized a RC-bound cytochrome with an external 77-amino acid insertion derived from the cassette. We characterized the RC-bound cytochrome of this mutant by EPR, time-resolved optical spectroscopy, and structural analysis. We also investigated the in vivo electron transfer rates between the two soluble electron donors and this RC-bound cytochrome. Our results demonstrated that the C244-P1 RC-bound cytochrome is still able to receive electrons from HiPIP, but it is no longer reducible by cytochrome c(8). Combining these experimental and theoretical protein-protein docking results, we conclude that cytochrome c(8) and HiPIP bind the RC-bound cytochrome at two distinct but partially overlapping sites.


Assuntos
Proteínas de Bactérias/metabolismo , Burkholderiaceae/metabolismo , Grupo dos Citocromos c/metabolismo , Citocromos c/química , Proteínas Ferro-Enxofre/química , Proteínas Ferro-Enxofre/metabolismo , Complexo de Proteínas do Centro de Reação Fotossintética/metabolismo , Sequência de Aminoácidos , Sequência de Bases , Sítios de Ligação , Divisão Celular , Membrana Celular/metabolismo , Citocromos/química , Citocromos/metabolismo , Espectroscopia de Ressonância de Spin Eletrônica , Elétrons , Ferricianetos/química , Cinética , Modelos Moleculares , Dados de Sequência Molecular , Mutação , Oxigênio/metabolismo , Fotossíntese , Estrutura Secundária de Proteína , Estrutura Terciária de Proteína , Especificidade da Espécie , Espectrofotometria , Fatores de Tempo
19.
J Nurs Res ; 10(4): 261-70, 2002 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-12522739

RESUMO

The purpose of this study was to examine the effectiveness of health promotion education programs for a group of elderly residents in a community. A one group pre- and post-test design was used in this study. Nurses, dietitians, and physical education teachers worked collaboratively to provide a series of comprehensive, integrated education programs. Course content included healthy life style and health promotion, disease prevention, nutrition, exercise, and medication education. A total of 140 elderly participated in this study. Ninety- seven subjects attended all of the education programs. A structured questionnaire was used for data collection. Information about demographics, health status, health promotion knowledge and behaviors was included. The health promotion behavior data were collected twice. The initial data set was collected prior to the first course and the second after the fifth course. Health promotion knowledge was assessed pre- and post-test in the second, third, and fourth courses. The research findings revealed that the education programs were effective in improving elderly health promotion knowledge and behaviors. The scores for health promotion knowledge and positive health behaviors were high among subjects who were aged 65-69 years, were married, lived with family members and had higher education levels. The results could be used as a reference in future health promotion education in the community.


Assuntos
Serviços de Saúde Comunitária/organização & administração , Educação em Saúde/organização & administração , Promoção da Saúde/organização & administração , Serviços de Saúde para Idosos/organização & administração , Idoso/psicologia , Atitude Frente a Saúde , Avaliação Educacional , Feminino , Comportamentos Relacionados com a Saúde , Conhecimentos, Atitudes e Prática em Saúde , Humanos , Estilo de Vida , Masculino , Pessoa de Meia-Idade , Ciências da Nutrição/educação , Prevenção Primária , Avaliação de Programas e Projetos de Saúde , Inquéritos e Questionários , Taiwan
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