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1.
Circ J ; 2024 Apr 04.
Artigo em Inglês | MEDLINE | ID: mdl-38569870

RESUMO

BACKGROUND: The safety and feasibility of using 1-month dual antiplatelet therapy (DAPT) followed by P2Y12inhibitor monotherapy for patients after percutaneous coronary intervention (PCI) with thin-strut biodegradable polymer drug-eluting stents (BP-DES) in daily clinical practice remain uncertain.Methods and Results: The REIWA region-wide registry is a prospective study conducted in 1 PCI center and 9 local hospitals in northern Japan. A total of 1,202 patients who successfully underwent final PCI using BP-DES (Synergy: n=400; Ultimaster: n=401; Orsiro: n=401), were enrolled in the registry, and received 1-month DAPT followed by P2Y12inhibitor (prasugrel 3.75 mg/day or clopidogrel 75 mg/day) monotherapy. The primary endpoint was a composite of cardiovascular and bleeding events at 12 months, including cardiovascular death, myocardial infarction (MI), definite stent thrombosis (ST), ischemic or hemorrhagic stroke, and Thrombolysis in Myocardial Infarction (TIMI) major or minor bleeding. Based on the results of a previous study, we set the performance goal at 5.0%. Over the 1-year follow-up, the primary endpoint occurred in 3.08% of patients, which was lower than the predefined performance goal (Pnon-inferiority<0.0001). Notably, definite ST occurred in only 1 patient (0.08%) within 1 year (at 258 days). No differences were observed in the primary endpoint between stent types. CONCLUSIONS: The REIWA region-wide registry suggests that 1-month DAPT followed by P2Y12inhibitor monotherapy is safe and feasible for Japanese patients with BP-DES.

2.
Transfusion ; 63(3): 463-469, 2023 03.
Artigo em Inglês | MEDLINE | ID: mdl-36597800

RESUMO

BACKGROUND: Flow cytometry (FC) has proven its utility in scrutinizing AB antigen expression in red blood cells (RBCs), cooperating with serological tests for accurate blood group typing. However, technical difficulties may impair the characterization of weak ABO subtypes when background noises appear at non-negligible levels. STUDY DESIGN AND METHODS: We sought to establish an FC method that could prevent antibody-induced hemagglutination and an increase in cellular autofluorescence, two major issues inherent to RBC-FC analysis of AB expression. We optimized fixatives, multicolor-staining protocols, and sequential gating strategies. Blood samples from weak ABO subtype cases, Bm and Ael , were analyzed with the established protocol. RESULTS: The optimized mixture of glutaraldehyde and formaldehyde successfully generated fixed RBCs resistant to agglutination while maintaining low autofluorescence. These features allowed co-staining of leukocyte- and erythrocyte-markers, which enabled sequential gating strategies facilitating the precise AB antigen analysis in purely single RBCs with minimum background noises. By the established FC analysis, we could detect in the Bm sample a small RBC population exhibiting weak B antigen expression. The assay also proved it feasible to identify a small population (0.04%) of RBCs weakly expressing the A antigen in the Ael sample confirmed as harboring a rare c.816dupG ABO variant allele. CONCLUSION: The RBC-FC analysis described here allows the detection of AB antigens weakly expressed in RBCs while achieving minimum background noise levels in negative control samples. Overall, the modified protocol provides a quick and reliable assay valuable in transfusion medicine and is potentially applicable to the characterization of rare weak ABO variants.


Assuntos
Sistema ABO de Grupos Sanguíneos , Eritrócitos , Humanos , Citometria de Fluxo/métodos , Eritrócitos/metabolismo , Anticorpos/metabolismo , Tipagem e Reações Cruzadas Sanguíneas , Antígenos/metabolismo
3.
Int J Oncol ; 61(6)2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36196892

RESUMO

Hesperetin, a predominant flavonoid found in citrus fruits, has received considerable attention for its potential anticancer activity through the reduction of cell viability and the induction of apoptosis. Several effector mechanisms have been demonstrated underlying the antitumor properties of hesperetin but its specific mechanisms have not yet been fully elucidated. In the present study, how hesperetin affects the proliferation of A549 cells and the related cell proliferation regulatory mechanisms, were inevstigated. To elucidate the mechanisms underlying the effects of hesperetin on A549 cells, MTT assay, colony formation assay, flow cytometry, immunoblotting, reverse transcription­quantitative PCR and JC­1 staining were performed. The data revealed that hesperetin inhibited cell proliferation and induced apoptosis in these cells. Hesperetin also decreased the level of heat shock protein 70 (Hsp70), a negative regulator of the mitochondrial apoptosis pathway, often overexpressed in various cancer cells and suspected to contribute to tumor development. Hesperetin­induced Hsp70 suppression was associated with reduced cytosolic Bax and increased mitochondrial Bax levels, leading to the enhancement of the mitochondrial apoptotic cascade. The Hsp70 overexpression­induced reduction in the level of hesperetin­induced apoptosis provides evidence to hesperetin­induced apoptosis being mediated by affecting Hsp70. Furthermore, it was demonstrated that hesperetin reduced Hsp70 expression by inducing a proteasome­mediated degradation via the upregulation of E3­ligase, C­terminus of Hsp70­interacting protein (CHIP). The present study highlighted the importance of the Bax activation­triggered mitochondria­mediated pathway for hesperetin­induced apoptosis and demonstrated a novel mechanism of how Hsp70 played a critical role in the negative regulation of this apoptotic network in cancer cells.


Assuntos
Proteínas de Choque Térmico HSP70 , Complexo de Endopeptidases do Proteassoma , Células A549 , Apoptose , Flavonoides/farmacologia , Proteínas de Choque Térmico HSP70/genética , Proteínas de Choque Térmico HSP70/farmacologia , Hesperidina , Humanos , Ligases/farmacologia , Proteína X Associada a bcl-2/metabolismo
4.
Med Biol Eng Comput ; 60(10): 2825-2840, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-35879527

RESUMO

Variability in swallowing electromyography (EMG) has been reported to occur due to individual differences, even in studies with appropriate control of factors affecting EMG such as food type, properties, and posture. The increased variability broadens the confidence intervals of measures obtained from EMG, such as time and amplitude, and makes it difficult to detect differences in muscle activity. This makes it impossible to detect slight changes in swallowing function at an early stage, which is required for clinical examination. In this study, we focused on the tipper type and dipper type of oral swallows, which differ in the timing of muscle activity. The frequency of occurrence of both types varies between participants, and both types could occur in the same participant. In this study, we measured swallowing EMG wherein participants were instructed to swallow with a tipper and a dipper. The results showed that there was a significant difference in the between-participant duration between these two types of swallows. Within-participant variability was significantly lower in the tipper-dipper instruction condition compared to the baseline condition, which assumed a mixture of tipper-dipper swallowing. These results demonstrate that instructions on swallowing method are effective in improving the reproducibility of EMG.


Assuntos
Deglutição , Deglutição/fisiologia , Eletromiografia/métodos , Humanos , Reprodutibilidade dos Testes
5.
Mod Rheumatol ; 32(3): 641-649, 2022 Apr 18.
Artigo em Inglês | MEDLINE | ID: mdl-34910187

RESUMO

OBJECTIVES: To clarify the longitudinal changes in patients with preoperative Stage-3 locomotive syndrome (LS) according to different types of surgeries, we investigated the changes in the LS stage in patients who underwent surgery for degenerative musculoskeletal diseases. METHODS: A prospective cohort study was conducted on 168 patients with degenerative diseases [46 spinal deformities treated with thoracolumbar interbody fusion (T/LIF), 86 hips with osteoarthritis treated with total hip arthroplasty (THA), and 36 knees with osteoarthritis treated with total knee arthroplasty (TKA)]. The results for the LS stage, stand-up test, two-step test, and 25-question Geriatric Locomotive Function Scale (GLFS-25) were evaluated preoperatively and at 6 months, 1 year, and 2 years postoperatively. RESULTS: Preoperatively, most patients had Stage-3 LS (89.1, 90.8, and 80.6% in the T/LIF, THA, and TKA groups, respectively). At 2 years postoperatively, the Stage-3 LS improved in 41.5, 75.6, and 55.2% of patients in the T/LIF, THA, and TKA groups, respectively. All groups showed similar improvements in the two-step test. The THA group showed the best result in the GLFS-25. CONCLUSIONS: LS stage improved in different patterns over 2 years postoperatively and the LS risk test revealed differences in postoperative movement ability according to the type of surgery.


Assuntos
Artroplastia de Quadril , Artroplastia do Joelho , Osteoartrite , Idoso , Artroplastia de Quadril/efeitos adversos , Artroplastia do Joelho/efeitos adversos , Humanos , Osteoartrite/etiologia , Estudos Prospectivos , Síndrome
6.
Clin Exp Dent Res ; 7(5): 868-876, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-33687150

RESUMO

BACKGROUNDS: Jaw and neck muscles may be activated by chewing load using a hard food. However, it remains unclear how effects the gum hardness to the coordinated features in jaw and neck muscle activities during chewing performance. OBJECTIVES: This study was conducted to quantitatively elucidate the effects of the hardness of the gum on coordinated features in jaw and neck muscle activities using intermuscular EMG-EMG transfer function and EMG-EMG coherence function analyses in 18 healthy subjects. METHODS: Jaw and neck muscle activities were aggregated into the first peak frequency of the power spectrum, and power, gain, phase, and coherence parameters between jaw and neck muscle activities were examined in the first peak frequencies during soft and hard gum chewing. RESULTS: The first peak frequency was not significantly different between soft and hard gum chewing. In contrast, power values of the jaw and neck muscles were significantly increased by chewing of hard gum as compared with soft gum, whereas gain, phase, and coherence were not significantly changed by gum hardness. CONCLUSIONS: The chewing rhythm, the quantitative and temporal coordination, and the functional coordination in jaw and neck muscle activities were not changed during soft and hard gum chewing, as well as increased jaw and neck muscles activities. It is therefore concluded that the chewing rhythmicity and jaw and neck muscles coordination accompanied with the increased jaw and neck muscle activities are maintained under the condition of the chewing load using gum hardness in the healthy individuals.


Assuntos
Arcada Osseodentária , Mastigação , Músculos do Pescoço , Eletromiografia , Voluntários Saudáveis , Humanos
7.
Front Neurosci ; 15: 588593, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33633532

RESUMO

BACKGROUND: The differences in the brain activities of the insular and the visual association cortices have been reported between oral and manual stereognosis. However, these results were not conclusive because of the inherent differences in the task performance-related motor sequence conditions. We hypothesized that the involvement of the prefrontal cortex may be different between finger and oral shape discrimination. This study was conducted to clarify temporal changes in prefrontal activities occurring in the processes of oral and finger tactual shape discrimination using prefrontal functional near-infrared spectroscopy (fNIRS). METHODS: Six healthy right-handed males [aged 30.8 ± 8.2 years (mean ± SD)] were enrolled. Measurements of prefrontal activities were performed using a 22-channel fNIRS device (ETG-100, Hitachi Medical Co., Chiba, Japan) during experimental blocks that included resting state (REST), nonsense shape discrimination (SHAM), and shape discrimination (SHAPE). RESULTS: No significant difference was presented with regard to the number of correct answers during trials between oral and finger SHAPE discrimination. Additionally, a statistical difference for the prefrontal fNIRS activity between oral and finger shape discrimination was noted in CH 1. Finger SHAPE, as compared with SHAM, presented a temporally shifting onset and burst in the prefrontal activities from the frontopolar area (FPA) to the orbitofrontal cortex (OFC). In contrast, oral SHAPE as compared with SHAM was shown to be temporally overlapped in the onset and burst of the prefrontal activities in the dorsolateral prefrontal cortex (DLPFC)/FPA/OFC. CONCLUSION: The prefrontal activities temporally shifting from the FPA to the OFC during SHAPE as compared with SHAM may suggest the segregated serial prefrontal processing from the manipulation of a target image to the decision making during the process of finger shape discrimination. In contrast, the temporally overlapped prefrontal activities of the DLPFC/FPA/OFC in the oral SHAPE block may suggest the parallel procession of the repetitive involvement of generation, manipulation, and decision making in order to form a reliable representation of target objects.

8.
J Prosthodont Res ; 65(2): 235-242, 2021 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-33041278

RESUMO

PURPOSE: This study was performed to examine how denture wearing improves jaw and neck muscle coordination during chewing in partially edentulous elderly patients. METHODS: Sixteen patients classified as Eichner's index B2 or B3 and 16 young dentate subjects were enrolled. Jaw and neck muscle activities during chewing were recorded using electromyography with and without denture wearing, then analyzed using intermuscular Electromyography (EMG)-EMG transfer and EMG-EMG coherence function analyses to clarify quantitative, temporal, and functional coordination of jaw and neck muscle activities while chewing. Occlusal force and masticatory scores were also determined. RESULTS: Denture wearing increased the power values for jaw closing muscle activities, and improved occlusal area and force, and masticatory score. Gain values for jaw closing and opening muscle activities were decreased in those wearing dentures compared to those not wearing dentures. Denture wearing resulted in equivalent gain values for jaw closing and opening muscle activities as compared to the young subjects. Coherence values for chewing and non-chewing side neck muscle activities were increased as compared to not denture wearing. CONCLUSIONS: The suitability of denture wearing can be evaluated from the viewpoint of gain as a quantitative parameter showing coordination between jaw closing and opening muscle activities. Such evaluation can be performed from the viewpoint of coherence as a parameter of functional coordination between jaw and neck muscle activities during chewing in partially edentulous elderly patients. The gain parameter in regard to jaw muscle activities may be compensated to a state equivalent to that seen in young subjects by wearing an appropriate denture.


Assuntos
Mastigação , Boca Edêntula , Idoso , Força de Mordida , Dentaduras , Eletromiografia , Humanos , Músculos da Mastigação , Músculos do Pescoço
9.
Mod Rheumatol ; 31(5): 1050-1058, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32924686

RESUMO

OBJECTIVES: Patients requiring total hip arthroplasty (THA) may possibly have locomotive syndrome (LS). Therefore, we investigated changes of LS in patients undergoing THA and clarified key factors that affected LS stage. METHODS: A prospective cohort study was conducted with 88 patients undergoing THA (74 females, 14 males, mean age: 67.6 years). Data collected using LS stage, stand-up test, two-step test, and 25-question Geriatric Locomotive Function Scale results were evaluated before THA, and 6 months, 1 year, and 2 years after THA. Key factors were determined using multivariate analysis and receiver operating characteristic (ROC) curve analysis. RESULTS: Before THA, all patients had fallen LS (stage1: 3.4% and stage2: 96.6%). Overall, 56.8% patients improved their LS stage, and 17.0% of patients overcame LS at 2 years after THA. The key factors that affected LS stage were preoperative two-step test and age. ROC analyses showed a preoperative two-step test score of 0.988 and an age of 67.5 years as a cut-off value for the change of LS stage. CONCLUSIONS: Patients experiencing LS due to hip disorders have the potential to recover after THA. Additional postoperative training may be beneficial for patients with low preoperative two-step test scores to improve their LS stage.


Assuntos
Artroplastia de Quadril , Idoso , Artroplastia de Quadril/efeitos adversos , Feminino , Humanos , Locomoção , Estudos Longitudinais , Masculino , Estudos Prospectivos , Resultado do Tratamento
10.
Sensors (Basel) ; 20(24)2020 Dec 10.
Artigo em Inglês | MEDLINE | ID: mdl-33321954

RESUMO

It is known that humans experience a haptic illusion, such as the sensation of being pulled in a particular direction, when asymmetric vibrations are presented. A pulling illusion has been used to provide a force feedback for a virtual reality (VR) system and a pedestrian navigation system, and the asymmetric vibrations can be implemented in any small non-grounded device. However, the design methodology of asymmetric vibration stimuli to induce the pulling illusion has not been fully demonstrated. Although the frequency of the asymmetric vibration is important, findings on the frequency have not been reported. In this study, we clarified the influences of the effects on the pulling illusion based on the investigation of asymmetric vibration frequency differences. Two psychophysical experiments that related to the frequency of asymmetric vibration were performed. Experiment I showed that the illusion occurs for specific vibration waveforms at 40 Hz and 75 Hz. As a result of Experiment II, the threshold was the lowest when the frequency was 40 Hz, and highest when the frequency was 110 Hz. This result supports the previous hypothesis that the Meissner corpuscles and the Ruffini endings contribute to the illusion, while the Pacinian corpuscles do not.

11.
J Oral Rehabil ; 47(11): 1358-1367, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32895952

RESUMO

BACKGROUND: Quantitative assessment of swallowing function is necessary to prevent swallowing impairment due to ageing. Though surface electromyography (EMG) has been widely used to measure swallowing activity, the relationship between EMG results and swallowing function is unclear. OBJECTIVE: This study examined the relationship between the temporal characteristics of muscle activity and laryngeal elevation (LE) during swallowing. METHODS: This study analysed 60 healthy volunteers in two age groups (young, between 20 and 38 years; old, between 65 and 75 years), each containing the same number of male and female participants. Surface EMG signals were recorded from the suprahyoid and infrahyoid muscle groups (SH-EMG and IH-EMG, respectively). LE was measured using an array of pressure sensors. The participants swallowed 3 mL of water under three swallowing speed conditions: fast, normal and slow swallowing. The EMG duration, EMG time intervals before and after the onset of LE (pre-LE and post-LE intervals, respectively), and the LE velocity were analysed. RESULTS: Both EMG duration and the post-LE interval of IH-EMG were significantly longer in the older group. As for the gender effect, the pre-LE interval of SH-EMG was significantly longer and the LE velocity was significantly higher in men than in women. Furthermore, there was a negative correlation between pre-LE interval and LE velocity in the fast swallowing condition. CONCLUSION: Though ageing slightly prolonged the muscle activity time, gender influenced swallowing activity in a more complex manner. Therefore, it is important to take gender into account when examining swallowing function with increasing age.


Assuntos
Transtornos de Deglutição , Deglutição , Eletromiografia , Feminino , Humanos , Masculino , Músculos do Pescoço
12.
Biosci Biotechnol Biochem ; 84(12): 2440-2447, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32841581

RESUMO

The anticancer effects of curcumin are based on the induction of apoptosis, but the specific mechanisms have not yet been fully elucidated. To address this issue, we investigated the effects of curcumin on the intrinsic apoptosis pathway using mitochondria from A549 cells. Curcumin decreased the levels of 14-3-3 proteins, key molecules that inhibit the activation of proapoptotic factors known as BH3-only proteins (e.g. Bad). Curcumin-induced suppression of 14-3-3 protein levels was associated with reduced cytosolic Bad and elevation of mitochondrial Bad, leading to a drop in the mitochondrial membrane potential. 14-3-3 proteins generally interact with Bad phosphorylated by AKT, thus preventing its translocation to the mitochondria where it can promote cell death. Curcumin not only decreased the expression of 14-3-3 proteins but also promoted Bad dephosphorylation in an AKT-dependent fashion. Our results provide novel evidence for the induction of apoptosis by curcumin at multiple stages of the mitochondrial cascade.


Assuntos
Proteínas 14-3-3/metabolismo , Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Curcumina/farmacologia , Neoplasias Pulmonares/patologia , Proteína de Morte Celular Associada a bcl/metabolismo , Células A549 , Humanos , Potencial da Membrana Mitocondrial/efeitos dos fármacos
13.
Cardiovasc Interv Ther ; 35(4): 398-404, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32776221

RESUMO

Several studies have demonstrated the safety and feasibility of short (3-6 months) and very short duration (< 2 months) dual antiplatelet therapy (DAPT) in patients with a durable-polymer drug-eluting stent (DP-DES). However, the clinical importance of using very short duration DAPT has yet to be established in patients with a biodegradable polymer drug-eluting stent (BP-DES). The aim of this REIWA registry (multicenter and prospective registry; investigation of clinical outcomes of patients treated with short duration dual antiplatelet therapy after implantation of biodresorbable-polymer drug-eluting stent: a multicenter, prospective registry from Iwate medical university affiliated hospitals) is to determine the safety and feasibility of using 1-month DAPT followed by P2Y12 inhibitor monotherapy in patients after BP-DES implantation. This study is an observational, prospective, multicenter registry encompassing the entire local medical region of Iwate Prefecture (northern area of mainland Japan). A total of 1200 patients who underwent successful PCI with a novel thin strut BP-DES (Synergy, Ultimaster or Orsiro) and are considered to be appropriate patients for very short DAPT, are registered and subsequently administered 1-month DAPT followed by P2Y12 inhibitor monotherapy (clopidogrel 75 mg/day or prasugrel 3.75 mg/day). The primary endpoint was a composite of cardiovascular and bleeding events, which included cardiovascular death, spontaneous myocardial infarction, definite stent thrombosis, ischemic or hemorrhagic stroke, or TIMI major or minor bleeding at 12 months. The REIWA registry (UMIN000037321) will demonstrate both the safety and feasibility of using 1-month DAPT in patients with BP-DES. Furthermore, results of this study will also be able to provide supportive evidence for P2Y12 inhibitor monotherapy after 1-month DAPT following BP-DES implantation.


Assuntos
Clopidogrel/administração & dosagem , Doença da Artéria Coronariana/terapia , Stents Farmacológicos , Intervenção Coronária Percutânea , Inibidores da Agregação Plaquetária/administração & dosagem , Cloridrato de Prasugrel/administração & dosagem , Implantes Absorvíveis , Clopidogrel/efeitos adversos , Clopidogrel/uso terapêutico , Doença da Artéria Coronariana/complicações , Doença da Artéria Coronariana/tratamento farmacológico , Esquema de Medicação , Quimioterapia Combinada/efeitos adversos , Stents Farmacológicos/efeitos adversos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Isquemia Miocárdica/tratamento farmacológico , Isquemia Miocárdica/etiologia , Isquemia Miocárdica/terapia , Estudos Observacionais como Assunto , Intervenção Coronária Percutânea/efeitos adversos , Intervenção Coronária Percutânea/instrumentação , Intervenção Coronária Percutânea/métodos , Inibidores da Agregação Plaquetária/efeitos adversos , Inibidores da Agregação Plaquetária/uso terapêutico , Polímeros , Cloridrato de Prasugrel/efeitos adversos , Cloridrato de Prasugrel/uso terapêutico , Estudos Prospectivos , Sistema de Registros , Fatores de Tempo , Resultado do Tratamento
14.
J Texture Stud ; 51(3): 389-397, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-31603533

RESUMO

The texture of foods is affected by concurrent auditory sensations. To improve the texture of nursing care foods, we developed a pseudo-mastication sound presentation device based on electromyogram (EMG) signals from the muscles of mastication. EMG signals have enabled us to promptly present care recipients with pseudo-mastication sounds. However, actual mastication sounds vary in intensity and duration more than EMG signals. Here, we investigated changes in EMG signals and actual mastication sounds during the mastication of two food types (rice crackers and Japanese pickles) to improve our device. We found that the intensity and duration of mastication sounds decreased as the number of mastication strokes increased. Furthermore, the intensity and duration of mastication sounds and the latency between the onset of EMG signals and the onset of mastication sounds also varied by food type. For EMG signals, only the intensity varied by food type. Based on our findings, we modified our pseudo-mastication sound presentation device to enable control of the intensity and duration of pseudo-mastication sounds based on the number of mastication strokes and food type. Reproducing more natural pseudo-mastication sounds can improve care recipients' motivation for ingesting nursing care foods, thus preventing malnutrition and frailty.


Assuntos
Serviços de Alimentação , Mastigação , Adulto , Deglutição , Eletromiografia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Cuidados de Enfermagem
15.
RSC Adv ; 9(45): 26214-26218, 2019 Aug 19.
Artigo em Inglês | MEDLINE | ID: mdl-35530990

RESUMO

We have prepared benzylated glucopyranans and evaluated the structural effects on the adhesion capacity. It was found that 97%-benzylated (1→2)-glucopyranan exhibited a unique shear-induced adhesion. The effects of structural factors on the adhesion behaviors are discussed through systematic adhesion tests, differential scanning calorimetry, theoretical models, and IR spectroscopy.

16.
J Mater Chem B ; 7(17): 2766-2770, 2019 05 07.
Artigo em Inglês | MEDLINE | ID: mdl-32255078

RESUMO

A new strategy for preparing peptide-based adhesive materials is provided. An exactly alternating peptide with glycine-N-butylphenyl glycine dipeptide repeating units exhibits excellent repeatable adhesion capacity. The adhesive properties are attributed to the viscoelastic properties and microfibril formation, which are tunable by simple manipulation of the reaction component on polymerization.


Assuntos
Adesivos/química , Glicina/química , Peptídeos/química , Humanos
17.
Blood Adv ; 2(17): 2262-2272, 2018 09 11.
Artigo em Inglês | MEDLINE | ID: mdl-30206099

RESUMO

During maturation, megakaryocytes (MKs) express ß1-tubulin (TUBB1) and rearrange their microtubule components to enlarge, form proplatelets, and eventually release platelets. The development of a platform to identify in vitro conditions that would efficiently promote MK development could potentially enable large-scale platelet production. Here, we show that an immortalized MK cell line (imMKCL) genetically modified to express the ß1-tubulin-Venus reporter provides a practical system to efficiently monitor the in vitro production of platelet-like particles (PLPs). The Venus transgene was inserted downstream of the TUBB1 locus in imMKCLs using CRISPR/Cas9, and the expression was visualized by Venus fluorescence intensity. This imMKCL reporter line was then used for high-throughput drug screening. We identified several compounds that significantly improved the efficiency of PLP production in vitro under feeder-free conditions and showed a significant tendency to recover platelets in vivo in a mouse thrombocytopenia model induced by anti-GPIbα antibody administration. Interestingly, most of these compounds, including a WNT signaling pathway inhibitor, Wnt-C59, antagonized the aryl hydrocarbon receptor (AhR) to increase PLP production, confirming the crucial role of AhR inhibition in MK maturation. Consistently, small interfering RNA treatment against AhR increased the Venus intensity and PLP production. TCS 359, an FLT3 inhibitor, significantly increased PLP production independently of FLT3 or AhR. This study highlights the usefulness of the ß1-tubulin reporter MK line as a useful tool to study the mechanisms underlying thrombopoiesis and to identify novel inducers of ex vivo platelet production.


Assuntos
Plaquetas/citologia , Descoberta de Drogas/métodos , Genes Reporter/genética , Megacariócitos/metabolismo , Tubulina (Proteína)/metabolismo , Animais , Linhagem Celular , Avaliação Pré-Clínica de Medicamentos/métodos , Humanos , Células-Tronco Pluripotentes Induzidas/citologia , Luciferases/genética , Masculino , Megacariócitos/citologia , Camundongos , Camundongos Endogâmicos C57BL , Receptores de Hidrocarboneto Arílico/metabolismo , Trombopoese
18.
Br J Haematol ; 181(6): 791-802, 2018 06.
Artigo em Inglês | MEDLINE | ID: mdl-29741776

RESUMO

Somatic mutations in the calreticulin (CALR) gene have been found in most patients with JAK2- and MPL-unmutated Philadelphia chromosome-negative myeloproliferative neoplasms (MPNs). It has recently been shown that mutant CALR constitutively activates the thrombopoietin receptor MPL and, thus, plays a causal role in the development of MPNs. However, the roles of mutant CALR in human haematopoietic cell differentiation remain predominantly elusive. To examine the impact of the 5-base insertion mutant CALR gene (Ins5) on haematopoietic cell differentiation, we generated induced pluripotent stem cells from an essential thrombocythaemia (ET) patient harbouring a CALR-Ins5 mutation and from a healthy individual (WT). Megakaryopoiesis was more prominent in Ins5-haematopoietic progenitor cells (Ins5-HPCs) than in WT-HPCs, implying that the system recapitulates megakaryocytosis observed in the bone marrow of CALR-mutant ET patients. Ins5-HPCs exhibited elevated expression levels of GATA1 and GATA2, suggesting a premature commitment to megakaryocytic differentiation in progenitor cells. We also demonstrated that 3-hydroxy anagrelide markedly perturbed megakaryopoiesis, but not erythropoiesis. Collectively, we established an in vitro model system that recapitulates megakaryopoiesis caused by mutant CALR. This system can be used to validate therapeutic compounds for MPN patients harbouring CALR mutations and in detailed studies on mutant CALR in human haematological cell differentiation.


Assuntos
Calreticulina/metabolismo , Diferenciação Celular , Células-Tronco Hematopoéticas/metabolismo , Células-Tronco Pluripotentes Induzidas/metabolismo , Megacariócitos/metabolismo , Mutação , Mielopoese , Calreticulina/genética , Feminino , Fator de Transcrição GATA1/genética , Fator de Transcrição GATA1/metabolismo , Fator de Transcrição GATA2/genética , Fator de Transcrição GATA2/metabolismo , Células-Tronco Hematopoéticas/citologia , Humanos , Células-Tronco Pluripotentes Induzidas/citologia , Masculino , Megacariócitos/citologia
19.
J Arrhythm ; 33(5): 488-493, 2017 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-29021855

RESUMO

BACKGROUND & PURPOSE: We have conducted a retrospective observational study to analyze the correlation between the CHADS2 score, the modified CHA2DS2-VASc (mCHA2DS2-VASc) score, and the incidence of all-cause death and congestive heart failure (CHF). METHODS: The study cohort consisted of 292 consecutive patients with nonvalvular atrial fibrillation (NVAF) admitted to our hospital from 2012 to 2014. Electronic medical records were used to confirm medical history including prior heart failure, hypertension, diabetes, stroke, and coronary disease. A follow-up survey for all-cause deaths and incidence of CHF was carried out from the baseline data to May 2015. We analyzed the correlation between each score and the endpoints using the Kaplan-Meier method and the Cox proportional hazards model. RESULT: During the follow up period (mean=1.6 years), 69 all-cause deaths and 58 CHF events occurred in the cohort. There was no significant association between these scores and all-cause death in our CHF cohort. The incidence of CHF significantly increased along with increased CHADS2 (p=0.018) or mCHA2DS2-VASc scores (p=0.044). The hazard ratio (HR) for CHF after adjustment for drug treatment was obtained from a Cox proportional hazards model. The HRs for the CHADS2 and mCHA2DS2-VASc scores were 1.38 (95% CI; 1.13-1.68) and 1.35 (95% CI; 1.24-1.59), respectively. CONCLUSION: Calculation of the CHADS2 and mCHA2DS2-VASc scores in order to evaluate the risk of systemic thromboembolism was useful to predict the onset of CHF, but not all-cause death, in patients with NVAF.

20.
Appetite ; 116: 493-501, 2017 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-28572067

RESUMO

Because chewing sounds influence perceived food textures, unpleasant textures of texture-modified diets might be improved by chewing sound modulation. Additionally, since inhomogeneous food properties increase perceived sensory intensity, the effects of chewing sound modulation might depend on inhomogeneity. This study examined the influences of texture inhomogeneity on the effects of chewing sound modulation. Three kinds of nursing care foods in two food process types (minced-/puréed-like foods for inhomogeneous/homogeneous texture respectively) were used as sample foods. A pseudo-chewing sound presentation system, using electromyogram signals, was used to modulate chewing sounds. Thirty healthy elderly participants participated in the experiment. In two conditions with and without the pseudo-chewing sound, participants rated the taste, texture, and evoked feelings in response to sample foods. The results showed that inhomogeneity strongly influenced the perception of food texture. Regarding the effects of the pseudo-chewing sound, taste was less influenced, the perceived food texture tended to change in the minced-like foods, and evoked feelings changed in both food process types. Though there were some food-dependent differences in the effects of the pseudo-chewing sound, the presentation of the pseudo-chewing sounds was more effective in foods with an inhomogeneous texture. In addition, it was shown that the pseudo-chewing sound might have positively influenced feelings.


Assuntos
Ingestão de Alimentos/psicologia , Potenciais Evocados/fisiologia , Serviços de Alimentação , Mastigação/fisiologia , Som , Percepção do Tato , Idoso , Eletromiografia , Feminino , Humanos , Masculino , Cuidados de Enfermagem , Inquéritos e Questionários , Paladar
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