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1.
Proc Natl Acad Sci U S A ; 121(17): e2320312121, 2024 Apr 23.
Artigo em Inglês | MEDLINE | ID: mdl-38625935

RESUMO

In gram-positive bacteria, phosphorylated arginine functions as a protein degradation signal in a similar manner as ubiquitin in eukaryotes. The protein-arginine phosphorylation is mediated by the McsAB complex, where McsB possesses kinase activity and McsA modulates McsB activity. Although mcsA and mcsB are regulated within the same operon, the role of McsA in kinase activity has not yet been clarified. In this study, we determined the molecular mechanism by which McsA regulates kinase activity. The crystal structure of the McsAB complex shows that McsA binds to the McsB kinase domain through a second zinc-coordination domain and the subsequent loop region. This binding activates McsB kinase activity by rearranging the catalytic site, preventing McsB self-assembly, and enhancing stoichiometric substrate binding. The first zinc-coordination and coiled-coil domains of McsA further activate McsB by reassembling the McsAB oligomer. These results demonstrate that McsA is the regulatory subunit for the reconstitution of the protein-arginine kinase holoenzyme. This study provides structural insight into how protein-arginine kinase directs the cellular protein degradation system.


Assuntos
Arginina Quinase , Proteínas Quinases , Proteínas Quinases/metabolismo , Arginina Quinase/metabolismo , Arginina/metabolismo , Proteínas de Bactérias/metabolismo , Fosforilação , Zinco
2.
PLoS One ; 19(3): e0297536, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38478548

RESUMO

Nasal endoscopy is routinely performed to distinguish the pathological types of masses. There is a lack of studies on deep learning algorithms for discriminating a wide range of endoscopic nasal cavity mass lesions. Therefore, we aimed to develop an endoscopic-examination-based deep learning model to detect and classify nasal cavity mass lesions, including nasal polyps (NPs), benign tumors, and malignant tumors. The clinical feasibility of the model was evaluated by comparing the results to those of manual assessment. Biopsy-confirmed nasal endoscopic images were obtained from 17 hospitals in South Korea. Here, 400 images were used for the test set. The training and validation datasets consisted of 149,043 normal nasal cavity, 311,043 NP, 9,271 benign tumor, and 5,323 malignant tumor lesion images. The proposed Xception architecture achieved an overall accuracy of 0.792 with the following class accuracies on the test set: normal = 0.978 ± 0.016, NP = 0.790 ± 0.016, benign = 0.708 ± 0.100, and malignant = 0.698 ± 0.116. With an average area under the receiver operating characteristic curve (AUC) of 0.947, the AUC values and F1 score were highest in the order of normal, NP, malignant tumor, and benign tumor classes. The classification performances of the proposed model were comparable with those of manual assessment in the normal and NP classes. The proposed model outperformed manual assessment in the benign and malignant tumor classes (sensitivities of 0.708 ± 0.100 vs. 0.549 ± 0.172, 0.698 ± 0.116 vs. 0.518 ± 0.153, respectively). In urgent (malignant) versus nonurgent binary predictions, the deep learning model achieved superior diagnostic accuracy. The developed model based on endoscopic images achieved satisfactory performance in classifying four classes of nasal cavity mass lesions, namely normal, NP, benign tumor, and malignant tumor. The developed model can therefore be used to screen nasal cavity lesions accurately and rapidly.


Assuntos
Aprendizado Profundo , Neoplasias , Humanos , Cavidade Nasal/diagnóstico por imagem , Algoritmos , Endoscopia/métodos
3.
ACS Nano ; 18(11): 8392-8410, 2024 Mar 19.
Artigo em Inglês | MEDLINE | ID: mdl-38450656

RESUMO

Therapeutic antibodies that block vascular endothelial growth factor (VEGF) show clinical benefits in treating nonsmall cell lung cancers (NSCLCs) by inhibiting tumor angiogenesis. Nonetheless, the therapeutic effects of systemically administered anti-VEGF antibodies are often hindered in NSCLCs because of their limited distribution in the lungs and their adverse effects on normal tissues. These challenges can be overcome by delivering therapeutic antibodies in their mRNA form to lung endothelial cells, a primary target of VEGF-mediated pulmonary angiogenesis, to suppress the NSCLCs. In this study, we synthesized derivatives of poly(ß-amino esters) (PBAEs) and prepared nanoparticles to encapsulate the synthetic mRNA encoding bevacizumab, an anti-VEGF antibody used in the clinic. Optimization of nanoparticle formulations resulted in a selective lung transfection after intravenous administration. Notably, the optimized PBAE nanoparticles were distributed in lung endothelial cells, resulting in the secretion of bevacizumab. We analyzed the protein corona on the lung- and spleen-targeting nanoparticles using proteomics and found distinctive features potentially contributing to their organ-selectivity. Lastly, bevacizumab mRNA delivered by the lung-targeting PBAE nanoparticles more significantly inhibited tumor proliferation and angiogenesis than recombinant bevacizumab protein in orthotopic NSCLC mouse models, supporting the therapeutic potential of bevacizumab mRNA therapy and its selective delivery through lung-targeting nanoparticles. Our proof-of-principle results highlight the clinical benefits of nanoparticle-mediated mRNA therapy in anticancer antibody treatment in preclinical models.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Animais , Camundongos , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , Bevacizumab/farmacologia , Bevacizumab/uso terapêutico , Fator A de Crescimento do Endotélio Vascular/genética , Fator A de Crescimento do Endotélio Vascular/metabolismo , Células Endoteliais/metabolismo , Nanomedicina , RNA Mensageiro/genética , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/genética , Fatores de Crescimento do Endotélio Vascular , Polímeros/uso terapêutico , Pulmão/metabolismo , Inibidores da Angiogênese/farmacologia , Inibidores da Angiogênese/uso terapêutico
4.
Laryngoscope Investig Otolaryngol ; 9(1): e1206, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38362197

RESUMO

Objectives: This study aimed to evaluate the characteristics and treatment outcomes of inverted papillomas involving the frontal sinus. Methods: Patients treated for inverted papilloma involving the frontal sinus between 2003 and 2020 were reviewed. Tumors were classified based on their extent (Extent 1: partially encroaching on the frontal sinus; Extent 2: completely filling the frontal sinus; Extent 3: eroding bony borders beyond the frontal sinus) and site of origin (Origin 1: originating outside the frontal sinus and prolapsing into the frontal sinus; Origin 2: originating from the frontal sinus walls medial to the vertical plane of the lamina papyracea; Origin 3: originating from the frontal sinus walls lateral to the vertical plane of the lamina papyracea). Treatment outcomes including tumor recurrence and patency of the frontal recess were analyzed according to tumor characteristics and surgical treatment modalities. Results: A total of 49 surgical cases were analyzed. Extent 1 were the most common type (n = 27), followed by Extent 2 (n = 15), and Extent 3 (n = 7). The most common sites of origin were Origin 1 (n = 23), followed by Origin 2 (n = 15), and Origin 3 (n = 11). Overall, there were nine recurrences (18.4%). Recurrence was not associated with tumor extent, whereas tumor origin, particularly Origin 3 was associated with higher recurrence; 1/23 (4.3%) for Origin 1, 3/15 (20.0%) for Origin 2, and 5/11 (45.5%) for Origin 3 (Log-rank p < .001). Draf III frontal sinusotomy was associated with in the highest patency rate (84.6%) during the follow-up. Conclusion: The recurrence rate of frontal sinus inverted papilloma depends on tumor origin rather than the extent of the tumor. In particular, lesions originating from the frontal sinus lateral to the lamina papyracea recur frequently. Draf III frontal sinusotomy can achieve patent frontal recess allowing active surveillance. Level of Evidence: IV.

5.
Cancer Res Treat ; 2024 Feb 13.
Artigo em Inglês | MEDLINE | ID: mdl-38351682

RESUMO

SMARCB1 or SMARCA4-deficient sinonasal carcinoma or thoracic undifferentiated tumor has aggressive nature with a poor prognosis. Patients with this disease were diagnosed by immunohistochemistry (IHC) or next-generation sequencing (NGS). Those who were able to receive a surgery tended to be cured, while the others treated with chemotherapy, radiation therapy, or immune checkpoint inhibitor were often insensitive to these therapies. However, one having CD274 (PD-L1) amplification showed the response to immune checkpoint inhibitor and a good prognosis. We believed that this report could provide promising information for determining the optimal treatment option.

6.
Artigo em Inglês | MEDLINE | ID: mdl-38404243

RESUMO

Objectives: Due to the rarity of olfactory neuroblastoma (ONB), there is an ongoing debate about optimal treatment strategies, especially for early staged or locally advanced cases. Therefore, our study aims to explore experiences from multiple centers, focusing on factors that influence the oncological outcomes of ONB. Methods: We retrospectively analyzed 195 ONB patients treated at nine tertiary hospitals in South Korea between December 1992 and December 2019. Kaplan-Meier survival analysis was used to evaluate oncological outcomes, and the Cox proportional hazards regression model was employed to analyze prognostic factors for survival outcomes. Furthermore, we conducted 1:1 nearest-neighbor matching to investigate differences in clinical outcomes according to the use of neoadjuvant chemotherapy. Results: In our cohort, the 5-year overall survival rate (OS) was 78.6%, and the 5-year disease-free survival rate (DFS) was 62.4%. The Cox proportional hazards model revealed that the mKadish stage and Dulguerov T status were significant for DFS, while the mKadish stage and Hyams grade were identified as prognostic factors for OS. The subgroup analyses indicated a trend toward improved 5-year DFS with dural resection in mKadish A and B cases, even though that result was statistically insignificant. Induction chemotherapy did not provide a survival benefit in this study after matching for the mKadish stage and nodal status. Conclusion: Clinical staging and pathologic grading are important prognostic factors in ONB. Dural resection in mKadish A and B did not show a significant survival benefit. Induction chemotherapy did not show a survival benefit, even after stage matching.

7.
Adv Sci (Weinh) ; 11(14): e2308978, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38279580

RESUMO

Innate immune training involves myelopoiesis, dynamic gene modulation, and functional reprogramming of myeloid cells in response to secondary heterologous challenges. The present study evaluates whether systemic innate immune training can protect tissues from local injury. Systemic pretreatment of mice with ß-glucan, a trained immunity agonist, reduces the mortality rate of mice with bleomycin-induced lung injury and fibrosis, as well as decreasing collagen deposition in the lungs. ß-Glucan pretreatment induces neutrophil accumulation in the lungs and enhances efferocytosis. Training of mice with ß-glucan results in histone modification in both alveolar macrophages (AMs) and neighboring lung epithelial cells. Training also increases the production of RvD1 and soluble mediators by AMs and efferocytes. Efferocytosis increases trained immunity in AMs by stimulating RvD1 release, thus inducing SIRT1 expression in neighboring lung epithelial cells. Elevated epithelial SIRT1 expression is associated with decreased epithelial cell apoptosis after lung injury, attenuating tissue damage. Further, neutrophil depletion dampens the effects of ß-glucan on macrophage accumulation, epigenetic modification in lung macrophages, epithelial SIRT1 expression, and injury-mediated fibrosis in the lung. These findings provide mechanistic insights into innate immune training and clues to the potential ability of centrally trained immunity to protect peripheral organs against injury-mediated disorders.


Assuntos
Lesão Pulmonar , beta-Glucanas , Camundongos , Animais , Sirtuína 1 , 60574 , Lesão Pulmonar/prevenção & controle , beta-Glucanas/farmacologia , Fibrose
8.
Int. arch. otorhinolaryngol. (Impr.) ; 27(2): 191-196, April-June 2023. tab, graf
Artigo em Inglês | LILACS-Express | LILACS | ID: biblio-1440217

RESUMO

Abstract Introduction Contact granulomas (CGs) and intubation granulomas (IGs) are known to have different clinical manifestations despite having the same pathological features. Objectives The purpose of the present study was to analyze the treatment results for CG and IG and to obtain clinical information. Methods We retrospectively reviewed the medical records of patients diagnosed with vocal process granuloma (VPG) between January 2015 and December 2018. The patient's age, sex, medical history, lesion size, lesion type, reflux finding score (RFS), response to treatment, duration of treatment, and follow-up period were compared. Results Eighteen patients with CG and 14 patients with IG were included in the study. The IG group had more female patients (p = 0.0009), showed better response to proton pump inhibitor (PPI) and steroid inhalation (SI) (p = 0.036), and had a shorter treatment period (p = 0.0029) than the CG group. Five patients who received botulinum toxin injections in their vocal cords had complete remission. Conclusions Compared with CG, IG was more responsive to treatment with PPI and SI and required a shorter duration of treatment.

9.
Int Arch Otorhinolaryngol ; 27(2): e191-e196, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-37125377

RESUMO

Introduction Contact granulomas (CGs) and intubation granulomas (IGs) are known to have different clinical manifestations despite having the same pathological features. Objective The purpose of the present study was to analyze the treatment results for CG and IG and to obtain clinical information. Methods We retrospectively reviewed the medical records of patients diagnosed with vocal process granuloma (VPG) between January 2015 and December 2018. The patient's age, sex, medical history, lesion size, lesion type, reflux finding score (RFS), response to treatment, duration of treatment, and follow-up period were compared. Results Eighteen patients with CG and 14 patients with IG were included in the study. The IG group had more female patients ( p = 0.0009), showed better response to proton pump inhibitor (PPI) and steroid inhalation (SI) ( p = 0.036), and had a shorter treatment period ( p = 0.0029) than the CG group. Five patients who received botulinum toxin injections in their vocal cords had complete remission. Conclusion Compared with CG, IG was more responsive to treatment with PPI and SI and required a shorter duration of treatment.

10.
J Immunol ; 210(12): 1974-1989, 2023 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-37163338

RESUMO

The gasdermins are a family of pore-forming proteins that has recently been suggested to play a central role in pyroptosis. In this study, we describe the novel roles of gasdermins in the biogenesis of apoptotic cell-derived exosomes. In apoptotic human HeLa and HEK293 cells, GSDMA, GSDMC, GSDMD, and GSDME increased the release of apoptotic exosomes. GSDMB and DFNB59, in contrast, negatively affected the release of apoptotic exosomes. GSDME at its full-length and cleaved forms was localized in the exosomes and exosomal membrane. Full-length and cleaved forms of GSDME are suggested to increase Ca2+ influx to the cytosol through endosomal pores and thus increase the biogenesis of apoptotic exosomes. In addition, the GSDME-mediated biogenesis of apoptotic exosomes depended on the ESCRT-III complex and endosomal recruitment of Ca2+-dependent proteins, that is, annexins A2 and A7, the PEF domain family proteins sorcin and grancalcin, and the Bro1 domain protein HD-PTP. Therefore, we propose that the biogenesis of apoptotic exosomes begins when gasdermin-mediated endosomal pores increase cytosolic Ca2+, continues through the recruitment of annexin-sorcin/grancalcin-HD-PTP, and is completed when the ESCRT-III complex synthesizes intraluminal vesicles in the multivesicular bodies of dying cells. Finally, we found that GSDME-bearing tumors released apoptotic exosomes to induce inflammatory responses in the in vivo mouse 4T1 orthotropic model of BALB/c breast cancer. The data indicate that the switch from apoptosis to pyroptosis could drive the transfer of mass signals to nearby or distant living cells and tissues by way of extracellular vesicles, and that gasdermins play critical roles in that process.

11.
Nat Commun ; 14(1): 1878, 2023 Apr 04.
Artigo em Inglês | MEDLINE | ID: mdl-37015941

RESUMO

Imaging an object embedded within a scattering medium requires the correction of complex sample-induced wave distortions. Existing approaches have been designed to resolve them by optimizing signal waves recorded in each 2D image. Here, we present a volumetric image reconstruction framework that merges two fundamental degrees of freedom, the wavelength and propagation angles of light waves, based on the object momentum conservation principle. On this basis, we propose methods for exploiting the correlation of signal waves from volumetric images to better cope with multiple scattering. By constructing experimental systems scanning both wavelength and illumination angle of the light source, we demonstrated a 32-fold increase in the use of signal waves compared with that of existing 2D-based approaches and achieved ultrahigh volumetric resolution (lateral resolution: 0.41 [Formula: see text], axial resolution: 0.60 [Formula: see text]) even within complex scattering medium owing to the optimal coherent use of the broad spectral bandwidth (225 nm).

12.
Sci Rep ; 13(1): 4383, 2023 03 16.
Artigo em Inglês | MEDLINE | ID: mdl-36928588

RESUMO

This study aimed to evaluate the alteration of PAP compliance after nasal surgery and to determine the optimal indications of nasal surgery in obstructive sleep apnea (OSA) subjects. Among OSA subjects using PAP devices, 29 subjects who underwent septoturbinoplasty due to nasal obstruction were included and their pre- and postoperative medical and PAP records were reviewed retrospectively. Postoperative autoPAP usage data was further assessed by grouping the compliance (the percentage of days with usage ≥ 4 h) data (group 1: the good compliance group; group 2: the poor compliance group). The data showed that 56% of subjects in group 1 complained of nasal obstruction as the only barrier to using a PAP device and about 89% reported experiencing the efficacy of PAP usage. Both the mean and peak average PAP pressures were significantly reduced in group 1 following nasal surgery. Group 2 had multiple subjective problems that interfered with wearing a PAP device and reported a lack of experiencing the efficacy of PAP usage. Preoperative nasal cavity volume values were smaller and absolute blood eosinophil counts were significantly lower in group 1. The current data demonstrate that nasal surgery might increase the compliance of PAP device wear in OSA subjects who complained of only nasal obstruction as a barrier to wearing PAP and who had small nasal cavity volumes combined with allergic inflammation.


Assuntos
Obstrução Nasal , Procedimentos Cirúrgicos Nasais , Apneia Obstrutiva do Sono , Humanos , Obstrução Nasal/cirurgia , Estudos Retrospectivos , Pressão Positiva Contínua nas Vias Aéreas , Apneia Obstrutiva do Sono/cirurgia
13.
Structure ; 31(5): 619-628.e4, 2023 05 04.
Artigo em Inglês | MEDLINE | ID: mdl-36963396

RESUMO

Peptidoglycan, a physical barrier that protects bacteria from the environment, is constantly degraded and resynthesized for remodeling during cell growth and division. Because excessive or insufficient peptidoglycan hydrolysis affects bacterial homeostasis and viability, peptidoglycan degradation must be precisely regulated. In Bacillus subtilis, DL-endopeptidases play an essential role in peptidoglycan remodeling, and their activity is regulated by IseA. Here, we report the crystal structure of peptidoglycan DL-endopeptidase LytE complexed with IseA. In the crystal structure, the inhibitory loop connecting the two lobes of IseA blocks the active site of LytE by mimicking its substrate. Consistently, mutations in the inhibitory loop resulted in the loss of IseA activity. The structure also shows that conformational rearrangements in both LytE and IseA restrict access of the inhibitory loop to the LytE catalytic site. These results reveal an inhibition mechanism of peptidoglycan DL-endopeptidase in which the inhibitory protein mimics the substrate but is not degraded.


Assuntos
Proteínas de Bactérias , Peptidoglicano , Peptidoglicano/metabolismo , Proteínas de Bactérias/química , Endopeptidases/química , Hidrólise , Mutação , Bacillus subtilis/genética , Bacillus subtilis/metabolismo , Parede Celular/metabolismo
14.
Sleep Breath ; 27(6): 2165-2173, 2023 12.
Artigo em Inglês | MEDLINE | ID: mdl-36959432

RESUMO

BACKGROUND: The lateral pharyngeal wall (LPW) is a critical anatomic structure in patients with obstructive sleep apnea (OSA). Resolving the retropalatal circumferential (RC) narrowing caused by combination of both LPW collapse and antero-posterior (AP) narrowing holds promise for surgical treatment of OSA. We sought to determine the clinical characteristics and distinctive alterations in sleep parameters of patients with OSA who have RC narrowing and LPW collapse. METHODS: Drug-induced sleep endoscopy (DISE), polysomnography findings, and sleep questionnaires were reviewed retrospectively in patients with OSA. RESULTS: Of the 106 OSA patients examined, 48% showed RC narrowing and 44% showed AP narrowing at the oropharynx level during sleep while 8% of the patients showed only LPW collapse. Patients with RC narrowing with LPW collapse exhibited a higher BMI than those with AP narrowing only. In addition, patients with RC narrowing showed more aggravated sleep parameters including apneic events than patients with AP narrowing alone. The degree of RC narrowing correlated significantly with the severity of OSA as shown by a higher apnea index and lower oxygen desaturations. CONCLUSIONS: Our clinical findings suggest that the presence of RC narrowing with LPW collapse in OSA is closely related to increased apneic and oxygen desaturation events. RC narrowing with LPW collapse may be targets for surgical correction in patients with OSA to improve therapeutic outcomes.


Assuntos
Relevância Clínica , Apneia Obstrutiva do Sono , Humanos , Estudos Retrospectivos , Apneia Obstrutiva do Sono/diagnóstico , Apneia Obstrutiva do Sono/cirurgia , Apneia Obstrutiva do Sono/etiologia , Sono , Endoscopia , Oxigênio
15.
Clin Exp Otorhinolaryngol ; 16(2): 141-147, 2023 May.
Artigo em Inglês | MEDLINE | ID: mdl-36791808

RESUMO

OBJECTIVES: To compare the efficacy and safety of high-intensity focused ultrasound (HIFU) therapy with coblation for the treatment of inferior turbinate hypertrophy (ITH). METHODS: In this randomized controlled clinical trial, 20 patients underwent inferior turbinate surgery, which consisted of either HIFU or coblation therapy. Efficacy, safety, and tolerability were evaluated by subjective symptom scores, acoustic rhinometry, and nasal endoscopy. RESULTS: The modified nasal obstruction symptom evaluation (NOSE) score and nasal obstruction visual analog scale (NO-VAS) significantly decreased in both groups 12 weeks postoperatively. The between-group differences in the evaluation scores were not statistically significant. On nasal endoscopy, the HIFU patients showed improvements in mucosal swelling sooner than the patients undergoing coblation therapy. Nasal crusting significantly increased in the patients undergoing coblation compared to the patients undergoing HIFU therapy until postoperative week 4. Mucosal preservation was superior in the HIFU patients. Although HIFU was less painful than coblation therapy during the procedure, the difference was not significant (4.9 vs. 6.3, P=0.143). The difference in global satisfaction between the two groups was not statistically significant, although satisfaction was slightly higher among the HIFU patients than among the coblation patients (4.6 vs. 4.1, P=0.393). CONCLUSION: HIFU provided results similar to those of coblation therapy for patients with nasal obstruction due to ITH, but HIFU therapy caused less discomfort during the procedure. HIFU therapy appears to be a good noninvasive alternative to the current surgical modalities for ITH.

16.
Sci Rep ; 13(1): 101, 2023 01 03.
Artigo em Inglês | MEDLINE | ID: mdl-36596838

RESUMO

Tranilast, an anti-allergic drug used in the treatment of bronchial asthma, was identified as an inhibitor of the transcription factor Forkhead box O-1 (FoxO-1) by high throughput chemical library screening in the present study. Based on FoxO-1's role in apoptotic cell death and differentiation, we examined the effect of tranilast on palmitic acid (PA)-induced cell damage in INS-1 cells. Tranilast substantially inhibited lipoapoptosis and restored glucose-stimulated insulin secretion under high PA exposure. Moreover, PA-mediated downregulation of PDX-1, MafA, and insulin expression was attenuated by tranilast. PA-induced oxidative and ER stress were also reduced in the presence of tranilast. These protective effects were accompanied by increased phosphorylation and decreased nuclear translocation of FoxO-1. Conversely, the effects of tranilast were diminished when treated in transfected cells with FoxO-1 phosphorylation mutant (S256A), suggesting that the tranilast-mediated effects are associated with inactivation of FoxO-1. Examination of the in vivo effects of tranilast using wild type and diabetic db/db mice showed improved glucose tolerance along with FoxO-1 inactivation in the pancreas of the tranilast-treated groups. Thus, we report here that tranilast has protective effects against PA-induced lipotoxic stress in INS-1 cells, at least partly, via FoxO-1 inactivation, which results in improved glucose tolerance in vivo.


Assuntos
Células Secretoras de Insulina , Ácido Palmítico , Camundongos , Animais , Ácido Palmítico/farmacologia , Células Secretoras de Insulina/metabolismo , Insulina/metabolismo , Apoptose , Glucose/metabolismo
17.
Ear Nose Throat J ; 102(2): 101-109, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-34427151

RESUMO

OBJECTIVE: To evaluate the clinical efficacy and safety of cefetamet pivoxil for the treatment of acute bacterial rhinosinusitis in Korean patients compared to treatment with cefdinir. METHODS: A prospective, multicenter, randomized double-blind, comparative study was conducted by the Departments of Otorhinolaryngology-Head and Neck Surgery at 17 hospitals or universities in the Republic of Korea from March 2017 to April 2019. A total of 309 patients were screened and 249 patients participated in the study. RESULTS: Treatment with cefetamet pivoxil for 2 weeks showed 82.4% clinical cure and improvement rates in patients with acute bacterial rhinosinusitis compared to 84.68% in those taking cefdinir for 2 weeks, showing that cefetamet pivoxil administered twice a day for 2 weeks was as effective as cefdinir 3 times a day for 2 weeks for the treatment of acute bacterial rhinosinusitis. The overall adverse reaction rates of both drugs were 10.56% in the cefetamet pivoxil group and 15.49% in the cefdinir group, without serious adverse events or drug reactions. CONCLUSIONS: Cefetamet pivoxil twice a day was as efficacious and safe as cefdinir 3 times a day for the treatment of acute bacterial rhinosinusitis, which suggested that cefetamet pivoxil may be a suitable alternative to cefdinir.


Assuntos
Ceftizoxima , Sinusite , Humanos , Cefdinir , Estudos Prospectivos , Ceftizoxima/efeitos adversos , Sinusite/tratamento farmacológico , Sinusite/induzido quimicamente , Bactérias
18.
Materials (Basel) ; 15(21)2022 Oct 30.
Artigo em Inglês | MEDLINE | ID: mdl-36363228

RESUMO

Conducting polymer composites consisting of carbon nanotubes (CNTs) as a conductive filler and polydimethylsiloxane (PDMS) as a polymer matrix were fabricated to investigate their capacitive and piezoresistive effects as pressure sensors. The pressure-sensing behavior and mechanism of the composites were compared in terms of basic configuration with a parallel plate structure. Various sensing experiments, such as sensitivity, repeatability, hysteresis, and temperature dependence according to the working principle, were conducted with varying filler contents. The hysteresis and repeatability of the pressure-sensing properties were investigated using cyclic tensile tests. In addition, a temperature test was performed at selected temperatures to monitor the change in the resistance/capacitance.

19.
Micromachines (Basel) ; 13(11)2022 Nov 17.
Artigo em Inglês | MEDLINE | ID: mdl-36422427

RESUMO

Compression and tension sensors with a porous structure have attracted attention recently. Porous sponge sensors have the advantage of a wide deformation range owing to their structural characteristics. In this study, a porous sponge structure was prepared by absorbing polydimethylsiloxane (PDMS) into the matrix of porous commercial sugar cubes. A conductive network was formed by coating the outside of the sponge skeleton with silver nanowires (AgNWs), which have a high aspect ratio. In addition, a liquid metal (LM), which does not directly form an electrical network but changes from zero-dimensional to one-dimensional under an external force was introduced into this porous sponge structure. The effects of the LM on the sensor sensitivity to pressure and strain were analyzed by comparing the electrical resistance changes of PDMS/AgNW and LM/PDMS/AgNW sponge sensors under tension and pressure. This study shows that the use of a porous structure and an LM may be useful for future wearable sensor design.

20.
Nanoscale Adv ; 4(21): 4570-4578, 2022 Oct 25.
Artigo em Inglês | MEDLINE | ID: mdl-36341283

RESUMO

A low interfacial contact resistance is a challenge in polymer nanocomposites based on conductive nanomaterials for high-performance wearable electrode applications. Herein, a polydimethylsiloxane (PDMS)-based flexible nanocomposite incorporating high-conductivity 1D single-walled carbon nanotubes (SWCNTs) and 2D reduced graphene oxide (r-GO) was developed for high-performance electrocardiogram (ECG) wearable electrodes. A PDMS-SWCNT (P-SW; type I) nanocomposite containing only SWCNTs (2 wt%), exhibited rough and non-uniform surface morphology owing to the strong bundling effect of as-grown SWCNTs and randomly entangled aggregate structures and because of inefficient vacuum degassing (i.e., R P-SW = 1871 Ω). In contrast, owing to the hybrid structure of the SWCNTs (1 wt%) and r-GO (1 wt%), the PDMS-SWCNTs/r-GO (P-SW/r-GO; type II) nanocomposite exhibited uniform surface characteristics and low contact resistance (i.e., R P-SW/r-GO = 63 Ω) through the formation of hybrid and long conducting pathways. The optimized nanocomposite (P-SW/r-GO/f; type III) possessed a fabric-assisted structure that enabled tunable and efficient vacuum degassing and curing conditions. Additionally, a long and wide conducting pathway was formed through more uniform and dense interconnected structures, and the contact resistance was drastically reduced (i.e., R P-SW/r-GO/f = 15 Ω). The performance of the electrodes fabricated using the optimized nanocomposites was the same or higher than that of commercial Ag/AgCl gel electrodes during real-time measurement for ECG Bluetooth monitoring. The developed high-performance hybrid conducting polymer electrodes are expected to contribute significantly to the expansion of the application scope of wearable electronic devices and wireless personal health monitoring systems.

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