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1.
Circ Res ; 132(9): 1110-1126, 2023 04 28.
Artigo em Inglês | MEDLINE | ID: mdl-36974722

RESUMO

BACKGROUND: Mitochondrial DNA (mtDNA)-induced myocardial inflammation is intimately involved in cardiac remodeling. ZBP1 (Z-DNA binding protein 1) is a pattern recognition receptor positively regulating inflammation in response to mtDNA in inflammatory cells, fibroblasts, and endothelial cells. However, the role of ZBP1 in myocardial inflammation and cardiac remodeling remains unclear. The aim of this study was to elucidate the role of ZBP1 in mtDNA-induced inflammation in cardiomyocytes and failing hearts. METHODS: mtDNA was administrated into isolated cardiomyocytes. Myocardial infarctionwas conducted in wild type and ZBP1 knockout mice. RESULTS: We here found that, unlike in macrophages, ZBP1 knockdown unexpectedly exacerbated mtDNA-induced inflammation such as increases in IL (interleukin)-1ß and IL-6, accompanied by increases in RIPK3 (receptor interacting protein kinase 3), phosphorylated NF-κB (nuclear factor-κB), and NLRP3 (nucleotide-binding domain and leucine-rich-repeat family pyrin domain containing 3) in cardiomyocytes. RIPK3 knockdown canceled further increases in phosphorylated NF-κB, NLRP3, IL-1ß, and IL-6 by ZBP1 knockdown in cardiomyocytes in response to mtDNA. Furthermore, NF-κB knockdown suppressed such increases in NLRP3, IL-1ß, and IL-6 by ZBP1 knockdown in response to mtDNA. CpG-oligodeoxynucleotide, a Toll-like receptor 9 stimulator, increased RIPK3, IL-1ß, and IL-6 and ZBP1 knockdown exacerbated them. Dloop, a component of mtDNA, but not Tert and B2m, components of nuclear DNA, was increased in cytosolic fraction from noninfarcted region of mouse hearts after myocardial infarction compared with control hearts. Consistent with this change, ZBP1, RIPK3, phosphorylated NF-κB, NLRP3, IL-1ß, and IL-6 were increased in failing hearts. ZBP1 knockout mice exacerbated left ventricular dilatation and dysfunction after myocardial infarction, accompanied by further increases in RIPK3, phosphorylated NF-κB, NLRP3, IL-1ß, and IL-6. In histological analysis, ZBP1 knockout increased interstitial fibrosis and myocardial apoptosis in failing hearts. CONCLUSIONS: Our study reveals unexpected protective roles of ZBP1 against cardiac remodeling as an endogenous suppressor of mtDNA-induced myocardial inflammation.


Assuntos
Infarto do Miocárdio , NF-kappa B , Camundongos , Animais , NF-kappa B/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Inflamassomos/metabolismo , DNA Mitocondrial/genética , Interleucina-6/metabolismo , Remodelação Ventricular , Células Endoteliais/metabolismo , Infarto do Miocárdio/genética , Infarto do Miocárdio/prevenção & controle , Infarto do Miocárdio/patologia , Inflamação/metabolismo , Camundongos Knockout , Interleucina-1beta/metabolismo , Proteínas de Ligação a RNA
2.
Mol Pain ; 20: 17448069241233744, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38323375

RESUMO

Methylglyoxal (MGO), a highly reactive dicarbonyl metabolite of glucose primarily formed during the glycolytic pathway, is a precursor of advanced glycation end-products (AGEs). Recently, numerous studies have shown that MGO accumulation can cause pain and hyperalgesia. However, the mechanism through which MGO induces pain in the spinal dorsal horn remains unclear. The present study investigated the effect of MGO on spontaneous excitatory postsynaptic currents (sEPSC) in rat spinal dorsal horn neurons using blind whole-cell patch-clamp recording. Perfusion of MGO increased the frequency and amplitude of sEPSC in spinal horn neurons in a concentration-dependent manner. Additionally, MGO administration increased the number of miniature EPSC (mEPSC) in the presence of tetrodotoxin, a sodium channel blocker. However, 6-cyano-7-nitroqiunocaline-2,3-dione (CNQX), an AMPA/kainate receptor antagonist, blocked the enhancement of sEPSC by MGO. HC-030031, a TRP ankyrin-1 (TRPA1) antagonist, and capsazepine, a TRP vanilloid-1 (TRPV1) antagonist, inhibited the action of MGO. Notably, the effects of MGO were completely inhibited by HC-030031 and capsazepine. MGO generates reactive oxygen species (ROS) via AGEs. ROS also potentially induce pain via TRPA1 and TRPV1 in the spinal dorsal horn. Furthermore, we examined the effect of MGO in the presence of N-tert-butyl-α-phenylnitrone (PBN), a non-selective ROS scavenger, and found that the effect of MGO was completely inhibited. These results suggest that MGO increases spontaneous glutamate release from the presynaptic terminal to spinal dorsal horn neurons through TRPA1, TRPV1, and ROS and could enhance excitatory synaptic transmission.


Assuntos
Acetanilidas , Capsaicina/análogos & derivados , Óxido de Magnésio , Purinas , Aldeído Pirúvico , Ratos , Animais , Espécies Reativas de Oxigênio/metabolismo , Aldeído Pirúvico/farmacologia , Aldeído Pirúvico/metabolismo , Ratos Sprague-Dawley , Óxido de Magnésio/metabolismo , Óxido de Magnésio/farmacologia , Corno Dorsal da Medula Espinal/metabolismo , Células do Corno Posterior/metabolismo , Dor/metabolismo , Transmissão Sináptica/fisiologia
3.
Anal Bioanal Chem ; 414(11): 3419-3428, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35169907

RESUMO

Microfluidic immunoassay devices are a promising technology that can quickly detect biomarkers with high sensitivity. Recently, many studies implementing this technology on paper substrates have been proposed for improving cost and user-friendliness. However, these studies have identified problems with the large volume of sample required, low sensitivity, and a lack of quantitative accuracy and precision. In this paper, we report a novel structure implemented as a cellulosic material-based microchannel device capable of quantitative immunoassay using small sample volumes. We fabricated microfluidic channels between a transparent cellophane film and water-resistant paper to facilitate loading of small-volume samples and reagents, with a 40-µm-wide immunoreaction matrix constructed in the center of the microchannel using highly precise photolithography. A fluorescence sandwich immunoassay for C-reactive protein (CRP) was successfully implemented that required only a 1-µL sample volume and a 20-min reaction time. We confirmed that the limit of detection of the device was 10-20 ng/mL with a coefficient of variation under 5.6%, which is a performance level comparable to conventional plastic-based human CRP enzyme-linked immunosorbent assay (ELISA) kits. We expect that such devices will lead to the elimination of large amounts of medical waste from the use of ubiquitous diagnostics, a result that is consistent with environmental sustainability goals.


Assuntos
Dispositivos Lab-On-A-Chip , Técnicas Analíticas Microfluídicas , Proteína C-Reativa/análise , Ensaio de Imunoadsorção Enzimática , Imunofluorescência , Humanos , Imunoensaio
4.
Anal Bioanal Chem ; 413(11): 3081-3091, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33733702

RESUMO

In plant research, measuring the physiological parameters of plants is vital for understanding the behavior and response of plants to changes in the external environment. Plant sap analysis provides an approach for elucidating the physiological condition of plants. However, to facilitate accurate sap analysis, a sampling device capable of collecting sap samples from plants is required. In this paper, a minimally invasive, needle-type micro-sampling device capable of collecting nanoliter (~ 91 nL) quantities of sap from plants is described. The developed micro-sampling system showed great reproducibility (3%) in experiments designed to assess sampling performance. As a proof of concept, sap samples were collected continuously from target plants with the micro-sampling system, and the dynamic changes in potassium ions, plant hormones and sugar levels inside plants were analyzed. The results demonstrated the feasibility of the micro-sampling device and its potential for developing a measurement system for plant research in the future.


Assuntos
Agulhas , Plantas/química , Manejo de Espécimes/instrumentação , Espectrometria de Massas/métodos
5.
Anal Chem ; 92(23): 15534-15541, 2020 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-33169984

RESUMO

Sweat sensors that can continuously sample sweat are critical for determining the time-dependent physiological responses occurring in normal daily life. Here, a new device, termed fluidic patch, for collecting human sweat samples at defined time intervals is developed, and the proof-of-concept is demonstrated. The device comprises micropumps and a disposable microfluidic patch attached to the human skin. The fluidic patch continuously collects aliquots of freshly secreted sweat accumulated in the fluidic pathway at accurately defined time windows (typically 5 min). By measuring the weight of the collected samples, the local sweat rate is calculated. The sweat sample collected can be directly subjected to a wide range of chemical analyses. For the proof-of-concept, we compared the sweat rates during passive heating in human trials using the fluidic patch and the conventional ventilated sweat capsule system. Although the sweat rate obtained using the fluidic patch highly correlated with that of the ventilated sweat capsule (R2 = 0.96, y = 1.4x - 0.05), the fluidic patch overestimated the sweat rate compared with the ventilated capsule system when the sweat rate exceeded 0.5 mg/(cm2·min). The sampled sweat was analyzed for sodium, potassium, chloride, lactate, pyruvate, and cortisol. The device could obtain the time courses of the concentrations of the abovementioned three ions; the concentrations of sodium and chloride increased linearly with the sweat rate during passive heating (R2 = 0.76 and 0.66, respectively). The device can reliably measure the sweat rate and collect sweat samples for chemical analysis. It can be utilized for real-time physiological investigations toward wider applications.


Assuntos
Testes de Química Clínica/instrumentação , Dispositivos Lab-On-A-Chip , Suor/química , Humanos , Pele
6.
Surg Today ; 48(6): 591-597, 2018 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-29468434

RESUMO

PURPOSE: Skin-sparing mastectomy (SSM) enables a radical cure of breast cancer while overcoming the cosmetic issues related to surgery. We review our experience of performing SSMs and assess whether preservation of the nipple-areola complex (NAC) could have been an option for some patients who underwent SSM. METHODS: The subjects of this retrospective study were women who underwent SSM that utilized four incision types; namely, the so-called tennis racket incision, a periareolar and midaxillary incision, an areola-sparing and midaxillary incision, and a small transverse elliptical incision. We assessed whether preservation of the NAC would have been an option in SSM, based on histologic examination of three serial cut surfaces of the specimen around the nipple, ruling out the option when evidence of the malignant lesion/s was found in at least one of the following locations: in the nipple, within a 1-cm radius from the base of the nipple, or within 1 cm from the surface of the NAC. RESULTS: We performed 193 SSMs. The cumulative 10-year local disease-free survival rate was 98%, with 89% of patients reporting levels of satisfaction with the reconstructed breast, of excellent, very good, or good. We evaluated that 70 of the 193 procedures could have been performed as nipple-sparing mastectomy (NSM). CONCLUSIONS: The outcomes of SSM in this series were excellent and NSM might have been an option for about one-third of the patients.


Assuntos
Neoplasias da Mama/cirurgia , Mastectomia/métodos , Mamilos/cirurgia , Tratamentos com Preservação do Órgão/métodos , Adulto , Idoso , Neoplasias da Mama/mortalidade , Neoplasias da Mama/patologia , Intervalo Livre de Doença , Feminino , Humanos , Mamoplastia/métodos , Mastectomia/mortalidade , Pessoa de Meia-Idade , Estudos Retrospectivos , Resultado do Tratamento
7.
World J Surg Oncol ; 11: 3, 2013 Jan 09.
Artigo em Inglês | MEDLINE | ID: mdl-23302293

RESUMO

BACKGROUND: Although adjuvant gemcitabine (GEM) chemotherapy for pancreatic cancer is standard, the quality of life (QOL) in those patients is still impaired by the standard regimen of GEM. Therefore, we studied whether mild dose-intensity adjuvant chemotherapy with bi-weekly GEM administration could provide a survival benefit with acceptable QOL to the patients with pancreatic cancer. METHODS: After a phase I trial, an adjuvant bi-weekly 1,000 mg/m2 of GEM chemotherapy was performed in 58 patients with pancreatic cancer for at least 12 courses (Group A). In contrast, 36 patients who declined the adjuvant bi-weekly GEM chemotherapy underwent traditional adjuvant 5FU-based chemotherapy (Group B). Careful periodical follow-ups for side effects of GEM and disease recurrence, and assessment of patients' QOL using the EORTC QOL questionnaire (QLQ-C30) and pancreatic cancer-specific supplemental module (QLQ-PAN26) were performed. Retrospectively, the degree of side effects, patients' QOL, compliance rate, disease-free survival (DFS), and overall survival (OS) in Group A were compared with those in Group B. RESULTS: No severe side effects (higher than Grade 2 according to the common toxicity criteria of ECOG) were observed, except for patients in Group B, who were switched to the standard GEM chemotherapy. Patients' QOL was better in Group A than B (fatigue: 48.9 ± 32.1 versus 68.1 ± 36.3, nausea and vomiting: 26.8 ± 20.4 versus 53.7 ± 32.6, diarrhea: 21.0 ± 22.6 versus 53.9 ± 38.5, difficulty gaining weight: 49.5 ± 34.4 versus 67.7 ± 40.5, P < 0.05). Compliance rates in Groups A and B were 93% and 47%. There was a significant difference in the median DFS between both groups (Group A : B =12.5 : 6.6 months, P < 0.001). The median OS of Group A was prolonged markedly compared with Group B (20.2 versus 11.9 months, P < 0.005). For OS between both groups, univariate analysis revealed no statistical difference in 69-year-old or under females, and T1-2 factors, moreover, multivariate analysis indicated three factors, such as bi-weekly adjuvant GEM chemotherapy, T2 or less, and R0. CONCLUSIONS: Adjuvant chemotherapy with bi-weekly GEM offered not only the advantage of survival benefits but the excellent compliance with acceptable QOL for postoperative pancreatic cancer patients.


Assuntos
Adenocarcinoma/tratamento farmacológico , Antimetabólitos Antineoplásicos/uso terapêutico , Desoxicitidina/análogos & derivados , Recidiva Local de Neoplasia/tratamento farmacológico , Neoplasias Pancreáticas/tratamento farmacológico , Qualidade de Vida , Adenocarcinoma/mortalidade , Adenocarcinoma/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Desoxicitidina/uso terapêutico , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/mortalidade , Recidiva Local de Neoplasia/patologia , Estadiamento de Neoplasias , Neoplasias Pancreáticas/mortalidade , Neoplasias Pancreáticas/patologia , Prognóstico , Estudos Retrospectivos , Taxa de Sobrevida , Gencitabina
8.
Anal Sci ; 39(8): 1269-1277, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37103769

RESUMO

The demand for multi-point water quality monitoring is increasing to solve the global problem of safe drinking water supply and environmental water contamination by industries. Therefore, compact devices are needed for on-site water quality analysis. On-site devices require low cost and high durability because they are placed outdoors, exposing them to strong ultraviolet rays and a wide range of temperatures. Our previous study reported on a compact and low-cost water quality meter that uses microfluidic devices with resin to monitor chemicals. In this study, we extended the fabrication range of the glass molding method to fabricate a glass microfluidic device with a 300 µm deep channel on a 50 mm in diameter substrate for constructing a low-cost and high-durability device. Finally, we developed a low-cost, highly robust glass device with a diamond-like carbon-coated channel surface to measure residual chlorine. The experimental results indicated that this device can endure outdoor conditions and be attached to small internet of things devices for analyzing chemical substances, such as residual chlorine.

9.
J Orthop Case Rep ; 13(12): 125-129, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38162353

RESUMO

Introduction: Disc sequestration is well known as a perforation of the fibrous ring and posterior longitudinal ligament, and migration of the fragment to the epidural space. Case Report: A 62-year-old man complained of increased pain and hypoesthesia and muscle weakness of the left lower limb that had started 1 month before. Magnetic resonance imaging revealed a tumor-like mass at the L2-3 level on the posterior side of the dura. The fragment was strongly adhered to the dural sac and was resected piece by piece. Disc herniation recognized at L2-3 compressed the left L3 nerve root and was removed. The histopathological diagnosis was consistent with a degenerated intervertebral disc. All symptoms improved after the surgery. Conclusion: There are few reports about the posterior migrated disc herniation at higher lumbar level. It may be associated with fused segments from L4 to the pelvis due to the previous surgery, which impacted the adjacent segment.

10.
Int Dent J ; 73(5): 674-679, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-36641344

RESUMO

OBJECTIVE: The purposes of this study were to analyse trends in primary tooth emergence patterns and to identify physical factors potentially associated with them. METHODS: The participants were 27,454 infants who underwent routine 18-month-old health examinations in Ebetsu City, Japan, between 1980 and 2012. This study was conducted using data from infants' 18-month-old health examinations over a 33-year period. The mean number of emerged primary teeth was analysed by sex using a general linear model. For logistic regression analysis, the proportion of infants with 16 emerged teeth or more at 18 months old was used as a dependent variable. Examination year; birth order; birth weight; weight, height, and chest girth at 18 months old; number of fused teeth; and mother's age were used as independent variables. RESULTS: The mean number of emerged primary teeth decreased over the 33-year period. Birth weight and weight and height at 18 months old decreased, and the proportion of low-birth-weight (<2500 g) infants increased over the 33-year period. On general linear model analysis, the yearly change in the mean number of emerged primary teeth was -0.0188 for boys and -0.0181 for girls. Birth weight and weight and height at 18 months old were significantly associated with the presence of 16 emerged primary teeth or more, according to the logistic regression analysis. CONCLUSIONS: The results demonstrated that, over the 33-year period examined, the mean number of emerged primary teeth decreased and birth weight and weight and height at 18 months old were associated with the pattern of tooth emergence.


Assuntos
População do Leste Asiático , Erupção Dentária , Dente Decíduo , Feminino , Humanos , Lactente , Masculino , Peso ao Nascer , Fatores Sexuais
11.
iScience ; 26(10): 107820, 2023 Oct 20.
Artigo em Inglês | MEDLINE | ID: mdl-37752956

RESUMO

Conventional competitive enzyme-linked immunosorbent assay (ELISA) to measure the cortisol level in body fluid consumes a large amount of time, owing to complicated operations involved and requirement for precise control of reagent addition. We developed an automatic microfluidic system to detect salivary cortisol rapidly, and an electrospun polystyrene (PS) microfiber-based reactor providing considerable binding sites for antibody immobilization, thus resolving the time limitations of competitive ELISA. Cortisol sample, horseradish peroxidase (HRP)-conjugated cortisol, and 3,3',5,5'-tetramethylbenzidine (TMB) substrate were delivered to the PS reactor from containers in sequence by pumps automatically. The color variation due to oxidized TMB complex reflects the cortisol concentration level measured using an RGB phototransistor. In addition, the entire procedure from sample introduction to obtaining the photocurrent took only 15 min. This system can be implemented to quantify cortisol from 0.37 ng/mL to 30 ng/mL, and the limit of detection was estimated at 0.37 ng/mL.

12.
Circ Heart Fail ; 16(10): e010347, 2023 10.
Artigo em Inglês | MEDLINE | ID: mdl-37522180

RESUMO

BACKGROUND: Cardiac autoantibodies (cAAbs) are involved in the progression of adverse cardiac remodeling in heart failure (HF). However, our understanding of cAAbs in HF is limited owing to the absence of relevant animal models. Herein, we aimed to establish and characterize a murine model of cAAb-positive HF after myocardial infarction (MI), thereby facilitating the development of therapeutics targeting cAAbs in post-MI HF. METHODS: MI was induced in BALB/c mice. Plasma cAAbs were evaluated using modified Western blot-based methods. Prognosis, cardiac function, inflammation, and fibrosis were compared between cAAb-positive and cAAb-negative MI mice. Rapamycin was used to inhibit cAAb production. RESULTS: Common cAAbs in BALB/c MI mice targeted cTnI (cardiac troponin I). Herein, 71% (24/34) and 44% (12/27) of the male and female MI mice, respectively, were positive for cAAbs against cTnI (cTnIAAb). Germinal centers were formed in the spleens and mediastinal lymph nodes of cTnIAAb-positive MI mice. cTnIAAb-positive MI mice showed progressive cardiac remodeling with a worse prognosis (P=0.014, by log-rank test), which was accompanied by cardiac inflammation, compared with that in cTnIAAb-negative MI mice. Rapamycin treatment during the first 7 days after MI suppressed cTnIAAb production (cTnIAAb positivity, 59% [29/49] and 7% [2/28] in MI mice treated with vehicle and rapamycin, respectively; P<0.001, by Pearson χ2 test), consequently improving the survival and ameliorating cardiac inflammation, cardiac remodeling, and HF in MI mice. CONCLUSIONS: The present post-MI HF model may accelerate our understanding of cTnIAAb and support the development of therapeutics against cTnIAAbs in post-MI HF.


Assuntos
Insuficiência Cardíaca , Infarto do Miocárdio , Camundongos , Masculino , Feminino , Animais , Insuficiência Cardíaca/etiologia , Insuficiência Cardíaca/complicações , Miocárdio/patologia , Troponina I , Modelos Animais de Doenças , Autoanticorpos , Remodelação Ventricular , Inflamação/patologia , Sirolimo
13.
JACC Basic Transl Sci ; 8(8): 992-1007, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37719427

RESUMO

Doxorubicin (DOX)-induced cardiomyopathy has poor prognosis, and myocardial inflammation is intimately involved in its pathophysiology. The role of invariant natural killer T (iNKT) cells has not been fully determined in this disease. We here demonstrated that activation of iNKT cells by α-galactosylceramide (GC) attenuated DOX-induced cardiomyocyte death and cardiac dysfunction. αGC increased interferon (IFN)-γ and phosphorylation of signal transducers and activators of transcription 1 (STAT1) and extracellular signal-regulated kinase (ERK). Administration of anti-IFN-γ neutralizing antibody abrogated the beneficial effects of αGC on DOX-induced cardiac dysfunction. These findings emphasize the protective role of iNKT cells in DOX-induced cardiomyopathy via the IFN-γ-STAT1-ERK pathway.

14.
Biosensors (Basel) ; 12(11)2022 Nov 09.
Artigo em Inglês | MEDLINE | ID: mdl-36354502

RESUMO

Laser-induced graphene (LIG) has been applied in many different sensing devices, from mechanical sensors to biochemical sensors. In particular, LIG fabricated on paper (PaperLIG) shows great promise for preparing cheap, flexible, and disposable biosensors. Distinct from the fabrication of LIG on polyimide, a two-step process is used for the fabrication of PaperLIG. In this study, firstly, a highly conductive PaperLIG is fabricated. Further characterization of PaperLIG confirmed that it was suitable for developing biosensors. Subsequently, the PaperLIG was used to construct a biosensor by immobilizing glucose oxidase, aminoferrocene, and Nafion on the surface. The developed glucose biosensor could be operated at a low applied potential (-90 mV) for amperometric measurements. The as-prepared biosensor demonstrated a limit of detection of (50-75 µM) and a linear range from 100 µM to 3 mM. The influence of the concentration of the Nafion casting solution on the performance of the developed biosensor was also investigated. Potential interfering species in saliva did not have a noticeable effect on the detection of glucose. Based on the experimental results, the simple-to-prepare PaperLIG-based saliva glucose biosensor shows great promise for application in future diabetes management.


Assuntos
Técnicas Biossensoriais , Grafite , Grafite/química , Glucose Oxidase/química , Técnicas Biossensoriais/métodos , Glucose/química , Lasers , Técnicas Eletroquímicas/métodos
15.
ACS Appl Mater Interfaces ; 14(2): 2605-2617, 2022 Jan 19.
Artigo em Inglês | MEDLINE | ID: mdl-35001615

RESUMO

In the field of tissue engineering and biomaterials, controlling the surface properties and mechanical properties of scaffold materials is crucial and has attracted much attention. Here, two types of bilayer polymer brushes composed of a hydrophilic underlying layer and a cationic surface layer [made of poly(2-aminoethyl methacrylate)] with a thickness gradient were prepared by surface-initiated atom-transfer radical polymerization. To investigate the influence of the stiffness as a mechanical property of the polymer brush on cell behavior, the underlayer was prepared from either 2-methacryloyloxyethyl phosphorylcholine or oligo(ethylene glycol) methyl ether methacrylate, with the bilayers designated as gradient poly(2-methacryloyloxyethyl phosphorylcholine)-block-poly(2-aminoethyl methacrylate) [grad-pMbA] and gradient poly(oligo[ethylene glycol] methyl ether methacrylate)-block-poly(2-aminoethyl methacrylate) [grad-pEGbA], respectively. Characterization of these surfaces was performed by spectroscopic ellipsometry, X-ray reflectivity, and determination of the zeta potential, static contact angle, and force curve. These diblock copolymer brushes with a thickness gradient helped to distinguish the effects of the mechanical and surface properties of the brushes on cell behavior. The attachment and motility of L929 fibroblasts and epithelial MCF 10A cells on the fabricated brushes were then assessed. L929 cells had a round shape on the thin surface layer of grad-pMbA and spread well on thicker areas. In contrast, MCF 10A cells spread well in areas of any thickness of either grad-pMbA or grad-pEGbA. Single MCF 10A cells migrated randomly on grad-pMbA, whereas grouped cells started to climb up along the thickness gradient of grad-pMbA. In contrast, both single and grouped MCF 10A cells migrated randomly on grad-pEGbA. These thickness gradient diblock copolymer brushes are simple, reproducible, and reasonable platforms that can facilitate practical applications of biomaterials, for example, in tissue engineering and biomaterials.


Assuntos
Materiais Biocompatíveis/farmacologia , Bicamadas Lipídicas/farmacologia , Polímeros/farmacologia , Animais , Materiais Biocompatíveis/química , Adesão Celular/efeitos dos fármacos , Linhagem Celular , Movimento Celular/efeitos dos fármacos , Humanos , Bicamadas Lipídicas/química , Teste de Materiais , Tamanho da Partícula , Polímeros/química , Propriedades de Superfície
16.
Sci Signal ; 15(758): eabn8017, 2022 11.
Artigo em Inglês | MEDLINE | ID: mdl-36318618

RESUMO

Clinical use of doxorubicin (DOX) is limited because of its cardiotoxicity, referred to as DOX-induced cardiomyopathy (DIC). Mitochondria-dependent ferroptosis, which is triggered by iron overload and excessive lipid peroxidation, plays a pivotal role in the progression of DIC. Here, we showed that DOX accumulated in mitochondria by intercalating into mitochondrial DNA (mtDNA), inducing ferroptosis in an mtDNA content-dependent manner. In addition, DOX disrupted heme synthesis by decreasing the abundance of 5'-aminolevulinate synthase 1 (Alas1), the rate-limiting enzyme in this process, thereby impairing iron utilization, resulting in iron overload and ferroptosis in mitochondria in cultured cardiomyocytes. Alas1 overexpression prevented this outcome. Administration of 5-aminolevulinic acid (5-ALA), the product of Alas1, to cultured cardiomyocytes and mice suppressed iron overload and lipid peroxidation, thereby preventing DOX-induced ferroptosis and DIC. Our findings reveal that the accumulation of DOX and iron in mitochondria cooperatively induces ferroptosis in cardiomyocytes and suggest that 5-ALA can be used as a potential therapeutic agent for DIC.


Assuntos
Ferroptose , Sobrecarga de Ferro , Camundongos , Animais , Cardiotoxicidade/etiologia , Cardiotoxicidade/metabolismo , DNA Mitocondrial/metabolismo , Ácido Aminolevulínico/metabolismo , Doxorrubicina/farmacologia , Mitocôndrias/genética , Miócitos Cardíacos/metabolismo , Sobrecarga de Ferro/complicações , Sobrecarga de Ferro/metabolismo , Ferro/metabolismo , Heme/metabolismo
17.
Kansenshogaku Zasshi ; 85(6): 674-7, 2011 Nov.
Artigo em Japonês | MEDLINE | ID: mdl-22250460

RESUMO

We report a case of emphysematous pyelonephritis coexisting with emphysematous cystitis. A 57-year-old woman seen for abdominal pain, diarrhea, and high fever had been referred after computed tomography (CT) elsewhere had shown an air density mass in the left kidney and pelvis. Abdominal CT on admission showed emphysematous change in the left renal parenchyma and intramural bladder. Serum analysis results showed disseminated intravascular coagulation (DIC) and uncontrolled diabetes. Klebsiella pneumoniae was isolated in the blood. She was diagnosed with sepsis based on these findings due to concurrent emphysematous pyelonephritis and cystitis caused by K. pneumoniae. She was treated conservatively with meropenem, intravenous immunoglobulin, and gabexate mesilate and cured. Concurrent emphysematous cystitis and pyelonephritis is rare., with ours only the fourth case reported in Japan.


Assuntos
Cistite/complicações , Enfisema/complicações , Infecções por Klebsiella/complicações , Klebsiella pneumoniae , Pielonefrite/complicações , Coagulação Intravascular Disseminada/etiologia , Feminino , Humanos , Pessoa de Meia-Idade
18.
J Mater Chem B ; 9(22): 4480-4487, 2021 06 02.
Artigo em Inglês | MEDLINE | ID: mdl-34031681

RESUMO

Biomimetic phospholipid copolymer films are known to possess antifouling properties against protein adsorption and biofilm formation. However, the interactions between bacterial cells and material surfaces are not fully understood. This work investigated the bacterial adhesion strength of phospholipid copolymer films using a shear stress-tunable microfluidic device. The copolymer, comprising 2-methacryloyloxyethyl phosphorylcholine (MPC), 3-methacryloxypropyl trimethoxysilane (MPTMSi), and 3-(methacryloyloxy) propyl-tris(trimethylsilyloxy) silane (MPTSSi), formed crosslinked films on glass substrates; the thickness of the coating film was controlled by the polymer concentration during dip-coating. Polymer films with two typical thicknesses, 20 and 40 nm (denoted as C-20 and C-40, respectively), were prepared on the bottom wall of the microfluidic device. After seeding S. aureus in the microfluidic device, several shear stresses were applied to evaluate the adhesion strength of the polymer films. S. aureus was found to have weaker adhesion strength on the C-40 surface than on the C-20 surface; numerous bacterial cells detached from the C-40 surface on application of identical shear stress. To mimic the presence of plasma protein, fibrinogen (Fg) was introduced into the device before performing the bacterial adhesion assay. The results showed that the adsorption of Fg promoted S. aureus adhesion and strong interactions under shear stress. However, the adhesion strength of S. aureus did not affect the Fg adsorption for both the C-20 and C-40 surfaces. Using the shear stress-tunable microfluidic device, we found that the adhesion of S. aureus on the thicker and softer phospholipid copolymer was weak, and the cells easily detached under high shear stress.


Assuntos
Antibacterianos/farmacologia , Aderência Bacteriana , Dispositivos Lab-On-A-Chip , Fosfolipídeos/química , Polímeros/química , Propriedades de Superfície
19.
iScience ; 24(12): 103517, 2021 Dec 17.
Artigo em Inglês | MEDLINE | ID: mdl-34934932

RESUMO

Molecular mechanisms mediating cardiac hypertrophy by glucose metabolism are incompletely understood. Hexosamine biosynthesis pathway (HBP), an accessory pathway of glycolysis, is known to be involved in the attachment of O-linked N-acetylglucosamine motif (O-GlcNAcylation) to proteins, a post-translational modification. We here demonstrate that glutamine-fructose-6-phosphate amidotransferase 2 (GFAT2), a critical HBP enzyme, is a major isoform of GFAT in the heart and is increased in response to several hypertrophic stimuli, including isoproterenol (ISO). Knockdown of GFAT2 suppresses ISO-induced cardiomyocyte hypertrophy, accompanied by suppression of Akt O-GlcNAcylation and activation. Knockdown of GFAT2 does not affect anti-hypertrophic effect by Akt inhibition. Administration of glucosamine, a substrate of HBP, induces protein O-GlcNAcylation, Akt activation, and cardiomyocyte hypertrophy. In mice, 6-diazo-5-oxo-L-norleucine, an inhibitor of GFAT, attenuates ISO-induced protein O-GlcNAcylation, Akt activation, and cardiac hypertrophy. Our results demonstrate that GFAT2 mediates cardiomyocyte hypertrophy by HBP-O-GlcNAcylation-Akt pathway and could be a critical therapeutic target of cardiac hypertrophy.

20.
ESC Heart Fail ; 7(3): 1145-1149, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32154667

RESUMO

Takotsubo syndrome (TTS), also referred to as stress cardiomyopathy, is characterized by transient left ventricular apical ballooning in the absence of obstructive coronary artery disease. Catecholamine-induced cardiac injury or vasospasm has been implicated in this pathophysiology. We present a case of a 67-year-old man 10 years after heart transplantation diagnosed with TTS. Sympathetic reinnervation could not be detected by iodine-123 meta iodobenzylguanidine uptake, suggesting that TTS can occur in the absence of functional sympathetic nerve systems reconstruction.


Assuntos
Transplante de Coração , Cardiomiopatia de Takotsubo , 3-Iodobenzilguanidina , Idoso , Coração , Transplante de Coração/efeitos adversos , Humanos , Masculino , Sistema Nervoso Simpático , Cardiomiopatia de Takotsubo/diagnóstico , Cardiomiopatia de Takotsubo/etiologia
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