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1.
Small ; 20(2): e2304555, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-37649204

RESUMEN

Toxic gases have surreptitiously influenced the health and environment of contemporary society with their odorless/colorless characteristics. As a result, a pressing need for reliable and portable gas-sensing devices has continuously increased. However, with their negligence to efficiently microstructure their bulky supportive layer on which the sensing and heating materials are located, previous semiconductor metal-oxide gas sensors have been unable to fully enhance their power efficiency, a critical factor in power-stringent portable devices. Herein, an ultrathin insulation layer with a unique serpentine architecture is proposed for the development of a power-efficient gas sensor, consuming only 2.3 mW with an operating temperature of 300 °C (≈6% of the leading commercial product). Utilizing a mechanically robust serpentine design, this work presents a fully suspended standalone device with a supportive layer thickness of only ≈50 nm. The developed gas sensor shows excellent mechanical durability, operating over 10 000 on/off cycles and ≈2 years of life expectancy under continuous operation. The gas sensor detected carbon monoxide concentrations from 30 to 1 ppm with an average response time of ≈15 s and distinguishable sensitivity to 1 ppm (ΔR/R0 = 5%). The mass-producible fabrication and heating efficiency presented here provide an exemplary platform for diverse power-efficient-related devices.

2.
Int J Mol Sci ; 25(11)2024 Jun 02.
Artículo en Inglés | MEDLINE | ID: mdl-38892335

RESUMEN

Regenerative medicine aims to address substantial defects by amplifying the body's natural regenerative abilities and preserving the health of tissues and organs. To achieve these goals, materials that can provide the spatial and biological support for cell proliferation and differentiation, as well as the micro-environment essential for the intended tissue, are needed. Scaffolds such as polymers and metallic materials provide three-dimensional structures for cells to attach to and grow in defects. These materials have limitations in terms of mechanical properties or biocompatibility. In contrast, biominerals are formed by living organisms through biomineralization, which also includes minerals created by replicating this process. Incorporating biominerals into conventional materials allows for enhanced strength, durability, and biocompatibility. Specifically, biominerals can improve the bond between the implant and tissue by mimicking the micro-environment. This enhances cell differentiation and tissue regeneration. Furthermore, biomineral composites have wound healing and antimicrobial properties, which can aid in wound repair. Additionally, biominerals can be engineered as drug carriers, which can efficiently deliver drugs to their intended targets, minimizing side effects and increasing therapeutic efficacy. This article examines the role of biominerals and their composite materials in regenerative medicine applications and discusses their properties, synthesis methods, and potential uses.


Asunto(s)
Materiales Biocompatibles , Medicina Regenerativa , Medicina Regenerativa/métodos , Humanos , Materiales Biocompatibles/química , Materiales Biocompatibles/farmacología , Animales , Andamios del Tejido/química , Ingeniería de Tejidos/métodos , Minerales/química , Biomineralización , Cicatrización de Heridas/efectos de los fármacos , Diferenciación Celular/efectos de los fármacos
3.
Crit Care ; 27(1): 442, 2023 11 15.
Artículo en Inglés | MEDLINE | ID: mdl-37968720

RESUMEN

BACKGROUND: Extracorporeal cardiopulmonary resuscitation (ECPR) has been proposed as a rescue therapy for patients with refractory cardiac arrest. This study aimed to evaluate the association between ECPR and clinical outcomes among patients with out-of-hospital cardiac arrest (OHCA) using risk-set matching with a time-dependent propensity score. METHODS: This was a secondary analysis of the JAAM-OHCA registry data, a nationwide multicenter prospective study of patients with OHCA, from June 2014 and December 2019, that included adults (≥ 18 years) with OHCA. Initial cardiac rhythm was classified as shockable and non-shockable. Patients who received ECPR were sequentially matched with the control, within the same time (minutes) based on time-dependent propensity scores calculated from potential confounders. The odds ratios with 95% confidence intervals (CI) for 30-day survival and 30-day favorable neurological outcomes were estimated for ECPR cases using a conditional logistic model. RESULTS: Of 57,754 patients in the JAAM-OHCA registry, we selected 1826 patients with an initial shockable rhythm (treated with ECPR, n = 913 and control, n = 913) and a cohort of 740 patients with an initial non-shockable rhythm (treated with ECPR, n = 370 and control, n = 370). In these matched cohorts, the odds ratio for 30-day survival in the ECPR group was 1.76 [95%CI 1.38-2.25] for shockable rhythm and 5.37 [95%CI 2.53-11.43] for non-shockable rhythm, compared to controls. For favorable neurological outcomes, the odds ratio in the ECPR group was 1.11 [95%CI 0.82-1.49] for shockable rhythm and 4.25 [95%CI 1.43-12.63] for non-shockable rhythm, compared to controls. CONCLUSION: ECPR was associated with increased 30-day survival in patients with OHCA with initial shockable and even non-shockable rhythms. Further research is warranted to investigate the reproducibility of the results and who is the best candidate for ECPR.


Asunto(s)
Reanimación Cardiopulmonar , Paro Cardíaco Extrahospitalario , Adulto , Humanos , Paro Cardíaco Extrahospitalario/terapia , Puntaje de Propensión , Estudios Prospectivos , Japón/epidemiología , Reproducibilidad de los Resultados , Reanimación Cardiopulmonar/métodos , Hospitales , Sistema de Registros , Estudios Retrospectivos
4.
Int J Mol Sci ; 24(22)2023 Nov 16.
Artículo en Inglés | MEDLINE | ID: mdl-38003614

RESUMEN

Antimicrobial peptides (AMPs) have emerged as a promising solution to tackle bacterial infections and combat antibiotic resistance. However, their vulnerability to protease degradation and toxicity towards mammalian cells has hindered their clinical application. To overcome these challenges, our study aims to develop a method to enhance the stability and safety of AMPs applicable to effective drug-device combination products. The KR12 antimicrobial peptide was chosen, and in order to further enhance its delivery and efficacy the human immunodeficiency virus TAT protein-derived cell-penetrating peptide (CPP) was fused to form CPP-KR12. A new product, CPP-KR12@Si, was developed by forming silica particles with self-entrapped CPP-KR12 peptide using biomimetic silica precipitability because of its cationic nature. Peptide delivery from CPP-KR12@Si to bacteria and cells was observed at a slightly delivered rate, with improved stability against trypsin treatment and a reduction in cytotoxicity compared to CPP-KR12. Finally, the antimicrobial potential of the CPP-KR12@Si/bone graft substitute (BGS) combination product was demonstrated. CPP-KR12 is coated in the form of submicron-sized particles on the surface of the BGS. Self-entrapped AMP in silica nanoparticles is a safe and effective AMP delivery method that will be useful for developing a drug-device combination product for tissue regeneration.


Asunto(s)
Antiinfecciosos , Péptidos de Penetración Celular , Animales , Humanos , Péptidos Antimicrobianos , Dióxido de Silicio/farmacología , Péptidos/farmacología , Antiinfecciosos/farmacología , Bacterias , Péptidos de Penetración Celular/farmacología , Mamíferos
5.
Vet Med (Praha) ; 68(6): 231-237, 2023 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-37982001

RESUMEN

Extracellular signal-regulated kinase (ERK) has been implicated in mammalian testicular and epididymal development. This study aimed to investigate ERK expression in the immature and mature testes and epididymides of bulls. We evaluated ERK expression using immunoblot analysis and immunohistochemistry. Immunoblot analysis revealed that immature bull testes and epididymides had higher phosphorylated ERK (pERK) expression than mature bull testes and epididymides. pERK immunoreactivity was higher in immature epididymides than in immature testes. pERK was localised mostly in spermatogonia, undifferentiated sustentacular (Sertoli) cells, and interstitial (Leydig) cells in immature testes, as well as in some spermatocytes and spermatids in mature testes. In immature epididymides, the body and tail had higher pERK expression than the head, whereas pERK was broadly distributed throughout the stereocilia, basal cells, and connective tissues. pERK distribution in the head of mature epididymides was similar to that in immature epididymides, whereas few connective tissue cells were expressed in the body and tail of mature epididymides. Collectively, these results suggest that ERK is expressed in the testis and epididymis of immature and mature bulls with varying intensities, and the role of ERK in male reproductive organs may include the specific function of its development.

6.
Heart Vessels ; 37(7): 1255-1264, 2022 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-35044522

RESUMEN

Dysnatremia is an electrolytic disorder commonly associated with mortality in various diseases. However, little is known about dysnatremia in out-of-hospital cardiac arrest (OHCA) cases. Here, we investigated the association between serum sodium level on hospital arrival and neurological outcomes after OHCA. This nationwide hospital-based observational study (The Japanese Association for Acute Medicine Out-of-Hospital Cardiac Arrest registry) enrolled patients with OHCA between 2014 and 2017. We included adult patients aged ≥ 18 years with non-traumatic OHCA who achieved return of spontaneous circulation (ROSC) and whose serum sodium level on hospital arrival was available. Based on the serum sodium level, patients were divided into three levels: hyponatremia (Na < 135 mEq/L), normal sodium level (Na ≥ 135 or ≤ 145 mEq/L), and hypernatremia (Na > 145 mEq/L). The primary outcome was 1-month survival with favourable neurological outcomes. Altogether, 34 754 patients with OHCA were documented, and 5160 patients with non-traumatic OHCA and who achieved ROSC were eligible for our analyses. The proportion of favourable neurological outcomes was highest in patients with normal sodium levels at 17.6% (677/3854), followed by patients with hyponatremia at 8.2% (57/696) and patients with hypernatremia at 5.7% (35/610). Moreover, hyponatremia and hypernatremia were associated with a decreased probability of favourable neurological outcomes compared with normal sodium level (vs. hyponatremia, adjusted odds ratio [AOR] 0.97, 95% confidence interval [CI] 0.95-0.99; vs. hypernatremia, AOR 0.96, 95% CI 0.94-0.98). Hypo- and hypernatremia on hospital arrival were associated with a decreased probability of favourable neurological outcomes in patients with non-traumatic OHCA who achieved ROSC.


Asunto(s)
Reanimación Cardiopulmonar , Hipernatremia , Hiponatremia , Paro Cardíaco Extrahospitalario , Adulto , Humanos , Hipernatremia/epidemiología , Hiponatremia/epidemiología , Japón/epidemiología , Paro Cardíaco Extrahospitalario/diagnóstico , Paro Cardíaco Extrahospitalario/terapia , Pronóstico , Sistema de Registros , Sodio
7.
BMC Emerg Med ; 22(1): 84, 2022 05 14.
Artículo en Inglés | MEDLINE | ID: mdl-35568800

RESUMEN

BACKGROUND: The association between spontaneous initial body temperature on hospital arrival and neurological outcomes has not been sufficiently studied in patients after out-of-hospital cardiac arrest (OHCA). METHODS: From the prospective database of the Comprehensive Registry of Intensive Care for OHCA Survival (CRITICAL) study in Osaka, Japan, we enrolled all patients with OHCA of medical origin aged > 18 years for whom resuscitation was attempted and who were transported to participating hospitals between 2012 and 2019. We excluded patients who were not witnessed by bystanders and treated by a doctor car or helicopter, which is a car/helicopter with a physician. The patients were categorized into three groups according to their temperature on hospital arrival: ≤35.9 °C, 36.0-36.9 °C (normothermia), and ≥ 37.0 °C. The primary outcome was 1-month survival, with a cerebral performance category of 1 or 2. Multivariable logistic regression analyses were performed to evaluate the association between temperature and outcomes (normothermia was used as the reference). We also assessed this association using cubic spline regression analysis. RESULTS: Of the 18,379 patients in our database, 5014 witnessed adult OHCA patients of medical origin from 16 hospitals were included. When analyzing 3318 patients, OHCA patients with an initial body temperature of ≥37.0 °C upon hospital arrival were associated with decreased favorable neurological outcomes (6.6% [19/286] odds ratio, 0.51; 95% confidence interval, 0.27-0.95) compared to patients with normothermia (16.4% [180/1100]), whereas those with an initial body temperature of ≤35.9 °C were not associated with decreased favorable neurological outcomes (11.1% [214/1932]; odds ratio, 0.78; 95% confidence interval, 0.56-1.07). The cubic regression splines demonstrated that a higher body temperature on arrival was associated with decreased favorable neurological outcomes, and a lower body temperature was not associated with decreased favorable neurological outcomes. CONCLUSIONS: In adult patients with OHCA of medical origin, a higher body temperature on arrival was associated with decreased favorable neurologic outcomes.


Asunto(s)
Reanimación Cardiopulmonar , Servicios Médicos de Urgencia , Paro Cardíaco Extrahospitalario , Adulto , Temperatura Corporal , Estudios de Cohortes , Hospitales , Humanos , Japón/epidemiología , Paro Cardíaco Extrahospitalario/terapia , Sistema de Registros
8.
Int J Mol Sci ; 23(23)2022 Nov 27.
Artículo en Inglés | MEDLINE | ID: mdl-36499161

RESUMEN

Experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis (MS), approximates the key histopathological, clinical, and immunological features of MS. Hippocampal dysfunction in MS and EAE causes varying degrees of cognitive and emotional impairments and synaptic abnormalities. However, the molecular alterations underlying hippocampal dysfunctions in MS and EAE are still under investigation. The purpose of this study was to identify differentially expressed genes (DEGs) in the hippocampus of mice with EAE in order to ascertain potential genes associated with hippocampal dysfunction. Gene expression in the hippocampus was analyzed by RNA-sequencing and validated by reverse transcription-quantitative polymerase chain reaction (RT-qPCR). Gene expression analysis revealed 1202 DEGs; 1023 were upregulated and 179 were downregulated in the hippocampus of mice with EAE (p-value < 0.05 and fold change >1.5). Gene ontology (GO) analysis showed that the upregulated genes in the hippocampi of mice with EAE were associated with immune system processes, defense responses, immune responses, and regulation of immune responses, whereas the downregulated genes were related to learning or memory, behavior, and nervous system processes in the GO biological process. The expressions of hub genes from the search tool for the retrieval of interacting genes/proteins (STRING) analysis were validated by RT-qPCR. Additionally, gene set enrichment analysis showed that the upregulated genes in the hippocampus were associated with inflammatory responses: interferon-γ responses, allograft rejection, interferon-α responses, IL6_JAK_STAT3 signaling, inflammatory responses, complement, IL2_STAT5 signaling, TNF-α signaling via NF-κB, and apoptosis, whereas the downregulated genes were related to synaptic plasticity, dendritic development, and development of dendritic spine. This study characterized the transcriptome pattern in the hippocampi of mice with EAE and signaling pathways underpinning hippocampal dysfunction. However, further investigation is needed to determine the applicability of these findings from this rodent model to patients with MS. Collectively, these results indicate directions for further research to understand the mechanisms behind hippocampal dysfunction in EAE.


Asunto(s)
Encefalomielitis Autoinmune Experimental , Esclerosis Múltiple , Animales , Ratones , Encefalomielitis Autoinmune Experimental/metabolismo , Ratones Endogámicos C57BL , Hipocampo/metabolismo , Perfilación de la Expresión Génica , Esclerosis Múltiple/metabolismo
9.
J Prosthet Dent ; 128(1): 79-88, 2022 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-33546857

RESUMEN

STATEMENT OF PROBLEM: The properties of dental computer-aided design and computer-aided manufacturing (CAD-CAM) materials vary. Studies regarding the effects of aging on the properties of these materials are lacking. PURPOSE: The purpose of this in vitro study was to evaluate the changes in the mechanical and surface properties of different CAD-CAM materials after thermocycling and mechanical loading. MATERIAL AND METHODS: In total, 150 bar-shaped specimens (17.0×4.0×2.0 mm) were prepared from feldspathic glass-ceramic (VM; Vitablocs Mark II), lithium disilicate glass-ceramic (EX; IPS e.max CAD), zirconia-reinforced lithium silicate glass-ceramic (CD; Celtra Duo), polymer-infiltrated ceramic network (VE; Vita Enamic), and resin-nanoceramic (CS; Cerasmart). Each type was divided into 2 groups (n=15; each). One group was subjected to thermocycling in distilled water at 5 °C to 55 °C for 6000 cycles and 50 N mechanical loading for 1.2×106 cycles. The other group was stored in 37 °C water for 24 hours. Nanoindentation hardness, Young modulus, and 3-point flexural strength were measured for the analyses of the mechanical properties. Surface roughness, surface microstructure, and elemental composition were measured to analyze the surface characteristics. Statistical analyses were performed with 1-way ANOVA with the Tukey HSD post hoc test, independent samples t test, Kruskal-Wallis test with Bonferroni post hoc test, Mann-Whitney U test, and 2-way ANOVA (α=.05). RESULTS: Before and after aging, CS exhibited the lowest hardness (1.20 to 1.04 GPa) and Young modulus (13.76 to 13.48 GPa) values (P<.05). EX exhibited the highest flexural strengths (393.43 to 391.86 MPa), and VM exhibited the lowest (109.98 to 112.73 MPa) values (P<.05). CS exhibited the highest surface roughness (Sa and Sq; 10.60 to 28.82, 14.21 to 38.27 nm) values (P<.05). After aging, the hardness and Young modulus of VM, EX, and VE decreased significantly (P<.001). No significant difference was observed in the flexural strengths of the CAD-CAM materials (P>.05). Significant increases were observed in the surface roughness of all the materials (P<.05), with altered microstructures. Except for the flexural strength, the mechanical properties and surface characteristics of the CAD-CAM materials were significantly affected by the material type after aging. CONCLUSIONS: Before and after aging, resin-nanoceramic exhibited the lowest hardness and Young modulus, and the highest surface roughness. Lithium disilicate glass-ceramic exhibited the highest flexural strength and feldspathic glass-ceramic exhibited the lowest value. After aging, increased surface roughness and microstructure alterations were observed. Significant interactions between aging process and material type were found for the mechanical properties and surface characteristics except for the flexural strength.


Asunto(s)
Cerámica , Porcelana Dental , Cerámica/química , Diseño Asistido por Computadora , Materiales Dentales/química , Resistencia Flexional , Dureza , Ensayo de Materiales , Propiedades de Superficie , Agua
10.
Exp Cell Res ; 389(2): 111897, 2020 04 15.
Artículo en Inglés | MEDLINE | ID: mdl-32035951

RESUMEN

Mucins are major macromolecular components of lung mucus that are mainly responsible for the viscoelastic property of mucus. MUC5AC is a major mucin glycoprotein that is hypersecreted in asthmatic individuals. Vascular endothelial growth factor (VEGF) has been implicated in inflammatory and airway blood vessel remodeling in asthmatics. Our previous studies indicate that VEGF upregulates MUC5AC expression by interacting with VEGF receptor 2 (VEGFR2). It has been shown that dexamethasone (Dex) downregulates MUC5AC expression; however, the underlying mechanisms have not been completely elucidated. Therefore, we sought to investigate the effect of Dex on MUC5AC expression induced by VEGF and study the underlying mechanisms. We tested the effects of Dex on VEGFR2 and RhoA activation, caveolin-1 expression, and the association of caveolin-1 and VEGFR2 in primary bronchial epithelial cells. Dex downregulated MUC5AC mRNA and protein levels in a dose- and time-dependent manner, and suppressed the activation of VEGFR2 and RhoA induced by VEGF. Additionally, Dex upregulated caveolin-1 protein levels in a dose- and time-dependent manner. Furthermore, phospho-VEGFR2 expression was decreased through overexpression of caveolin-1 and increased after caveolin-1 knockdown. Dex treatment attenuated the VEGF-decreased association of caveolin-1 and VEGFR2. Collectively, our findings suggest that Dex downregulates VEGF-induced MUC5AC expression by inactivating VEGFR2 and RhoA. Furthermore, decreased MUC5AC expression by Dex was related to the increased association of caveolin-1 with VEGFR2. Further studies characterizing these mechanisms are required to facilitate the development of improved treatment strategies for asthma.


Asunto(s)
Asma/patología , Bronquios/metabolismo , Dexametasona/farmacología , Células Epiteliales/metabolismo , Regulación de la Expresión Génica/efectos de los fármacos , Mucina 5AC/metabolismo , Factor A de Crecimiento Endotelial Vascular/metabolismo , Asma/metabolismo , Bronquios/citología , Bronquios/efectos de los fármacos , Caveolina 1/genética , Caveolina 1/metabolismo , Células Cultivadas , Células Epiteliales/citología , Células Epiteliales/efectos de los fármacos , Glucocorticoides/farmacología , Humanos , Mucina 5AC/genética , Factor A de Crecimiento Endotelial Vascular/genética , Receptor 2 de Factores de Crecimiento Endotelial Vascular/genética , Receptor 2 de Factores de Crecimiento Endotelial Vascular/metabolismo , Proteína de Unión al GTP rhoA/genética , Proteína de Unión al GTP rhoA/metabolismo
11.
Clin Lab ; 67(2)2021 Feb 01.
Artículo en Inglés | MEDLINE | ID: mdl-33616343

RESUMEN

BACKGROUND: The American Thyroid Association suggested selective performance of the thyroid function test (TFT) in pregnant women with risk factors such as age over 30 years. We evaluated the limited indication of TFT based on age by analyzing our institution's retrospective data about TFT in pregnant women. METHODS: We retrospectively analyzed the results of thyroid stimulating hormone (TSH) and free thyroxine (FT4) with the antithyroid autoantibody test using the Cobas 8000 e801 module (Roche Diagnostics, Mannheim, Germany) performed during the first trimester of pregnancy. Data were analyzed and compared between subjects younger or older than 30 years. RESULTS: The mean values of TSH and FT4 did not show any significant differences according to age. Also, the two groups had similar prevalence of overt/subclinical hypothyroidism. It was analyzed that over 20% of overt hypothyroidism could be missed by applying age-based screening. CONCLUSIONS: Selective screening according to age (> 30 years) can miss a considerable number of pregnant women with hypothyroidism. Considering the value of appropriate screening and treatment in pregnant women with hypothyroidism, universal screening is necessary rather than selective screening considering the age of pregnant women.


Asunto(s)
Complicaciones del Embarazo , Pruebas de Función de la Tiroides , Adulto , Asia , Femenino , Alemania , Humanos , Edad Materna , Embarazo , Complicaciones del Embarazo/diagnóstico , Complicaciones del Embarazo/epidemiología , Primer Trimestre del Embarazo , Valores de Referencia , Estudios Retrospectivos , Tirotropina , Tiroxina
12.
Lipids Health Dis ; 20(1): 111, 2021 Sep 20.
Artículo en Inglés | MEDLINE | ID: mdl-34544435

RESUMEN

BACKGROUND: Limited data are available for validation of low-density lipoprotein cholesterol (LDL) calculation (LDLcal) in the adult Korean population. The aim of this study was to develop and validate a new equation for LDLcal and to compare it with previous such equations in a Korean population. METHODS: A new equation for LDLcal was developed (LDLChoi). LDLChoi and 11 other previously published equations were applied and compared with directly measured LDL concentration (LDLdirect) in a development cohort (population 1), an independent validation cohort in the same laboratory (population 2), and the Korea National Health and Nutrition Examination Survey 2017 cohort (population 3). RESULTS: Among the 12 equations, the newly-developed equation (LDLChoi = total cholesterol - 0.87 x high-density lipoprotein cholesterol - 0.13 x triglycerides) had the highest intraclass correlation coefficient (ICC) and the lowest mean systemic difference and median absolute percentage error in populations 1 and 2 but not in population 3. Subgroup analysis showed good agreement between LDLChoi and LDLdirect (ICC > 0.75) in population 2, whose LDLdirect < 70 mg/dL. For samples with high triglycerides (> 400 mg/dL), equation accuracy varied. Categorization concordance according to the National Cholesterol Education Program Adult Treatment Panel III criteria with the other 11 equations were less than 80%; that of LDLChoi was 87.6 and 87.4% in populations 1 and 2, respectively. CONCLUSIONS: Accuracy of 12 equations for LDLcal varied by cohort and subgroup based on LDLdirect and triglycerides. A laboratory-specific equation for LDLcal and/or LDLdirect may be needed for accurate evaluation of LDL status.


Asunto(s)
HDL-Colesterol/sangre , LDL-Colesterol/sangre , Triglicéridos/sangre , Adulto , Femenino , Humanos , Análisis de Clases Latentes , Metabolismo de los Lípidos/fisiología , Masculino , Persona de Mediana Edad , Encuestas Nutricionales , República de Corea
13.
J Integr Neurosci ; 20(2): 307-320, 2021 Jun 30.
Artículo en Inglés | MEDLINE | ID: mdl-34258929

RESUMEN

We evaluated the practicability of using the rarely utilized C57BL/6N mouse as a Parkinson's disease model established via the acute MPTP/probenecid (MPTP/p) protocol. We confirmed dopaminergic degeneration in terms of decreased expression levels of tyrosine hydroxylase in the substantia nigra and striatum of MPTP/p-lesioned mice. In addition, acute MPTP/p-lesioned mice demonstrated initial motor dysfunctions followed by spontaneous recovery. Interestingly, these MPTP/p-lesioned mice exhibited anxiolytic and antidepressive behaviors upon recovery from these motor deficits. Additionally, increased expression of norepinephrine transporters in several brain regions, including the hippocampus, medial prefrontal cortex, and striatum, and an elevated rate of adult neurogenesis (in terms of increased numbers of doublecortin-positive neuroblasts) in the hippocampus were observed after recovery from motor dysfunctions. We suggest that the emotional alterations observed under these experimental conditions may be associated with enhanced adult neurogenesis, increased levels of norepinephrine transporters, and/or a possible interplay between these two factors. Consequently, this acute MPTP/p model adequately satisfies the criteria for the validity of a Parkinson's disease model regarding dopaminergic loss and motor impairment. However, the non-motor findings may offer novel evidence against the practicability of utilizing the acute MPTP/p-lesioned mice for modeling the emotional aberrations found in Parkinson's disease patients.


Asunto(s)
Conducta Animal/efectos de los fármacos , Dopaminérgicos/farmacología , Neurogénesis/efectos de los fármacos , Proteínas de Transporte de Noradrenalina a través de la Membrana Plasmática/efectos de los fármacos , Enfermedad de Parkinson Secundaria/inducido químicamente , Enfermedad de Parkinson Secundaria/fisiopatología , 1-Metil-4-fenil-1,2,3,6-Tetrahidropiridina/farmacología , Animales , Modelos Animales de Enfermedad , Masculino , Ratones Endogámicos C57BL
14.
Int J Mol Sci ; 22(10)2021 May 19.
Artículo en Inglés | MEDLINE | ID: mdl-34069373

RESUMEN

Despite liver cancer being the second-leading cause of cancer-related death worldwide, few systemic drugs have been approved. Sorafenib, the first FDA-approved systemic drug for unresectable hepatocellular carcinoma (HCC), is limited by resistance. However, the precise mechanisms underlying this phenomenon are unknown. Since fibrinogen-like 1 (FGL1) is involved in HCC progression and upregulated after anticancer therapy, we investigated its role in regulating sorafenib resistance in HCC. FGL1 expression was assessed in six HCC cell lines (HepG2, Huh7, Hep3B, SNU387, SNU449, and SNU475) using western blotting. Correlations between FGL1 expression and sorafenib resistance were examined by cell viability, colony formation, and flow cytometry assays. FGL1 was knocked-down to confirm its effects on sorafenib resistance. FGL1 expression was higher in HepG2, Huh7, and Hep3B cells than in SNU387, SNU449, and SNU475 cells; high FGL1-expressing HCC cells showed a lower IC50 and higher sensitivity to sorafenib. In Huh7 and Hep3B cells, FGL1 knockdown significantly increased colony formation by 61% (p = 0.0013) and 99% (p = 0.0002), respectively, compared to that in controls and abolished sorafenib-induced suppression of colony formation, possibly by modulating ERK and autophagy signals. Our findings demonstrate that sorafenib resistance mediated by FGL1 in HCC cells, suggesting FGL1 as a potential sorafenib-resistance biomarker and target for HCC therapy.


Asunto(s)
Carcinoma Hepatocelular/metabolismo , Resistencia a Antineoplásicos/fisiología , Fibrinógeno/metabolismo , Apoptosis/efectos de los fármacos , Autofagia/efectos de los fármacos , Biomarcadores de Tumor/metabolismo , Carcinoma Hepatocelular/genética , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Resistencia a Antineoplásicos/genética , Fibrinógeno/fisiología , Expresión Génica/efectos de los fármacos , Expresión Génica/genética , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Humanos , Concentración 50 Inhibidora , Neoplasias Hepáticas/metabolismo , Sistema de Señalización de MAP Quinasas/efectos de los fármacos , Niacinamida/farmacología , Compuestos de Fenilurea/uso terapéutico , Transducción de Señal/efectos de los fármacos , Sorafenib/metabolismo , Sorafenib/farmacología
15.
Int J Mol Sci ; 22(2)2021 Jan 12.
Artículo en Inglés | MEDLINE | ID: mdl-33445535

RESUMEN

This study aimed to investigate whether the Protaetia brevitarsis seulensis (PB)' water extract (PBWE) ameliorates trimethyltin (TMT)-induced seizures and hippocampal neurodegeneration. To investigate the potential neuroprotective effect of the PBWE in vitro, a lactate dehydrogenase (LDH) assay was conducted in TMT-treated primary cultures of mouse hippocampal neurons. In TMT-treated adult C57BL/6 mice, behavioral and histopathological changes were evaluated by seizure scoring and Fluoro-Jade C staining, respectively. In our in vitro assay, we observed that pretreating mice hippocampal neuron cultures with the PBWE reduced TMT-induced cytotoxicity, as indicated by the decreased LDH release. Furthermore, pretreatment with the PBWE alleviated seizures and hippocampal neurodegeneration in TMT-treated mice. The antioxidant activity of the PBWE increased in a dose-dependent manner; moreover, pretreatment with the PBWE mitigated the TMT-induced Nrf2 stimulation. In addition, six major compounds, including adenine, hypoxanthine, uridine, adenosine, inosine, and benzoic acid, were isolated from the PBWE, and among them, inosine and benzoic acid have been confirmed to have an essential antioxidative activity. In conclusion, the PBWE ameliorated TMT-induced toxicity in hippocampal neurons in both in vitro and in vivo assays, through a potential antioxidative effect. Our findings suggest that the PBWE may have pharmacotherapeutic potential in neurodegenerative diseases such as seizures or epilepsy.


Asunto(s)
Productos Biológicos/química , Productos Biológicos/farmacología , Escarabajos/química , Hipocampo/efectos de los fármacos , Fármacos Neuroprotectores/química , Fármacos Neuroprotectores/farmacología , Animales , Productos Biológicos/aislamiento & purificación , Biomarcadores , Cromatografía Líquida de Alta Presión , Escarabajos/anatomía & histología , Escarabajos/clasificación , Escarabajos/genética , Modelos Animales de Enfermedad , Técnica del Anticuerpo Fluorescente , Genes de Insecto , Pruebas Genéticas , Hipocampo/metabolismo , Hipocampo/patología , Degeneración Nerviosa/tratamiento farmacológico , Degeneración Nerviosa/etiología , Degeneración Nerviosa/metabolismo , Degeneración Nerviosa/patología , Neuronas/efectos de los fármacos , Neuronas/metabolismo , Fármacos Neuroprotectores/aislamiento & purificación , Estrés Oxidativo , Fenotipo , Convulsiones/tratamiento farmacológico , Convulsiones/etiología , Compuestos de Trimetilestaño/efectos adversos
16.
Int J Mol Sci ; 22(11)2021 Jun 05.
Artículo en Inglés | MEDLINE | ID: mdl-34198910

RESUMEN

Changes in structural and functional neuroplasticity have been implicated in various neurological disorders. Sterol regulatory element-binding protein (SREBP)-1c is a critical regulatory molecule of lipid homeostasis in the brain. Recently, our findings have shown the potential involvement of SREBP-1c deficiency in the alteration of novel modulatory molecules in the hippocampus and occurrence of schizophrenia-like behaviors in mice. However, the possible underlying mechanisms, related to neuronal plasticity in the hippocampus, are yet to be elucidated. In this study, we investigated the hippocampus-dependent memory function and neuronal architecture of hippocampal neurons in SREBP-1c knockout (KO) mice. During the passive avoidance test, SREBP-1c KO mice showed memory impairment. Based on Golgi staining, the dendritic complexity, length, and branch points were significantly decreased in the apical cornu ammonis (CA) 1, CA3, and dentate gyrus (DG) subregions of the hippocampi of SREBP-1c KO mice, compared with those of wild-type (WT) mice. Additionally, significant decreases in the dendritic diameters were detected in the CA3 and DG subregions, and spine density was also significantly decreased in the apical CA3 subregion of the hippocampi of KO mice, compared with that of WT mice. Alterations in the proportions of stubby and thin-shaped dendritic spines were observed in the apical subcompartments of CA1 and CA3 in the hippocampi of KO mice. Furthermore, the corresponding differential decreases in the levels of SREBP-1 expression in the hippocampal subregions (particularly, a significant decrease in the level in the CA3) were detected by immunofluorescence. This study suggests that the contributions of SREBP-1c to the structural plasticity of the mouse hippocampus may have underlain the behavioral alterations. These findings offer insights into the critical role of SREBP-1c in hippocampal functioning in mice.


Asunto(s)
Espinas Dendríticas/genética , Memoria/fisiología , Neuronas/metabolismo , Proteína 1 de Unión a los Elementos Reguladores de Esteroles/genética , Animales , Región CA1 Hipocampal/metabolismo , Región CA1 Hipocampal/fisiología , Espinas Dendríticas/patología , Regulación de la Expresión Génica/genética , Hipocampo/metabolismo , Hipocampo/patología , Humanos , Ratones , Ratones Noqueados , Plasticidad Neuronal/genética , Neuronas/patología , Proteína 1 de Unión a los Elementos Reguladores de Esteroles/deficiencia
17.
Int J Mol Sci ; 21(11)2020 Jun 10.
Artículo en Inglés | MEDLINE | ID: mdl-32531902

RESUMEN

Lipid homeostasis is an important component of brain function, and its disturbance causes several neurological disorders, such as Huntington's, Alzheimer's, and Parkinson's diseases as well as mood disorders. Sterol regulatory element-binding protein-1c (SREBP-1c) is a key modulatory molecule involved in lipid homeostasis in the central nervous system. However, little is known about the biological effects of SREBP-1c in the brain. Our previous study uncovered that mice deficient in SREBP-1c exhibit schizophrenia-like behaviors. To investigate whether there are novel molecular mechanisms involved in the neurological aberrations caused by SREBP-1c deficiency, we analyzed the transcriptomes of the hippocampus of SREBP-1c knockout (KO) mice and wild-type mice. We found seven differentially expressed genes (three up-regulated and four down-regulated genes) in the hippocampus of SREBP-1c KO mice. For further verification, we selected the three most significantly changed genes: glucagon-like peptide 2 receptors (GLP2R) involved in hippocampal neurogenesis and neuroplasticity as well as in cognitive impairments; necdin (NDN) which is related to neuronal death and neurodevelopmental disorders; and Erb-B2 receptor tyrosine kinase 4 (ERBB4) which is a receptor for schizophrenia-linked protein, neuregulin-1. The protein levels of GLP2R and NDN were considerably decreased, but the level of ERBB4 was significantly increased in the hippocampus of SREBP-1c KO mice. However, further confirmation is warranted to establish the translatability of these findings from this rodent model into human patients. We suggest that these data provide novel molecular evidence for the modulatory role of SREBP-1c in the mouse hippocampus.


Asunto(s)
Conducta Animal/fisiología , Hipocampo/fisiología , Proteína 1 de Unión a los Elementos Reguladores de Esteroles/genética , Animales , Diferenciación Celular/genética , Supervivencia Celular/genética , Perfilación de la Expresión Génica , Hipocampo/patología , Ratones Endogámicos C57BL , Ratones Noqueados , Mapas de Interacción de Proteínas/genética , Reacción en Cadena en Tiempo Real de la Polimerasa , Reproducibilidad de los Resultados , Esquizofrenia/genética , Transducción de Señal/genética , Proteína 1 de Unión a los Elementos Reguladores de Esteroles/metabolismo
18.
Respir Res ; 20(1): 282, 2019 Dec 12.
Artículo en Inglés | MEDLINE | ID: mdl-31831011

RESUMEN

BACKGROUND: Airway mucus hypersecretion is an important pathophysiological feature in asthma. Mucins are glycoproteins that are mainly responsible for the viscoelastic property of mucus, and MUC5AC is a major mucin glycoprotein that is overproduced in asthma. Vascular endothelial growth factor (VEGF) has been implicated in inflammatory and airway blood vessel remodeling in asthmatics. Therefore, we sought to investigate the effect of VEGF on MUC5AC expression and study the underlying mechanisms. METHODS: In order to elucidate the precise mechanism underlying the effect of VEGF on MUC5AC expression, we tested the effects of VEGF on RhoA activation and the association of caveolin-1 and VEGFR2 in Primary Bronchial Epithelial Cells. RESULTS: VEGF up-regulated MUC5AC mRNA and protein levels in a dose- and time-dependent manner, and activated RhoA. Additionally, VEGF-induced MUC5AC expression and RhoA activation were enhanced by disrupting caveolae with cholesterol depletion and reversed by cholesterol repletion, and inhibited by a selective VEGF receptor 2 (VEGFR2) inhibitor SU1498. Furthermore, phospho-VEGFR2 expression was decreased via overexpression of caveolin-1. VEGF treatment reduced the association of caveolin-1 and VEGFR2. CONCLUSION: Collectively, our findings suggest that VEGF up-regulates MUC5AC expression and RhoA activation by interaction with VEGFR2, and this phenomenon was related with the association of caveolin-1 and VEGFR2. Further studies on these mechanisms are needed to facilitate the development of treatments for asthma.


Asunto(s)
Asma/metabolismo , Bronquios/efectos de los fármacos , Células Epiteliales/efectos de los fármacos , Mucina 5AC/metabolismo , Factor A de Crecimiento Endotelial Vascular/farmacología , Asma/genética , Asma/fisiopatología , Bronquios/metabolismo , Bronquios/fisiopatología , Caveolina 1/genética , Caveolina 1/metabolismo , Células Cultivadas , Células Epiteliales/metabolismo , Humanos , Mucina 5AC/genética , Fosforilación , Regulación hacia Arriba , Receptor 2 de Factores de Crecimiento Endotelial Vascular/agonistas , Receptor 2 de Factores de Crecimiento Endotelial Vascular/genética , Receptor 2 de Factores de Crecimiento Endotelial Vascular/metabolismo , Proteína de Unión al GTP rhoA/genética , Proteína de Unión al GTP rhoA/metabolismo
19.
J Anesth ; 33(2): 238-249, 2019 04.
Artículo en Inglés | MEDLINE | ID: mdl-30617546

RESUMEN

PURPOSE: Procedural sedation and analgesia (PSA) is widely performed outside of the operating theater, often in emergency departments (EDs). The practice and safety of PSA in the ED in an aging society such as in Japan have not been well described. We aimed to characterize the practice pattern of PSA including indications, pharmacology and incidence of adverse events (AEs) in Japan. METHODS: We formed the Japanese Procedural Sedation and Analgesia Registry, a multicenter prospective observation registry of ED patients undergoing PSA. We included all patients who received PSA in the ED. PSA was defined as any systemic pharmacological intervention intended to facilitate a painful or uncomfortable procedure. The main variables in this study were patients' demographics, American Society of Anesthesiologists (ASA) physical status, indication of PSA, medication choices, and AEs. The primary outcome measure was overall AEs from PSA. RESULTS: We enrolled 332 patients in four EDs during the 12-month period. The median age was 67 years (IQR, 46-78). In terms of ASA physical status, 79 (23.8%), 172 (51.8%), and 81 (24.4%) patients were class 1, 2, 3 or higher, respectively. The most common indication was cardioversion (44.0%). The most common sedative used was thiopental (38.9%), followed by midazolam (34.0%) and propofol (19.6%). Among all patients, 72 (21.7%, 95% confidence interval, 17-26) patients experienced one or more AEs. The most common AE was hypoxia (9.9%), followed by apnea (7.2%) and hypotension (3.5%). All of the AEs were transient and no patient had a serious AE. CONCLUSION: In a multicenter prospective registry in Japan, PSA in the ED appears safe particularly since the patients who underwent PSA were older and had a higher risk profile compared to patients in previous studies in different countries.


Asunto(s)
Analgesia/métodos , Sedación Consciente/métodos , Servicio de Urgencia en Hospital , Hipnóticos y Sedantes/administración & dosificación , Anciano , Analgesia/efectos adversos , Anestesia/métodos , Cardioversión Eléctrica/estadística & datos numéricos , Femenino , Humanos , Japón , Masculino , Midazolam/uso terapéutico , Persona de Mediana Edad , Dolor/tratamiento farmacológico , Propofol/uso terapéutico , Tiopental/administración & dosificación
20.
Opt Express ; 26(22): 28634-28640, 2018 Oct 29.
Artículo en Inglés | MEDLINE | ID: mdl-30470036

RESUMEN

We investigated the effect of phosphor deposition methods on the correlated color temperature (CCT), luminous flux and thermal characteristics of packaged white light-emitting diodes (WLEDs) for use in mobile display products. For both the samples, the CCT decreased with increasing viewing angle. Phosphor sedimentation samples displayed much better angular color uniformity than phosphor dispersion samples. The phosphor sedimentation sample had higher luminous flux and luminous efficacy at 20 mA than the phosphor dispersion sample. The phosphor sedimentation sample displayed much better high-temperature/humidity (85 °C/85%) reliability and lower package temperatures compared with the phosphor dispersion sample.

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