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1.
Regul Toxicol Pharmacol ; : 105664, 2024 Jun 17.
Artigo em Inglês | MEDLINE | ID: mdl-38897446

RESUMO

Plasticizers are necessary for the usability of various products, including food contact materials. Exposure to plasticizers is most commonly made through the oral route. Several plasticizers have been reported to have adverse effects on humans and the environment. Thus, the present study aimed to determine the long-term toxicity and carcinogenicity of a novel plasticizer called bis(2-ethylhexyl) cyclohexane-1,4-dicarboxylate (Eco-DEHCH), which is an ecofriendly and biologically less harmful replacer. Groups of 50 male and 50 female Han Wistar rats were fed Eco-DEHCH at daily doses of 1,600, 5,000, or 16,000 ppm in their diet for at least 104 weeks. The rats were regularly monitored for mortality, clinical signs, body weight, food consumption, food efficiency, and perceivable mass. All animals were subjected to complete necropsy and histopathological examination. The results indicate that the rats well tolerated chronic exposure to Eco-DEHCH at highest daily doses of 16,000 ppm, with was equivalent to 805.1 mg/kg/day in males and 1,060.6 mg/kg/day in females and did not show signs of toxicity or carcinogenicity. In conclusion, Eco-DEHCH could be a safe and promising alternative plasticizer.

2.
Biomacromolecules ; 24(11): 5342-5352, 2023 11 13.
Artigo em Inglês | MEDLINE | ID: mdl-37734002

RESUMO

This study develops a novel drug delivery system using a hyaluronic acid (HA) hydrogel for controlled release of epidermal growth factor (EGF) to enhance skin wound healing. Conventional hydrogel-based methods suffer from a burst release and limited drug delivery times. To address this, we employ bioconjugation to introduce an acrylate group to EGF, enabling chemical bonding to the HA hydrogel matrix through thiol-ene cross-linking. This approach results in sustained-release delivery of EGF based on the degradation rate of the HA matrix, overcoming diffusion-based limitations. We confirm the introduction of the acrylate group using matrix-assisted laser desorption ionization-time-of-flight (MALDI-TOF) mass spectrometry. We evaluated the hydrogel morphology and rheological properties following binding of acrylate-conjugated EGF to the HA matrix. Assessment of the EGF release profile demonstrates delayed release compared to unconjugated EGF. We evaluate the impact on cells through cell proliferation and scratch assays, indicating the system's efficacy. In a rat wound healing model, the sustained release of EGF from the hydrogel system promotes appropriate tissue healing and restores it to a normal state. These findings suggest that this practical drug delivery system, involving the modification of growth factors or drugs to chemically bind healing factors to hydrogels, can achieve long-lasting effects.


Assuntos
Fator de Crescimento Epidérmico , Ácido Hialurônico , Ratos , Animais , Fator de Crescimento Epidérmico/farmacologia , Fator de Crescimento Epidérmico/química , Ácido Hialurônico/química , Hidrogéis/farmacologia , Hidrogéis/química , Preparações de Ação Retardada/farmacologia , Cicatrização , Acrilatos/farmacologia
3.
Sensors (Basel) ; 23(17)2023 Aug 24.
Artigo em Inglês | MEDLINE | ID: mdl-37687830

RESUMO

In this study, a combined convolutional neural network for the diagnosis of three benign skin tumors was designed, and its effectiveness was verified through quantitative and statistical analysis. To this end, 698 sonographic images were taken and diagnosed at the Department of Dermatology at Severance Hospital in Seoul, Korea, between 10 November 2017 and 17 January 2020. Through an empirical process, a convolutional neural network combining two structures, which consist of a residual structure and an attention-gated structure, was designed. Five-fold cross-validation was applied, and the train set for each fold was augmented by the Fast AutoAugment technique. As a result of training, for three benign skin tumors, an average accuracy of 95.87%, an average sensitivity of 90.10%, and an average specificity of 96.23% were derived. Also, through statistical analysis using a class activation map and physicians' findings, it was found that the judgment criteria of physicians and the trained combined convolutional neural network were similar. This study suggests that the model designed and trained in this study can be a diagnostic aid to assist physicians and enable more efficient and accurate diagnoses.


Assuntos
Aprendizado Profundo , Neoplasias Cutâneas , Humanos , Ultrassonografia , Hospitais , Julgamento , Neoplasias Cutâneas/diagnóstico por imagem
4.
J Med Syst ; 46(10): 68, 2022 Sep 14.
Artigo em Inglês | MEDLINE | ID: mdl-36100792

RESUMO

A prediction algorithm for hypoglycemic events is proposed using glucose levels and electrocardiogram (ECG) with support vector machine (SVM). We extracted the corrected QT interval and five heart rate variability parameters from the ECG, along with glucose level from a continuous glucose monitoring system (CGMS). This feature set is used as input to the SVM, and hypoglycemic events are predicted every 5 min using the trained SVM model for up to 30 min in advance. The proposed algorithm was developed and evaluated for nine Type-1 diabetes patients in the D1NAMO dataset. The prediction sensitivity, specificity, and accuracy values for the test set were 91.1%, 87.0%, and 89.0% (10 min before); 88.0%, 84.3%, and 86.2% (20 min before); 80.1%, 83.3%, and 81.7% (30 min before), respectively. These results show higher performance of the proposed method compared to previous studies and suggest the possibility of predicting hypoglycemia in advance.


Assuntos
Hipoglicemia , Máquina de Vetores de Suporte , Algoritmos , Glicemia , Automonitorização da Glicemia , Eletrocardiografia/métodos , Humanos , Hipoglicemia/diagnóstico , Hipoglicemiantes
5.
BMC Neurosci ; 22(1): 43, 2021 06 22.
Artigo em Inglês | MEDLINE | ID: mdl-34157971

RESUMO

BACKGROUND: Autism, a childhood behavioral disorder, belongs to a large suite of diseases, collectively referred to as autism spectrum disorders (ASD). Though multifactorial in etiology, approximately 10% of ASD are associated with atopic dermatitis (AD). Moreover, ASD prevalence increases further as AD severity worsens, though these disorders share no common causative mutations. We assessed here the link between these two disorders in the standard, valproic acid mouse model of ASD. In prior studies, there was no evidence of skin involvement, but we hypothesized that cutaneous involvement could be detected in experiments conducted in BALB/c mice. BALB/c is an albino, laboratory-bred strain of the house mouse and is among the most widely used inbred strains used in animal experimentation. METHODS: We performed our studies in valproic acid (VPA)-treated BALB/c hairless mice, a standard mouse model of ASD. Mid-trimester pregnant mice received a single intraperitoneal injection of either valproic acid sodium salt dissolved in saline or saline alone on embryonic day 12.5 and were housed individually until postnatal day 21. Only the brain and epidermis appeared to be affected, while other tissues remain unchanged. At various postnatal time points, brain, skin and blood samples were obtained for histology and for quantitation of tissue sphingolipid content and cytokine levels. RESULTS: AD-like changes in ceramide content occurred by day one postpartum in both VPA-treated mouse skin and brain. The temporal co-emergence of AD and ASD, and the AD phenotype-dependent increase in ASD prevalence correlated with early appearance of cytokine markers (i.e., interleukin [IL]-4, 5, and 13), as well as mast cells in skin and brain. The high levels of interferon (IFN)γ not only in skin, but also in brain likely account for a significant decline in esterified very-long-chain N-acyl fatty acids in brain ceramides, again mimicking known IFNγ-induced changes in AD. CONCLUSION: Baseline involvement of both AD and ASD could reflect concurrent neuro- and epidermal toxicity, possibly because both epidermis and neural tissues originate from the embryonic neuroectoderm. These studies illuminate the shared susceptibility of the brain and epidermis to a known neurotoxin, suggesting that the atopic diathesis could be extended to include ASD.


Assuntos
Transtorno Autístico/induzido quimicamente , Transtorno Autístico/metabolismo , Dermatite Atópica/induzido quimicamente , Dermatite Atópica/metabolismo , Fenótipo , Ácido Valproico/toxicidade , Animais , Anticonvulsivantes/toxicidade , Transtorno Autístico/genética , Dermatite Atópica/genética , Feminino , Mediadores da Inflamação/metabolismo , Aprendizagem em Labirinto/efeitos dos fármacos , Aprendizagem em Labirinto/fisiologia , Camundongos , Camundongos Endogâmicos BALB C , Gravidez , Efeitos Tardios da Exposição Pré-Natal/induzido quimicamente , Efeitos Tardios da Exposição Pré-Natal/genética , Efeitos Tardios da Exposição Pré-Natal/metabolismo
6.
Int J Mol Sci ; 22(22)2021 Nov 22.
Artigo em Inglês | MEDLINE | ID: mdl-34830464

RESUMO

The genus Fragaria encompass fruits with diverse colors influenced by the distribution and accumulation of anthocyanin. Particularly, the fruit colors of strawberries with different ploidy levels are determined by expression and natural variations in the vital structural and regulatory genes involved in the anthocyanin pathway. Among the regulatory genes, MYB10 transcription factor is crucial for the expression of structural genes in the anthocyanin pathway. In the present study, we performed a genome wide investigation of MYB10 in the diploid and octoploid Fragaria species. Further, we identified seven quantitative trait loci (QTLs) associated with fruit color in octoploid strawberry. In addition, we predicted 20 candidate genes primarily influencing the fruit color based on the QTL results and transcriptome analysis of fruit skin and flesh tissues of light pink, red, and dark red strawberries. Moreover, the computational and transcriptome analysis of MYB10 in octoploid strawberry suggests that the difference in fruit colors could be predominantly influenced by the expression of MYB10 from the F. iinumae subgenome. The outcomes of the present endeavor will provide a platform for the understanding and tailoring of anthocyanin pathway in strawberry for the production of fruits with aesthetic colors.


Assuntos
Fragaria/genética , Proteínas de Plantas/genética , Locos de Características Quantitativas/genética , Fatores de Transcrição/genética , Antocianinas/genética , Cor , Fragaria/crescimento & desenvolvimento , Frutas/genética , Frutas/crescimento & desenvolvimento , Perfilação da Expressão Gênica , Regulação da Expressão Gênica de Plantas/genética , Estudo de Associação Genômica Ampla , Poliploidia
7.
Int J Mol Sci ; 21(3)2020 Feb 03.
Artigo em Inglês | MEDLINE | ID: mdl-32028642

RESUMO

Human epidermis is positioned at the interface with the external environment, protecting our bodies against external challenges, including air pollutants. Emerging evidence suggests that diesel particulate extract (DPE), a major component of air pollution, leads to impairment of diverse cellular functions in keratinocytes (KC). In this study, we investigated the cellular mechanism underlying DPE-induced KC apoptosis. We first addressed cell death occurring in KC exposed to DPE, paralleled by increased activation of NADPH oxidases (NOXs) and subsequent ROS generation. Blockade of NOX activation with a specific inhibitor attenuated the expected DPE-induced KC apoptosis. In contrast, pre-treatment with a specific inhibitor of reactive oxygen species (ROS) generation did not reverse DPE/NOX-mediated increase in KC apoptosis. We next noted that NOX-mediated KC apoptosis is mainly attributable to neutral sphingomyelinase (SMase)-mediated stimulation of ceramides, which is a well-known pro-apoptotic lipid. Moreover, we found that inhibition of NOX activation significantly attenuated DPE-mediated increase in the ratio of ceramide to its key metabolite sphingosine-1-phosphate (S1P), an important determinant of cell fate. Together, these results suggest that activation of neutral SMase serves as a key downstream signal for the DPE/NOX activation-mediated alteration in ceramide and S1P productions, and subsequent KC apoptosis.


Assuntos
Apoptose , Óleos Combustíveis/toxicidade , Queratinócitos/patologia , NADPH Oxidases/metabolismo , Petróleo/toxicidade , Esfingomielina Fosfodiesterase/metabolismo , Ceramidas/metabolismo , Humanos , Queratinócitos/efeitos dos fármacos , Queratinócitos/metabolismo , Lisofosfolipídeos/metabolismo , NADPH Oxidases/genética , Oxirredução , Espécies Reativas de Oxigênio/metabolismo , Transdução de Sinais , Esfingomielina Fosfodiesterase/genética , Esfingosina/análogos & derivados , Esfingosina/metabolismo , Emissões de Veículos/toxicidade
8.
Int J Mol Sci ; 21(5)2020 Mar 02.
Artigo em Inglês | MEDLINE | ID: mdl-32131547

RESUMO

Tumor cell resistance to anti-cancer drugs is a major obstacle in tumor therapy. In this study, we investigated the mechanism of cordycepin-mediated resensitization to cisplatin in T24R2 cells, a T24-derived cell line. Treatment with cordycepin or cisplatin (2 µg/mL) alone failed to induce cell death in T24R2 cells, but combination treatment with these drugs significantly induced apoptosis through mitochondrial pathways, including depolarization of mitochondrial membranes, decrease in anti-apoptotic proteins Bcl-2, Bcl-xL, and Mcl-1, and increase in pro-apoptotic proteins Bak and Bax. High expression levels of MDR1 were the cause of cisplatin resistance in T24R2 cells, and cordycepin significantly reduced MDR1 expression through inhibition of MDR1 promoter activity. MDR1 promoter activity was dependent on transcription factor Ets-1 in T24R2 cells. Although correlation exists between MDR1 and Ets-1 expression in bladder cancer patients, active Ets-1, Thr38 phosphorylated form (pThr38), was critical to induce MDR1 expression. Cordycepin decreased pThr-38 Ets-1 levels and reduced MDR1 transcription, probably through its effects on PI3K signaling, inducing the resensitization of T24R2 cells to cisplatin. The results suggest that cordycepin effectively resensitizes cisplatin-resistant bladder cancer cells to cisplatin, thus serving as a potential strategy for treatment of cancer in patients with resistance to anti-cancer drugs.


Assuntos
Antineoplásicos/farmacologia , Cisplatino/farmacologia , Desoxiadenosinas/farmacologia , Resistencia a Medicamentos Antineoplásicos , Neoplasias da Bexiga Urinária/metabolismo , Subfamília B de Transportador de Cassetes de Ligação de ATP/genética , Subfamília B de Transportador de Cassetes de Ligação de ATP/metabolismo , Morte Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Interações Medicamentosas , Humanos , Proteína Proto-Oncogênica c-ets-1/metabolismo
9.
J Korean Med Sci ; 34(2): e22, 2019 Jan 14.
Artigo em Inglês | MEDLINE | ID: mdl-30636948

RESUMO

BACKGROUND: Several studies have been conducted regarding people with disabilities, however no studies have estimated the disease burden due to premature death. As such, we aimed to compare the years of life lost (YLLs) due to premature death between a population with disabilities and the total population of Korea. METHODS: To calculate the YLLs in people with disabilities, we combined disability registration data from the 2002-2011 Ministry of Health and Welfare of Korea and the causes of mortality data by Statistics Korea for 3,158,231 people. RESULTS: YLLs of people with disabilities were 517,337, which accounted for 23.4% of YLLs of the total population. YLLs per 100,000 people with disabilities were approximately 3.8 times higher than those in the total Korean population. Ischemic stroke was associated with the highest YLLs per 100,000 people, followed by ischemic heart disease, hemorrhagic, and other non-ischemic stroke, diabetes mellitus, and self-harm. Among individuals with physical disabilities, ischemic heart disease was associated with the highest YLLs. For intellectual disability, epilepsy contributed to the most YLLs. For individuals with mental disability, self-harm was the largest contributor to YLLs. CONCLUSION: The burden of disease was higher in the population with disabilities than that in the general population. Cardiovascular diseases and cancer had a higher burden of disease than did other diseases in the population with disabilities; thus, overall, non-communicable diseases have a higher burden of disease than communicable diseases or injuries in the population with disabilities than in the general population.


Assuntos
Pessoas com Deficiência , Carga Global da Doença , Mortalidade Prematura , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Causas de Morte , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Pessoa de Meia-Idade , Anos de Vida Ajustados por Qualidade de Vida , República da Coreia , Acidente Vascular Cerebral/mortalidade , Acidente Vascular Cerebral/patologia , Adulto Jovem
10.
J Korean Med Sci ; 34(Suppl 1): e80, 2019 Mar 26.
Artigo em Inglês | MEDLINE | ID: mdl-30923489

RESUMO

BACKGROUND: Disease burden can be represented by health-related parameters such as disability-adjusted life years and economic burden. Economic burden is an important index, as it estimates the maximum possible cost reduction if a disease is prevented. This study aimed to determine the economic burden of 238 diseases and 22 injuries in Korea in 2015. METHODS: Economic burden was estimated with a human resources approach from a social perspective, and direct and indirect costs were calculated from insurance claims data and a cause of death database. Direct costs were divided into medical costs (including hospital admission, outpatient visit, and medication use) and nonmedical costs (including transportation and caregiver costs). Indirect costs from lost productivity, either from the use of healthcare service or premature death, were analyzed. RESULTS: In 2015, the estimated economic burden was USD 133.7 billion (direct: USD 65.5 billion, indirect: USD 68.2 billion). The total cost of communicable diseases was USD 16.0 billion (11.9%); non-communicable diseases, USD 92.3 billion (69.1%); and injuries, USD 25.4 billion (19.0%). Self-harm had the highest costs (USD 8.3 billion), followed by low back pain (LBP, USD 6.6 billion). For men, self-harm had the highest cost (USD 7.1 billion), while LBP was the leading cost (USD 3.7 billion) for women. CONCLUSION: A high percentage of Korea's total socioeconomic disease burden is due to chronic diseases; however, unnoticed conditions such as infectious diseases, injuries, and LBP are high in certain age groups and differ by gender, emphasizing the need for targeted social interventions to manage and prevent disease risk factors.


Assuntos
Efeitos Psicossociais da Doença , Carga Global da Doença/economia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Causas de Morte , Criança , Pré-Escolar , Feminino , Carga Global da Doença/estatística & dados numéricos , Humanos , Lactente , Recém-Nascido , Masculino , Pessoa de Meia-Idade , República da Coreia , Adulto Jovem
11.
Liver Int ; 38(10): 1751-1759, 2018 10.
Artigo em Inglês | MEDLINE | ID: mdl-29377574

RESUMO

BACKGROUND: The serum alanine aminotransferase (ALT) level has been used to identify at-risk patients with chronic hepatitis B (CHB) who need antiviral therapy. However, the level associated with increased liver-related mortality requiring active treatment is still unclear. METHODS: We used a Health Examination Cohort of the National Health Insurance Service of Korea that included approximately 0.5 million individuals aged 40-79 years. In total, 12 486 patients with CHB and no other concurrent liver disease were enrolled, and patients' liver-related mortality, including that owing to liver cancer, was investigated over 9 years. RESULTS: The serum ALT level was correlated positively with liver-related mortality. The rates in men were 0.14, 0.17, 0.24, 0.57, 0.63 and 0.85 per 100 person-years (%) for serum ALT levels of <20, 20-29, 30-39, 40-49, 50-79 and ≥80 U/L, respectively, and the corresponding liver-related mortality rates in women were 0.03%, 0.09%, 0.12%, 0.63%, 0.65% and 0.32%. In patients with ALT levels of 40-79 U/L, the liver-related mortality rates were 0.60% in men and 0.64% in women, which were similar to the overall mortality rate of age- and sex-matched subjects without CHB (0.69%). The best cut-off values for liver-related mortality prediction were >34 U/L in men and >30 U/L in women. CONCLUSIONS: The liver-related mortality rate increased significantly, even in CHB patients with relatively low serum ALT levels. Careful monitoring or earlier antiviral therapy should be considered for patients aged >40 years with serum ALT levels above the upper limit of normal.


Assuntos
Alanina Transaminase/sangue , Hepatite B Crônica/sangue , Hepatite B Crônica/mortalidade , Adulto , Distribuição por Idade , Idoso , Estudos de Coortes , Feminino , Humanos , Fígado/patologia , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Modelos de Riscos Proporcionais , República da Coreia/epidemiologia , Distribuição por Sexo
13.
Can Vet J ; 56(6): 571-4, 2015 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-26028676

RESUMO

An 8-year-old American cocker spaniel dog was diagnosed with dilated cardiomyopathy. Four years earlier, the dog had been diagnosed with multicentric lymphoma and had received 4 cycles of multi-agent chemotherapy, including doxorubicin and epirubicin. The total cumulative dose of epirubicin was 168 mg/m(2). Dilated cardiomyopathy was considered a consequence of epirubicin toxicity.


Cardiomyopathie induite par l'anthracycline chez un chien traité à l'épirubicine. Un chien Épagneul cocker américain a été diagnostiqué avec une cardiomyopathie dilatée. Quatre années plus tôt, le chien avait été diagnostiqué avec un lymphome multicentrique et avait reçu 4 cycles de chimiothérapie multi-agents, y compris la doxorubicine et l'épirubicine. La dose cumulative totale d'épirubicine était de 168 mg/m2. La cardiomyopathie dilatée est considérée comme une conséquence de la toxicité de l'épirubicine.(Traduit par Isabelle Vallières).


Assuntos
Antibióticos Antineoplásicos/efeitos adversos , Cardiomiopatia Dilatada/veterinária , Doenças do Cão/induzido quimicamente , Epirubicina/efeitos adversos , Linfoma/veterinária , Animais , Antibióticos Antineoplásicos/uso terapêutico , Cardiomiopatia Dilatada/induzido quimicamente , Cães , Epirubicina/uso terapêutico , Insuficiência Cardíaca/veterinária , Linfoma/tratamento farmacológico , Masculino
14.
Environ Pollut ; 342: 123074, 2024 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-38048870

RESUMO

Chlorine (Cl)-containing chemicals, including hydrogen chloride, generated during thermal degradation of polyvinyl chloride (PVC) and corresponding mixture impede the chemical recycling of PVC-containing plastic wastes. While upgrading plastic-derived vapors, the presence of Cl-containing chemicals may deactivate the catalysts. Accordingly, herein, catalytic upgrading of pyrolysis vapor prepared from a mixture of PVC and polyolefins is performed using a fixed-bed reactor comprising zeolites. Among the H-forms of zeolites (namely, ZSM-5, Y, ß, and chabazite) used in this study, a higher yield of gas products composed of hydrocarbons with lower carbon numbers is obtained using H-ZSM-5, thus indicating further decomposition of the pyrolysis vapor to C1-C4 hydrocarbons on it. Although the formation of aromatic compounds is better on H-ZSM-5, product distributions can be adjusted by further modifying the acidic properties via the alteration of the Si/Al molar ratio, and maximum yields of C1-C4 compounds (60.8%) and olefins (64.7%) are achieved using a Si/Al molar ratio of 50. Additionally, metal ion exchange on H-ZSM-5 is conducted, and upgrading of PVC-containing waste-derived vapor to aromatic chemicals and small hydrocarbon molecules was successfully performed using Co-substituted H-ZSM-5. It reveals that the highest yield of gas products on 1.74 wt% cobalt (Co)-substituted H-ZSM-5 is acquired via the selection of an appropriate metal and metal ion concentration adjustment. Nevertheless, introduction of excess Co into the H-ZSM-5 surface decreases the cracking activity, thereby implying that highly distributed Co is required to achieve excellent cracking activity. The addition of Co also adjusted the acid types of H-ZSM-5, and more Lewis acid sites compared to Brønsted acid sites selectively produced olefins and naphthenes over paraffins and aromatics. The proposed approach can be a feasible process to produce valuable petroleum-replacing chemicals from Cl-containing mixed plastic wastes, contributing to the closed loops for upcycling plastic wastes.


Assuntos
Cloro , Zeolitas , Zeolitas/química , Hidrocarbonetos , Alcenos/química , Catálise
15.
Cell Rep ; 43(2): 113752, 2024 Feb 27.
Artigo em Inglês | MEDLINE | ID: mdl-38341852

RESUMO

We here demonstrate that SERTAD1 is an adaptor protein responsible for the regulation of lysine 63 (K63)-linked NLRP3 polyubiquitination by the Cullin1 E3 ubiquitin ligase upon inflammasome activation. SERTAD1 specifically binds to NLRP3 but not to other inflammasome sensors. This endogenous interaction increases after inflammasome activation, interfering with the interaction between NLRP3 and Cullin1. Interleukin (IL)-1ß and IL-18 secretion, as well as the cleavage of gasdermin D, are decreased in SERTAD1 knockout bone-marrow-derived macrophages, together with reduced formation of the NLRP3 inflammasome complex. Additionally, SERTAD1-deficient mice show attenuated severity of monosodium-uric-acid-induced peritonitis and experimental autoimmune encephalomyelitis. Analysis of public datasets indicates that expression of SERTAD1 mRNA is significantly increased in the patients of autoimmune diseases. Thus, our findings uncover a function of SERTAD1 that specifically reduces Cullin1-mediated NLRP3 polyubiquitination via direct binding to NLRP3, eventually acting as a crucial factor to regulate the initiation of NLRP3-mediated inflammasome activation.


Assuntos
Inflamassomos , Proteína 3 que Contém Domínio de Pirina da Família NLR , Animais , Humanos , Camundongos , Inflamassomos/metabolismo , Macrófagos/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Ubiquitina-Proteína Ligases/metabolismo , Ubiquitinação
16.
ACS Appl Mater Interfaces ; 16(22): 28379-28390, 2024 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-38771721

RESUMO

This study proposes a titanium silicide (TiSi2) recombination layer for perovskite/tunnel oxide passivated contact (TOPCon) 2-T tandem solar cells as an alternative to conventional transparent conductive oxide (TCO)-based recombination layers. TiSi2 was formed while TiO2 was made by oxidizing a Ti film deposited on the p+-Si layer. The reaction formation mechanism was proposed based on the diffusion theory supported by experimental results. The optical and electrical properties of the TiSi2 layer were optimized by controlling the initial Ti thicknesses (5-100 nm). With the initial Ti of 50 nm, the lowest reflectance and highly ohmic contact between the TiO2 and p+-Si layers with a contact resistivity of 161.48 mΩ·cm2 were obtained. In contrast, the TCO interlayer shows Schottky behavior with much higher contact resistivities. As the recombination layer of TiSi2 and the electron transport layer of TiO2 are formed simultaneously, the process steps become simpler. Finally, the MAPbI3/TOPCon tandem device yielded an efficiency of 16.23%, marking the first reported efficiency for a device including a silicide-based interlayer.

17.
Nat Commun ; 15(1): 5117, 2024 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-38879551

RESUMO

Hepatocellular carcinoma frequently recurs after surgery, necessitating personalized clinical approaches based on tumor avatar models. However, location-dependent oxygen concentrations resulting from the dual hepatic vascular supply drive the inherent heterogeneity of the tumor microenvironment, which presents challenges in developing an avatar model. In this study, tissue samples from 12 patients with hepatocellular carcinoma are cultured directly on a chip and separated based on preference of oxygen concentration. Establishing a dual gradient system with drug perfusion perpendicular to the oxygen gradient enables the simultaneous separation of cells and evaluation of drug responsiveness. The results are further cross-validated by implanting the chips into mice at various oxygen levels using a patient-derived xenograft model. Hepatocellular carcinoma cells exposed to hypoxia exhibit invasive and recurrent characteristics that mirror clinical outcomes. This chip provides valuable insights into treatment prognosis by identifying the dominant hepatocellular carcinoma type in each patient, potentially guiding personalized therapeutic interventions.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Oxigênio , Microambiente Tumoral , Carcinoma Hepatocelular/patologia , Carcinoma Hepatocelular/metabolismo , Humanos , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/metabolismo , Animais , Camundongos , Oxigênio/metabolismo , Linhagem Celular Tumoral , Masculino , Feminino , Ensaios Antitumorais Modelo de Xenoenxerto , Pessoa de Meia-Idade , Dispositivos Lab-On-A-Chip
18.
Nutrients ; 16(1)2023 Dec 21.
Artigo em Inglês | MEDLINE | ID: mdl-38201869

RESUMO

Vitamin D status is reportedly associated with risk factors for cardiovascular disease (CVD), although conflicting data have been generated. The healthy lifestyle score (HLS) was formulated as a primary approach toward preventing CVD; however, data on the association between the HLS and vitamin D status remain insufficient. This study aimed to investigate the associations of CVD risk factors and the HLS with serum 25-hydroxyvitamin D concentration in adults who participated in a national survey. HLS components, including body mass index, smoking status, alcohol consumption, physical activity, and dietary pattern, as well as other risk factors, including diabetes mellitus (DM), hypertension (HTN), and dyslipidemia (DL), were fitted in multiple linear regression models to determine their association with vitamin D status. DM, HTN, and DL were inversely associated whereas a balanced dietary pattern, alcohol consumption, and physical activity were positively associated with serum vitamin D concentration (p < 0.01). Furthermore, a strong association was observed between the total HLS and serum vitamin D concentration (p for trend <0.01); the regression coefficient estimate (95% confidence interval) for the highest score was 1.41 (0.65, 2.17) (p < 0.01) compared with that for the lowest. These findings suggest that CVD risk factors and the HLS may reflect vitamin D status.


Assuntos
Doenças Cardiovasculares , Hipertensão , Adulto , Humanos , Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/etiologia , Fatores de Risco , Vitamina D , Vitaminas , Fatores de Risco de Doenças Cardíacas
19.
Sci Rep ; 13(1): 11975, 2023 07 24.
Artigo em Inglês | MEDLINE | ID: mdl-37488184

RESUMO

Benign paroxysmal positional vertigo (BPPV), the most common vestibular disorder, is diagnosed by an examiner changing the posture of the examinee and inducing nystagmus. Among the diagnostic methods used to observe nystagmus, video-nystagmography has been widely used recently because it is non-invasive. A specialist with professional knowledge and training in vertigo diagnosis is needed to diagnose BPPV accurately, but the ratio of vertigo patients to specialists is too high, thus necessitating the need for automated diagnosis of BPPV. In this paper, a convolutional neural network-based nystagmus extraction system, ANyEye, optimized for video-nystagmography data is proposed. A pupil was segmented to track the exact pupil trajectory from real-world data obtained during field inspection. A deep convolutional neural network model was trained with the new video-nystagmography dataset for the pupil segmentation task, and a compensation algorithm was designed to correct pupil position. In addition, a slippage detection algorithm based on moving averages was designed to eliminate the motion artifacts induced by goggle slippage. ANyEye outperformed other eye-tracking methods including learning and non-learning-based algorithms with five-pixel error detection rate of 91.26%.


Assuntos
Inteligência Artificial , Nistagmo Patológico , Humanos , Técnicas de Diagnóstico Oftalmológico , Algoritmos , Redes Neurais de Computação , Vertigem Posicional Paroxística Benigna
20.
Materials (Basel) ; 16(3)2023 Jan 31.
Artigo em Inglês | MEDLINE | ID: mdl-36770225

RESUMO

Riboflavin (RF), which is also known as vitamin B2, is a water-soluble vitamin. RF is a nontoxic and biocompatible natural substance. It absorbs light (at wavelengths of 380 and 450 nm) in the presence of oxygen to form reactive singlet oxygen (1O2). The generated singlet oxygen acts as a photoinitiator to induce the oxidation of biomolecules, such as amino acids, proteins, and nucleotides, or to initiate chemical reactions, such as the thiol-ene reaction and crosslinking of tyramine and furfuryl groups. In this review, we focus on the chemical mechanism and utilization of the photochemistry of RF, such as protein crosslinking and hydrogel formation. Currently, the crosslinking method using RF as a photoinitiator is actively employed in ophthalmic clinics. However, a significant broadening is expected in its range of applications, such as in tissue engineering and drug delivery.

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