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2.
Acta Pharmacol Sin ; 2024 Aug 19.
Artigo em Inglês | MEDLINE | ID: mdl-39160244

RESUMO

Pulmonary fibrosis (PF) is a chronic, progressive and irreversible interstitial lung disease characterized by unremitting pulmonary myofibroblasts activation, extracellular matrix (ECM) deposition and inflammatory recruitment. PF has no curable medication yet. In this study we investigated the molecular pathogenesis and potential therapeutic targets of PF and discovered drug lead compounds for PF therapy. A murine PF model was established in mice by intratracheal instillation of bleomycin (BLM, 5 mg/kg). We showed that the protein level of pulmonary protein phosphatase magnesium-dependent 1A (PPM1A, also known as PP2Cα) was significantly downregulated in PF patients and BLM-induced PF mice. We demonstrated that TRIM47 promoted ubiquitination and decreased PPM1A protein in PF progression. By screening the lab in-house compound library, we discovered otilonium bromide (OB, clinically used for treating irritable bowel syndrome) as a PPM1A enzymatic activator with an EC50 value of 4.23 µM. Treatment with OB (2.5, 5 mg·kg-1·d-1, i.p., for 20 days) significantly ameliorated PF-like pathology in mice. We constructed PF mice with PPM1A-specific knockdown in the lung tissues, and determined that by targeting PPM1A, OB treatment suppressed ECM deposition through TGF-ß/SMAD3 pathway in fibroblasts, repressed inflammatory responses through NF-κB/NLRP3 pathway in alveolar epithelial cells, and blunted the crosstalk between inflammation in alveolar epithelial cells and ECM deposition in fibroblasts. Together, our results demonstrate that pulmonary PPM1A activation is a promising therapeutic strategy for PF and highlighted the potential of OB in the treatment of the disease.

3.
BMC Neurol ; 24(1): 254, 2024 Jul 24.
Artigo em Inglês | MEDLINE | ID: mdl-39048961

RESUMO

OBJECTIVE: The primary objective of this study was to explore the clinical characteristics of apoplectic intratumoral hemorrhage in gliomas and offer insights for improving the diagnosis and treatment of this disease. METHODS: We analyzed the clinical data of 35 patients with glioma and hemorrhage. There were eight cases of multiple cerebral lobe involvement, and 22 cases involved a single lobe. Twenty-one patients had a preoperative Glasgow Coma Scale (GCS) score of ≥ 9 and had a craniotomy with tumor resection and hematoma evacuation after undergoing preoperative preparation. A total of 14 patients with GCS < 9, including one with thalamic hemorrhage breaking into the ventricles and acute obstructive hydrocephalus, underwent craniotomy for tumor resection after external ventricular drainage (EVD). One patient had combined thrombocytopenia, which was surgically treated after platelet levels were normalized through transfusion. The remaining 12 patients received immediate intervention in the form of craniotomy hematoma evacuation and tumor resection. RESULTS: We performed subtotal resection on three tumors of thalamic origin and two tumors of corpus callosum origin, but we were able to successfully resect all the tumors in other locations that were gross total resection Pathology results showed that 71.43% of cases accounted for WHO-grade 4 tumors. Among the 21 patients with a GCS score of ≥ 9, two died perioperatively. Fourteen patients had a GCS score < 9, of which eight patients died perioperatively. CONCLUSIONS: Patients with a preoperative GCS score ≥ 9 who underwent subemergency surgery and received aggressive treatment showed a reasonable prognosis. We found their long-term outcomes to be correlated with the pathology findings. On the other hand, patients with a preoperative GCS score < 9 required emergency treatment and had a high perioperative mortality rate.


Assuntos
Neoplasias Encefálicas , Glioma , Humanos , Glioma/complicações , Glioma/cirurgia , Masculino , Feminino , Neoplasias Encefálicas/cirurgia , Neoplasias Encefálicas/complicações , Pessoa de Meia-Idade , Adulto , Idoso , Adulto Jovem , Adolescente , Hemorragia Cerebral/cirurgia , Hemorragia Cerebral/diagnóstico , Hemorragia Cerebral/complicações , Criança , Craniotomia/métodos , Escala de Coma de Glasgow , Estudos Retrospectivos , Resultado do Tratamento
4.
Int J Mol Sci ; 25(13)2024 Jun 24.
Artigo em Inglês | MEDLINE | ID: mdl-39000019

RESUMO

Isoscopoletin is a compound derived from various plants traditionally used for the treatment of skin diseases. However, there have been no reported therapeutic effects of isoscopoletin on atopic dermatitis (AD). AD is a chronic inflammatory skin disease, and commonly used treatments have side effects; thus, there is a need to identify potential natural candidate substances. In this study, we aimed to investigate whether isoscopoletin regulates the inflammatory mediators associated with AD in TNF-α/IFN-γ-treated HaCaT cells and PMA/ionomycin treated RBL-2H3 cells. We determined the influence of isoscopoletin on cell viability through an MTT assay and investigated the production of inflammatory mediators using ELISA and RT-qPCR. Moreover, we analyzed the transcription factors that regulate inflammatory mediators using Western blots and ICC. The results showed that isoscopoletin did not affect cell viability below 40 µM in either HaCaT or RBL-2H3 cells. Isoscopoletin suppressed the production of TARC/CCL17, MDC/CCL22, MCP-1/CCL2, IL-8/CXCL8, and IL-1ß in TNF-α/IFN-γ-treated HaCaT cells and IL-4 in PMA/ionomycin-treated RBL-2H3 cells. Furthermore, in TNF-α/IFN-γ-treated HaCaT cells, the phosphorylation of signaling pathways, including MAPK, NF-κB, STAT, and AKT/PKB, increased but was decreased by isoscopoletin. In PMA/ionomycin-treated RBL-2H3 cells, the activation of signaling pathways including PKC, MAPK, and AP-1 increased but was decreased by isoscopoletin. In summary, isoscopoletin reduced the production of inflammatory mediators by regulating upstream transcription factors in TNF-α/IFN-γ-treated HaCaT cells and PMA/ionomycin-treated RBL-2H3 cells. Therefore, we suggest that isoscopoletin has the potential for a therapeutic effect, particularly in skin inflammatory diseases such as AD, by targeting keratinocytes and basophils.


Assuntos
Basófilos , Sobrevivência Celular , Citocinas , Queratinócitos , Humanos , Queratinócitos/efeitos dos fármacos , Queratinócitos/metabolismo , Citocinas/metabolismo , Basófilos/efeitos dos fármacos , Basófilos/metabolismo , Sobrevivência Celular/efeitos dos fármacos , Células HaCaT , Linhagem Celular , Fator de Necrose Tumoral alfa/metabolismo , Interferon gama/farmacologia , Interferon gama/metabolismo , Transdução de Sinais/efeitos dos fármacos , Regulação da Expressão Gênica/efeitos dos fármacos , Dermatite Atópica/tratamento farmacológico , Dermatite Atópica/metabolismo
5.
Antioxidants (Basel) ; 13(5)2024 Apr 26.
Artigo em Inglês | MEDLINE | ID: mdl-38790637

RESUMO

Apart from being utilized as a commercial fiber at maturity, kenaf shoots have potential as a food and feed source because of their diverse bioactivities. Previous studies have focused on mature stems because of their high biomass, whereas the antioxidant activities (AA) and the destination of AA contributors of kenaf stems and their high-yielding byproduct leaves during the growth stage have rarely been studied. Therefore, we investigated changes in AA and its relative components in kenaf leaves and stems during the four vital growth stages. Higher ABTS radical cation and DPPH radical scavenging abilities and ferric reducing antioxidant power, total phenolic content, total flavonoid content, and total polysaccharide content were observed at all leaf stages and in the late stem stages. Chlorogenic acid (CGA) and kaempferol glycosides, especially kaempferitrin (Kfr), were identified as representative phenolic acids and flavonoids in both kenaf leaves and stems. The content of CGA in both leaves and stems increased corresponding to the plant's growth stage, whereas kaempferol glycosides were enhanced in leaves but declined in stems. The highest correlation was observed between TPC and AA in all organs. Further evaluation of CGA and Kfr verified that CGA was the predominant contributor to AA, surpassing Kfr. These findings suggest that kenaf leaves increase antioxidant levels as they grow and can be a useful source of stem harvesting byproducts.

7.
Sci Rep ; 14(1): 5251, 2024 03 04.
Artigo em Inglês | MEDLINE | ID: mdl-38438402

RESUMO

Congenital and infantile (CI) cataract is one of the most important and preventable cause of blindness in children, but the incidence has not been studied in Korea. We collected data from the national claims database of the National Health Insurance Service of Korea from 2002 through 2019. We identified children who underwent cataract surgery within the age of 5 years, and cumulative incidence rates were calculated for each of the three age criteria. 989 patients out of 4,221,459 births underwent surgery with CI cataract during the period. The cumulative incidence rates per 10,000 births were 1.60 (0-1 years), 2.38 (0-3 years), and 2.95 (0-5 years), respectively. The incidence peaked in the 2007 birth cohort, which coincides with the start of the national screening program for infants/children. Primary intraocular lens implantation was performed in 439 patients (44%). Strabismus and glaucoma requiring surgery occurred in 291 patients (29.4%) and 32 patients (3.2%), respectively, within 8 years after cataract surgery. The incidence rates of CI cataract in Korea appear to be comparable to previous studies in other regions. The early screening program for infants may reduce delayed diagnosis and increase the proportion of patients undergoing surgery at a critical time for visual development.


Assuntos
Extração de Catarata , Catarata , Oftalmologia , Criança , Lactente , Humanos , Pré-Escolar , Incidência , Catarata/epidemiologia , República da Coreia/epidemiologia
8.
Stud Health Technol Inform ; 310: 48-52, 2024 Jan 25.
Artigo em Inglês | MEDLINE | ID: mdl-38269763

RESUMO

Observational Medical Outcome Partners - Common Data Model (OMOP-CDM) is an international standard model for standardizing electronic medical record data. However, unstructured data such as medical image data which is beyond the scope of standardization by the current OMOP-CDM is difficult to be used in multi-institutional collaborative research. Therefore, we developed the Radiology-CDM (R-CDM) which standardizes medical imaging data. As a proof of concept, 737,500 Optical Coherence Tomography (OCT) data from two tertiary hospitals in South Korea is standardized in the form of R-CDM. The relationship between chronic disease and retinal thickness was analyzed by using the R-CDM. Central macular thickness and retinal nerve fiber layer (RNFL) thickness were significantly thinner in the patients with hypertension compared to the control cohort. It is meaningful in that multi-institutional collaborative research using medical image data and clinical data simultaneously can be conducted very efficiently.


Assuntos
Face , Radiologia , Humanos , Radiografia , Retina/diagnóstico por imagem , Registros Eletrônicos de Saúde
9.
JMIR Public Health Surveill ; 9: e49852, 2023 Dec 08.
Artigo em Inglês | MEDLINE | ID: mdl-38064251

RESUMO

BACKGROUND: Exudative age-related macular degeneration (AMD), one of the leading causes of blindness, requires expensive drugs such as anti-vascular endothelial growth factor (VEGF) agents. The long-term regular use of effective but expensive drugs causes an economic burden for patients with exudative AMD. However, there are no studies on the long-term patient-centered economic burden of exudative AMD after reimbursement of anti-VEGFs. OBJECTIVE: This study aimed to evaluate the patient-centered economic burden of exudative AMD for 2 years, including nonreimbursement and out-of-pocket costs, compared with nonexudative AMD using the Observational Medical Outcomes Partnership (OMOP) Common Data Model (CDM). METHODS: This retrospective cohort study was conducted using the OMOP CDM, which included 2,006,478 patients who visited Seoul National University Bundang Hospital from June 2003 to July 2019. We defined the exudative AMD group as patients aged >50 years with a diagnosis of exudative AMD and a prescription for anti-VEGFs or verteporfin. The control group was defined as patients aged >50 years without a diagnosis of exudative AMD or a prescription for anti-VEGFs or verteporfin. To adjust for selection bias, controls were matched by propensity scores using regularized logistic regression with a Laplace prior. We measured any medical cost occurring in the hospital as the economic burden of exudative AMD during a 2-year follow-up period using 4 categories: total medical cost, reimbursement cost, nonreimbursement cost, and out-of-pocket cost. To estimate the average cost by adjusting the confounding variable and overcoming the positive skewness of costs, we used an exponential conditional model with a generalized linear model. RESULTS: We identified 931 patients with exudative AMD and matched 783 (84.1%) with 2918 patients with nonexudative AMD. In the exponential conditional model, the total medical, reimbursement, nonreimbursement, and out-of-pocket incremental costs were estimated at US $3426, US $3130, US $366, and US $561, respectively, in the first year and US $1829, US $1461, US $373, and US $507, respectively, in the second year. All incremental costs in the exudative AMD group were 1.89 to 4.25 and 3.50 to 5.09 times higher in the first and second year, respectively, than those in the control group (P<.001 in all cases). CONCLUSIONS: Exudative AMD had a significantly greater economic impact (P<.001) for 2 years on reimbursement, nonreimbursement, and out-of-pocket costs than nonexudative AMD after adjusting for baseline demographic and clinical characteristics using the OMOP CDM. Although economic policies could relieve the economic burden of patients with exudative AMD over time, the out-of-pocket cost of exudative AMD was still higher than that of nonexudative AMD for 2 years. Our findings support the need for expanding reimbursement strategies for patients with exudative AMD given the significant economic burden faced by patients with incurable and fatal diseases both in South Korea and worldwide.


Assuntos
Estresse Financeiro , Degeneração Macular , Humanos , Degeneração Macular/epidemiologia , Degeneração Macular/diagnóstico , Assistência Centrada no Paciente , Estudos Retrospectivos , Verteporfina , Pessoa de Meia-Idade
10.
Heliyon ; 9(12): e22932, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38125474

RESUMO

Hyperproduction of immune cell-derived inflammatory molecules and recruitment of immune cells promote the development of allergic asthma (AA). Aromadendrin (ARO) has various biological properties including anti-inflammatory effects. In this study, we evaluated the ameliorative effects of ARO on the development of AA in vitro and in vivo. Phorbol 12-myristate 13-acetate (PMA, 100 nM) was used to induce inflammation in A549 airway epithelial cells. The cohesion of A549 and eosinophil EOL-1 cells was studied. Ovalbumin (30 or 60 µg)/Alum (3 mg) mixture was adapted for AA induction in mice. ARO (5 or 10 mg/kg, p. o.) was administered to mice to investigate its ameliorative effect on AA development. Enzyme-linked immunosorbent assay, western blotting, and hematoxylin and eosin/periodic acid Schiff staining were performed to study the ameliorative effect of ARO on bronchial inflammation. In PMA-stimulated A549 cells, the upregulation of cytokines (interleukin [IL]-1ß/IL-6/tumor necrosis factor alpha [TNF-α]/monocyte chemoattractant protein [MCP]-1]) and nuclear factor kappa B (NF-κB) activation was effectively reduced by ARO pretreatment. ARO suppressed the adhesion of A549 cells and eosinophils. In ovalbumin-induced AA mice, the levels of cells, such as eosinophils, Th2 cytokines, MCP-1 in bronchoalveolar lavage fluid, IgE in serum, and inducible nitric oxide synthase/cyclooxygenase-2 expression in the lung tissue were upregulated, which were all suppressed by ARO. In addition, the increase in cell inflow and mucus formation in the lungs of AA mice was reversed by ARO as per histological analysis. ARO also modulated NF-κB activation in the lungs of AA mice. Overall, the anti-inflammatory properties of ARO in vitro/in vivo studies of AA were notable. Thus, ARO has a modulatory effect on bronchial inflammation and may be a potential adjuvant for AA treatment.

11.
Animals (Basel) ; 13(22)2023 Nov 13.
Artigo em Inglês | MEDLINE | ID: mdl-38003116

RESUMO

The COVID-19 pandemic is caused by the zoonotic SARS-CoV-2 virus. A wide range of animals that interact with humans have been investigated to identify potential infections. As the extent of infection became more apparent, extensive animal monitoring became necessary to assess their susceptibility. This study analyzed nasal swabs and blood samples collected from randomly selected Korean native cattle and Korean native black goats. The tests conducted included real-time qPCR to detect SARS-CoV-2 antigens, an ELISA to detect antibodies, and a plaque reduction neutralization test (PRNT) to determine the presence of neutralizing antibodies. Among the 1798 animals tested (consisting of 1174 Korean native cattle and 624 Korean native black goats), SARS-CoV-2 viral RNA was detected in one Korean native cattle and one Korean native black goat. ELISA testing revealed positive results for antibodies in 54 Korean native cattle (4.60%) and 16 Korean native black goats (2.56%), while PRNTs yielded positive results in 51 Korean native cattle (4.34%) and 14 Korean native black goats (2.24%). The presence of SARS-CoV-2 antigens and/or antibodies was identified in animals on farms where farmworkers were already infected. It is challenging to completely rule out the possibility of reverse zoonotic transmission from humans to livestock in Korea, although the transmission is not to the same extent as it is in highly susceptible animal species like minks, cats, and dogs. This is due to the limited geographical area and the dense, intensive farming practices implemented in these regions. In conclusion, continuous viral circulation between humans and animals is inevitable, necessitating ongoing animal monitoring to ensure public health and safety.

12.
Chemosphere ; 343: 140198, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37717916

RESUMO

Regular water quality monitoring is becoming desirable due to the increase in water pollution caused by both climate change and the generation of industrial chemicals. Unmanned vehicles have emerged as key technologies for remote data acquisition, providing fast and accurate methods for water quality monitoring. However, current research on unmanned vehicles has not systematically examined their features and limitations, which are crucial for identifying future research directions and applications of unmanned vehicle technologies. Therefore, this study extensively reviews the advancements in remote data acquisition and processing using unmanned vehicle technologies for water quality monitoring to provide valuable insights for future research. First, the types of unmanned vehicles and their application ranges for water quality monitoring are summarized. Among the unmanned vehicle technologies, unmanned aerial vehicles are considered primary platforms for water quality monitoring due to their wide data acquisition range and their ability to accommodate diverse sensors and samplers. Also, the types of samplers and sensors mounted on the unmanned vehicles are analyzed based on their characteristics. It is concluded that spectral sensors offer the most cost-effective approach for acquiring real-time water quality data. Furthermore, algorithms that convert image data into water quality data are examined, focusing on data preprocessing, analysis, and validation. The findings reveal a close relationship between the analysis of spectral characteristics of each water quality parameter and the wavelength ranges of red and red-edge. Lastly, future research directions for unmanned vehicle technologies are further suggested based on the summarized technological limitations.

13.
J Korean Med Sci ; 38(23): e174, 2023 Jun 12.
Artigo em Inglês | MEDLINE | ID: mdl-37309694

RESUMO

BACKGROUND: A paucity of data addressing real-world treatment of myopic choroidal neovascularization (mCNV) in the era of anti-vascular endothelial growth factor (VEGF) drugs led us to investigate real-world treatment intensity and treatment patterns in patients with mCNV. METHODS: This is a retrospective, observational study using the Observational Medical Outcomes Partnership-Common Data Model database of treatment-naïve patients with mCNV over the 18-year study period (2003-2020). Outcomes were treatment intensity (time trends of total/average number of prescriptions, mean number of prescriptions in the first year and the second year after initiating treatment, proportion of patients with no treatment in the second year) and treatment patterns (subsequent patterns of treatment according to the initial treatment). RESULTS: Our final cohort included 94 patients with at-least 1-year observation period. Overall, 96.8% of patients received anti-VEGF drugs as first-line treatment, with most of injections from bevacizumab. The number of anti-VEGF injections in each calendar year showed an increasing trend over time; however, there was a drop in the mean number of injections in the second year compared to the first year from 2.09 to 0.47. About 77% of patients did not receive any treatment in their second year of treatment regardless of drugs. Most of patients (86.2%) followed non-switching monotherapy only and bevacizumab was the most popular choice either in the first-line (68.1%) or in the second-line (53.8%) of treatment. Aflibercept was increasingly used as the first-line treatment for patients with mCNV. CONCLUSION: Anti-VEGF drugs have become the treatment of choice and second-line treatment for mCNV over the past decade. Anti-VEGF drugs are effective for the treatment of mCNV as the non-switching monotherapy is the main treatment regimen in most cases and the number of treatments decreases significantly in the second year of treatment.


Assuntos
Oftalmologia , Humanos , Bevacizumab , Bases de Dados Factuais , Pacientes
14.
Vet Sci ; 10(5)2023 May 18.
Artigo em Inglês | MEDLINE | ID: mdl-37235443

RESUMO

The factors that influence the pathogenicity of African swine fever (ASF) are still poorly understood, and the host's immune response has been indicated as crucial. Although an increasing number of studies have shown that gut microbiota can control the progression of diseases caused by viral infections, it has not been characterized how the ASF virus (ASFV) changes a pig's gut microbiome. This study analyzed the dynamic changes in the intestinal microbiome of pigs experimentally infected with the high-virulence ASFV genotype II strain (N = 4) or mock strain (N = 3). Daily fecal samples were collected from the pigs and distributed into the four phases (before infection, primary phase, clinical phase, and terminal phase) of ASF based on the individual clinical features of the pigs. The total DNA was extracted and the V4 region of the 16 s rRNA gene was amplified and sequenced on the Illumina platform. Richness indices (ACE and Chao1) were significantly decreased in the terminal phase of ASF infection. The relative abundances of short-chain-fatty-acids-producing bacteria, such as Ruminococcaceae, Roseburia, and Blautia, were decreased during ASFV infection. On the other hand, the abundance of Proteobacteria and Spirochaetes increased. Furthermore, predicted functional analysis using PICRUSt resulted in a significantly reduced abundance of 15 immune-related pathways in the ASFV-infected pigs. This study provides evidence for further understanding the ASFV-pig interaction and suggests that changes in gut microbiome composition during ASFV infection may be associated with the status of immunosuppression.

15.
Front Neurosci ; 17: 1059965, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36816131

RESUMO

Mitochondrial networks are defined as a continuous matrix lumen, but the morphological feature of neuronal mitochondrial networks is not clear due to the lack of suitable analysis techniques. The aim of the present study is to develop a framework to capture and analyze the neuronal mitochondrial networks by using 4-step process composed of 2D and 3D observation, primary and secondary virtual reality (VR) analysis, with the help of artificial intelligence (AI)-powered Aivia segmentation an classifiers. In order to fulfill this purpose, we first generated the PCs-Mito-GFP mice, in which green fluorescence protein (GFP) could be expressed on the outer mitochondrial membrane specifically on the cerebellar Purkinje cells (PCs), thus all mitochondria in the giant neuronal soma, complex dendritic arborization trees and long projection axons of Purkinje cells could be easily detected under a laser scanning confocal microscope. The 4-step process resolved the complicated neuronal mitochondrial networks into discrete neuronal mitochondrial meshes. Second, we measured the two parameters of the neuronal mitochondrial meshes, and the results showed that the surface area (µm2) of mitochondrial meshes was the biggest in dendritic trees (45.30 ± 53.21), the smallest in granular-like axons (3.99 ± 1.82), and moderate in soma (27.81 ± 22.22) and silk-like axons (17.50 ± 15.19). These values showed statistically different among different subcellular locations. The volume (µm3) of mitochondrial meshes was the biggest in dendritic trees (9.97 ± 12.34), the smallest in granular-like axons (0.43 ± 0.25), and moderate in soma (6.26 ± 6.46) and silk-like axons (3.52 ± 4.29). These values showed significantly different among different subcellular locations. Finally, we found both the surface area and the volume of mitochondrial meshes in dendritic trees and soma within the Purkinje cells in PCs-Mito-GFP mice after receiving the training with the simulating long-term pilot flight concentrating increased significantly. The precise reconstruction of neuronal mitochondrial networks is extremely laborious, the present 4-step workflow powered by artificial intelligence and virtual reality reconstruction could successfully address these challenges.

16.
Nat Commun ; 14(1): 828, 2023 02 14.
Artigo em Inglês | MEDLINE | ID: mdl-36788244

RESUMO

Vitamin K is a vital micronutrient implicated in a variety of human diseases. Warfarin, a vitamin K antagonist, is the most commonly prescribed oral anticoagulant. Patients overdosed on warfarin can be rescued by administering high doses of vitamin K because of the existence of a warfarin-resistant vitamin K reductase. Despite the functional discovery of vitamin K reductase over eight decades ago, its identity remained elusive. Here, we report the identification of warfarin-resistant vitamin K reductase using a genome-wide CRISPR-Cas9 knockout screen with a vitamin K-dependent apoptotic reporter cell line. We find that ferroptosis suppressor protein 1 (FSP1), a ubiquinone oxidoreductase, is the enzyme responsible for vitamin K reduction in a warfarin-resistant manner, consistent with a recent discovery by Mishima et al. FSP1 inhibitor that inhibited ubiquinone reduction and thus triggered cancer cell ferroptosis, displays strong inhibition of vitamin K-dependent carboxylation. Intriguingly, dihydroorotate dehydrogenase, another ubiquinone-associated ferroptosis suppressor protein parallel to the function of FSP1, does not support vitamin K-dependent carboxylation. These findings provide new insights into selectively controlling the physiological and pathological processes involving electron transfers mediated by vitamin K and ubiquinone.


Assuntos
Proteínas Reguladoras de Apoptose , NAD(P)H Desidrogenase (Quinona) , Varfarina , Humanos , Anticoagulantes/farmacologia , Sistemas CRISPR-Cas , NAD(P)H Desidrogenase (Quinona)/metabolismo , Ubiquinona/farmacologia , Ubiquinona/metabolismo , Vitamina K/metabolismo , Vitamina K Epóxido Redutases/genética , Vitamina K Epóxido Redutases/metabolismo , Varfarina/farmacologia , Proteínas Reguladoras de Apoptose/genética
17.
Int J Mol Sci ; 23(23)2022 Nov 28.
Artigo em Inglês | MEDLINE | ID: mdl-36499236

RESUMO

Methyl p-coumarate (methyl p-hydroxycinnamate) (MH) is a natural compound found in a variety of plants. In the present study, we evaluated the ameliorative effects of MH on airway inflammation in an experimental model of allergic asthma (AA). In this in vitro study, MH was found to exert anti-inflammatory activity on PMA-stimulated A549 airway epithelial cells by suppressing the secretion of IL-6, IL-8, MCP-1, and ICAM-1. In addition, MH exerted an inhibitory effect not only on NF-κB (p-NF-κB and p-IκB) and AP-1 (p-c-Fos and p-c-Jun) activation but also on A549 cell and EOL-1 cell (eosinophil cell lines) adhesion. In LPS-stimulated RAW264.7 macrophages, MH had an inhibitory effect on TNF-α, IL-1ß, IL-6, and MCP-1. The results from in vivo study revealed that the increases in eosinophils/Th2 cytokines/MCP-1 in the bronchoalveolar lavage fluid (BALF) and IgE in the serum of OVA-induced mice with AA were effectively inhibited by MH administration. MH also exerted a reductive effect on the immune cell influx, mucus secretion, and iNOS/COX-2 expression in the lungs of mice with AA. The effects of MH were accompanied by the inactivation of NF-κB. Collectively, the findings of the present study indicated that MH attenuates airway inflammation in mice with AA, suggesting its potential as an adjuvant in asthma therapy.


Assuntos
Asma , NF-kappa B , Animais , Camundongos , Líquido da Lavagem Broncoalveolar , Citocinas/metabolismo , Modelos Animais de Doenças , Células Epiteliais/metabolismo , Inflamação/tratamento farmacológico , Inflamação/metabolismo , Interleucina-6 , Camundongos Endogâmicos BALB C , NF-kappa B/metabolismo , Ovalbumina
18.
ACS Omega ; 7(50): 47202-47213, 2022 Dec 20.
Artigo em Inglês | MEDLINE | ID: mdl-36570298

RESUMO

Direct solar-driven thermochemical energy storage system puts forward new requirements for calcium-based materials with high optical absorption, high capacity of energy storage density, high cycling stability, and low costs. In this work, the novelty relies on the fact that calcium-based composites modified by transition metal elements can directly capture solar energy for storing. Meanwhile, this work provides the design criteria of calcium-based materials with high optical absorption in theory and screens appropriate decorating elements to modify CaCO3 for satisfying multiple demands in experiments. The design criteria for promoting light absorption of calcium-based materials were established by electromagnetic theory while the dark transition metal elements (Cr, Mn, Fe, Co, Ni, and Cu) were doped in binary combination to experimentally modify calcium-based composites through the sol-gel method. The results indicate that calcium-based materials with porous structure (doped with Mn element) not only have high optical absorption (>75%) but also possess high cycling stability (attenuation <9% after 20 cycles) and high capacity of energy storage density (>1260 kJ/kg). After comprehensive consideration of optical absorption, cycling stability, capacity of energy storage density, and economic cost, the samples of Ca-Mn-Fe = 100-2-4 and Ca-Cr-Mn = 100-2-4 stand out to be the most promising candidates for large-scale application of thermochemical energy storage. This work provides novel promising calcium-based materials for direct solar-driven thermochemical energy storage system to realize high-efficiency solar thermal conversion.

19.
Animals (Basel) ; 12(20)2022 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-36290173

RESUMO

The COVID-19 pandemic was caused by the zoonotic SARS-CoV-2. A variety of animals involved in human life worldwide have been investigated for infection. As the degree of infection increased, extensive monitoring in animals became necessary to determine the degree of infection in animals. The study was conducted on a sample of dogs and cats, which were randomly sampled according to the number of confirmed cases in the region. Animals from both COVID-19-confirmed households and generally disease-negative families and animal shelters were included. Tests included real-time qPCR tests for SARS-CoV-2 antigens, ELISA for antibodies, and plaque reduction neutralization tests (PRNT) for neutralizing antibodies. As a result, SARS-CoV-2 viral RNA was detected in 2 cats out of 1018 pets (672 dogs and 346 cats). A total of 16 dogs (2.38%) and 18 cats (5.20%) tested positive using ELISA, and 14 dogs (2.08%) and 17 cats (4.91%) tested positive using PRNT. Antigens of- and/or antibodies to SARS-CoV-2 were detected in the animals regardless of whether the companion family was infected; this was the case even in animal shelters, which have been regarded as relatively safe from transmission. In conclusion, continuous viral circulation between humans and animals is inevitable; therefore, continuous monitoring in animals is required.

20.
Sci Rep ; 12(1): 10162, 2022 06 17.
Artigo em Inglês | MEDLINE | ID: mdl-35715561

RESUMO

Despite many studies, optimal treatment sequences or intervals are still questionable in retinal vein occlusion (RVO) macular edema. The aim of this study was to examine the real-world treatment patterns of RVO macular edema. A retrospective analysis of the Observational Medical Outcomes Partnership Common Data Model, a distributed research network, of four large tertiary referral centers (n = 9,202,032) identified 3286 eligible. We visualized treatment pathways (prescription volume and treatment sequence) with sunburst and Sankey diagrams. We calculated the average number of intravitreal injections per patient in the first and second years to evaluate the treatment intensities. Bevacizumab was the most popular first-line drug (80.9%), followed by triamcinolone (15.1%) and dexamethasone (2.28%). Triamcinolone was the most popular drug (8.88%), followed by dexamethasone (6.08%) in patients who began treatment with anti-vascular endothelial growth factor (VEGF) agents. The average number of all intravitreal injections per person decreased in the second year compared with the first year. The average number of injections per person in the first year increased throughout the study. Bevacizumab was the most popular first-line drug and steroids were considered the most common as second-line drugs in patients first treated with anti-VEGF agents. Intensive treatment patterns may cause an increase in intravitreal injections.


Assuntos
Edema Macular , Oftalmologia , Oclusão da Veia Retiniana , Inibidores da Angiogênese/uso terapêutico , Bevacizumab/uso terapêutico , Dexametasona/uso terapêutico , Glucocorticoides/uso terapêutico , Humanos , Injeções Intravítreas , Edema Macular/tratamento farmacológico , Edema Macular/etiologia , Oclusão da Veia Retiniana/complicações , Oclusão da Veia Retiniana/tratamento farmacológico , Estudos Retrospectivos , Tomografia de Coerência Óptica/efeitos adversos , Resultado do Tratamento , Triancinolona/uso terapêutico , Fator A de Crescimento do Endotélio Vascular , Acuidade Visual
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