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1.
Proc Natl Acad Sci U S A ; 119(23): e2113488119, 2022 06 07.
Artículo en Inglés | MEDLINE | ID: mdl-35639691

RESUMEN

The tocopherol biosynthetic pathway, encoded by VTE genes 1 through 6, is highly conserved in plants but most large effect quantitative trait loci for seed total tocopherols (totalT) lack VTE genes, indicating other activities are involved. A genome-wide association study of Arabidopsis seed tocopherols showed five of seven significant intervals lacked VTE genes, including the most significant, which mapped to an uncharacterized, seed-specific, envelope-localized, alpha/beta hydrolase with esterase activity, designated AtVTE7. Atvte7 null mutants decreased seed totalT 55% while a leaky allele of the maize ortholog, ZmVTE7, decreased kernel and leaf totalT 38% and 49%, respectively. Overexpressing AtVTE7 or ZmVTE7 partially or fully complemented the Atvte7 seed phenotype and increased leaf totalT by 3.6- and 6.9-fold, respectively. VTE7 has the characteristics of an esterase postulated to provide phytol from chlorophyll degradation for tocopherol synthesis, but bulk chlorophyll levels were unaffected in vte7 mutants and overexpressing lines. Instead, levels of specific chlorophyll biosynthetic intermediates containing partially reduced side chains were impacted and strongly correlated with totalT. These intermediates are generated by a membrane-associated biosynthetic complex containing protochlorophyllide reductase, chlorophyll synthase, geranylgeranyl reductase (GGR) and light harvesting-like 3 protein, all of which are required for both chlorophyll and tocopherol biosynthesis. We propose a model where VTE7 releases prenyl alcohols from chlorophyll biosynthetic intermediates, which are then converted to the corresponding diphosphates for tocopherol biosynthesis.


Asunto(s)
Arabidopsis , Hidrolasas , Arabidopsis/genética , Arabidopsis/metabolismo , Cloroplastos/fisiología , Estudio de Asociación del Genoma Completo , Hidrolasas/metabolismo , Fitol/metabolismo , Fitomejoramiento , Plantas/genética , Plantas/metabolismo , Tocoferoles/metabolismo , Vitamina E/metabolismo
2.
Vet Radiol Ultrasound ; 65(3): 246-249, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38414109

RESUMEN

A 13-year-old spayed female Persian cat presented with dyspnea and nasal discharge. Thoracic radiography revealed a dome-shaped soft-tissue opacity in the carina. Computed tomography confirmed a soft tissue-attenuating mass in the carina and the left and right proximal main bronchi that appeared to arise from the tracheal wall. Tracheoscopy revealed an intraluminal broad-based mass with multilobulated borders at the same location. Histopathological evaluation revealed a benign neoplastic process of the glandular epithelial lineage, which was considered an adenoma. Tracheal adenomas should be included in the differential diagnosis of tracheal masses.


Asunto(s)
Adenoma , Enfermedades de los Gatos , Tomografía Computarizada por Rayos X , Neoplasias de la Tráquea , Animales , Gatos , Femenino , Enfermedades de los Gatos/diagnóstico por imagen , Enfermedades de los Gatos/patología , Neoplasias de la Tráquea/veterinaria , Neoplasias de la Tráquea/diagnóstico por imagen , Adenoma/veterinaria , Adenoma/diagnóstico por imagen , Adenoma/patología , Tomografía Computarizada por Rayos X/veterinaria , Diagnóstico Diferencial , Tráquea/diagnóstico por imagen , Tráquea/patología , Radiografía Torácica/veterinaria
3.
BMC Vet Res ; 19(1): 269, 2023 Dec 12.
Artículo en Inglés | MEDLINE | ID: mdl-38087262

RESUMEN

BACKGROUND: Meningoencephalomyelitis of unknown etiology (MUE) is a comprehensive term for non-infectious inflammatory brain diseases of the central nervous system (CNS) caused by abnormal autoimmune responses. This study aims to compare the differences in survival and clinical response of MUE according to the adjuvant immunosuppressant use. Medical records of 82 dogs diagnosed with MUE were reviewed retrospectively. RESULTS: The overall survival time was 769 days (range 14-2687 days). The median survival time for each adjunctive was: leflunomide 1035 days (range 126-2163 days), mycophenolate mofetil 865 days (range 39-2191 days), cyclosporin 441 days (range 11-2176 days), cytosine arabinoside 754 days (range 6-1898 days) and a combination of mycophenolate mofetil and cytosine arabinoside 132 days (range 23-1227 days). There was no significant difference in the incidence rate of adverse events according to the immunosuppressants, but moderate to severe anemia was confirmed in 3 patients (18.7%) in the leflunomide group. CONCLUSIONS: The survival time and response rate of MUE dogs differed depending on which adjunctive immunosuppressants were used. Leflunomide showed a long survival time and a relatively good response rate in dogs with MUE. However, a large-scale further study with standardized doses of immunosuppressants and supportive treatment and constant monitoring interval is needed.


Asunto(s)
Enfermedades de los Perros , Encefalomielitis , Meningoencefalitis , Humanos , Perros , Animales , Inmunosupresores/efectos adversos , Estudios Retrospectivos , Ácido Micofenólico/efectos adversos , Leflunamida/uso terapéutico , Pronóstico , Meningoencefalitis/tratamiento farmacológico , Meningoencefalitis/veterinaria , Citarabina/efectos adversos , Encefalomielitis/veterinaria , Enfermedades de los Perros/diagnóstico
4.
Molecules ; 28(8)2023 Apr 17.
Artículo en Inglés | MEDLINE | ID: mdl-37110777

RESUMEN

Due to the limitations of organic liquid electrolytes, current development is towards high performance all-solid-state lithium batteries (ASSLBs). For high performance ASSLBs, the most crucial is the high ion-conducting solid electrolyte (SE), with a focus on interface analysis between SE and active materials. In the current study, we successfully synthesized the high ion-conductive argyrodite-type (Li6PS5Cl) solid electrolyte, which has 4.8 mS cm-1 conductivity at room temperature. Additionally, the present study suggests the quantitative analysis of interfaces in ASSLBs. The measured initial discharge capacity of a single particle confined in a microcavity electrode was 1.05 nAh for LiNi0.6Co0.2Mn0.2O2 (NCM622)-Li6PS5Cl solid electrolyte materials. The initial cycle result shows the irreversible nature of active material due to the formation of the solid electrolyte interphase (SEI) layer on the surface of the active particle; further second and third cycles demonstrate high reversibility and good stability. Furthermore, the electrochemical kinetic parameters were calculated through the Tafel plot analysis. From the Tafel plot, it is seen that asymmetry increases gradually at high discharge currents and depths, which rise asymmetricity due to the increasing of the conduction barrier. However, the electrochemical parameters confirm the increasing conduction barrier with increased charge transfer resistance.

5.
Vet Radiol Ultrasound ; 64(1): 140-148, 2023 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-36049077

RESUMEN

The renal cortical thickness (RCT) has been correlated with renal function. Previous studies have also reported that the RCT:Abdominal aorta(Ao) ratio is constant in normal dogs with various physical factors. This multi-center, retrospective, analytical study aimed to determine if there are differences between actual RCT and predicted value of RCT considering physical factors in dogs with acute or chronic renal disease. We also aimed to demonstrate whether the RCT and Ao ratio index would be useful for evaluating renal pathology. A total of 54 dogs with acute or chronic renal disease and 30 normal healthy dogs were included in this study. The RCT was measured at the center of the renal pyramid as the shortest distance perpendicular to the renal capsule from the base of the renal medullary pyramid at three points. The diameter of the Ao was measured just caudal to the branch of the left renal artery in the sagittal plane in systole. The RCT:Ao ratio of chronic kidney disease (CKD) patients was 0.50 ± 0.11 (mean ± standard deviation). The RCT:Ao ratio in normal dogs was 0.67 ± 0.07. The RCT:Ao ratio in patients with acute kidney injury (AKI) was 0.83 ± 0.05. There was a statistically significant difference between normal dogs and dogs with CKD (P < 0.001) and between normal dogs and dogs with AKI (P < 0.001). In conclusion, findings from the current study supported using the RCT:Ao ratio as a non-invasive quantitative method for characterizing kidney pathology in dogs with acute or chronic renal disease.


Asunto(s)
Lesión Renal Aguda , Enfermedades de los Perros , Insuficiencia Renal Crónica , Perros , Animales , Insuficiencia Renal Crónica/diagnóstico por imagen , Insuficiencia Renal Crónica/veterinaria , Riñón/diagnóstico por imagen , Lesión Renal Aguda/veterinaria , Aorta Abdominal/diagnóstico por imagen , Enfermedades de los Perros/diagnóstico por imagen
6.
Anal Chem ; 94(22): 7752-7758, 2022 06 07.
Artículo en Inglés | MEDLINE | ID: mdl-35609248

RESUMEN

Peptide fragmentation spectra contain critical information for the identification of peptides by mass spectrometry. In this study, we developed an algorithm that more accurately predicts the high-intensity peaks among the peptide spectra. The training data are composed of 180,833 peptides from the National Institute of Standards and Technology and Proteomics Identification database, which were fragmented by either quadrupole time-of-flight or triple-quadrupole collision-induced dissociation methods. Exploratory analysis of the peptide fragmentation pattern was focused on the highest intensity peaks that showed proline, peptide length, and a sliding window of four amino acid combination that can be exploited as key features. The amino acid sequence of each peptide and each of the key features were allocated to different layers of the model, where recurrent neural network, convolutional neural network, and fully connected neural network were used. The trained model, PrAI-frag, accurately predicts the fragmentation spectra compared to previous machine learning-based prediction algorithms. The model excels at high-intensity peak prediction, which is advantageous to selective/multiple reaction monitoring application. PrAI-frag is provided via a Web server which can be used for peptides of length 6-15.


Asunto(s)
Aprendizaje Profundo , Espectrometría de Masas en Tándem , Iones/química , Péptidos/química , Proteómica/métodos , Espectrometría de Masas en Tándem/métodos
7.
J Virol ; 95(14): e0237420, 2021 06 24.
Artículo en Inglés | MEDLINE | ID: mdl-33910954

RESUMEN

We describe a mammalian cell-based assay to identify coronavirus 3CL protease (3CLpro) inhibitors. This assay is based on rescuing protease-mediated cytotoxicity and does not require live virus. By enabling the facile testing of compounds across a range of 15 distantly related coronavirus 3CLpro enzymes, we identified compounds with broad 3CLpro-inhibitory activity. We also adapted the assay for use in compound screening and in doing so uncovered additional severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) 3CLpro inhibitors. We observed strong concordance between data emerging from this assay and those obtained from live-virus testing. The reported approach democratizes the testing of 3CLpro inhibitors by developing a simplified method for identifying coronavirus 3CLpro inhibitors that can be used by the majority of laboratories, rather than the few with extensive biosafety infrastructure. We identified two lead compounds, GC376 and compound 4, with broad activity against all 3CL proteases tested, including 3CLpro enzymes from understudied zoonotic coronaviruses. IMPORTANCE Multiple coronavirus pandemics have occurred over the last 2 decades. This has highlighted a need to be proactive in the development of therapeutics that can be readily deployed in the case of future coronavirus pandemics. We developed and validated a simplified cell-based assay for the identification of chemical inhibitors of 3CL proteases encoded by a wide range of coronaviruses. This assay is reporter free, does not require specialized biocontainment, and is optimized for performance in high-throughput screening. By testing reported 3CL protease inhibitors against a large collection of 3CL proteases with variable sequence similarity, we identified compounds with broad activity against 3CL proteases and uncovered structural insights into features that contribute to their broad activity. Furthermore, we demonstrated that this assay is suitable for identifying chemical inhibitors of proteases from families other than 3CL proteases.


Asunto(s)
COVID-19/enzimología , Proteasas 3C de Coronavirus , Inhibidores de Cisteína Proteinasa , SARS-CoV-2/enzimología , Proteasas 3C de Coronavirus/antagonistas & inhibidores , Proteasas 3C de Coronavirus/química , Proteasas 3C de Coronavirus/metabolismo , Inhibidores de Cisteína Proteinasa/química , Inhibidores de Cisteína Proteinasa/farmacología , Células HEK293 , Humanos , Tratamiento Farmacológico de COVID-19
8.
Macromol Rapid Commun ; 43(1): e2100467, 2022 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-34643991

RESUMEN

Even though plastic improved the human standard of living, handling the plastic waste represents an enormous challenge. It takes more than 100 years to decompose discarded or buried waste plastics. Microplastics are one of the causes of significantly pervasive environmental pollutants. The incineration of plastic waste generates toxic gases, underscoring the need for new approaches, in contrast to conventional strategies that are required for recycling plastic waste. Therefore, several studies have attempted to upcycle plastic waste into high value-added products. Converting plastic waste into carbonaceous materials is an excellent upcycling technique due to their diverse practical applications. This review summarizes various studies dealing with the upcycling of plastic waste into carbonaceous products. Further, this review discusses the applications of carbonaceous products synthesized from plastic waste including carbon fibers, absorbents for water purification, and electrodes for energy storage. Based on the findings, future directions for effective upcycling of plastic waste into carbonaceous materials are suggested.


Asunto(s)
Plásticos , Reciclaje , Gases , Humanos
9.
Sensors (Basel) ; 22(2)2022 Jan 07.
Artículo en Inglés | MEDLINE | ID: mdl-35062397

RESUMEN

Distinguishing between wireless and wired traffic in a network middlebox is an essential ingredient for numerous applications including security monitoring and quality-of-service (QoS) provisioning. The majority of existing approaches have exploited the greater delay statistics, such as round-trip-time and inter-packet arrival time, observed in wireless traffic to infer whether the traffic is originated from Ethernet (i.e., wired) or Wi-Fi (i.e., wireless) based on the assumption that the capacity of the wireless link is much slower than that of the wired link. However, this underlying assumption is no longer valid due to increases in wireless data rates over Gbps enabled by recent Wi-Fi technologies such as 802.11ac/ax. In this paper, we revisit the problem of identifying Wi-Fi traffic in network middleboxes as the wireless link capacity approaches the capacity of the wired. We present Weigh-in-Motion, a lightweight online detection scheme, that analyzes the traffic patterns observed at the middleboxes and infers whether the traffic is originated from high-speed Wi-Fi devices. To this end, we introduce the concept of ACKBunch that captures the unique characteristics of high-speed Wi-Fi, which is further utilized to distinguish whether the observed traffic is originated from a wired or wireless device. The effectiveness of the proposed scheme is evaluated via extensive real experiments, demonstrating its capability of accurately identifying wireless traffic from/to Gigabit 802.11 devices.

10.
Vet Radiol Ultrasound ; 63(3): 337-344, 2022 May.
Artículo en Inglés | MEDLINE | ID: mdl-35023240

RESUMEN

The renal cortical thickness (RCT) reflects the pathological condition of the kidney, and measuring this parameter can help diagnose renal fibrosis in dogs. The normal reference range of RCT in dogs is broad (3-8 mm) because of the extreme diversity in body size. Therefore, this retrospective, reference interval, and observational design study aimed to establish a normal reference range for RCT in dogs measured using ultrasound by considering bodyweight (BW), body surface area (BSA), body condition score (BCS), and abdominal aorta (Ao) diameter. A total of 60 dogs met the inclusion criteria, and abdominal ultrasound images and medical records of these dogs were analyzed. RCT was measured at 1-3 points where the renal capsule and broad base of the medullary pyramid were clearly observed. Ao diameter was measured caudal to the branch of the left renal artery in the mid-sagittal view. The RCT showed positive correlations with BW and BSA and a negative correlation with BCS, which can be described as follows: RCT (mm) = 0.131 × BW - 0.166 × BCS + 3.580. The RCT:Ao ratio was 0.70 ± 0.09 (mean ± standard deviation). No significant differences were found in the RCT:Ao ratio depending on BW or BCS. In conclusion, the RCT:Ao ratio and relative RCT considering both BW and BCS are potentially useful for evaluating the normality of the renal cortex on ultrasound examination in dogs with various physiques.


Asunto(s)
Aorta Abdominal , Riñón , Animales , Aorta Abdominal/diagnóstico por imagen , Peso Corporal , Perros , Riñón/diagnóstico por imagen , Valores de Referencia , Estudios Retrospectivos , Ultrasonografía/veterinaria
11.
Biochem Biophys Res Commun ; 539: 28-33, 2021 02 05.
Artículo en Inglés | MEDLINE | ID: mdl-33418190

RESUMEN

Ciliogenesis is often impaired in some cancer cells, leading to acceleration of cancer phenotypes such as cell migration and proliferation. From the investigation of primary cilia of 16 gastric cancer cells (GCs), we found that GCs could be grouped into four primary cilia (PC)-positive GCs and 12 PC-negative GCs. The proliferation of the PC-positive GCs was lower than that of PC-negative GCs. To explore the role of fatty acid binding protein 4 (FABP4), which is a known oncogenic factor, in ciliogenesis, FABP4 expression and function were inhibited by transfection of cells with short interfering RNA targeting FABP4 (siFABP4) or FABP4 inhibitor treatment. Notably, the proliferation and migration of the cilia-forming GCs was effectively suppressed by inhibition of FABP4. In addition, the primary cilia in GCs were restored by a factor greater than two, suggesting a negative role of FABP4 in ciliogenesis in these GCs and FABP4 as a potential anticancer target.


Asunto(s)
Compuestos de Bifenilo/farmacología , Cilios/metabolismo , Proteínas de Unión a Ácidos Grasos/antagonistas & inhibidores , Pirazoles/farmacología , Neoplasias Gástricas/tratamiento farmacológico , Línea Celular Tumoral , Movimiento Celular/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Cilios/patología , Proteínas de Unión a Ácidos Grasos/genética , Humanos , ARN Interferente Pequeño/metabolismo , Neoplasias Gástricas/metabolismo , Neoplasias Gástricas/patología
12.
Biochem Biophys Res Commun ; 552: 44-51, 2021 05 07.
Artículo en Inglés | MEDLINE | ID: mdl-33743348

RESUMEN

Hepatocellular carcinoma (HCC) is the fifth common types of cancer with poor prognosis in the world. Honokiol (HNK), a natural biphenyl compound derived from the magnolia plant, has been reported to exert anticancer effects, but its mechanism has not been elucidated exactly. In the present study, HNK treatment significantly suppressed the migration ability of HepG2 and Hep3B human hepatocellular carcinoma. The treatment reduced the expression levels of the genes associated with cell migration, such as S100A4, MMP-2, MMP-9 and Vimentin. Interestingly, treatment with HNK significantly reduced the expression level of Cyclophilin B (CypB) which stimulates cancer cell migration. However, overexpressed CypB abolished HNK-mediated suppression of cell migration, and reversed the apoptotic effects of HNK. Altogether, we concluded that the suppression of migration activities by HNK was through down-regulated CypB in HCC. These finding suggest that HNK may be a promising candidate for HCC treatment via regulation of CypB.


Asunto(s)
Compuestos de Bifenilo/farmacología , Carcinoma Hepatocelular/genética , Movimiento Celular/efectos de los fármacos , Ciclofilinas/genética , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Lignanos/farmacología , Neoplasias Hepáticas/genética , Antineoplásicos Fitogénicos/farmacología , Apoptosis/efectos de los fármacos , Apoptosis/genética , Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/patología , Línea Celular Tumoral , Movimiento Celular/genética , Supervivencia Celular/efectos de los fármacos , Supervivencia Celular/genética , Ciclofilinas/metabolismo , Regulación hacia Abajo/efectos de los fármacos , Células Hep G2 , Humanos , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/patología , Transducción de Señal/efectos de los fármacos , Transducción de Señal/genética
13.
Ann Surg Oncol ; 28(8): 4458-4470, 2021 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-33423177

RESUMEN

BACKGROUND: Few studies have presented evidence pertaining to the adequate minimum number of adjuvant chemotherapy (AC) cycles required to achieve an oncologic benefit for gastric cancer. METHODS: From January 2012 to December 2013, data from patients who underwent curative radical gastrectomy and consequently received AC for pathologic stage 2 or 3 gastric cancer at 27 institutions in South Korea were analyzed. RESULTS: The study enrolled 925 patients, 661 patients (71.5%) who completed 8 cycles of AC and 264 patients (28.5%) who did not. Compared with the mean disease-free survival (DFS) of the patients who completed 8 AC cycles (69.3 months), the mean DFS of patients who completed 6 AC cycles (72.4 months; p = 0.531) and those who completed 7 AC cycles (63.7 months; p = 0.184) did not differ significantly. However, the mean DFS of the patients who completed 5 AC cycles (48.2 months; p = 0.016) and those who completed 1-4 AC cycles (62.9 months; p = 0.036) was significantly lower than the DFS of those who completed 8 AC cycles. In the multivariate Cox proportional hazards analysis, the mean DFS was significantly affected by advanced stage, large tumor size, positive vascular invasion, and number of completed AC cycles (1-5 cycles: hazard ratio 1.45; 95% confidence interval 1.01-2.08; p = 0.041). CONCLUSION: The current multicenter observational cohort study showed that the mean DFS for 6 or 7 AC cycles was similar to that for 8 AC cycles as an adjuvant treatment for gastric cancer.


Asunto(s)
Neoplasias Gástricas , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Quimioterapia Adyuvante , Estudios de Cohortes , Supervivencia sin Enfermedad , Gastrectomía , Humanos , Estadificación de Neoplasias , República de Corea , Estudios Retrospectivos , Neoplasias Gástricas/tratamiento farmacológico , Neoplasias Gástricas/cirugía
14.
BMC Cancer ; 21(1): 558, 2021 May 17.
Artículo en Inglés | MEDLINE | ID: mdl-34001012

RESUMEN

BACKGROUND: Noggin and RNA-binding protein for multiple splicing 2 (RBPMS2) are known to regulate the expression of smooth muscle cells, endothelial cells, and osteoblasts. However, the prognostic role of combined Noggin and RBPMS2 expression in resected gastric cancer (GC) is unclear. METHODS: A total of 163 patients with GC who underwent gastrectomy were included in this study. The expression of Noggin and RBPMS2 proteins in tumor cells at the tumor center and invasive front of resected GC was evaluated by immunohistochemistry, and in conjunction with clinicopathological parameters the patient survival was analyzed. RESULTS: RBPMS2 protein expression was high at the tumor center (n = 86, 52.8%) and low at the invasive front (n = 69, 42.3%), while Noggin protein expression was high in both tumor center (n = 91, 55.8%) and the invasive front (n = 90, 55.2%). Noggin expression at the invasive front and tumor center was significantly decreased in advanced T stage, non-intestinal-type (invasive front, P = 0.008 and P <  0.001; tumor center lesion, P = 0.013 and P = 0.001). RBPMS2 expression at the invasive front was significantly decreased in non-intestinal-type and positive lymphatic invasion (P <  0.001 and P = 0.013). Multivariate analysis revealed that high Noggin protein expression of the invasive front was an independent prognostic factor for overall survival (hazard ratio [HR], 0.58; 95% confidence interval [CI]; 0.35-0.97, P <  0.036), but not at the tumor center (HR, 1.35; 95% CI; 0.81-2.26, P = 0.251). CONCLUSIONS: Our study indicates that high Noggin expression is a crucial prognostic factor for favorable outcomes in patients with resected GC.


Asunto(s)
Proteínas Portadoras/metabolismo , Gastrectomía , Recurrencia Local de Neoplasia/epidemiología , Proteínas de Unión al ARN/metabolismo , Neoplasias Gástricas/cirugía , Adulto , Anciano , Anciano de 80 o más Años , Biomarcadores de Tumor/análisis , Biomarcadores de Tumor/metabolismo , Proteínas Portadoras/análisis , Supervivencia sin Enfermedad , Mucosa Gástrica/patología , Mucosa Gástrica/cirugía , Humanos , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Pronóstico , Factores Protectores , Proteínas de Unión al ARN/análisis , Estudios Retrospectivos , Neoplasias Gástricas/diagnóstico , Neoplasias Gástricas/mortalidad , Neoplasias Gástricas/patología , Tasa de Supervivencia , Análisis de Matrices Tisulares
15.
Int J Mol Sci ; 22(12)2021 Jun 21.
Artículo en Inglés | MEDLINE | ID: mdl-34205595

RESUMEN

Tinnitus is associated with increased social costs and reduced quality of life through sleep disorders or psychological distress. The pathophysiology of chronic subjective tinnitus, which accounts for most tinnitus, has not been clearly elucidated. This is because chronic subjective tinnitus is difficult to evaluate objectively, and there are no objective markers that represent the diagnosis or therapeutic effect of tinnitus. Based on the results of studies on patients with chronic subjective tinnitus, objective and measurable biomarkers that help to identify the pathophysiology of tinnitus have been summarized. A total of 271 studies in PubMed, 303 in EMBASE, and 45 in Cochrane Library were found on biomarkers related to chronic subjective tinnitus published until April 2021. Duplicate articles, articles not written in English, review articles, case reports, and articles that did not match our topic were excluded. A total of 49 studies were included. Three specimens, including blood, saliva, and urine, and a total of 58 biomarkers were used as indicators for diagnosis, evaluation, prognosis, and therapeutic effectiveness of tinnitus. Biomarkers were classified into eight categories comprising metabolic, hemostatic, inflammatory, endocrine, immunological, neurologic, and oxidative parameters. Biomarkers can help in the diagnosis, measure the severity, predict prognosis, and treatment outcome of tinnitus.


Asunto(s)
Biomarcadores/sangre , Acúfeno , Animales , Enfermedad Crónica , Humanos
16.
Int J Mol Sci ; 22(12)2021 Jun 17.
Artículo en Inglés | MEDLINE | ID: mdl-34204438

RESUMEN

Hepatitis C virus (HCV) is associated with various liver diseases. Chronic HCV infection is characterized by an abnormal host immune response. Therefore, it is speculated that to suppress HCV, a well-regulated host immune response is necessary. 2-O-methylhonokiol was identified by the screening of anti-HCV compounds using Renilla luciferase assay in Huh 7.5/Con 1 genotype 1b replicon cells. Here, we investigated the mechanism by which 2-O-methylhonokiol treatment inhibits HCV replication using real-time PCR. Our data shows that treatment with 2-O-methylhonokiol activated innate immune responses via nuclear factor kappa-light-chain-enhancer of activated B cells (NF-kB) pathway. Additionally, the immunoprecipitation result shows that treatment with 2-O-methylhonokiol augmented tumor necrosis factor receptor (TNFR)-associated factor 6 (TRAF6) by preventing p62 from binding to TRAF6, resulting in reduced autophagy caused by HCV. Finally, we reproduced our data with the conditioned media from 2-O-methylhonokiol-treated cells. These findings strongly suggest that 2-O-methylhonokiol enhances the host immune response and suppresses HCV replication via TRAF6-mediated NF-kB activation.


Asunto(s)
Hepacivirus/fisiología , Hepatitis C/metabolismo , Hepatitis C/virología , Interacciones Huésped-Patógeno , FN-kappa B/metabolismo , Factor 6 Asociado a Receptor de TNF/metabolismo , Replicación Viral , Linfocitos B/inmunología , Linfocitos B/metabolismo , Línea Celular , Células Cultivadas , Hepatitis C/inmunología , Interacciones Huésped-Patógeno/inmunología , Humanos , Inmunidad Innata , Modelos Biológicos , Estructura Molecular
17.
Int J Mol Sci ; 21(16)2020 Aug 05.
Artículo en Inglés | MEDLINE | ID: mdl-32764395

RESUMEN

Cyclin-dependent kinase 5 regulatory subunit-associated protein 1-like 1 (CDKAL1) is one of the strongest diabetes loci identified to date; evidence suggests that it plays an important role in insulin secretion. Dietary factors that affect insulin demand might enhance the risk of diabetes associated with CDKAL1 variants. Our aim was to examine the interactions between dietary protein and fat intake and CDKAL1 genetic variants in relation to the risk of diabetes in Korean adults. Single nucleotide polymorphisms (SNPs) were selected with a genome-wide association study (GWAS) for diabetes after adjustment for age, gender, and examination site. Using data from the Health Examinees (HEXA) Study of the Korean Genome and Epidemiology Study (KoGES), 3988 middle-aged Korean adults between 40-76 years of age (2034 men and 1954 women) were included in the study. Finally, rs7756992 located within the CDKAL1 gene region was selected from GWAS (p-value < 5 × 10-8). Multivariable logistic regression models were used to evaluate the interactions between genotypes and dietary protein and fat intake in relation to diabetes risk after adjustment for age, gender, BMI, waist circumference, physical activity, smoking status, drinking habits, and examination site. Significant interactions between CDKAL1 rs7756992 and dietary protein and fat intake for the risk of diabetes were observed in men (p-value < 0.05). In women, significant interactions between dietary protein and fat intake and CDKAL1 variants (rs7756992) were associated with increased risk of diabetes (p-value < 0.05). Dietary protein and fat intake interacted differently with CDKAL1 variants in relation to the risk of diabetes in Korean adults of both genders. These findings indicate that CDKAL1 variants play a significant role in diabetes and that dietary protein and fat intake could affect these associations.


Asunto(s)
Diabetes Mellitus/genética , Grasas de la Dieta/metabolismo , Proteínas en la Dieta/metabolismo , Predisposición Genética a la Enfermedad , ARNt Metiltransferasas/genética , Adulto , Anciano , Diabetes Mellitus/epidemiología , Diabetes Mellitus/metabolismo , Diabetes Mellitus/patología , Femenino , Estudio de Asociación del Genoma Completo , Humanos , Masculino , Persona de Mediana Edad , Polimorfismo de Nucleótido Simple/genética , República de Corea/epidemiología , Factores de Riesgo
18.
Int J Mol Sci ; 21(15)2020 Aug 01.
Artículo en Inglés | MEDLINE | ID: mdl-32752233

RESUMEN

Hepatic hepcidin is a well-known major iron regulator and has been reported to be closely related to hepatitis C virus (HCV) replication. However, pharmacological targeting of the hepcidin in HCV replication has not been reported. A short-chain fatty acid, 4-Phenyl butyrate (4-PBA), is an acid chemical chaperone that acts as a histone deacetylase inhibitor (HDACi) to promote chromosomal histone acetylation. Here, we investigated the therapeutic effect of 4-PBA on hepcidin expression and HCV replication. We used HCV genotype 1b Huh 7.5-Con1 replicon cells and engraftment of NOD/SCID mice as in vitro and in vivo models to test the effect of 4-PBA. It was found that 4-PBA inhibited HCV replication in Huh7.5-Con1 replicon cells in a concentration- and time-dependent manner through the induction of hepcidin expression by epigenetic modification and subsequent upregulation of interferon-α signaling. HCV formed a membranous web composed of double-membrane vesicles and was utilized for RNA replication. Moreover, 4-PBA also disrupted the integrity of the membranous web and interfered with the molecular interactions critical for the assembly of the HCV replication complex. These findings suggest that 4-PBA is a key epigenetic inducer of anti-HCV hepatic hepcidin and might at least in part play a role in targeting host factors related to HCV infection as an attractive complement to current HCV therapies.


Asunto(s)
Epigénesis Genética/efectos de los fármacos , Hepacivirus/efectos de los fármacos , Hepcidinas/genética , Fenilbutiratos/farmacología , Bibliotecas de Moléculas Pequeñas/farmacología , Replicación Viral/efectos de los fármacos , Animales , Línea Celular Tumoral , Expresión Génica/efectos de los fármacos , Hepacivirus/genética , Hepacivirus/fisiología , Hepatitis C/prevención & control , Hepatitis C/virología , Hepcidinas/metabolismo , Interacciones Huésped-Patógeno/efectos de los fármacos , Humanos , Hígado/efectos de los fármacos , Hígado/metabolismo , Ratones Endogámicos NOD , Ratones SCID , Estructura Molecular , Fenilbutiratos/química , Bibliotecas de Moléculas Pequeñas/química , Replicación Viral/genética
19.
Proc Natl Acad Sci U S A ; 113(39): 10974-9, 2016 09 27.
Artículo en Inglés | MEDLINE | ID: mdl-27625425

RESUMEN

In mammals, initial detection of olfactory stimuli is mediated by sensory neurons in the main olfactory epithelium (MOE) and the vomeronasal organ (VNO). The heterotrimeric GTP-binding protein Go is widely expressed in the MOE and VNO of mice. Early studies indicated that Go expression in VNO sensory neurons is critical for directing social and sexual behaviors in female mice [Oboti L, et al. (2014) BMC Biol 12:31]. However, the physiological functions of Go in the MOE have remained poorly defined. Here, we examined the role of Go in the MOE using mice lacking the α subunit of Go Development of the olfactory bulb (OB) was perturbed in mutant mice as a result of reduced neurogenesis and increased cell death. The balance between cell types of OB interneurons was altered in mutant mice, with an increase in the number of tyrosine hydroxylase-positive interneurons at the expense of calbindin-positive interneurons. Sexual behavior toward female mice and preference for female urine odors by olfactory sensory neurons in the MOE were abolished in mutant male mice. Our data suggest that Go signaling is essential for the structural and functional integrity of the MOE and for specification of OB interneurons, which in turn are required for the transmission of pheromone signals and the initiation of mating behavior with the opposite sex.


Asunto(s)
Subunidades alfa de la Proteína de Unión al GTP Gi-Go/metabolismo , Mucosa Olfatoria/metabolismo , Conducta Sexual Animal , Animales , Apoptosis/genética , Recuento de Células , Células Cultivadas , Subunidades alfa de la Proteína de Unión al GTP Gi-Go/deficiencia , Subunidades alfa de la Proteína de Unión al GTP Gi-Go/genética , Eliminación de Gen , Interneuronas/metabolismo , Masculino , Ratones , Modelos Biológicos , Neurogénesis/genética , Bulbo Olfatorio/metabolismo , ARN Mensajero/genética , ARN Mensajero/metabolismo , Transducción de Señal , Tirosina 3-Monooxigenasa/metabolismo , Órgano Vomeronasal/metabolismo
20.
Pancreatology ; 18(1): 22-28, 2018 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-29246689

RESUMEN

OBJECTIVES: This study aims to evaluate the diagnostic value of magnetic resonance cholangiopancreatography (MRCP) in detecting common bile duct (CBD) stones in acute biliary pancreatitis (ABP). METHODS: The medical records of patients presenting with ABP from January 2008 to July 2013 were reviewed to assess the value of MRCP in detecting CBD stones in ABP. Endoscopic retrograde cholangiopancreatography (ERCP) was used as the reference standard to assess the diagnostic yield of MRCP in detecting choledocholithiasis. When ERCP was unavailable, intraoperative cholangiography or clinical follow-up was used as the reference standard. RESULTS: Seventy-eight patients who underwent MRCP were diagnosed with ABP, and thirty of the 78 patients (38%) were confirmed to have CBD stones per the study protocol. The sensitivity of MRCP in detecting CBD stones in ABP was 93.3% compared to 66.7% for abdominal CT (P < 0.008). The overall accuracy of MRCP in detecting choledocholithiasis was 85.9% compared to 74.0% for abdominal CT (P < 0.041). The area under the receiver operating characteristic curve (AUC) of MRCP in detecting CBD stones was 0.882, which was more accurate than the AUC of 0.727 for abdominal CT (P = 0.039). In 38 patients who underwent ERCP, the sensitivity and negative predictive value of MRCP in detecting CBD stones were both 100% regardless of the dilatation of the bile duct (≥7 mm versus < 7 mm). CONCLUSION: MRCP is an effective, noninvasive modality to detect CBD stones in ABP and can help identify patients who require ERCP.


Asunto(s)
Colangiopancreatografia Retrógrada Endoscópica , Pancreatocolangiografía por Resonancia Magnética , Coledocolitiasis/diagnóstico por imagen , Cálculos Biliares/diagnóstico por imagen , Pancreatitis/diagnóstico por imagen , Enfermedad Aguda , Coledocolitiasis/complicaciones , Humanos , Pancreatitis/complicaciones , Estudios Retrospectivos
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