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BACKGROUND: The prevalence of sudden sensorineural hearing loss and facial palsy in patients with vestibular schwannoma and the association of sudden sensorineural hearing loss or facial palsy with vestibular schwannoma were investigated based on the population data of Korea. METHODS: This retrospective study used the Korean National Health Insurance Service data. Patients with vestibular schwannoma and those with a previous history of sudden sensorineural hearing loss or facial palsy were identified based on diagnostic, medication, magnetic resonance imaging, or audiometric codes from 2005 to 2020. The control group was established with propensity score matching. The risk for vestibular schwannoma in patients with a previous history of sudden sensorineural hearing loss or facial palsy was analyzed. RESULTS: There were 5751 patients in the vestibular schwannoma group and 23004 in the control group. The rate of patients with a previous history of sudden sensorineural hearing loss in the vestibular schwannoma group (25.8%) was significantly higher than in the control group (P -lt; .0001), as was the rate of patients with a previous history of facial palsy in the vestibular schwannoma group (4.7%) (P -lt; .0001). Previous history of sudden sensorineural hearing loss was a significant risk factor for vestibular schwannoma (hazard ratio=7.109, 95% confidence interval=6.696-7.547). Previous history of facial palsy was also a significant risk factor for vestibular schwannoma (hazard ratio=3.048, 95% confidence interval=2.695-3.447). CONCLUSION: The prevalence of sudden sensorineural hearing loss or facial palsy was significantly higher in patients with vestibular schwannoma than in those without vestibular schwannoma. Based on the population data of Korea, sudden sensorineural hearing loss and facial palsy were significant risk factors for vestibular schwannoma.
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Parálisis de Bell , Parálisis Facial , Pérdida Auditiva Sensorineural , Pérdida Auditiva Súbita , Neuroma Acústico , Humanos , Neuroma Acústico/complicaciones , Neuroma Acústico/epidemiología , Neuroma Acústico/diagnóstico , Parálisis Facial/epidemiología , Estudios Retrospectivos , Pérdida Auditiva Sensorineural/etiología , Pérdida Auditiva Sensorineural/complicaciones , Pérdida Auditiva Súbita/etiología , Pérdida Auditiva Súbita/complicaciones , Parálisis de Bell/complicaciones , Parálisis de Bell/epidemiología , República de Corea/epidemiologíaRESUMEN
Kex2 protease (Kex2p) is a membrane-bound serine protease responsible for the proteolytic maturation of various secretory proteins by cleaving after dibasic residues in the late Golgi network. In this study, we present an application of Kex2p as an alternative endoprotease for the in vitro processing of recombinant fusion proteins produced by the yeast Saccharomyces cerevisiae. The proteins were expressed with a fusion partner connected by a Kex2p cleavage sequence for enhanced expression and easy purification. To avoid in vivo processing of fusion proteins by Kex2p during secretion and to guarantee efficient removal of the fusion partners by in vitro Kex2p processing, P1', P2', P4, and P3 sites of Kex2p cleavage sites were elaborately manipulated. The general use of Kex2p in recombinant protein production was confirmed using several recombinant proteins.
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Proteínas de Saccharomyces cerevisiae , Saccharomyces cerevisiae , Péptido Hidrolasas/metabolismo , Proproteína Convertasas/metabolismo , Proteínas Recombinantes/genética , Proteínas Recombinantes/metabolismo , Saccharomyces cerevisiae/genética , Saccharomyces cerevisiae/metabolismo , Proteínas de Saccharomyces cerevisiae/genética , Proteínas de Saccharomyces cerevisiae/metabolismo , Serina Endopeptidasas/metabolismo , Subtilisinas/químicaRESUMEN
Carbon dioxide (CO2) is the most abundant component of greenhouse gases (GHGs) and directly creates environmental issues such as global warming and climate change. Carbon capture and storage have been proposed mainly to solve the problem of increasing CO2 concentration in the atmosphere; however, more emphasis has recently been placed on its use. Among the many methods of using CO2, one of the key environmentally friendly technologies involves biologically converting CO2 into other organic substances such as biofuels, chemicals, and biomass via various metabolic pathways. Although an efficient biocatalyst for industrial applications has not yet been developed, biological CO2 conversion is the needed direction. To this end, this review briefly summarizes seven known natural CO2 fixation pathways according to carbon number and describes recent studies in which natural CO2 assimilation systems have been applied to heterogeneous in vivo and in vitro systems. In addition, studies on the production of methanol through the reduction of CO2 are introduced. The importance of redox cofactors, which are often overlooked in the CO2 assimilation reaction by enzymes, is presented; methods for their recycling are proposed. Although more research is needed, biological CO2 conversion will play an important role in reducing GHG emissions and producing useful substances in terms of resource cycling.
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Efecto Invernadero , Gases de Efecto Invernadero , Dióxido de Carbono/metabolismo , Cambio Climático , Oxidación-ReducciónRESUMEN
OBJECTIVES: Voice abuse in noisy environments can result in voice disorders. However, insufficient studies have sought to differentiate vocal cord lesions through laryngoscopic examinations among workers in noisy environments. This study investigated the relationship between a history of noise exposure in the workplace and benign vocal fold lesions (BVFLs). METHODS: We used Korea National Health and Nutrition Examination Survey data from 2010 to 2012. The chi-square test was used to compare characteristics between two groups according to the presence or absence of BVFLs. To investigate the association between BVFLs and noise exposure in the workplace, we calculated adjusted odds ratios and 95% confidence intervals (CIs) using multiple logistic regression analysis. RESULTS: In total, 10,170 participants with available laryngoscopy. RESULTS: were enrolled. Smoking history, hypertension, diabetes, and exposure to noise for more than 3 months at the workplace were significantly more common in participants with BVFLs. After adjusting for age, sex, smoking, drinking, obesity, hypertension, diabetes, income, education, and occupation as confounders, we confirmed that BVFLs were 1.52 times more likely (95% CI, 1.157-1.990) to occur in individuals with occupational noise exposure. CONCLUSION: Working in a noisy environment could induce BVFLs in workers through voice abuse. Social recognition that a noisy environment is a risk factor for BVFLs needs to be improved, and preventive measures should be implemented.
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Cancer-associated fibroblasts (CAFs) are key structural components of the tumor microenvironment and are closely associated with tumor invasion and metastasis. Lysophosphatidic acid (LPA) is a biolipid produced extracellularly and involved in tumorigenesis and metastasis. LPA has recently been implicated in the education and transdifferentiation of normal fibroblasts (NFs) into CAFs. However, little is known about the effects of LPA on CAFs and their participation in cancer cell invasion. In the present study, we identified a critical role of LPA-induced amphiregulin (AREG) secreted from CAFs in cancer invasiveness. CAFs secrete higher amounts of AREG than NFs, and LPA induces AREG expression in CAFs to augment their invasiveness. Strikingly, knocking out the AREG gene in CAFs attenuates cancer invasiveness and metastasis. Mechanistically, LPA induces Yes-associated protein (YAP) activation and Zinc finger E-box binding homeobox 1 (Zeb1) expression through the LPAR1 and LPAR3/Gi/Rho signaling axes, leading to AREG expression. Furthermore, we provide evidence that metformin, a biguanide derivative, significantly inhibits LPA-induced AREG expression in CAFs to attenuate cancer cell invasiveness. Collectively, the present data show that LPA induces AREG expression through YAP and Zeb1 in CAFs to promote cancer cell invasiveness, with the process being inhibited by metformin, providing potential biomarkers and therapeutic avenues to interdict cancer cell invasion.
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The major source of ATP in cancer cells remains unclear. Here, we examined energy metabolism in gastric cancer cells and found increased fatty acid oxidation and increased expression of ALDH3A1. Metabolic analysis showed that lipid peroxidation by reactive oxygen species led to spontaneous production of 4-hydroxynonenal, which was converted to fatty acids with NADH production by ALDH3A1, resulting in further fatty acid oxidation. Inhibition of ALDH3A1 by knock down using siRNA of ALDH3A1 resulted in significantly reduced ATP production by cancer cells, leading to apoptosis. Oxidative phosphorylation by mitochondria in gastric cancer cells was driven by NADH supplied via fatty acid oxidation. Therefore, blockade of ALDH3A1 together with mitochondrial complex I using gossypol and phenformin led to significant therapeutic effects in a preclinical gastric cancer model.
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Aldehído Deshidrogenasa/metabolismo , Ácidos Grasos/metabolismo , Neoplasias Gástricas/metabolismo , Adenosina Trifosfato/biosíntesis , Aldehído Deshidrogenasa/deficiencia , Aldehído Deshidrogenasa/genética , Animales , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Femenino , Técnicas de Silenciamiento del Gen , Gosipol/farmacología , Humanos , Masculino , Ratones , Oxidación-Reducción , Fenformina/farmacología , Neoplasias Gástricas/patologíaRESUMEN
PURPOSE: This study aimed to quantitatively evaluate colon perfusion patterns using indocyanine green (ICG) angiography to find the most reliable predictive factor of anastomotic complications after laparoscopic colorectal surgery. METHODS: Laparoscopic fluorescence imaging was applied to colorectal cancer patients (n = 86) from July 2015 to December 2017. ICG (0.25 mg/kg) was slowly injected into peripheral blood vessels, and the fluorescence intensity of colonic flow was measured sequentially, producing perfusion graphs using a video analysis and modeling tool. Colon perfusion patterns were categorized as either fast, moderate, or slow based on their fluorescence slope, T1/2MAX and time ratio (TR = T1/2MAX/TMAX). Clinical factors and quantitative perfusion factors were analyzed to identify predictors for anastomotic complications. RESULTS: The mean age of patients was 65.4 years, and the male-to-female ratio was 63:23. Their operations were laparoscopic low anterior resection (55 cases) and anterior resection (31 cases). The incidence of anastomotic complication was 7%, including colonic necrosis (n = 1), anastomotic leak (n = 3), delayed pelvic abscess (n = 1), and delayed anastomotic dehiscence (n = 1). Based on quantitative analysis, the fluorescence slope, T1/2MAX, and TR were related with anastomotic complications. The cut-off value of TR to categorize the perfusion pattern was determined to be 0.6, as shown by ROC curve analysis (AUC 0.929, P < 0.001). Slow perfusion (TR > 0.6) was independent factor for anastomotic complications in a logistic regression model (OR 130.84; 95% CI 6.45-2654.75; P = 0.002). Anastomotic complications were significantly correlated with the novel factor TR (> 0.6) as the most reliable predictor of perfusion and anastomotic complications. CONCLUSIONS: Quantitative analysis of ICG perfusion patterns using T1/2MAX and TR can be applied to detect segments with poor perfusion, thereby reducing anastomotic complications during laparoscopic colorectal surgery.
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Fuga Anastomótica/diagnóstico , Angiografía/métodos , Colon/irrigación sanguínea , Neoplasias del Colon/cirugía , Neoplasias Colorrectales/cirugía , Cirugía Colorrectal/métodos , Verde de Indocianina/administración & dosificación , Laparoscopía/métodos , Anciano , Anastomosis Quirúrgica/métodos , Fuga Anastomótica/etiología , Colon/cirugía , Procedimientos Quirúrgicos del Sistema Digestivo/efectos adversos , Femenino , Humanos , Masculino , Persona de Mediana Edad , Complicaciones Posoperatorias/diagnóstico , Valor Predictivo de las PruebasRESUMEN
Unfortunately, there are some errors in Fig. 1b and Fig. 3a of the article.
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Peroxiredoxin (Prx), a family of ubiquitous thiol peroxidases, functions as a redox signaling regulator that controls cellular H2O2 in mammalian cells and has recently received attention for being overexpressed in various cancer types. In this study, we show that Prx type II (PrxII) is rather silenced in gastric cancer cells. PrxII expression is severely downregulated in 9 out of the 28 gastric cancer cell lines. Strikingly, PrxII expression is completely lost in three cell lines, MKN28, MKN74 and SNU484. Loss of PrxII expression is due to DNA methyltransferase 1-dependent methylation at the promoter region of the PrxII gene. Restoration of PrxII expression using a retroviral system markedly reduces the colony-forming ability and migratory activity of both MKN28 and SNU484 cells by inhibiting Src kinase. Mechanistically, PrxII peroxidase activity is essential for regulating gastric cancer cell migration. Bioinformatics analysis from The Cancer Genome Atlas stomach cancer data (STAD) revealed significantly low PrxII expression in gastric cancer patients and a negative correlation between PrxII expression and methylation levels. More importantly, low PrxII expression also strongly correlates with poor survival in cancer patients. Thus our study suggests that PrxII may be the first thiol peroxidase that simultaneously regulates both survival and metastasis in gastric cancer cells with high clinical relevance.
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Metilación de ADN , Silenciador del Gen , Peroxirredoxinas/genética , Regiones Promotoras Genéticas , Neoplasias Gástricas/genética , Biomarcadores de Tumor , Línea Celular Tumoral , Movimiento Celular/genética , Proliferación Celular , Supervivencia Celular/genética , Regulación Neoplásica de la Expresión Génica , Humanos , Peróxido de Hidrógeno/metabolismo , Estimación de Kaplan-Meier , Peroxirredoxinas/metabolismo , Pronóstico , ARN Interferente Pequeño/genética , Neoplasias Gástricas/metabolismo , Neoplasias Gástricas/mortalidad , Familia-src Quinasas/antagonistas & inhibidores , Familia-src Quinasas/metabolismoRESUMEN
Stress hormone norepinephrine (NE) has been associated with acquisition of cancer progression, and naturally occurring phytoalexin resveratrol (REV) has been known to suppress cancer growth and progression. In the present study, we determine the effect of REV on NE-induced ovarian cancer invasiveness. Pretreatment of REV significantly inhibited NE-induced ovarian cancer cell epithelial-to-mesenchymal transition with concomitant recovery of E-cadherin expression. In addition, our data showed that REV downregulates NE-induced human telomerase reverse transcriptase (hTERT) expression through inhibiting Src phosphorylation and HIF-1α expression. Further, REV reduced NE-induced Slug expression and subsequent ovarian cancer invasion. More importantly, combined treatment of REV with a pharmacological inhibitor of beta adrenergic receptor significantly attenuated NE-induced ovarian cancer invasion compared to single treatment. Therefore, we demonstrate interference of a Src and HIF-1α/hTERT/Slug signaling cascade by REV, providing potential therapeutic targets and inhibition of ovarian cancer.