RESUMEN
BACKGROUND: Seasonal variations in systemic immunity have been reported. This study aimed to evaluate whether seasonality affects the efficacy of anticancer immunotherapy. METHODS: A total of 604 patients with lung cancer receiving single anti-programmed cell death (ligand) 1 (anti-PD-[L]1) inhibitors from two prospective observational cohorts were screened. Primary outcomes were progression-free survival (PFS) and overall survival (OS). Patients were classified into two groups according to the season when the treatment started: winter (November-February) and other seasons (March-October). Kaplan-Meier analysis and Cox proportional hazards models were fitted to evaluate the impact of seasonality on survival. For validation, propensity score matching was performed. RESULTS: A total of 484 patients with advanced non-small cell lung cancer were included. In an unmatched population, multivariable analysis demonstrated that the winter group (n = 173) had a significantly lower risk of progression or death from immunotherapy than the other group (n = 311) (PFS: hazard ratio [HR], 0.77 [95% confidence interval (CI), 0.62-0.96]; p = .018; OS: HR, 0.77 [95% CI, 0.1-0.98]; p = .032). In a propensity score-matched population, the winter group (n = 162) showed significantly longer median PFS (2.8 months [95% CI, 1.9-4.1 months] vs. 2.0 months [95% CI, 1.4-2.7 months]; p = .009) than the other group (n = 162). The winter group's median OS was also significantly longer than that of the other group (13.4 months [95% CI, 10.2-18.0 months] vs. 8.0 months [95% CI, 3.6-8.7 months]; p = .012). The trend toward longer survival in the winter group continued in subgroup analyses. CONCLUSIONS: Starting an anti-PD-(L)1 inhibitor in winter was associated with better treatment outcomes in patients with lung cancer compared to other seasons.
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Human CtIP maintains genomic integrity primarily by promoting 5' DNA end resection, an initial step of the homologous recombination (HR). A few mechanisms have been suggested as to how CtIP recruitment to damage sites is controlled, but it is likely that we do not yet have full understanding of the process. Here, we provide evidence that CtIP recruitment and functioning are controlled by the SIAH2 E3 ubiquitin ligase. We found that SIAH2 interacts and ubiquitinates CtIP at its N-terminal lysine residues. Mutating the key CtIP lysine residues impaired CtIP recruitment to DSBs and stalled replication forks, DSB end resection, overall HR repair capacity of cells, and recovery of stalled replication forks, suggesting that the SIAH2-induced ubiquitination is important for relocating CtIP to sites of damage. Depleting SIAH2 consistently phenocopied these results. Overall, our work suggests that SIAH2 is a new regulator of CtIP and HR repair, and emphasizes that SIAH2-mediated recruitment of the CtIP is an important step for CtIP's function during HR repair.
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Reparación del ADN , Replicación del ADN , Endodesoxirribonucleasas/metabolismo , Proteínas Nucleares/metabolismo , Ubiquitina-Proteína Ligasas/metabolismo , Proteínas Portadoras/genética , Proteínas Portadoras/metabolismo , Roturas del ADN de Doble Cadena , Endodesoxirribonucleasas/genética , Humanos , Ubiquitina-Proteína Ligasas/genética , UbiquitinaciónRESUMEN
BACKGROUND AND AIM: Discordant reports of the signature gut microbes involved in nonalcoholic fatty liver disease (NAFLD) have hampered understanding of the pathogenesis of the disease, and thus its diagnosis. Thus, we investigated diagnostic factors and the potential mechanisms for heterogenous NAFLD based on the gut environment, including microbes and functional pathways. METHODS: Stools from 16 biopsy-proven NAFLD patients were analyzed for bacterial taxonomy and functional pathways based on 16s rRNA gene sequencing. Data from the physical examination, serum biochemistry, and the gut environment were subjected to a decision tree classifier to identify diagnostic markers. RESULTS: We identified two NAFLD subpopulations: those with and without a gut microbiota similar to health controls (HCs), defined as PHC-like and P patients, respectively. Stools of PHC-like patients were significantly populated with Enterobacteriaceae and were inferred to be rich in metabolites degraded from dicarboxylic acid sugars. Significant colonization of Prevotella was observed in the stools of P patients, in parallel with enrichment of metabolites from heme b biosynthesis and sulfate reduction. As a potential mechanism, we suggest that protoporphyrin IX and/or protoheme from Prevotella participates in hepatic injury, and that endogenous hydrogen sulfide increases serum IL-6 level in P patients. However, endotoxin-producing Enterobacteriaceae are thought to produce glycerate, triggering a peroxisome proliferator- activated receptor-alpha-mediated decrease in IL-6 level and fat accumulation in PHC-like patients. CONCLUSIONS: Heterogenous NAFLD subpopulations were identified, defined according to gut microbial composition and their potential underlying pathogenic mechanisms; our results raise the possibility of personalized treatment for NALFD patients.
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Microbioma Gastrointestinal , Enfermedad del Hígado Graso no Alcohólico , Enterobacteriaceae , Humanos , Interleucina-6/metabolismo , Hígado/patología , Enfermedad del Hígado Graso no Alcohólico/patología , ARN Ribosómico 16SRESUMEN
BACKGROUND: Rickettsia spp. are important tick-borne pathogens that cause various human and animal diseases worldwide. A tool for rapid and accurate detection of the pathogens from its vectors is necessary for prevention of Rickettsioses propagation in humans and animals, which are infested by ticks. Therefore, this study was conducted to evaluate a molecular tool, ultra-rapid real-time PCR (UR-qPCR), for rapid and accurate detection of Rickettsia spp. from 5644 ticks in 408 pools collected from livestock and their surrounding environments in Gangwon and Jeju province in South Korea. RESULTS: The UR-qPCR of Rickettsia DNA showed a limit of detection of 2.72 × 101 copies of Rickettsia DNA and no cross reaction with other tick-borne pathogens, namely Anaplasma phagocytophilum, Ehrlichia chaffeensis, E. canis, Toxoplasma gondii, and Borrelia burgdorferi. In addition, the PCR assay also showed possibility of various Rickettsia species detection including R. monacensis, "Candidatus R. longicornii", R. japonica, R. roultii, and R. tamurae. The collected ticks were identified with major species belonged to Haemaphysalis longicornis (81.62%), followed by H. flava (15.19%), and Ixodes nipponensis (3.19%). Rickettsia detection from tick samples using the UR-qPCR showed that the minimum infection rate (MIR) of Rickettsia in collected ticks was 1.24 and that all positive pools contained H. longicornis, equal to the MIR of 1.39 of this species. Additionally, MIR of Rickettsia spp. detected in ticks collected in Gangwon and Jeju was 1.53 and 0.84, respectively. Furthermore, the sequencing results of the 17 kDa protein antigen gene and ompA gene showed that Rickettsia spp. sequences from all pools were related to "Candidatus R. longicornii" and "Candidatus R. jingxinensis". CONCLUSIONS: The UR-qPCR system was demonstrated to be useful tool for accurate and rapid detection of Rickettsia from its vector, ixodid ticks, within 20 min. The data on Rickettsia spp. in ticks detected in this study provide useful information on the distribution of Rickettsia in previously unstudied Korean provinces, which are important for the prevention and control of the spread of rickettsioses in both animals and humans in the country.
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Ixodes , Ixodidae , Infecciones por Rickettsia , Rickettsia , Animales , Ixodes/microbiología , Ixodidae/microbiología , Prevalencia , Reacción en Cadena en Tiempo Real de la Polimerasa/veterinaria , Rickettsia/genética , Infecciones por Rickettsia/epidemiología , Infecciones por Rickettsia/veterinariaRESUMEN
BACKGROUND: Both short and long sleep duration have been consistently studied as a risk factor for obesity, hyperglycemia and hypertension. In this cross-sectional study, we provide an updated analysis of the Health Examinees (HEXA) study on the association between sleep duration and metabolic syndrome (MetS) occurrence among Koreans age 40-69 year olds. METHODS: A total of 133,608 subjects (44,930 men, 88,678 women) were enrolled in the HEXA study 2004-2013. Sleep duration was categorized into 4 sleep categories (< 6 h, 6 to < 8 h, 8 to < 10 h, ≥10 h). MetS criterion was based on the National Cholesterol Education Program, Adult Treatment Panel III. Logistic regression was used to calculate adjusted odds ratios (ORs) and 95% confidence intervals (CIs). RESULTS: Compared with individuals sleeping 6 to < 8 h per day, less than 6 h of sleep was associated with MetS (multivariable adjusted OR: 1.12, 95% CI: 1.05-1.19) and elevated waist circumference (1.15, 1.08-1.23) among men; with elevated waist circumference (1.09, 1.04-1.14) among women. Greater than 10 h of sleep was associated with MetS (1.28, 1.08-1.50) and elevated triglycerides (1.33, 1.14-1.56) among men; with MetS (1.40, 1.24-1.58), elevated waist circumference (1.14, 1.02-1.27), elevated triglycerides (1.41, 1.25-1.58), reduced high-density lipoprotein cholesterol (HDL-C) (1.24, 1.12-1.38), and elevated fasting glucose (1.39, 1.23-1.57) among women. CONCLUSIONS: Less than 6 h of sleep is associated with elevated waist circumference among both men and women and with MetS among men only. Greater than 10 h of sleep is associated with MetS and elevated triglycerides among both men and women and with elevated waist circumference, reduced HDL-C, and elevated fasting glucose among women only.
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Síndrome Metabólico/epidemiología , Obesidad/epidemiología , Privación de Sueño/epidemiología , Adulto , HDL-Colesterol/sangre , Estudios Transversales , Femenino , Humanos , Hipertensión/epidemiología , Hipertrigliceridemia/epidemiología , Modelos Logísticos , Masculino , Síndrome Metabólico/sangre , Persona de Mediana Edad , Obesidad/sangre , Oportunidad Relativa , Factores de Riesgo , Privación de Sueño/sangre , Circunferencia de la CinturaRESUMEN
Of growing amount of food waste, the integrated food waste and waste water treatment was regarded as one of the efficient modeling method. However, the load of food waste to the conventional waste treatment process might lead to the high concentration of total nitrogen (T-N) impact on the effluent water quality. The objective of this study is to establish two machine learning models-artificial neural networks (ANNs) and support vector machines (SVMs), in order to predict 1-day interval T-N concentration of effluent from a wastewater treatment plant in Ulsan, Korea. Daily water quality data and meteorological data were used and the performance of both models was evaluated in terms of the coefficient of determination (R2), Nash-Sutcliff efficiency (NSE), relative efficiency criteria (drel). Additionally, Latin-Hypercube one-factor-at-a-time (LH-OAT) and a pattern search algorithm were applied to sensitivity analysis and model parameter optimization, respectively. Results showed that both models could be effectively applied to the 1-day interval prediction of T-N concentration of effluent. SVM model showed a higher prediction accuracy in the training stage and similar result in the validation stage. However, the sensitivity analysis demonstrated that the ANN model was a superior model for 1-day interval T-N concentration prediction in terms of the cause-and-effect relationship between T-N concentration and modeling input values to integrated food waste and waste water treatment. This study suggested the efficient and robust nonlinear time-series modeling method for an early prediction of the water quality of integrated food waste and waste water treatment process.
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Redes Neurales de la Computación , Nitrógeno/análisis , Máquina de Vectores de Soporte , Aguas Residuales/química , Purificación del Agua/métodos , Calidad del Agua , Pronóstico , República de Corea , Sensibilidad y EspecificidadRESUMEN
Aerobic methanotrophs are a specialized microbial group, catalyzing the oxidation of methane. Disturbance-induced loss of methanotroph diversity/abundance, thus results in the loss of this biological methane sink. Here, we synthesized and conceptualized the resilience of the methanotrophs to sporadic, recurring, and compounded disturbances in soils. The methanotrophs showed remarkable resilience to sporadic disturbances, recovering in activity and population size. However, activity was severely compromised when disturbance persisted or reoccurred at increasing frequency, and was significantly impaired following change in land use. Next, we consolidated the impact of agricultural practices after land conversion on the soil methane sink. The effects of key interventions (tillage, organic matter input, and cover cropping) where much knowledge has been gathered were considered. Pairwise comparisons of these interventions to nontreated agricultural soils indicate that the agriculture-induced impact on the methane sink depends on the cropping system, which can be associated to the physiology of the methanotrophs. The impact of agriculture is more evident in upland soils, where the methanotrophs play a more prominent role than the methanogens in modulating overall methane flux. Although resilient to sporadic disturbances, the methanotrophs are vulnerable to compounded disturbances induced by anthropogenic activities, significantly affecting the methane sink function.
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Resiliencia Psicológica , Suelo , Metano , Microbiología del Suelo , Agricultura , Oxidación-ReducciónRESUMEN
OBJECTIVE: Alzheimer disease (AD) brains are deficient in brain-derived neurotrophic factor (BDNF), which regulates synaptic plasticity and memory. MicroRNAs (miRNAs) are â¼22-nucleotide small noncoding RNAs that control a variety of physiological and disease processes. Here, we show that miR-206 regulates BDNF and memory function in AD mice. METHODS: Expression of miRNAs was analyzed in Tg2576 AD transgenic mice and human AD brain samples. Regulation of BDNF by a selected miRNA was validated by in silico prediction, target gene luciferase assay, and dendritic spine responses in neurons. AM206, a neutralizing inhibitor of miR-206 (antagomir), was injected into the third ventricle of Tg2576 mice, after which memory function, synaptogenesis, neurogenesis, and target gene expression were assessed. For noninvasive delivery, antagomirs were administered intranasally. RESULTS: The brains of Tg2576 mice and the temporal cortex of human AD brains had increased levels of miR-206. This miRNA targeted BDNF transcripts, and AM206 prevented the detrimental effects of amyloid-ß42 on BDNF and dendritic spine degeneration in Tg2576 neurons. Injection of AM206 into the cerebral ventricles of AD mice increased the brain levels of BDNF and improved their memory function. In parallel, AM206 enhanced the hippocampal synaptic density and neurogenesis. Furthermore, intranasally administered AM206 also reached the brain and increased BDNF levels and memory function in AD mice. INTERPRETATION: Our findings demonstrate a novel miRNA-dependent regulation of BDNF in AD and suggest possible therapeutic approaches, such as noninvasive intranasal delivery of AM206.
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Enfermedad de Alzheimer/metabolismo , Enfermedad de Alzheimer/patología , Factor Neurotrófico Derivado del Encéfalo/metabolismo , Encéfalo/metabolismo , MicroARNs/metabolismo , Enfermedad de Alzheimer/tratamiento farmacológico , Enfermedad de Alzheimer/genética , Animales , Bencilaminas/uso terapéutico , Encéfalo/efectos de los fármacos , Encéfalo/patología , Espinas Dendríticas/efectos de los fármacos , Espinas Dendríticas/patología , Modelos Animales de Enfermedad , Miedo/efectos de los fármacos , Miedo/psicología , Regulación de la Expresión Génica/genética , Proteína Ácida Fibrilar de la Glía/metabolismo , Humanos , Aprendizaje/efectos de los fármacos , Aprendizaje por Laberinto/efectos de los fármacos , Ratones , Ratones Transgénicos , Análisis por Micromatrices , Neurogénesis/efectos de los fármacos , Niacina/análogos & derivados , Niacina/uso terapéutico , Oligodesoxirribonucleótidos Antisentido/uso terapéutico , Estadísticas no Paramétricas , Sinaptofisina/metabolismoRESUMEN
Genotyping of Coxiella burnetii using multispacer sequence typing (MST) and multiple locus variable number tandem repeat analysis (MLVA) was conducted from infected animals for the first time in the Republic of Korea. C. burnetii was detected by real-time PCR, and followed by MST and MLVA genotyping. The result showed that detected C. burnetii all had the same MLVA genotype, 6-13-2-7-9-10 for markers MS23-MS24-MS27-MS28-MS33-MS34, respectively, and genotype group 61 for MST. The same genotypes were previously identified in Poland. Importantly, this MLVA type was detected in humans in France, suggesting that the Korean strain can also potentially cause Q fever in humans. MST and MLVA were very useful tools for analyzing the molecular epidemiology of C. burnetii and helpful for interpreting the epidemiological relationship between isolates from domestic and international resources.
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Enfermedades de los Bovinos , Coxiella burnetii , Fiebre Q , Humanos , Bovinos , Animales , Coxiella burnetii/genética , Repeticiones de Minisatélite/genética , Genotipo , Fiebre Q/epidemiología , Fiebre Q/veterinaria , Fiebre Q/genética , Enfermedades de los Bovinos/epidemiología , Enfermedades de los Bovinos/genéticaRESUMEN
Migratory birds disperse ticks and associated tick-borne pathogens along their migratory routes. Four selected pathogens of medical importance (Coxiella burnetii, Rickettsia spp., Francisella tularensis, and Toxoplasma gondii) were targeted for detection in 804 ticks (365 pools) collected from migratory birds at Hong and Heuksan Islands in the Republic of Korea (ROK) from 2010 to 2011 and 2016. Toxoplasma gondii and Rickettsia spp., were detected in 1/365 (0.27%) and 34/365 (9.32%) pools of ticks, respectively. T. gondii and five rickettsial species were recorded in ticks collected from migratory birds for the first time in ROK. The five rickettsial species (R. monacensis, Candidatus Rickettsia longicornii, R. japonica, R. raoultii, and R. tamurae) were identified using sequence and phylogenetic analysis using ompA and gltA gene fragments. Rickettsia spp. are important pathogens that cause rickettsiosis in humans, with cases recorded in the ROK. These results provide important evidence for the potential role of migratory birds in the introduction and dispersal of T. gondii and Rickettsia spp. along their migratory routes and raise awareness of potential transmission of zoonotic tick-borne pathogens associated with migratory birds in the ROK.
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Rickettsia , Garrapatas , Toxoplasma , Animales , Aves , Humanos , Filogenia , República de Corea , Rickettsia/genética , Toxoplasma/genéticaRESUMEN
MicroRNAs (miRNAs) are small noncoding RNAs comprising 21-23 nucleotides that regulate gene expression by transcriptionally repressing their complementary mRNAs. In particular, let-7 miRNA has been postulated to function as a tumor suppressor in various cancer cells, but not yet in glioblastoma. In this study, we investigated the anti-tumorigenic effect of let-7 miRNA in glioblastoma cells. Human glioblastoma cells (U251 or U87 cells) were transfected with let-7 miRNA and assayed for in-vitro proliferation, migration, and in-vivo tumor formation. Transfection of let-7 miRNA reduced expression of pan-RAS, N-RAS, and K-RAS in the glioblastoma cells. Let-7 miRNA also reduced the in-vitro proliferation and migration of the cells, and reduced the sizes of the tumors produced after transplantation into nude mice. However, let-7 miRNA exerted no effect on the proliferation of normal human astrocytes. These results indicate that let-7 miRNA has an anti-tumorigenic effect on glioblastoma cells, and suggest possible use of let-7 miRNA for treating glioblastoma.
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Neoplasias Encefálicas/patología , Proliferación Celular , Glioblastoma/patología , MicroARNs/fisiología , Animales , Western Blotting , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/metabolismo , Adhesión Celular , Movimiento Celular , Glioblastoma/genética , Glioblastoma/metabolismo , Humanos , Técnicas para Inmunoenzimas , Masculino , Ratones , Ratones Desnudos , ARN Mensajero/genética , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Células Tumorales Cultivadas , Ensayos Antitumor por Modelo de Xenoinjerto , Proteínas ras/antagonistas & inhibidores , Proteínas ras/genética , Proteínas ras/metabolismoRESUMEN
BACKGROUND: Q fever, a zoonosis caused by Coxiella burnetii, has adverse effects on public health. Ticks are vectors of C. burnetii and they contribute to the transmission of the pathogen. A tool for rapid, sensitive, and accurate detection of C. burnetii from ticks is important for the prevention of Q fever. METHODS: Ultra-rapid real-time PCR (UR-qPCR) as a chip-based real-time PCR system was developed for the detection of C. burnetii from ticks. The UR-qPCR system was established and evaluated for the rapidity, sensitivity, and specificity of C. burnetii detection. RESULTS: C. burnetii was detected using UR-qPCR from 5644 larval, nymphal, and adult ticks from 408 pools collected from livestock and epidemiologically linked environments in two provinces, Gangwon and Jeju, in Korea. Ticks from three species were identified; Haemaphysalis longicornis accounted for the highest number, present in 333 of 408 pools (81.62%), followed by Haemaphysalis flava in 62 pools (15.19%) and Ixodes nipponensis in 13 pools (3.19%). The rapidity and sensitivity of PCR detection was demonstrated with the sufficient amplification and detection of approximately 56 copies of C. burnetii DNA with only 20 min of PCR amplification. The kappa value for the diagnostic agreement between UR-qPCR and stationary qPCR was in perfect agreement (κ = 1). PCR detection and sequencing indicated that C. burnetii was present in 5 of the 408 pools (1.23%), in which four pools contained H. longicornis and one pool contained H. flava. The infection rates of C. burnetii in the tick pools collected from Gangwon and Jeju Provinces were 1.70% and 0.58%, respectively. Phylogenetic analysis indicated a close relationship between the detected C. burnetii and those originating from goats, humans, and ticks in different countries, such as the USA, France, Germany, and Serbia. CONCLUSIONS: The methods described in this study could be important for the prevention and control of Q fever in the two provinces. The UR-qPCR, with its features of mobility, sensitivity, and rapidity, is helpful for constructing early alert systems in the field for C. burnetii in ticks and could help alleviate the transmission of and economic damage due to Q fever.
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Coxiella burnetii/aislamiento & purificación , Ixodidae/microbiología , Reacción en Cadena en Tiempo Real de la Polimerasa/métodos , Animales , Vectores Artrópodos/microbiología , Coxiella burnetii/genética , Genes Bacterianos , Humanos , Fiebre Q/diagnóstico , Fiebre Q/prevención & control , Fiebre Q/transmisión , Sensibilidad y Especificidad , Enfermedades por Picaduras de Garrapatas/microbiología , Enfermedades por Picaduras de Garrapatas/prevención & control , Enfermedades por Picaduras de Garrapatas/transmisiónRESUMEN
Ticks are important vectors of various pathogens that result in clinical illnesses in humans and domestic and wild animals. Information regarding tick infestations and pathogens transmitted by ticks is important for the identification and prevention of disease. This study was a large-scale investigation of ticks collected from dogs and their associated environments in the Republic of Korea (ROK). It included detecting six prevalent tick-borne pathogens (Anaplasma spp., A. platys, Borrelia spp., Babesia gibsoni, Ehrlichia canis, and E. chaffeensis). A total of 2293 ticks (1110 pools) were collected. Haemaphysalis longicornis (98.60%) was the most frequently collected tick species, followed by Ixodes nipponensis (0.96%) and H. flava (0.44%). Anaplasma spp. (24/1110 tick pools; 2.16%) and Borrelia spp. (4/1110 tick pools; 0.36%) were detected. The phylogenetic analyses using 16S rRNA genes revealed that the Anaplasma spp. detected in this study were closely associated with A. phagocytophilum reported in humans and rodents in the ROK. Borrelia spp. showed phylogenetic relationships with B. theileri and B. miyamotoi in ticks and humans in Mali and Russia. These results demonstrate the importance of tick-borne disease surveillance and control in dogs in the ROK.
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The horse industry has grown rapidly as a leisure industry in the Republic of Korea (ROK) in parallel with an increased demand for equestrian activities. As a result, there has been an increase in horse breeding and equestrian population and potential exposure to ticks and their associated pathogens. To provide a better understanding of the potential disease risks of veterinary and medical importance, a study was conducted to determine the geographical distribution and diversity of ticks collected from horses and vegetation associated with horse racetracks/ranches throughout the ROK. This included a survey of five associated common pathogens, Anaplasma phagocytophilum, Ehrlichia chaffeensis, Borrelia spp., Babesia caballi, and Theileria equi. A total 9220 ticks were collected from horses and associated pastures. Ticks were identified to species, stage of development, and sex. Two species of ticks, Haemaphysalis longicornis (99.9%) and Ixodes nipponensis (0.1%) were identified. Two of the target pathogens, A. phagocytophilum and Borrelia spp., were detected in 5/1409 tick pools (0.35%) and 4/1409 pools (0.28%) of H. longicornis, respectively, both of which are zoonotic pathogens of medical importance. The results of 16S rRNA phylogenetic analysis of A. phagocytophilum showed a close relationship to strains distributed in China, USA, Germany, Italy, Turkey, and Poland. Borrelia spp. showed a close relationship, based on 16S rRNA gene, to the strains reported from the USA (B. burgdorferi and B. americana) and Japan (B. tanukii and B. garinii). These results provide information about the potential risks of veterinary and medical importance and the development of mitigation strategies for disease prevention.
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Salterns are hypersaline environments that are inhabited by diverse halophilic microorganisms, including fungi. In this study, we isolated a fungal strain SK1-1 from a saltern in the Republic of Korea, which was identified as Asperillus reticulatus. This is the first reported saline-environment-derived A. reticulatus that belongs to the Aspergillus penicillioides clade and encompasses xerophilic fungi. SK1-1 was halophilic, obligately requiring NaCl for growth, with a maximum radial growth of 6%-9% (w/v) NaCl. To facilitate the biotechnological application of halophilic fungi, we screened the SK1-1 strain for proteolytic activity. Proteases have widespread applications in food processing, detergents, textiles, and waste treatment, and halophilic proteases can enable protein degradation in high salt environments. We assessed the proteolytic activity of the extracellular crude enzyme of SK1-1 using azocasein as a substrate. The crude protease exhibited maximum activity at 40-50 °C, pH 9.5-10.5, and in the absence of NaCl. It was also able to retain up to 69% of its maximum activity until 7% NaCl. Protease inhibitor assays showed complete inhibition of the proteolytic activity of crude enzymes by Pefabloc® SC. Our data suggest that the halophilic A. reticulatus strain SK1-1 produces an extracellular alkaline serine protease.
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BACKGROUND/AIM: Alpha/beta-hydrolase domain containing 12 (ABHD12) is a serine hydrolase that regulates immunological and neurological mechanisms. This study aimed to elucidate the oncogenic effect of ABHD12 on human breast cancer. MATERIALS AND METHODS: ABHD12 expression was confirmed in breast cancer tissues and breast cancer cell lines by immunohistochemistry and quantitative RT-PCR. To determine the role of ABHD12, ABHD12 siRNA-suppressed breast cancer cells (MCF7 and MDA-MB-231 cells) were investigated for cell proliferation, migration, and invasion capabilities using MTT assays, EdU assays, colony formation assays, and Boyden chamber assays. RESULTS: Immunohistochemical staining showed a higher ABHD12 expression in breast cancer tissues than in normal tissues. Additionally, ABHD12 knockdown was found to inhibit cell growth, proliferation, migration, and invasion in breast cancer cells. CONCLUSION: ABHD12 plays a crucial role in cell proliferation, migration, and invasion of breast cancer cells.
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Neoplasias de la Mama/genética , Neoplasias de la Mama/patología , Movimiento Celular , Técnicas de Silenciamiento del Gen , Monoacilglicerol Lipasas/metabolismo , Línea Celular Tumoral , Movimiento Celular/genética , Proliferación Celular/genética , Femenino , Regulación Neoplásica de la Expresión Génica , Humanos , Monoacilglicerol Lipasas/genética , Invasividad Neoplásica , ARN Mensajero/genética , ARN Mensajero/metabolismo , ARN Interferente Pequeño/metabolismo , Receptores de Cannabinoides/metabolismo , Regulación hacia Arriba/genéticaRESUMEN
BACKGROUND/AIM: Caspase recruitment domain family, member 14 (CARD14) is a member of the CARD family of proteins, which play an important role in immune and inflammatory response, and cell survival and proliferation. Here, we identified the role of CARD14 in human breast cancer. MATERIALS AND METHODS: Immunohistochemistry was performed to evaluate CARD14 expression in breast cancer. Using CARD14 knockdown cells by small interfering RNA, colony formation and MTT assays, flow cytometry analyses, and migration assays were performed to evaluate the proliferation, cell cycle distribution, apoptosis, and migration ability of MCF7 and SK-BR-3 cells. RESULTS: CARD14 expression was significantly higher in breast cancer samples than in normal breast samples. CARD14 knockdown inhibited cell proliferation and migration, caused cell cycle arrest at the G1/S boundary, and promoted apoptosis. CONCLUSION: CARD14 regulates the proliferation and migration of MCF7 and SK-BR-3 cells; it is thus, a novel potential therapeutic target in breast cancer.
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Neoplasias de la Mama/genética , Proteínas Adaptadoras de Señalización CARD/genética , Movimiento Celular/genética , Proliferación Celular/genética , Guanilato Ciclasa/genética , Proteínas de la Membrana/genética , Apoptosis/genética , Neoplasias de la Mama/patología , Ciclo Celular/genética , Puntos de Control del Ciclo Celular/genética , Femenino , Regulación Neoplásica de la Expresión Génica/genética , Técnicas de Silenciamiento del Gen , Humanos , Células MCF-7 , ARN Interferente Pequeño/genéticaRESUMEN
BACKGROUND/AIM: Non-structural maintenance of chromosomes condensin I complex subunit H (NCAPH) is implicated in correct chromosome condensation and segregation during mitosis. However, the functional role of NCAPH in the pathogenesis of non-small-cell lung cancer (NSCLC) remains unclear. The aim of this study was to elucidate the role of NCAPH in NSCLC cells. MATERIALS AND METHODS: A549 and H1299 NSCLC cells were transfected with small-interfering RNA (siRNA) against NCAPH. Subsequently, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, colony-formation assay and flow cytometry analysis were performed to reveal the role of NCAPH in NSCLC cells. In addition, migration and invasion assay were also performed. RESULTS: NCAPH knockdown inhibited cell proliferation, induced cell-cycle arrest at G2/M phase, and prevented colony formation, migration and invasion by NSCLC cells. CONCLUSION: NCAPH is involved in NSCLC progression and development, and may be a potential therapeutic target for NSCLC treatment.
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Carcinoma de Pulmón de Células no Pequeñas/metabolismo , Carcinoma de Pulmón de Células no Pequeñas/patología , Proteínas de Ciclo Celular/metabolismo , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patología , Proteínas Nucleares/metabolismo , Células A549 , Carcinoma de Pulmón de Células no Pequeñas/genética , Puntos de Control del Ciclo Celular/fisiología , Proteínas de Ciclo Celular/biosíntesis , Proteínas de Ciclo Celular/deficiencia , Proteínas de Ciclo Celular/genética , Línea Celular Tumoral , Movimiento Celular/fisiología , Proliferación Celular/fisiología , Técnicas de Silenciamiento del Gen , Humanos , Neoplasias Pulmonares/genética , Invasividad Neoplásica , Proteínas Nucleares/biosíntesis , Proteínas Nucleares/deficiencia , Proteínas Nucleares/genética , ARN Interferente Pequeño/administración & dosificación , ARN Interferente Pequeño/genética , Transfección , Regulación hacia ArribaRESUMEN
INTRODUCTION: Differentiating between multiple primary lung cancer (MPLC) and intrapulmonary metastasis (IPM) is critical for developing a therapeutic strategy to treat multiple lung cancers with multiple pulmonary sites of involvement. METHODS: We retrospectively included 252 lesions (126 pairs) from 126 patients with surgically resected multiple lung adenocarcinomas. Each pair was classified as MPLC or IPM based on histopathologic findings as the reference standard. A novel algorithm was established with four sequential decision steps based on the combination of computed tomography (CT) lesion types (step 1), CT lesion morphology (step 2), difference of maximal standardized uptake values on positron-emission tomography/CT (step 3), and presence of N2/3 lymph node metastasis or distant metastasis (step 4). The diagnostic accuracy of the algorithm was analyzed. Performances of 11 observers were assessed without and with knowledge of algorithm. RESULTS: Among 126 pairs, 90 (71.4%) were classified as MPLCs and 36 (28.6%) as IPMs. On applying the diagnostic algorithm, the overall accuracy for diagnosis of IPM among conclusive cases up to step 4 was 88.9%, and 65 and 44 pairs were correctly diagnosed based on step 1 and step 2, respectively. Specificity and positive predictive value for diagnosis of IPM increased significantly in all observers compared with reading rounds without the algorithm. CONCLUSIONS: Application of the algorithm based on comprehensive information on clinical and imaging variables can allow differentiation between MPLCs and IPMs. When both of two suspected malignant lesions appear as solid predominant lesions without spiculation or air-bronchogram on CT, IPM should be considered.
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Neoplasias Pulmonares , Neoplasias Primarias Múltiples , Algoritmos , Humanos , Pulmón , Neoplasias Pulmonares/diagnóstico por imagen , Tomografía de Emisión de Positrones , Estudios RetrospectivosRESUMEN
We aimed to assess whether allelic variants of dopamine receptor, glutamate receptor, and serotonin transporter genes are associated with the appearance of impulse control and related behaviors (ICRB) in Parkinson's disease (PD) with dopamine replacement therapy (DRT). We surveyed ICRB in consecutive Korean patients with PD who were treated with stable DRT using modified Minnesota Impulsive Disorders Interview over a period of 4 months. In the 404 patients who completed the interview and the 559 Korean healthy normal controls, genotyping was performed for variants of the DRD3 p.S9G, DRD2 Taq1A, GRIN2B c.366C>G, c.2664C>T and c.-200T>G, and the promoter region of the serotonin transporter gene (5-HTTLPR). Behavioral abnormalities suggestive of ICRB including compulsive buying, gambling, sexual behavior and eating, and punding, were present in 14.4% of the patients. Variants of DRD2 and 5-HTTLPR were not associated with the risk of developing ICRB. However, the AA genotype of DRD3 p.S9G and the CC genotype of GRIN2B c.366C>G were more frequent in patients with ICRB than in nonaffected patients (odds ratio [OR] = 2.21, P = 0.0094; and 2.14, P = 0.0087, after adjusting for age and sex). After controlling for clinical variables in the multivariate analysis, carriage of either AA genotype of DRD3 or CC genotype of GRIN2B was identified as an independent risk factor for ICRB (adjusted OR: 2.57, P = 0.0087). Variants of DRD3 p.S9G and GRIN2B c.366C>G may be associated with the appearance of ICRB in PD.