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1.
Parasitol Res ; 123(4): 192, 2024 Apr 23.
Artículo en Inglés | MEDLINE | ID: mdl-38652173

RESUMEN

The pathogenic free-living amoebae, Naegleria fowleri and Acanthamoeba polyphaga, are found in freshwater, soil, and unchlorinated or minimally chlorinated swimming pools. N. fowleri and A. polyphaga are becoming problematic as water leisure activities and drinking water are sources of infection. Chlorine dioxide (ClO2) gas is a potent disinfectant that is relatively harmless to humans at the concentration used for disinfection. In this study, we examined the amoebicidal effects of ClO2 gas on N. fowleri and A. polyphaga. These amoebae were exposed to ClO2 gas from a ready-to-use product (0.36 ppmv/h) for 12, 24, 36, and 48 h. Microscopic examination showed that the viability of N. fowleri and A. polyphaga was effectively inhibited by treatment with ClO2 gas in a time-dependent manner. The growth of N. fowleri and A. polyphaga exposed to ClO2 gas for 36 h was completely inhibited. In both cases, the mRNA levels of their respective actin genes were significantly reduced following treatment with ClO2 gas. ClO2 gas has an amoebicidal effect on N. fowleri and A. polyphaga. Therefore, ClO2 gas has been proposed as an effective agent for the prevention and control of pathogenic free-living amoeba contamination.


Asunto(s)
Acanthamoeba , Compuestos de Cloro , Desinfectantes , Naegleria fowleri , Óxidos , Compuestos de Cloro/farmacología , Naegleria fowleri/efectos de los fármacos , Acanthamoeba/efectos de los fármacos , Óxidos/farmacología , Desinfectantes/farmacología , Factores de Tiempo , Análisis de Supervivencia , Amebicidas/farmacología
2.
BMC Cancer ; 20(1): 316, 2020 Apr 15.
Artículo en Inglés | MEDLINE | ID: mdl-32293356

RESUMEN

BACKGROUND: We investigated whether head and neck squamous cell carcinoma (HNSCC) patient-derived xenografts (PDXs) reaffirm patient responses to anti-cancer therapeutics. METHODS: Tumors from HNSCC patients were transplanted into immunodeficient mice and propagated via subsequent implantation. We evaluated established PDXs by histology, genomic profiling, and in vivo anti-cancer efficacy testing to confirm them as the authentic in vivo platform. RESULTS: From 62 HNSCCs, 15 (24%) PDXs were established. The primary cancer types were tongue (8), oropharynx (3), hypopharynx (1), ethmoid sinus cancer (1), supraglottic cancer (1), and parotid gland (1); six PDXs (40%) were established from biopsy specimens from advanced HNSCC. PDXs mostly retained donor characteristics and remained stable across passages. PIK3CA (H1047R), HRAS (G12D), and TP53 mutations (H193R, I195T, R248W, R273H, E298X) and EGFR, CCND1, MYC, and PIK3CA amplifications were identified. Using the acquisition method, biopsy showed a significantly higher engraftment rate when compared with that of surgical resection (100% [6/6] vs. 16.1% [9/56], P < 0.001). Specimens obtained from metastatic sites showed a significantly higher engraftment rate than did those from primary sites (100% [9/9] vs. 11.3% [6/53], P < 0.001). Three PDX models from HPV-positive tumors were established, as compared to 12 from HPV-negative (15.8% [3/19] and 27.9% [12/43] respectively, P = 0.311), suggesting that HPV positivity tends to show a low engraftment rate. Drug responses in PDX recapitulated the clinical responses of the matching patients with pan-HER inhibitors and pan-PI3K inhibitor. CONCLUSIONS: Genetically and clinically annotated HNSCC PDXs could be useful preclinical tools for evaluating biomarkers, therapeutic targets, and new drug discovery.


Asunto(s)
Afatinib/administración & dosificación , Aminopiridinas/administración & dosificación , Carcinoma de Células Escamosas/tratamiento farmacológico , Redes Reguladoras de Genes , Neoplasias de Cabeza y Cuello/tratamiento farmacológico , Metotrexato/administración & dosificación , Morfolinas/administración & dosificación , Afatinib/farmacología , Aminopiridinas/farmacología , Animales , Biopsia , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/patología , Carcinoma de Células Escamosas/virología , Amplificación de Genes , Variación Genética , Neoplasias de Cabeza y Cuello/genética , Neoplasias de Cabeza y Cuello/patología , Neoplasias de Cabeza y Cuello/virología , Secuenciación de Nucleótidos de Alto Rendimiento , Humanos , Metotrexato/farmacología , Ratones , Morfolinas/farmacología , Infecciones por Papillomavirus/tratamiento farmacológico , Infecciones por Papillomavirus/genética , Infecciones por Papillomavirus/patología , Modelación Específica para el Paciente , Resultado del Tratamiento , Células Tumorales Cultivadas , Ensayos Antitumor por Modelo de Xenoinjerto
3.
Int J Syst Evol Microbiol ; 68(5): 1771-1775, 2018 May.
Artículo en Inglés | MEDLINE | ID: mdl-29620497

RESUMEN

A novel bacterial strain, designated hydD52T, was isolated from a sample of tidal flat sediment of the Yellow Sea in the Republic of Korea. The cells were motile, rod-shaped and Gram-stain-negative. Phylogenetic analysis based on the 16S rRNA gene sequences revealed that strain hydD52T was a member of the genus Sulfitobacter and most closely related to Sulfitobacter dubius DSM 16472T (98.0 %), Sulfitobacter indolifex HEL-45T (97.8 %) and Sulfitobacter delicatus DSM 28223T (97.6 %). The major fatty acids (>5 %) of hydD52T were C18 : 1ω7c/C18 : 1ω6c, C16 : 0, C18 : 1ω7c 11-methyl and C19 : 0ω8c. The respiratory quinone of strain hydD52T was ubiquinone-10. The major polar lipids were diphosphatidylglycerol, phosphatidylglycerol, phosphatidylcholine, phosphatidylethanolamine and an unidentified amino lipid. The G+C content of this strain was 64.0 mol%. The DNA-DNA relatedness values of hydD52T with the type strains of S. dubius, S. indolifex and S. delicatus were 18.8, 13.1 and 15.7 %, respectively. Based on the results of morphological, physiological and chemotaxonomic characterization, DNA-DNA hybridization relatedness, and 16S rRNA genes analysis, we concluded that strain hydD52T represents a novel species, for which the name Sulfitobacter aestuarii sp. nov. is proposed. The type strain is hydD52T (=KCTC 32982T=TISTR 2562T).


Asunto(s)
Sedimentos Geológicos/microbiología , Filogenia , Rhodobacteraceae/clasificación , Agua de Mar/microbiología , Técnicas de Tipificación Bacteriana , Composición de Base , ADN Bacteriano/genética , Ácidos Grasos/química , Hibridación de Ácido Nucleico , Fosfolípidos/química , ARN Ribosómico 16S/genética , República de Corea , Rhodobacteraceae/genética , Rhodobacteraceae/aislamiento & purificación , Análisis de Secuencia de ADN , Ubiquinona/química
4.
Int J Syst Evol Microbiol ; 68(3): 917-923, 2018 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-29458484

RESUMEN

A Gram-stain-negative, aerobic, non-motile, rod-shaped and pale yellow-pigmented bacterium, designated strain TX0661T, was isolated from an automotive air conditioning system collected in the Republic of Korea. 16S rRNA gene sequence analysis showed that the strain TX0661T was grouped with members of the genus Flavisolibacter and the strain had 98.2-95.3 % 16S rRNA gene sequence similarities to the species of the genus Flavisolibacter. DNA-DNA relatedness between TX0661T and Flavisolibacter ginsenosidimutans KCTC 22818T and Flavisolibacter ginsengisoli KCTC 12657T was less than 30 %. The low levels of DNA-DNA relatedness identified strain TX0661T as a novel species in the genus Flavisolibacter. The strain grew at 28-37 °C (optimum, 37 °C), at pH 6.0-7.0 (optimum, pH 6.5) and in the presence of 0-0.5 % (w/v, optimum, 0.5 %) NaCl. It contained summed feature 3 (C16 : 1ω7c and/or C16 : 1ω6c), iso-C15 : 0 and iso-C17 : 0 3-OH as major fatty acids and MK-7 as the predominant menaquinone. The polar lipid profile revealed that the presence of phosphatidylethanolamine, aminoglycophospholipid, two unidentified aminolipids and two unidentified lipids. The DNA G+C content of the strain was 49.1 mol%. Based on phenotypic, genotypic and chemotaxonomic data, strain TX0661T represents a novel species in the genus Flavisolibacter, for which the name Flavisolibactermetallilatus sp. nov. (=KACC 19145T=KCTC 52779T=NBRC 111784T) is proposed.


Asunto(s)
Aire Acondicionado , Automóviles , Bacteroidetes/clasificación , Filogenia , Técnicas de Tipificación Bacteriana , Bacteroidetes/genética , Bacteroidetes/aislamiento & purificación , Composición de Base , ADN Bacteriano/genética , Ácidos Grasos/química , Hibridación de Ácido Nucleico , Fosfolípidos/química , Pigmentación , ARN Ribosómico 16S/genética , República de Corea , Análisis de Secuencia de ADN , Vitamina K 2/análogos & derivados , Vitamina K 2/química
5.
Antonie Van Leeuwenhoek ; 111(11): 1969-1976, 2018 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-29671178

RESUMEN

A Gram-stain negative, aerobic, non-motile, rod-shaped and yellow bacterium, designated TX0651T, was isolated from an automotive air-conditioning system. Phylogenetically, the strain groups with the members of the genus Flavisolibacter and exhibits high 16S rRNA gene sequence similarities with Flavisolibacter ginsenosidimutans Gsoil 636T (97.4%), Flavisolibacter ginsengiterrae Gsoil 492T (96.3%) and Flavisolibacter ginsengisoli Gsoil 643T (96.2%). DNA-DNA relatedness between TX0651T and F. ginsenosidimutans KCTC 22818T and F. ginsengiterrae KCTC 12656T were determined to be less than 40%. The low levels of DNA-DNA relatedness identifies the strain TX0651T as a novel species in the genus Flavisolibacter. The major cellular fatty acids were identified as iso-C15:0, summed feature 3 (C16:1 ω7c and/or C16:1 ω6c), iso-C15:1 G and iso-C17:0 3-OH. The predominant respiratory quinone was identified as MK-7. The polar lipids were found to be comprised of phosphatidylethanolamine, unidentified amino-glycophospholipids, an unidentified aminophospholipid, an unidentified amino lipid and unidentified lipids. The DNA G+C content of the strain was determined to be 31.2 mol%. On the basis of the phenotypic, genotypic and chemotaxonomic characteristics, strain TX0651T should be classified in a novel species in the genus Flavisolibacter, for which the name Flavisolibacter carri sp. nov. (= KACC 19014T = KCTC 52836T = NBRC 111784T) is proposed.


Asunto(s)
Aire Acondicionado , Automóviles , Bacteroidetes/aislamiento & purificación , Bacteroidetes/genética , Bacteroidetes/metabolismo , Técnicas de Genotipaje , Fenotipo , Fosfatidiletanolaminas/metabolismo
6.
Exp Parasitol ; 192: 19-24, 2018 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-30031120

RESUMEN

Amoebae from the genus Acanthamoeba are facultative pathogens of humans and other animals. In humans they most frequently infect the eye causing a sight threatening infection known as Acanthamoeba keratitis (AK), and also cause an often fatal encephalitis (GAE). A mannose-binding protein (MBP) has been identified as being important for Acanthamoeba infection especially in AK. This lectin has previously been characterized from Acanthamoeba castellanii as consisting of multiple 130 kDa subunits. MBP expression correlates with pathogenic potential and is expressed in a number of Acanthamoeba species. Here we report the purification of a similar lectin from Acanthamoeba culbertsoni and the production of a monoclonal antibody to it. The A. culbertsoni MBP was isolated by affinity chromatography using α-D-mannose agarose and has an apparent molecular weight of 83 kDa. The monoclonal antibody is an IgM that is useful in both western blots and immunofluorescence. We expect that this antibody will be useful in the study of the pathology of A. culbertsoni and in its identification in clinical samples.


Asunto(s)
Acanthamoeba/inmunología , Anticuerpos Monoclonales/biosíntesis , Anticuerpos Antiprotozoarios/biosíntesis , Lectina de Unión a Manosa/inmunología , Proteínas Protozoarias/inmunología , Acanthamoeba/química , Queratitis por Acanthamoeba/parasitología , Animales , Antígenos de Protozoos/inmunología , Western Blotting , Electroforesis en Gel de Poliacrilamida , Ensayo de Inmunoadsorción Enzimática , Hibridomas , Sueros Inmunes/sangre , Isotipos de Inmunoglobulinas , Inmunohistoquímica , Ratones , Ratones Endogámicos BALB C
7.
Int J Syst Evol Microbiol ; 67(11): 4820-4824, 2017 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-28984219

RESUMEN

Cells of strain SW33T, isolated from the seawater of Asan Bay, Republic of Korea, were characterized as Gram-stain-negative, aerobic, rod-shaped, motile and non-spore-forming. Phylogenetic analysis revealed that strain SW33T belonged to the genus Psychrosphaera and clustered distantly with the other genera in the family Pseudoalteromonadaceae in the phylogenetic tree. The 16S rRNA sequences of strain SW33T revealed high similarities to Psychrosphaera saromensis SA4-48T (98.7 %), Psychrosphaera haliotis KDW4T (97.4 %) and Psychrosphaera aestuarii PSC101T (97.3 %). The major fatty acids were C16 : 0 (27.9 %), summed feature 3 (32.2 %) and summed feature 8 (17.2 %). The predominant quinone was Q-8, and the polar lipid profile consisted of diphosphatidylglycerol, phosphatidylethanolamine, phosphatidylglycerol and an unidentified amino lipid. The DNA G+C content was 38.3 mol%. The DNA-DNA relatedness values with the three species of Psychrosphaera saromensis KCTC 23240T, Psychrosphaera haliotis KCTC 22500T and Psychrosphaera aestuarii KCTC 32274T were 22, 23 and 18 %, respectively. Based on the phenotypic characteristics and taxonomic analyses, we propose that strain SW33T represents a novel species within the genus Psychrosphaera, for which the name Psychrosphaera aquimarina sp. nov. with the type strain SW33T (=KCTC 52743T=CICC 24249T) is proposed.


Asunto(s)
Gammaproteobacteria/clasificación , Filogenia , Agua de Mar/microbiología , Técnicas de Tipificación Bacteriana , Composición de Base , Bahías , ADN Bacteriano/genética , Ácidos Grasos/química , Gammaproteobacteria/genética , Gammaproteobacteria/aislamiento & purificación , Hibridación de Ácido Nucleico , Fosfolípidos/química , ARN Ribosómico 16S/genética , República de Corea , Análisis de Secuencia de ADN , Vitamina K 2/análogos & derivados , Vitamina K 2/química
8.
Int J Syst Evol Microbiol ; 67(10): 3960-3964, 2017 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-28884678

RESUMEN

A novel strain designated Aerobe-19T was isolated from a soil sample collected from a lawn located in Seoul National University in Korea. The cells were Gram-stain-positive, aerobic, and coccus-shaped. Colonies were circular with entire edges, convex, opaque and pale yellow. The strain grew at 15-30 ˚C (optimum, 30 ˚C), pH 5.0-7.0 (optimum, 6.0) and in the presence of 0-0.5 % (w/v) NaCl. Phylogenetically, the strain was found to be closely related to members of the genus Oryzihumus and showed 16S rRNA gene sequence similarities of 96.4 and 96.3 % with Oryzihumus leptocrescens NRRL B-24347T and Oryzihumus terrae KACC 16543T, respectively. The major cellular fatty acids were anteiso-C17 : 0, iso-C15 : 0, anteiso-C15 : 0 and iso-C16 : 0. The predominant menaquinone was MK-8 (H4). The polar lipids profile revealed the presence of diphosphatidylglycerol, glycolipids, unknown amino-glycophospholipid, unknown phospholipid and unknown lipids. The peptidoglycan type was A1γ. The DNA G+C content of this stain was 73.9 mol%. On the basis of data presented, strain Aerobe-19T is considered to represent a novel species of the genus Oryzihumus, for which the name Oryzihumus soli sp. nov. is proposed. The type strain is Aerobe-19T (=KACC 18485T =KCTC 39705T=NBRC 111450T).


Asunto(s)
Actinomycetales/clasificación , Filogenia , Microbiología del Suelo , Actinomycetales/genética , Actinomycetales/aislamiento & purificación , Técnicas de Tipificación Bacteriana , Composición de Base , ADN Bacteriano/genética , Ácidos Grasos/química , Glucolípidos/química , Peptidoglicano/química , Fosfolípidos/química , ARN Ribosómico 16S/genética , República de Corea , Análisis de Secuencia de ADN , Vitamina K 2/análogos & derivados , Vitamina K 2/química
9.
Dis Esophagus ; 30(1): 1-5, 2017 Jan 01.
Artículo en Inglés | MEDLINE | ID: mdl-26822541

RESUMEN

Ectopic sebaceous glands in the esophagus have rarely been reported and, thus, represent an obscure medical condition. The aim of this study is to identify the prevalence rate and clinical characteristics of this lesion in an asymptomatic population. We prospectively enrolled health screen examinees who underwent esophagogastroduodenoscopy for gastric cancer screening. An esophageal biopsy was performed in the cases in which esophageal ectopic sebaceous glands were suspected. The general characteristics of the examinees were analyzed based on their medical records. A total of 9989 examinees were enrolled, and five examinees were diagnosed with esophageal ectopic sebaceous glands between December 2012 and June 2014. The endoscopic findings of the esophageal ectopic sebaceous glands indicated multiple yellowish patches or papules, which varied in size. The histopathological findings indicated several lobulated sebaceous glands in the squamous epithelium with inflammatory infiltration. The follow-up endoscopic findings indicated that there was no grossly discernible change. In conclusion, esophageal ectopic sebaceous glands are present in 0.05% of asymptomatic subjects. This lesion is thought to be benign and is not related to clinical symptoms. Therefore, esophageal ectopic sebaceous glands do not require further treatment or follow-up, which makes endoscopists free from active efforts for differential diagnosis with other malignant diseases.


Asunto(s)
Enfermedades Asintomáticas , Coristoma/epidemiología , Enfermedades del Esófago/epidemiología , Esófago/patología , Glándulas Sebáceas , Adulto , Coristoma/patología , Endoscopía del Sistema Digestivo , Enfermedades del Esófago/patología , Neoplasias Esofágicas/epidemiología , Esofagitis/epidemiología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Papiloma/epidemiología , Pólipos/epidemiología , Prevalencia , Estudios Prospectivos , República de Corea/epidemiología
10.
PLoS One ; 18(10): e0292795, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37851630

RESUMEN

This paper suggests an alternative approach to measuring systemic risk in financial markets by examining the interconnectedness among heterogeneous investors. Utilizing variance decomposition and a trading database from the Korea Stock Exchange spanning 2002-2018, we find that systemic risk, as quantified by total connectedness based on microlevel investor activity, intensifies during both domestic and global financial crises. In addition, our analysis indicates that retail investors, often termed noise traders, are pivotal contributors to the propagation of financial shocks. We also find that portfolios constructed by the sensitivity of total connectedness yield additional returns. This study could enhance our understanding of the contagion effect by incorporating the investor perspective, and the findings could offer valuable insights for policy-makers and regulators.


Asunto(s)
Personal Administrativo , Mercadotecnía , Humanos , Bases de Datos Factuales , Reproducción
11.
Medicine (Baltimore) ; 102(39): e35484, 2023 Sep 29.
Artículo en Inglés | MEDLINE | ID: mdl-37773791

RESUMEN

Vaccination is important for patients undergoing hemodialysis (HD) to prevent coronavirus disease 2019 (COVID-19) infection since they are more vulnerable. However, they exhibit a weak response to vaccines, underscoring the importance of understanding whether antibodies are sufficiently produced and their durability post-COVID-19 vaccination. This prospective observational study assessed the antibody response of Korean patients undergoing HD for 1 year. We compared the antibody responses of patients undergoing HD to the COVID-19 vaccine with those of healthy volunteers from 2021 to 2022. The patient and control groups received 2 doses of ChAdOx1 nCoV-19 and mRNA-1273, respectively. Immunoglobulin G (IgG) and neutralizing antibody levels were measured weeks or months apart after 2 doses for 1 year using enzyme-linked immunosorbent and fluorescence-based competitive severe acute respiratory syndrome coronavirus 2 neutralizing assays, respectively. We analyzed the third dose's effect on the patient group by categorizing the group into patients who received the third dose and those who did not since it was initiated midway through the study. In the control group, we enrolled participants who had completed 3 doses of mRNA-1273 since almost all participants received the third dose. Thirty-two patients undergoing HD and 15 healthy participants who received 2 doses of ChAdOx1 nCoV-19 and 3 of mRNA-1273, respectively, were enrolled. Although antibody production was weaker in the patient group than in the control group (P < .001), patients showed an increase in IgG levels (0.408 ± 0.517 optical density (OD) pre-vaccination, 2.175 ± 1.241 OD in patients with 2 doses, and 2.134 ± 1.157 OD in patients with 3 doses 1 year after the second dose) and neutralizing antibodies (23 ± 8% pre-vaccination, 87 ± 23% in patients with 2 doses, and 89 ± 18% in patients with 3 doses 1 year after the second dose) post-vaccination (P < .001). In the patient group, 19 patients received a third dose (BNT162b2 or mRNA-1273); however, it did not increase the antibody levels (P = 1.000). Furthermore, the antibodies produced by the vaccination did not wane until 1 year. Two doses of vaccination resulted in a significant antibody response in patients undergoing HD, and antibody levels did not wane until 1 year.


Asunto(s)
Vacuna nCoV-2019 mRNA-1273 , COVID-19 , Humanos , Formación de Anticuerpos , Vacuna BNT162 , COVID-19/prevención & control , Vacunas contra la COVID-19 , ChAdOx1 nCoV-19 , SARS-CoV-2 , Vacunación , Anticuerpos Neutralizantes , Inmunoglobulina G , Anticuerpos Antivirales
12.
Clin Exp Vaccine Res ; 12(3): 249-259, 2023 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-37599806

RESUMEN

Purpose: Since patients on hemodialysis (HD) are known to be vulnerable to coronavirus disease 2019 (COVID-19), many studies were conducted regarding the effectiveness of the COVID-19 vaccine in HD patients in Western countries. Here, we assessed antibody response of HD patients for 6 months post-vaccination to identify the duration and effectiveness of the COVID-19 vaccine in the Asian population. Materials and Methods: We compared antibody response of the COVID-19 vaccine in HD patients with healthy volunteers. Patient and control groups had two doses of ChAdOx1 nCoV-19 and mRNA-1273, respectively. Immunoglobulin G (IgG) was measured before vaccination, 2 weeks after the first dose, 2 and 4 weeks, 3 and 6 months after the second dose. Neutralizing antibody was measured before vaccination and at 2 weeks, 3 and 6 months after second dose. Since the third dose was started in the middle of the study, we analyzed the effect of the third dose as well. Results: Although antibody production was weaker than the control group (n=22), the patient group (n=39) showed an increase in IgG and neutralizing antibody after two doses. And, 21/39 patients and 14/22 participants had a third dose (BNT162b2 or mRNA-1273 in the patient group, mRNA-1273 in the control group), and it did not affect antibody response in both group. Trend analysis showed IgG and neutralizing antibody did not decrease over time. Age, sex, and HD vintage did not affect antibody production in HD patients. Patients with higher body mass index displayed better seroresponse, while those on immunosuppressants showed poor seroresponse. Conclusion: Two doses of vaccination led to significant antibody response in HD patients, and the antibody did not wane until 6 months.

13.
Microorganisms ; 10(9)2022 Aug 25.
Artículo en Inglés | MEDLINE | ID: mdl-36144313

RESUMEN

Although the prevalence of Acanthamoeba keratitis (AK) is rare, its incidence in contact lens wearers has increased. Acanthamoeba infections can lead to the loss of vision if the diagnosis and treatment are delayed. In this study, we investigated the diagnostic potential of two antibodies raised against the adenylyl cyclase-associated protein (ACAP) and periplasmic binding protein (PBP) of A. castellanii in the AK mouse model. The specificity of ACAP and PBP antibodies to Acanthamoeba was confirmed by immunocytochemistry. AK mouse models were produced by corneal infections with A. castellanii trophozoites for 7 days and 21 days. Enzyme-linked immunosorbent assay results revealed that both ACAP and PBP antibodies successfully detected Acanthamoeba antigens in the tears and eyeball lysates of the AK mouse model. The detection levels of Acanthamoeba antigens were similar at both infection time points. Anti-Acanthamoeba IgG, IgA, and IgM antibodies were evaluated from the sera of the AK mouse model. Notably, IgM and IgA antibody responses were highest and lowest at both time points, respectively. Our findings revealed that both ACAP and PBP antibodies could detect Acanthamoeba antigens in the tears and eyeball lysates of the AK mouse model. These results provide important information for understanding Acanthamoeba infections and developing a new diagnostic tool for AK.

14.
Anim Cells Syst (Seoul) ; 25(3): 171-181, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34262660

RESUMEN

To identify the specific region of eCG involved in FSH-like activity, the following mutant expression vectors were constructed targeting the amino acid residues 102-104 of the eCG ß-subunit: single mutants, eCGßV102G/α, eCGßF103P/α, and eCGßR104K/α; double mutants, eCGßV102G;F103P/α, eCGßV102G;R104K/α, and eCGßF103P;R104K/α; triple mutant, eCGßV102G;F103P;R104K/α. The LH-like and FSH-like activities of eCG mutants were examined in CHO-K1 cells expressing rat LH/CG receptor and rat FSH receptor. The levels of eCGßV102G/α, eCGßR104K/α, and eCGßV102G;R104K/α in the culture supernatant were markedly lower than those of eCGß/α-wt. The other mutants and rec-eCGß/α-wt were efficiently secreted into the culture supernatant. The LH-like activities of eCGV104G/α, eCGßV102G;R104K/α, and eCGßF103P;R104K/α were approximately 61%, 52%, and 54%, respectively, of those of eCG-wt. The Rmax values of the mutants were 58.9%-78.8% those of eCG-wt with eCGßR104K/α exhibiting the lowest value. The FSH-like activities of single mutants were only 16%-20% of those of eCG-wt. Additionally, the FSH-like activity of double mutants was less than 10% of that of eCG-wt. In particular, the FSH-like activities of ßV102G;R104K/α and ßF103P;R104K/α were 2.5-2.9% of that of eCG-wt. These results suggest that the amino acid residues 102-104 of the eCG ß-subunit are dispensable and that the residue 104 of the eCG ß-subunit plays a pivotal role in signal transduction through the rat FSH receptor. Thus, these mutants may aid future studies on eCG interactions with mammalian FSH receptors in vitro and in vivo.

15.
Clin Cancer Res ; 27(15): 4397-4409, 2021 08 01.
Artículo en Inglés | MEDLINE | ID: mdl-34083237

RESUMEN

PURPOSE: Patient-derived organoids (PDO) of lung cancer has been recently introduced, reflecting the genomic landscape of lung cancer. However, clinical relevance of advanced lung adenocarcinoma organoids remains unknown. Here, we examined the ability of PDOs to predict clinical responses to targeted therapies in individual patients and to identify effective anticancer therapies for novel molecular targets. EXPERIMENTAL DESIGN: Eighty-four organoids were established from patients with advanced lung adenocarcinoma. Formalin-fixed, paraffin-embedded tumor specimens from corresponding patients were analyzed by whole-exome sequencing (n = 12). Organoids were analyzed by whole-exome sequencing (n = 61) and RNA sequencing (n = 55). Responses to mono or combination targeted therapies were examined in organoids and organoid-derived xenografts. RESULTS: PDOs largely retained somatic alterations including driver mutations of matching patient tumors. PDOs were able to recapitulate progression-free survival and objective responses of patients with non-small cell lung cancer receiving clinically approved tyrosine kinase inhibitors. PDOs recapitulated activity of therapeutic strategies under clinical investigation. YUO-071 harboring an EGFR exon 19 deletion and a BRAF G464A mutation and the matching patient responded to dabrafenib/trametinib combination therapy. YUO-004 and YUO-050 harboring an EGFR L747P mutation was sensitive to afatinib, consistent with the response in the matching patient of YUO-050. Furthermore, we utilized organoids to identify effective therapies for novel molecular targets by demonstrating the efficacy of poziotinib against ERBB2 exon 20 insertions and pralsetinib against RET fusions. CONCLUSIONS: We demonstrated translational relevance of PDOs in advanced lung adenocarcinoma. PDOs are an important diagnostic tool, which can assist clinical decision making and accelerate development of therapeutic strategies.


Asunto(s)
Adenocarcinoma del Pulmón/tratamiento farmacológico , Antineoplásicos/farmacología , Antineoplásicos/uso terapéutico , Neoplasias Pulmonares/tratamiento farmacológico , Organoides/efectos de los fármacos , Adenocarcinoma del Pulmón/patología , Humanos , Neoplasias Pulmonares/patología , Modelos Biológicos , Estadificación de Neoplasias
16.
Sci Rep ; 11(1): 4183, 2021 02 18.
Artículo en Inglés | MEDLINE | ID: mdl-33603075

RESUMEN

Acanthamoeba castellanii, the causative agent of Acanthamoeba keratitis (AK), occurs mainly in contact lens users with poor eye hygiene. The findings of many in vitro studies of AK, as well as the testing of therapeutic drugs, need validation in in vivo experiments. BALB/c mice were used in this study to establish in vivo AK model. A. castellanii cell suspensions (equal mixtures of trophozoites and cysts) were loaded onto 2-mm contact lens pieces and inserted into mouse eyes that were scratched using an ophthalmic surgical blade under anesthesia and the eyelids of the mice were sutured. The AK signs were grossly observed and PCR was performed using P-FLA primers to amplify the Acanthamoeba 18S-rRNA gene from mouse ocular tissue. The experimental AK mouse model was characterized by typical hazy blurring and melting of the mouse cornea established on day 1 post-inoculation. AK was induced with at least 0.3 × 105 A. castellanii cells (optimal number, 5 × 104), and the infection persisted for two months. The PCR products amplified from the extracted mouse eye DNA confirmed the development of Acanthamoeba-induced keratitis during the infection periods. In conclusion, the present AK mouse model may serve as an important in vivo model for the development of various therapeutic drugs against AK.


Asunto(s)
Queratitis por Acanthamoeba/microbiología , Acanthamoeba castellanii/genética , ADN/genética , Animales , Lentes de Contacto/microbiología , Córnea/microbiología , Modelos Animales de Enfermedad , Femenino , Ratones , Ratones Endogámicos BALB C , Trofozoítos/genética
17.
Sci Rep ; 10(1): 335, 2020 01 15.
Artículo en Inglés | MEDLINE | ID: mdl-31942007

RESUMEN

The free-living amoebae Naegleria spp. and Acanthamoeba spp. exist in the natural environment and are sometimes causal agents of lethal primary amoebic meningoencephalitis (PAM), amoebic keratitis (AK) and granulomatous amebic encephalitis (GAE) in humans, respectively. To ascertain the existence of free-living amoebae in Korea, water samples were collected from the Korean hydrosphere, Namhangang (southern Han River), an active location for water skiing and recreation. Samples underwent two-step filtration and were cultured on non-nutrient agar medium with inactivated E. coli. The remaining samples were subjected to PCR for primarily the 18S small ribosomal RNA gene and gene sequencing. Similarities in 18S rDNA sequences, in comparison with various reference amoebae in GenBank, showed 86~99% homology with N. gruberi, N. philippinensis, N. clarki, A. polyphaga, A. castellannii, and Hartmannella (Vermamoeba) vermiformis. Therefore, this study will be useful for seasonal detection of free-living amoebae from various Korean hydrospheres in future studies.


Asunto(s)
Amoeba/metabolismo , Ríos/parasitología , Amoeba/clasificación , Amoeba/genética , Amoeba/aislamiento & purificación , Secuencia de Bases , Filogenia , ARN Ribosómico 18S/química , ARN Ribosómico 18S/clasificación , ARN Ribosómico 18S/genética , República de Corea , Alineación de Secuencia , Análisis de Secuencia de ADN
18.
Cancer Res ; 80(11): 2257-2272, 2020 06 01.
Artículo en Inglés | MEDLINE | ID: mdl-32193288

RESUMEN

Quiescent cancer cells are believed to cause cancer progression after chemotherapy through unknown mechanisms. We show here that human non-small cell lung cancer (NSCLC) cell line-derived, quiescent-like, slow-cycling cancer cells (SCC) and residual patient-derived xenograft (PDX) tumors after chemotherapy experience activating transcription factor 6 (ATF6)-mediated upregulation of various cytokines, which acts in a paracrine manner to recruit fibroblasts. Cancer-associated fibroblasts (CAF) underwent transcriptional upregulation of COX2 and type I collagen (Col-I), which subsequently triggered a slow-to-active cycling switch in SCC through prostaglandin E2 (PGE2)- and integrin/Src-mediated signaling pathways, leading to cancer progression. Both antagonism of ATF6 and cotargeting of Src/COX2 effectively suppressed cytokine production and slow-to-active cell cycling transition in SCC, withholding cancer progression. Expression of COX2 and Col-I and activation of Src were observed in patients with NSCLC who progressed while receiving chemotherapy. Public data analysis revealed significant association between COL1A1 and SRC expression and NSCLC relapse. Overall, these findings indicate that a proinflammatory niche created by the interplay between SCC and CAF triggers tumor progression. SIGNIFICANCE: Cotargeting COX2 and Src may be an effective strategy to prevent cancer progression after chemotherapy.


Asunto(s)
Fibroblastos Asociados al Cáncer/patología , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Carcinoma de Pulmón de Células no Pequeñas/patología , Citocinas/metabolismo , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/patología , Factor de Transcripción Activador 6/metabolismo , Animales , Protocolos de Quimioterapia Combinada Antineoplásica/farmacología , Fibroblastos Asociados al Cáncer/efectos de los fármacos , Fibroblastos Asociados al Cáncer/metabolismo , Carcinoma Pulmonar de Lewis/tratamiento farmacológico , Carcinoma Pulmonar de Lewis/metabolismo , Carcinoma Pulmonar de Lewis/patología , Carcinoma de Pulmón de Células no Pequeñas/metabolismo , Celecoxib/administración & dosificación , Comunicación Celular/efectos de los fármacos , Comunicación Celular/fisiología , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Colágeno Tipo I/metabolismo , Ciclooxigenasa 2/metabolismo , Inhibidores de la Ciclooxigenasa 2/farmacología , Citocinas/biosíntesis , Dasatinib/administración & dosificación , Progresión de la Enfermedad , Resistencia a Antineoplásicos , Femenino , Humanos , Inflamación/metabolismo , Inflamación/patología , Neoplasias Pulmonares/metabolismo , Ratones , Ratones SCID , Recurrencia Local de Neoplasia/metabolismo , Recurrencia Local de Neoplasia/patología , Recurrencia Local de Neoplasia/prevención & control , Familia-src Quinasas/antagonistas & inhibidores
19.
J Microbiol ; 57(1): 18-22, 2019 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-30456752

RESUMEN

A Gram-stain-negative, aerobic, non-motile, rod-shaped, and yellow-pigmented bacterium, designated strain ID1709T, was isolated from an automotive air conditioning system collected in Korea. Analysis of 16S rRNA gene sequence similarity showed that strain ID1709T had 92.2-94.3% similarities with the type strains of members of the genus Flavisolibacter. The major cellular fatty acids were iso-C15:0, iso-C15:1 G, iso-C17:0 3-OH, and summed feature 3 (C16:1ω7c and/or C16:1ω6c). The predominant respiratory quinone was MK-7. The polar lipids comprised phosphatidylethanolamine, aminoglycophospholipid, two unidentified aminolipids, and three unidentified lipids. The DNA G + C content of the strain was 35.6 mol%. Based on phenotypic, chemotaxonomic, and genotypic data, strain ID1709T represents a novel species in the genus Flavisolibacter, for which the name Flavisolibacter aluminii sp. nov. (= KACC 19451T = KCTC 52778T = NBRC 112870T), is proposed.


Asunto(s)
Aire Acondicionado/instrumentación , Bacteroidetes/aislamiento & purificación , Técnicas de Tipificación Bacteriana , Bacteroidetes/clasificación , Bacteroidetes/genética , Bacteroidetes/metabolismo , Composición de Base , ADN Bacteriano/genética , Ácidos Grasos/química , Ácidos Grasos/metabolismo , Fosfatidiletanolaminas/metabolismo , Filogenia , ARN Ribosómico 16S/genética , República de Corea
20.
Artículo en Inglés | MEDLINE | ID: mdl-30533909

RESUMEN

Streptomyces sp. strains AC1-42T and AC1-42W, isolated from bat guano from Cabalyorisa Cave, Mabini, Pangasinan, Philippines, are active against Bacillus subtilis subsp. subtilis KCTC 3135T. The near-complete genome sequences reported here represent a possible source of ribosomally synthesized, posttranslationally modified peptides, such as lantipeptides, bacteriocins, linaridin, and a lasso peptide.

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