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1.
Nano Lett ; 23(5): 1673-1679, 2023 Mar 08.
Artigo em Inglês | MEDLINE | ID: mdl-36849129

RESUMO

Boron-based two-dimensional (2D) materials are an excellent platform for nanoelectronics applications. Rhombohedral boron monosulfide (r-BS) is attracting particular attention because of its unique layered crystal structure suitable for exploring various functional properties originating in the 2D nature. However, studies to elucidate its fundamental electronic states have been largely limited because only tiny powdered crystals were available, hindering a precise investigation by spectroscopy such as angle-resolved photoemission spectroscopy (ARPES). Here we report the direct mapping of the band structure with a tiny (∼20 × 20 µm2) r-BS powder crystal by utilizing microfocused ARPES. We found that r-BS is a p-type semiconductor with a band gap of >0.5 eV characterized by the anisotropic in-plane effective mass. The present results demonstrate the high applicability of micro-ARPES to tiny powder crystals and widen an opportunity to access the yet-unexplored electronic states of various novel materials.

2.
EMBO J ; 38(17): e98441, 2019 09 02.
Artigo em Inglês | MEDLINE | ID: mdl-31361039

RESUMO

Long non-coding RNAs (lncRNAs) function in a wide range of processes by diverse mechanisms, though their roles in regulation of oncogenes and/or tumor suppressors remain rather elusive. We performed a global search for lncRNAs affecting MYC activity using a systems biology-based approach with a K supercomputer and the GIMLET algorism based on local distance correlations. Consequently, MYMLR was identified and experimentally shown to maintain MYC transcriptional activity and cell cycle progression despite the low levels of expression. A proteomic search for MYMLR-binding proteins identified PCBP2, while it was also found that MYMLR places a 557-kb upstream enhancer region in the proximity of the MYC promoter in cooperation with PCBP2. These findings implicate a crucial role for MYMLR in regulation of the archetypical oncogene MYC and warrant future studies regarding the involvement of low copy number lncRNAs in regulation of other crucial oncogenes and tumor suppressor genes.


Assuntos
Neoplasias Pulmonares/genética , Proteínas Proto-Oncogênicas c-myc/genética , Proteínas Proto-Oncogênicas c-myc/metabolismo , RNA Longo não Codificante/genética , Proteínas de Ligação a RNA/genética , Células A549 , Animais , Ciclo Celular , Linhagem Celular Tumoral , Proliferação de Células , Regulação para Baixo , Elementos Facilitadores Genéticos , Regulação Neoplásica da Expressão Gênica , Humanos , Neoplasias Pulmonares/metabolismo , Camundongos , Transplante de Neoplasias , Proteômica , Proteínas de Ligação a RNA/metabolismo , Biologia de Sistemas
3.
J Infect Chemother ; 29(9): 833-837, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37211085

RESUMO

OBJECTIVES: Clostridioides difficile infection (CDI) is a leading cause of antimicrobial-associated colitis and is a global clinical concern. Probiotics are considered a CDI-preventive measure; however, highly inconsistent data have been previously reported. Thus, we evaluated the CDI-preventive effect of prescribed probiotics in high-risk older patients receiving antibiotics. METHODS: Older patients (aged ≥65 years) admitted to the emergency department who received antibiotics between 2014 and 2017 were enrolled in this single-center retrospective cohort study. Propensity score-matched analysis was used to compare the CDI incidence in patients who took the prescribed probiotics within 2 days of receiving antibiotics for at least 7 days with those who did not. The rates of severe CDI and associated hospital mortality were also evaluated. RESULTS: Among 6148 eligible patients, 221 were included in the prescribed probiotic group. A propensity score-matched (221 matched pairs) well-balanced for patient characteristics was obtained. The incidence of primary nosocomial CDI did not differ significantly between the prescribed and non-prescribed probiotic groups (0% [0/221] vs. 1.0% [2/221], p = 0.156). Of the 6148 eligible patients, 0.5% (30/6148) developed CDI, with a severe CDI rate of 33.3% (10/30). Furthermore, no CDI-associated in-hospital mortality was observed in the study cohort. CONCLUSIONS: The evidence from this study does not support recommendations for the routine use of prescribed probiotics to prevent primary CDI in older patients receiving antibiotics in situations where the CDI is infrequent.


Assuntos
Infecções por Clostridium , Probióticos , Humanos , Idoso , Estudos Retrospectivos , Antibacterianos/efeitos adversos , Infecções por Clostridium/epidemiologia , Infecções por Clostridium/prevenção & controle , Infecções por Clostridium/tratamento farmacológico , Hospitalização , Probióticos/uso terapêutico
4.
Cancer Sci ; 113(1): 65-78, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34699654

RESUMO

Cancer susceptibility is a critical factor in the understanding of carcinogenesis. Intraperitoneal (i.p.) injection of an iron chelate, ferric nitrilotriacetate (Fe-NTA), produces hydroxyl radicals via Fenton reaction to induce ferroptosis in renal proximal tubules. Rats or mice subjected to repeated i.p. injections of Fe-NTA develop renal cell carcinoma (RCC). To elucidate the molecular mechanisms that cause susceptibility to renal carcinogenesis, we first established an inter-strain difference in the susceptibility to Fe-NTA-induced renal carcinogenesis in mice. Based on a previous observation of a low incidence of RCC with this model in C57BL/6J strain mice, we investigated A/J strain mice here, which demonstrated significantly higher susceptibility to Fe-NTA-induced renal carcinogenesis. Homozygous deletion of the Cdkn2a/2b tumor suppressor locus was detected for the first time in A/J strain mice. Focusing on ferroptosis and iron metabolism, we explored the mechanisms involved that lead to the difference in RCC development. We compared the protective responses in the kidney of A/J and C57BL/6J strains after Fe-NTA treatment. After 3-week Fe-NTA treatment, A/J mice maintained higher levels of expression of glutathione peroxidase 4 and xCT (SLC7A11), leading to a lower level of lipid peroxidation. Simultaneously, A/J mice had decreased expression of transferrin receptor and increased expression of ferritin to greater degrees than C57BL/6 mice. After a single Fe-NTA injection, higher levels of oxidative cell damage and cytosolic catalytic Fe(II) were observed in C57BL/6J mice, accompanied by a greater increase in lipocalin-2. Lipocalin-2 deficiency significantly decreased oxidative renal damage. Our results suggest that a genetic trait favoring ferroptosis resistance contributes to high susceptibility to Fe-NTA-induced RCC in A/J strain.


Assuntos
Carcinoma de Células Renais/patologia , Compostos Férricos/efeitos adversos , Redes Reguladoras de Genes , Neoplasias Renais/patologia , Ácido Nitrilotriacético/análogos & derivados , Deleção de Sequência , Animais , Carcinoma de Células Renais/induzido quimicamente , Carcinoma de Células Renais/genética , Transportador 1 de Aminoácidos Catiônicos/genética , Inibidor de Quinase Dependente de Ciclina p15/genética , Inibidor p16 de Quinase Dependente de Ciclina/genética , Ferritinas/genética , Ferroptose , Regulação Neoplásica da Expressão Gênica , Homozigoto , Injeções Intraperitoneais , Neoplasias Renais/induzido quimicamente , Neoplasias Renais/genética , Peroxidação de Lipídeos , Lipocalina-2/genética , Masculino , Camundongos , Neoplasias Experimentais , Ácido Nitrilotriacético/efeitos adversos , Estresse Oxidativo , Receptores da Transferrina/genética , Especificidade da Espécie , Regulação para Cima
5.
Opt Express ; 30(15): 28182-28189, 2022 Jul 18.
Artigo em Inglês | MEDLINE | ID: mdl-36236971

RESUMO

We surveyed the longitudinal-mode linewidth of five homemade mode-locked Yb:fiber lasers by taking the beat note with a Hz-level narrow-linewidth CW laser. We systematically varied the resolution bandwidth of the spectrum analyzer and found that the linewidth can be as narrow as 200 Hz, which surpassed the records for free-running mode-locked lasers in the literature to our best knowledge. Based on the survey, we propose that making the cavity long and simple is a good working hypothesis for narrowing the linewidth and provide practical techniques to reduce the environmental fluctuations.

6.
Phys Rev Lett ; 129(20): 206402, 2022 Nov 11.
Artigo em Inglês | MEDLINE | ID: mdl-36461993

RESUMO

Kagome metals AV_{3}Sb_{5} (A=K, Rb, and Cs) exhibit a characteristic superconducting ground state coexisting with a charge density wave (CDW), whereas the mechanisms of the superconductivity and CDW have yet to be clarified. Here we report a systematic angle-resolved photoemission spectroscopy (ARPES) study of Cs(V_{1-x}Nb_{x})_{3}Sb_{5} as a function of Nb content x, where isovalent Nb substitution causes an enhancement of superconducting transition temperature (T_{c}) and the reduction of CDW temperature (T_{CDW}). We found that the Nb substitution shifts the Sb-derived electron band at the Γ point downward and simultaneously moves the V-derived band around the M point upward to lift up the saddle point (SP) away from the Fermi level, leading to the reduction of the CDW-gap magnitude and T_{CDW}. This indicates a primary role of the SP density of states to stabilize the CDW. The present result also suggests that the enhancement of superconductivity by Nb substitution is caused by the cooperation between the expansion of the Sb-derived electron pocket and the recovery of the V-derived density of states at the Fermi level.

7.
Langmuir ; 38(44): 13401-13406, 2022 Nov 08.
Artigo em Inglês | MEDLINE | ID: mdl-36307095

RESUMO

Nanomaterials based on monoatomic bismuth (Bi) are attracting particular attention because they are candidates of two-dimensional (2D) topological insulators and Rashba metals useful for spintronic applications. We report convenient selective fabrication of two different types of ultrathin Bi films, bismuthene and α-Bi on hydrogen-terminated SiC(0001), by combining the molecular-beam-epitaxy (MBE) method and the low-temperature and low-pressure hydrogen chemical etching of SiC. We have succeeded in selectively fabricating these two different Bi phases by simply tuning the substrate temperature during the MBE process. We observed that while bismuthene and α-Bi showed a similar low-energy electron diffraction pattern of the (√3 × âˆš3)R30° periodicity, angle-resolved photoemission spectroscopy revealed a sizable difference in the band structure; bismuthene shows a massive Dirac cone, a signature of 2D topological insulators, whereas α-Bi exhibits an insulating behavior with a large band gap of more than 1.8 eV. We discuss the underlying mechanism of selective fabrication in terms of hydrogen desorption from the hydrogen-terminated SiC substrate.

8.
J Infect Chemother ; 28(11): 1571-1574, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-35870789

RESUMO

We evaluated the feasibility of type II-A clustered regularly interspaced short palindromic repeats (CRISPR) array-based genogrouping using Streptococcus dysgalactiae subsp. Equisimilis isolates from 32 humans and 8 companion animals and compared Simpson's diversity index of this genogrouping to those of multilocus sequence typing (MLST) and emm genotyping. CRISPRCasFinder detected a type II-A CRISPR array with the same repeat sequences in three whole-genome sequences. Subsequently, optimized polymerase chain reaction-based II-A CRISPR array amplification was performed to sequence the region around the leader and terminal repeat sequences. We conducted spacer genogrouping by evaluating the spacer sequence similarities. A phylogenetic dendrogram was constructed, and spacer content and polymorphisms were illustrated. Simpson's diversity indices were calculated for the CRISPR array genogrouping, MLST, and emm genotyping. We analyzed the association between the spacer genogroup with sequence type (ST)/emm genotype for each isolate. Of the 40 isolates, 39 with the II-A CRISPR array were amplified, sequenced, and assigned to 13 genogroups (A-M). The Simpson's diversity indices for the three typing were 0.874, 0.914, and 0.924, respectively. We found genetic lineages between genogroup M and ST127/stG245.0 and between genogroup I and ST29/stG485.0. These observations suggest the feasibility of II-A CRISPR array genogrouping and the genetic relationship between spacer genogroups and STs/emm genotypes in the isolates.


Assuntos
Repetições Palindrômicas Curtas Agrupadas e Regularmente Espaçadas , Infecções Estreptocócicas , Animais , Repetições Palindrômicas Curtas Agrupadas e Regularmente Espaçadas/genética , Humanos , Tipagem de Sequências Multilocus , Animais de Estimação , Filogenia , Streptococcus
9.
J Infect Chemother ; 28(3): 389-395, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-34848122

RESUMO

OBJECTIVE: We aimed to investigate dog/cat-origin quinolone-resistant Streptococcus agalactiae isolates with point mutations in quinolone resistance-determining regions (QRDRs) and to define the relatedness between quinolone-resistant isolates and their microbiological features of capsular genotype, sequence type (ST)/clonal complex (CC), and antimicrobial resistance (AMR) gene. METHODS: With dog/cat-origin 22 isolates, type strain, and human-origin 6 isolates, we performed antimicrobial susceptibility testing by agar plate dilution method using levofloxacin, ciprofloxacin, and moxifloxacin. We also determined amino acid sequences in QRDRs of gyrA/gyrB/parC/parE genes and their point mutations. We conducted capsular genotyping, multilocus sequence typing, and AMR genotyping in our previous investigations. Correlations between quinolone-resistant population and their microbiological features were examined. RESULTS: We found dog/cat-origin seven (31.8%) quinolone-resistant isolates harboring minimum inhibitory concentrations (MICs) of levofloxacin 16-32 µg/mL, ciprofloxacin 32 µg/mL, and moxifloxacin 2-4 µg/mL: human three isolates indicated MICs of levofloxacin 16-64 µg/mL, ciprofloxacin 32 µg/mL, and moxifloxacin 2-16 µg/mL. Point mutations Ser81Leu in gyrA and Ser79Phe/Ser79Tyr/Asp83Asn/Gly128Asp in parC were observed among these resistant isolates: mutations Leu495Ile/Val503Ile in parE was found among quinolone-nonresistant isolates. There was a significant correlation between dog/cat-origin quinolone-resistant population and ST10 (p = 0.023)/CC10 (p = 0.021). CONCLUSION: To our best knowledge, this is the first report assessing dog/cat-origin quinolone-resistant S. agalactiae. Our observations could be applied in future, by veterinarians while treating dogs and cats with clinical symptoms/signs suggestive of streptococcal infections.


Assuntos
Doenças do Gato , Doenças do Cão , Quinolonas , Animais , Antibacterianos/farmacologia , Gatos , DNA Girase/genética , DNA Topoisomerase IV/genética , Cães , Farmacorresistência Bacteriana/genética , Testes de Sensibilidade Microbiana , Mutação , Mutação Puntual , Quinolonas/farmacologia , Streptococcus agalactiae/genética
10.
J Infect Chemother ; 28(7): 982-986, 2022 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-35288022

RESUMO

As the COVID-19 pandemic persists, pregnant women have been increasingly affected worldwide. Women during the last trimester of pregnancy are susceptible to severe COVID-19, and there are many challenges towards its treatment. Monoclonal antibody treatment (MAT) is approved for COVID-19 patients to reduce disease severity. However, there are few reports on the MAT in perinatal women. Herein, we report a 39-year-old pregnant female (36 weeks and 6 days of gestation) with improvement in COVID-19 pneumonia after treatment with casiribimab/imdevimab, resulting in successful vaginal delivery (a 2.868 kg male newborn), along with a literature review. Early diagnosis and treatment of pregnant women with COVID-19 are important. Infectious diseases doctors and/or obstetricians should be aware of the MAT option administered to perinatal COVID-19 women to reduce disease severity.


Assuntos
Tratamento Farmacológico da COVID-19 , Complicações Infecciosas na Gravidez , Adulto , Anticorpos Monoclonais/uso terapêutico , Anticorpos Monoclonais Humanizados , Parto Obstétrico/métodos , Feminino , Humanos , Recém-Nascido , Masculino , Pandemias , Gravidez , Complicações Infecciosas na Gravidez/diagnóstico , Resultado da Gravidez , SARS-CoV-2
11.
Proc Natl Acad Sci U S A ; 116(49): 24470-24474, 2019 Dec 03.
Artigo em Inglês | MEDLINE | ID: mdl-31744873

RESUMO

The discovery of high-temperature (T c) superconductivity in monolayer FeSe on SrTiO3 raised a fundamental question: Whether high T c is commonly realized in monolayer iron-based superconductors. Tetragonal FeS is a key material to resolve this issue because bulk FeS is a superconductor with T c comparable to that of isostructural FeSe. However, difficulty in synthesizing tetragonal monolayer FeS due to its metastable nature has hindered further investigations. Here we report elucidation of band structure of monolayer FeS on SrTiO3, enabled by a unique combination of in situ topotactic reaction and molecular-beam epitaxy. Our angle-resolved photoemission spectroscopy on FeS and FeSe revealed marked similarities in the electronic structure, such as heavy electron doping and interfacial electron-phonon coupling, both of which have been regarded as possible sources of high T c in FeSe. However, surprisingly, high-T c superconductivity is absent in monolayer FeS. This is linked to the weak superconducting pairing in electron-doped multilayer FeS in which the interfacial effects are absent. Our results strongly suggest that the cross-interface electron-phonon coupling enhances T c only when it cooperates with the pairing interaction inherent to the superconducting layer. This finding provides a key insight to explore heterointerface high-T c superconductors.

12.
Cancer Sci ; 112(3): 1225-1234, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33370472

RESUMO

We have previously identified receptor tyrosine kinase-like orphan receptor 1 (ROR1) as a direct transcriptional target of TTF-1/NKX2-1, a lineage-survival oncogene in lung adenocarcinoma. ROR1 sustains prosurvival signaling from multiple receptor tyrosine kinases including epidermal growth factor receptor, MET, and insulin-like growth factor 1 receptor in part by maintaining the caveolae structure as a scaffold protein of cavin-1 and caveolin-1. In this study, a high throughput screening of the natural product library containing 2560 compounds was undertaken using a cell-based FluoPPI assay detecting ROR1-cavin-1 interaction. As a result, geldanamycin (GA), a known inhibitor of heat shock protein 90 (HSP90), was identified as a potential inhibitor of ROR1. Geldanamycin, as well as two GA derivatives tested in the clinic, 17-allylamino-17-demethoxygeldanamycin (17-AAG) and 17-dimethylaminoethylamino-17-demethoxygeldanamycin (17-DMAG), decreased ROR1 protein expression. We found that ROR1 physically interacted with HSP90α, but not with other HSP90 paralogs, HSP90ß or GRP94. Geldanamycin in turn destabilized and degraded ROR1 protein in a dose- and time-dependent manner through the ubiquitin/proteasome pathway, resulting in a significant suppression of cell proliferation in lung adenocarcinoma cell lines, for which the kinase domain of ROR1, but not its kinase activity or N-glycosylation, was required. Our findings indicate that HSP90 is required to sustain expression of ROR1 crucial for lung adenosarcoma survival, suggesting that inhibition of HSP90 could be a promising therapeutic strategy in ROR1-positive lung adenocarcinoma.


Assuntos
Adenocarcinoma de Pulmão/tratamento farmacológico , Antibióticos Antineoplásicos/farmacologia , Proteínas de Choque Térmico HSP90/antagonistas & inibidores , Neoplasias Pulmonares/tratamento farmacológico , Receptores Órfãos Semelhantes a Receptor Tirosina Quinase/metabolismo , Adenocarcinoma de Pulmão/patologia , Antibióticos Antineoplásicos/uso terapêutico , Benzoquinonas/farmacologia , Benzoquinonas/uso terapêutico , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Ensaios de Seleção de Medicamentos Antitumorais , Técnicas de Silenciamento de Genes , Proteínas de Choque Térmico HSP90/genética , Proteínas de Choque Térmico HSP90/metabolismo , Ensaios de Triagem em Larga Escala , Humanos , Lactamas Macrocíclicas/farmacologia , Lactamas Macrocíclicas/uso terapêutico , Neoplasias Pulmonares/patologia , Complexo de Endopeptidases do Proteassoma/metabolismo , Proteólise/efeitos dos fármacos , Proteínas de Ligação a RNA/metabolismo
13.
Cancer Sci ; 112(4): 1614-1623, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33506575

RESUMO

We previously reported that ROR1 is a crucial downstream gene for the TTF-1/NKX2-1 lineage-survival oncogene in lung adenocarcinoma, while others have found altered expression of ROR1 in multiple cancer types. Accumulated evidence therefore indicates ROR1 as an attractive molecular target, though it has yet to be determined whether targeting Ror1 can inhibit tumor development and growth in vivo. To this end, genetically engineered mice carrying homozygously floxed Ror1 alleles and an SP-C promoter-driven human mutant EGFR transgene were generated. Ror1 ablation resulted in marked retardation of tumor development and progression in association with reduced malignant characteristics and significantly better survival. Interestingly, gene set enrichment analysis identified a hypoxia-induced gene set (HALLMARK_HYPOXIA) as most significantly downregulated by Ror1 ablation in vivo, which led to findings showing that ROR1 knockdown diminished HIF-1α expression under normoxia and clearly hampered HIF-1α induction in response to hypoxia in human lung adenocarcinoma cell lines. The present results directly demonstrate the importance of Ror1 for in vivo development and progression of lung adenocarcinoma, and also identify Ror1 as a novel regulator of Hif-1α. Thus, a future study aimed at the development of a novel therapeutic targeting ROR1 for treatment of solid tumors such as seen in lung cancer, which are frequently accompanied with a hypoxic tumor microenvironment, is warranted.


Assuntos
Adenocarcinoma de Pulmão/genética , Subunidade alfa do Fator 1 Induzível por Hipóxia/genética , Neoplasias Pulmonares/genética , Receptores Órfãos Semelhantes a Receptor Tirosina Quinase/genética , Adenocarcinoma de Pulmão/patologia , Animais , Linhagem Celular Tumoral , Regulação para Baixo/genética , Regulação Neoplásica da Expressão Gênica/genética , Humanos , Hipóxia/genética , Neoplasias Pulmonares/patologia , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Camundongos Knockout , Camundongos Transgênicos , Oncogenes/genética , Transdução de Sinais/genética , Fator Nuclear 1 de Tireoide/genética , Microambiente Tumoral/genética
14.
Cancer Sci ; 112(7): 2770-2780, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-33934437

RESUMO

Ceramide synthase 6 (CERS6) promotes lung cancer metastasis by stimulating cancer cell migration. To examine the underlying mechanisms, we performed luciferase analysis of the CERS6 promoter region and identified the Y-box as a cis-acting element. As a parallel analysis of database records for 149 non-small-cell lung cancer (NSCLC) cancer patients, we screened for trans-acting factors with an expression level showing a correlation with CERS6 expression. Among the candidates noted, silencing of either CCAAT enhancer-binding protein γ (CEBPγ) or Y-box binding protein 1 (YBX1) reduced the CERS6 expression level. Following knockdown, CEBPγ and YBX1 were found to be independently associated with reductions in ceramide-dependent lamellipodia formation as well as migration activity, while only CEBPγ may have induced CERS6 expression through specific binding to the Y-box. The mRNA expression levels of CERS6, CEBPγ, and YBX1 were positively correlated with adenocarcinoma invasiveness. YBX1 expression was observed in all 20 examined clinical lung cancer specimens, while 6 of those showed a staining pattern similar to that of CERS6. The present findings suggest promotion of lung cancer migration by possible involvement of the transcription factors CEBPγ and YBX1.


Assuntos
Proteínas Estimuladoras de Ligação a CCAAT/metabolismo , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Movimento Celular , Neoplasias Pulmonares/metabolismo , Proteínas de Membrana/metabolismo , Pseudópodes , Esfingosina N-Aciltransferase/metabolismo , Proteína 1 de Ligação a Y-Box/metabolismo , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/patologia , Carcinoma Pulmonar de Células não Pequenas/secundário , Linhagem Celular Tumoral , Humanos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Proteínas de Membrana/genética , Invasividade Neoplásica , Regiões Promotoras Genéticas , Pseudópodes/genética , RNA Mensageiro/metabolismo , Esfingosina N-Aciltransferase/genética , Ativação Transcricional , Regulação para Cima , Proteína 1 de Ligação a Y-Box/genética , Proteínas rac1 de Ligação ao GTP
15.
Biochem Biophys Res Commun ; 578: 170-176, 2021 11 12.
Artigo em Inglês | MEDLINE | ID: mdl-34597914

RESUMO

Receptor tyrosine kinase-like orphan receptor 1 (ROR1) is highly expressed in a wide variety of hematological and solid cancers, but is low or absent in adult tissues. Here, we show that ROR1 is released with exosomes from ROR1-positive cancer cells. We also developed a simple dissociation-enhanced lanthanide fluorescence immunoassay (DELFIA) to detect cancer-derived ROR1-positive exosomes, which are captured by two anti-ROR1 antibodies and detected by the fluorescence of free chelating europium. This new DELFIA method can detect cancer-derived ROR1-positive exosomes in the cell supernatant and serum with a wide range and rapidly compared with the conventional Western blot assay. This method may be useful as a companion diagnostics for ROR1-positive cancers.


Assuntos
Antígenos de Neoplasias/metabolismo , Biomarcadores Tumorais/sangue , Exossomos/patologia , Imunoensaio/métodos , Neoplasias/patologia , Receptores Órfãos Semelhantes a Receptor Tirosina Quinase/metabolismo , Animais , Biomarcadores Tumorais/metabolismo , Linhagem Celular Tumoral , Modelos Animais de Doenças , Exossomos/metabolismo , Feminino , Humanos , Camundongos , Camundongos Endogâmicos BALB C , Neoplasias/sangue , Neoplasias/metabolismo
16.
Bioorg Med Chem Lett ; 40: 127961, 2021 05 15.
Artigo em Inglês | MEDLINE | ID: mdl-33741461

RESUMO

An efficient method for the synthesis of substituted 5-(hydroxymethyl)piperazin-2-ones was established by using an automated synthesis process. Thirteen piperazinones were synthesized from chiral α-bromocarboxylic acids and Garner's aldehyde which were prepared by using our originally developed automated synthesizer, ChemKonzert®. The automated method of synthesizing chiral α-bromocarboxylic acids was efficient and safe because the rate of the dropwise addition of the reagent can be controlled using the automated synthesizer. This method is expected to contribute to the synthesis of pharmaceuticals.


Assuntos
Aldeídos/química , Aminoácidos/química , Piperazinas/síntese química , Ciclização , Estrutura Molecular , Oxirredução , Estereoisomerismo
17.
J Infect Chemother ; 27(6): 814-819, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33526285

RESUMO

OBJECTIVE: Following the construction of a bacterial pan-genome from the whole genome sequences on a web-based pipeline, all coding DNA sequences (CDSs) can be clustered into pan-genome orthologous groups (POGs), which is a similar approach to comparative genome hybridization on glass microscope slides. We aimed to clarify the genomic characteristics of Streptococcus agalactiae based on the POG analysis. METHODS: Sixty-six S. agalactiae isolates obtained from invasive specimens (blood and cerebrospinal fluid) and non-invasive specimens (urine and vaginal discharge) between 2010 and 2017 in Korea were subjected to whole genome sequencing (WGS). Based on the WGS data, we conducted the POG analysis and constructed a phylogenetic tree along with capsular polysaccharide (CPS) genotyping. We compared the genomics of invasive vs. non-invasive isolates, as well as CPS III vs. non-CPS III genotypes. RESULTS: Predicted pan- and core-genome sizes were 3416 and 1658 genes, respectively. We found four clusters consisting of CPS genotypes (III, VIII, Ib/VI, and Ia) in the phylogenetic tree. There were significant differences in two metabolic pathways specific to invasiveness, and in six metabolic pathways specific to CPS III type produced by CDSs. CONCLUSION: Our observations reveal the pan- and core-genome sizes, four clusters of genomes distributed by CPS genotypes, and unique CDS features of S. agalactiae by comparative genomics in terms of invasiveness and CPS genotype.


Assuntos
Infecções Estreptocócicas , Streptococcus agalactiae , Feminino , Genômica , Genótipo , Humanos , Filogenia , República da Coreia , Streptococcus agalactiae/genética
18.
J Infect Chemother ; 27(4): 578-584, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33309630

RESUMO

INTRODUCTION: Mucoid (MTB313) and nonmucoid (MTB314) strains of group A streptococcus (GAS) emm (antiphagocytic M protein) type 1 were simultaneously isolated from a single patient suffering from streptococcal meningitis. In a CD46-expressing transgenic (CD46 Tg) mouse model of subcutaneous infection into both hind footpads with MTB313 or MTB314, MTB313 showed considerably higher virulence than MTB314. METHODS: The comparative genomic analysis based on the whole-genome sequencing revealed that MTB313 possessed an amber codon within rocA (sensory transduction protein kinase), but MTB314 did not carry this stop codon. Thereafter, MAT101 was generated from MTB313 by introducing pRocA, which contained the full-length rocA from MTB314, into the cloning plasmid pLZ12-Km2. MAT100 was also generated by introducing pLZ12-Km2 into MTB313. RESULTS: Although MTB313 and MAT100 showed large quantities of cell-associated hyaluronic acid (HA) in the culture pellets, MTB314 and MAT101 showed small quantities of HA production. Finally, higher mortalities were observed in the MTB313- or MAT100-infected CD46 Tg mice than the MTB314- or MAT101-infected CD46 Tg mice. CONCLUSIONS: These data indicate the possibility that a spontaneous point mutation in the rocA gene led to the highly virulent phenotype of M1 GAS.


Assuntos
Infecções Estreptocócicas , Streptococcus pyogenes , Transativadores/genética , Animais , Proteínas de Bactérias/genética , Humanos , Camundongos , Fenótipo , Mutação Puntual , Streptococcus pyogenes/genética
19.
J Infect Chemother ; 27(11): 1571-1577, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34217606

RESUMO

OBJECTIVE: We evaluated biofilm production ability (BPA) of Streptococcus agalactiae isolates from companion animals/humans and clarified the relationship between BPA populations and other microbiological features. METHODS: Companion animal-/human-origin isolates were collected with host information. We measured BPA using crystal violet staining, via virulence-associated gene profiling (hylB-pavA-pilB-spb1-srtC1-brpA), capsular genotyping, multilocus sequence typing, and antimicrobial resistance (AMR) phenotyping/genotyping. Significant difference in BPA of isolates from different hosts was assessed. We analyzed the association between BPA populations and the virulence genotypes, capsular genotypes, sequence types/clonal complexes, and AMR phenotypes/genotypes. Inhibitory effect of berberine on BPA was evaluated. RESULTS: Five, twenty-six, and twenty-six isolates belonged to strong, moderate, and weak biofilm producers, whereas seventeen showed no biofilm production. We defined strong, moderate, or weak biofilm producers as the producer group (n = 57) to conduct a comparative analysis between the producer and non-producer populations. There was a significant correlation between the producer population and vaginal specimen. We found significant associations between the producer group and presence (57.9%) of pilB and between the non-producer population and presence (70.6%) of spb1. There was no association between the producer group and capsular genotypes, sequence types/clonal complexes, and AMR phenotypes/genotypes (except for a significant correlation between the producer group and AMR to minocycline). We confirmed inhibitory effect of berberine at sub-minimum inhibitory concentrations (MICs) against the type strain on BPA. CONCLUSION: Our observations suggest that S. agalactiae harboring pilB is more capable of producing biofilms, with berberine inhibitory effect at sub-MICs on BPA.


Assuntos
Animais de Estimação , Streptococcus agalactiae , Animais , Antibacterianos/farmacologia , Biofilmes , Feminino , Genótipo , Humanos , Testes de Sensibilidade Microbiana , Streptococcus agalactiae/genética , Fatores de Virulência/genética
20.
J Infect Chemother ; 27(7): 999-1004, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-33663930

RESUMO

OBJECTIVE: This study evaluated the cell invasion ability (CIA) of Streptococcus agalactiae isolates from humans and companion animals and clarified the relationship between CIA populations and their microbiological features. METHODS: Human-origin and companion animal-origin isolates were collected along with host information. We measured CIA using human-lineage colon cancer epithelium (Caco-2) and keratinocyte (HaCaT) cell lines, via virulence-associated gene profiling (bca-rib-bac-lmb-cylE-hylB-pavA-pilB-spb1-srtC1-brpA), capsular genotyping, multilocus sequence typing, and antimicrobial resistance (AMR) phenotyping/genotyping. Significant differences in data regarding CIA into epithelium and keratinocytes and those of isolates from different hosts were assessed. We analyzed the association of CIA populations with the virulence genotypes, capsular genotypes, sequence types/clonal complexes, and AMR phenotypes/genotypes. RESULTS: A comparative analysis was performed between human (n = 15) and canine (n = 17) non-invasive isolates. There was a difference in CIA data between Caco-2 and HaCaT cells using human and animal isolates. For percent invasion ability into Caco-2 cells, we designated values ≥ 0.1 as high-frequency CIA and values < 0.1 as low-frequency CIA. Fourteen isolates harbored high-frequency and 18 isolates harbored low-frequency strains. There was no association between the high-frequency population and the virulence genotypes, capsular genotypes, sequence types/clonal complexes, and AMR phenotypes/genotypes. CONCLUSION: This is the first report assessing the invasion ability of S. agalactiae into HaCaT and Caco-2 cells. Our observations suggest that S. agalactiae is more capable of entering Caco-2 rather than HaCaT.


Assuntos
Infecções Estreptocócicas , Streptococcus agalactiae , Adulto , Animais , Células CACO-2 , Cães , Genótipo , Humanos , Japão , Animais de Estimação , Infecções Estreptocócicas/veterinária , Streptococcus agalactiae/genética , Fatores de Virulência
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