Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 450
Filtrar
1.
Bioorg Med Chem Lett ; 40: 127961, 2021 Mar 17.
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.

2.
J Infect Chemother ; 2021 Mar 02.
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.

3.
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.

4.
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
5.
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.

6.
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
7.
AACE Clin Case Rep ; 6(6): e305-e310, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33244490

RESUMO

Objective: Dystrophic scoliosis is a serious skeletal manifestation of neurofibromatosis 1 (NF1). The condition requires surgical intervention that is frequently associated with poor outcome due to the high rate of impaired bone healing, pseudoarthrosis, and loosening of the spinal instrumentation. New therapeutic approaches are needed to improve surgical outcomes. Methods: Clinical, laboratory, and radiographic data are presented. Results: A 54-year-old woman with severe NF1 related dystrophic scoliosis and 3 prior surgical interventions underwent revision of lumbar fusion with intraoperative recombinant human bone morphogenetic protein (rhBMP-2) for loosening and a fracture of the left vertical rod at the L4 pedicle screw connection. Two days after surgery, a computed tomography (CT) scan revealed a left posterior iliac periscrew fracture. Given a high risk of mechanical failure, zoledronic acid and asfotase alfa were also administered at 3 and 7 months after surgery. At 14 months after surgery, back pain improved, and a CT scan showed stable spinal fusion and a healed left posterior iliac screw fracture. Conclusion: Combination therapy including asfotase alfa with rhBMP-2 and bisphosphonate resulted in solid arthrodesis after spinal surgery in NF1-related dystrophic scoliosis.

8.
IDCases ; 22: e00980, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33204629

RESUMO

Background: Group A Streptococcus pyogenes (GAS) causes necrotizing soft tissue infections (NSTIs) necessitating exploration, surgical debridement, and possibly limb amputation. Case presentation: A 45-year-old man presented with traumatic injury of the left carpal region, vomiting, and diarrhea. The swelling and pain in the left forearm worsened with sensorimotor deficits, and his skin color deteriorated. Emergent exploration was performed for limb preservation; GAS was detected in an exudate, and debridement was performed on postoperative day 2 for streptococcal toxic shock syndrome. He recovered uneventfully and was discharged; however, he returned after 2 months with GAS-induced STI at the same site and received antimicrobial treatment. Conclusion: Exploration and subsequent debridement are crucial for effective treatment of NSTI.

9.
Adv Mater ; 32(48): e2005838, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33118240

RESUMO

3D integration of graphene has attracted attention for realizing carbon-based electronic devices. While the 3D integration can amplify various excellent properties of graphene, the influence of 3D curved surfaces on the fundamental physical properties of graphene has not been clarified. The electronic properties of 3D nanoporous graphene with a curvature radius down to 25-50 nm are systematically investigated and the ambipolar electronic states of Dirac fermions are essentially preserved in the 3D graphene nanoarchitectures, while the 3D curvature can effectively suppress the slope of the linear density of states of Dirac fermion near the Fermi level are demonstrated. Importantly, the 3D curvature can be utilized to tune the back-scattering-suppressed electrical transport of Dirac fermions and enhance both electron localization and electron-electron interaction. As a result, nanoscale curvature provides a new degree of freedom to manipulate 3D graphene electrical properties, which may pave a new way to design new 3D graphene devices with preserved 2D electronic properties and novel functionalities.

10.
Int J Spine Surg ; 14(4): 527-533, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32986573

RESUMO

BACKGROUND: The radiologist interpretation of scoliosis films is non-standardized, with some practitioners providing detailed measurements of the deformity whereas others defer the interpretation of the deformity to the ordering surgeon. For radiologists, the standard of care is not clear, and this creates confusion in terms of how much interpretation is required. However, detailed radiologist reports sometimes conflict with the surgeon's interpretation, which can create confusion for patients who receive the reports, or in extreme cases can lead to insurance denials. Thus, the purpose of this study was to help establish a standard for interpretation of these films by surveying the ordering surgeons and documenting expert opinion about the amount and type of radiologist interpretation that is requested. METHODS: We designed a SurveyMonkey survey which aimed to look at standard practice for radiologist dictation of scoliosis radiographs. Twelve questions were sent to Lumbar Spine Research Society membership via email with a description of the study. One follow-up email was also sent to non-responders. RESULTS: The rate of completed surveys was 46 out of 185 Lumbar Spine Research Society members (25%). Thirty-seven respondents (80%) worked in academic institutions, 33 were orthopedists (71%), and 13 were neurosurgeons (28%). Fifty percent reported that radiologists' level of detail in dictations was inconsistent at their institution. Detailed numeric reporting was rare (6.5%). When the radiologist did provide numeric measurements, surgeons reported that they often differed from the surgeon's own measurements, with only 4% reporting that the measurements "rarely" differed from the surgeon's; 49% reported that the radiologist's measurements that differed from the surgeon's had led to insurance denials for their patients. The majority of respondents (70%) did not want the radiologist to provide detailed numeric measurements of the deformity, and 91% reported that the radiologist's measurements had no impact on their clinical decision making. CONCLUSIONS: Detailed deformity measurements are time consuming for the radiologist, and would seem to have low clinical utility for the responding surgeons in this survey, with significant potential for discrepancies in interpretation to lead to insurance denials. LEVEL OF EVIDENCE: IV.

11.
J Cell Mol Med ; 24(20): 11949-11959, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32902157

RESUMO

Sphingolipids constitute a class of bio-reactive molecules that transmit signals and exhibit a variety of physical properties in various cell types, though their functions in cancer pathogenesis have yet to be elucidated. Analyses of gene expression profiles of clinical specimens and a panel of cell lines revealed that the ceramide synthase gene CERS6 was overexpressed in non-small-cell lung cancer (NSCLC) tissues, while elevated expression was shown to be associated with poor prognosis and lymph node metastasis. NSCLC profile and in vitro luciferase analysis results suggested that CERS6 overexpression is promoted, at least in part, by reduced miR-101 expression. Under a reduced CERS6 expression condition, the ceramide profile became altered, which was determined to be associated with decreased cell migration and invasion activities in vitro. Furthermore, CERS6 knockdown suppressed RAC1-positive lamellipodia/ruffling formation and attenuated lung metastasis efficiency in mice, while forced expression of CERS6 resulted in an opposite phenotype in examined cell lines. Based on these findings, we consider that ceramide synthesis by CERS6 has important roles in lung cancer migration and metastasis.

12.
Jpn J Infect Dis ; 2020 Aug 31.
Artigo em Inglês | MEDLINE | ID: mdl-32863352

RESUMO

This study evaluated cell invasion ability (CIA) of Streptococcus canis isolates and clarified the relationship between high-frequency CIA and microbiological features. Of the companion animal-origin isolates (n = 117) in 2017, 40 isolates were randomly selected with the host information, and two human blood-origin isolates were included. We measured the CIA using human colon carcinoma epithelium and the hemolytic activity (HA) using sheep blood, along with S. canis M-like protein (SCM) allele typing, sequence type (ST) determination, and antimicrobial resistance (AMR) phenotyping/genotyping. CIA measurements revealed that 19 isolates were high-frequency and 24 isolates were low-frequency. The HA assessment revealed that 24 isolates were categorized as high-level and 19 isolates were low-level. There was no difference in the high/low-level HA between the high-frequency/low-frequency CIA populations. There was a significant difference in the high/low-frequency CIA between SCM group I/II populations. There was also significantly higher CIA in the SCM allele type 10/type 11 than in others. We found a significant association between high-frequency CIA and ST21/ST41 populations. There was no difference in the high/low-frequency CIA between the presence and absence of AMR phenotype/genotype. Our observations suggest a relationship between high-frequency CIA and its microbiological characteristics (SCM allele type 10/type 11 or ST21/ST41).

13.
Microbiol Resour Announc ; 9(33)2020 Aug 13.
Artigo em Inglês | MEDLINE | ID: mdl-32817161

RESUMO

This study reports the complete genome sequences of four strains of Streptococcus canis isolated from dogs in South Korea. Their genomes ranged from 2.157 to 2.265 Mbp, with a G+C content of 39.6% to 39.7%. The sequence types, antimicrobial resistance genes, and S. canis M-like protein alleles were characterized.

14.
Microbiol Resour Announc ; 9(35)2020 Aug 27.
Artigo em Inglês | MEDLINE | ID: mdl-32855249

RESUMO

The draft genome sequence of the blood-origin Streptococcus canis strain FU149, isolated from a dog with a necrotizing soft tissue infection in Japan, is reported. The genome size was 2.108 Mbp, with a G+C content of 39.5%. Sequences unmapped to the reference genome sequence of NCTC 12191T (GenBank accession number LR134293) were characterized.

15.
J Vet Med Sci ; 82(9): 1316-1320, 2020 Oct 07.
Artigo em Inglês | MEDLINE | ID: mdl-32713891

RESUMO

We aimed to clarify antimicrobial susceptibility patterns of anaerobes from diseased companion animals. Bacterial identification was based on the Japanese 2012 guidelines for the testing of anaerobic bacteria. AST was performed using the broth microdilution method. The anaerobe-containing samples collected from 2014 to 2018 included blood (anaerobe recovery rate, 5.0%), bile (9.4%), joint fluids (0.6%), pleural effusions (42.6%), ascites (64.1%), cerebrospinal fluids (3.0%), and punctures (75.0%). The anaerobes identified included Bacteroides spp. (33.2%), Peptostreptococcus spp. (19.6%), Prevotella spp. (13.6%), Propionibacterium spp. (10.3%), Clostridium spp. (9.3%), and Fusobacterium spp. (7.5%). Bacteroides fragilis group isolates were resistant to penicillin G (100%), ampicillin (100%), cefmetazole (63.6%), ceftizoxime (90.0%), and clindamycin (40.0%). Our observations demonstrated antimicrobial susceptibility in anaerobes isolated from Japanese companion animals.

16.
Methods Mol Biol ; 2169: 43-52, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32548817

RESUMO

Fluorescence microscopy is currently one of the more powerful and versatile techniques available for biological studies. With conventional biological immunofluorescence microscopy, caveolin-1 (CAV1) is visualized as numerous small dots, which are often distributed as a linear array or along the edge of the cell. Although its presence, as well as that of other proteins, can be detected by conventional immunofluorescence microscopy, those results do not clarify whether two different proteins exist in the plasma membrane of a specimen or how they are distributed two-dimensionally. Here, we describe an unroofing procedure that clearly reveals CAV1 localization in a single plane of the plasma membrane and also demonstrate a super-resolution structured illumination microscopy technique for observation of CAV1 in the plasma membrane.

17.
Skeletal Radiol ; 49(12): 1987-1994, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32564102

RESUMO

OBJECTIVE: To evaluate whether a commonly used surgical grading scale, when applied to acetabular labral findings on MRI, could improve preoperative planning and counseling for patients undergoing hip arthroscopy. MATERIALS AND METHODS: We evaluated 76 clinical MRIs performed on patients with femoroacetabular impingement. Three musculoskeletal radiologists and one musculoskeletal fellow reviewed each scan in a blinded fashion, classifying the acetabular labrum from 12:00 to 4:00 using the Beck scale, a common surgical grading scale. Clinical correlation was provided via surgical examination and classification. Reliability was determined between readers and between reader and surgical data using Cohen's kappa and Krippendorff's alpha at each clock position and for the worst grading for each scan. In addition, a simplified version of the scale comprised of only two grades, potentially reparable and not potentially reparable, was evaluated. RESULTS: When the scale was simplified into categories of potentially reparable and not potentially reparable, the sensitivity was excellent, ranging from 85.5 to 96%. Observer agreement when using individual Beck grades was found to range from poor to fair; Kappa ranged from 0.03 to 0.19, and Alpha ranged from - 0.27 to 0.22. CONCLUSION: The simplified version of the Beck labral scale when applied to MRI is a highly sensitive predictor of potentially reparable labral pathology while excluding normal and grossly degenerative tissue. Use of this scale provides clinically relevant information that can drive preoperative planning and improve patient counseling. It does so in a standardized fashion that can be applied across practice sites and without additional cost.

18.
Nat Genet ; 52(7): 669-679, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32514122

RESUMO

The overwhelming majority of participants in current genetic studies are of European ancestry. To elucidate disease biology in the East Asian population, we conducted a genome-wide association study (GWAS) with 212,453 Japanese individuals across 42 diseases. We detected 320 independent signals in 276 loci for 27 diseases, with 25 novel loci (P < 9.58 × 10-9). East Asian-specific missense variants were identified as candidate causal variants for three novel loci, and we successfully replicated two of them by analyzing independent Japanese cohorts; p.R220W of ATG16L2 (associated with coronary artery disease) and p.V326A of POT1 (associated with lung cancer). We further investigated enrichment of heritability within 2,868 annotations of genome-wide transcription factor occupancy, and identified 378 significant enrichments across nine diseases (false discovery rate < 0.05) (for example, NKX3-1 for prostate cancer). This large-scale GWAS in a Japanese population provides insights into the etiology of complex diseases and highlights the importance of performing GWAS in non-European populations.


Assuntos
Predisposição Genética para Doença , Estudo de Associação Genômica Ampla , Estudos de Coortes , Feminino , Predisposição Genética para Doença/etnologia , Variação Genética , Humanos , Padrões de Herança , Japão , Masculino , Fatores Sexuais , Fatores de Transcrição/genética
19.
Biol Pharm Bull ; 43(6): 951-958, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32475917

RESUMO

The fungal 13-membered cyclodepsipeptides, beauveriolides I and III, were previously reported to be atheroprotective activity in mouse models via inhibiting sterol O-acyltransferase (SOAT) activity. A total of 149 beauveriolide derivatives (BVDs) synthesized combinatorially were evaluated in in silico absorption, distribution, metabolism and excretion (ADME) analysis and inhibitory activity toward the two SOAT isozymes, SOAT1 and SOAT2. Hence, only 11 BVDs exhibited SOAT2-selective inhibition. Among these, we chose BVD327, which had the highest ADME score, for further evaluation. BVD327 administration (50 mg/kg/d, per os (p.o.)) significantly decreased atherosclerotic lesions in the aorta and heart (25.4 ± 6.9 and 20.6 ± 2.9%, respectively) in apolipoprotein E knockout (Apoe-/-) mice fed a cholesterol-enriched diet (0.2% cholesterol and 21% fat) for 12 weeks. These findings indicate that beauveriolide derivatives can be used as anti-atherosclerotic agents.

20.
J Infect Chemother ; 26(9): 908-915, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32354600

RESUMO

OBJECTIVE: We aimed to determine novel alleles and their prevalence in Streptococcus canis M-like protein (SCM) and to elucidate association of their alleles with sequence types (STs)/clonal complexes (CCs) and antimicrobial resistance (AMR) phenotypes/genotypes. METHODS: We amplified and sequenced scm, by using primers reported by Pinho recently, for 40 isolates in 2015 and 2017, in which the sequences could not be determined with conventional primers. Isolates, for which SCM alleles, STs, and AMR phenotypes/genotypes were previously determined, were included as controls. A phylogenetic tree of SCM amino acid sequences was constructed. Alleles, based on the tree positions with their prevalence, as well as STs/CCs and AMR phenotypes/genotypes were characterized. RESULTS: Although one isolate possessed SCM allele type 1, 39 isolates had novel allele types 10-15, based on cluster analysis. The 11 and 12 allele types were firstly found in this study. We designated novel allele types as group II and non-novel allele types as group I. Prevalence of group II alleles was 29.9% and 16.2% in 2015 and 2017. Prevalent group II types were allele 10 (10.3%), allele 11 (2.7%), and allele 15 (3.3%) through both periods. There was a significant difference in distribution of STs/CCs between groups I/II SCM populations. We found significant differences in distribution of macrolide/lincosamide AMR genotype (7.7% vs. 26.8%) and AMR rates of fluoroquinolone (0% vs. 12.5%) between the two populations. CONCLUSION: Our study presents group II scm sequences and their prevalence among diseased companion animals in Japan, with association of their alleles with STs.

SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...