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1.
J Neuroimmunol ; 352: 577475, 2021 Mar 15.
Artículo en Inglés | MEDLINE | ID: mdl-33454554

RESUMEN

In this study, we assessed circulating immune cells and plasma cytokine levels in 15 pediatric patients with drug-resistant epilepsy (DRE). DRE patients had a significantly higher percentage of CD14+ monocytes positive for IL-1ß, IL-1 receptor antagonist, IL-6, and TNF-α than controls. Significantly higher intracellular levels of IFN-γ in CD4+ T cells and NK cells were also found in DRE patients. The level of IL-1ß+ CD14+ monocytes correlated with seizure frequency, and intracellular levels of IFN-γ in NKT-like cells were negatively correlated with the duration of epilepsy. Peripheral immune cells might be involved in the pathogenesis of DRE.

2.
Org Biomol Chem ; 19(6): 1305-1314, 2021 Feb 18.
Artículo en Inglés | MEDLINE | ID: mdl-33503080

RESUMEN

1,6-Conjugate additions of in situ generated δ-CF3-δ-substituted p-quinone methides have been achieved with a variety of heteronucleophiles under mild conditions, which led to facile and practical construction of fully substituted carbon centers including a heteroatom and a CF3 group. In particular, it was revealed that some amines themselves worked for efficient cleavage of the TBS protective group, and addition of a catalytic amount of an appropriate Brønsted acid was found to sometimes improve the progress of the desired process.

3.
Microbiol Immunol ; 65(2): 89-94, 2021 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-33393685

RESUMEN

As part of a series of studies regarding the microbiota in manned space environments, we isolated the fungal strains from nasal and pharyngeal smears and saliva of 21 astronauts preflight, in-flight, and postflight. On the ground, 120 strains from 43 genera of environmental fungi were isolated from the astronauts. The dominant fungal genera were Cladosporium, Penicillium, and Aspergillus. Only 18 strains from four genera were isolated from the astronauts inside the International Space Station. These fungi are currently thought to be harmless, but regular screening and cleaning are necessary to prevent fungus-related health disorders.

4.
Eur Spine J ; 2021 Jan 29.
Artículo en Inglés | MEDLINE | ID: mdl-33512588

RESUMEN

PURPOSE: Surgical site infection (SSI) is one of the most devastating complications following spinal instrumented fusion surgeries because it may lead to a significant increase in morbidity, mortality, and poor clinical outcomes. Identifying the risk factors for SSI can help in developing strategies to reduce its occurrence. However, data on the risk factors for SSI in degenerative diseases are limited. This study aimed to identify risk factors for deep SSI following posterior instrumented fusion for degenerative diseases in the thoracic and/or lumbar spine in adult patients. METHODS: This was a multicenter, observational cohort study conducted at 10 study hospitals between July 2010 and June 2015. The subjects were consecutive adult patients who underwent posterior instrumented fusion surgery for degenerative diseases in the thoracic and/or lumbar spine and developed SSI. Detailed patient-specific and procedure-specific potential risk variables were prospectively recorded using a standardized data collection chart and retrospectively reviewed. RESULTS: Of the 2913 enrolled patients, 35 developed postoperative deep SSI (1.2%). Multivariable regression analysis identified three independent risk factors: male sex (P = 0.002) and American Society of Anesthesiologists (ASA) score of ≥ 3 (P = 0.003) as patient-specific risk factors, and operation including the thoracic spine (P = 0.018) as a procedure-specific risk factor. CONCLUSION: Thoracic spinal surgery, an ASA score of ≥ 3, and male sex were risk factors for deep SSI after routine thoracolumbar instrumented fusion surgeries for degenerative diseases. Awareness of these risk factors can enable surgeons to develop a more appropriate management plan and provide better patient counseling.

5.
Med Mycol ; 2020 Aug 24.
Artículo en Inglés | MEDLINE | ID: mdl-32838424

RESUMEN

Analysis of the skin mycobiome of an astronaut during a 1-year stay on the International Space Station (ISS) revealed an increased relative abundance of Malassezia restricta and level of Malassezia colonization, and the presence of Cyberlindnera jadinii and Candida boidinii, uncommon skin mycobiome taxa. Similar observations were made in astronauts during a 6-month stay on the ISS (Med Mycol. 2016; 54: 232-239). Future plans for extended space travel should consider the effect of high levels of Malassezia colonization over long periods on astronauts' skin, and the abnormal proliferation of uncommon microorganisms that may occur in closed environments such as the ISS.

6.
Mass Spectrom (Tokyo) ; 9(1): A0087, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-32802701

RESUMEN

Peptides larger than 3-4 kDa, such as neuropeptide Y (NPY), orexin-B, and alpha-MSH, have practical issues that arise when conducting direct and sensitive quantitative liquid chromatography (LC) orbitrap-FT mass spectrometry (MS) due to their adsorption and low ionization efficiency, especially in standard solutions. A mixing solvent consisting of 0.5% trifluoroacetic acid (TFA) and 35-50% aq. acetonitrile was developed as the standard NPY for creating calibration curves, as well as a matrix to block the experimental tube surface to minimize adsorption. The mixture matrix effectively blocked non-specific adsorption of the standard peptides with tryptic digested bovine serum albumin (BSA) (small fragment peptides) and orexin-B (a large chain peptide). A sample containing 1 : 100 peptide:water was detected in the developed sample solution. Finally, 2 to 1,000 fmol/µL NPY could be analyzed quantitatively and reproducibly using conventional LC-MS. Parameters of the calibration curves, such as X-intercept, Bias (%), and relative standard deviation (RSD), were adjusted to optimize the sample solutions and the sensitive and quantitative LC-MS analyses.

7.
Sci Rep ; 10(1): 13562, 2020 08 11.
Artículo en Inglés | MEDLINE | ID: mdl-32782316

RESUMEN

NLRP3, an intracellular pattern recognition receptor, recognizes numerous pathogens and/or its own damage-associated molecules, and forms complexes with the adaptor protein ASC. These complexes constitute the NLRP3 inflammasome, a platform for processing interleukin (IL)-1ß and/or IL-18. Several NLRP3 mutations result in constitutive activation of the NLRP3 inflammasome, causing cryopyrin-associated periodic syndrome (CAPS). To the best of our knowledge, small compounds that specifically inhibit inflammasome activation through the pyrin domain (PYD) have not yet been developed. This study describes an attempt to develop small compounds targeting the NLRP3 inflammasome. A core chemical library of 9,600 chemicals was screened against reconstituted NLRP3 inflammasome in a cell-free system with an amplified luminescence proximity homogeneous assay and a cell-based assay by human peripheral blood mononuclear cells (PBMCs). Inflammasome activation was evaluated by ASC-speck formation in human PBMCs, accompanied by IL-1ß secretion and processing, and by using IL-1ß-based dual operating luciferase (IDOL) mice. The activity of these compounds was evaluated clinically using PBMCs from a patient with Muckle-Wells syndrome (MWS), a type of CAPS, with an R260W mutation in NLRP3. Screening identified KN3014, a piperidine-containing compound targeting the interaction between NLRP3 and ASC through the PYD. KN3014 reduced ASC-speck formation in human PBMCs, luminescence from IDOL mice, and auto-secretion of IL-1ß by PBMCs from the patient with MWS. These findings suggest that KN3014 may be an attractive candidate for treatment of MWS, as well as other NLRP3 inflammasomopathies.

8.
Sci Rep ; 10(1): 13605, 2020 08 12.
Artículo en Inglés | MEDLINE | ID: mdl-32788637

RESUMEN

Scale-up of production is needed for industrial applications and clinical translation of human induced pluripotent stem cells (hiPSCs). However, in cryopreservation of hiPSCs, successful rewarming of vitrified cells can only be achieved by convective warming of small volumes (generally 0.2 mL). Here, we present a scalable nano-warming technology for hiPSC cryopreservation employing inductive heating of magnetic nanoparticles under an alternating magnetic field. The conventional method by water bath heating at 37 °C resulted in a decrease of cell viability owing to devitrification caused by slow warming of samples with large volumes (≥ 20 mL). Nano-warming showed uniform and rapid rewarming of vitrified samples and improved viability of hiPSCs in the 20-mL system. In addition to single cells, hiPSC aggregates prepared using a bioreactor-based approach were successfully cryopreserved by the nano-warming technique. These results demonstrate that nano-warming is a promising methodology for cryopreservation in mass production of hiPSCs.

9.
Org Biomol Chem ; 18(24): 4638-4644, 2020 Jun 24.
Artículo en Inglés | MEDLINE | ID: mdl-32520052

RESUMEN

New and successful results for the construction of new and structurally interesting compounds are reported via N-heterocyclic carbene (NHC)-catalyzed 1,6-conjugate additions of a variety of aldehydes to δ-CF3-δ-substituted p-quinone methides generated in situ, and the products are used for the 1,2-addition reactions of appropriate metal nucleophiles, enabling us to furnish highly diastereoselective products with a unique successive quaternary carbon-tertiary alcohol framework (up to dr = >99 : 1).

10.
RNA Biol ; 17(10): 1383-1390, 2020 10.
Artículo en Inglés | MEDLINE | ID: mdl-32449435

RESUMEN

Burkitt lymphoma (BL) is an aggressive B-cell lymphoma characterized by translocation and deregulation of the proto-oncogene c-MYC. Transcription factor 3 (TCF3) has also been shown to be involved in BL pathogenesis. In BL, TCF3 is constitutively active, and/or expression of its transcriptional targets are altered as a result of BL-associated mutations. Here, we found that BL-related TCF3 mutations affect TCF3 alternative splicing, in part by reducing binding of the splicing regulator hnRNPH1 to exon 18b. This leads to greater exon 18b inclusion, thereby generating more of the mutated E47 isoform of TCF3. Interestingly, upregulation of E47 dysregulates the expression of TCF3 targets PTPN6, and perhaps CCND3, which are known to be involved in BL pathogenesis. Our findings thus reveal a mechanism by which TCF3 somatic mutations affect multilayered gene regulation underlying BL pathogenesis.

11.
Astrobiology ; 20(7): 820-829, 2020 07.
Artículo en Inglés | MEDLINE | ID: mdl-32207981

RESUMEN

The plant cell wall provides each cell with structural support and mechanical strength, and thus, it plays an important role in supporting the plant body against the gravitational force. We investigated the effects of microgravity on the composition of cell wall polysaccharides and on the expression levels of genes involved in cell wall metabolism using rice shoots cultivated under artificial 1 g and microgravity conditions on the International Space Station. The bulk amount of the cell wall obtained from microgravity-grown shoots was comparable with that from 1 g-grown shoots. However, the analysis of sugar constituents of matrix polysaccharides showed that microgravity specifically reduced the amount of glucose (Glc)-containing polysaccharides such as 1,3:1,4-ß-glucans, in shoot cell walls. The expression level of a gene for endo-1,3:1,4-ß-glucanase, which hydrolyzes 1,3:1,4-ß-glucans, largely increased under microgravity conditions. However, the expression levels of genes involved in the biosynthesis of 1,3:1,4-ß-glucans were almost the same under both gravity conditions. On the contrary, microgravity scarcely affected the level and the metabolism of arabinoxylans. These results suggest that a microgravity environment promotes the breakdown of 1,3:1,4-ß-glucans, which, in turn, causes the reduced level of these polysaccharides in growing rice shoots. Changes in 1,3:1,4-ß-glucan level may be involved in the modification of mechanical properties of cell walls under microgravity conditions in space.

12.
Chem Commun (Camb) ; 56(20): 3031-3034, 2020 Mar 10.
Artículo en Inglés | MEDLINE | ID: mdl-32048635

RESUMEN

Development of a new synthetic method for the construction of quaternary centers with a trifluoromethyl group was realized by way of 1,6-addition of various nucleophiles including active methylene compounds to highly reactive δ-trifluoromethylated p-quinone methides generated in situ from the corresponding tertiary carbonates with a catalytic amount of an appropriate base.

13.
Org Lett ; 22(5): 2044-2048, 2020 Mar 06.
Artículo en Inglés | MEDLINE | ID: mdl-32083887

RESUMEN

Our computation has successfully clarified the reluctant behavior of trans- and cis-1,3,3,3-tetrafluoropropene oxides 1c toward nucleophiles and led to the expectation that these epoxides would react under the Brønsted acid activation conditions. Actually, this was the case, and these epoxides smoothly opened with CF3SO3H, whose elimination after the protection of the resultant OH group afforded the enol benzoates as the enolate precursors, which nicely allowed us to construct the corresponding aldol products by reactions with various aldehydes.

14.
World Neurosurg ; 134: e524-e529, 2020 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-31669691

RESUMEN

BACKGROUND: Surgical site infection (SSI) is a dire complication in spinal surgeries, resulting in reoperation, prolonged hospitalization, and increased expenses. Patients with traumatized spine have been reported to have a high risk of postoperative SSI. Precise identification of risk factors associated with SSI can be helpful in its prevention. However, there are only a limited number of studies investigating risk factors of SSI after posterior instrumented fusion for traumatized spine. METHODS: From July 2010 to June 2015, we conducted an observational study on deep SSI after posterior instrumented fusion surgery for spinal trauma in adult patients at 10 research hospitals. Detailed clinical data were prospectively collected using a standardized data collection chart and were retrospectively analyzed. SSI was diagnosed based on the definition by the Centers for Disease Control and Prevention. RESULTS: A total of 623 consecutive adult patients were enrolled in this study, of which 20 (3.2%) developed deep SSI. According to multivariate regression analysis, surgery at academic hospitals (P = 0.004) and an American Society of Anesthesiologists (ASA) score ≥3 (P = 0.017) were independent predictors of deep SSI after posterior instrumented fusion surgery for spinal trauma. CONCLUSIONS: The complexity of patients and resident involvement in surgeries may be greater at academic than at nonacademic hospitals. ASA score can be considered as an accessible and comprehensive tool for surgeons to preoperatively gauge the potential risk of SSI, a complex clinical entity. The results of this study can improve clinicians' risk perception in those undergoing posterior fusion for spinal trauma.


Asunto(s)
Fusión Vertebral , Infección de la Herida Quirúrgica/epidemiología , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Factores de Riesgo , Fusión Vertebral/métodos , Traumatismos Vertebrales/epidemiología , Traumatismos Vertebrales/cirugía , Columna Vertebral/cirugía , Infección de la Herida Quirúrgica/etiología , Adulto Joven
15.
RNA ; 25(11): 1497-1508, 2019 11.
Artículo en Inglés | MEDLINE | ID: mdl-31391218

RESUMEN

TCF3, also known as E2A, is a well-studied transcription factor that plays an important role in stem cell maintenance and hematopoietic development. The TCF3 gene encodes two related proteins, E12 and E47, which arise from mutually exclusive alternative splicing (MEAS). Since these two proteins have different DNA binding and dimerization domains, this AS event must be strictly regulated to ensure proper isoform ratios. Previously, we found that heterogeneous nuclear ribonucleoprotein (hnRNP) H1/F regulates TCF3 AS by binding to exonic splicing silencers (ESSs) in exon 18b. Here, we identify conserved intronic splicing silencers (ISSs) located between, and far from, the two mutually exclusive exons, and show that they are essential for MEAS. Further, we demonstrate that the hnRNP PTBP1 binds the ISS and is a regulator of TCF3 AS. We also demonstrate that hnRNP H1 and PTBP1 regulate TCF3 AS reciprocally, and that position-dependent interactions between these factors are essential for proper TCF3 MEAS. Our study provides a new model in which MEAS is regulated by cooperative actions of distinct hnRNPs bound to ISSs and ESSs.


Asunto(s)
Empalme Alternativo , Factores de Transcripción con Motivo Hélice-Asa-Hélice Básico/genética , Ribonucleoproteínas Nucleares Heterogéneas/metabolismo , Proteína de Unión al Tracto de Polipirimidina/metabolismo , ARN Helicasas DEAD-box/metabolismo , Exones , Células HeLa , Humanos , Intrones , Unión Proteica
16.
J Org Chem ; 84(15): 9509-9518, 2019 Aug 02.
Artículo en Inglés | MEDLINE | ID: mdl-31264871

RESUMEN

It was reported for the first time that single-electron oxidants such as CAN or K2S2O8 affected facile ring opening of simple gem-difluorocyclopropanes to afford 1,3-dibromo-2,2-difluoropropanes in good yields by the action of KBr, and the appropriate choice of conditions allowed to incorporate not only second halogen atoms but also hydroxy or acetamido groups at the C1 position in the difluoropropane structures in a regiospecific fashion after initiation of the reaction by the introduction of the first bromine atom at the C3 position.

18.
Gan To Kagaku Ryoho ; 46(2): 300-302, 2019 Feb.
Artículo en Japonés | MEDLINE | ID: mdl-30914540

RESUMEN

A 68-year-old woman underwent Miles' surgery with a diagnosis of a rectalgastrointestinalstromaltumor (GIST)in 2004. In 2005 and 2006, she developed liver metastases that were surgically removed, but once again in June 2006, she presented with liver metastasis, and imatinib therapy(400mg/day)was administered. In October 2016, she was diagnosed with progression of liver metastasis, and a tumor in the pancreatic body was identified on a CT scan. The patient was referred to our institution for treatment. We performed right hepatectomy and distalpancreatectomy in January 2017. Immunohistochemically, the recurrent tumor was positive for c-kit and CD34, and the diagnosis of GIST was confirmed. The pathological diagno- sis was a high-risk GIST showing 43mitoses per 50 high-power fields. Imatinib therapy(400mg/day)was administered after surgery. She is currently alive without recurrence.


Asunto(s)
Tumores del Estroma Gastrointestinal , Neoplasias Hepáticas , Neoplasias Pancreáticas , Anciano , Antineoplásicos/uso terapéutico , Femenino , Tumores del Estroma Gastrointestinal/patología , Tumores del Estroma Gastrointestinal/terapia , Humanos , Mesilato de Imatinib/uso terapéutico , Neoplasias Hepáticas/secundario , Recurrencia Local de Neoplasia , Neoplasias Pancreáticas/secundario
19.
Mass Spectrom (Tokyo) ; 8(2): S0083, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-33299733

RESUMEN

We describe systematic troubleshooting of the carry-over of neuropeptide Y (NPY) in LC-MS analysis. The objective was to remove candidate parts of the LC-MS system that are responsible for carry over one-by-one. The findings indicate that the carry-over of NPY occurs on the column, particularly in the guard column and at the consumable seals of the sample-needle and high-pressure valves. The methodology demonstrates that it is possible to troubleshoot carry-over in an LC-MS system in a systematic and logical manner.

20.
J Biosci Bioeng ; 127(6): 721-725, 2019 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-30573386

RESUMEN

Poly(lactate-co-3-hydroxybutyrate) [P(LA-co-3HB)] is produced in engineered Escherichia coli harboring the genes encoding an LA-polymerizing enzyme (LPE) and monomer-supplying enzymes. In this study, high cell-density fed-batch jar fermentation was developed using xylose and/or glucose as the carbon source. Fed-batch fermentation was initially performed with 20 g/L sugar during the batch phase for 24 h, and subsequent sugar feeding from 24 to 86 h. The feeding rate was increased in a stepwise manner. When xylose alone was used for cultivation, the cells produced the polymer at 11.6 g/L, which was higher than the 4.3 g/L obtained using glucose as the sole carbon source. However, in the first 24 h the growth in the glucose culture was greater than in the xylose culture. Based on these results, glucose was used for cell growth (at the initial stage) and xylose was used for polymer production (at the feeding stage). As expected, in the glucose/xylose switching fermentation method, polymer production was significantly enhanced, eventually reaching 26.7 g/L. The enhanced polymer production obtained by using xylose was presumably due to overflow metabolism. In fact, during xylose feeding, acetic acid excretion was greater than that in case of the glucose grown culture, suggesting the channeling of the metabolic flux from acetyl-CoA towards polymer production over into the tricarboxylic acid cycle in the xylose-fed cultures. Therefore, this sequential glucose/xylose feed strategy is potentially useful for production of acetyl-CoA derived compounds in E. coli.


Asunto(s)
Biotecnología/métodos , Escherichia coli/citología , Escherichia coli/metabolismo , Fermentación , Glucosa/metabolismo , Poliésteres/metabolismo , Xilosa/metabolismo , Técnicas de Cultivo de Célula , Ácido Láctico/metabolismo
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