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1.
Mucosal Immunol ; 2022 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-35013573

RESUMO

Dietary ω3 fatty acids have important health benefits and exert their potent bioactivity through conversion to lipid mediators. Here, we demonstrate that microbiota play an essential role in the body's use of dietary lipids for the control of inflammatory diseases. We found that amounts of 10-hydroxy-cis-12-cis-15-octadecadienoic acid (αHYA) and 10-oxo-cis-12-cis-15-octadecadienoic acid (αKetoA) increased in the feces and serum of specific-pathogen-free, but not germ-free, mice when they were maintained on a linseed oil diet, which is high in α-linolenic acid. Intake of αKetoA, but not αHYA, exerted anti-inflammatory properties through a peroxisome proliferator-activated receptor (PPAR)γ-dependent pathway and ameliorated hapten-induced contact hypersensitivity by inhibiting the development of inducible skin-associated lymphoid tissue through suppression of chemokine secretion from macrophages and inhibition of NF-κB activation in mice and cynomolgus macaques. Administering αKetoA also improved diabetic glucose intolerance by inhibiting adipose tissue inflammation and fibrosis through decreased macrophage infiltration in adipose tissues and altering macrophage M1/M2 polarization in mice fed a high-fat diet. These results collectively indicate that αKetoA is a novel postbiotic derived from α-linolenic acid, which controls macrophage-associated inflammatory diseases and may have potential for developing therapeutic drugs as well as probiotic food products.

2.
Artigo em Inglês | MEDLINE | ID: mdl-34864880

RESUMO

In natural indigo dyeing, the water-insoluble indigo included in the composted indigo leaves called sukumo is converted to water-soluble leuco-indigo through the reduction activities of microorganisms under alkaline conditions. To understand the relationship between indigo reduction and microorganisms in indigo-fermentation suspensions, we isolated and identified the microorganisms that reduce indigo and analyzed the microbiota in indigo-fermentation suspensions. Indigo-reducing microorganisms, which were not isolated by means of a conventional indigo carmine-reduction assay method, were isolated by using indigo as a direct substrate and further identified and characterized. We succeeded in isolating bacteria closely related to Corynebacterium glutamicum, Chryseomicrobium aureum, Enterococcus sp. for the first time. Anthraquinone was found to be an effective mediator that facilitated the indigo-reduction activity of the isolated strains. On analysis of the microbiota in indigo-fermentation suspensions, the ratio of indigo-reducing bacteria and others was found to be important for maintaining the indigo-reduction activity.

3.
J Biosci Bioeng ; 2021 Dec 07.
Artigo em Inglês | MEDLINE | ID: mdl-34893429

RESUMO

ω3-Docosapentaenoic acid (ω3-DPA), an ω3-polyunsaturated fatty acid (ω3-PUFA), is expected to have beneficial physiological functions to humans; however, because of its rarity in nature, it has not been fully analyzed. We isolated an ω3-DPA producing microorganism strain T7 from brackish areas in Japan. Although most oleaginous microorganisms rarely accumulate ω3-DPA (<5% of total lipid), strain T7 accumulated ω3-DPA with more than 20% of total fatty acids. The strain T7 was identified as a related species of Aurantiochytrium. In Aurantiochytrium sp. T7, ω3-DPA production reached 164 mg/L culture broth, and the ω3-DPA content reached 23.5% of the total fatty acids when cultivated in a medium containing 2% glucose as the carbon source and 1% yeast extract as the nitrogen source, with a salinity equivalent to 50% of that of seawater and a pH in the acidic range (pH < 5.5). Aurantiochytrium sp. T7 is a promising producer of high-purity ω3-DPA containing-lipid for the functional analysis of ω3-DPA whose physiological function has hardly been elucidated, and a useful strain for investigating the novel metabolic pathway of fatty acids.

4.
Sci Rep ; 11(1): 23715, 2021 Dec 09.
Artigo em Inglês | MEDLINE | ID: mdl-34887468

RESUMO

Cruciferous vegetables are rich sources of glucosinolates (GSLs). GSLs are degraded into isothiocyanates, which are potent anticarcinogens, by human gut bacteria. However, the mechanisms and enzymes involved in gut bacteria-mediated GSL metabolism are currently unclear. This study aimed to elucidate the enzymes involved in GSL metabolism in lactic acid bacteria, a type of gut bacteria. Companilactobacillus farciminis KB1089 was selected as a lactic acid bacteria strain model that metabolizes sinigrin, which is a GSL, into allylisothiocyanate. The sinigrin-metabolizing activity of this strain is induced under glucose-absent and sinigrin-present conditions. A quantitative comparative proteomic analysis was conducted and a total of 20 proteins that were specifically expressed in the induced cells were identified. Three candidate proteins, ß-glucoside-specific IIB, IIC, IIA phosphotransferase system (PTS) components (CfPttS), 6-phospho-ß-glucosidase (CfPbgS) and a hypothetical protein (CfNukS), were suspected to be involved in sinigrin-metabolism and were thus investigated further. We hypothesize a pathway for sinigrin degradation, wherein sinigrin is taken up and phosphorylated by CfPttS, and subsequently, the phosphorylated entity is degraded by CfPbgS. As expression of both pttS and pbgS genes clearly gave Escherichia coli host strain sinigrin converting activity, these genes were suggested to be responsible for sinigrin degradation. Furthermore, heterologous expression analysis using Lactococcus lactis suggested that CfPttS was important for sinigrin degradation and CfPbgS degraded phosphorylated sinigrin.

5.
Chembiochem ; : e202100606, 2021 Dec 20.
Artigo em Inglês | MEDLINE | ID: mdl-34929055

RESUMO

Fatty acid hydratases (FAHs) catalyze regio- and stereo-selective hydration of unsaturated fatty acids to produce hydroxy fatty acids. Fatty acid hydratase-1 (FA-HY1) from Lactobacillus Acidophilus is the most promiscuous and regiodiverse FAH identified so far. Here, we engineered binding site residues of FA-HY1 (S393, S395, S218 and P380) by semi-rational protein engineering to alter regioselectivity. Although it was not possible to obtain a completely new type of regioselectivity with our mutant libraries, a significant shift of regioselectivity was observed towards cis-5, cis-8, cis-11, cis-14, cis-17-eicosapentaenoic acid (EPA). We identified mutants (S393/S395 mutants) with excellent regioselectivity, generating a single hydroxy fatty acid product from EPA (15-OH product), which is advantageous from application perspective. This result is impressive given that wild-type FA-HY1 produces a mixture of 12-OH and 15-OH products at 63 : 37 ratio (12-OH : 15-OH). Moreover, our results indicate that native FA-HY1 is at its limit in terms of promiscuity and regiospecificity, thus it may not be possible to diversify its product portfolio with active site engineering. This behavior of FA-HY1 is unlike its orthologue, fatty acid hydratase-2 (FA-HY2; 58 % sequence identity to FA-HY1), which has been shown earlier to exhibit significant promiscuity and regioselectivity changes by a few active site mutations. Our reverse engineering from FA-HY1 to FA-HY2 further demonstrates this conclusion.

6.
J Clin Neurosci ; 93: 112-115, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34656233

RESUMO

Decompression surgery is the most common surgical treatment for lumbar spinal stenosis (LSS). Relatively low satisfaction rate was reported. Patients often complaint of residual numbness despite significant pain relief. We hypothesized that numbness had a significant impact on patient satisfaction, but had not been evaluated, which is associated with low satisfaction rate. This study aimed to examine how much numbness is associated with patient satisfaction. We retrospectively reviewed prospectively collected data from consecutive patients who underwent decompression without fusion for LSS. We evaluated the Numeric Rating Scale (NRS) scores of low back pain (LBP), leg pain, and leg numbness preoperatively and at the final follow-up visit. Improvement was evaluated using minimum clinically important differences (MCIDs). Patient satisfaction was evaluated using the question, "How satisfied are you with the overall result of your back operation?". There are four possible answers consisting of "very satisfied (4-point)", "somewhat satisfied (3-point)", "somewhat dissatisfied (2-point)", or "very dissatisfied (1-point)". Spearman correlation was used to evaluate the association between patient satisfaction and reaching MCIDs. A total of 116 patients were included. All three components had correlation with patient satisfaction with the correlation efficient of 0.30 in LBP, 0.22 in leg pain, and 0.33 in numbness. Numbness had greatest correlation efficient value. We showed that numbness has a greater impact than leg/back pain on patient satisfaction in patients undergoing decompression for LSS. We suggest not only LBP and leg pain but also numbness should be evaluated pre- and postoperatively.


Assuntos
Dor Lombar , Estenose Espinal , Descompressão Cirúrgica , Humanos , Hipestesia/etiologia , Perna (Membro) , Dor Lombar/cirurgia , Vértebras Lombares/cirurgia , Satisfação do Paciente , Estudos Retrospectivos , Estenose Espinal/complicações , Estenose Espinal/cirurgia , Resultado do Tratamento
7.
iScience ; 24(9): 102963, 2021 Sep 24.
Artigo em Inglês | MEDLINE | ID: mdl-34466786

RESUMO

Long-chain triglycerides (LCTs) intake strongly stimulates GIP secretion from enteroendocrine K cells and induces obesity and insulin resistance partly due to GIP hypersecretion. In this study, we found that medium-chain triglycerides (MCTs) inhibit GIP secretion after single LCT ingestion and clarified the mechanism underlying MCT-induced inhibition of GIP secretion. MCTs reduced the CCK effect after single LCT ingestion in wild-type (WT) mice, and a CCK agonist completely reversed MCT-induced inhibition of GIP secretion. In vitro studies showed that medium-chain fatty acids (MCFAs) inhibit long-chain fatty acid (LCFA)-stimulated CCK secretion and increase in intracellular Ca2+ concentrations through inhibition of GPR120 signaling. Long-term administration of MCTs reduced obesity and insulin resistance in high-LCT diet-fed WT mice, but not in high-LCT diet-fed GIP-knockout mice. Thus, MCT-induced inhibition of GIP hypersecretion reduces obesity and insulin resistance under high-LCT diet feeding condition.

8.
Biosci Biotechnol Biochem ; 85(5): 1252-1265, 2021 Apr 24.
Artigo em Inglês | MEDLINE | ID: mdl-33728459

RESUMO

ω3 Polyunsaturated fatty acids are currently obtained mainly from fisheries; thus, sustainable alternative sources such as oleaginous microorganisms are required. Here, we describe the isolation, characterization, and application of 3 novel ω3 desaturases with ω3 polyunsaturated fatty acid-producing activity at ordinary temperatures (28 °C). First, we selected Pythium sulcatum and Plectospira myriandra after screening for oomycetes with high eicosapentaenoic acid/arachidonic acid ratios and isolated the genes psulω3 and pmd17, respectively, which encode ω3 desaturases. Subsequent characterization showed that PSULω3 exhibited ω3 desaturase activity on both C18 and C20 ω6 polyunsaturated fatty acids while PMD17 exhibited ω3 desaturase activity exclusively on C20 ω6 polyunsaturated fatty acids. Expression of psulω3 and pmd17 in the arachidonic acid-producer Mortierella alpina resulted in transformants that produced eicosapentaenoic acid/total fatty acid values of 38% and 40%, respectively, at ordinary temperatures. These ω3 desaturases should facilitate the construction of sustainable ω3 polyunsaturated fatty acid sources.


Assuntos
Ácido Eicosapentaenoico/biossíntese , Ácidos Graxos Dessaturases/genética , Ácidos Graxos Insaturados/biossíntese , Mortierella/genética , Oomicetos/genética , Pythium/genética , Ácido Araquidônico/biossíntese , Clonagem Molecular , Ácidos Graxos Dessaturases/metabolismo , Ácidos Graxos Insaturados/classificação , Expressão Gênica , Biblioteca Gênica , Engenharia Metabólica/métodos , Mortierella/enzimologia , Oomicetos/classificação , Oomicetos/enzimologia , Filogenia , Plasmídeos/química , Plasmídeos/metabolismo , Pythium/classificação , Pythium/enzimologia , Saccharomyces cerevisiae/enzimologia , Saccharomyces cerevisiae/genética , Transformação Genética , Transgenes
9.
J Biosci Bioeng ; 131(5): 565-571, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33582015

RESUMO

Cyclic voltammetry was successfully applied to in-vivo monitoring of leuco-indigo in indigo-fermenting suspensions under quiescent conditions without deoxygenation; the working and counter electrodes were kept on the surface of each suspension by a polyethylene vinyl alcohol tube holder. The anodic peak current was used as a measure of the leuco-indigo concentration. The voltammetric wave shape suggested partial solubilization of the indigo with some macromolecules in the fermenting suspensions, which lead to an in-situ method without any electrode surface pretreatment. The anodic peak current well reflected the dyeing activity of a suspensions. The results obtained for laboratory-level fermentation systems clarified the number of days required for dye fermentation, the effectiveness of addition of old suspension as an additive for preparing fresh fermenting suspensions, and the importance of addition of a nitrogen-based nutrient as well as a glucose-based one to recover the indigo-reducing activity. The method can also be applied to determine the amounts of indigo in used dye suspensions and extracts of fermented indigo leaves (sukumo) by adding a chemical reduction pretreatment.


Assuntos
Corantes/química , Fermentação , Índigo Carmim/química , Corantes/metabolismo , Eletroquímica , Eletrodos , Índigo Carmim/metabolismo , Suspensões
10.
Commun Biol ; 4(1): 16, 2021 01 04.
Artigo em Inglês | MEDLINE | ID: mdl-33398074

RESUMO

The high-valent iron-oxo species formed in the non-heme diiron enzymes have high oxidative reactivity and catalyze difficult chemical reactions. Although the hydroxylation of inert methyl groups is an industrially promising reaction, utilizing non-heme diiron enzymes as such a biocatalyst has been difficult. Here we show a three-component monooxygenase system for the selective terminal hydroxylation of α-aminoisobutyric acid (Aib) into α-methyl-D-serine. It consists of the hydroxylase component, AibH1H2, and the electron transfer component. Aib hydroxylation is the initial step of Aib catabolism in Rhodococcus wratislaviensis C31-06, which has been fully elucidated through a proteome analysis. The crystal structure analysis revealed that AibH1H2 forms a heterotetramer of two amidohydrolase superfamily proteins, of which AibHm2 is a non-heme diiron protein and functions as a catalytic subunit. The Aib monooxygenase was demonstrated to be a promising biocatalyst that is suitable for bioprocesses in which the inert C-H bond in methyl groups need to be activated.


Assuntos
Aminobutiratos/metabolismo , Oxigenases de Função Mista/metabolismo , Rhodococcus/enzimologia , Hidroxilação , Estrutura Quaternária de Proteína
11.
Global Spine J ; 11(2): 212-218, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32875871

RESUMO

STUDY DESIGN: Retrospective observational study. OBJECTIVES: There is no consensus to predict improvement of lower back pain (LBP) in lumbar spinal stenosis after decompression surgery. The aim of this study was to evaluate the improvement of LBP and analyze the preoperative predicting factors for residual LBP. METHODS: We retrospectively reviewed 119 patients who underwent lumbar decompression surgery without fusion and had a minimum follow-up of 1 year. LBP was evaluated using the numerical rating scale (NRS), Japanese Orthopaedic Association Back Pain Evaluation Questionnaire (JOABPEQ) LBP score, and Roland-Morris Disability Questionnaire (RMDQ). All patients were divided into LBP improved group (group I) and LBP residual group (group R) according to the NRS score. Radiographic images were examined preoperatively and at the final follow-up. We evaluated spinopelvic radiological parameters and analyzed the differences between group I and group R. RESULTS: LBP was significantly improved after decompression surgery (LBP NRS, 5.7 vs 2.6, P < .001; JOABPEQ LBP score, 41.3 vs 79.6, P < .001; RMDQ, 10.3 vs 3.6, P < .001). Of 119 patients, 94 patients were allocated to group I and 25 was allocated to group R. There was significant difference in preoperative thoracolumbar kyphosis between group I and group R. CONCLUSIONS: Most cases of LBP in lumbar spinal stenosis were improved after decompression surgery without fusion. Preoperative thoracolumbar kyphosis predicted residual LBP after decompression surgery.

13.
J Alzheimers Dis ; 78(4): 1493-1507, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33185595

RESUMO

BACKGROUND: We previously reported the enhanced effects of physical exercise when combined with music (ExM) on cognitive function in community-dwelling normal elderly people compared to exercise alone. Following that study, participants voluntarily continued the ExM classes for 5 years. OBJECTIVE: To identify the effects of a 5-year ExM intervention on cognitive function in normal elderly people. METHODS: Fifty-four subjects continued the ExM classes once a week for 5 years (ExM group). Thirty-three subjects retired from the ExM class during the 5 years (Retired group). Twenty-one subjects never participated in any intervention over the 5 years (No-exercise group). Cognitive function and ADLs were assessed using neuropsychological batteries and the functional independence measure (FIM), respectively. The voxel-based specific regional analysis system for Alzheimer's disease (VSRAD) was used to investigate medial temporal lobe atrophy. RESULTS: Analyses of the raw scores after the 5-year intervention showed significant differences between the ExM and No-exercise groups in their MMSE scores, Raven's colored progressive matrices (RCPM) time, logical memory (LM)-I, as well as the total and physical exercise sub-scores of the FIM. Analysis of subjects aged 70- 79 years at the beginning of this project showed significantly quicker performance on the RCPM in the ExM compared to No-exercise groups. The correlation coefficients between the total number of ExM sessions attended and the degree of changes in physical, neuropsychological, and VSRAD scores were significant for RCPM performance time and LM-I scores. CONCLUSION: Long-term ExM intervention reinforces multifaceted cognitive function in normal elderly people, and is especially beneficial for psychomotor speed.


Assuntos
Atividades Cotidianas , Cognição , Exercício Físico , Música , Lobo Temporal/diagnóstico por imagem , Idoso , Idoso de 80 Anos ou mais , Atrofia , Feminino , Seguimentos , Estado Funcional , Humanos , Vida Independente , Imageamento por Ressonância Magnética , Masculino , Testes Neuropsicológicos , Lobo Temporal/patologia
14.
Sci Rep ; 10(1): 13009, 2020 08 03.
Artigo em Inglês | MEDLINE | ID: mdl-32747669

RESUMO

Faecal lipopolysaccharides (LPS) have attracted attention as potent elements to explain a correlation between the gut microbiota and cardiovascular disease (CVD) progression. However, the underlying mechanism of how specific gut bacteria contribute to faecal LPS levels remains unclear. We retrospectively analysed the data of 92 patients and found that the abundance of the genus Bacteroides was significantly and negatively correlated with faecal LPS levels. The controls showed a higher abundance of Bacteroides than that in the patients with CVD. The endotoxin units of the Bacteroides LPS, as determined by the limulus amoebocyte lysate (LAL) tests, were drastically lower than those of the Escherichia coli LPS; similarly, the Bacteroides LPS induced relatively low levels of pro-inflammatory cytokine production and did not induce sepsis in mice. Fermenting patient faecal samples in a single-batch fermentation system with Bacteroides probiotics led to a significant increase in the Bacteroides abundance, suggesting that the human gut microbiota could be manipulated toward decreasing the faecal LPS levels. In the clinical perspective, Bacteroides decrease faecal LPS levels because of their reduced LAL activity; therefore, increasing Bacteroides abundance might serve as a novel therapeutic approach to prevent CVD via reducing faecal LPS levels and suppressing immune responses.


Assuntos
Bacteroides/metabolismo , Doenças Cardiovasculares/metabolismo , Fezes/química , Lipopolissacarídeos/metabolismo , Probióticos , Idoso , Animais , Bacteroides/genética , Doenças Cardiovasculares/microbiologia , Estudos de Casos e Controles , Fezes/microbiologia , Feminino , Microbioma Gastrointestinal , Humanos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Pessoa de Meia-Idade , Células RAW 264.7 , RNA Ribossômico 16S/genética , Estudos Retrospectivos
15.
Biochem Biophys Res Commun ; 530(1): 342-347, 2020 09 10.
Artigo em Inglês | MEDLINE | ID: mdl-32828309

RESUMO

We evaluated the effect of gut bacterial metabolites of polyunsaturated fatty acids on inflammation and found that 10-oxo-cis-6,trans-11-octadecadienoic acid (γKetoC) strikingly suppressed LPS-induced IL-6 release from bone marrow-derived macrophages (BMMs), which was accompanied by reduced mRNA expression of Il6, TNF, and Il1b. γKetoC decreased the cAMP concentration in BMMs, suggesting that γKetoC stimulated G protein-coupled receptors. A Gq agonist significantly suppressed LPS-induced IL-6 expression in BMMs, whereas a Gi inhibitor partially abrogated γKetoC-mediated IL-6 suppression. Cytosolic Ca2+ was markedly increased by γKetoC, which was partly but not fully abrogated by an ion channel inhibitor. Taken together, these data suggest that γKetoC suppresses inflammatory cytokine expression in macrophages primarily through Gq and partially through Gi. γKetoC suppressed osteoclast development and IL-6 expression in synovial fibroblasts from rheumatoid arthritis (RA) patients, suggesting the beneficial effect of γKetoC on the prevention or treatment of RA.


Assuntos
Ácidos Graxos Insaturados/metabolismo , Microbioma Gastrointestinal , Lactobacillales/metabolismo , Monócitos/metabolismo , Animais , Artrite Reumatoide/etiologia , Artrite Reumatoide/metabolismo , Linhagem Celular , Células Cultivadas , Citocinas/metabolismo , Feminino , Humanos , Inflamação/etiologia , Inflamação/metabolismo , Macrófagos/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Fatores de Proteção , Células RAW 264.7
16.
Global Spine J ; 10(5): 627-632, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32677560

RESUMO

STUDY DESIGN: Retrospective cohort study. OBJECTIVES: Decompression without fusion is a standard surgical treatment for lumbar spinal stenosis (LSS) with reasonable surgical outcomes. Nevertheless, some studies have reported low patient satisfaction (PS) following decompression surgery. The cause of the discrepancy between reasonable clinical outcomes and PS is unknown; moreover, the factors associated with PS are expected to be complex, and little is known about them. This study aimed to identify satisfaction rate and to clarify the factors related to PS following decompression surgery in LSS patients. METHODS: We retrospectively reviewed 126 patients who underwent lumbar decompression with a minimum follow-up of 1 year. Patients were divided into 2 groups based on the PS question. The Japanese Orthopaedic Association (JOA) scores, and the Numeric Rating Scale (NRS) scores of low back pain (LBP), leg pain, and leg numbness were compared between the 2 groups preoperatively and at the latest visit. To identify the prognostic factors for dissatisfaction, multiple logistic regression analysis was performed. RESULTS: Overall satisfaction rate was 75%. The JOA recovery rate, NRS improvement, and Short Form-8 (SF-8) were significantly higher in the satisfied group. Postoperative NRS scores of LBP, leg pain, and leg numbness were significantly lower in the satisfied group. Multivariate logistic regression analysis showed that smoking and scoliosis were significant risk factors for dissatisfaction. CONCLUSIONS: Overall satisfaction rate was 75% in patients with LSS undergoing decompression surgery. This study found that smoking status and scoliosis were associated with patient dissatisfaction following decompression in LSS patients.

17.
Biosci Biotechnol Biochem ; 84(11): 2390-2400, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32729393

RESUMO

Maltol derivatives are used in a variety of fields due to their metal-chelating abilities. In the previous study, it was found that cytochrome P450 monooxygenase, P450nov, which has the ability to effectively convert the 2-methyl group in a maltol derivative, transformed 3-benzyloxy-2-methyl-4-pyrone (BMAL) to 2-(hydroxymethyl)-3-(phenylmethoxy)-4H-pyran-4-one (BMAL-OH) and slightly to 3-benzyloxy-4-oxo-4 H-pyran-2-carboxaldehyde (BMAL-CHO). We isolated Pseudomonas nitroreducens SB32154 with the ability to convert BMAL-CHO to BMAL-COOH from soil. The enzyme responsible for aldehyde oxidation, a BMAL-CHO dehydrogenase, was purified from P. nitroreducens SB32154 and characterized. The purified BMAL-CHO dehydrogenase was found to be a xanthine oxidase family enzyme with unique structure of heterodimer composed of 75 and 15 kDa subunits containing a molybdenum cofactor and [Fe-S] clusters, respectively. The enzyme showed broad substrate specificity toward benzaldehyde derivatives. Furthermore, one-pot conversion of BMAL to BMAL-COOH via BMAL-CHO by the combination of the BMAL-CHO dehydrogenase with P450nov was achieved.


Assuntos
Aldeído Desidrogenase/química , Aldeído Desidrogenase/metabolismo , Molibdênio , Pseudomonas/química , Pironas/metabolismo , Biocatálise , Oxirredução
18.
Clin Neurol Neurosurg ; 196: 105966, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32485521

RESUMO

OBJECTIVE: A minimum clinically important difference (MCID) has been increasingly well known in the current era of patient-centered care because it reflects a smallest change that is meaningful for patients following a clinical intervention. Previous studies suggested MCID values are disease and/or procedure dependent. No MCID values have been reported on the lumbar spinal stenosis (LSS) following decompression surgery despite LSS is the most common spinal disease and the main treatment is decompression surgery. Therefore, this study aimed to determine the MCID values as major outcome measures including the Numeric Rating Scale (NRS) of back pain, leg pain and numbness, Roland-Morris Disability Questionnaire (RMDQ), and Physical Component Summary (PCS) and Mental Component Summary (MCS) of Short Form 8 (SF-8) for patients with LSS undergoing decompression surgery. PATIENTS AND METHODS: This is a retrospective cohort study using prospectively collected data from consecutive patients who underwent lumbar decompression without fusion for LSS at a single institution between May 2014 and March 2016. Inclusion criteria were 1) minimum 1-year follow-up 2) a complete set of preoperative and final follow-up questionnaires available, including the NRS, RMDQ, and SF-8. Revision surgery or non-degenerative etiology such as infection or tumor was excluded. MCIDs of each outcome measure were determined using two major approaches, distribution- and anchor-based methods. The distribution-based method uses the distributional characteristics of the sample. This method expresses the observed degree of variation to obtain a standardized metric such as the standard deviation or standard error of measurement. The anchor-based method uses an external criterion known as anchor to determine the factors that should be considered by patients for an important improvement. Anchor-based methods assess how much changes in the measurement instrument correspond with a minimal important change defined on the anchor. We used symptom severity, physical function, and satisfaction scores from Zurich Claudication Questionnaire as anchors for NRS and RMDQ, PCS, and MCS, respectively. RESULTS: A total of 126 patients were included. From the anchor-based method, MCIDs were determined to be 2 points for back pain, 4 points for leg pain and numbness, 5 points for RMDQ, 5 points for PCS, and 2 points for MCS. From the distribution-based method, MCIDs were determined to be 2 points for back pain, leg pain and numbness, 3-4 points for RMDQ, 6 points for PCS, and 5 points for MCS. CONCLUSION: We first identified the MCIDs of the NRS, RMDQ, and SF-8 specific to patients undergoing decompression surgery for LSS.


Assuntos
Descompressão Cirúrgica , Vértebras Lombares/cirurgia , Medidas de Resultados Relatados pelo Paciente , Estenose Espinal/cirurgia , Idoso , Idoso de 80 Anos ou mais , Avaliação da Deficiência , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Medição da Dor , Satisfação do Paciente , Estudos Retrospectivos , Resultado do Tratamento
19.
Clin Neurol Neurosurg ; 196: 105952, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32535396

RESUMO

OBJECTIVE: Decompression surgery is a mainstay of surgical treatment for lumbar spinal stenosis (LSS). However, up to 30% of patients have low satisfaction due to residual symptoms. In the clinical setting, improvements in leg pain are more significant than those in leg numbness. Residual numbness could be related to the relatively low satisfaction rate. However, few studies have focused on numbness; thus, elucidating the risk factors and rate of residual numbness would benefit surgeons and patients. This study aimed to clarify the risk factors for and rate of residual numbness after decompression surgery. PATIENTS AND METHODS: We retrospectively reviewed prospectively collected data from consecutive patients who underwent lumbar decompression without fusion for LSS at a single institution between January 2014 and March 2016. Patients were included if preoperative and final follow-up questionnaires and radiographs were available. A minimum one-year follow-up was required. We evaluated the Numeric Rating Scale (NRS) scores of low back pain, leg pain, and leg numbness preoperatively and at the final follow-up visit. Residual numbness was defined as a postoperative NRS ≥ 1, whereas persistent numbness was defined as a postoperative NRS ≥ 5. We compared the clinical data of patients with or without residual numbness to those of patients with or without persistent numbness. Multivariate logistic regression analysis was performed to identify risk factors for residual and persistent numbness. RESULTS: A total of 116 patients (73 men, 43 women) were included. Of them, 60% had residual numbness with a mean follow-up period of 25 months. Only durotomy differed significantly between patients with and those without residual numbness. However, the significance did not persist after logistic regression analysis. A total of 16% had persistent numbness. Diabetes mellitus, intraoperative durotomy, and preoperative NRS of numbness were identified as risk factors. There were no differences in smoking status, presence of spondylolisthesis or scoliosis, or severity of stenosis. CONCLUSIONS: We found three risk factors for persistent numbness following decompression surgery for LSS; diabetes mellitus and durotomy were modifiable, whereas preoperative numbness was not. Our findings would help surgeons minimize the incidence of persistent numbness by adequately controlling diabetes and avoiding durotomy during surgery. Providing information about the potential for residual numbness during the informed consent process is important to ensuring realistic patient expectations.


Assuntos
Descompressão Cirúrgica/efeitos adversos , Hipestesia/etiologia , Dor Lombar/cirurgia , Vértebras Lombares/cirurgia , Estenose Espinal/cirurgia , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/etiologia , Estudos Retrospectivos , Fatores de Risco , Resultado do Tratamento
20.
FASEB Bioadv ; 2(1): 59-71, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-32123857

RESUMO

Dietary intake of ω3 polyunsaturated fatty acids such as eicosapentaenoic acid and docosahexaenoic acid is beneficial for health control. We recently identified 17,18-epoxyeicosatetraenoic acid (17,18-EpETE) as a lipid metabolite endogenously generated from eicosapentaenoic acid that exhibits potent anti-allergic and anti-inflammatory properties. However, chemically synthesized 17,18-EpETE is enantiomeric due to its epoxy group-17(S),18(R)-EpETE and 17(R),18(S)-EpETE. In this study, we demonstrated stereoselective differences of 17(S),18(R)-EpETE and 17(R),18(S)-EpETE in amelioration of skin contact hypersensitivity and found that anti-inflammatory activity was detected in 17(S),18(R)-EpETE, but not in 17(R),18(S)-EpETE. In addition, we found that cytochrome P450 BM-3 derived from Bacillus megaterium stereoselectively converts EPA into 17(S),18(R)-EpETE, which effectively inhibited the development of skin contact hypersensitivity by inhibiting neutrophil migration in a G protein-coupled receptor 40-dependent manner. These results suggest the new availability of a bacterial enzyme to produce a beneficial lipid mediator, 17(S),18(R)-EpETE, in a stereoselective manner. Our findings highlight that bacterial enzymatic conversion of fatty acid is a promising strategy for mass production of bioactive lipid metabolites.

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