RESUMO
SARS-CoV-2 infection has been associated with the increased incidence of acute macular neuroretinopathy (AMN), an infrequent ocular disorder. However, the precise mechanisms underpinning AMN in the context of SARS-CoV-2 infection (AMN-SARS-CoV-2) remain elusive. In this case-control study, 14 patients diagnosed with AMN-SARS-CoV-2 between 2022/12 and 2023/3 were enrolled and compared with 14 SARS-CoV-2-infected individuals without AMN, who served as controls (SARS-CoV-2-no AMN). Metabolomic profiling using ultrahigh-performance liquid chromatography-online electrospray mass spectrometry revealed significant alterations in serum metabolites in AMN-SARS-CoV-2 patients. Coagulation abnormalities were observed in AMN-SARS-CoV-2 patients, and their relationship with metabolic disorders was studied. Finally, a predictive model for AMN-SARS-CoV-2 was established. Seventy-six upregulated and 42 downregulated metabolites were identified in AMN-SARS-CoV-2 cases. Notably, arginine metabolism within the urea cycle was significantly altered, evidenced by variations in ornithine, citrulline, l-proline, and ADAM levels, correlating with abnormal coagulation markers like platelet crit, fibrinogen degradation product, and fibrinogen. Additionally, increased arginase 1 (AGR1) activity within the urea cycle and reduced nitric oxide synthase activity were observed in AMN-SARS-CoV-2. The integration of urea cycle metabolite levels with coagulation parameters yielded a robust discriminatory model for AMN-SARS-CoV-2, as evidenced by an area under the curve of 0.96. The findings of the present study enhance our comprehension of the underlying metabolic mechanisms associated with AMN-SARS-CoV-2 and offer potential diagnostic markers for this uncommon ocular disorder within the context of SARS-CoV-2 infection.
Assuntos
COVID-19 , SARS-CoV-2 , Humanos , COVID-19/sangue , COVID-19/diagnóstico , COVID-19/metabolismo , Estudos de Casos e Controles , Masculino , Feminino , Pessoa de Meia-Idade , Adulto , Metabolômica/métodos , Idoso , Coagulação Sanguínea , Doenças Retinianas/virologia , Doenças Retinianas/sangue , Doenças Retinianas/diagnósticoRESUMO
Light can influence many psychophysiological functions beyond vision, including alertness, circadian rhythm, and sleep, namely the non-image forming (NIF) effects of light. Melanopic equivalent daylight illuminance (mel-EDI) is currently recommended as the predictor of the NIF effects of light. Although light dose is also critical for entraining and regulating circadian cycle, it is still unknown whether relatively low mel-EDI light exposure for prolonged duration in the evening would affect pre-sleep arousal and subsequent sleep. In all, 18 healthy college students (10 females, mean [standard deviation] age 21.67 [2.03] years) underwent 2 experimental nights with a 1 week interval in a simulated bedroom environment. During experimental nights, participants were either exposed to high or low mel-EDI light (73 versus 38 lx mel-EDI, 90 versus 87 photopic lx at eye level, 150 photopic lx at table level) for 3.5 h before regular bedtime, and their sleep was monitored by polysomnography. Subjective sleepiness, mood, and resting-state electroencephalography during light exposure were also investigated. Results showed no significant differences in sleep structure and sleep quality between the two light conditions, whereas 3.5 h of exposure to high versus low mel-EDI light induced marginally higher physiological arousal in terms of a lower delta but higher beta power density before sleep, as well as a lower delta power density during sleep. Moreover, participants felt happier before sleep under exposure to high versus low mel-EDI light. These findings together with the current literature suggest that evening prolonged relatively low mel-EDI light exposure may mildly increase arousal before and during sleep but affected sleep structure less.
Assuntos
Nível de Alerta , Ritmo Circadiano , Eletroencefalografia , Luz , Polissonografia , Sono , Humanos , Feminino , Nível de Alerta/fisiologia , Adulto Jovem , Masculino , Sono/fisiologia , Ritmo Circadiano/fisiologia , Afeto/fisiologia , Adulto , Qualidade do SonoRESUMO
BACKGROUND: Inflammation and immune dysfunction with classically activated macrophages(M1) infiltration are important mechanisms in the progression of atherosclerosis (AS). Dynamin-related protein 1 (DRP1)-dependent mitochondrial fission is a novel target for alleviating inflammatory diseases. This study aimed to investigate the effects of DRP1 inhibitor Mdivi-1 on AS. METHODS: ApoE-/- mice were fed with a high-fat diet supplemented with or without Mdivi-1. RAW264.7 cells were stimulated by ox-LDL, pretreated with or without MCC950, Mito-TEMPO, or Mdivi-1. The burden of plaques and foam cell formation were determined using ORO staining. The blood lipid profles and inflammatory cytokines in serum were detected by commercial kits and ELISA, respectively. The mRNA expression of macrophage polarization markers, activation of NLRP3 and the phosphorylation state of DRP1 were detected. Mitochondrial reactive oxygen species (mito-ROS), mitochondrial staining, ATP level and mitochondrial membrane potential were detected by mito-SOX, MitoTracker, ATP determination kit and JC-1 staining, respectively. RESULTS: In vivo, Mdivi-1 reduced the plaque areas, M1 polarization, NLRP3 activation and DRP1 phosphorylation at Ser616. In vitro, oxidized low-density lipoprotein (ox-LDL) triggered M1 polarization, NLRP3 activation and abnormal accumulation of mito-ROS. MCC950 and Mito-TEMPO suppressed M1 polarization mediated foam cell formation. Mito-TEMPO significantly inhibited NLRP3 activation. In addition, Mdivi-1 reduced foam cells by inhibiting M1 polarization. The possible mechanisms responsible for the anti-atherosclerotic effects of Mdivi-1 on reducing M1 polarization were associated with suppressing mito-ROS/NLRP3 pathway by inhibiting DRP1 mediated mitochondrial fission. In vitro, similar results were observed by DRP1 knockdown. CONCLUSION: Inhibition of DRP1-dependent mitochondrial fission by Mdivi-1 alleviated atherogenesis via suppressing mito-ROS/NLRP3-mediated M1 polarization, indicating DRP1-dependent mitochondrial fission as a potential therapeutic target for AS.
Assuntos
Aterosclerose , Indenos , Animais , Camundongos , Dinâmica Mitocondrial , Proteína 3 que Contém Domínio de Pirina da Família NLR , Espécies Reativas de Oxigênio , Aterosclerose/tratamento farmacológico , Dinaminas , Furanos , Trifosfato de AdenosinaRESUMO
The deleterious effects of sleep loss on sleep-dependent memory and emotional function have been documented in the current literature. Yet, the effects of insomnia-induced chronic sleep disturbance on emotional short-term memory have been scarcely investigated. Twenty-one participants with subclinical insomnia disorder (SID) and 20 healthy participants (healthy control, HC) performed a delayed recognition task of emotional faces, and event-related potentials (ERPs) involved in memory encoding, retention, and retrieval of faces across different emotional valences were assessed. Behavioral findings revealed that participants in the SID group had a larger response bias, being more likely to perceive negative faces as "old" faces presented in the retrieval phase than those in the HC group. ERP findings revealed that emotional faces in the SID vs. HC group induced significantly smaller P1 and late P3b and larger N170 amplitudes in the encoding phase and smaller negative slow wave (NSW) in the retention phase. In retrieval phase, the interaction between Sleep group and Valence were revealed for P1 and early P3b amplitudes, but no group differences were found after Bonferroni correction. These findings suggested that insomnia induced chronic sleep disturbance would influence performance on emotional working memory and induced processing phase specific regulation of neurophysiology in emotional working memory regardless of valence.
Assuntos
Memória de Curto Prazo , Distúrbios do Início e da Manutenção do Sono , Humanos , Memória de Curto Prazo/fisiologia , Distúrbios do Início e da Manutenção do Sono/complicações , Emoções/fisiologia , Potenciais Evocados/fisiologia , Reconhecimento Psicológico/fisiologiaRESUMO
OBJECTIVES: To evaluate myocardial viability in patients with myocardial ischemia reperfusion injury (MIRI) via dual-energy computed tomography myocardial blood pool imaging (DECT MBPI). METHODS: Between September 2017 and January 2019, we prospectively recruited 59 patients with acute myocardial infarction (AMI) who developed MIRI after revascularization during invasive coronary angiography (ICA). Then, they received DECT MBPI, SPECT, and PET sequentially within 1 week after the onset of MIRI. A total of 1003 myocardial segments of 59 patients were recruited for this study. The iodine reduction areas and delayed enhancement areas were calculated by cardiac iodine map with SPECT rest myocardial perfusion imaging (MPI) + PET myocardial metabolism imaging (MMI) as reference criteria. The paired sample t-test was used to measure the difference of the myocardial iodine value. Cohen's Kappa analysis was used to test the consistency among different observers. ROC analysis was used to calculate the myocardial viability of DECT MBPI. RESULTS: ROC showed the AUCs of DECT MBPI iodine value to identify a normal myocardium, an ischemic myocardium, and an infarcted myocardium were 0.957, 0.900, and 0.906 (p < 0.001). The sensitivity, specificity, and accuracy of DECT MBPI in identifying an ischemic myocardium were 87.6%, 89.3%, and 97.9% (p < 0.001). The sensitivity, specificity, and accuracy of DECT MBPI in identifying an infarcted myocardium were 88.9%, 92.2%, and 98.6% (p < 0.001). The cutoff value for DECT MBPI to differentiate between an ischemic and a normal myocardium was 0.84 mg I/mL. The cutoff value for DECT MBPI to differentiate between an infarct and a normal myocardium was 2.01 mg I/mL. CONCLUSION: DECT MBPI can be used to assess myocardial viability in patients with MIRI with high sensitivity and specificity. KEY POINTS: ⢠Dual-energy computed tomography myocardial blood pool imaging (DECT MBPI) can evaluate myocardial viability of myocardial ischemia-reperfusion injury (MIRI). ⢠DECT MBPI is a non-invasive and timesaving method for evaluation on myocardial ischemia-reperfusion injury in patients with acute myocardial infarction after coronary intervention.
Assuntos
Iodo , Infarto do Miocárdio , Isquemia Miocárdica , Traumatismo por Reperfusão Miocárdica , Humanos , Traumatismo por Reperfusão Miocárdica/diagnóstico por imagem , Tomografia Computadorizada por Raios X/métodos , Miocárdio , Infarto do Miocárdio/diagnóstico por imagemRESUMO
Atherosclerosis, a chronic inflammatory disease characterized by arterial plaque formation, is one of the most prominent causes of cardiovascular diseases. However, the current treatments often do not adequately compromise the chronic inflammation-mediated plaque accumulation and the disease progression. Therefore, a new and effective strategy that blocks atherosclerosis-associated inflammation is urgently needed to further reduce the risk. Colchicine, a potent anti-inflammatory medication, has shown great potential in the treatment of atherosclerosis, but its adverse effects have hampered its clinical application. Herein, we developed a novel delivery nanosystem encapsulated with colchicine (VHPK-PLGA@COL), which exhibited improved biosafety and sustained drug release along with the gradual degradation of PLGA and PEG as confirmed both in vitro and in vivo. Surface modification of the nanoparticles with the VHPK peptide ensured its capability to specifically target inflammatory endothelial cells and alleviate atherosclerotic plaque accumulation. In the ApoE - / - atherosclerotic mouse model, both colchicine and VHPK-PLGA@COL treatment significantly decreased the plaque area and enhanced plaque stability by blocking the NF-κB/NLRP3 pathways, while VHPK-PLGA@COL exhibited enhanced therapeutic effects due to its unique ability to target inflammatory endothelial cells without obvious long-term safety concerns. In summary, VHPK-PLGA@COL has the potential to overcome the key translational barriers of colchicine and open new avenues to repurpose this drug for anti-atherosclerotic therapy.
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Aterosclerose , Nanopartículas , Placa Aterosclerótica , Animais , Camundongos , NF-kappa B/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Células Endoteliais/metabolismo , Colchicina/farmacologia , Colchicina/metabolismo , Colchicina/uso terapêutico , Aterosclerose/metabolismo , Placa Aterosclerótica/tratamento farmacológico , Inflamação/tratamento farmacológico , Inflamação/metabolismo , Nanopartículas/químicaRESUMO
The chaperone-assisted soluble expression and characterization of high molecular weight chitinase chiZJ408 in Escherichia coli BL21 were investigated. Chitin degradation products by chitinase chiZJ408 were analyzed. The results indicated that the introduction of the chaperone GroELS promoted the correct folding of chitinase chiZJ408 and increased its soluble expression by 14.9% (p < 0.05) in E. coli BL21. The optimal pH and temperature of chitinase chiZJ408 were respectively 6.0 and 50 °C. Chitinase chiZJ408 was stable at pHs of 4.0 â¼ 7.0 and at below 40 °C. Mg2+and Ca2+ had a significant impact on improving the activity of chitinase chiZJ408. Chitinase chiZJ408 was demonstrated to be exochitinase that cleaved the ß-1,4-glycosidic bond of the chitin chain to generate only N,N'-diacetylchitobiose. This study broadens our understanding of chitinase and provides a basis for solving the problem of inclusion body formed by long fragment gene expression in E. coli.
Assuntos
Quitina/metabolismo , Quitinases/genética , Escherichia coli/genética , Chaperonas Moleculares/metabolismo , Quitinases/metabolismo , Hidrólise , Proteínas Recombinantes/metabolismo , SolubilidadeRESUMO
Pyridoxal 5'-phosphate (PLP) is the coenzyme of more than 140 enzymes and is widely used in various fields. In this study, to enhance the production of PLP in Escherichia coli BL21, the recombinant strain E. coli BL21/pETDuet-1-pdxj-zwf-dxs was constructed. The concentration of PLP in this strain was 82.69 mg/L, which was increased by 1.38-fold as compared to that in E. coli BL21. Glucose, yeast extract, and pH had an obvious impact on the concentration of PLP, and their optimal levels were 34.89 g/L, 31.17 g/L, and 10.07, respectively. The concentration of PLP under the optimal condition reached 2.23 g/L. The time-course analysis showed that the highest concentration of PLP was 2.32 g/L in recombinant strain after the induction for 12 h by 0.1 mM IPTG in a 1 L shake flask, which was increased by 38.76-fold as compared to that in E. coli BL21. This study provides a good basis for the efficient production of PLP in E. coli BL21.
Assuntos
Proteínas de Escherichia coli , Escherichia coli , Escherichia coli/genética , Ligases , Fosfatos , Fosfato de Piridoxal/químicaRESUMO
Ghrelin is a peptide hormone with strong anti-inflammatory properties. In fact, Ghrelin was reported to improve endothelial dysfunction caused by excessive fat. However, its role in preserving the integrity of brain microvascular, under conditions of lipid dysregulation and inflammation, is not known. The objective of this study is to characterize the role of Ghrelin in the protection of cerebral microvascular integrity, during atherosclerosis, and uncover its underlying molecular mechanism. Our results demonstrated that an atherosclerotic condition, brought on by a high fat diet (HFD), can produce massive increases in serum inflammatory factors, blood lipids, cerebral microvascular leakage, and activation of the p38 mitogen-activated protein kinase (MAPK) and c-Jun N-terminal kinase (JNK) (p38 MAPK-JNK) pathway. It also produced significantly damaged pericytes morphology, resulting in pericyte decrease. Ghrelin treatment, on the other hand, protected against cerebral microvascular leakage and pericytes damage. Ghrelin effectively downregulated the expression of pro-inflammatory cytokines, and it also suppressed the p38 MAPK-JNK signaling pathway. Additionally, in isolated mouse cerebral microvascular pericytes, ox-LDL lead to increased apoptosis and secretion of inflammatory factors, along with an elevation in phosphorylated p38 MAPK-JNK proteins. Alternately, Ghrelin administration markedly lowered expression of inflammatory factors, suppressed the p38 MAPK-JNK signaling path, and halted cell apoptosis. However, pretreatment of Hesperetin, a p38 MAPK-JNK agonist, abrogated the Ghrelin-mediated suppression of inflammation and apoptosis in pericytes. Taken together, these results suggest that Ghrelin restored cerebral microvascular integrity and reduced vascular leakage in atherosclerosis mice, in part, by its regulation of inflammatory and apoptotic signaling pathways in pericytes.
Assuntos
Apoptose/efeitos dos fármacos , Circulação Cerebrovascular/efeitos dos fármacos , Grelina/farmacologia , Inflamação/prevenção & controle , MAP Quinase Quinase 4/metabolismo , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo , Animais , Aterosclerose/metabolismo , Aterosclerose/fisiopatologia , Aterosclerose/prevenção & controle , Células Cultivadas , Dieta Hiperlipídica/efeitos adversos , Grelina/administração & dosagem , Inflamação/metabolismo , Inflamação/fisiopatologia , Injeções Intraperitoneais , Lipoproteínas LDL/antagonistas & inibidores , Lipoproteínas LDL/sangue , Lipoproteínas LDL/metabolismo , Masculino , Camundongos Knockout , Pericitos/citologia , Pericitos/efeitos dos fármacos , Pericitos/metabolismo , Transdução de Sinais/efeitos dos fármacosRESUMO
Previous research revealed inconsistent effects of bright light or a short nap at noon on alertness and performance across different tasks. The current study aimed to explore whether the effects of bright light and a short nap at noon on task performance depended on the cognitive domain. Bright light (1,200 lx, 4,000 K at eye level), nap (near darkness) and control (200 lx, 4,000 K at eye level) conditions were performed from 1:00 to 1:40 PM on three non-consecutive days with a counterbalanced order across participants. After being assigned to one of three conditions, participants underwent two repeated test sessions, each including a psychomotor vigilance task, a go/no-go task, and a paced visual serial addition task, with an interval of more than 1 h, to assess the persistent effects of napping and bright light. Subjective sleepiness, vitality, self-control and mood were also measured. Results showed that accuracy on the go/no-go task and the paced visual serial addition task improved significantly throughout the entire experiment session after napping, whereas reaction speed on the paced visual serial addition task improved time-dependently in the bright light intervention, with a higher reaction speed in only the first test session. Nearly all subjective states benefited from napping but not from bright light. These findings suggested that the effects of bright light and an afternoon nap on task performance would depend on the cognitive domain. An afternoon nap may elicit more effective and persistent benefits on task performance and subjective states.
Assuntos
Cognição/efeitos da radiação , Desempenho Psicomotor/efeitos da radiação , Sono/fisiologia , Análise e Desempenho de Tarefas , Atenção/efeitos da radiação , Feminino , Humanos , Masculino , Adulto JovemRESUMO
BACKGROUND The purpose of this study was to screen and identify key genes in the occurrence and development of hepatocellular carcinoma (HCC) based on bioinformatics analysis. MATERIAL AND METHODS Three Gene Expression Omnibus (GEO) series (GSE) - GSE121248, GSE87630, and GSE84598 - were downloaded from the GEO database. GEO2R was used to screen different genes and a Venn diagram was drawn to screen coexpressed differentially expressed genes (DEGs). Coexpressed DEGs were obtained by Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analysis, a protein-protein interaction network diagram was produced by Cytoscape, and module genes were calculated by the Molecular Complex Detection Cytoscape plug-in. Finally, overall survival, progression-free survival, and relapse-free survival analysis of the key genes selected were performed using the online Kaplan-Meier plotter. For the target genes, the online network UCSC Cancer Genome Browser was used to analyze the gene expression profiles of the grade and vascular invasion of HCC. RESULTS A total of 296 coexpressed DEGs were obtained from the 3 GSEs and 12 key genes were obtained from the modular analysis. Survival analysis showed that the upregulated genes UBE2T and FBLN5 were involved in the poor prognosis of HCC. Furthermore, the expression of UBE2T was significantly related to the grade and vascular invasion of HCC. CONCLUSIONS The expression of the UBE2T gene was significantly upregulated in HCC tissue compared to in normal liver tissue. UBE2T may be a new marker for the diagnosis and subsequent therapy of HCC.
Assuntos
Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/mortalidade , Enzimas de Conjugação de Ubiquitina/genética , Biomarcadores Tumorais/genética , Carcinoma Hepatocelular/metabolismo , Biologia Computacional/métodos , Bases de Dados Genéticas , Progressão da Doença , Perfilação da Expressão Gênica/métodos , Regulação Neoplásica da Expressão Gênica/genética , Ontologia Genética , Redes Reguladoras de Genes , Humanos , Estimativa de Kaplan-Meier , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/metabolismo , Prognóstico , Mapas de Interação de Proteínas/genética , Análise de Sobrevida , Transcriptoma/genética , Enzimas de Conjugação de Ubiquitina/metabolismoRESUMO
INTRODUCTION: In recent years, gamma-glutamyl transpeptidase to platelet ratio (GPR) has been proposed as a new inflammatory marker. We aimed to evaluate the association between GPR and outcomes after cardiac arrest (CA). METHODS: A total of 354 consecutive patients with CA were included in this retrospective study. Patients were divided into three groups according to tertiles of GPR (low, n = 119; middle, n = 117; and high, n = 118). To determine the relationship between GPR and prognosis, a logistic regression analysis was performed. The ability of GPR to predict the outcomes was evaluated by receiver operating characteristic (ROC) curve analysis. Two prediction models were established, and the likelihood ratio test (LRT) and the Akaike Information Criterion (AIC) were utilized for model comparison. RESULTS: Among the 354 patients (age 62 [52, 74], 254/354 male) who were finally included in the analysis, those in the high GPR group had poor outcomes. Multivariate logistic regression analysis revealed that GPR was independently associated with the three outcomes, for ICU mortality (odds ratios (OR) = 1.738, 95% confidence interval (CI): 1.221-2.474, P = 0.002), hospital mortality (OR = 1.676[1.164 - 2.413], P = 0.005), and unfavorable neurologic outcomes (OR = 1.623[1.121 - 2.351], P = 0.010). The area under the ROC curve was 0.611 (95% Cl: 0.558-0.662) for ICU mortality, 0.600 (95% CI: 0.547-0.651) for hospital mortality, and 0.602 (95% CI: 0.549-0.653) for unfavorable neurologic outcomes. Further, the LRT analysis showed that compared with the model without GPR, the GPR-combined model had a higher likelihood ratio χ 2 score and smaller AIC. CONCLUSION: GPR, as an inflammatory indicator, was independently associated with outcomes after CA. GPR is helpful in estimating the clinical outcomes of patients with CA.
Assuntos
Parada Cardíaca , gama-Glutamiltransferase , Feminino , Humanos , Cirrose Hepática , Masculino , Pessoa de Meia-Idade , Contagem de Plaquetas , Prognóstico , Curva ROC , Estudos RetrospectivosRESUMO
The compound γ-aminobutyric acid (GABA) was widely used in various fields. To enhance the production of GABA in Escherichia coli BL21(DE3), the enzymes of the regeneration pathway of the coenzyme factor pyridoxal 5'-phosphate (PLP) were engineered. The recombinant E. coli strain was screened and identified. The initial concentrations of L-monosodium glutamate (L-MSG) had an obvious influence on the production of GABA. The highest concentration of GABA in recombinant E. coli BL21/pET28a-gadA was 5.54 g/L when the initial L-MSG concentration was 10 g/L, whereas it was 8.45 g/L in recombinant E. coli BL21/pET28a-gadA-SNO1-SNZ1 at an initial L-MSG concentration of 15 g/L. The corresponding conversion yields of GABA in these two strains were 91.0% and 92.7%, respectively. When the initial concentrations of L-MSG were more than 15 g/L, the concentrations of GABA in E. coli BL21/pET28a-gadA-SNO1-SNZ1 were significantly higher as compared to those in recombinant E. coli BL21/pET28a-gadA, and it reached a maximum of 13.20 g/L at an initial L-MSG concentration of 25 g/L, demonstrating that the introduction of the enzymes of the regeneration pathway of PLP favored to enhance the production of GABA. This study provides new insight into producing GABA effectively in E. coli BL21(DE3).
Assuntos
Coenzimas/metabolismo , Escherichia coli/genética , Escherichia coli/metabolismo , Fosfato de Piridoxal/metabolismo , Ácido gama-Aminobutírico/biossíntese , Vias Biossintéticas , Engenharia Metabólica , Glutamato de Sódio/metabolismoRESUMO
In this study, the conversion of vitamin D3 (VD3) to its two active forms 25(OH)VD3 and 1α, 25(OH)2VD3 was carried out by engineering the hydroxylase CYP105A1 and its redox partners Fdx and Fdr. CYP105A1 and Fdx-Fdr were respectively expressed in E. coli BL21(DE3) and purified. The electron transport chain Fdx-Fdr had higher selectivity for the coenzyme NADH than NADPH. HPLC analysis showed that CYP105A1 could hydroxylate the C25 and C1α sites of VD3 and convert VD3 to its active forms. Finally, a one-bacterium-multi-enzyme system was constructed and used in whole-cell catalytic experiments. The results indicated that 2.491 mg/L of 25(OH)VD3 and 0.698 mg/L of 1α, 25(OH)2VD3 were successfully produced under the condition of 1.0% co-solvent DMSO, 1 mM coenzyme NADH and 35 g/L biocatalyst loading. This study contributes to a basis for the industrial production of active VD3 in future.
Assuntos
Proteínas de Bactérias/metabolismo , Colecalciferol/biossíntese , Sistema Enzimático do Citocromo P-450/metabolismo , Transporte de Elétrons , Escherichia coli/enzimologia , Escherichia coli/metabolismo , Oxigenases de Função Mista/metabolismo , Proteínas de Bactérias/genética , Catálise , Sistema Enzimático do Citocromo P-450/genética , Engenharia Genética , Microbiologia Industrial , Oxigenases de Função Mista/genética , OxirreduçãoRESUMO
Multifactor and multistep processes were elucidated to participate in the progression of non-small-cell lung cancer (NSCLC). Circular RNA 0031250 (circ-PRMT5) was a vital factor in NSCLC. However, the role of circ-PRMT5 in cisplatin (DDP)-resistance needed to be further highlighted. Expression profiles of circ-PRMT5, microRNA (miR)-4458, and EV3-like DNA-directed polymerase ζ catalytic subunit (REV3L) were detected using quantitative real-time polymerase chain reaction. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide, flow cytometry, and transwell assays were performed to determine the half-maximal inhibitory concentration of DDP, cell viability, apoptosis, and invasion in vitro. Besides, the protein levels of REV3L and indicated proteins were examined by adopting western blot. Dual-luciferase reporter assay was performed to analyze the interaction between miR-4458 and circ-PRMT5 or REV3L. The functional role of circ-PRMT5 was explored using a xenograft tumor model. Levels of circ-PRMT5 and REV3L were markedly increased, while miR-4458 was downregulated in resistant tissues and cells. Knockdown of circ-PRMT5 enhanced cell apoptosis, DDP-sensitivity, and declined metastasis in NSCLC with DDP resistance. Besides, miR-4458 inhibition or REV3L upregulation could revert circ-PRMT5 absence-mediated effect on DDP-sensitivity in vitro. Mechanically, circ-PRMT5 was a sponge of miR-4458 to regulate REV3L. Importantly, circ-PRMT5 silencing could interact with DDP treatment expedite the decrease of tumor growth in vivo. Circ-PRMT5 promoted DDP resistance via REV3L by sponging miR-4458 in NSCLC, thus providing a novel therapeutic strategy for patients with NSCLC.
Assuntos
Carcinoma Pulmonar de Células não Pequenas/genética , Resistencia a Medicamentos Antineoplásicos/genética , Proteína-Arginina N-Metiltransferases/genética , Células A549 , Animais , Apoptose/efeitos dos fármacos , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/genética , China , Cisplatino/farmacologia , Proteínas de Ligação a DNA/genética , Proteínas de Ligação a DNA/metabolismo , DNA Polimerase Dirigida por DNA/genética , DNA Polimerase Dirigida por DNA/metabolismo , Resistencia a Medicamentos Antineoplásicos/fisiologia , Feminino , Humanos , Masculino , Camundongos , Camundongos Nus , MicroRNAs/genética , MicroRNAs/metabolismo , Proteína-Arginina N-Metiltransferases/metabolismo , RNA Circular/genética , RNA Circular/metabolismo , Ensaios Antitumorais Modelo de Xenoenxerto/métodosRESUMO
BACKGROUND AND OBJECTIVE: Anastomotic leakage is a serious complication after arterial resection of rectal cancer. It has been found that anastomotic leakage is related to the oncological outcome. The purpose of the study is to evaluate the long-term outcome of the rectal tumor after anastomotic leakage. METHODS: The effect of anastomotic leakage on the oncological outcome of rectal cancer was studied by electronic literature retrieval. Using the DerSimonian Laird random effect model to calculate the odds ratio and 95% confidence interval. Research heterogeneity was evaluated by Q statistics and I2 , and bias was evaluated by funnel plot and Begg's test. RESULTS: A total of 35 studies and 44 698 patients were included in the study. The studies have shown that anastomotic leakage is associated with local recurrence (OR = 1.93; 95% CI, 1.57-2.38; P < .0001), overall survival (OR = 1.64; 95% CI, 1.37-1.95; P < .00001), disease-free survival (OR = 2.07; 95% CI, 1.50-2.87; P < .00001) and cancer-specific survival (OR = 1.32; 95% CI, 1.02-1.70; P = .012), while it was not related to distant recurrence (OR = 1.25; 95% CI, 0.95-1.65; P = .12). CONCLUSIONS: The results showed that anastomotic leakage after anterior resection increased the risk of local recurrence, decreased the overall survival, cancer-specific survival and disease-free survival.
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Anastomose Cirúrgica/efeitos adversos , Fístula Anastomótica/epidemiologia , Recidiva Local de Neoplasia/epidemiologia , Neoplasias Retais/cirurgia , Anastomose Cirúrgica/métodos , Anastomose Cirúrgica/estatística & dados numéricos , Fístula Anastomótica/etiologia , Humanos , Recidiva Local de Neoplasia/etiologia , Resultado do TratamentoRESUMO
BACKGROUND: To determine whether intermittent hypoxia (IH) can reduce the infarct size (IS) after acute myocardial infarction (AMI) in rats. METHODS: Articles were identified in PubMed, EMBASE and the Web of Science and were included if they evaluated the effect of IH on the changes in the infarcted area after AMI in rats. RESULTS: A preliminary search identified 3633 articles and 29 data sets from 23 articles (12 in vivo, 16 in vitro). The IS decreased after AMI in IH rats both in vitro (SMD -1.46, 95% CI [- 2.37, - 0.55]; I2 = 85.6%, P = 0.000) and in vivo (SMD -1.43, 95% CI [- 2.05, - 0.82], I2 = 73.6%, P = 0.000). Sensitivity analysis indicated that IH had a strong protective effect against myocardial infarction, and the hypoxia concentration was significantly correlated with the change in IS after AMI. CONCLUSION: IH can reduce IS after AMI in rats. This effect of IH may be related to the dose of hypoxia, and the oxygen concentration may be one of the most important influencing factors.
Assuntos
Hipóxia/metabolismo , Infarto do Miocárdio/prevenção & controle , Miocárdio/patologia , Oxigênio/metabolismo , Animais , Modelos Animais de Doenças , Infarto do Miocárdio/metabolismo , Infarto do Miocárdio/patologia , Miocárdio/metabolismo , RatosRESUMO
BACKGROUND: Recently, sclerostin, a bone-derived protein, has been shown to play a key role in atherosclerosis progression. However, few studies have investigated the influence of sclerostin on cardiovascular disease prognosis. We investigated the relationship between serum sclerostin levels and adverse outcomes in elderly patients with stable coronary artery disease (SCAD) who were undergoing percutaneous coronary intervention (PCI). METHODS: We enrolled 310 elderly SCAD patients who underwent PCI in this study and followed them 3 years. According to the median serum sclerostin levels, subjects were stratified into a low sclerostin (low scl) group (n = 144) and a high sclerostin (high scl) group (n = 166). Time-to-event analyses were performed with the Kaplan-Meier method. Associations between sclerostin levels and main adverse cardiovascular and cerebrovascular events (MACCEs) and mortality were evaluated by Cox multivariate regression analysis. The prognostic power of predictive models was verified by the concordance index and receiver operating characteristic curve analysis. RESULTS: The high scl group had a significantly higher MACCE-free rate and better survival than the low scl group. Serum sclerostin was an independent predictor and could improve the prognostic power for adverse outcomes. In addition, serum sclerostin levels were significantly associated with bone turnover markers, a lower presence of multivessel disease and a lower CCS angina class. CONCLUSIONS: Serum sclerostin is a prognostic parameter for predicting and intervening in the adverse outcomes of elderly SCAD patients undergoing PCI, which may be explained by its potential role in the bone-vascular axis.
Assuntos
Doença da Artéria Coronariana , Intervenção Coronária Percutânea , Idoso , Idoso de 80 Anos ou mais , Canadá , Doença da Artéria Coronariana/cirurgia , Feminino , Humanos , Masculino , Intervenção Coronária Percutânea/efeitos adversos , Prognóstico , Curva ROC , Fatores de Risco , Resultado do TratamentoRESUMO
As the continuous scientific research, seven new 1-oxygenated cholestane glycosides named osaundersiosides 1 A - 1 G were isolated from an EtOH extract of the bulbs of Ornithogalum saundersiae. Their structures were deduced by means of spectroscopic data, chemical evidence and the results of hydrolytic cleavage. The cytotoxicity and anti-inflammatory effects of osaundersiosides 1 A - 1 G were evaluated, but none of them displayed significant activities. [Formula: see text].
Assuntos
Antineoplásicos Fitogênicos , Colestanos , Ornithogalum , Glicosídeos , Estrutura MolecularRESUMO
This study examines whether the benefits of a short midday nap on habitual nappers' mental performance depend on the cognitive domain and the task difficulty. Eighteen healthy college students with the long-term habit of a midday nap (13:00-14:00 hours) participated in a nap-deprivation study. On two separate days with at least 3 days in between, participants either took a nap or remained awake, and were subsequently tested on a simple sustained attention task (Psychomotor Vigilance Test), two more complex attention tasks (Go/No-Go and Flanker task) and one working memory task (2-back). For each task, an easy and a difficult version were administered. The time course of subjective sleepiness and mood were also measured in both napping conditions. The results revealed that short midday nap deprivation significantly impaired participants' performance on both the easy and difficult versions of the Psychomotor Vigilance Test task, as well as accuracy but not reaction speed in the Go/No-Go task. Accuracy in the difficult version of the Flanker task and the 2-back task was also lower in the no-nap condition, while reaction speed in the 2-back task but not the Flanker task was reduced without a nap in both the easy and difficult versions. Moreover, subjective sleepiness was significantly increased after nap deprivation, but moods remained unaffected in the no-nap condition. These findings contribute to current research suggesting that effects of a midday nap on task performance depend on the cognitive domain as well as task difficulty. Our study highlights the importance of considering task characteristics to evaluate the benefits of a regular midday nap in practical working life.