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1.
Front Med ; 16(2): 240-250, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35416629

RESUMO

The continuing discoveries of novel classes of RNA modifications in various organisms have raised the need for improving sensitive, convenient, and reliable methods for quantifying RNA modifications. In particular, a subset of small RNAs, including microRNAs (miRNAs) and Piwi-interacting RNAs (piRNAs), are modified at their 3'-terminal nucleotides via 2'-O-methylation. However, quantifying the levels of these small RNAs is difficult because 2'-O-methylation at the RNA 3'-terminus inhibits the activity of polyadenylate polymerase and T4 RNA ligase. These two enzymes are indispensable for RNA labeling or ligation in conventional miRNA quantification assays. In this study, we profiled 3'-terminal 2'-O-methyl plant miRNAs in the livers of rice-fed mice by oxidative deep sequencing and detected increasing amounts of plant miRNAs with prolonged oxidation treatment. We further compared the efficiency of stem-loop and poly(A)-tailed RT-qPCR in quantifying plant miRNAs in animal tissues and identified stem-loop RT-qPCR as the only suitable approach. Likewise, stem-loop RT-qPCR was superior to poly(A)-tailed RT-qPCR in quantifying 3'-terminal 2'-O-methyl piRNAs in human seminal plasma. In summary, this study established a standard procedure for quantifying the levels of 3'-terminal 2'-O-methyl miRNAs in plants and piRNAs. Accurate measurement of the 3'-terminal 2'-O-methylation of small RNAs has profound implications for understanding their pathophysiologic roles in biological systems.


Assuntos
MicroRNAs , Animais , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Metilação , Camundongos , MicroRNAs/genética , Estresse Oxidativo , RNA Interferente Pequeno/metabolismo , Reação em Cadeia da Polimerase em Tempo Real
2.
Ginekol Pol ; 2022 Jan 24.
Artigo em Inglês | MEDLINE | ID: mdl-35072224

RESUMO

OBJECTIVES: Mesenchymal stem cell (MSC)-based therapies are expected to restore the fertility of infertile patients. In addition to MSC-derived paracrine effects to improve reproductive function, the differentiation of MSCs into germ cell (GC)-like cells is still a promising method to repair the injured reproductive system. The aim of this study was to examine the effect and potential mechanism of BMP4 in inducing umbilical cord MSC (UcMSC) transdifferentiation into GC-like cells. MATERIAL AND METHODS: UcMSCs were isolated, cultured and identified by flow cytometry and multilineage differentiation assays. After induction with 12.5 ng/mL BMP4 for 21 days, UcMSCs were collected for further examination. Immunofluorescence was used to detect the expression of Prdm1 and Prdm14; RT-PCR and RNA sequencing were used to detect differential gene expression (DEGs). RESULTS: The morphology of UcMSCs became large and flat after treatment with BMP4; the expression of GC-related genes (OCT4, Prdm1, Ifitm3 and Stella) was significantly downregulated, and further immunofluorescence results also confirmed the significant downregulation of Prdm1 in UcMSCs with BMP4 induction, while the expression of Prdm14 was significantly upregulated. The results of RNA sequencing and further analysis revealed no explicit correlation between BMP4 induction and the differentiation of UcMSCs into GC-like cells based on the 662 screened DEGs in UcMSCs with or without BMP4 induction. CONCLUSIONS: The differentiation of MSCs into GC-like cells is rather complex, and BMP4 alone is insufficient to induce UcMSCs to differentiate into GC-like cells, regardless of protein level or gene expression level.

3.
Front Med ; 16(2): 176-184, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-34515940

RESUMO

Studies of human and mammalian have revealed that environmental exposure can affect paternal health conditions as well as those of the offspring. However, studies that explore the mechanisms that meditate this transmission are rare. Recently, small noncoding RNAs (sncRNAs) in sperm have seemed crucial to this transmission due to their alteration in sperm in response to environmental exposure, and the methodology of microinjection of isolated total RNA or sncRNAs or synthetically identified sncRNAs gradually lifted the veil of sncRNA regulation during intergenerational inheritance along the male line. Hence, by reviewing relevant literature, this study intends to answer the following research concepts: (1) paternal environmental factors that can be passed on to offspring and are attributed to spermatozoal sncRNAs, (2) potential role of paternal spermatozoal sncRNAs during the intergenerational inheritance process, and (3) the potential mechanism by which spermatozoal sncRNAs meditate intergenerational inheritance. In summary, increased attention highlights the hidden wonder of spermatozoal sncRNAs during intergenerational inheritance. Therefore, in the future, more studies should focus on the origin of RNA alteration, the target of RNA regulation, and how sncRNA regulation during embryonic development can be sustained even in adult offspring.


Assuntos
Pequeno RNA não Traduzido , Animais , Exposição Ambiental , Epigênese Genética , Feminino , Humanos , Masculino , Mamíferos/genética , Gravidez , Pequeno RNA não Traduzido/genética , Espermatozoides
4.
J Colloid Interface Sci ; 610: 334-346, 2022 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-34923271

RESUMO

Fe, N atoms deposited on porous biochar (Fe-N@BC) composites were synthesized and employed as an efficient catalyst for organic pollutant removal and CrVI reduction. Naturally abundant, renewable and N-rich pomelo peel as a carbon and nitrogen source and unsubstituted phthalocyanine/iron phthalocyanine complexes as a Fe and nitrogen resource were used to develop the Fe-N@BC via a carbonization process. It is found that Fe-N@BC hybrids have homogeneous dispersion of Fe and N atoms on 3D hierarchically porous biochar, which significantly improves the performance toward the detoxification of organic pollutants using peroxymonosulfate as an oxidant, as well as the reduction of hexavalent chromium by formic acid as a reductant. Furthermore, the effects of Fe loading and pyrolytic temperature on catalysis were comprehensively analyzed and optimized. The excellent activity of Fe-N@BC in acid media can be attributed to the high dispersion of Fe species, high content of doped nitrogen as well as hierarchical micro-mesopores, which induce to expose more active sites for catalysis. Owing to the structure-enabled acidic stability, Fe-N@BC efficiently retains its activity as well as its structural stability after several cycles of reactions. This work provides a new approach to construct Fe, N-doped biochar as an effective catalyst for the detoxification of organic and inorganic pollutants.


Assuntos
Poluentes Ambientais , Poluentes Químicos da Água , Adsorção , Catálise , Carvão Vegetal , Cromo/análise , Ferro , Nitrogênio , Poluentes Químicos da Água/análise
5.
J Hazard Mater ; 422: 126776, 2022 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-34399226

RESUMO

Bimetallic Fe- and Mo-embedded N-enriched porous biochar (Fe-Mo@N-BC) is developed and serves as a cost-effective and highly efficient catalyst for mineralization of non-biodegradation organic contaminants. Fe-Mo@N-BC was prepared by pyrolysis of complex Fe/Mo -containing precursors. Transmission electron microscopy and elemental mapping suggested that Fe and Mo are uniformly dispersed in nitrogen-doped biochar with hierarchical mesopores. In comparison to Fe@N-BC and Mo@N-BC, Fe-Mo@N-BC exhibited a superior activity for activating peroxymonosulfate (PMS). The stable activity was ascribed to N-doping and synergistic effect of Fe and Mo species, where both Fe-Nx and Mo-Nx can simultaneously serve as the active sites and N-BC can act as a carrier and an activator as well as an electron mediator. Electron paramagnetic resonance and quenching experiments indicated that HO•, O2•- and 1O2 were responsible for organic degradation. The effects of PMS dosage, initial Orange II concentration, temperature, solution pH, coexisting anions and humic acids on organic degradation were also investigated. With the assistance of an external magnet, Fe-Mo@N-BC can be easily separated after reaction and remains stable in the reusability tests. This work demonstrates a feasible strategy towards the fabrication of Fe, Mo-embedded N-enriched porous biochar catalysts for the detoxification of organic contaminants.

6.
Elife ; 112022 Mar 14.
Artigo em Inglês | MEDLINE | ID: mdl-35286254

RESUMO

The bifunctional enzyme Δ1-pyrroline-5-carboxylate synthase (P5CS) is vital to the synthesis of proline and ornithine, playing an essential role in human health and agriculture. Pathogenic mutations in the P5CS gene (ALDH18A1) lead to neurocutaneous syndrome and skin relaxation connective tissue disease in humans, and P5CS deficiency seriously damages the ability to resist adversity in plants. We have recently found that P5CS forms cytoophidia in vivo and filaments in vitro. However, it is difficult to appreciate the function of P5CS filamentation without precise structures. Using cryo-electron microscopy, here we solve the structures of Drosophila full-length P5CS in three states at resolution from 3.1 to 4.3 Å. We observe distinct ligand-binding states and conformational changes for the GK and GPR domains, respectively. Divergent helical filaments are assembled by P5CS tetramers and stabilized by multiple interfaces. Point mutations disturbing those interfaces prevent P5CS filamentation and greatly reduce the enzymatic activity. Our findings reveal that filamentation is crucial for the coordination between the GK and GPR domains, providing a structural basis for the catalytic function of P5CS filaments.


Assuntos
Ornitina-Oxo-Ácido Transaminase , Prolina , Microscopia Crioeletrônica , Citoesqueleto , Mutação , Ornitina-Oxo-Ácido Transaminase/genética
7.
Mol Plant Pathol ; 2021 Dec 06.
Artigo em Inglês | MEDLINE | ID: mdl-34873812

RESUMO

Extracellular vesicles (EVs) are rounded vesicles enclosed by a lipid bilayer membrane, released by eukaryotic cells and by bacteria. They carry various types of bioactive substances, including nucleic acids, proteins, and lipids. Depending on their cargo, EVs have a variety of well-studied functions in mammalian systems, including cell-to-cell communication, cancer progression, and pathogenesis. In contrast, EVs in plant cells (which have rigid walls) have received very little research attention for many decades. Increasing evidence during the past decade indicates that both plant cells and plant pathogens are able to produce and secrete EVs, and that such EVs play key roles in plant-pathogen interactions. Plant EVs contains small RNAs (sRNAs) and defence-related proteins, and may be taken up by pathogenic fungi, resulting in reduced virulence. On the other hand, EVs released by gram-negative bacteria contain a wide variety of effectors and small molecules capable of activating plant immune responses via pattern-recognition receptor- and BRI1-ASSOCIATED RECEPTOR KINASE- and SUPPRESSOR OF BIR1-mediated signalling pathways, and salicylic acid-dependent and -independent processes. The roles of EVs in plant-pathogen interactions are summarized in this review, with emphasis on important molecules (sRNAs, proteins) present in plant EVs.

8.
Artigo em Inglês | MEDLINE | ID: mdl-34236807

RESUMO

INTRODUCTION: The objective of this study is to evaluate the left ventricular systolic function of patients with coronary microvascular dysfunction (CMD) using the three-dimensional speckle-tracking imaging (3D-STI) technique. METHODS: From June 2018 to June 2019,72 subjects from Huzhou Central Hospital were enrolled, including 42 CMD in-patients with typical chest pain or chest tightness and positive treadmill exercise stress test, but without coronary stenosis on coronary angiography, (the CMD group) and another 30 healthy individuals who were undergoing physical examinations in an outpatient clinic (the control group). Using 3D-STI technique, the global longitudinal strain (GLS), global radial strain (GRS), global circumferential strain (GCS), global area strain (GAS), and left ventricle were measured. RESULTS: Compared with the control group, GLS and GAS were significantly reduced in the CMD group (P<0.05), while GRS and GCS were similar in both groups (P>0.05). Univariate logistic regression analysis showed that GLS and GAS were the influencing factors of CMD. For the diagnosis of CMD, the area under the receiver operating characteristic (ROC) curve of GLS was 0.883, and the area under the ROC curve of GAS was 0.875. GAS of -29.3% (log-rank test chi-square=34.245, P<0.001) was a strong predictor of major adverse cardiac events. CONCLUSION: 3D-STI technique has obvious advantages in the evaluation of the left ventricular systolic function for CMD patients. Moreover, 3D-STI parameters, especially GLS and GAS, can detect the early abnormal changes in the ischaemic myocardium. Being timelier and more sensitive than echocardiography, 3D-STI should be recommended for clinical application.

9.
Proc Natl Acad Sci U S A ; 118(30)2021 07 27.
Artigo em Inglês | MEDLINE | ID: mdl-34301892

RESUMO

Cytidine triphosphate synthase (CTPS), which comprises an ammonia ligase domain and a glutamine amidotransferase domain, catalyzes the final step of de novo CTP biosynthesis. The activity of CTPS is regulated by the binding of four nucleotides and glutamine. While glutamine serves as an ammonia donor for the ATP-dependent conversion of UTP to CTP, the fourth nucleotide GTP acts as an allosteric activator. Models have been proposed to explain the mechanisms of action at the active site of the ammonia ligase domain and the conformational changes derived by GTP binding. However, actual GTP/ATP/UTP binding modes and relevant conformational changes have not been revealed fully. Here, we report the discovery of binding modes of four nucleotides and a glutamine analog 6-diazo-5-oxo-L-norleucine in Drosophila CTPS by cryo-electron microscopy with near-atomic resolution. Interactions between GTP and surrounding residues indicate that GTP acts to coordinate reactions at both domains by directly blocking ammonia leakage and stabilizing the ammonia tunnel. Additionally, we observe the ATP-dependent UTP phosphorylation intermediate and determine interacting residues at the ammonia ligase. A noncanonical CTP binding at the ATP binding site suggests another layer of feedback inhibition. Our findings not only delineate the structure of CTPS in the presence of all substrates but also complete our understanding of the underlying mechanisms of the allosteric regulation and CTP synthesis.


Assuntos
Trifosfato de Adenosina/metabolismo , Amônia/metabolismo , Carbono-Nitrogênio Ligases/química , Carbono-Nitrogênio Ligases/metabolismo , Drosophila melanogaster/enzimologia , Glutamina/metabolismo , Uridina Trifosfato/metabolismo , Regulação Alostérica , Animais , Sítios de Ligação , Catálise , Microscopia Crioeletrônica , Hidrólise , Cinética , Ligantes , Conformação Proteica
10.
Sci Adv ; 7(7)2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33568480

RESUMO

Evidence that offspring traits can be shaped by parental life experiences in an epigenetically inherited manner paves a way for understanding the etiology of depression. Here, we show that F1 offspring born to F0 males of depression-like model are susceptible to depression-like symptoms at the molecular, neuronal, and behavioral levels. Sperm small RNAs, and microRNAs (miRNAs) in particular, exhibit distinct expression profiles in F0 males of depression-like model and recapitulate paternal depressive-like phenotypes in F1 offspring. Neutralization of the abnormal miRNAs in zygotes by antisense strands rescues the acquired depressive-like phenotypes in F1 offspring born to F0 males of depression-like model. Mechanistically, sperm miRNAs reshape early embryonic transcriptional profiles in the core neuronal circuits toward depression-like phenotypes. Overall, the findings reveal a causal role of sperm miRNAs in the inheritance of depression and provide insight into the mechanism underlying susceptibility to depression.

11.
Nicotine Tob Res ; 23(1): 85-91, 2021 01 07.
Artigo em Inglês | MEDLINE | ID: mdl-31504860

RESUMO

INTRODUCTION: The effect of weight gain following smoking cessation on cardiovascular risks is unclear. We aimed to prospectively investigate the association of weight gain following smoking cessation with the trajectory of estimated risks of coronary heart disease (CHD). METHODS: In a cohort of 18 562 Japanese male employees aged 30-64 years and initially free of cardiovascular diseases, participants were exclusively grouped into sustained smokers, quitters with weight gain (body weight increase ≥5%), quitters without weight gain (body weight increase <5% or weight loss), and never smokers. Global 10-year CHD risk was annually estimated by using a well-validated prediction model for the Japanese population. Linear mixed models and piecewise linear mixed models were used to compare changes in the estimated 10-year CHD risk by smoking status and weight change following smoking cessation. RESULTS: During a maximum of 8-year follow-up, both quitters with and without weight gain had a substantially decreased level of estimated 10-year CHD risk after quitting smoking, compared with sustained smokers (all ps for mean differences < .001). The estimated 10-year CHD risk within the first year after cessation decreased more rapidly in quitters without weight gain than in quitters with weight gain (change rate [95% confidence interval, CI] -0.90 [-1.04 to -0.75] vs. -0.40 [-0.60 to -0.19] % per year, p < .0001). Thereafter, the estimated 10-year CHD risk in both groups increased at similar rates (change rate [95% CI] -0.07 [-0.21 to 0.07] vs. 0.11 [-0.09 to 0.30] % per year, p = .16, from year 1 to year 2; and 0.10 [0.05 to 0.15] vs. 0.11 [0.04 to 0.18] % per year, p = .80, from year 2 to year 8). CONCLUSIONS: In this population of middle-aged, Japanese male workers, smoking cessation greatly reduces the estimated 10-year risk of CHD. However, weight gain weakens the beneficial effect of quitting smoking in a temporary and limited fashion. IMPLICATIONS: To the best of our knowledge, this study is the first to examine the effect of weight gain following smoking cessation on the trajectory of the absolute risk of CHD. Our data imply that the benefits of cessation for reducing the absolute risk of CHD outweigh the potential risk increase due to weight gain, and suggest that in order to maximize the beneficial effects of quitting smoking, interventions to control post-cessation weight gain might be warranted.


Assuntos
Doenças Cardiovasculares/epidemiologia , Abandono do Hábito de Fumar/métodos , Fumar/efeitos adversos , Ganho de Peso , Adulto , Doenças Cardiovasculares/etiologia , Seguimentos , Humanos , Incidência , Japão/epidemiologia , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Fatores de Risco , Abandono do Hábito de Fumar/estatística & dados numéricos
12.
Cell Tissue Bank ; 21(4): 667-673, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32870439

RESUMO

Rapid freezing and vitrification using sucrose are two simple and cost-effective sperm cryopreservation methods. However, it is still unclear which method is better and what the optimal concentration of sucrose is. This study aimed to determine the optimal sucrose concentration for human sperm cryopreservation and compare the cryoprotective effects of rapid freezing versus vitrification using different closed straw systems in terms of sperm motility and DNA integrity. Our data showed that: (1) The optimal sucrose concentration for vitrification was 0.25 mol/l among the tested 0, 0.125, 0.25 and 0.5 mol/l concentrations; (2) Sperm total motility and progressive motility were cryopreserved significantly better by rapid freezing than vitrification in standard 0.5 ml cryostraws (P < 0.05); and (3) Sperm total motility and progressive motility were cryopreserved significantly better by vitrification in the straw-in-straw system than rapid freezing in the standard 0.5 cryostraw (P < 0.05), but no difference was found in sperm nuclear DNA fragmentation level between the two cryopreservation methods (P > 0.05). It was concluded that sucrose at 0.25 mol/l concentration is suitable for human sperm rapid freezing and vitrification, and sperm cryopreservation can be achieved by rapid freezing using closed standard 0.5 ml straws or by vitrification using the novel straw-in-straw system made of standard 0.25 and 0.5 ml straws.


Assuntos
Criopreservação , Congelamento , Espermatozoides/fisiologia , Sacarose/farmacologia , Vitrificação , Adulto , Cromatina/metabolismo , Dano ao DNA , Humanos , Masculino , Espermatozoides/efeitos dos fármacos , Adulto Jovem
13.
Eur J Clin Pharmacol ; 76(11): 1517-1527, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32632713

RESUMO

PURPOSE: Dual antiplatelet therapy (DAT) with clopidogrel and aspirin is not suitable for clopidogrel resistance (CR) patients with aspirin intolerance. To investigate the prevalence of CR in patients with aspirin intolerance after ischemic stroke (IS) and to assess the relationship between CR and CYP2C19, P2Y12 receptor genotypes in patients with aspirin intolerance after IS. METHODS: We enrolled 126 IS patients with aspirin intolerance from Han Chinese in Shangqiu from January 2016 to November 2018. All IS patients with aspirin intolerance were treated with clopidogrel for 7 days. Adenosine diphosphate-induced platelet inhibition rate was measured by thrombelastography (TEG) mapping assay. The SNPs CYP2C19*2, CYP2C19*3, and P2Y12 receptor (52 G >T) were genotyped by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) technique. Binary logistic regression analyses were performed using SPSS version 20.0. RESULTS: The prevalence of CR in patients with aspirin intolerance after IS was approximately 31.0%. Multivariate regression analysis showed that body weight (OR 1.091 (95% CI 1.031-1.155), p = 0.003), CYP2C19 phenotype intermediate metabolizer (IM) (OR 3.820 (95% CI 1.021-14.288), p = 0.046), and CYP2C19 phenotype poor metabolizer (PM) (OR 14.481 (95% CI 2.791-75.129), p = 0.001) significantly increased the risk of CR and P2Y12 receptors (52 G >T) (OR 3.498 [95% CI 1.251-9.784], p = 0.017) increased the risk of CR. CONCLUSIONS: The patients with high body weight, the CYP2C19 phenotypes, and P2Y12 receptor (52 G >T) variant alleles are at risk of CR during clopidogrel treatment in Chinese IS patients with aspirin intolerance. The higher body weight and relevant polymorphisms may help to predict CR in Chinese IS patients with aspirin intolerance.


Assuntos
Aspirina/uso terapêutico , Clopidogrel/uso terapêutico , Citocromo P-450 CYP2C19/genética , AVC Isquêmico/tratamento farmacológico , Polimorfismo de Nucleotídeo Único , Receptores Purinérgicos P2Y12/genética , Idoso , Peso Corporal , Estudos de Coortes , Resistência a Medicamentos , Feminino , Genótipo , Humanos , AVC Isquêmico/genética , Masculino , Pessoa de Meia-Idade
14.
Ther Adv Reprod Health ; 14: 2633494120909375, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32518916

RESUMO

Rapid freezing and vitrification are becoming popular for sperm freezing in humans; however, basic and critical issues relevant to sperm cryopreservation remain to be resolved. The aims of the present study were to study the effects of osmolality of freezing medium, sperm concentrations, thawing methods, and sugars (sucrose and trehalose) on sperm motility and DNA integrity by rapid freezing using 0.5 ml standard straws loaded with 100 µl sperm each. The results showed that (1) the post-thaw recovery rates of total motility and progressive motility of sperm cryopreserved in freezing medium containing 0.25 M sucrose with 442 mOsm/kg osmolality were significantly higher (p < 0.05) than that of sperm cryopreserved in freezing medium containing 0.25 M sucrose with 536 mOsm/kg osmolality (36.5 ± 2.8% and 36.9 ± 1.7% versus 30.4 ± 1.9% and 30.3 ± 2.9%, respectively), (2) cryopreservation of both total and progressive motilities was not significantly affected (p > 0.05) by sperm concentrations in the range from 5 to 20 × 106 sperm/ml, (3) thawing method 37°C for 2 min was better than 42°C for 15 s in terms of post-thaw recovery rates of both total and progressive motilities (p < 0.05), (4) 0.25 M trehalose was better than 0.25 M sucrose in cryopreserving both total and progressive motilities (p < 0.05), and (5) sperm nuclear DNA is relatively resistant to the changes of the above factors compared with sperm motility. It was concluded that human sperm can be best cryopreserved by rapid freezing using 0.25 M sucrose or trehalose with osmolality 442 to 457 mOsm/kg at high sperm concentration followed by thawing at 37°C. Trehalose is a stronger cryoprotectant than sucrose for sperm cryopreservation.

15.
Cancer Cell Int ; 20: 266, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32595415

RESUMO

BACKGROUND: The effect of lncRNA FTX on non-alcoholic fatty liver disease (NAFLD) conversion to hepatocellular carcinoma (HCC) is unclear. METHODS: In our study, C57BL/6 mice was fed with high fat diet for obtaining NAFLD mouse model, and diethylnitrosamine induced the formation of HCC tumor. The expression of iNOS and CD206 in tissues were examined using immunohistochemistry. In addition, qRT-PCR was implemented to detect the expression of FTX and mRNAs. The percentage of M1 and M2 Kupffer cells (KCs) were determined using flow cytometry. The pathological change in liver tissues was displayed by H&E staining. Besides, immunofluorescence assay was performed to ensure the primary KCs through labeling F4/80. RESULTS: Here, we found that the expression of FTX and the ratio of M1/M2 KCs in liver tissues from NAFLD-transformed HCC (NAFLD-HCC) patients lower than in liver tissues from NAFLD patients. Subsequently, we revealed that the expression of FTX and M1/M2 KCs ratio were downregulated during NAFLD conversion to HCC. Importantly, increasing of FTX inhibited HCC tumor growth, improved liver damage and promoted M1 polarization of KCs during NAFLD conversion to HCC, while these effects of FTX were reversed by inactivating of KCs. Finally, in vitro experiments, our data indicated that FTX facilitated the M1 polarization of KCs. CONCLUSION: In conclusion, our results demonstrated that upregulation of FTX suppressed NAFLD conversion to HCC though promoting M1 polarization of KCs. Our findings presented a new regulatory mechanism for NAFLD conversion to HCC, and provided a new biomarker for inhibiting this conversion.

16.
J Genet Genomics ; 47(3): 131-143, 2020 03 20.
Artigo em Inglês | MEDLINE | ID: mdl-32317150

RESUMO

Compartmentation of enzymes via filamentation has arisen as a mechanism for the regulation of metabolism. In 2010, three groups independently reported that CTP synthase (CTPS) can assemble into a filamentous structure termed the cytoophidium. In searching for CTPS-interacting proteins, here we perform a yeast two-hybrid screening of Drosophila proteins and identify a putative CTPS-interacting protein, △1-pyrroline-5-carboxylate synthase (P5CS). Using the Drosophila follicle cell as the in vivo model, we confirm that P5CS forms cytoophidia, which are associated with CTPS cytoophidia. Overexpression of P5CS increases the length of CTPS cytoophidia. Conversely, filamentation of CTPS affects the morphology of P5CS cytoophidia. Finally, in vitro analyses confirm the filament-forming property of P5CS. Our work links CTPS with P5CS, two enzymes involved in the rate-limiting steps in pyrimidine and proline biosynthesis, respectively.


Assuntos
Carbono-Nitrogênio Ligases/genética , Citoesqueleto/genética , Ornitina-Oxo-Ácido Transaminase/genética , Prolina/biossíntese , Animais , Citidina Trifosfato/genética , Citidina Trifosfato/metabolismo , Citoesqueleto/metabolismo , Drosophila melanogaster/enzimologia , Regulação Enzimológica da Expressão Gênica/genética , Prolina/genética , Pirimidinas/metabolismo
17.
Ind Health ; 58(3): 246-253, 2020 Jun 09.
Artigo em Inglês | MEDLINE | ID: mdl-31611479

RESUMO

In occupational settings, smokers may take quitting smoking seriously if they experienced long-term sick leave due to cancer or cardiovascular disease (CVD). However, no study has elucidated the smoking cessation rate after long-term sick leave. We examined the smoking cessation rate after long-term sick leave due to cancer and CVD in Japan. We followed 23 survivors who experienced long-term sick leave due to cancer and 39 survivors who experienced long-term sick leave due to CVD who reported smoking at the last health exam before the leave. Their smoking habits before and after the leave were self-reported. Logistic regression was used to calculate adjusted smoking cessation rates. Smoking cessation rate after long-term sick leave due to cancer was approximately 70% and that due to CVD exceeded 80%. The adjusted smoking cessation rate was 67.6% (95% confidence interval [CI]: 47.0, 88.2) for cancer and 80.7% (95% CI: 67.7, 93.8) for CVD. Smoking cessation rate after a longer duration of sick leave (≥60 d) tended to increase for both CVD and cancer. Although any definite conclusion cannot be drawn, the data suggest that smoking cessation rate after long-term sick leave due to CVD is slightly higher than that for cancer.


Assuntos
Doenças Cardiovasculares , Neoplasias , Licença Médica/estatística & dados numéricos , Abandono do Hábito de Fumar/estatística & dados numéricos , Adulto , Estudos de Coortes , Feminino , Humanos , Japão , Masculino , Pessoa de Meia-Idade , Fatores de Tempo
18.
J Hazard Mater ; 389: 121844, 2020 05 05.
Artigo em Inglês | MEDLINE | ID: mdl-31879108

RESUMO

Nonprecious bimetallic molybdenum and iron embedded into N-doped carbon (MoFe-NC) hybrids were designed and fabricated by pyrolysis of mixed precursors and then immobilized on poly (vinylidene fluoride) (PVDF) films via a phase inversion process to obtain novel catalytic membranes (MoFe-NC@PVDF) for toxic CrVI reduction. The catalytic membranes are highly active for aqueous CrVI reduction using formic acid (FA) as a sacrificial electron donor under mild conditions. The results demonstrated that the parameters of synthesis process can efficiently adjust the morphology and textural properties of the as-synthesized MoFe-NC@PVDF membrane, and thus have a significant impact on the catalytic behavior. CrVI reduction rates significantly increased with increasing FA concentrations (0.234-0.936 M) and reaction temperature (5-35℃), but declined with the increase of CrVI concentrations (5-40 mg/L) and pH values of solution (1.87-4.62). Mo-Nx, Fe-Nx, and C-Nx are the active sites, boosting the dissociation of FA molecules into active H* species for effective catalytic reduction of CrVI. The catalytic PVDF membrane exhibited distinct porous structure and numerous interaction sites, which not only stabilized metallic nanoparticles, but also promoted mass transfer across the membrane. This cost-effective catalytic membrane provides a new approach toward the treatment of CrVI-containing water.

20.
J Occup Health ; 62(1): e12098, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31750612

RESUMO

OBJECTIVES: We aimed to compare the association of body mass index (BMI), waist circumference (WC), and waist-to-height ratio (WHtR) with risk of cardiovascular disease (CVD) among middle-aged working Japanese men. METHODS: A nested case-control study was performed among middle-aged male employees who underwent periodic health checkup. A total of 241 CVD cases were identified and matched individually on age, gender, and worksite with 1205 controls. Data on BMI, WC, WHtR, smoking, hypertension, diabetes, and dyslipidemia collected at 4 years before the event/index date were retrieved. Associations between BMI, WC, WHtR, and CVD risk were assessed by using conditional logistic regression models. RESULTS: The strength of the association of BMI, WC, and WHtR with CVD risk was similar. The smoking-adjusted odds ratio (95% confidence interval) for CVD was 1.60 (1.38-1.85), 1.53 (1.33-1.78), and 1.56 (1.35-1.81) for a 1 SD unit increase in BMI, WC, and WHtR respectively. After further adjustment for hypertension, diabetes, and dyslipidemia, these associations were attenuated but remained statistically significant. CONCLUSIONS: Measures of general (BMI) and abdominal (WC and WHtR) obesity were similarly associated with CVD in middle-aged Japanese men.


Assuntos
Índice de Massa Corporal , Doenças Cardiovasculares/etiologia , Obesidade/complicações , Circunferência da Cintura , Razão Cintura-Estatura , Adulto , Estudos de Casos e Controles , Humanos , Japão , Masculino , Pessoa de Meia-Idade , Fatores de Risco
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