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1.
Int Wound J ; 21(4): e14834, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38650426

RESUMO

A meta-analysis was conducted comprehensively to investigate the impact of evidence-based nursing (EBN) interventions on pressure injury (PI) in the intensive care unit (ICU) patients. Computer searches were performed, from databases inception to November 2023, in Wanfang, PubMed, China National Knowledge Infrastructure, Google Scholar, Embase, and Cochrane Library for randomized controlled trials (RCTs) on the application of EBN interventions in ICU patients. Two independent researchers conducted screenings of the literature, extracted data, and carried out quality evaluations. Stata 17.0 software was employed for data analysis. Overall, 25 RCTs, involving 2494 ICU patients, were included. It was found that compared to conventional care methods, the implementation of EBN interventions in ICU patients markedly decreased the occurrence of PI (odds ratio [OR]: 0.22, 95% confidence interval [CI]: 0.17-0.30, p < 0.001), delayed the onset time of pressure ulcers (standardized mean difference [SMD]: -1.61, 95% CI: -2.00 to -1.22, p < 0.001), and also improved nursing satisfaction (OR: 1.18, 95% CI: 1.14-1.23, p < 0.001). Our findings suggest the implementation of EBN interventions in the care of PI in ICU patients is highly valuable, can reduce the occurrence of PI, can delay the time of appearance, and is associated with relatively higher nursing satisfaction, making it worthy of promotion.


Assuntos
Enfermagem Baseada em Evidências , Unidades de Terapia Intensiva , Úlcera por Pressão , Úlcera por Pressão/enfermagem , Úlcera por Pressão/prevenção & controle , Humanos , Enfermagem Baseada em Evidências/métodos , Feminino , Masculino , Pessoa de Meia-Idade , Adulto , Idoso , Ensaios Clínicos Controlados Aleatórios como Assunto
2.
Nat Genet ; 56(1): 136-142, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38082204

RESUMO

Most fresh bananas belong to the Cavendish and Gros Michel subgroups. Here, we report chromosome-scale genome assemblies of Cavendish (1.48 Gb) and Gros Michel (1.33 Gb), defining three subgenomes, Ban, Dh and Ze, with Musa acuminata ssp. banksii, malaccensis and zebrina as their major ancestral contributors, respectively. The insertion of repeat sequences in the Fusarium oxysporum f. sp. cubense (Foc) tropical race 4 RGA2 (resistance gene analog 2) promoter was identified in most diploid and triploid bananas. We found that the receptor-like protein (RLP) locus, including Foc race 1-resistant genes, is absent in the Gros Michel Ze subgenome. We identified two NAP (NAC-like, activated by apetala3/pistillata) transcription factor homologs specifically and highly expressed in fruit that directly bind to the promoters of many fruit ripening genes and may be key regulators of fruit ripening. Our genome data should facilitate the breeding and super-domestication of bananas.


Assuntos
Fusarium , Musa , Musa/genética , Fusarium/genética , Triploidia , Melhoramento Vegetal , Fatores de Transcrição/genética , Doenças das Plantas/genética
3.
Mol Biotechnol ; 66(5): 1082-1094, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38151617

RESUMO

Cerebral ischemia is a severe neurological disability related to neuronal apoptosis and cellular stress response. Circular RNAs (circRNAs) are emerging regulators of cerebral ischemia. Herein, this study proposed to probe the action of circ_0000115 in cerebral ischemia injury. The mouse neuroblastoma cells N2a and HT22 underwent oxygen-glucose deprivation (OGD) were used as a model of in vitro cerebral ischemia. Levels of genes and proteins were detected by qRT-PCR and western blotting. Cell proliferation and apoptosis were determined by EdU assay and flow cytometry. Western blotting was used to detect the protein level of pro-inflammatory factors. The oxidative stress injury was evaluated by detecting reactive oxygen species (ROS), malondialdehyde (MDA) and superoxide dismutase (SOD) generation. Dual-luciferase reporter and RIP assays were used to confirm the target relationship between miR-1224-5p and circ_0000115 or nitric oxide synthase 3 (NOS3). OGD exposure decreased circ_0000115 and NOS3 expression, and increased miR-1224-5p in N2a and HT22 cells in a time-dependent manner. Circ_0000115 silencing attenuated OGD-induced apoptosis, oxidative stress and inflammation in N2a and HT22 cells. Mechanistically, circ_0000115 directly sponged miR-1224-5p, which targeted NOS3. Furthermore, rescue experiments showed that miR-1224-5p overexpression abolished the neuroprotective effect of circ_0000115 in N2a and HT22 cells under OGD treatment. Besides that, silencing of miR-1224-5p protected N2a and HT22 cells against OGD-evoked injury, which was counteracted by NOS3 knockdown. Circ_0000115 protects N2a and HT22 cells against OGD-evoked neuronal apoptosis, inflammation, and oxidative stress via the miR-1224-5p/NOS3 axis, providing an exciting view of the pathogenesis of cerebral ischemia.


Assuntos
Apoptose , Isquemia Encefálica , Inflamação , MicroRNAs , Neurônios , Estresse Oxidativo , RNA Circular , MicroRNAs/genética , MicroRNAs/metabolismo , Animais , RNA Circular/genética , RNA Circular/metabolismo , Apoptose/genética , Camundongos , Isquemia Encefálica/genética , Isquemia Encefálica/metabolismo , Isquemia Encefálica/patologia , Neurônios/metabolismo , Neurônios/patologia , Inflamação/genética , Inflamação/metabolismo , Inflamação/patologia , Linhagem Celular Tumoral , Glucose/metabolismo , Glucose/deficiência , Espécies Reativas de Oxigênio/metabolismo , Óxido Nítrico Sintase Tipo III
4.
Plant Physiol ; 193(1): 855-873, 2023 08 31.
Artigo em Inglês | MEDLINE | ID: mdl-37279567

RESUMO

Banana (Musa spp.) fruits, as typical tropical fruits, are cold sensitive, and lower temperatures can disrupt cellular compartmentalization and lead to severe browning. How tropical fruits respond to low temperature compared to the cold response mechanisms of model plants remains unknown. Here, we systematically characterized the changes in chromatin accessibility, histone modifications, distal cis-regulatory elements, transcription factor binding, and gene expression levels in banana peels in response to low temperature. Dynamic patterns of cold-induced transcripts were generally accompanied by concordant chromatin accessibility and histone modification changes. These upregulated genes were enriched for WRKY binding sites in their promoters and/or active enhancers. Compared to banana peel at room temperature, large amounts of banana WRKYs were specifically induced by cold and mediated enhancer-promoter interactions regulating critical browning pathways, including phospholipid degradation, oxidation, and cold tolerance. This hypothesis was supported by DNA affinity purification sequencing, luciferase reporter assays, and transient expression assay. Together, our findings highlight widespread transcriptional reprogramming via WRKYs during banana peel browning at low temperature and provide an extensive resource for studying gene regulation in tropical plants in response to cold stress, as well as potential targets for improving cold tolerance and shelf life of tropical fruits.


Assuntos
Conservação de Alimentos , Frutas , Musa , Musa/genética , Musa/fisiologia , Frutas/fisiologia , Temperatura Baixa , Histonas/metabolismo , Cromatina , Proteínas de Plantas/metabolismo , Elementos Facilitadores Genéticos , Código das Histonas , Fatores de Transcrição/metabolismo , Lipídeos de Membrana/metabolismo
5.
Plants (Basel) ; 12(8)2023 Apr 10.
Artigo em Inglês | MEDLINE | ID: mdl-37111823

RESUMO

SNAREs (soluble N-ethylmaleimide-sensitive-factor attachment protein receptors) are engines for almost all of the membrane fusion and exocytosis events in organism cells. In this study, we identified 84 SNARE genes from banana (Musa acuminata). Gene expression analysis revealed that the expression of MaSNAREs varied a lot in different banana organs. By analyzing their expression patterns under low temperature (4 °C), high temperature (45 °C), mutualistic fungus (Serendipita indica, Si) and fungal pathogen (Fusarium oxysporum f. sp. Cubense Tropical Race 4, FocTR4) treatments, many MaSNAREs were found to be stress responsive. For example, MaBET1d was up-regulate by both low and high temperature stresses; MaNPSN11a was up-regulated by low temperature but down-regulated by high temperature; and FocTR4 treatment up-regulated the expression of MaSYP121 but down-regulated MaVAMP72a and MaSNAP33a. Notably, the upregulation or downregulation effects of FocTR4 on the expression of some MaSNAREs could be alleviated by priorly colonized Si, suggesting that they play roles in the Si-enhanced banana wilt resistance. Foc resistance assays were performed in tobacco leaves transiently overexpressing MaSYP121, MaVAMP72a and MaSNAP33a. Results showed that transient overexpression of MaSYP121 and MaSNPA33a suppressed the penetration and spread of both Foc1 (Foc Race 1) and FocTR4 in tobacco leaves, suggesting that they play positive roles in resisting Foc infection. However, the transient overexpression of MaVAMP72a facilitated Foc infection. Our study can provide a basis for understanding the roles of MaSNAREs in the banana responses to temperature stress and mutualistic and pathogenic fungal colonization.

6.
J Cancer Res Clin Oncol ; 149(8): 5037-5045, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-36326914

RESUMO

PURPOSE: Chemical modification plays a critical role in regulating human cancer progression, especially N6-methyladenosine (m6A). However, m6A writer KIAA1429-mediated m6A modification in gastric cancer (GC) tumorigenesis remains largely unknown. METHODS: The levels of mRNA and protein were detected using RT-qPCR and western blot. The half maximal inhibitory concentration (IC50) of oxaliplatin (OXA) resistance is detected using CCK-8 assay. The binding within moleculars was identified using RIP-PCR. RESULTS: Results found that KIAA1429 was upregulated in GC tissue samples and its high expression acted as a prognostic factor of poor survival in patients with GC. Functional assays indicated that KIAA1429 promoted the proliferation of GC cells, besides, KIAA1429 accelerated the half maximal inhibitory concentration (IC50) of oxaliplatin (OXA) resistance. Mechanistically, online prediction found that there was possible m6A modification site on FOXM1 mRNA. KIAA1429 could target the m6A modification site on FOXM1. Notably, KIAA1429 facilitated the GC OXA resistance in GC cells by promoting FOXM1 mRNA stability. CONCLUSIONS: Taken together, our study reveals the functions and mechanism for KIAA1429 and exposes KIAA1429 as a key player in GC chemoresistance.


Assuntos
Neoplasias Gástricas , Humanos , Oxaliplatina/farmacologia , Neoplasias Gástricas/tratamento farmacológico , Neoplasias Gástricas/genética , Neoplasias Gástricas/metabolismo , Resistencia a Medicamentos Antineoplásicos/genética , Linhagem Celular Tumoral , RNA Mensageiro , Proteína Forkhead Box M1/genética , Proteína Forkhead Box M1/metabolismo
7.
Int J Mol Sci ; 23(19)2022 Oct 07.
Artigo em Inglês | MEDLINE | ID: mdl-36233216

RESUMO

Ca2+-ATPases have been confirmed to play very important roles in plant growth and development and in stress responses. However, studies on banana (Musa acuminata) Ca2+-ATPases are very limited. In this study, we identified 18 Ca2+-ATPase genes from banana, including 6 P-IIA or ER (Endoplasmic Reticulum) type Ca2+-ATPases (MaEACs) and 12 P-IIB or Auto-Inhibited Ca2+-ATPases (MaACAs). The MaEACs and MaACAs could be further classified into two and three subfamilies, respectively. This classification is well supported by their gene structures, which are encoded by protein motif distributions. The banana Ca2+-ATPases were all predicted to be plasma membrane-located. The promoter regions of banana Ca2+-ATPases contain many cis-acting elements and transcription factor binding sites (TFBS). A gene expression analysis showed that banana Ca2+-ATPases were differentially expressed in different organs. By investigating their expression patterns in banana roots under different concentrations of Ca2+ treatments, we found that most banana Ca2+-ATPase members were highly expressed under 4 mM and 2 mM Ca2+ treatments, but their expression decreased under 1 mM and 0 mM Ca2+ treatments, suggesting that their downregulation might be closely related to reduced Ca accumulation and retarded growth under low Ca2+ and Ca2+ deficiency conditions. Our study will contribute to the understanding of the roles of Ca2+-ATPases in banana growth and Ca management.


Assuntos
Musa , Adenosina Trifosfatases/metabolismo , Regulação da Expressão Gênica de Plantas , Musa/genética , Musa/metabolismo , Filogenia , Proteínas de Plantas/metabolismo , Fatores de Transcrição/metabolismo
8.
Hum Exp Toxicol ; 41: 9603271221120652, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36124980

RESUMO

PURPOSE: Ovarian cancer is a malignant tumor in women all over the world. Ropivacaine is identified as a potential drug for the treatment of malignant tumors, but the role and mechanism of ropivacaine in ovarian cancer remains unknown. MATERIALS AND METHODS: Ovarian cancer cells were treated with different doses of ropivacaine. The function of ropivacaine in ovarian cancer was assessed using Cell Counting Kit-8 assay, flow cytometry, sphere-formation assay, Western blot, Fe2+ level analysis, and immunofluorescence. Meanwhile, the mechanism of ropivacaine in ovarian cancer was investigated by multiple molecular experiments. The protective function of ropivacaine in ovarian cancer was further confirmed by in vivo assay. RESULTS: The functional research data indicated that the growth and stemness of ovarian cancer cells were restrained after ropivacaine treatment, while the ferroptosis in ovarian cancer cells was facilitated. The mechanism results confirmed that ropivacaine inactivated the PI3K/AKT signaling pathway in ovarian cancer cells. Furthermore, in vivo assay demonstrated that ropivacaine repressed the proliferation of ovarian cancer cells in vivo and had a protective function in ovarian cancer. CONCLUSION: Ropivacaine restrained ovarian cancer cell stemness and accelerated cell ferroptosis by inactivating PI3K/AKT signaling pathway.


Assuntos
Ferroptose , Neoplasias Ovarianas , Linhagem Celular Tumoral , Proliferação de Células , Feminino , Humanos , Neoplasias Ovarianas/tratamento farmacológico , Neoplasias Ovarianas/metabolismo , Neoplasias Ovarianas/patologia , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Ropivacaina/farmacologia , Ropivacaina/uso terapêutico , Transdução de Sinais
9.
Ther Adv Endocrinol Metab ; 13: 20420188221118750, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36157308

RESUMO

Background and purpose: With the progressive increase in the prevalence of type 2 diabetes mellitus (T2DM), diabetic nephropathy (DN) - one of the most common chronic microvascular complications - has evolved into a significant cause of death worldwide among end-stage renal disease patients. Academic researchers have for decades focused on the development of DN and recently found that free fatty acids (FFAs) constituted an independent risk factor for vascular complications in T2DM patients. It is therefore critical to determine whether the metabolic profile of FFAs is related to DN. Methods: This study comprised 611 research subjects in Dalian, a city in northeast China: 52 DN patients, 115 T2DM patients, and 444 healthy controls. We determined 15 forms of serum FFAs, including arachidonic acid (AA, C20:4), docosahexaenoic acid (DHA, C22:6), erucic acid (C22:1), nervonic acid (NA, C24:1), estimated total omega-3s, total omega-6s, the omega-3/omega-6 ratio, and total FFA content by liquid chromatography-mass spectrometry (LC-MS). Results: The levels of NA (mean = 45.27, range = 0.84-76.57) and DHA (mean = 324.58, range = 205.38-450.03) in DN patients were slightly lower than those in T2DM patients or healthy controls. The serum omega-3 polyunsaturated fatty acid (PUFA) DHA (C22:6) was significantly negatively correlated with microalbuminuria (MAU), the albumin/creatinine ratio (ACR), body mass index (BMI), fasting plasma glucose (FPG), and glycosylated hemoglobin (HbA1c). The serum monounsaturated fatty acid (MUFA) NA (C24:1) was significantly negatively correlated with BMI, FPG, and HbA1c. After adjustment of variables, multiple logistic regression analysis revealed significant odds ratios (ORs) [with confidence intervals (CIs)] for DHA (0.991, 0.985-0.997; p = 0.002) and NA (0.978, 0.958-0.999; p = 0.037). Conclusion: In this study, we ascertained that the contents of NA and DHA in patients with DN were relatively low, and that DHA was negatively correlated with MAU and the ACR. However, large-scale, population-based studies focusing on the role of NA and DHA in the pathogenesis of DN are still required in the future.

10.
Eur Child Adolesc Psychiatry ; 31(11): 1827-1845, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-35831670

RESUMO

Mental disorders account for a large and increasing health burden worldwide, as shown in the Global Burden of Diseases (GBD) Study 2010. Unpacking how this burden in children and adolescents varies with sex, geographical regions, and ethnicities and how it has changed in the last 3 decades are important to improve the existing public health policies and prevention strategies. The study was conducted using GBD 2019 database. The burden of children and adolescents' (< 20 years old) mental disorders was displayed as prevalence, incidence, disability-adjusted life-years (DALYs), years of life lost, and years lived with disability globally between 1990 and 2019. The number of DALYs in children and adolescents diagnosed with mental disorders was 21.5 million (95% CI: 15.2-29.6 million) in 2019. From 1990 to 2019, the age-standardized rates of DALYs of mental disorders increased from 803.8 per 100,000 (95% CI: 567.7-1104.3 per 100,000) to 833.2 per 100,000 (95% CI: 589.0-1146.1 per 100,000) population. Over the past 30 years, there had been a huge increase in the number of individuals suffering from anxiety disorders, major depressive disorders, and conduct disorders including an alarming increase in the rate of eating disorders such as 24.3% in bulimia nervosa and 17.0% in anorexia nervosa. Globally, 8.8% of children and adolescents have been diagnosed with varieties of mental illnesses, accounting for a heavy disease burden on public health. Besides, the worldwide increasing rates of anxiety disorders, major depressive disorders, and eating disorders have brought considerable challenges to public health undertakings, for which further prevention and treatment countermeasures are urgently needed.


Assuntos
Transtorno Depressivo Maior , Transtornos da Alimentação e da Ingestão de Alimentos , Criança , Adolescente , Humanos , Adulto Jovem , Adulto , Carga Global da Doença , Anos de Vida Ajustados por Qualidade de Vida , Efeitos Psicossociais da Doença
11.
Ther Adv Endocrinol Metab ; 13: 20420188221090012, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35464880

RESUMO

Background: Thyroid cancer has become increasingly prevalent and threatens human health. Few studies have explored the incidence of thyroid cancer in Asia and its relationship with social-progress factors. Methods: We analyzed Global Burden of Disease (GBD) Study 2019 data specific to thyroid cancer. Incidence, prevalence, mortality, and disability-adjusted life year (DALY) rates were used to evaluate the burden of thyroid cancer. Results: The age-standardized incidence, prevalence, and DALY rates per 100,000 population were 1.34% (95% UI, 2.44-3.07), 2.79% (95% UI, 18.82-23.77) and 16.49% (95% UI, 14.6-18), respectively, for all of Asia in 2019. In 2019, the DALY rate of thyroid cancer in the High-income Asia-Pacific region was the highest and mortality due to thyroid cancer in the High-income Asia-Pacific region was also the highest. The growth trend of DALYs in the High-income Asia-Pacific region was much steeper than those in other Asian regions. In all Asian regions and in the High-income Asia-Pacific region, the incidence, prevalence, mortality and DALY rates of thyroid cancer in female patients were drastically higher than those in male patients. Among Asian patients with thyroid cancer, the DALY rate was higher in men aged 80-89 years than in women. The DALY rate gradually increased with age. In the High-income Asia-Pacific region, the mortality rate of patients with thyroid cancer decreased with age. The prevalence was highest in those aged 40-79 years. Conclusion: The disease burden of thyroid cancer in the High-income Asia-Pacific region was significantly higher than those in other regions, which may be due to overdiagnosis. The increasing incidence of thyroid cancer seems to indicate that thyroid cancer is still a public health problem in Asia. Therefore, some health policy adjustments will be meaningful.

12.
Front Nutr ; 9: 1047129, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36618688

RESUMO

Background: Understanding the burdens and trends of non-alcoholic fatty liver disease (NAFLD) is necessary for developing effective intervention strategies. In this study, Global Burden of Disease (GBD) 2019 study data were extracted and analyzed to elucidate trends of NAFLD. Methods: The prevalence, incidence, disability-adjusted life year (DALY), and death rates of NAFLD in geographic populations worldwide from 1990 to 2019 were extracted from the GBD 2019 study data. The global temporal trend of NAFLD from 1990 to 2019 was evaluated using estimated annual percentage changes (EAPCs) and age-standardized rates. Results: Globally, between 1999 and 2019, the age-standardized prevalence rate of NAFLD increased, with EAPCs of 0.77 [95% CI (0.69, 0.85)], whereas the DALY and Death rates decreased, with EAPCs of -0.82 [95% CI (-0.92, -0.71)], and -0.67 [95% CI (-0.76, -0.58)], respectively. Geographically, the age-standardized prevalence rate showed the most serious upward trend in high-income North America with an EAPC of 0.98 [95% CI (0.95, 1.02)], and the age-standardized incidence rate showed an upward trend in Central Asia with an EAPC of 3.17 [95% CI (2.2, 2.49)]. The most significant upward trend of DALY and death rates appeared in Eastern Europe, with EAPCs of 4.06 [95% CI (3.31, 4.82)], and 3.36 [95% CI (2.77, 3.96)], respectively. At the country level, the age-standardized rates showed an upward trend in Armenia, Belarus, and Republic of Korea. Regarding age groups, the percentage change of prevalence was the highest in the 40 to 44 group [0.29 (0.26, 0.34)] from 1990 to 2019; the percentage change of incidence was the highest in the 85 to 89 group [0.46 (0.12, 0.71)] from 1990 to 2019; the percentage change of DALY was the highest in the 80 to 84 group [0.25 (0.11, 0.39)] from 1990 to 2019; and the percentage change of death rate was the highest in the 15 to 19 group [0.36 (0.17, 0.60)] from 1990 to 2019. The percentage change of prevalence of liver cancer due to NASH was the highest in the group of 85 to 89, whereas those of incidence, DALY, and death were the highest in the group above 95 from 1990 to 2019. Regarding the sociodemographic index (SDI), the highest age-standardized prevalence, incidence, and Death rates of NAFLD occurred in middle-SDI countries, and the highest DALY rates of NAFLD occurred in low-SDI countries. Conclusion: Global NAFLD burdens have increased since 1990. Our findings provide a reference for policymakers to reduce the burden of NAFLD, especially in middle and low-SDI countries.

13.
Folia Neuropathol ; 58(3): 213-222, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33099291

RESUMO

Brain ischaemia is one of the leading causes of mortality and disability worldwide, and the damage caused by ischaemia not only induces primary damage but also that induced by ischaemia-reperfusion (I/R) injury. Multiple processes including inflammation and oxidative stress response play important roles in the development of brain ischaemia injury. Sevoflurane is a well-known volatile anaesthetic, and a recent study discovered the role of sevoflurane in suppression of the inflammation response process via inhibition of inflammatory infiltrates and production, maintaining the balance of cytokine responses, although the possible mechanism was not fully clear. NLRC3 is a member of the nucleotide-binding domain and leucine-rich repeat containing (NLR) family, and it has been regarded as a regulator of the inflammation process via the regulation of inflammasome formation, which is an initiator of inflammatory events. In the present study, we found that overexpression of NLRC3 reduced the apoptosis in a cellular model of ischaemia reperfusion, and the expression of pro-inflammatory cytokines was also decreased. Further study found that these effects might be mediated by the TRAF6/TLR4/NF-kB signalling pathway. Thus, we speculate that overexpression might enhance the effect of sevoflurane in inhibiting the inflammatory response process in an ischaemia reperfusion model, which might be a new therapeutic strategy.


Assuntos
Inflamação/metabolismo , Peptídeos e Proteínas de Sinalização Intercelular/metabolismo , Traumatismo por Reperfusão/metabolismo , Sevoflurano/farmacologia , Transdução de Sinais/efeitos dos fármacos , Animais , Inflamassomos/metabolismo , Inflamação/genética , Peptídeos e Proteínas de Sinalização Intercelular/genética , NF-kappa B/metabolismo , Células PC12 , Ratos , Fator 6 Associado a Receptor de TNF/metabolismo , Receptor 4 Toll-Like/metabolismo
14.
Biochem Biophys Res Commun ; 532(2): 271-279, 2020 11 05.
Artigo em Inglês | MEDLINE | ID: mdl-32868081

RESUMO

Vincristine (VCR) is a well-known anticancer drug, and frequently causes painful neuropathy and impairs the quality of life of patients. However, the molecular mechanisms revealing VCR-induced neuropathy are still unclear, and effectively therapeutic strategy is still necessary. Bromodomain-containing protein 4 (BRD4) has long been implicated in many different pathological processes, in particular, the development of oxidative stress and inflammation. In the present study, we showed that BRD4 played a mechanistic role in VCR-induced peripheral neuropathy. Using the in vivo transfection of BRD4 siRNA, we found that BRD4 suppression markedly alleviated VCR-induced neuropathic pain. Macrophage infiltration in sciatic nerve was effectively inhibited in VCR-challenged mice with BRD4 knockdown, as evidenced by the markedly reduced expression of F4/80. In the VCR-induced sciatic nerve tissues, we found that the mRNA and protein expression levels of C-X3-C motif chemokine receptor 1 (CX3CR1) and C-C chemokine receptor type 2 (CCR2) were greatly elevated, which were, however, mitigated by siBRD4 injection. In addition, oxidative stress induced by VCR was markedly restrained in sciatic nerve from mice with BRD4 knockdown, which was closely associated with the improved activation of nuclear factor erythroid 2-related factor 2 (Nrf-2) signaling. The in vitro studies indicated that in H2O2-stimulated primary neurons, BRD4 silence markedly reduced reactive oxygen species (ROS) production and improved Nrf-2 activation, exhibiting anti-oxidant effects. Finally, BRD4 selective inhibitor JQ1 was subjected to mice challenged with VCR. The results confirmed that reducing BRD4 expression by JQ1 effectively ameliorated VCR-induced peripheral neuropathy also through repressing macrophage infiltration, inflammatory response and oxidative stress. Taken together, these findings demonstrated that BRD4 played a critical role in VCR-induced neuropathy, and developing novel and new therapies might be effective for the treatment of VCR-induced neuropathic pain.


Assuntos
Azepinas/farmacologia , Proteínas Nucleares/genética , Doenças do Sistema Nervoso Periférico/induzido quimicamente , Doenças do Sistema Nervoso Periférico/prevenção & controle , Fatores de Transcrição/genética , Triazóis/farmacologia , Vincristina/efeitos adversos , Animais , Antineoplásicos Fitogênicos/efeitos adversos , Gânglios Espinais/citologia , Técnicas de Silenciamento de Genes , Hiperalgesia/induzido quimicamente , Macrófagos/efeitos dos fármacos , Macrófagos/patologia , Masculino , Camundongos Endogâmicos C57BL , Camundongos Mutantes , Proteínas Nucleares/antagonistas & inibidores , Proteínas Nucleares/metabolismo , Dor/induzido quimicamente , Doenças do Sistema Nervoso Periférico/genética , Receptores CCR2/metabolismo , Receptores CXCR3/metabolismo , Nervo Isquiático/efeitos dos fármacos , Nervo Isquiático/metabolismo , Nervo Isquiático/patologia , Fatores de Transcrição/antagonistas & inibidores , Fatores de Transcrição/metabolismo
15.
Nat Ecol Evol ; 4(9): 1213-1219, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32661403

RESUMO

Though it is well accepted that mitochondria originated from an alphaproteobacteria-like ancestor, the phylogenetic relationship of the mitochondrial endosymbiont to extant Alphaproteobacteria is yet unresolved. The focus of much debate is whether the affinity between mitochondria and fast-evolving alphaproteobacterial lineages reflects true homology or artefacts. Approaches such as site exclusion have been claimed to mitigate compositional heterogeneity between taxa, but this comes at the cost of information loss, and the reliability of such methods is so far unproven. Here we demonstrate that site-exclusion methods produce erratic phylogenetic estimates of mitochondrial origin. Thus, previous phylogenetic hypotheses on the origin of mitochondria based on pretreated datasets should be re-evaluated. We applied alternative strategies to reduce phylogenetic noise by systematic taxon sampling while keeping site substitution information intact. Cross-validation based on a series of trees placed mitochondria robustly within Alphaproteobacteria, sharing an ancient common ancestor with Rickettsiales and currently unclassified marine lineages.


Assuntos
Alphaproteobacteria , Alphaproteobacteria/genética , Mitocôndrias/genética , Filogenia , Reprodutibilidade dos Testes
16.
Can J Anaesth ; 66(12): 1489-1500, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31264195

RESUMO

BACKGROUND: Delirium is a frequent postoperative complication in elderly patients after non-cardiac surgery. We performed this updated meta-analysis to ascertain more precisely the efficacy of dexmedetomidine (DEX) on the incidence of postoperative delirium (POD) in elderly patients after non-cardiac surgery. METHODS: We searched PubMed, EMBASE, the Cochrane Library, Web of Science, and the Cumulative Index of Nursing and Allied Health Literature (CINAHL) from inception until February 24, 2019. In this meta-analysis, we included randomized-controlled trials comparing the effect of DEX vs normal saline (NS) or other anesthetic drugs on POD incidence in elderly (either ≥ 60 or ≥ 65 yr old) patients undergoing non-cardiac surgery. We performed subgroup analyses of the DEX dosing strategy (starting time, dose, and duration of administration, with or without loading dose) and the strategy of various control drugs. A random-effects model was used for all analyses. RESULTS: We included 11 studies involving 2,890 patients in our meta-analysis. The pooled results of these studies revealed that DEX significantly reduced the incidence of POD (relative risk [RR], 0.47; 95% confidence interval [CI], 0.38 to 0.58; P < 0.001) compared with the control group. Meanwhile, the incidences of hypotension (RR, 1.20; 95% CI, 1.04 to 1.39; P = 0.01) and bradycardia (RR, 1.33; 95% CI, 1.08 to 1.63; P = 0.007) were increased in the DEX group. Subgroup analyses revealed a decrease in POD incidence when DEX was administered intraoperatively (RR, 0.43; 95% CI, 0.33 to 0.57; P < 0.001) and postoperatively (RR, 0.38; 95% CI, 0.27 to 0.54; P < 0.001) with a loading dose (RR, 0.49; 95% CI, 0.36 to 0.69; P < 0.001) compared with NS (RR, 0.49; 95% CI, 0.37 to 0.64; P < 0.001) and other anesthetic drugs (RR, 0.40; 95% CI, 0.26 to 0.60; P < 0.001). There were significant differences in the time to extubation (standardized mean difference, -0.60; 95% CI, -1.17 to -0.03; P = 0.04) and the length of hospital stay (mean difference, -0.50 days; 95% CI, -0.97 to -0.03; P = 0.04). The amount of data for the duration of mechanical ventilation and length of intensive care unit stay were insufficient to perform a meta-analysis. CONCLUSION: Perioperative dexmedetomidine reduces the incidence of POD in elderly patients after non-cardiac surgery, but this comes at the cost of an increased incidence of hypotension and bradycardia.


Assuntos
Dexmedetomidina/uso terapêutico , Delírio do Despertar/prevenção & controle , Hipnóticos e Sedativos/uso terapêutico , Complicações Pós-Operatórias/prevenção & controle , Idoso , Idoso de 80 Anos ou mais , Humanos , Pessoa de Meia-Idade , Ensaios Clínicos Controlados Aleatórios como Assunto
17.
Aging Clin Exp Res ; 31(5): 575-593, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30097811

RESUMO

AIMS: The aim of this systematic review and meta-analysis was to quantify the effect of high-intensity interval training (HIIT) on glycemic control and cardiorespiratory fitness compared with moderate-intensity training (MICT) and no training at all in patients with type 2 diabetes (T2D). METHODS: Relevant articles were sourced from PubMed, Embase, the Web of Science, EBSCO, and the Cochrane Library. Randomized-controlled trials were included based upon the following criteria: participants were clinically diagnosed with T2D, outcomes that included glycemic control (e.g., hemoglobin A1c); body composition (e.g., body weight); cardiorespiratory fitness (e.g., VO2peak) are measured at baseline and post-intervention and compared with either a MICT or control group. RESULTS: Thirteen trials involving 345 patients were finally identified. HIIT elicited a significant reduction in BMI, body fat, HbA1c, fasting insulin, and VO2peak in patients with type 2 diabetes. Regarding changes in the body composition of patients, HIIT showed a great improvement in body weight (mean difference: - 1.22 kg, 95% confidence interval [CI] - 2.23 to - 0.18, P = 0.02) and body mass index (mean difference: - 0.40 kg/m2, 95% CI - 0.78 to - 0.02, P = 0.04) than MICT did. Similar results were also found with respect to HbA1c (mean difference: - 0.37, 95% CI - 0.55 to - 0.19, P < 0.0001); relative VO2peak (mean difference: 3.37 ml/kg/min, 95% CI 1.88 to 4.87, P < 0.0001); absolute VO2peak (mean difference: 0.37 L/min, 95% CI 0.28 to 0.45, P < 0.00001). CONCLUSIONS: HIIT may induce more positive effects in cardiopulmonary fitness than MICT in T2D patients.


Assuntos
Aptidão Cardiorrespiratória/fisiologia , Diabetes Mellitus Tipo 2/terapia , Treinamento Intervalado de Alta Intensidade/métodos , Índice de Massa Corporal , Peso Corporal/fisiologia , Feminino , Hemoglobinas Glicadas/análise , Humanos , Masculino , Ensaios Clínicos Controlados Aleatórios como Assunto , Resultado do Tratamento
18.
Clin Rehabil ; 31(12): 1573-1582, 2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-28580801

RESUMO

OBJECTIVE: To comprehensively assess the effectiveness and safety of wheelchair skills training program in improving wheelchair skills capacity. DATA SOURCES: PubMed, OVID, EBSCO, ScienceDirect, Web of Science, CINAHL, Cochrane Library, Google Scholar, and China Knowledge Resource Integrated Database were searched up to March 2017. METHODS: Controlled clinical trials that compared a wheelchair skills training program with a control group that received other interventions and used the wheelchair skills test scores to evaluate wheelchair skills capacity were included. Two authors independently screened articles, extracted data, and assessed the methodological quality using the Cochrane risk-of-bias tool in randomized controlled trial (RCT) and methodological index for non-randomized studies. The data results of wheelchair skills test scores were extracted. RESULTS: Data from 455 individuals in 10 RCTs and from 140 participants in seven non-randomized studies were included for meta-analysis using Stata version 12.0 (Stata Corporation, College Station, TX, USA). In the short term (immediately to one week) post-intervention, relative to a control group, manual wheelchair skills training could increase the total wheelchair skills test scores by 13.26% in RCTs (95% confidence interval (CI), 6.19%-20.34%; P < 0.001) and by 23.44% in non-randomized studies (95% CI, 13.98%-32.90%; P < 0.001). Few adverse events occurred during training; however, compared with a control group, evidence was insufficient to support the effectiveness of powered wheelchair skills training and the long-term (3-12 months) advantage of manual wheelchair skills training ( P = 0.755). CONCLUSION: The limited evidence suggests that wheelchair skills training program is beneficial in the short term, but its long-term effects remain unclear.


Assuntos
Pessoas com Deficiência/reabilitação , Cadeiras de Rodas , Humanos , Ensaios Clínicos Controlados Aleatórios como Assunto
19.
J Agric Food Chem ; 64(12): 2612-8, 2016 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-26961750

RESUMO

Inulooligosaccharides (IOS) represent an important class of oligosaccharides at industrial scale. An efficient conversion of inulin to IOS through endoinulinase from Aspergillus niger is presented. A 1482 bp codon optimized gene fragment encoding endoinulinase from A. niger DSM 2466 was cloned into pPIC9K vector and was transformed into Pichia pastoris KM71. Maximum activity of the recombinant endoinulinase, 858 U/mL, was obtained at 120 h of the high cell density fermentation process. The optimal conditions for inulin hydrolysis using the recombinant endoinulinase were investigated. IOS were harvested with a high concentration of 365.1 g/L and high yield up to 91.3%. IOS with different degrees of polymerization (DP, mainly DP 3-6) were distributed in the final reaction products.


Assuntos
Aspergillus niger/química , Proteínas Fúngicas/metabolismo , Glicosídeo Hidrolases/metabolismo , Inulina/metabolismo , Oligossacarídeos/metabolismo , Aspergillus niger/enzimologia , Clonagem Molecular , Códon , Fermentação , Concentração de Íons de Hidrogênio , Hidrólise , Inulina/química , Estrutura Molecular , Pichia/genética , Proteínas Recombinantes/metabolismo
20.
Chin Med Sci J ; 29(2): 85-90, 2014 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-24998229

RESUMO

OBJECTIVE: To study the expression level of peptidylarginine deiminase 4 (PADI4) and protein tyrosine phosphatase nonreceptor type 22 (PTPN22) in the synovium of rat model of collagen-induced arthritis, and to explore their possible therapeutic role in rheumatoid arthritis. METHODS: Thirty-two female Wistar rats weighing 100±20 g were randomly assigned into 3-week collagen-induced arthritis (CIA) model group (n=8), 4-week CIA model group (n=8), 6-week CIA model group (n=8), and the control group (n=8). The body weight changes of each group were recorded. The expression levels of PADI4 and PTPN22 were detected and compared by the methods of immunohistochemical staining and Western blot. RESULTS: Arthritis of rat began to form 14 days after sensitization and the joint swelling reached peak at 28 days. The weights of the rats slowly grew both in CIA model groups and the control group. Immunohistochemical staining results showed that the positive expression of PADI4 and PTPN22 was mainly located in cartilage peripheral mononuclear cells, the cytoplasm of infiltrated cells, and bone marrow cavity. There were significant differences in the optical density of PADI4 and PTPN22 among CIA model groups and the control group (PADI4, 0.2898±0.012, 0.2982±0.022, 0.2974±0.031, 0.2530±0.013 in 3-week CIA model, 4-week CIA model, 6-week CIA model and control groups; PTPN22, 0.2723±0.004, 0.2781±0.010, 0.2767±0.008, 0.2422±0.019; all P <0.05). The expression bands of PADI4 were observed in Western blot 3 weeks after initial immunization, the thickest in the 4th week, and decreased in the 6th week. The expression bands of PTPN2 were observed at all the time points, with no obvious time-dependent trend. CONCLUSIONS: PADI4 and PTPN22 are obviously correlated with CIA in rat model. PADI4 is expressed at early stage of the disease, while the expression of PTPN22 sustains throughout the course.


Assuntos
Artrite Experimental/metabolismo , Colágeno/administração & dosagem , Hidrolases/metabolismo , Proteína Tirosina Fosfatase não Receptora Tipo 22/metabolismo , Membrana Sinovial/metabolismo , Animais , Artrite Experimental/enzimologia , Western Blotting , Feminino , Imuno-Histoquímica , Proteína-Arginina Desiminase do Tipo 4 , Desiminases de Arginina em Proteínas , Ratos , Ratos Wistar , Membrana Sinovial/enzimologia
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