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1.
Mediators Inflamm ; 2020: 9706140, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32617076

RESUMO

Inflammatory bowel disease (IBD) is a chronic inflammatory disorder of the gastrointestinal tract resulting from the homeostasis imbalance of intestinal microenvironment, immune dysfunction, environmental and genetic factors, and so on. This disease is associated with multiple immune cells including regulatory T cells (Tregs). Tregs are a subset of T cells regulating the function of various immune cells to induce immune tolerance and maintain intestinal immune homeostasis. Tregs are correlated with the initiation and progression of IBD; therefore, strategies that affect the differentiation and function of Tregs may be promising for the prevention of IBD-associated pathology. It is worth noting that tryptophan (Trp) metabolism is effective in inducing the differentiation of Tregs through microbiota-mediated degradation and kynurenine pathway (KP), which is important for maintaining the function of Tregs. Interestingly, patients with IBD show Trp metabolism disorder in the pathological process, including changes in the concentrations of Trp and its metabolites and alteration in the activities of related catalytic enzymes. Thus, manipulation of Treg differentiation through Trp metabolism may provide a potential target for prevention of IBD. The purpose of this review is to highlight the relationship between Trp metabolism and Treg differentiation and the role of this interaction in the pathogenesis of IBD.

2.
DNA Cell Biol ; 39(7): 1282-1289, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32522048

RESUMO

Pancreatic cancer (PC) is one of the most lethal malignancies with an extremely poor prognosis. In this study, we aim to construct a long noncoding RNA (lncRNA)-based panel biomarker to predict the overall survival of PC patients. The lncRNA expression profiles of PC samples were extracted from The Cancer Genome Atlas (TCGA-PAAD, n = 176) and International Cancer Genome Consortium (PACA-CA, n = 180). We then developed a risk score model according to the lncRNAs expressions from the TCGA-PAAD cohort and further validated it in the PACA-CA cohort. The potential biological functions for the prognostic lncRNAs were investigated using gene set enrichment analysis (GSEA). In the TCGA-PAAD cohort, three lncRNAs (AC009014.3, RP11-48O20.4, and UCA1) were found to be strongly associated with the prognosis of PC. These lncRNAs were integrated to build a three-lncRNA prognostic model that could divide individuals into low- and high-risk groups. Patients of TCGA-PAAD cohort in the high-risk group showed a poorer overall survival than those in the low-risk group (median: 17.3 months vs. 30.4 months, log-rank p < 0.001). Similar results were documented in the PACA-CA cohort (median: 15.2 months vs. 21.0 months, log-rank p < 0.001) and in the stratified analyses by patients' age and TNM stage. In addition, the signature exhibited an independent prognostic power and was significantly correlated with tumor relapse and patients' response to chemotherapy. GSEA indicated that the three-lncRNA signature may be involved in many known biological functions in cancer, especially the epithelial mesenchymal transformation. In conclusion, the identified three-lncRNA signature in our study may serve as a robust and useful prognostic biomarker in PC patients.

3.
J Hosp Infect ; 2020 Jun 20.
Artigo em Inglês | MEDLINE | ID: mdl-32574702

RESUMO

BACKGROUND: Globally, there have been many cases of COVID-2019 cases among medical staff, however, the main factors associated with the infection are not well understood. AIM: To identify the super-factors causing COVID-19 infection in medical staff in China. METHODS: A cross-sectional study was conducted between Jan. 1st, and Feb. 30th, 2020, where front line members of medical staff that took part in the care and treatment of patients with COVID-19 were enrolled. Epidemiological and demographic data between infected and uninfected groups were collected and compared. Social network analysis (SNA) was used to establish socio-metric social links between influencing factors. FINDINGS: A total of 92 medical staff were enrolled. In all participant groups, the super-factor identified by the network was wearing a medical protective mask or surgical mask correctly (degree = 572; closeness =25; betweenness centrality = 3·23). Touching the cheek, nose, and mouth while working was the super-factor in the infected group. This was the biggest node in the network and had the strongest influence (degree = 370; closeness = 29; betweenness centrality = 0·37). Self-protection score was the super-factor in the uninfected group but was the isolated factor in the infected group (degree = 201; closeness = 28; betweenness centrality = 5·64). For family members, the exposure history to Huanan Seafood Wholesale Market and the contact history to wild animals were two isolated nodes. CONCLUSION: High self-protection score was the main factor that prevented medical staff from contracting COVID-19 infection. The main factor that contributed to COVID-19 infections among medical staff was touching the cheek, nose and mouth while working.

4.
J Biomater Sci Polym Ed ; : 1-23, 2020 Jun 10.
Artigo em Inglês | MEDLINE | ID: mdl-32462969

RESUMO

Multi-stimuli- responsive mechanical strong stretchable hydrogel has grabbed extensive attention in recent years. Here, a novel stretchable conductive biocompatible near-infrared light(NIR)-/thermal-/pH-/ionic concentration- responsive carboxymethyl chitosan (CMCTs)/graphene oxide (GO)/poly(N-isopropylacrylamide)(PNIPAm) nanocomposite double network hydrogel was fabricated through a simple one-pot in situ free radical polymerization, which is initiated by ultraviolet (UV) light and using N-(3-dimethylaminopropyl)-N-ethylcarbodiimidehydrochloride (EDC) and N,N'-bis(acryloyl)cystamine (BAC) as cross-linkers respectively, instead of toxic organic molecules. When the concentration of CMCTs, GO, EDC and BAC is 22.50, 0.103, 7.50 and 0.467 mg/mL respectively, the obtained hydrogel sample owns the highest tensile strength of 1046 kPa at failure strain of 1286% and a corresponding compressive stress of 2.37 MPa at deformation of 90%. Besides, these hydrogels have an obvious pH-/thermal-/ionic concentration-responsive properties depending on the concentration of the above mentioned factors, and their good conductive property makes them as candidate material for healthcare biosensors. Finally, we attempt to design a novel thermal-/NIR-responsive double network structure bilayer hydrogel, which has the potential use as remote actuator in dangerous places in the future.

5.
Int J Mol Med ; 45(6): 1814-1824, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32236577

RESUMO

Non­small cell lung carcinoma (NSCLC) accounts for 85% of all lung cancers and the five­year survival rate is ~1% in the late stage. Circular RNAs (circRNAs) were reported to be involved in the progression of diverse human cancers. However, the role of circ­ACACA in NSCLC progression remains elusive. Quantitative polymerase chain reaction was conducted to detect the expression levels of circ­ACACA and microRNA (miR)­1183 in NSCLC tissues and cells. A Cell Counting Kit­8 assay and transwell assay were employed to check proliferation and migration, respectively. Metabolic alternations in NSCLC cells were monitored by the Seahorse XFe96 analyzer. The protein levels of cellular myelocytomatosis, matrix metallopeptidase 9, glucose transporter 1, phosphatase and tensin homolog, phosphoinositide 3­kinases (PI3K), phosphorylated PI3K (p­PI3K), protein kinase B (PKB) and p­PKB in samples were measured by western blotting. The interaction between circ­ACACA and miR­1183 was predicted by circular RNA Interactome, which was verified by dual­luciferase reporter assay, RNA immunoprecipitation assay and RNA pull­down assay. Xenograft tumor model was established to investigate the biological roles of circ­ACACA in vivo. The level of circ­ACACA was markedly upregulated in NSCLC tissues and cells, which was contrary to the expression of miR­1183. Knockdown of circ­ACACA inhibited proliferation and migration of NSCLC cells and also reduced the glycolysis rate. In addition, miR­1183 was a target of circ­ACACA and its downregulation reversed circ­ACACA silencing­mediated inhibitory impact on NSCLC progression. Further studies indicated that circ­ACACA regulated the PI3K/PKB pathway through interacting with miR­1183 and downregulation of circ­ACACA suppressed tumor growth. Knockdown of circ­ACACA impeded NSCLC progression by sponging miR­1183 and inactivating the PI3K/PKB signaling pathway.

6.
Artigo em Inglês | MEDLINE | ID: mdl-32169934

RESUMO

Fimbriae mediate the initial adherence of ETEC to the piglet small intestine and play an important role in development of ETEC-driven post-weaning diarrhea (PWD). PWD inflicts huge economic losses on the swine industry each year, making development of alternative treatment and prevention measures for PWD essential. Vaccine candidates that induce anti-fimbriae antibodies that block the initial attachment and colonization of ETEC pathogens with fimbriae are one approach that could help prevent PWD. In this study, we constructed two multi-epitope fusion antigens (MEFAs) that carried, expressed, and displayed representative epitopes of F4, F5, F6, F18 and F41 ETEC fimbriae. These MEFAs used either the F4 major subunit FaeG or the F18 adhesive subunit FedF as a backbone. To assess the potential of these MEFAs as anti-fimbriae vaccine candidates that could help prevent PWD, we generated computational models of the MEFAs, constructed them, and then tested their immunogenicity by using them to immunize mice. Computational modeling showed that all relevant epitopes were exposed on the MEFA surface. We found that co-administration of our MEFAs in mice successfully induced five fimbriae specific antibodies in accordance with the epitopes included in the MEFA constructs. Furthermore, the induced antibodies can significantly inhibit the ability of ETEC strains that express F4, F5, F6, F18, and F41 fimbriae adhere to piglet small intestinal IPEC-1 and IPEC-J2 cells. Our findings indicate that the anti-fimbriae antibodies induced by our FaeG-Fim41a-FanC-FasA and FedF-FasA-Fim41a-FanC fimbriae MEFAs blocked adherence of five ETEC fimbriae, suggesting these multivalent fimbriae MEFAs may be useful for developing broadly protective anti-fimbriae vaccines against PWD caused by ETEC infections.ImportanceEnterotoxigenic Escherichia coli (ETEC)-associated post-weaning diarrhea (PWD) is still a leading disease in recently weaned piglets. Vaccination is considered to be the most ideal and efficacious strategy for preventing PWD. Recently, a commercialized live monovalent F4 oral vaccine and a bivalent F4/F18 oral vaccine have been demonstrated to effectively protect piglets in the F4+ and F18+ ETEC challenge models. However, they will not provide cross-protection against F5+, F6+, or F41+ ETEC-associated PWD cases due to lack of expressing these fimbriae antigens. Thus, a multivalent vaccine containing all ETEC five fimbriae would be more effective in preventing against ETEC-driven PWD. In this study, we designed two fimbriae-targeted MEFAs using the MEFA technology, further study demonstrated co-administrated these MEFAs in mice can induced protective antibodies against five fimbriae expressed by ETEC. These MEFAs could be used as an efficient PWD vaccine candidate, furthermore, MEFA-based structural technology provides an alternative and promising strategy for the development of vaccines against pathogens with heterogeneous virulence factors.

7.
Clin Infect Dis ; 2020 Mar 17.
Artigo em Inglês | MEDLINE | ID: mdl-32179890

RESUMO

Corona Virus Disease 2019 (COVID-19) originated in Wuhan, China has caused many healthcare workers (HCWs) infected. Seventy-two HCWs manifested with acute respiratory illness were retrospectively enrolled to analyze the risk factors. The high-risk department, longer duty hours, and suboptimal hand hygiene after contacting with patients were linked to COVID-19.

8.
Medicine (Baltimore) ; 99(8): e19167, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-32080095

RESUMO

To verify the validity of functional health literacy scale and analyze what influences functional health literacy.Using convenience sampling method based on cross-sectional data to select 589 left-behind senior high-school students in an ethnic minority area, using the functional health literacy scale.The scale results were relatively strong, and the absolute fitness index, value-added fitness index, and simple fitness index reached the fitness standards. The overall functional health literacy score was (0.65 ±â€Š0.12), which falls within the upper middle class. Gender(t = 2.40, P < .05), ethnicity (t = 4.28, P < .001), place of residence (t =  = 4.51, P < .001), mother's education level (F = 3.608, P < .05), self-assessment of grades for 1 year (F = 25.781, P < .001), and whether the participant liked the health education content (F = 9.416, P < .001) had impacts on overall functional health literacy.The study results show that relatively satisfactory reliability and validity and can be applied further analysis for improving students functional health literacy levels.


Assuntos
Grupos Étnicos/estatística & dados numéricos , Letramento em Saúde/estatística & dados numéricos , Grupos Minoritários/estatística & dados numéricos , Inquéritos e Questionários/normas , Sucesso Acadêmico , Adolescente , China/epidemiologia , Estudos Transversais , Feminino , Educação em Saúde/estatística & dados numéricos , Humanos , Masculino , Reprodutibilidade dos Testes , República da Coreia/etnologia , Características de Residência/estatística & dados numéricos , População Rural/estatística & dados numéricos , Fatores Sexuais
9.
Exp Cell Res ; 388(1): 111809, 2020 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-31891682

RESUMO

Staphylococcal nuclease domain-containing protein 1 (SND1) is known to be involved in the progression of a variety of human cancers. However, the role of SND1 in cervical cancer remains unclear. Here, we found that the expression of SND1 in cervical cancer tissue was higher than that in normal cervical tissue. Importantly, high SND1 expression was closely associated with tumorigenic phenotype and shorter survival among cervical cancer patients. Functional assays demonstrated that SND1 knockdown inhibited the migration and invasion capabilities of cervical cancer cells in vitro. Additionally, a xenograft assay showed that silencing SND1 in cervical cancer cells suppressed lung metastasis in vivo. Further investigation revealed that knockdown of SND1 inhibited epithelial-to-mesenchymal transition (EMT) of cervical cancer cells by enhancing FOXA2 expression. Moreover, the pro-metastasis effect of SND1 in cervical cancer was at least in part dependent on FOXA2 inhibition. Mechanistically, we found that SND1-induced FOXA2 ubiquitination resulted in degradation, mediated by the E3 ligase enzyme Smurf1. In summary, SND1 plays a crucial role in cervical cancer metastasis, and we provide evidence that SND1 may serve as a prognostic and therapeutic target in cervical cancer.

10.
ACS Synth Biol ; 9(2): 412-426, 2020 02 21.
Artigo em Inglês | MEDLINE | ID: mdl-31944664

RESUMO

F4 (K88) and F18 fimbriaed enterotoxigenic Escherichia coli (ETEC) are the predominant causes of porcine postweaning diarrhea (PWD), and vaccines are considered the most effective preventive approach against PWD. Since heterologous DNA integrated into bacterial chromosomes could be effectively expressed with stable inheritance, we chose probiotic EcNc (E. coli Nissle 1917 prototype cured of cryptic plasmids) as a delivery vector to express the heterologous F4 or both F4 and F18 fimbriae and sequentially assessed their immune efficacy of anti-F4 and F18 fimbriae in both murine and piglet models. Employing the CRISPR-cas9 technology, yjcS, pcadA, lacZ, yieN/trkD, maeB, and nth/tppB sites in the chromosome of an EcNc strain were targeted as integration sites to integrate F4 or F18 fimbriae cluster genes under the Ptet promotor to construct two recombinant integration probiotic strains (RIPSs), i.e., nth integration strain (EcNcΔnth/tppB::PtetF4) and multiple integration strain (EcNc::PtetF18x4::PtetF4x2). Expression of F4, both F4 and F18 fimbriae on the surfaces of two RIPSs, was verified with combined methods of agglutination assay, Western blot, and immunofluorescence microscopy. The recombinant strains have improved adherence to porcine intestinal epithelial cell lines. Mice and piglets immunized with the nth integration strain and multiple integration strain through gavage developed anti-F4 and both anti-F4 and anti-F18 IgG immune responses. Moreover, the serum antibodies from the immunized mice and piglets significantly inhibited the adherence of F4+ or both F4+ and F18+ ETEC wild-type strains to porcine intestinal cell lines in vitro, indicating the potential of RIPSs as promising probiotic strains plus vaccine candidates against F4+/F18+ ETEC infection.

11.
Am J Health Behav ; 44(1): 40-53, 2020 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-31783931

RESUMO

Objectives: In this study, we explored the association between sleep quality, duration and prevalence of rheumatoid arthritis (RA) among low-income adults in rural areas of China. Methods: Face-to-face investigation were conducted in 2017, and completed questionnaires were obtained from 16,648 individuals. Sleep quality and duration were evaluated using the standard Pittsburgh Sleep Quality Index. RA was based on self-reported physician diagnosis. Logistic regression analysis and restricted cubic spline models were performed. Results: Sleep duration shorter than 7 hours was associated with increased odds of RA, with an odds ratio (OR) of 1.49 for 6-<7 hours and 1.70 for <6 hours. Poor sleep quality was associated with RA, with an OR of 1.68. The combination category of poor sleep quality and any group of sleep duration was associated with a significantly increased risk of developing RA. Combined groups of good sleep quality with short sleep duration (<7 hours) were also found to be related to prevalence of RA. There was a non-linear relationship between sleep quality, duration and the odds of RA. Conclusions: Poor sleep quality and short sleep duration may be trigger or risk factors for RA.

12.
J Psychosom Res ; 127: 109848, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31670193

RESUMO

OBJECTIVE: The relationship among sleep quality, sleep duration and hypertension prevalence is controversial in different age groups and genders. This study aimed to investigate sleep quality, sleep duration and their association with hypertension prevalence among low-income oldest-old in a rural area of China. METHODS: A cross-sectional survey was conducted in a representative sample of 1066 adults aged 80-99 years in 2017. Logistic regression analysis was performed. RESULTS: Among males, sleep durations of <6 h and 6-<7 h were significantly associated with hypertension prevalence, with odds ratios (ORs) of 3.15 (95% confidence interval (CI) 1.37 to 7.23) and 2.38 (95% CI 1.22 to 4.63), respectively. Among females, only the sleep duration of <6 h was associated with increased OR of hypertension of 3.49 (95% CI 1.50 to 8.09). Poor sleep quality was associated with hypertension for both genders (ORmen 1.67, 95% CI 1.12 to 2.49; ORwomen 1.91, 95% CI 1.29 to 2.82). For women, a combination of poor sleep quality and any group of sleep duration, except for 7-<8 h, was associated with higher hypertension prevalence. For men, only the combination of poor sleep quality and short sleep duration (<7 h) was associated with high hypertension prevalence. CONCLUSION: Short sleep duration and poor sleep quality are associated with hypertension prevalence of oldest-old. The prevention of hypertension in older adults should be investigated from the perspective of sleep improvement.

13.
BMJ Open ; 9(10): e029929, 2019 10 22.
Artigo em Inglês | MEDLINE | ID: mdl-31640996

RESUMO

OBJECTIVES: To explore the association between the number of teeth and frailty among older Chinese adults using a nationally representative sample. DESIGN: Cross-sectional analysis was carried out using the 2014 wave data from the Chinese Longitudinal Healthy Longevity Survey, which used a targeted random-sampling design. SETTING: This research was conducted in communities from nearly half of the counties and cities in 22 out of 31 provinces throughout China. PARTICIPANTS: Of the 6934 interviewees aged ≥65 years, the final analysis included 3635 older adults who had completed the 2014 wave survey on the variables included in the study. PRIMARY AND SECONDARY OUTCOME MEASURES: Outcome variables included frailty, measured by the Frailty Index, and number of teeth. Covariates included demographic characteristics (ie, age, sex, co-residence, marital status, years of education and financial support), body mass index (BMI) and health behaviours (ie, smoking, drinking and exercise). A univariate logistic regression was used to test the factors associated with frailty. A multiple logistic regression model was used, using the frailty score as the dependent variable and the number of teeth together with significant covariates as the independent variables. RESULTS: The prevalence of frailty was 27.68%. The mean number of teeth present was 9.23 (SD=10.03). The multiple logistic regression showed that older adults' demographic variables, health behaviours, BMI, tooth number and chewing pain were significantly associated with frailty. After adjusting for the covariates, older adults with fewer teeth had significantly higher odds of frailty than those with 20 or more teeth (no teeth: OR=2.07, 95% CI 1.53 to 2.80; 1 to 10 teeth: OR=1.77, 95% CI 1.31 to 2.38), except for older adults with 11 to 20 teeth (OR=1.30, 95% CI 0.93 to 1.82). CONCLUSIONS: The presence of fewer teeth is significantly associated with frailty status among older Chinese adults. Future studies are needed to explain the specific mechanisms underlying how oral health status is associated with frailty.

14.
Sci Rep ; 9(1): 14257, 2019 10 03.
Artigo em Inglês | MEDLINE | ID: mdl-31582797

RESUMO

Replication protein A (RPA) binds to and stabilizes single-stranded DNA and is essential for the genome stability. We reported that an E3 ubiquitin ligase, HERC2, suppresses G-quadruplex (G4) DNA by regulating RPA-helicase complexes. However, the precise mechanism of HERC2 on RPA is as yet largely unknown. Here, we show essential roles for HERC2 on RPA2 status: induction of phosphorylation and degradation of the modified form. HERC2 interacted with RPA through the C-terminal HECT domain. Ubiquitination of RPA2 was inhibited by HERC2 depletion and rescued by reintroduction of the C-terminal fragment of HERC2. ATR-mediated phosphorylation of RPA2 at Ser33 induced by low-level replication stress was inhibited by depletion of HERC2. Contrary, cells lacking HERC2 catalytic residues constitutively expressed an increased level of Ser33-phosphorylated RPA2. HERC2-mediated ubiquitination of RPA2 was abolished by an ATR inhibitor, supporting a hypothesis that the ubiquitinated RPA2 is a phosphorylated subset. Functionally, HERC2 E3 activity has an epistatic relationship with RPA in the suppression of G4 when judged with siRNA knockdown experiments. Together, these results suggest that HERC2 fine-tunes ATR-phosphorylated RPA2 levels through induction and degradation, a mechanism that could be critical for the suppression of secondary DNA structures during cell proliferation.

15.
Iran J Public Health ; 48(4): 621-631, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31110972

RESUMO

Background: Studies related to the prevention and control of myopia in adolescents have increased rapidly, but only a few have measured the levels of scientific collaboration among authors, institutions and countries in this field. Thus, in this study, we aimed to reveal the status and levels of scientific collaboration in this field. Methods: The research population included all published papers in the field of adolescent myopia prevention and control indexed in the Web of Science databases from 1997-2016. The co-authorship networks were drawn using SATI (Statistical Analysis Toolkit for Informetrics), Ucinet and VOS viewer (Visualisation of Similarities viewer). Active authors and some measures of co-author network, including degree centrality, closeness, betweenness, density and diameter, were also assessed. Results: Overall, 610 records were obtained, and a number of publications developed through an increase in different collaboration types, with cooperation among authors and institutions as the most apparent ones. The top ten active authors and institutions were identified. The density of cooperative networks of the top 70 authors and the first 69 institutions were 0.043 and 0.011, respectively, with corresponding diameters of five and six, respectively. Seven distinct clusters formed the cooperation network among 38 countries. The top three clusters were centered in China, the United States and Australia, also identified as the most productive countries. Conclusion: The flow of information is slow and the collaboration among authors and institutions in the network are not close enough. Thus, multiple collaboration types should be encouraged in this field, especially among countries.

16.
Physiol Plant ; 167(1): 5-20, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-30891756

RESUMO

To explore the mechanisms of 5-aminolevulinic acid (ALA)-improved plant salt tolerance, strawberries (Fragaria × ananassa Duch. cv. 'Benihoppe') were treated with 10 mg l-1 ALA under 100 mmol l-1 NaCl stress. We found that the amount of Na+ increased in the roots but decreased in the leaves. Laser scanning confocal microscopy (LSCM) observations showed that ALA-induced roots had more Na+ accumulation than NaCl alone. Measurement of the xylem sap revealed that ALA repressed Na+ concentrations to a large extent. The electron microprobe X-ray assay also confirmed ALA-induced Na+ retention in roots. qRT-PCR showed that ALA upregulated the gene expressions of SOS1 (encoding a plasma membrane Na+ /H+ antiporter), NHX1 (encoding a vacuolar Na+ /H+ antiporter) and HKT1 (encoding a protein of high-affinity K+ uptake), which are associated with Na+ exclusion in the roots, Na+ sequestration in vacuoles and Na+ unloading from the xylem vessels to the parenchyma cells, respectively. Furthermore, we found that ALA treatment reduced the H2 O2 content in the leaves but increased it in the roots. The exogenous H2 O2 promoted plant growth, increased root Na+ retention and stimulated the gene expressions of NHX1, SOS1 and HKT1. Diphenyleneiodonium (DPI), an inhibitor of H2 O2 generation, suppressed the effects of ALA or H2 O2 on Na+ retention, gene expressions and salt tolerance. Therefore, we propose that ALA induces H2 O2 accumulation in roots, which mediates Na+ transporter gene expression and more Na+ retention in roots, thereby improving plant salt tolerance.


Assuntos
Ácido Aminolevulínico/farmacologia , Fragaria/efeitos dos fármacos , Fragaria/metabolismo , Peróxido de Hidrogênio/metabolismo , Raízes de Plantas/efeitos dos fármacos , Raízes de Plantas/metabolismo , Sódio/farmacologia , Tolerância ao Sal , Plantas Tolerantes a Sal/efeitos dos fármacos , Plantas Tolerantes a Sal/metabolismo
17.
Int J Geriatr Psychiatry ; 34(2): 243-248, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-29984420

RESUMO

OBJECTIVE: We aimed to assess the effect of socioeconomic status and physical activity on cognitive function using a large population-based survey data in China. METHODS: We took advantage of the Chinese Longitudinal Healthy Longevity Survey conducted in 2014 to examine the relationship between sociodemographic, physical activity, and cognitive function in older adults (OAs) for persons aged above 65 (N = 2848). Socioeconomic status was assessed by sex, age, co-residence situation, category of residence, years of schooling, and marital status. Multiple linear regression for predictors was utilized. Physical activity was assessed using activities of daily living (ADL) and instrumental activities of daily living (IADL) measures. Cognitive function was assessed by the Modified Mini-Mental State Examination. RESULTS: The mean age of the OAs was 80.65 years (SD = 8.55). Their mean Mini-Mental State Examination score was 21.55 (SD = 2.38), mean ADL Total score was 6.24 (SD = 0.95), and mean IADL Total score was 10.21 (SD = 3.84). OAs' age at testing, co-residence and category of residence significantly predicted both ADL Total score and IADL Total score (P < 0.05), sex significantly predicted IADL Total score (R2  = 0.02, ß = 0.13, P = 0.000) but not ADL Total score (R2  = 0.00, ß = 0.02, P = 0.211). OAs' sex, age, co-residence, and years of schooling significantly predicted cognitive function (P < 0.05), IADL total score significantly predicted cognitive function (P < 0.01), while the relationship between ADL total score and cognitive function was not significant (P = 0.94). CONCLUSION: OAs' sex, age, co-residence, years of schooling, and IADL were significantly associated with cognitive function. Improving OAs' IADL, especially in lower social classes, may help to improve the overall cognitive function of the OAs.


Assuntos
Cognição/fisiologia , Exercício Físico/fisiologia , Exercício Físico/psicologia , Atividades Cotidianas , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , China , Estudos Transversais , Escolaridade , Feminino , Humanos , Estudos Longitudinais , Masculino , Testes de Estado Mental e Demência , Fatores Sexuais , Fatores Socioeconômicos
18.
Exp Gerontol ; 116: 93-105, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30590123

RESUMO

Due to dramatic growth of the aging population worldwide, there has been an urgent call for a public health strategy to manage healthy aging, with the ultimate goal being advancement of aging research. Considerable progress has been made in uncovering the mystery of aging process using multidisciplinary methods. There is a growing consensus in the field that aging traits which were originally thought to be disparate are likely to be interconnected. Thus, emerging research is needed to incorporate current findings of aging by building multiscale network models. This study reported the network of healthy aging research using bibliometric approaches. Based on the results, aging of the brain and muscle is a primary research focus which is a critical part of the multiscale network regulating the aging process. Among aging-associated diseases, Alzheimer's disease and frailty are among the main research focuses, and emerging work has focused on developing diagnostic tools for these diseases. For research on anti-aging interventions, calorie restriction, physical activity, and anti-aging pharmacology are the main interventions, of which the underlying mechanisms have been comprehensively studied in animal models.

19.
J Clin Invest ; 128(12): 5603-5619, 2018 12 03.
Artigo em Inglês | MEDLINE | ID: mdl-30418174

RESUMO

The agonistic/antagonistic biocharacter of selective estrogen receptor modulators (SERMs) can have therapeutic advantages, particularly in the case of premenopausal breast cancers. Although the contradictory effects of these modulators have been studied in terms of crosstalk between the estrogen receptor α (ER) and coactivator dynamics and growth factor signaling, the molecular basis of these mechanisms is still obscure. We identify a series of regulatory mechanisms controlling cofactor dynamics on ER and SERM function, whose activities require F-box protein 22 (Fbxo22). Skp1, Cullin1, F-box-containing complex (SCFFbxo22) ubiquitylated lysine demethylase 4B (KDM4B) complexed with tamoxifen-bound (TAM-bound) ER, whose degradation released steroid receptor coactivator (SRC) from ER. Depletion of Fbxo22 resulted in ER-dependent transcriptional activation via transactivation function 1 (AF1) function, even in the presence of SERMs. In living cells, TAM released SRC and KDM4B from ER in a Fbxo22-dependent manner. SRC release by TAM required Fbxo22 on almost all ER-SRC-bound enhancers and promoters. TAM failed to prevent the growth of Fbxo22-depleted, ER-positive breast cancers both in vitro and in vivo. Clinically, a low level of Fbxo22 in tumor tissues predicted a poorer outcome in ER-positive/human epidermal growth factor receptor type 2-negative (HER2-negative) breast cancers with high hazard ratios, independently of other markers such as Ki-67 and node status. We propose that the level of Fbxo22 in tumor tissues defines a new subclass of ER-positive breast cancers for which SCFFbxo22-mediated KDM4B degradation in patients can be a therapeutic target for the next generation of SERMs.


Assuntos
Neoplasias da Mama/metabolismo , Receptor alfa de Estrogênio/metabolismo , Proteínas F-Box/metabolismo , Histona Desmetilases com o Domínio Jumonji/metabolismo , Proteínas de Neoplasias/metabolismo , Proteólise , Receptores Citoplasmáticos e Nucleares/metabolismo , Animais , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/genética , Neoplasias da Mama/patologia , Receptor alfa de Estrogênio/genética , Proteínas F-Box/genética , Feminino , Humanos , Histona Desmetilases com o Domínio Jumonji/genética , Células MCF-7 , Camundongos , Camundongos Endogâmicos NOD , Camundongos SCID , Proteínas de Neoplasias/genética , Receptores Citoplasmáticos e Nucleares/genética , Tamoxifeno/farmacologia , Ensaios Antitumorais Modelo de Xenoenxerto
20.
Cancer Res ; 78(22): 6371-6385, 2018 11 15.
Artigo em Inglês | MEDLINE | ID: mdl-30279242

RESUMO

BLM and WRN are RecQ DNA helicasesessential for genomic stability. Here, we demonstrate that HERC2, a HECT E3 ligase, is critical for their functions to suppress G-quadruplex (G4) DNA. HERC2 interacted with BLM, WRN, and replication protein A (RPA) complexes during the S-phase of the cell cycle. Depletion of HERC2 dissociated RPA from BLM and WRN complexes and significantly increased G4 formation. Triple depletion revealed that HERC2 has an epistatic relationship with BLM and WRN in their G4-suppressing function. In vitro, HERC2 released RPA onto single-stranded DNA (ssDNA) rather than anchoring onto RPA-coated ssDNA. CRISPR/Cas9-mediated deletion of the catalytic ubiquitin-binding site of HERC2 inhibited ubiquitination of RPA2, caused RPA accumulation in the helicase complexes, and increased G4, indicating an essential role for E3 activity in the suppression of G4. Both depletion of HERC2 and inactivation of E3 sensitized cells to the G4-interacting compounds telomestatin and pyridostatin. Overall, these results indicate that HERC2 is a master regulator of G4 suppression that affects the sensitivity of cells to G4 stabilizers. Given that HERC2 expression is frequently reduced in many types of cancers, G4 accumulation as a result of HERC2 deficiency may provide a therapeutic target for G4 stabilizers.Significance: HERC2 is revealed as a master regulator of G-quadruplex, a DNA secondary structure that triggers genomic instability and may serve as a potential molecular target in cancer therapy.Graphical Abstract: http://cancerres.aacrjournals.org/content/canres/78/22/6371/F1.large.jpg Cancer Res; 78(22); 6371-85. ©2018 AACR.


Assuntos
Quadruplex G , Fatores de Troca do Nucleotídeo Guanina/metabolismo , RecQ Helicases/metabolismo , Proteína de Replicação A/metabolismo , Helicase da Síndrome de Werner/metabolismo , Aminoquinolinas/farmacologia , Domínio Catalítico , Ciclo Celular , Reparo do DNA , Replicação do DNA , DNA de Cadeia Simples/genética , Instabilidade Genômica , Células HCT116 , Células HEK293 , Células HeLa , Humanos , Neoplasias/metabolismo , Oxazóis/farmacologia , Fenótipo , Ácidos Picolínicos/farmacologia , Ligação Proteica , RNA Interferente Pequeno/metabolismo
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