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1.
Bioorg Chem ; 109: 104723, 2021 Feb 10.
Artigo em Inglês | MEDLINE | ID: mdl-33618250

RESUMO

Natural products are a rich source of lead compounds and have shown promise for epigenetic drug discovery. In this work, we discovered higenamine from our natural product library as a potent, selective and cellular active natural LSD1 inhibitor. Higenamine shows acceptable potency against LSD1 and high selectivity towards LSD1 over MAOA/B. Higenamine significantly increases expression of LSD1 substrates H3K4me1 and H3K4me2 in MLL-rearranged leukemia cells MV4-11 and MOLM-13, but nearly had no effect on LSD1 and H3K4Me3. Meanwhile, higenamine dose-dependently suppresses the levels of HOXA9 and MEIS1 that are overexpressed in leukemia cell lines. Notably, higenamine induces cell differentiation of MV4-11 and MOLM-13 cells accompanying by increased expression of CD11b, CD14 and CD86. Higenamine promotes cell apoptosis, inhibits colony formation, but does not inhibit proliferation of leukemia cells significantly. In addition, the expression levels of p53 are dramatically changed by higenamine in an LSD1-dependent manner in MV4-11 cells. Taken together, higenamine could be employed as a starting point for the development of more selective and potent LSD1 inhibitors. Our work firstly reveals the non-classical epigenetic regulation mechanism of higenamine in cancers, and also demonstrates the efficacy of higenamine for MLL-rearranged leukemia therapy.

2.
Spectrochim Acta A Mol Biomol Spectrosc ; 252: 119469, 2021 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-33530031

RESUMO

Since 1, 2, 3-Benzotriazole (BTA) is one of the most commonly used metal passivators in transformer oil, on-site and quantitative detection of BTA plays a significant role in fast evaluation of the performance of the insulating oil. Herein, we proposed a cycle-growth synthetic protocol for yielding two-dimensional (2D) plane-based surface-enhanced Raman scattering (SERS) substrates with tunable optical property and controllable interparticle distance, and an extraction material, so called colloidal lignin particles (CLPs), for the fast separation of BTA from oil matrix. After BTA from transformer oil were adsorbed by hydrophilic CLPs, highly reproducible SERS signal of BTA can be obtained by dropping on the substrate. The characteristic Raman shift at 1386 cm-1 of BTA has been selected to establish a good linearity between its relative intensity and concentration in the range of 1-300 mg/L, and the detection limit for BTA was down to 0.12 mg/L. Moreover, the time consumption for the whole detection process of real sample including sample pretreatment and SERS measurements was less than 30 min. It is highly expected that the combination of CLPs with SERS can accomplish the on-site detection of trace BTA in transformer oil.

3.
Acta Neuropathol Commun ; 9(1): 23, 2021 02 08.
Artigo em Inglês | MEDLINE | ID: mdl-33557929

RESUMO

Mutations in the DNAJB6 gene have been identified as rare causes of myofibrillar myopathies. However, the underlying pathophysiologica mechanisms remain elusive. DNAJB6 has two known isoforms, including the nuclear isoform DNAJB6a and the cytoplasmic isoform DNAJB6b, which was thought to be the pathogenic isoform. Here, we report a novel recessive mutation c.695_699del (p. Val 232 Gly fs*7) in the DNAJB6 gene, associated with an apparently recessively inherited late onset distal myofibrillar myopathy in a Chinese family. Notably, the novel mutation localizes to exon 9 and uniquely encodes DNAJB6a. We further identified that this mutation decreases the mRNA and protein levels of DNAJB6a and results in an age-dependent recessive toxic effect on skeletal muscle in knock-in mice. Moreover, the mutant DNAJB6a showed a dose-dependent anti-aggregation effect on polyglutamine-containing proteins in vitro. Taking together, these findings reveal the pathogenic role of DNAJB6a insufficiency in myofibrillar myopathies and expand upon the molecular spectrum of DNAJB6 mutations.

4.
J Asian Nat Prod Res ; : 1-9, 2021 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-33583279

RESUMO

Seven benzophenone compounds were synthesized in one or two steps, then their antitumor activity was evaluated. The total yields ranged from 9% to 44%. Compounds 3c-5c exhibited obvious antitumor activity. Among them, compounds 3c and 4c exhibited excellent and broad-spectrum antitumor activity. Compound 3c exhibited much stronger inhibitory activities against fourteen cancer cells than cisplatin. In particular, compound 3c exhibited stronger cytotoxicity against hepatocarcinoma SMMC-7721 cells than Taxol, with a half maximal inhibitory concentration (IC50) of approximately 0.111 µM. These results demonstrated that compounds 3c, 4c and 5c were very promising antitumor leads for further structural modification.

5.
Plant Physiol Biochem ; 161: 65-73, 2021 Feb 03.
Artigo em Inglês | MEDLINE | ID: mdl-33578286

RESUMO

Mulberry (Morus sp., Moraceae) is an important economic crop plant and mulberry fruits are rich in anthocyanidins. Chalcone isomerase (CHI) catalyzes the conversion of chalcones to flavanones providing precursors for biosynthesis of anthocyanidins. In this study, bona fide CHIs were cloned and characterized from different Morus species with differently colored fruits (Morus multicaulis, Mm and Morus alba variety LvShenZi, LSZ). Enzymatic assay of MmCHI1 and MmCHI2 showed that they can utilize naringenin chalcone as substrate. The catalytic efficiency of MmCHI2 and LSZCHI2 are approximately 200 and 120-fold greater than that of MmCHI1 respectively. Phylogenetic analysis showed the two mulberry CHIs belonged to different sub-clade of Type I CHI1 named type IA (CHI2) and type IB (CHI1). Type IB CHIs are mulberry specific. MmCHI1 and MmCHI2 had similar expression profiles and showed preferred expression in fruits. In addition, both mulberry CHI1 and CHI2 played roles in the response to excess zinc stress and sclerotiniose pathogen infection. Both MmCHI1 and MmCHI2 expression levels showed positive close relationship with anthocyanins content during fruit ripening process. The co-expression of MmCHI1 and MmCHI2 was observed during fruit ripening process and in transgenic mulberry. VIGS (virus induced gene silence) targeting on MmCHI1 and MmCHI2 showed significant down-regulation of MmCHI2 instead of MmCHI1 would result in significant (about 50%) decrease in anthocyanins content. MmCHI2 is the dominant CHI for anthocyanins accumulation in mulberry. The results presented in this work provided insight on bona fide CHIs in mulberry and reveal their roles in anthocyanins accumulation.

6.
Environ Res ; 195: 110867, 2021 Feb 11.
Artigo em Inglês | MEDLINE | ID: mdl-33582130

RESUMO

Ambient air pollution has been identified as one of the leading causes of global burden of disease. The relationship between ambient air pollution exposure and risk of chronic kidney disease (CKD) has stimulated increasing scientific interest in the past few years. However, evidence from human epidemiological studies is still limited and inconsistent. We performed an updated systematic review and meta-analysis to clarify the potential association comprehensively. Selected electronic databases were searched for related English language studies until March 1, 2020 with a final follow-up in December 31, 2020. Risk of bias assessment for individual studies were assessed using the OHAT (Office of Health Assessment and Translation) risk-of-bias rating tool. Confidence rating and level-of-evidence conclusions were developed for bodies of evidence for a given ambient air pollutant. Summary effect estimates were calculated using random-effects meta-analyses when three or more studies are identified for the same air pollutant-CKD combination. A total of 13 studies were finally identified in our study. The meta-analytic estimates (ORs) for risk of CKD were 1.15 (95% CI: 1.07, 1.24) for each 10 µg/m3 increase in PM2.5, 1.25 (95% CI: 1.11, 1.40) for each 10 µg/m3 increase in PM10, 1.10 (95% CI: 1.03, 1.17) for each 10 ppb increase in NO2, 1.06 (95% CI: 0.98, 1.15) for each 1 ppb increase in SO2 and 1.04 (95% CI: 1.00, 1.08) for each 0.1 ppm increase in CO, respectively. The level of evidence was appraised as moderate for four of the five tested air pollutant-CKD combinations using an adaptation of the GRADE (Grading of Recommendations Assessment, Development and Evaluation) tool. In conclusion, this study suggests that certain ambient air pollutant exposure was significantly associated with an increased risk of CKD. Given the limitations, the results of this study should be interpreted with caution, and further well-designed epidemiological studies are needed to draw a definite evidence of a causal relationship.

7.
J Transl Med ; 19(1): 82, 2021 Feb 18.
Artigo em Inglês | MEDLINE | ID: mdl-33602263

RESUMO

BACKGROUND: Although chimeric antigen receptor (CAR)-T cell therapy has been remarkably successful for haematological malignancies, its efficacy against solid tumors is limited. The combination of CAR-T cell therapy with immune checkpoint inhibitors (CPIs), such as PD-1, PD-L1, and CTLA-4 antibodies, is a promising strategy for enhancing the antitumor efficacy of CAR-T cells. However, because most patients acquire resistance to CPIs, investigating other strategies is necessary to further improve the antitumor efficacy of CAR-T cell therapy for solid tumors. Recently, CD40 agonist antibodies showed potential antitumor efficacy by activating the CD40 pathway. RESULTS: Based on the piggyBac transposon system, rather than the widely used viral vectors, we constructed a meso3-CD40 CAR-T targeting region III of mesothelin (MSLN) that possessed the ability to secrete anti-CD40 antibodies. Compared with meso3 CAR-T cells, which did not secrete the anti-CD40 antibody, meso3-CD40 CAR-T cells secreted more cytokines and had a relatively higher proportion of central memory T (TCM) cells after stimulation by the target antigen. In addition, compared with meso3 CAR-T cells, meso3-CD40 CAR-T cells had a more powerful cytotoxic effect on target cells at a relatively low effector-to-target ratio. More importantly, we demonstrated that the antitumor activity of meso3-CD40 CAR-T cells was enhanced in a human ovarian cancer xenograft model in vivo. CONCLUSIONS: In conclusion, these results highlight anti-CD40-secreting CAR-T cells generated by nonviral vectors as a potential clinical strategy for improving the efficacy of CAR-T cell therapies.

8.
J Proteomics ; : 104137, 2021 Feb 03.
Artigo em Inglês | MEDLINE | ID: mdl-33548507

RESUMO

Extracellular vesicles (EVs) are important for the transport of biomolecular materials and intercellular communication in eukaryotes. Recent research has revealed that they are involved in plant-pathogen interaction and pathogenesis of infected cells. Phytophthora capsici is a highly devastating oomycete pathogen with a broad host range. To increase infection and facilitate colonization, it secretes effector proteins during interaction with plants. In this study, we characterize for the first time the EVs from pathogen P. capsici through transmission electron microscopy. For the biological study of EVs, results showed that mixing high concentrations of EVs with zoospores could enhance the virulence of P. capsici. By sequencing the protein composition of EVs by liquid chromatography in tandem with mass spectrometry we found that there are many proteins related to metabolism, oxidation/reduction, and transport in EVs, indicating that they have important roles in pathogenesis and immunological processes within the host. SIGNIFICANCE: Extracellular vesicles (EVs) are important both at normal physiological processes as well as pathological progression during pathogen and host interaction. In this paper we first establish the extraction method of EVs from the important oomycete pathogen Phytophthora capsici. Bioinformatics analysis of EV proteomics revealed a variety of pathogenic-related proteins, like oxidation/reduction-related proteins, stress response proteins as well as elicitors. Our results will help better understanding the biological function of the EVs during plant and P. capsici interaction and providing the evidence for the role of EVs in pathogenesis of the P. capsici.

9.
J Med Internet Res ; 23(2): e21465, 2021 Feb 02.
Artigo em Inglês | MEDLINE | ID: mdl-33528372

RESUMO

BACKGROUND: Human papillomavirus (HPV) vaccination is effective in the prevention of vaccine-type genital warts and cancers among men who have sex with men (MSM). OBJECTIVE: The primary objective of this randomized controlled trial (RCT) is to evaluate the efficacies of 2 web- and theory-based interventions with and without brief motivational interviewing (MI) over the phone to increase the completion of HPV vaccination among unvaccinated participants within a 24-month follow-up period compared with the control group. METHODS: A 3-arm parallel-group RCT was conducted between July 2017 and December 2019. Five telephone surveys were conducted at baseline and at 3, 6, 9, and 24 months by blinded interviewers. Participants were Hong Kong Chinese-speaking MSM aged between 18 and 45 years with regular internet access who were recruited from outreaching at venues, web-based recruitment, and peer referral. Those who had ever received HPV vaccination were excluded. A total of 624 participants were randomized into either the online tutorial (OT) only group (n=208), the OT plus MI group (OT-MI; n=208), or the control group (n=208). In total, 459 (459/624, 73.6%) completed the follow-up evaluation at 24 months. Participants in the OT group received a fully automated OT developed based on the health belief model. On top of the same OT, the OT-MI group received brief MI over the phone. Reminders were sent to the participants of the OT and OT-MI groups after 1, 2, 4, 6, and 8 months. Participants in the control group received web-based health communication messages unrelated to HPV or HPV vaccination. The research team validated the self-reported HPV vaccination uptake. Intention-to-treat analysis was used for outcome analyses. Logistic regression models and multivariable linear regression models were used to test the between-group differences in primary and secondary outcomes. Baron and Kenny's methods were used to test the mediation hypothesis. RESULTS: The participants in the OT-MI group reported a significantly higher validated completion of HPV vaccination at 24 months than the control group (36/208, 17.3% vs 15/208, 7.2%; P=.006). However, the difference in HPV vaccination completion between the OT and the control groups (24/208, 11.5% vs 15/208, 7.2%; P=.17), or between OT-MI and OT groups (P=.13), was not statistically significant. The association between randomization status (OT-MI group vs control group) and HPV vaccination completion became statistically nonsignificant after controlling for changes in the perceived susceptibility to HPV (24 months vs baseline), whereas perceived susceptibility remained strongly associated with HPV vaccination uptake in the model (P<.001). Changes in perceived susceptibility fully mediated the intervention effect. CONCLUSIONS: Theory-based OT with brief MI over the phone was effective in increasing HPV vaccination completion among Chinese MSM. Perceived susceptibility is an active theoretical component that causes behavioral changes. TRIAL REGISTRATION: ClinicalTrials.gov NCT03286907; https://clinicaltrials.gov/ct2/show/NCT03286907.

10.
Nucleic Acids Res ; 2021 Feb 09.
Artigo em Inglês | MEDLINE | ID: mdl-33561291

RESUMO

Simultaneous dysregulation of multiple microRNAs (miRs) affects various pathological pathways related to cardiac failure. In addition to being potential cardiac disease-specific markers, miR-23b/27b/24-1 were reported to be responsible for conferring cardiac pathophysiological processes. In this study, we identified a conserved guanine-rich RNA motif within the miR-23b/27b/24-1 cluster that can form an RNA G-quadruplex (rG4) in vitro and in cells. Disruption of this intragenic rG4 significantly increased the production of all three miRs. Conversely, a G4-binding ligand tetrandrine (TET) stabilized the rG4 and suppressed miRs production in human and rodent cardiomyocytes. Our further study showed that the rG4 prevented Drosha-DGCR8 binding and processing of the pri-miR, suppressing the biogenesis of all three miRs. Moreover, CRISPR/Cas9-mediated G4 deletion in the rat genome aberrantly elevated all three miRs in the heart in vivo, leading to cardiac contractile dysfunction. Importantly, loss of the G4 resulted in reduced targets for the aforementioned miRs critical for normal heart function and defects in the L-type Ca2+ channel-ryanodine receptor (LCC-RyR) coupling in cardiomyocytes. Our results reveal a novel mechanism for G4-dependent regulation of miR biogenesis, which is essential for maintaining normal heart function.

11.
Complement Ther Med ; : 102676, 2021 Feb 06.
Artigo em Inglês | MEDLINE | ID: mdl-33561530

RESUMO

BACKGROUND: Virtual reality (VR) training are regarded as promising new tools for rehabilitation, but the effect on patients' daily participation is controversial. This study aimed to evaluate the effect of virtual reality (VR) training on different types of patients' daily participation through a meta-analysis. METHODS: The PubMed, Cochrane central register of controlled trials, Embase, and web science databases were searched for studies published through September 2020. Thirty-five randomized controlled trials of virtual reality (VR) training compared with conventional treatment, Other electronic rehabilitation systems, usual care for various types of patients were included. All of the studies were available in English. Standardized mean differences (SMD), 95% confidence intervals (CI), publication bias, and heterogeneity were calculated. RESULTS: The Virtual reality (VR) training group is better than the control group in daily participation improvement on all types of patients. There was a small, significant effect(p<0.001; SMD = 0.25[95%CI,0.14 to 0.36], I2 = 0.00% ). Observing only the type of Stroke, the VR training group is still better than the control group in improving patients' daily participation (p<0.001, SMD = 0.24[95%CI, 0.11 to 0.37], I2 = 0.00%). Using the cumulative Meta-analysis method to observe the included literature according to the timeline, Using the cumulative Meta-analysis method to observe the included literature according to the timeline, and it has only achieved positive results since 2015 (Nam-YoNg Lee 2015, p = 0.048, SMD = 0.22[95%CI,0.00 to 0.44]). The heterogeneity of the studies was not detected, but there is obvious publication bias. CONCLUSIONS: Because of controversy over obvious publication bias, we need to be cautious about the conclusion that VR is better than the control group in promoting the patient's daily participation.

12.
J Adv Nurs ; 2021 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-33590585

RESUMO

AIMS: To provide an overview of the parental, child, and socio-contextual factors related to general parenting self-efficacy (PSE) in the general population. DESIGN: Systematic review. DATA SOURCES: Medline Ovid, Web of Science, Embase, and PsycINFO Ovid were systematically searched for studies published between January 1980-June 2020. REVIEW METHODS: Studies were included if they described associations between factor(s) and PSE among parents of children aged 0-18 years old in the general population, and published in an English language peer-reviewed journal. Studies with participants from specific populations, studies describing the development of instruments for PSE, qualitative studies, reviews, theses, conference papers and book chapters were excluded. Belsky's process model of parenting guided the data synthesis. RESULTS: Of 3,819 articles, 30 articles met the inclusion criteria. Eighty-nine factors were identified. There was evidence of associations between child temperament, maternal parenting satisfaction, parenting stress, maternal depression, household income, perceived social support and PSE. Evidence was inconsistent for an association of educational level, parity, number of children in the household and PSE in mothers. There was no evidence of an association for child gender, age, marital status and PSE in both mothers and fathers; ethnicity, age, employment status in mothers; household income in fathers; and educational level, parenting fatigue in parents. CONCLUSION: A range of factors studied in relation to PSE was identified in this systematic review. However, the majority of the factors was reported by one or two studies often implementing a cross-sectional design. IMPACT: There is some evidence for an association between some potentially modifiable factors and PSE in the general population, this information may be used by health and social professionals supporting child health and well-being. Future longitudinal studies are recommended to study parental, child and socio-contextual factors associated with PSE to inform the development of intervention strategies.

13.
J Vasc Res ; : 1-5, 2021 Feb 08.
Artigo em Inglês | MEDLINE | ID: mdl-33556943

RESUMO

This study tested the hypothesis that endothelium-specific GTP cyclohydrolase I (GTPCH I) overexpression (Tg-GCH) restores age-associated endothelial dysfunction in vivo. Aortic GTPCH I expression and serum nitric oxide (NO) release were measured in young and aged mice. Aortic rings from young and aged wild-type (WT) mice and aged Tg-GCH mice were suspended for isometric tension recording. A hind limb ischemia model was used to measure blood flow recovery. Aged mice showed reduced GTPCH I expression in the aorta and decreased NO levels in serum. Compared with aged WT mice, Tg-GCH significantly elevated NO levels in serum in aged Tg-GCH mice, restored the impaired aortic relaxation in response to acetylcholine, and significantly elevated aortic constriction in response to L-NAME. Importantly, aged Tg-GCH mice displayed a significant increase in blood flow recovery compared with aged WT mice. GTPCH I reduction contributes to aging-associated endothelial dysfunction, which can be retarded by Tg-GCH.

14.
Acta Pharmacol Sin ; 2021 Feb 08.
Artigo em Inglês | MEDLINE | ID: mdl-33558654

RESUMO

Accumulating evidence shows that agents targeting gut dysbiosis are effective for improving symptoms of irritable bowel syndrome (IBS). However, the potential mechanisms remain unclear. In this study we investigated the effects of berberine on the microbiota-gut-brain axis in two rat models of visceral hypersensitivity, i.e., specific pathogen-free SD rats subjected to chronic water avoidance stress (WAS) and treated with berberine (200 mg· kg-1 ·d-1, ig, for 10 days) as well as germ-free (GF) rats subjected to fecal microbiota transplantation (FMT) from a patient with IBS (designated IBS-FMT) and treated with berberine (200 mg· kg-1 ·d-1, ig, for 2 weeks). Before the rats were sacrificed, visceral sensation and depressive behaviors were evaluated. Then colonic tryptase was measured and microglial activation in the dorsal lumbar spinal cord was assessed. The fecal microbiota was profiled using 16S rRNA sequencing, and short chain fatty acids (SCFAs) were measured. We showed that berberine treatment significantly alleviated chronic WAS-induced visceral hypersensitivity and activation of colonic mast cells and microglia in the dorsal lumbar spinal cord. Transfer of fecal samples from berberine-treated stressed donors to GF rats protected against acute WAS. FMT from a patient with IBS induced visceral hypersensitivity and pro-inflammatory phenotype in microglia, while berberine treatment reversed the microglial activation and altered microbial composition and function and SCFA profiles in stools of IBS-FMT rats. We demonstrated that berberine did not directly influence LPS-induced microglial activation in vitro. In both models, several SCFA-producing genera were enriched by berberine treatment, and positively correlated to the morphological parameters of microglia. In conclusion, activation of microglia in the dorsal lumbar spinal cord was involved in the pathogenesis of IBS caused by dysregulation of the microbiota-gut-brain axis, and the berberine-altered gut microbiome mediated the modulatory effects of the agent on microglial activation and visceral hypersensitivity, providing a potential option for the treatment of IBS.

15.
J Food Biochem ; 45(2): e13623, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33491221

RESUMO

Diabetic retinopathy is a major complication in patients with diabetes. Herein, we investigate how hawthorn polyphenol extract (HPE) affects high glucose-induced oxidation, inflammation, and apoptosis in ARPE-19 cells. HPLC-MS/MS was used to determine HPE content and composition. Reactive oxygen species (ROS) production was assessed using fluorescence microscopy, while glucose-induced gene and protein expressions were analyzed using real-time PCR and western blotting in cells transfected with miR-34a mimics. We found that treating cells with 10 µg/ml of HPE, 30 µM procyanidin B2, chlorogenic acid, epicatechin, or resveratrol (positive control) significantly reduced ROS production and decreased apoptosis and inflammation-related factors (p < .01). Moreover, the expression level of SIRT1 was increased, while that of acetylated NF-κB p65 and p53 proteins was decreased. These data suggest that HPE can inhibit oxidative damage, inflammation, and apoptosis through the AMPK/SIRT1/NF-κB pathway, and decrease miR-34a/SIRT1/p53 pathway activation in ARPE-19 cells, thereby demonstrating a potential use as a food additive to mitigate hyperglycemia-induced retinal damage. PRACTICAL APPLICATIONS: Hawthorn polyphenol extract (HPE) significantly reduced ROS levels, apoptosis, and the expression of inflammation-related factors in ARPE-19 cells. HPE also inhibited the AMPK/SIRT1/NF-κB and miR-34a/SIRT1/p53 pathways, which are involved in hyperglycemia-induced inflammation and apoptosis of ARPE-19 cells by regulating acetylation. Thus, HPE, as a potential food additive, may mitigate hyperglycemia-induced retinal damage.

16.
Cell Cycle ; 20(4): 369-382, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33507122

RESUMO

Circular RNAs (circRNAs), the new stars of endogenous non-coding RNAs, are dysregulated in various tumors including pancreatic cancer. Here, we aimed to investigate the biological functions of hsa_circ_0071036 in the tumourigenesis and progression of pancreatic ductal adenocarcinoma (PDAC) and its clinical implications. The differential expression profile of circRNAs in 4 pairs of PDAC tissues was analyzed by microarray assay. Quantitative real-time PCR and fluorescence in situ hybridization (FISH) were utilized to determine the expression patterns and their clinical significance. Functional experiments in vitro and in vivo were performed to explore whether hsa_circ_0071036 functions as an oncogenic circRNA in PDAC. Mechanistically, RT-qPCR, dual luciferase reporter and RNA pull-down assays were conducted to identify the interaction between hsa_circ_0071036 and miR-489 in PDAC. Hsa_circ_0071036 was remarkably overexpressed in PDAC cell lines and tissue samples, which negatively correlated with miR-489 expression. Aberrant expression of hsa_circ_0071036 correlated with poor clinicopathological characteristics and prognoses of PDAC patients. Knockdown of hsa_circ_0071036 suppressed proliferation and invasion and induced apoptosis in vitro. Moreover, the in vivo xenograft model confirmed that silencing of hsa_circ_0071036 attenuated tumor growth. Mechanistic analyses indicated that hsa_circ_0071036 acted as an efficient miRNA sponge for miR-489 in PDAC. In summary, our study revealed that upregulated hsa_circ_0071036 promotes PDAC pathogenesis and progression by directly sponging miR-489, which implies an important role for this circRNA-miRNA functional network.

17.
J Nurs Manag ; 2021 Jan 22.
Artigo em Inglês | MEDLINE | ID: mdl-33480056

RESUMO

AIMS: To explore the association between cognitive emotion regulation strategies and anxiety and depression among nurses during the COVID-19 outbreak. BACKGROUND: Nurses play a vital role in responding to the COVID-19 outbreak, but many of them suffer from psychological problems due to the excessive workload and stress. Understanding the correlation between cognitive emotion regulation strategies and anxiety and depression will promote targeted psychosocial interventions for these affected nurses. METHODS: This cross-sectional study of 586 nurses was conducted in Eastern China. Participants completed online questionnaires that investigated anxiety, depression and cognitive emotion regulation strategies. RESULTS: The prevalence of nurses' anxiety and depression was 27.6% and 32.8%, respectively. Lower self-blame, rumination and catastrophizing, as well as greater acceptance and positive refocusing, were related to fewer symptoms of anxiety or depression. CONCLUSION: The cognitive emotion regulation strategies of acceptance and positive refocusing contribute to reducing anxiety or depression. These strategies should be considered when implementing psychotherapeutic interventions to improve nurses' adverse emotional symptoms. IMPLICATIONS FOR NURSING MANAGEMENT: This study highlights the need to assess cognitive emotion regulation strategies use in screening for anxiety and depression. Nurse managers should develop psychosocial interventions including appropriate strategies to help nurses with adverse emotions during a pandemic.

19.
Artigo em Inglês | MEDLINE | ID: mdl-33498026

RESUMO

We report growth, electronic structure and superconductivity of ultrathin epitaxial CoSi2 films on Si(111). At low coverages, preferred islands with 2, 5 and 6 monolayers height develop, which agrees well with the surface energy calculation. We observe clear quantum well states as a result of electronic confinement and their dispersion agrees well with density functional theory calculations, indicating weak correlation effect despite strong contributions from Co 3d electrons. Ex-situ transport measurements show that superconductivity persists down to at least 10 monolayers, with reduced Tc but largely enhanced upper critical field. Our study opens up the opportunity to study the interplay between quantum confinement, interfacial symmetry breaking and superconductivity in an epitaxial silicide film, which is technologically relevant in microelectronics.

20.
Pharmacol Res ; : 105439, 2021 Jan 22.
Artigo em Inglês | MEDLINE | ID: mdl-33493658

RESUMO

The gut microbiota is recognized as a promising therapeutic target for anxiety. Berberine (BBR) has shown efficacy in the treatment of diseases such as postmenopausal osteoporosis, obesity, and type 2 diabetes through regulating the gut microbiota. However, the effects of BBR on postmenopausal anxiety are still unclear. The purpose of the study is to test whether BBR ameliorates anxiety by modulating intestinal microbiota under estrogen-deficient conditions. Experimental anxiety was established in specific pathogen-free (SPF) ovariectomized (OVX) rats, which were then treated with BBR for 4 weeks before undergoing behavioral tests. Open field and elevated plus maze tests demonstrated that BBR treatment significantly ameliorated anxiety-like behaviors of OVX rats compared with vehicle-treated counterparts. Moreover, as demonstrated by 16S rRNA sequencing and liquid chromatography/mass spectrometry (LC/MS) analysis, BBR-treated OVX rats harbored a higher abundance of beneficial gut microbes, such as Bacteroides, Bifidobacterium, Lactobacillus, and Akkermansia, and exhibited increased equol generation. Notably, gavage feeding of BBR had no significant anti-anxiety effects on germ-free (GF) rats that underwent ovariectomy, whereas GF rats transplanted with fecal microbiota from SPF rats substantially phenocopied the donor rats in terms of anxiety-like symptoms and isoflavone levels. This study indicates that the gut microbiota is critical in the treatment of ovariectomy-aggravated anxiety, and that BBR modulation of the gut microbiota is a promising therapeutic strategy for treating postmenopausal symptoms of anxiety.

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