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1.
Mol Cell Probes ; 59: 101764, 2021 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-34534618

RESUMO

An outbreak of African swine fever (ASF) in China in 2018 caused substantial economic losses to the swine industry. To accurately diagnose clinical infection with ASF virus (ASFV), we developed a TaqMan probe-based duplex real-time PCR that simultaneously detected two discontinuous genes in the virus genome, thereby preventing the inaccurate results obtained with only one reaction. Two sets of ASFV gene-specific primers, along with two fluorescent TaqMan probes were designed to target conserved regions of the B646L and B438L genes. This method had high sensitivity and specificity, with a limit of detection of 10 copies/µL, and it did not cross-react with the genomes of other viral pathogens that affect pigs (i.e., CSFV, PRRSV, PEDV, PRV, PPV and PCV2). Overall, 180 clinical samples from ASFV-infected pig farms were used to compare this method with a commercial kit, which yielded excellent consistency (98.3%). This new diagnostic method should greatly improve the efficiency of ASFV surveillance and reduce economic losses, providing benefits for both animal and public health.

2.
J Agric Food Chem ; 69(37): 10830-10837, 2021 Sep 22.
Artigo em Inglês | MEDLINE | ID: mdl-34496207

RESUMO

Small-molecule inhibitors of insect chitinolytic enzymes are potential insecticides. However, the reported inhibitors that target one enzyme usually exhibit unsatisfactory bioactivity. On the basis of the multitarget strategy, we performed a high-throughput screening of a natural product library to find insecticide leads against four chitinolytic enzymes from the Asian corn borer Ostrinia furnacalis (OfChtI, OfChtII, OfChi-h, and OfHex1). Several phytochemicals were discovered to be multitarget inhibitors of these enzymes and were predicted to occupy the -1 substrate-binding subsite and engage in polar interactions with catalytically important residues. Shikonin and wogonin, which had good inhibitory activities toward all four enzymes, also exhibited significant insecticidal activities against lepidopteran agricultural pests. This study provides the first example of using a multitarget high-throughput screening strategy to exploit natural products as insecticide leads against chitin biodegradation during insect molting.

3.
Cell Signal ; 87: 110145, 2021 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-34517087

RESUMO

Endometriosis is a debilitating gynecological disease affecting millions of women worldwide, but its exact pathogenesis remains unclear. Circular RNAs (circRNAs) have been demonstrated to be important regulators in multiple diseases. Nonetheless, the potential regulatory mechanism of aberrant circRNA expression in endometriosis has been elusive. The up-regulated circZFPM2 in ectopic endometrial tissues was previously screened by circRNA high-throughput sequencing and was furtherly validated by quantitative real time reverse transcriptase polymerase chain reaction (RT-qPCR). Overexpression of circZFPM2 promoted the proliferation, migration, invasion, and epithelial-mesenchymal transition (EMT) in Ishikawa and End1/E6E7 cells, whereas silencing circZFPM2 produced the opposite effect. Luciferase reporter assays validated that circZFPM2 could directly target miR-205-5p and miR-205-5p target ZEB1. RT-qPCR results showed that miR-205-5p was underexpressed while ZEB1 was overexpressed in ectopic endometrial tissues compared with their expression in eutopic endometria and non-endometriosis control endometria. The expression level of miR-205-5p was inversely proportional and that of ZEB1 was directly proportional with the proliferative, migrative, and invasive ability of endometrial cells. Further in vitro investigation indicated that miR-205-5p could inhibit EMT by targeting ZEB1. Subsequent rescue experiments confirmed that circZFPM2 could induce EMT and promote cell proliferation, migration, and invasion cascades through the miR-205-5p /ZEB1 signaling pathway. Conclusively, circZFPM2 may present a promising biomarker in the diagnosis and treatment of endometriosis.

4.
Cancer Lett ; 522: 32-43, 2021 Sep 11.
Artigo em Inglês | MEDLINE | ID: mdl-34520819

RESUMO

Indoleamine 2,3-dioxygenase 1 (IDO1) catalyzing the conversion of tryptophan (Trp) to kynurenine (Kyn) in kynurenine pathway (KP) is involved in the immunosuppression in pancreatic cancer (PC), but the value of IDO1 as an independent prognostic marker for PC is uncertain. Moreover, the correlation between tryptophan 2,3-dioxygenase (TDO), an isozyme of IDO1, and PC is largely unknown. Using TCGA database, the correlation between IDO1 and/or TDO expression and PC patients' survival was analyzed. The expressions of IDO1 and TDO in PC cells and PC mice were examined. The effects of IDO1, TDO or dual inhibition on IDO1 and TDO effector pathway (Aryl hydrocarbon receptor, AhR) and on migration and invasion of PC cells were investigated. The block effect of IDO1/TDO dual inhibitor RY103 on KP was evaluated. The preclinical efficacy of RY103 and its immunomodulatory effect on KPIC orthotopic PC mice and Pan02 tumor-bearing mice were explored. Results showed that IDO1/TDO co-expression is an independent prognostic marker for PC. RY103 can significantly block KP and target Kyn-AhR pathway to blunt the migration and invasion of PC cells, exhibit preclinical efficacy and ameliorate IDO1/TDO-mediated immunosuppression in PC mice.

5.
Brain Inj ; : 1-13, 2021 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-34543111

RESUMO

OBJECTIVE: : To determine age- and sex-specific predictors of discharge destination among patients with traumatic brain injury (TBI) receiving inpatient rehabilitation facility (IRF) care. DESIGN: : Secondary analysis of Uniform Data System for Medical Rehabilitation data. METHODS: : Logistic regression of patients (N = 221,961) age ≥18, TBI diagnosis, admitted to IRF between 2002 and 2018. OUTCOME: : Discharge destination (subacute vs. home/community settings). RESULTS: : Approximately 16% were discharged to subacute vs. 84% home. Younger versus older adults had lower odds of subacute discharge [OR = 0.72; 95% CI: 0.69, 0.76]. Younger females had lower odds of subacute discharge (vs. home) than older females [OR = 0.68; 95% CI: 0.63, 0.74]; younger males had lower odds of subacute discharge (vs. home) than older males [OR = 0.74; 95% CI: 0.70, 0.78]. Younger females versus younger males had lower odds of subacute discharge (vs. home) [OR = 0.83; 95% CI: 0.79, 0.87]. Older females versus older males had lower odds of subacute discharge (vs. home) [OR = 0.93; 95% CI: 0.90, 0.97]. Predictors of discharge destination for age- and sex-stratified groups varied. CONCLUSIONS: : Younger (vs. older) and female (vs. male) patients had lower odds of subacute discharge vs. home.

6.
Ginekol Pol ; 2021 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-34541637

RESUMO

OBJECTIVES: This study aims to investigate the expression and role of Endoglin (ENG) in endometriosis (EM). MATERIAL AND METHODS: In this study, quantitative real-time polymerase chain reaction, western blot and immunohistochemistry were used to examine the expression of ENG in tissues. Cellular experiments were performed to evaluate the effect of ENG on cellular biological function. Western blot was used to examine the expression of epithelial to mesenchymal transition-related proteins. RESULTS: The expression of ENG was significantly higher in the ectopic endometriotic tissues than that in eutopic endometriotic tissues. Knockdown of ENG inhibited cell viability, migration and invasion, and induced cell apoptosis in hEM15A cells. Additionally, silenced ENG caused increased levels of E-cadherin and decreased levels of N-cadherin, vimentin, MMP-2 and MMP-9. CONCLUSIONS: These results confirmed that ENG may be involved in the development of endometriosis by promoting EMT process, revealing a new insight into the pathogenesis of endometriosis and contributing to the exploration of molecular therapeutic strategies against endometriosis.

7.
Planta ; 254(4): 64, 2021 Sep 06.
Artigo em Inglês | MEDLINE | ID: mdl-34487243

RESUMO

MAIN CONCLUSION: Thirty CcMYB were identified to involve in flavonoid and lignin biosynthesis in pigeon pea genome. A comprehensive analysis of gene structure, phylogenetic relationships, distribution on chromosomes, gene duplication, and expression patterns was performed. MYB transcription factor is one of the largest gene families in plants and plays critical roles in plant growth and development, as well as resistance to biotic and abiotic stress. However, the function of MYB genes in pigeon pea (Cajanus cajan) remains largely unknown. Here, 30 R2R3-MYB which involved flavonoid and lignin biosynthesis were identified in the pigeon pea genome and were classified into five groups based on phylogenetic analysis. Simultaneously, another 122 key enzyme genes from biosynthetic pathways of flavonoid and lignin were identified and all of them were mapped on 11 chromosomes with the co-linearity relationship. Among these genes, the intron/exon organization and motif compositions were conserved and they have undergone a strong purifying selection and tandem duplications during evolution. Expression profile analysis demonstrated most of these genes were expressed in different tissues and responded significantly to MeJA, RNA-seq analysis revealed clear details of genes varied with time of induction. Ten key genes from the phenylpropanoid pathway were selected to further verify whether they responded to induction under different abiotic stress conditions (UV-B, cold, heat, salt, drought, and GA3). This study elaborates on potential regulatory relationships between R2R3-MYB genes and some key genes involved in flavonoid and lignin biosynthesis under MeJA treatment, as well as adding to the understanding of improving abiotic stress tolerance and regulating the secondary metabolism in woody crops. A simplified discussion model for the different regulation networks involved with flavonoid and lignin biosynthesis in pigeon pea is proposed.


Assuntos
Cajanus , Cajanus/genética , Cajanus/metabolismo , Regulação da Expressão Gênica de Plantas , Família Multigênica , Filogenia , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Metabolismo Secundário
8.
J Transl Med ; 19(1): 382, 2021 09 08.
Artigo em Inglês | MEDLINE | ID: mdl-34496868

RESUMO

BACKGROUND: Glycolysis affects tumor growth, invasion, chemotherapy resistance, and the tumor microenvironment. In this study, we aimed to construct a glycolysis-related prognostic model for ovarian cancer and analyze its relationship with the tumor microenvironment's immune cell infiltration. METHODS: We obtained six glycolysis-related gene sets for gene set enrichment analysis (GSEA). Ovarian cancer data from The Cancer Genome Atlas (TCGA) database and two Gene Expression Omnibus (GEO) datasets were divided into two groups after removing batch effects. We compared the tumor environments' immune components in high-risk and low-risk groups and analyzed the correlation between glycolysis- and immune-related genes. Then, we generated and validated a predictive model for the prognosis of ovarian cancer using the glycolysis-related genes. RESULTS: Overall, 27/329 glycolytic genes were associated with survival in ovarian cancer, 8 of which showed predictive value. The tumor cell components in the tumor microenvironment did not differ between the high-risk and low-risk groups; however, the immune score differed significantly between groups. In total, 13/24 immune cell types differed between groups, including 10 T cell types and three other immune cell types. Eight glycolysis-related prognostic genes were related to the expression of multiple immune-related genes at varying degrees, suggesting a relationship between glycolysis and immune response. CONCLUSIONS: We identified eight glycolysis-related prognostic genes that effectively predicted survival in ovarian cancer. To a certain extent, the newly identified gene signature was related to the tumor microenvironment, especially immune cell infiltration and immune-related gene expression. These findings provide potential biomarkers and therapeutic targets for ovarian cancer.


Assuntos
Neoplasias Ovarianas , Microambiente Tumoral , Feminino , Regulação Neoplásica da Expressão Gênica , Glicólise/genética , Humanos , Neoplasias Ovarianas/genética , Prognóstico , Microambiente Tumoral/genética
9.
JAMA ; 326(10): 916-925, 2021 09 14.
Artigo em Inglês | MEDLINE | ID: mdl-34519801

RESUMO

Importance: Standard first-line therapy for advanced or metastatic esophageal carcinoma is chemotherapy, but the prognosis remains poor. Camrelizumab (an anti-programmed death receptor 1 [PD-1] antibody) showed antitumor activity in previously treated advanced or metastatic esophageal squamous cell carcinoma. Objective: To evaluate the efficacy and adverse events of camrelizumab plus chemotherapy vs placebo plus chemotherapy as a first-line treatment in advanced or metastatic esophageal squamous cell carcinoma. Design, Setting, and Participants: This randomized, double-blind, placebo-controlled, multicenter, phase 3 trial (ESCORT-1st study) enrolled patients from 60 hospitals in China between December 3, 2018, and May 12, 2020 (final follow-up, October 30, 2020). A total of 751 patients were screened and 596 eligible patients with untreated advanced or metastatic esophageal squamous cell carcinoma were randomized. Interventions: Patients were randomized 1:1 to receive either camrelizumab 200 mg (n = 298) or placebo (n = 298), combined with up to 6 cycles of paclitaxel (175 mg/m2) and cisplatin (75 mg/m2). All treatments were given intravenously every 3 weeks. Main Outcomes and Measures: Coprimary end points were overall survival (significance threshold, 1-sided P < .02) and progression-free survival (significance threshold, 1-sided P < .005). Results: Of the 596 patients randomized (median age, 62 years [interquartile range, 56-67 years]; 523 men [87.8%]), 1 patient in the placebo-chemotherapy group did not receive planned treatment. A total of 490 patients (82.2%) had discontinued the study treatment. The median follow-up was 10.8 months. The overall survival for the camrelizumab-chemotherapy group was a median of 15.3 months (95% CI, 12.8-17.3; 135 deaths) vs a median of 12.0 months (95% CI, 11.0-13.3; 174 deaths) for the placebo-chemotherapy group (hazard ratio [HR] for death, 0.70 [95% CI, 0.56-0.88]; 1-sided P = .001). Progression-free survival for camrelizumab plus chemotherapy was a median of 6.9 months (95% CI, 5.8-7.4; 199 progression or deaths) vs 5.6 months (95% CI, 5.5-5.7; 229 progression or deaths) for the placebo-chemotherapy group (HR for progression or death, 0.56 [95% CI, 0.46-0.68]; 1-sided P < .001). Treatment-related adverse events of grade 3 or higher occurred in 189 patients (63.4%) in the camrelizumab-chemotherapy group and 201 (67.7%) in the placebo-chemotherapy group, including treatment-related deaths among 9 patients (3.0%) and 11 patients (3.7%), respectively. Conclusions and Relevance: Among patients with advanced or metastatic esophageal squamous cell carcinoma, the addition of camrelizumab to chemotherapy, compared with placebo and chemotherapy, significantly improved overall survival and progression-free survival. Trial Registration: ClinicalTrials.gov Identifier: NCT03691090.

10.
J Agric Food Chem ; 69(36): 10606-10616, 2021 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-34482683

RESUMO

We previously identified peptides derived from round scad as potential Nrf2 activators. However, the neuroprotection of these peptides is still unclear. In this study, we aimed to investigate the neuroprotective effect of WCPFSRSF against glutamate-induced neurotoxicity, and the memory-improving effects of WCPFSRSF in mice were also explored. Results showed that WCPFSRSF ameliorated oxidative stress by improving the activities of antioxidant enzymes and promoting the Nrf2-mediated endogenous defense system. Moreover, there is an interaction between the up-regulation of Nrf2 and the down-regulation of NFκB induced by the peptide, which was related to the generation of reactive oxygen species (ROS) and could be abolished by the Akt inhibitor LY294002. Further analysis demonstrated that WCPFSRSF may act as a radical scavenger and Nrf2 activator. The antioxidant and anti-inflammatory effects might be related to the Cys and Trp in WCPFSRSF. Moreover, WCPFSRSF could improve spatial memory impairment in sleep-deprived mice. Thus, this work provided evidence for WCPFSRSF as a potential candidate against neurotoxicity and memory deficits.


Assuntos
Fator 2 Relacionado a NF-E2/metabolismo , NF-kappa B/metabolismo , Fármacos Neuroprotetores , Animais , Antioxidantes/farmacologia , Camundongos , Fator 2 Relacionado a NF-E2/genética , Neuroproteção , Fármacos Neuroprotetores/farmacologia , Estresse Oxidativo , Proteínas Proto-Oncogênicas c-akt/genética , Proteínas Proto-Oncogênicas c-akt/metabolismo , Espécies Reativas de Oxigênio , Transdução de Sinais
11.
J Cardiovasc Nurs ; 2021 Sep 07.
Artigo em Inglês | MEDLINE | ID: mdl-34495915

RESUMO

BACKGROUND: The application of latent class growth analysis (LCGA) has been limited in behavioral studies on high-cardiovascular-risk populations. AIM: The current study aimed to identify distinct health behavior trajectories in high-cardiovascular-risk populations using LCGA. We also examined the baseline individual characteristics associated with different health behavior trajectories and determined which trajectory is associated with improved cardiovascular risk outcomes at 52 weeks. METHODS: This secondary analysis of a clinical trial included 200 patients admitted to primary care clinics. Latent class growth analysis was conducted to identify the trajectories of physical activity and dietary intake; these were measured at 4 different time points during a 52-week study period. Analysis of variance/χ2 test was used to assess the associations between baseline individual characteristics and trajectories, and logistic regression analysis was used to identify associations between trajectories and cardiovascular risk outcomes at 52 weeks. RESULTS: Three trajectories were identified for physical activity (low-, moderate-, and high-stable). Risk perception, patient activation, and depressive symptoms predicted the trajectories. High-stable trajectory for physical activity was associated with better cardiovascular risk outcomes at the 52-week follow-up. Two trajectories (low-stable and high-decreasing) were identified for percent energy from fat, but the factors that can predict trajectories were limited. CONCLUSIONS: Interventions are needed to target patients who begin with a lower physical activity level, with the goal of enhanced cardiovascular health. The predictors identified in the study may facilitate earlier and more tailored interventions.

12.
Pharmazie ; 76(9): 431-436, 2021 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-34481534

RESUMO

20(S)-Ginsenoside Rg3 (S-Rg3) has good antitumor activity and has been used in clinical oral antitumor therapy. However, the effect of S-Rg3 on the Hedgehog (Hh) signaling pathway has not been reported. In this study, we used CCK8, cell wound healing, Transwell, and western blotting assays as well as small interfering RNA to decrease GLI1 protein expression to investigate the effect of S-Rg3 on the Hh pathway in A549 cells. The results showed that S-Rg3 substantially inhibited the proliferation, migration, and invasion of A549 cells in a concentration-dependent manner. Furthermore, S-Rg3 had significant regulatory effects on PTCH1 and GLI1, key proteins in the Hh pathway, causing significant upregulation of PTCH1 levels and downregulation of GLI1 expression. After silencing the Hh signaling pathway, the inhibitory effect of S-Rg3 administration on the expression of epithelial mesenchymal transition-related proteins was further enhanced. Molecular dynamics simulations showed that Rg3 molecules could bind stably to PTCH1 protein through hydrophobic interactions, hydrogen bonds, and π-π stacking forces. Thus, S-Rg3 can regulate Hh signaling pathway transduction in A549 cells to inhibit lung cancer cell proliferation, migration, invasion, and epithelial mesenchymal transition.

13.
Sci Total Environ ; 805: 150292, 2021 Sep 12.
Artigo em Inglês | MEDLINE | ID: mdl-34536857

RESUMO

Since the loss of honeybees in hives could have a greater impact on colony health than those of their foraging bees, it is imperative to know beehives' pesticide exposure via oral ingestion of contaminated in-hive matrices. Here, a 4-year monitoring survey of 64 pesticide residues in pollen, nectar and related beehive matrices (beebread and honey) from China's main honey producing areas was carried out using a modified version of the QuEChERS multi-residue method. The results showed that 93.6% of pollen, 81.5% of nectar, 96.6% of beebread, and 49.3% of honey containing at least one target pesticide were detected either at or above the method detection limits (MDLs), respectively, with up to 19 pesticides found per sample. Carbendazim was the most frequently detected pesticide (present in >85% of the samples), and pyrethroids were also abundant (median concentration = 134.3-279.0 µg/kg). The transfer of pesticides from the environment into the beehive was shown, but the pesticide transference ratio may be affected by complex factors. Although the overall risk to colony health from pesticides appears to be at an acceptable level, the hazard quotient/hazard index (HQ/HI) value revealed that pyrethroids were clearly the most influential contributor, accounting for up to 45% of HI. Collectively, these empirical findings provide further insights into the extent of contamination caused by agricultural pesticide use on honeybee colonies.

14.
Water Res ; 204: 117656, 2021 Sep 11.
Artigo em Inglês | MEDLINE | ID: mdl-34537628

RESUMO

The current lack of research on the evaluation of marine ecosystem services makes the value of marine protection, development and restoration underestimated during the decision-making process. Based on the non-monetary ecosystem service evaluation framework, a marine ecosystem service classification and accounting method has been established in this study, and the world's coastal ecosystem services have been measured as an example. The results show that (1) the world's coastal ecosystem service value is about 4.13E+23 sej/yr, of which Asia and North America contribute about 55% of the total service value; (2) the top ten countries in terms of the world's coastal ecosystem service values are Canada, Indonesia, Australia, the United States, Brazil, the Russian Federation, Norway, the Philippines, Mexico, and China, which contribute about 60% of the total service value; (3) estuaries have the highest ecosystem service values, followed by mangroves, seagrass beds, tidal flats, salt marshes, and warm water coral reefs; (4) developed countries can make better use of their coastal resources and pay more attention to the marine protection while the opposite is true in developing countries, which means that developed countries still occupy an advantageous position in the process of marine protection, development and utilization. This study assesses the coastal ecosystem service values in various coastal countries from the perspective of ecosystem contributors, emphasizes the importance of protecting them in marine management, and provides a certain reference basis and theoretical support for decision-makers in formulating marine-related protection and development strategies.

15.
Cell Chem Biol ; 2021 Sep 14.
Artigo em Inglês | MEDLINE | ID: mdl-34547225

RESUMO

Proprotein convertase subtilisin/kexin type 9 (PCSK9) regulates plasma low-density lipoprotein cholesterol (LDL-C) levels by promoting hepatic LDL receptor (LDLR) degradation. Therapeutic antibodies that disrupt PCSK9-LDLR binding reduce LDL-C concentrations and cardiovascular disease risk. The epidermal growth factor precursor homology domain A (EGF-A) of the LDLR serves as a primary contact with PCSK9 via a flat interface, presenting a challenge for identifying small molecule PCSK9-LDLR disruptors. We employ an affinity-based screen of 1013in vitro-translated macrocyclic peptides to identify high-affinity PCSK9 ligands that utilize a unique, induced-fit pocket and partially disrupt the PCSK9-LDLR interaction. Structure-based design led to molecules with enhanced function and pharmacokinetic properties (e.g., 13PCSK9i). In mice, 13PCSK9i reduces plasma cholesterol levels and increases hepatic LDLR density in a dose-dependent manner. 13PCSK9i functions by a unique, allosteric mechanism and is the smallest molecule identified to date with in vivo PCSK9-LDLR disruptor function.

16.
Oncol Rep ; 46(5)2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34549306

RESUMO

Colorectal cancer (CRC) is a common malignancy with significant prevalence and mortality rates. Circular RNA FOXO3 (circ­FOXO3; hsa_circ_0006404) has been reported to be involved in cancer regulation; however, its role in CRC is yet to be fully elucidated. Therefore, the aim of the present study was to investigate the effect of circ­FOXO3 on CRC progression and identify its underlying mechanism. In the present study, the expression of circ­FOXO3 was investigated in CRC tissues and cells via reverse transcription­quantitative PCR. A Cell Counting Kit­8 and colony formation assays were used to assess cell proliferation. The cell migratory and invasive abilities were detected using the Transwell migration and invasion assays. The luciferase assay and RNA pull­down assay were conducted to verify the relationship of circ­FOXO3, microRNA (miR)­543 and Large tumor suppressor kinase 1 (LATS1). The results demonstrated that circ­FOXO3 expression was downregulated in CRC tissues and cells, and was associated with poor overall survival of patients with CRC. Moreover, circ­FOXO3 was associated with tumor size, distant metastasis, differentiation, lymph node metastasis and TMN stages of patients with CRC. circ­FOXO3 overexpression suppressed CRC cell proliferation, migration and invasion. Luciferase assay and RNA pull­down assay results indicated that circ­FOXO3 functioned as a sponge for miR­543. In addition, circ­FOXO3 increased the expression of LATS1 via sponging miR­543, thus inhibiting CRC cell aggressive features. Collectively, the present results suggested that circ­FOXO3 inhibited CRC metastasis and progression via elevated LATS1 expression by sponging miR­543. Therefore, circ­FOXO3 may be a promising target for CRC therapy.

17.
Mol Oncol ; 2021 Aug 11.
Artigo em Inglês | MEDLINE | ID: mdl-34382324

RESUMO

Dysregulation of deubiquitination has been reported to contribute to carcinogenesis. However, the function and mechanism of deubiquitinating enzyme 26S proteasome non-ATPase regulatory subunit 14 (PSMD14) in the progression of ovarian cancer (OV), the deadliest gynecological cancer, still remains to be characterized. The present study demonstrated that PSMD14 was overexpressed in OV tissues and its higher levels correlated with a higher International Federation of Gynecology and Obstetrics (FIGO) stage in OV patients. A high level of PSMD14 expression was related to poor survival in OV patients. Knockdown and overexpression experiments elucidated that PSMD14 stimulated OV cell proliferation, invasion, and migration in vitro. Repression of PSMD14 suppressed OV tumor growth in vivo. PSMD14 inhibitor O-phenanthroline (OPA) effectively attenuated malignant behaviors of OV cells in vitro and OV tumor growth in vivo. Mechanistically, we uncovered that PSMD14 was involved in post-translational regulation of pyruvate kinase M2 isoform (PKM2). PSMD14 decreased K63-linked ubiquitination on PKM2, downregulated the ratio of PKM2 tetramers to dimers and monomers, and subsequently diminished pyruvate kinase activity and induced nuclear translocation of PKM2, contributing to aerobic glycolysis in OV cells. Collectively, our findings highlight the potential roles of PSMD14 as a biomarker and therapeutic candidate for OV.

18.
J Dig Dis ; 2021 Aug 27.
Artigo em Inglês | MEDLINE | ID: mdl-34453408

RESUMO

OBJECTIVE: To confirm the hypothesis that thiopurines are better than mesalamine for preventing postoperative recurrence of Crohn's disease (CD) in patients with more than two risk factors. METHODS: In total 87 consecutive CD patients who underwent curative ileocolonic resection and ileocolic anastomosis were retrospectively recruited, including 43 prescribed with thiopurines and 44 with mesalamine after surgery. Four risk factors were predefined for subgroup analyses: smoking, penetrating disease, perianal disease and previous resection. End-points included clinical (Crohn's disease activity index >200) and endoscopic recurrence (Rutgeerts score ≥i2) within 52 weeks. RESULTS: There were no significant differences in clinical (37.2% vs 54.5%, P = 0.105) and endoscopic recurrence (55.8% vs 75.0%, P = 0.060) between the thiopurines and mesalamine groups by week 52. In the subgroup analysis of patients with two or more risk factors, clinical (35.7% vs 81.8%, P = 0.042) and endoscopic recurrence (64.3% vs 100%, P= 0.046) were less frequent in the thiopurine group than the mesalamine group. With one additional risk factor, the risk of endoscopic recurrence in the thiopurines group increased by 2.201-fold (95% confidence interval [CI] 1.178-4.115), adjusted for treatment intervention. While the risk of clinical and endoscopic recurrence in patients treated with mesalamine increased by 3.383-fold and 5.884-fold (95% CI 1.260-9.081 and 1.598-21.662). Three patients treated with thiopurines withdrew for adverse events. CONCLUSIONS: Thiopurines may be superior to mesalamine for preventing postoperative recurrence of CD in patients with two or more risk factors. Caution is needed in light of the adverse events caused by thiopurines.

19.
Eur J Radiol ; 143: 109909, 2021 Aug 16.
Artigo em Inglês | MEDLINE | ID: mdl-34455133

RESUMO

PURPOSE: Evaluating degree of hepatic steatosis is of great value for prognosis of liver transplantation. There is an urgent need for a non-invasive method to assess hepatic steatosis grade of donor livers. Purpose of our study was to evaluate diagnostic accuracy of attenuation coefficient estimation (ACE) by reference frequency method (RFM) in detecting hepatic steatosis of donor livers. METHOD: We retrospectively enrolled 62 potential liver donors which underwent ACE by RFM ex-vivo, in-vivo or both. We acquired raw data of B-mode images of liver parenchyma and offline-processes for attenuation estimation. Finally, we calculated and compared diagnostic performance of ACEs for steatosis grade detection and used histological results as the gold standard. RESULTS: ACEs with none, mild and moderate hepatic steatosis were 0.57, 0.73 and 0.80 dB/cm/MHz in potential donor livers. The cutoff value to diagnose mild hepatic steatosis was 0.63 dB/cm/MHz and 0.77 dB/cm/MHz for moderate hepatic steatosis, and values for the area under the receiver operating characteristic curve for diagnosis of mild and moderate hepatic steatosis were 0.92 and 0.90, respectively. CONCLUSIONS: According to our results, ACE by RFM is an accurate non-invasive method in detecting hepatic steatosis, which may be of great help for clinical evaluation of donor livers before liver transplantation.

20.
Science ; 373(6555): 692-696, 2021 08 06.
Artigo em Inglês | MEDLINE | ID: mdl-34353954

RESUMO

Incorporating passive radiative cooling structures into personal thermal management technologies could effectively defend humans against intensifying global climate change. We show that large-scale woven metafabrics can provide high emissivity (94.5%) in the atmospheric window and high reflectivity (92.4%) in the solar spectrum because of the hierarchical-morphology design of the randomly dispersed scatterers throughout the metafabric. Through scalable industrial textile manufacturing routes, our metafabrics exhibit desirable mechanical strength, waterproofness, and breathability for commercial clothing while maintaining efficient radiative cooling ability. Practical application tests demonstrated that a human body covered by our metafabric could be cooled ~4.8°C lower than one covered by commercial cotton fabric. The cost-effectiveness and high performance of our metafabrics present substantial advantages for intelligent garments, smart textiles, and passive radiative cooling applications.

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