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1.
Neural Regen Res ; 18(2): 344-349, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-35900428

RESUMO

The current animal models of stroke primarily model a single intracerebral hemorrhage (ICH) attack, and there is a lack of a reliable model of recurrent ICH. In this study, we established 16-month-old C57BL/6 male mouse models of ICH by injecting collagenase VII-S into the left striatum. Twenty-one days later, we injected collagenase VII-S into the right striatum to simulate recurrent ICH. Our results showed that mice subjected to bilateral striatal hemorrhage had poorer neurological function at the early stage of hemorrhage, delayed recovery in locomotor function, motor coordination, and movement speed, and more obvious emotional and cognitive dysfunction than mice subjected to unilateral striatal hemorrhage. These findings indicate that mouse models of bilateral striatal hemorrhage can well simulate clinically common recurrent ICH. These models should be used as a novel tool for investigating the pathogenesis and treatment targets of recurrent ICH.

2.
Langmuir ; 38(37): 11236-11249, 2022 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-36074728

RESUMO

Hydrophobic surface drag reduction techniques are effective in reducing the frictional resistance of fluids, the adsorption of liquid molecules on hydrophobic surfaces can reflect the resistance to fluid flow through such solid surfaces. Based on molecular simulation technology, we investigate the adsorption characteristics of water molecules on hydrophobic surfaces to achieve rapid screening of hydrophobic materials in fire-fighting water supply systems. The Monte Carlo method was used to simulate the adsorption process of polymers and to analyze the effects of temperature and fixed adsorption quantity. Contact angle tests were also done to verify polymer hydrophobicity. The isothermal adsorption heat, water molecule distribution, and energy distribution were studied by molecular mechanics and molecular dynamics methods. Then, adsorption localization simulations and electrostatic potential distributions were used to predict possible adsorption sites on hydrophobic surfaces and single-molecule chains. Finally, the interaction energy, diffusion coefficient, and free volume were investigated to explain the adsorption mechanism at the molecular level. Simulation results show that, overall, PTFE was more hydrophobic and PES was more hydrophilic and at 298 K, the number of adsorbed water molecules was ranked as follows: PTFE < PVDF < PVC < PMMA < PPS < CSM < BD-HDI < BD-MDI < BD-TDI < PES. Furthermore, PTFE, PVDF, PVC, PES, and PPS have more stable adsorption configurations on the (0 -1 0) surface. According to the findings, hydrogen bonding dominates the interaction between water molecules and hydrophilic polymers, whereas π-π interactions increase water molecules' diffusion resistance in polymers with benzene rings. In addition, PES contains many sulfone groups and ether bonds, which disorganize the chain arrangement to provide more free volume, whereas the water adsorption rate of PTFE is reduced because its molecular chains are less convoluted and more organized.

3.
Front Pharmacol ; 13: 948173, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36059969

RESUMO

Background: Cordyceps is a precious Chinese herbal medicine with rich bio-active ingredients and is used for regulating arrhythmia alongside routine treatments. However, the efficacy and potential mechanisms of Cordyceps on patients with arrhythmia remain unclear. Methods: Randomized controlled trials of bradycardia treatment with Cordyceps were retrieved from diverse databases and available data. Dichotomous variables were expressed as a risk ratio (RR) with a 95% confidence interval (CI). Continuous variables were expressed as a standardized mean difference (SMD) with a 95% CI. Network pharmacology was used to identify potential targets of Cordyceps for arrhythmia. Metascape was used for gene ontology (GO) and genome (KEGG) pathway enrichment analysis. Results: Nineteen trials included 1,805 patients with arrhythmia, of whom 918 were treated with Ningxinbao capsule plus routine drugs, and, as a control, 887 were treated with only routine drugs. Six trials reported on bradycardia and the other 13 on tachycardia. Treatment with Cordyceps significantly improved the total efficacy rate in both bradycardia (RR = 1.24; 95% CI, 1.15 to 1.35; Pz <0.00001) and tachycardia (RR = 1.27; 95% CI, 1.17 to 1.39; Pz <0.00001). Cordyceps also had beneficial secondary outcomes. No serious adverse events occurred in patients treated with Cordyceps. The results of KEGG pathway enrichment analysis were mainly connected to adrenergic signaling in cardiomyocytes and the PI3K-Akt signaling pathway. IL6, TNF, TP53, CASP3, CTNNB1, EGF, and NOS3 might be key targets for Cordyceps in the treatment of arrhythmia. Conclusion: This study confirmed that Cordyceps has a certain positive effect on the treatment of arrhythmia and that its main mechanism may be through the regulation of adrenergic signaling in cardiomyocytes and the PI3K-Akt signaling pathway.

4.
Contrast Media Mol Imaging ; 2022: 7998725, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36072626

RESUMO

In order to investigate the clinical efficacy of acupuncture combined with traditional Chinese medicine fumigation in the treatment of rheumatoid arthritis (RA) by meta-analysis, literature related to the treatment of rheumatoid arthritis by acupuncture combined with traditional Chinese medicine fumigation are searched in line with the research direction. Meta-analysis is conducted by RevMan 5.2 software. A total of 17 literature are included and the publication bias of the included literature is low. The experimental results show that acupuncture combined with traditional Chinese medicine fumigation can reduce the inflammatory response and clinical symptoms of RA patients, and the addition of acupuncture can improve the clinical efficacy, which has a certain feasibility of promotion.


Assuntos
Terapia por Acupuntura , Artrite Reumatoide , Terapia por Acupuntura/métodos , Artrite Reumatoide/terapia , Fumigação , Humanos , Medicina Tradicional Chinesa , Resultado do Tratamento
5.
Nurs Open ; 2022 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-36086928

RESUMO

AIM: The primary objective of this study was to assess the patient safety culture in a general hospital in Shanghai, China, through a modified Manchester Patient Safety Framework (MaPSaF). DESIGN: This study has a qualitative interview design. Data were collected through group interviews and analyses performed through content analysis. METHODS: The MaPSaF was translated into Chinese and used to assess the patient safety culture in a large general hospital in Shanghai, China. Group interviews using the MaPSaF were conducted with 15 nurses in the obstetric ward. Participants rated their safety practice individually on each of the nine MaPSaF safety culture dimensions. The dimensions and scores were then collectively discussed and a practice-wide consensus score for each dimension was agreed. Discussions were recorded, transcribed and analysed to assess patient safety in the obstetric ward. RESULTS: It took about 2 hr to complete the discussion focusing on patients' safety employing the MaPSaF. Most participants recognized the process as acceptable and useful. The MaPSaF directed team discussion about patient safety issues and facilitated communication, prompting some practice changes. All participants responded positively to the discussion and perceived MaPSaF as a good safety culture assessment tool, with clear, comprehensive and understandable entries. The process demonstrated that the department of obstetrics in the hospital already had a positive patient safety culture, but certain areas were highlighted as still needing improvement. Based on participants' positive experience and perception of the MaPSaF, it can be concluded that there is potential benefit in its adaptation and use in obstetrics wards of Chinese hospitals. The MaPSaF has the potential to strengthen existing safety cultures and improve general safety through collaborative measures.

6.
Food Chem ; 402: 134257, 2022 Sep 17.
Artigo em Inglês | MEDLINE | ID: mdl-36148765

RESUMO

Although intelligent films containing various anthocyanins have exhibited a good pH-response, high light-transmittance makes it difficult to accurately observe color changes in monitoring food freshness. In this study, black corn seed powder (BCSP) containing anthocyanins, starch, lipid and fibers, was used to provide κ-carrageenan film (κCF) with simultaneous intelligent color change and high haze. As the mass ratio of BCSP to κ-carrageenan increased from 1:4 to 1:1, the haze of composite films increased from 49.44 % to 79.25 %, the transmittance decreased from 43.62 % to 18.90 %, respectively. The composite films turned from red to green along with the increase of pH from 2 to 10. When the TVB-N of pork increased from 2.7 ± 0.15 mg/100 g to 14.03 ± 0.14 mg/100 g, the 50BC50κC changed from pink to greyish-green and the haze increased up to 91.83 %, which will make it more visible and effective to indicate food freshness and popular for use.

7.
Cell Death Dis ; 13(9): 776, 2022 Sep 08.
Artigo em Inglês | MEDLINE | ID: mdl-36075896

RESUMO

Numerous studies have shown that circRNAs are aberrantly expressed in various cancers and play a significant role in tumor progression. However, the molecular mechanisms of circRNAs in triple-negative breast cancer (TNBC) remain ambiguous. By intersecting throughput data and qRT-PCR results from tissues and cell lines, circ-TRIO was identified as a potential oncogenic regulator of TNBC. Moreover, circ-TRIO expression was detected in TNBC tissues and was correlated with the recurrence and prognosis of TNBC patients. The circular characteristics of circ-TRIO were verified by RNase R and CHX assays. Functionally, the knockdown of circ-TRIO inhibited the proliferation, migration and invasion of TNBC cells, while the overexpression of circ-TRIO resulted in the opposite impacts. Mechanistically, a dual luciferase reporter assay and RNA immunoprecipitation were performed and indicated that circ-TRIO could combine with miR-432-5p to regulate the expression of coiled-coil domain containing 58 (CCDC58). In summary, our study illustrates that circ-TRIO plays an important role in the progression of TNBC by regulating the miR-432-5p/CCDC58 axis, which could broaden our insight into the underlying mechanisms and provide a novel prognostic marker of TNBC in the clinic.


Assuntos
MicroRNAs , Fatores de Transcrição/metabolismo , Neoplasias de Mama Triplo Negativas , Linhagem Celular Tumoral , Movimento Celular/genética , Proliferação de Células/genética , Regulação Neoplásica da Expressão Gênica/genética , Humanos , MicroRNAs/metabolismo , RNA Circular/genética , Neoplasias de Mama Triplo Negativas/genética , Neoplasias de Mama Triplo Negativas/patologia
8.
J Fam Psychol ; 2022 Sep 22.
Artigo em Inglês | MEDLINE | ID: mdl-36136830

RESUMO

To address a gap in the translational research on marital and family conflict intervention, we used a series of multilevel models to examine how interparental constructive conflict behavior, conflict resolution, and conflict knowledge improved up to 3 years postintervention in the Family Communication Project (FCP). The FCP was an experimental, longitudinal intervention focused on family conflict, communication, and adolescent adjustment. Participants consisted of adolescents and their two primary caregivers (N = 225 families). Each family was randomly assigned to one of two treatment groups (parent-adolescent or parent only) or two control groups (self-study or no treatment). Relative to controls, who showed no statistically significant improvement in conflict behavior, resolution, or knowledge, parents in the two-treatment conditions showed improvement in a nonlinear fashion. Modeled with piece-wise slopes, average change trajectories showed statistically significant increases from pretest to posttest, followed by declines but overall significant sustained growth by 3 years. Baseline marital hostility moderated this change, whereby couples who had higher levels of baseline marital hostility responded more favorably to treatment, but also declined more rapidly. Fathers in the study were shown to have stronger long-term treatment effects for conflict knowledge relative to mothers, and higher marital adjustment among fathers at baseline predicted less decline in dyadic conflict resolution after the intervention. The results highlight how examining within-family changes over time and between-family differences in change trajectories can contribute to practical insights about when and for whom interventions are most effective. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

9.
Front Oncol ; 12: 962970, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36059675

RESUMO

Background: Stellera chamaejasme L (RXLD) has been demonstrated with good clinical effects and medicinal value in the treatment of cancer in vivo and in vitro. Specifically, RXLD can eliminate aggregation accumulation, which is depicted as a vital characteristic feature of intracranial tumors. The potential pharmacological mechanisms of anti-glioblastoma (GBM) have not been adequately identified. Methods: The 3D structures of the chemical ingredients in RXLD were imported into the PharmMapper database to construct the pharmacophore models. The gene targets of GBM were obtained from databases. The pharmacophore-targets network and the protein-protein interactions (PPI) were constructed using the String database and were visualized by using Cytoscape. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes pathway (KEGG) enrichment analyses were conducted using Bioconductor software. Cytoscape visualized the relationship of pathways and candidate genes to screen for key target genes. Software packages PyMOL, AutoDock, and Vina acquired the molecular docking results. In vitro experiments were undertaken to characterize RXLD extracts' effects on A172 cell line proliferation, viability, apoptosis, cell cycle, cell wound healing, cell migration, reactive oxygen species generation, and mitochondrial membrane potential. The expression of core genes in the related pathways was detected by Western blotting. Results: We identified 216 potential targets associated with GBM. The core components in RXLD were neochamaejasmin A, wikstrol A, isochamaejasmin, chamaejasmine, and subtoxin A. The undertaken GO enrichment analysis revealed that oxidative stress, cell proliferation, cell cycle, cell invasion, and cell migration were involved in the biological processes. The KEGG enrichment analysis revealed that the crucial pathway was MAPK pathway, while HRAS, PRKCB, MAPK9, CCND1, and TP53 were distributed in core locations. A total of seven RXLD pharmacophores demonstrated strong spontaneous docking activities with MAPK9. In vitro assays indicated that RXLD can induce apoptosis, block the cell cycle in the G2/M and S phases, inhibit cell migration via the Wnt/ß-catenin pathway, and inhibited p62/Nrf2 pathway. Conclusions: We speculate that the RAS/MAPK pathway might be an upstream pathway through which the RXLD exerts its anti-GBM effects and might be able to regulate further the Wnt/ß-catenin, the oxidative stress, and the ferroptosis pathways.

10.
J Cardiothorac Surg ; 17(1): 225, 2022 Sep 02.
Artigo em Inglês | MEDLINE | ID: mdl-36056376

RESUMO

BACKGROUND: Previous study found that C-reactive protein (CRP) can predict bleeding after on-pump CABG. To evaluate whether preoperative C-reactive protein (CRP) can be a novel marker of postoperative bleeding in patients having off-pump coronary artery bypass grafting (CABG). METHODS: This is a retrospective cohort study. Multiple variable regression analyses were performed. 537 patients undergoing off-pump isolated primary CABG at Fuwai Hospital from September 2017 to July 2018 were recorded. The primary endpoint was bleeding volume within 24 h after surgery. RESULTS: Data of 537 patients undergoing off-pump isolated primary CABG at Fuwai Hospital were recorded. The correlations between bleeding volume within 24 h after surgery and preoperative data were analyzed with univariate and multivariate linear regression. Much more preoperative CRP concentration (B = -0.089, P < 0.05) was associated with less postoperative bleeding volume and fibrinogen (B = 0.594, p < 0.001). CONCLUSIONS: Preoperative CRP concentration is independently correlated with the postoperative volume of bleeding within 24 h. CRP may become a novel coagulation index in coronary artery atherosclerotic disease.


Assuntos
Ponte de Artéria Coronária sem Circulação Extracorpórea , Doença da Artéria Coronariana , Proteína C-Reativa , Estudos de Coortes , Ponte de Artéria Coronária/efeitos adversos , Ponte de Artéria Coronária sem Circulação Extracorpórea/efeitos adversos , Doença da Artéria Coronariana/cirurgia , Humanos , Complicações Pós-Operatórias , Hemorragia Pós-Operatória , Estudos Retrospectivos , Resultado do Tratamento
11.
Science ; : eabo7923, 2022 Sep 08.
Artigo em Inglês | MEDLINE | ID: mdl-36074823

RESUMO

Translational regulation plays a critical role during the oocyte-to-embryo transition (OET) and zygotic genome activation (ZGA). Here, we integrated ultra-low-input Ribo-seq with mRNA-seq to co-profile the translatome and transcriptome in human oocytes and early embryos. Comparison with mouse counterparts identified widespread differentially translated genes functioning in epigenetic reprogramming, transposon defense, and small RNA biogenesis, in part driven by species-specific regulatory elements in 3' untranslated regions. Moreover, PRD-like homeobox transcription factors, including TPRXL, TPRX1, and TPRX2, are highly translated around ZGA. TPRX1/2/L knockdown leads to defective ZGA and preimplantation development. Ectopically expressed TPRXs bind and activate key ZGA genes in human embryonic stem cells. These data reveal the conservation and divergence of translation landscapes during OET and identify critical regulators of human ZGA.

12.
Commun Biol ; 5(1): 943, 2022 Sep 09.
Artigo em Inglês | MEDLINE | ID: mdl-36085336

RESUMO

Interferon regulatory factor 3 (IRF3) is a key transcription factor required for the secretion of type I interferons (IFN-α/ß) and initiation of antiviral immune response. However, the negative feedback regulator of IRF3-directed antiviral response remains unknown. In this study, we demonstrated that viral infection induced the interaction of the transducer of ERBB2.1 (TOB1) with IRF3, which bound to the promoter region of Ifnb1 in macrophages. TOB1 inhibited Ifnb1 transcription by disrupting IRF3 binding and recruiting histone deacetylase 8 (HDAC8) to the Ifnb1 promoter region. Consequently, TOB1 attenuated IRF3-directed IFN-ß expression in virus-infected macrophages. Tob1 deficiency enhanced antiviral response and suppressed viral replication in vivo. Thus, we identified TOB1 as a feedback inhibitor of host antiviral innate immune response and revealed a mechanism underlying viral immune escape.


Assuntos
Fator Regulador 3 de Interferon , Interferon beta , Antivirais , Histona Desacetilases/genética , Histona Desacetilases/metabolismo , Fator Regulador 3 de Interferon/genética , Fator Regulador 3 de Interferon/metabolismo , Interferon beta/genética , Transdutores
13.
Front Cardiovasc Med ; 9: 881881, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35966564

RESUMO

Objectives: Postoperative major bleeding is a common problem in patients undergoing cardiac surgery and is associated with poor outcomes. We evaluated the performance of machine learning (ML) methods to predict postoperative major bleeding. Methods: A total of 1,045 patients who underwent isolated coronary artery bypass graft surgery (CABG) were enrolled. Their datasets were assigned randomly to training (70%) or a testing set (30%). The primary outcome was major bleeding defined as the universal definition of perioperative bleeding (UDPB) classes 3-4. We constructed a reference logistic regression (LR) model using known predictors. We also developed several modern ML algorithms. In the test set, we compared the area under the receiver operating characteristic curves (AUCs) of these ML algorithms with the reference LR model results, and the TRUST and WILL-BLEED risk score. Calibration analysis was undertaken using the calibration belt method. Results: The prevalence of postoperative major bleeding was 7.1% (74/1,045). For major bleeds, the conditional inference random forest (CIRF) model showed the highest AUC [0.831 (0.732-0.930)], and the stochastic gradient boosting (SGBT) and random forest models demonstrated the next best results [0.820 (0.742-0.899) and 0.810 (0.719-0.902)]. The AUCs of all ML models were higher than [0.629 (0.517-0.641) and 0.557 (0.449-0.665)], as achieved by TRUST and WILL-BLEED, respectively. Conclusion: ML methods successfully predicted major bleeding after cardiac surgery, with greater performance compared with previous scoring models. Modern ML models may enhance the identification of high-risk major bleeding subpopulations.

14.
Nucl Med Commun ; 43(9): 1042-1052, 2022 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-35950358

RESUMO

OBJECTIVE: To explore whether the markedly fluorine-18 fluorodeoxyglucose (18F-FDG) uptake in the liver (named hepatic superscan) is a specific manifestation of malignant involvement. METHODS: From January 2014 to June 2019, 23 patients with such presentations were retrospectively reviewed. 18F-FDG uptake was semiquantified using maximal standardized uptake value (SUVmax), liver to cerebellum (L/C) ratio, liver to mediastinum (L/M) ratio, mean standardized uptake value (SUVmean), peak standardized uptake value (SUVpeak), metabolic tumor volume (MTV) and total lesion glycolysis (TLG). Some related laboratory examinations were also collected and analyzed. For comparison, 37 patients with mildly and moderately uptake in the liver were selected as the control group. RESULTS: The hepatic SUVmax, L/C ratio, L/M ratio, SUVmean, MTV and TLG of the superscan group were significantly higher than that of mild- or moderate-uptake group (P < 0.005). Malignant hematological tumors accounted for 91.3% of the superscan group, which was significantly higher than 51.4% of mild- or moderate-uptake group (P = 0.004). ß2-microglobulin was observed to be significantly higher in the superscan group compared with mild- or moderate-uptake group (P < 0.001), but not lactate dehydrogenase (LDH) (P = 0.409). On the contrary, C-reactive protein (CRP) was significantly higher in mild- or moderate-uptake group than that in the superscan group (P < 0.001). CONCLUSION: Our study demonstrates that hepatic superscan is a strong indicator of malignant hematological tumors invading the liver.


Assuntos
Neoplasias Hematológicas , Leucemia , Linfoma , Radioisótopos de Flúor , Fluordesoxiglucose F18 , Humanos , Fígado/diagnóstico por imagem , Linfoma/diagnóstico por imagem , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Prognóstico , Compostos Radiofarmacêuticos , Estudos Retrospectivos , Carga Tumoral
15.
Front Immunol ; 13: 946825, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35911688

RESUMO

Background: Guillain-Barré syndrome (GBS) is the most common severe acute paralytic neuropathy, with a mortality rate of 5% and permanent sequelae rate of 10%. Currently, the cause of GBS remains unclear. Therefore, we sought to determine potential predictors for GBS and its severity. Methods: A case-control study was performed at Tiantan Hospital in Beijing from January 2017 to December 2021. Laboratory and clinical characteristics were assessed in recruited GBS patients and healthy control individuals (matched by sex and age). The potential risk factors for GBS and severe GBS were assessed using a logistic regression analysis. The mRNA levels of toll-like receptor 4 (TLR4), toll-like receptor 2 (TLR2) and nuclear factor κB (NF-κB) in GBS patients and control PBMCs were detected by fluorescence quantitative PCR. THP-1 cells were costimulated with LPS and free cholesterol to demonstrate the effect of free cholesterol on monocyte activation. Results: A total of 147 GBS patients and 153 healthy individuals were included in the study. Logistic regression analyses showed that preceding infection, alcohol consumption, remnant cholesterol, homocysteine and the dyslipidemia index were correlated with a higher risk of GBS. In contrast, increased HDL cholesterol was correlated with a lower risk of GBS. Moreover, remnant cholesterol and the dyslipidemia index were significantly correlated with severe GBS. The mRNA levels of TLR4, TLR2 and NF-κB in the PBMCs of GBS patients were significantly higher than those of healthy individuals. LPS activated THP-1 cells, and free cholesterol treatment increased the expression of TLR4, TLR2, NF-κB and IL-1ß mRNA in LPS-activated THP-1 cells. Conclusion: Dyslipidemia was correlated with the risk of GBS and severe GBS. Remnant cholesterol may promote the activation of monocytes in GBS patients. It may be valuable to control lipid levels in the prevention of GBS and severe GBS.


Assuntos
Colesterol , Dislipidemias , Síndrome de Guillain-Barré , Monócitos , Estudos de Casos e Controles , Dislipidemias/complicações , Síndrome de Guillain-Barré/etiologia , Síndrome de Guillain-Barré/metabolismo , Humanos , Lipopolissacarídeos , Monócitos/metabolismo , NF-kappa B , RNA Mensageiro , Fatores de Risco , Receptor 2 Toll-Like/genética , Receptor 4 Toll-Like/genética
16.
J Hematol Oncol ; 15(1): 122, 2022 08 29.
Artigo em Inglês | MEDLINE | ID: mdl-36038948

RESUMO

BACKGROUND: Circular RNAs (circRNAs) represent a novel type of regulatory RNA characterized by high evolutionary conservation and stability. CircRNAs are expected to be potential diagnostic biomarkers and therapeutic targets for a variety of malignancies. However, the regulatory functions and underlying mechanisms of circRNAs in triple-negative breast cancer (TNBC) are largely unknown. METHODS: By using RNA high-throughput sequencing technology, qRT-PCR and in situ hybridization assays, we screened dysregulated circRNAs in breast cancer and TNBC tissues. Then in vitro assays, animal models and patient-derived organoids (PDOs) were utilized to explore the roles of the candidate circRNA in TNBC. To investigate the underlying mechanisms, RNA pull-down, RNA immunoprecipitation (RIP), co immunoprecipitation (co-IP) and Western blotting assays were carried out. RESULTS: In this study, we demonstrated that circRNA-CREIT was aberrantly downregulated in doxorubicin resistant triple-negative breast cancer (TNBC) cells and associated with a poor prognosis. The RNA binding protein DHX9 was responsible for the reduction in circRNA-CREIT by interacting with the flanking inverted repeat Alu (IRAlu) sequences and inhibiting back-splicing. By utilizing in vitro assays, animal models and patient-derived organoids, we revealed that circRNA-CREIT overexpression significantly enhanced the doxorubicin sensitivity of TNBC cells. Mechanistically, circRNA-CREIT acted as a scaffold to facilitate the interaction between PKR and the E3 ligase HACE1 and promoted proteasomal degradation of PKR protein via K48-linked polyubiquitylation. A reduced PKR/eIF2α signaling axis was identified as a critical downstream effector of circRNA-CREIT, which attenuated the assembly of stress granules (SGs) to activate the RACK1/MTK1 apoptosis signaling pathway. Further investigations revealed that a combination of the SG inhibitor ISRIB and doxorubicin synergistically inhibited TNBC tumor growth. Besides, circRNA-CREIT could be packaged into exosomes and disseminate doxorubicin sensitivity among TNBC cells. CONCLUSIONS: Our study demonstrated that targeting circRNA-CREIT and SGs could serve as promising therapeutic strategies against TNBC chemoresistance.


Assuntos
MicroRNAs , Neoplasias de Mama Triplo Negativas , eIF-2 Quinase/metabolismo , Animais , Linhagem Celular Tumoral , Proliferação de Células/genética , Doxorrubicina/farmacologia , Doxorrubicina/uso terapêutico , Regulação Neoplásica da Expressão Gênica , Humanos , MicroRNAs/genética , RNA/genética , RNA Circular/genética , Grânulos de Estresse , Neoplasias de Mama Triplo Negativas/tratamento farmacológico , Neoplasias de Mama Triplo Negativas/genética , Neoplasias de Mama Triplo Negativas/metabolismo , Ubiquitina-Proteína Ligases/genética , Ubiquitina-Proteína Ligases/metabolismo
17.
Arch Gerontol Geriatr ; 103: 104786, 2022 Aug 04.
Artigo em Inglês | MEDLINE | ID: mdl-35961107

RESUMO

Oxidative stress plays an important role in the pathogenesis of Alzheimer's disease (AD). As a potent antioxidant, serum bilirubin is decreased in AD and may be related to its pathogenesis, but the causal association between serum bilirubin and AD has not been reported. This was investigated in the present study by bidirectional two-sample Mendelian randomization (MR) analysis. Genetic instruments at the genome-wide significance level (P < 5 × 10-8) were selected from the United Kingdom Biobank (n = 342,829). Summary-level AD data were obtained from a large-scale genome-wide association study (n = 63,926). Causal estimates were evaluated using the inverse variance weighted (IVW) approach and other five complementary methods. MR-Egger, IVW and MR pleiotropy residual sum and outlier (MR-PRESSO) methods were used for sensitivity analyses. The results showed that there was no significant association between serum total bilirubin and AD (odds ratio=1.003, 95% confidence interval: 0.967-1.041, P = 0.865). Inverse MR revealed that serum total bilirubin was increased in AD (beta = 0.009, SE = 0.003, P = 0.010). These results indicate that serum total bilirubin is not causally associated with AD and cannot be used for screening or diagnosis, but can potentially serve as a biomarker of disease severity, and it needs further clinical studies.

18.
J Am Chem Soc ; 144(35): 16191-16198, 2022 Sep 07.
Artigo em Inglês | MEDLINE | ID: mdl-35972889

RESUMO

The selective separation of structurally similar aliphatic/aromatic hydrocarbons is an essential goal in industrial processes. In this study, we report the synthesis of a water-soluble (Tr2M3)4L4 (Tr = cycloheptatrienyl ring; M = metal; L = organosulfur ligand) molecular cage (1) via self-assembly of the water-soluble acceptor tripalladium sandwich species [(Tr2Pd3)(CH3CN)][NO3]2 and the attachment onto L of solubilizing methoxyethoxy appendants to be utilized in an energy-friendly alternative approach to the separation of structurally similar molecules under ambient conditions. Cage 1, comprising a hydrophobic inner cavity, exhibited good solubility and stability in aqueous media. It also demonstrated excellent performance in the sequential separation of alkanes (C6-C9), xylene, and other disubstituted benzene isomers and cis/trans-decalin.


Assuntos
Alcanos , Água , Alcanos/química , Hidrocarbonetos , Interações Hidrofóbicas e Hidrofílicas , Isomerismo , Ligantes , Metais , Água/química
19.
Ecotoxicol Environ Saf ; 243: 114016, 2022 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-36027713

RESUMO

Nitrobenzene is widely present in industrial wastewater and soil. Biodegradation has become an ideal method to remediate organic pollutants due to its low cost, high efficiency, and absence of secondary pollution. In the present study, 10 exogenous genes that can completely degrade nitrobenzene were introduced into Escherichia coli, and their successful expression in the strain was verified by fluorescence quantitative polymerase chain reaction and proteomic analysis. The results of the degradation experiment showed that the engineered strain could completely degrade 4 mM nitrobenzene within 8 h. The formation of intermediate metabolites was detected, and the final metabolites entered the E. coli tricarboxylic acid cycle smoothly. This process was discovered by isotope tracing method. Results indicated the integrality of the degradation pathway and the complete degradation of nitrobenzene. Finally, further experiments were conducted in soil to verify its degradation ability and showed that the engineered strain could also degrade 1 mM nitrobenzene within 10 h. In this study, engineered bacteria that can completely degrade nitrobenzene have been constructed successfully. The construction of remediation-engineered bacteria by synthetic biology laid the foundation for the industrial application of biological degradation of organic pollutants.


Assuntos
Poluentes Ambientais , Escherichia coli , Bactérias/metabolismo , Biodegradação Ambiental , Poluentes Ambientais/metabolismo , Escherichia coli/genética , Escherichia coli/metabolismo , Nitrobenzenos/metabolismo , Proteômica , Solo
20.
Chem Commun (Camb) ; 58(74): 10392-10395, 2022 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-36039808

RESUMO

An Rh-catalyzed tandem reaction was performed to construct an AIE-active furo[2,3-c]pyridine-based photosensitizer, named LIQ-TF. LIQ-TF showed near-infrared emission with high quantum yield, and high 1O2 and ˙OH generation efficiency, and could be used for specific imaging and photodynamic ablation of Gram-positive bacteria in vitro and in vivo, showing great potential for combating multiple drug-resistant bacteria.


Assuntos
Fotoquimioterapia , Fármacos Fotossensibilizantes , Diagnóstico por Imagem , Bactérias Gram-Positivas , Fotoquimioterapia/métodos , Fármacos Fotossensibilizantes/farmacologia , Fármacos Fotossensibilizantes/uso terapêutico , Piridinas/farmacologia
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