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1.
J Am Chem Soc ; 2022 May 05.
Artigo em Inglês | MEDLINE | ID: mdl-35511107

RESUMO

Water oxidation is the step limiting the efficiency of electrocatalytic hydrogen production from water. Spectroelectrochemical analyses are employed to make a direct comparison of water oxidation reaction kinetics between a molecular catalyst, the dimeric iridium catalyst [Ir2(pyalc)2(H2O)4-(µ-O)]2+ (IrMolecular, pyalc = 2-(2'pyridinyl)-2-propanolate) immobilized on a mesoporous indium tin oxide (ITO) substrate, with that of an heterogeneous electrocatalyst, an amorphous hydrous iridium (IrOx) film. For both systems, four analogous redox states were detected, with the formation of Ir(4+)-Ir(5+) being the potential-determining step in both cases. However, the two systems exhibit distinct water oxidation reaction kinetics, with potential-independent first-order kinetics for IrMolecular contrasting with potential-dependent kinetics for IrOx. This is attributed to water oxidation on the heterogeneous catalyst requiring co-operative effects between neighboring oxidized Ir centers. The ability of IrMolecular to drive water oxidation without such co-operative effects is explained by the specific coordination environment around its Ir centers. These distinctions between molecular and heterogeneous reaction kinetics are shown to explain the differences observed in their water oxidation electrocatalytic performance under different potential conditions.

2.
Mycorrhiza ; 2022 May 13.
Artigo em Inglês | MEDLINE | ID: mdl-35556179

RESUMO

Medicinal plants are an important source of therapeutic compounds used in the treatment of many diseases since ancient times. Interestingly, they form associations with numerous microorganisms developing as endophytes or symbionts in different parts of the plants. Within the soil, arbuscular mycorrhizal fungi (AMF) are the most prevalent symbiotic microorganisms forming associations with more than 70% of vascular plants. In the last decade, a number of studies have reported the positive effects of AMF on improving the production and accumulation of important active compounds in medicinal plants.In this work, we reviewed the literature on the effects of AMF on the production of secondary metabolites in medicinal plants. The major findings are as follows: AMF impact the production of secondary metabolites either directly by increasing plant biomass or indirectly by stimulating secondary metabolite biosynthetic pathways. The magnitude of the impact differs depending on the plant genotype, the AMF strain, and the environmental context (e.g., light, time of harvesting). Different methods of cultivation are used for the production of secondary metabolites by medicinal plants (e.g., greenhouse, aeroponics, hydroponics, in vitro and hairy root cultures) which also are compatible with AMF. In conclusion, the inoculation of medicinal plants with AMF is a real avenue for increasing the quantity and quality of secondary metabolites of pharmacological, medical, and cosmetic interest.

3.
Int J Mol Sci ; 23(9)2022 Apr 24.
Artigo em Inglês | MEDLINE | ID: mdl-35563093

RESUMO

Cotton Verticillium wilt, caused by the notorious fungal phytopathogen Verticillium dahliae (V. dahliae), is a destructive soil-borne vascular disease and severely decreases cotton yield and quality worldwide. Transcriptional and post-transcriptional regulation of genes responsive to V. dahliae are crucial for V. dahliae tolerance in plants. However, the specific microRNAs (miRNAs) and the miRNA/target gene crosstalk involved in cotton resistance to Verticillium wilt remain largely limited. To investigate the roles of regulatory RNAs under V. dahliae induction in upland cotton, mRNA and small RNA libraries were constructed from mocked and infected roots of two upland cotton cultivars with the V. dahliae-sensitive cultivar Jimian 11 (J11) and the V. dahliae-tolerant cultivar Zhongzhimian 2 (Z2). A comparative transcriptome analysis revealed 8330 transcripts were differentially expressed under V. dahliae stress and associated with several specific biological processes. Moreover, small RNA sequencing identified a total of 383 miRNAs, including 330 unique conserved miRNAs and 53 novel miRNAs. Analysis of the regulatory network involved in the response to V. dahliae stress revealed 31 differentially expressed miRNA-mRNA pairs, and the up-regulation of GhmiR395 and down-regulation of GhmiR165 were possibly involved in the response to V. dahliae by regulating sulfur assimilation through the GhmiR395-APS1/3 module and the establishment of the vascular pattern and secondary cell wall formation through GhmiR165-REV module, respectively. The integrative analysis of mRNA and miRNA expression profiles from upland cotton lays the foundation for further investigation of regulatory mechanisms of resistance to Verticillium wilt in cotton and other crops.

4.
J Alzheimers Dis ; 2022 Apr 11.
Artigo em Inglês | MEDLINE | ID: mdl-35431253

RESUMO

BACKGROUND: Epidemiologic evidence suggests that physical activity benefits cognition, but results from randomized trials in sedentary individuals are limited and inconsistent. OBJECTIVE: To evaluate the effects of physical activity on cognition among sedentary older adults. OBJECTIVE: A systematic literature search for eligible studies published up to January 1, 2021, was performed on six international (PubMed, Cochrane Library, Web of Science, Sinomed, FMRS, and OVID) and three Chinese databases (Wanfang, China National Knowledge Infrastructure, and VIP). We estimated the effect of physical activity on the cognition of sedentary elderly by standardized mean differences (SMD) and 95% confidence intervals (CI) using a random-effects model. We evaluated publication bias using funnel plots and heterogeneity using I2 statistics. Subgroup analyses were conducted by baseline cognition, intervention duration, activity type, and country. RESULTS: Seven randomized controlled trials (RCTs) comprising 321 (experimental group, 164; control group, 157) sedentary older adults were included in the meta-analysis. Physical activity significantly improved cognition in sedentary elderly adults compared with controls (SMD: 0.50, 95% CI:0.09-0.92). Subgroup analyses showed significant effects of baseline cognition impairment (SMD: 9.80, 95% CI: 5.81-13.80), intervention duration >  12 weeks (SMD: 2.85, 95% CI: 0.73-4.96), aerobic exercise (SMD: 0.74, CI: 0.19-1.29), and countries other than the United States (SMD: 10.50, 95% CI: 7.08-13.92). CONCLUSION: Physical activity might have a general positive effect on the cognition of sedentary older adults. Intervention >  12 weeks and aerobic exercise can effectively delay their cognitive decline; however, more rigorous RCTs are needed to support our findings.

5.
Front Cardiovasc Med ; 9: 814873, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35433861

RESUMO

Objective: Jailed balloon technique (JBT) is an active side branch (SB) protection strategy and is considered to be superior to the jailed wire technique (JWT) in reducing SB occlusion. However, no randomized trials have proved that. We aim to investigate whether JBT could decrease the SB occlusion rate. Methods: Conventional versus Intentional straTegy in patients with high Risk prEdiction of Side branch OccLusion in coronary bifurcation interVEntion (CIT-RESOLVE) (NCT02644434, registered on December 31, 2015) (https://clinicaltrials.gov) is a randomized trial that assessed the effects of different strategies on SB occlusion rate in patients with a high risk of SB occlusion. The present subgroup analysis enrolled bifurcation lesions (2 mm ≤ reference vessel diameter of SB < 2.5 mm) with Visual estimation for Risk prEdiction of Side branch OccLusion in coronary bifurcation intervention (V-RESOLVE) score ≥ 12 points. The primary endpoint is SB occlusion. One-year clinical events were compared. Results: A total of 284 subjects at 16 sites were randomly assigned to the JBT group (n = 143) or the JWT group (n = 141). The rate of SB occlusion (9.1 vs. 19.9%, p = 0.02) and periprocedural myocardial infarction (defined by WHO, 7 vs. 14.9%, p = 0.03) is significantly lower in the JBT group than in the JWT group. The JBT and JWT groups showed no significant differences in cardiac death (0.7 vs. 0.7%, p = 1), myocardial infarction (MI, 6.3 vs. 7.1%, p = 0.79), target lesion revascularization (TLR, 1.4 vs. 2.1%, p = 0.68), and major cardiac adverse events (MACE, a composite of all-cause death, MI, or TLR, 8.4 vs. 10.6%, p = 0.52) during a 1-year follow-up. Conclusion: In patients with a high risk of SB occlusion (V-RESOLVE score ≥ 12 points), JBT is superior to JWT in reducing SB occlusion. However, no significant differences were detected in 1-year MACE.

6.
Front Oncol ; 12: 823459, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35463336

RESUMO

Penile squamous cell carcinoma is a rare malignant tumor of the male reproductive system. We report two cases of advanced penile squamous cell carcinoma with persistent partial response/complete response after sintilimab combined with chemotherapy and analyze the relevant tumor biomarkers.

7.
Bioact Mater ; 18: 199-212, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-35387162

RESUMO

Although ultra-small nanoclusters (USNCs, < 2 nm) have immense application capabilities in biomedicine, the investigation on body-wide organ responses towards USNCs is scant. Here, applying a novel strategy of single-cell mass cytometry combined with Nano Genome Atlas of multi-tissues, we systematically evaluate the interactions between the host and calcium phosphate (CaP) USNCs at the organism level. Combining single-cell mass cytometry, and magnetic luminex assay results, we identify dynamic immune responses to CaP USNCs at the single cell resolution. The innate immune is initially activated and followed by adaptive immune activation, as evidenced by dynamic immune cells proportions. Furthermore, using Nano Genome Atlas of multi-tissues, we uncover CaP USNCs induce stronger activation of the immune responses in the cartilage and subchondral bone among the five local tissues while promote metabolic activities in the liver and kidney. Moreover, based on the immunological response profiles, histological evaluation of major organs and local tissue, and a body-wide transcriptomics, we demonstrate that CaP USNCs are not more hazardous than the Food and Drug Administration-approved CaP nanoparticles after 14 days of injection. Our findings provide valuable information on the future clinical applications of USNCs and introduce an innovative strategy to decipher the whole body response to implants.

8.
Cell Rep ; 39(4): 110762, 2022 04 26.
Artigo em Inglês | MEDLINE | ID: mdl-35476985

RESUMO

Tendon maturation lays the foundation for postnatal tendon development, its proper mechanical function, and regeneration, but the critical cell populations and the entangled mechanisms remain poorly understood. Here, by integrating the structural, mechanical, and molecular properties, we show that post-natal days 7-14 are the crucial transitional stage for mouse tendon maturation. We decode the cellular and molecular regulatory networks at the single-cell level. We find that a nerve growth factor (NGF)-secreting Cd9+Cd271+ tendon stem/progenitor cell population mainly prompts conversion from neonate to adult tendon. Through single-cell gene regulatory network analysis, in vitro inhibitor identification, and in vivo tendon-specific Shp2 deletion, we find that SHP2 signaling is a regulator for tendon maturation. Our research comprehensively reveals the dynamic cell population transition during tendon maturation, implementing insights into the critical roles of the maturation-related stem cell population and SHP2 signaling pathway during tendon differentiation and regeneration.


Assuntos
Células-Tronco , Tendões , Adapaleno/metabolismo , Animais , Diferenciação Celular , Camundongos , Transdução de Sinais/fisiologia , Células-Tronco/metabolismo
9.
Clin Chim Acta ; 530: 104-112, 2022 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-35314173

RESUMO

Multiple acyl-CoA dehydrogenase deficiency (MADD) is a rare autosomal recessive metabolic disease. Patients present with metabolic decompensation, muscle weakness, respiratory failure, and cardiomyopathy. Late-onset MADD is primarily caused by mutations in the ETFDH gene. Here, we report a patient who has been diagnosed with Down syndrome after birth following karyotype analysis and simultaneously carrying compound heterozygous variants of ETFDH (c.3G > C (p. M1?); c.725C > T (p. T242I), which is novel). Further molecular analyses revealed that the novel c.725C > T (p. T242I) mutation enhances the degradation of electron transfer flavoprotein-ubiquinone oxidoreductase (ETF-QO) via the ubiquitin proteasome pathway. Five ubiquitin E3 ligases (STUB1, RNF40, UBE3C, CUL3, and CUL1) and one ubiquitin modification site (Cystein, C101) of the ETF-QO were reported in this study. Our study not only expanded the pathogenic variant spectrum of ETFDH gene but also proved that the c.725C > T (p. T242I) will promote protein degradation through ubiquitin proteasome pathway.


Assuntos
Deficiência Múltipla de Acil Coenzima A Desidrogenase , Humanos , Deficiência Múltipla de Acil Coenzima A Desidrogenase/genética , Deficiência Múltipla de Acil Coenzima A Desidrogenase/metabolismo , Mutação , Complexo de Endopeptidases do Proteassoma/genética , Complexo de Endopeptidases do Proteassoma/metabolismo , Proteólise , Ubiquitina/genética , Ubiquitina/metabolismo , Ubiquitina-Proteína Ligases/genética , Ubiquitina-Proteína Ligases/metabolismo
10.
J Sci Food Agric ; 2022 Mar 11.
Artigo em Inglês | MEDLINE | ID: mdl-35275410

RESUMO

BACKGROUND: Gliadin nanoparticles are used as a delivery system for active substances because of their amphiphilicity and bioavailability. However, they are susceptible to destabilization by external agents. In this study, gliadin nanoparticles stabilized by soluble soybean polysaccharide (SSPS) were prepared by antisolvent precipitation. Formed stable complex nanoparticles were applied to protect and deliver curcumin (Cur). RESULTS: Gliadin/SSPS nanoparticles with the smallest particle size (196.66 nm, polydispersity index < 0.2) were fabricated when the mass ratio of gliadin to SSPS was 1:1 at pH 5.0. SSPS-stabilized gliadin nanoparticles had excellent stability at pH 3.0-8.0, 0.02-0.1 mol L-1 NaCl and at 90 °C heat. Gliadin/SSPS nanoparticles were used to encapsulate the Cur. The encapsulation efficiency of the Cur-loaded gliadin/SSPS nanoparticles was 84.59%. Fourier transform infrared spectroscopy and fluorescence spectrophotometry showed that the main forces were hydrogen bonds, electrostatic interactions and hydrophobic interactions between gliadin and SSPS. The X-ray diffraction patterns exhibited that the crystalline form of Cur converted to an amorphous substance. The retention rates of Cur-loaded gliadin/SSPS nanoparticles reached 79.03%, 73.43% and 87.92% after ultraviolet irradiation for 4 h, heating at 90 °C and storage at 25 °C for 15 days, respectively. Additionally, simulated digestion demonstrated that the bioavailability of gliadin/SSPS-Cur nanoparticles was four times higher than that of free Cur. CONCLUSION: This study showed that SSPS improved the stability of gliadin nanoparticles. Gliadin/SSPS nanoparticles have the function of loading and delivering Cur. © 2022 Society of Chemical Industry.

11.
Front Plant Sci ; 13: 841328, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35251110

RESUMO

Flower color is an important trait in Brassica species. However, genes responsible for the dark yellow flower trait in Chinese cabbage have not been reported. In this study, we identified a dark-yellow-flowered Chinese cabbage line SD369. Genetic analysis indicated that the dark yellow flower trait in SD369 was controlled by a single recessive locus, Br-dyp1 (dark yellow petal color 1 in Brassica rapa). Using bulked segregant RNA sequencing and kompetitive allele-specific PCR assays, Br-dyp1 was fine-mapped to an interval of 53.6 kb on chromosome A09. Functional annotation analysis, expression analysis, and sequence variation analysis revealed that Bra037130 (BraA09.ZEP), which encodes a zeaxanthin epoxidase, was the most likely candidate gene for Br-dyp1. Carotenoid profile analysis suggested that Bra037130 (BraA09.ZEP) might participate in the epoxidation from zeaxanthin to violaxanthin. The 679 bp insertion in dark yellow petal caused premature stop codon, thus caused the loss-of-function of the enzyme zeaxanthin epoxidase (ZEP), which disturbed the carotenoid metabolism, and caused the increased accumulation of total carotenoid, and finally converted the flower color from yellow to dark yellow. Comparative transcriptome analysis also showed that the "carotenoid biosynthesis" pathway was significantly enriched, and genes involved in carotenoid degradation and abscisic acid biosynthesis and metabolism were significantly downregulated. Furthermore, we developed and validated the functional marker Br-dyp1-InDel for Br-dyp1. Overall, these results provide insight into the molecular basis of carotenoid-based flower coloration in B. rapa and reveal valuable information for marker-assisted selection breeding in Chinese cabbage.

12.
Trials ; 23(1): 178, 2022 Feb 24.
Artigo em Inglês | MEDLINE | ID: mdl-35209934

RESUMO

BACKGROUND: Hypertension is currently the leading modifiable cause of global morbidity and mortality, leading to substantial health and financial burdens. Although multiple studies of management models and innovative therapeutic strategies for hypertension have been conducted, there are still gaps in the field, with a poor control rate reflecting a lack of novel, effective, clinically translated medication or intervention options. Recent animal and human studies repeatedly confirmed a link between the microbiota and hypertension. Of note is our previous study establishing a cause-and-effect relationship between the gut microbiota and blood pressure elevation. A hypothesis of gut microbiota intervention for treating hypertension is thus postulated, and fecal microbiota transplantation (FMT) from healthy donors was performed. METHODS: A multicenter, randomized, placebo-controlled, blinded clinical trial will be performed in 120 grade 1 hypertensive patients for 3 months. All recruited patients will be randomly assigned in a 1:1 ratio to take oral FMT capsules or placebo capsules on day 1, day 7, and day 14 and will be followed up on day 30, day 60, and day 90. The primary outcome is the change in office systolic blood pressure from baseline to day 30. The main secondary outcomes are BP indicators, including changes in systolic and diastolic blood pressure from office and 24-h ambulatory blood pressure monitoring; assessments of ankle-branchial index and pulse wave velocity; profiling of fecal microbial composition and function; profiling of fecal and serum metabolome; changes in levels of blood glucose, blood lipids, and body mass index; and assessment of adverse events as a measure of safety. DISCUSSION: Expanding upon our previous research on the role of the gut microbiota in the pathogenesis of hypertension, this study serves as a clinical translation advancement and explores the potential of fecal microbiota transplantation for treating hypertension. The underlying mechanisms, particularly the roles of specific microorganisms or their postbiotics in blood pressure amelioration, will also be investigated via multiple approaches, such as metagenomic sequencing and metabolomic profiling. TRIAL REGISTRATION: ClinicalTrials.gov NCT04406129 . Registered on May 28, 2020.


Assuntos
Transplante de Microbiota Fecal , Microbioma Gastrointestinal , Hipertensão , Monitorização Ambulatorial da Pressão Arterial , Humanos , Hipertensão/terapia , Estudos Multicêntricos como Assunto , Análise de Onda de Pulso , Ensaios Clínicos Controlados Aleatórios como Assunto , Resultado do Tratamento
13.
Toxicon ; 210: 49-57, 2022 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-35217023

RESUMO

With the continued influx and accumulation of polycyclic aromatic hydrocarbons (PAHs) in eutrophic waters, the effects of PAHs on cyanobacteria bloom need to be clarified. PAHs usually existed as mixtures in aquatic environments, but the combined toxicity of PAH mixtures to toxigenic cyanobacteria remained unknown. This study investigated the effects of phenanthrene (Phe) and benzo [a]pyrene (BaP), alone or in combination, on the growth and physiology of Microcystis aeruginosa. The results showed that a hormesis effect on growth at low doses of the single Phe (≤1 mg/L) or PAH mixtures (≤0.279 mg/L) was observed, whereas the single BaP induced significant growth inhibitions at all concentrations (≥0.2 mg/L). The median effective concentrations (96 h) for Phe, BaP and their mixtures were 4.29, 1.29 and 1.07 mg/L, respectively. Mixture toxicity models showed that Phe and BaP elicited a synergistic interaction on M. aeruginosa. The synergy may be ascribed to the excessive oxidative stress induced by PAH mixtures, which further led to membrane structure damages, photosynthesis inhibitions and decreased metabolic activity. Moreover, the microcystins (MCs) release significantly increased by 25.3% and 31.9% upon exposure to 0.558 and 1.116 mg/L of PAH mixtures. In all, this study suggested that the enhanced release of MCs by PAH mixtures might exacerbate potential risks to the aquatic environment.


Assuntos
Microcystis , Hidrocarbonetos Policíclicos Aromáticos , Microcistinas/metabolismo , Microcistinas/toxicidade , Estresse Oxidativo , Hidrocarbonetos Policíclicos Aromáticos/metabolismo , Hidrocarbonetos Policíclicos Aromáticos/toxicidade
14.
Chem Commun (Camb) ; 58(15): 2581, 2022 Feb 17.
Artigo em Inglês | MEDLINE | ID: mdl-35133389

RESUMO

Correction for 'Recent advances in fluorescent probes for lipid droplets' by Yanyan Zhao et al., Chem. Commun., 2022, 58, 1495-1509, DOI: 10.1039/D1CC05717K.

15.
Lab Invest ; 2022 Feb 18.
Artigo em Inglês | MEDLINE | ID: mdl-35184139

RESUMO

The ability of cisplatin (cis-diamminedichloroplatinum II) toxicity to induce acute kidney injury (AKI) has attracted attention and concern for a long time, but the molecular mechanism of action for cisplatin is not clear. MicroRNA-483 is involved in several diseases, such as tumorigenesis and osteoarthritis, but its renal target and potential role in AKI are unknown. In this study, we explored the pathogenic role and underlying mechanism of miR-483-5p in cisplatin-induced AKI, using transgenic mice, clinical specimen, and in vitro cell line. We found that miR-483-5p was significantly upregulated by cisplatin in a cisplatin-induced mouse model, in serum samples of patients who received cisplatin therapy, and in NRK-52E cells. Overexpression of miR-483-5p in mouse kidneys by stereotactic renal injection of lentiviruses mediated miR-483-5p or generation of conditional miR-483-overexpressing transgenic mice accentuated cisplatin-induced AKI by increasing oxidative stress, promoting apoptosis, and inhibiting autophagy of tubular cells. Furthermore, our results revealed miR-483-5p directly targeted to GPX3, overexpression of which rescued cisplatin-induced AKI by inhibiting oxidative stress and apoptosis of tubular cells, but not by regulating autophagy. Collectively, miR-483-5p is upregulated by cisplatin and exacerbates cisplatin-induced AKI via negative regulation of GPX3 and contributing oxidative stress and tubular cell apoptosis. These findings reveal a pathogenic role for miR-483-5p in cisplatin-induced AKI and suggest a novel target for the diagnosis and treatment of AKI.

16.
Int J Cardiol ; 352: 33-39, 2022 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-35101540

RESUMO

BACKGROUND: The simulated residual quantitative flow ratio (QFR) computed from pre-intervention three-dimensional (3-D) coronary angiograms, which could theoretically predict actual post-percutaneous coronary intervention (PCI) QFR value, can be used for enhanced PCI via augmented reality. The study sought to investigate the concordance between simulated residual QFR and actual post-PCI QFR, and the prognostic value of simulated residual QFR. METHODS: QFR assessment was retrospectively performed in treated vessels from the all-comers PANDA III trial. Three-step analysis was performed: 1) concordance between simulated residual QFR and post-PCI QFR; 2) prognostic value of simulated residual QFR; and 3) forecast of outcomes by virtual randomized controlled trials (RCTs) between residual QFR and angiographic guidance. RESULTS: Of 2989 treated vessels, 2146 (71.8%) with paired analyzable simulated residual QFR and post-PCI QFR were included. The simulated residual QFR and post-PCI QFR were strongly correlated (r = 0.976). Low simulated residual QFR (≤0.92) was independently associated with higher risk of 2-year vessel-oriented composite endpoint (adjusted hazard ratio: 5.50; 95% confidence interval: 3.03 to 10.0). Based upon 5000 iterations of virtual RCTs, simulated residual QFR-guided strategy was anticipated to have a 2.6% absolute reduction of 2-year incidence of target vessel failure compared with the angiography-guided strategy. CONCLUSIONS: With high consistency to actual post-PCI QFR, the simulated residual QFR computed from pre-PCI 3-D coronary angiograms and augmented reality could predict functional outcome of the procedure and 2-year prognosis. Using data from PANDA III trial, the present study forecasted superiority of residual QFR-guided PCI strategy over angiographic guidance. Clinical Trial Registration Information URL: https://www.clinicaltrials.gov; Unique identifier: NCT02017275.


Assuntos
Realidade Aumentada , Doença da Artéria Coronariana , Reserva Fracionada de Fluxo Miocárdico , Intervenção Coronária Percutânea , Angiografia Coronária , Doença da Artéria Coronariana/diagnóstico por imagem , Doença da Artéria Coronariana/cirurgia , Vasos Coronários/diagnóstico por imagem , Vasos Coronários/cirurgia , Humanos , Valor Preditivo dos Testes , Resultado do Tratamento
17.
J Interv Cardiol ; 2022: 3895205, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35095347

RESUMO

BACKGROUND: There is a paucity of real-world data regarding the clinical impact of dual antiplatelet therapy (DAPT) interruption (temporary or permanent) among patients at high ischemic risk. The aim of this study was to assess the risk of cardiovascular events after interruption of DAPT in high-risk PCI population. METHODS: This study used data from the Fuwai PCI registry, a large, prospective cohort of consecutive patients who underwent PCI. We assessed 3,931 patients with at least 1 high ischemic risk criteria of stent-related recurrent ischemic events proposed in the 2017 ESC guidelines for focused update on DAPT who were free of major cardiac events in the first 12 months. The primary ischemic endpoint was 30-month major adverse cardiac and cerebrovascular events, and the key safety endpoints were BARC class 2, 3, or 5 bleeding and net adverse clinical events. RESULTS: DAPT interruption within 12 months occurred in 1,122 patients (28.5%), most of which were due to bleeding events or patients' noncompliance to treatment. A multivariate Cox regression model, propensity score (PS) matching, and inverse probability of treatment weighting (IPTW) based on the propensity score demonstrated that DAPT interruption significantly increased the risk of primary ischemic endpoint compared with prolonged DAPT (3.9% vs. 2.2%; Cox-adjusted hazard ratio (HR): 1.840; 95% confidence interval (CI): 1.247 to 2.716; PS matching-HR: 2.049 [1.236-3.399]; IPTW-adjusted HR: 1.843 [1.250-2.717]). This difference was driven mainly by all-cause death (1.8% vs. 0.7%) and MI (1.3% vs. 0.5%). Furthermore, the rate of net adverse clinical events (4.9% vs. 3.2%; Cox-adjusted HR: 1.581 [1.128-2.216]; PS matching-HR: 1.639 [1.075-2.499]; IPTW-adjusted HR: 1.554 [1.110-2.177]) was also higher in patients with DAPT interruption (≤12 months), whereas no significant differences between groups were observed in terms of BARC 2, 3, or 5 bleeding. These findings were consistent across various stent-driven high-ischemic risk subsets with respect to the primary ischemic endpoints, with a greater magnitude of harm among patients with diffuse multivessel diabetic coronary artery disease. CONCLUSIONS: In patients undergoing high-risk PCI, interruption of DAPT in the first 12 months occurred infrequently and was associated with a significantly higher adjusted risk of major adverse cardiovascular events and net adverse clinical events. 2017 ESC stent-driven high ischemic risk criteria may help clinicians to discriminate patient selection in the use of long-term DAPT when the ischemic risk certainly overcomes the bleeding one.


Assuntos
Stents Farmacológicos , Intervenção Coronária Percutânea , Humanos , Intervenção Coronária Percutânea/efeitos adversos , Inibidores da Agregação Plaquetária/efeitos adversos , Estudos Prospectivos , Stents/efeitos adversos
18.
Chem Commun (Camb) ; 58(10): 1495-1509, 2022 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-35019910

RESUMO

Lipid droplets (LDs) have been known as a non-negligible cellular organelle for lipid storage and metabolism. Fluorescent probes for imaging LDs would be paramount for depicting their functions in cells. Although commercially available Nile Red and BODIPYtm 493/503 have been widely used for labelling LDs, they exhibit unsatisfactory specificity and spectroscopic properties. This feature article reviews the recent advances in organic fluorescent probes for imaging LDs. We first introduce the key points for probe design, including regulating hydrophobicity and enhancing fluorescence quantum yield in LDs. Then, we summarize the structural features and biological applications of some representative LD probes classified by their frameworks. In addition, the current challenges and future research trends for the fluorescent probes of LDs are discussed as well.


Assuntos
Corantes Fluorescentes/química , Gotículas Lipídicas/química , Animais , Linhagem Celular , Cumarínicos/química , Flavonas/química , Humanos , Microscopia de Fluorescência , Naftalimidas/química , Hidrocarbonetos Policíclicos Aromáticos/química
19.
Talanta ; 241: 123223, 2022 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-35030500

RESUMO

Separation, purification, and identification of glycoproteins are essential for understanding their vital roles in biological and pathological processes. However, glycoproteins are difficult to be captured due to their low abundance, strong interference from non-glycosylated proteins. Here, we report a promising dipeptide-based saccharide recognition platform to selectively enrich two typical glycoproteins, named immunoglobin G (IgG) and horseradish peroxidase (HRP). Different from the conventional glycoprotein enrichment method based on boronic acid affinity or hydrophilic interaction with glycans, the present method was established based on affinity between Pro-Glu (PE) dipeptide and mannose, which is a key unit in the pentasaccharide core of the IgG and HRP glycans. The prepared PE homopolymer surface was proved to selectively bind IgG and HRP superior to that of bovine serum albumin (BSA). Benefiting from this feature, selective enrichment of IgG and HRP was achieved from a protein mixture containing 200-fold BSA interference by using polyPE@SiO2 under a dispersive solid-phase extraction (dSPE) mode. High adsorption capacity, controllable and selective adsorption behaviors, as well as satisfactory recovery demonstrated the high potential of the dipeptide-based polymeric material in IgG and HRP enrichment. This study might provide a new insight to solve the challenging problem of glycoprotein separation.


Assuntos
Glicoproteínas , Dióxido de Silício , Dipeptídeos , Glicopeptídeos , Peroxidase do Rábano Silvestre , Imunoglobulina G
20.
Neurotox Res ; 40(1): 1-13, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-34851489

RESUMO

Background Emerging studies illustrate that long non-coding RNA TUG1 (TUG1) participates in neuron death after ischemia. However, the role of TUG1 in cerebral ischemia/reperfusion (CI/R) injury through cerebrovascular pathology was undetermined yet. Methods Expression of TUG1, miRNA-410-3p (miR-410), and forkhead box O3 (FOXO3) was detected by RT-qPCR and western blot. Neural function, apoptosis, and inflammatory damage were assessed by triphenyltetrazolium chloride straining, modified neurological severity score, fluorescence-activated cell sorting method, and western blot. The relationship among TUG1, miR-410, and FOXO3 was identified by dual-luciferase reporter assay, RNA pull-down, and RNA immunoprecipitation. Results TUG1 was upregulated in middle cerebral artery occlusion/reperfusion (MCAO/R) mice and oxygen-glucose deprivation/reoxygenation (OGD/R)-induced mouse brain microvascular endothelial cells (BMECs) in a certain of time-dependent manner. Blockage of TUG1 decreased infarct volume and increased neurological score in MCAO/R mice, accompanied with elevated Bcl-2 expression and declined expression of IL-1ß, IL-6, TNF-α, Bax, and cleaved caspase 3. Abovementioned proteins were similarly expressed in OGD/R-induced BMECs with TUG1 knockdown, paralleled with diminished apoptosis rate. Either, miR-410 overexpression and FOXO3 interference could suppress OGD/R-induced inflammatory and apoptotic responses. Of note, TUG1 and FOXO3 are competing endogenous RNAs (ceRNAs) for miR-410 via target binding. Depleting miR-410 counteracted the role of TUG1 exhaustion, and reinforcing FOXO3 abated the effect of miR-410 overexpression. Conclusion Exhausting TUG1 could alleviate CI/R-induced inflammatory injury and apoptosis in brain tissues and BMECs via targeting miR-410/FOXO3 axis, suggesting an innovative perspective from cerebrovascular endothelial cells in the pathogenesis and treatment of CI/R.


Assuntos
Isquemia Encefálica , MicroRNAs , Traumatismo por Reperfusão , Animais , Apoptose/genética , Isquemia Encefálica/complicações , Células Endoteliais/metabolismo , Camundongos , MicroRNAs/genética , MicroRNAs/metabolismo , Reperfusão , Traumatismo por Reperfusão/metabolismo
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