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1.
Chin Med J (Engl) ; 134(20): 2465-2474, 2021 Oct 07.
Artigo em Inglês | MEDLINE | ID: mdl-34620747

RESUMO

BACKGROUND: Ubiquitin-conjugating enzyme E2C (UBE2C) has been shown to be associated with the occurrence of various cancers and involved in many tumorigenic processes. This study aimed to investigate the specific molecular mechanism through which UBE2C affects breast cancer (BC) proliferation. METHODS: BC-related datasets were screened according to filter criteria in the Gene Expression Omnibus (GEO) database and The Cancer Genome Atlas (TCGA) database. Then differentially expressed genes (DEGs) were identified using Venn diagram analysis. By using DEGs, we conducted the following analyses including Gene ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), protein-protein interaction (PPI), and survival analysis, and then validated the function of the hub gene UBE2C using quantitative reverse transcription-polymerase chain reaction (RT-qPCR), cell counting kit-8 (CCK-8) assay, transwell assay, and Western blot assay. RESULTS: In total, 151 DEGs were identified from the GEO and TCGA databases. The results of GO analysis demonstrated that the DEGs were significantly enriched with mitotic nuclear division, lipid droplet, and organic acid-binding. KEGG analysis showed that the peroxisome proliferators-activated receptor (PPAR) signaling pathway, regulation of lipolysis in adipocytes, and proximal tubule bicarbonate reclamation were significantly enriched in the signal transduction pathway category. The top three hub genes that resulted from the PPI network were FOXM1, UBE2C, and CDKN3. The results of survival analysis showed a close relationship between UBE2C and BC. The results of CCK-8 and transwell assays suggested that the proliferation and invasion of UBE2C knockdown cells were significantly inhibited (P < 0.050). The results of Western blot assay showed that the level of phosphorylated phosphatase and tensin homology deleted on chromosome 10 (p-PTEN) was obviously increased (P < 0.050), whereas the levels of phosphorylated protein kinase B (p-AKT), phosphorylated mammalian target of rapamycin (p-mTOR), and hypoxia-inducible factor-1 alpha (HIF-1α) were dramatically decreased (P < 0.050) in the UBE2C knockdown cell. CONCLUSION: UBE2C can promote BC proliferation by activating the AKT/mTOR signaling pathway.


Assuntos
Neoplasias , Proteínas Proto-Oncogênicas c-akt , Biomarcadores Tumorais , Proliferação de Células/genética , Biologia Computacional , Regulação Neoplásica da Expressão Gênica , Proteínas Proto-Oncogênicas c-akt/genética , Transdução de Sinais/genética , Serina-Treonina Quinases TOR/genética
2.
Biomater Sci ; 2021 Oct 13.
Artigo em Inglês | MEDLINE | ID: mdl-34643189

RESUMO

Fabrication of anti-wetting coatings with anti-biofouling and anti-biofilm properties has become a hot spot of attention in recent years. However, the anti-biofilm mechanism of anti-bacterial adhesion coatings with different wet resistance properties has not been explored in detail. In this work, SiOx micro-nano particles were prepared by the Stöber method and were in situ modified. The SiOx/waterborne polyurethane (WPU) coatings were prepared by the drop coating method, and the coatings with different hydrophobic and oleophobic properties were constructed by modifying the process conditions using SiOx micro-nano particles as the roughness construction factor. Taking the dominant spoilage bacteria of aquatic products, Shewanella putrefaciens as the object, the anti-bacterial adhesion properties and anti-biofilm mechanism of the SiOx/WPU coatings were investigated. The results show that, with the unmodified SiOx particles increasing from 1.2% (w/V) to 4.0% (w/V), the hydrophobicity and thermal stability of the SiOx/WPU coatings are significantly enhanced, but the oil repellency becomes worse due to the mesoporous structure. After SiOx micro-nano particles are modified with 1H,1H,2H,2H-perfluorooctyl trichlorosilane (PFOTS), the surface energy of the SiOx/WPU coatings is decreased, the liquid repellency is improved, and the surfaces are rough with the appearance of fluorocarbon compounds, but the thermal stabilities are slightly reduced. Among them, after the secondary modification of SiOx micro-nano particles, the SiOx/WPU coatings showed excellent oil repellency, lower surface energies and higher fluorocarbon content on the surface. Particularly, SiOx/WPU coatings exhibited super-amphiphobicity after adjusting the amount of concentrated ammonia added during the secondary modification process. Meanwhile, we found that for the hydrophobic SiOx/WPU coatings, the stronger the oleophobic property, the greater the anti-bacterial adhesion ability is, while the anti-bacterial adhesion ability of hydrophobic and selectively oleophobic or superhydrophobic and oleophobic SiOx/WPU coatings is poor than that of amphiphilic SiOx/WPU coatings. However, because the super-amphiphobic SiOx/WPU coatings can be in the Cassie state with the bacterial solution for a long time, it can "capture" enough air to inhibit the irreversible adhesion of the bacteria. More importantly, the coatings can also inhibit the metabolic activity, secretion of extracellular polysaccharides, and activities of ATPase and AKP of the adherent bacteria, so it has a better anti-biofilm property. The anti-biofilm coatings can be used as food packaging materials or coated on the inner surface of packaging boxes to prevent the microbial infection.

3.
Environ Pollut ; 292(Pt A): 118327, 2021 Oct 08.
Artigo em Inglês | MEDLINE | ID: mdl-34634410

RESUMO

Biochar has advantages of a large specific surface area and micropore structure, which is beneficial for immobilization remediation of heavy metal‒contaminated soils. A field experiment was conducted to investigate the effects of rice husk biochar (BC) (7.5, 15, and 15 t hm-2) on Cd availability in soils and accumulation in maize (Zea mays L), soil aggregate structure, and microbial community abundance. The results show that BC treatment promoted the formation of large aggregates (5-8 and 2-5 mm) and enhanced aggregate stability, whereas it decreased the proportion of ≤0.25 mm soil aggregates. The geometric mean diameter and mean weight diameter under BC‒treated soils increased by 9.9%-40.5% and 3.6%-32.7%, respectively, indicating that the stability of soil aggregates increased. Moreover, BC facilitated the migration of Cd from large particles (>0.5 mm aggregates) to small particles (<0.25 mm aggregates). The application of BC decreased diethylenetriamine pentaacetic acid ‒extractable Cd by 17.6%-32.12% in contrast with the control. The amount of Cd in maize was reduced by 56.7%-81.1% for zhengdan958, 52.4%-85.9% for Sanbei218, and 73.7%-90.4% for Liyu16. When compared with the control groups, BC addition significantly (P < 0.05) increased the number of Ace observed, Shannon diversity indices, and the relative abundances of Proteobacteria, Acidobacteria, and Bacteroidetes. Therefore, rice husk BC exhibited a certain feasibility in immobilizing remediation of weakly alkaline Cd‒contaminated soils.

4.
Front Public Health ; 9: 660514, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34513778

RESUMO

Objectives: The aim of this systematic review is to assess the published cost-effectiveness analyses of aprepitant for patients with chemotherapy-induced nausea and vomiting (CINV). Methods: A systematic literature search was performed on PubMed, EMbase, the Cochrane Library, CNKI, WANFANG DATA, and CBM database. The date of publication is up to January 2019. Two reviewers independently reviewed titles, abstracts, and articles sequentially to select studies for data abstraction based on the inclusion and exclusion criteria. Disagreements were resolved and reviewers reached a consensus. The quality of the included studies was assessed according to the 24-item checklist of the consolidated health economic evaluation reporting standards (CHEERS). The costs reported by the included studies were converted to US dollars via purchasing power parities (PPP) in the year 2019 using the CCEMG-EPPI-Certer Cost Converter. Results: Thirteen articles were included based on the inclusion criteria for cost-effectiveness analysis and cost-utility analysis. Twelve studies were rated as good quality and one as a moderate quality based on the CHEERS checklist. Eight studies compared aprepitant plus 5-hydroxytryptamine-3 receptor antagonist (5-HT3RA) and dexamethasone with the standard regimen (5-HT3RA and dexamethasone). It was concluded that aprepitant plus standard regimen was a cost-effective strategy for preventing CINV. Only one study that compared aprepitant plus 5-HT3RA with 5-HT3RA, concluded that the addition of aprepitant reduced the incidence of severe nausea, and it might also provide an economic benefit in the overall management. Four studies that compared aprepitant with other antiemetic drugs concluded that aprepitant is a cost-effective strategy for preventing CINV compared with metoclopramide. However, netupitan + palonosetron and olanzapine are cost-effective compared with aprepitant. Conclusion: This study is the first systematic evaluation of adding aprepitant to standard regimens for patients with CINV. Most economic evaluations of antiemetic medications are reported to be of good quality. Adding aprepitant to standard regimens is found to be a cost-effective strategy for preventing CINV.


Assuntos
Antineoplásicos , Náusea , Antineoplásicos/efeitos adversos , Aprepitanto/uso terapêutico , Análise Custo-Benefício , Humanos , Náusea/induzido quimicamente , Vômito/induzido quimicamente
5.
Front Neurol ; 12: 693554, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34526955

RESUMO

Background: Early shunt obstruction (SO) remains the most common cause of lumboperitoneal shunt (LPS) failure. Although there is anecdotal evidence that the level of cerebrospinal fluid (CSF) parameters might affect shunt performance, its association with early LPS obstruction in adults with post-hemorrhagic hydrocephalus (PHH) is unclear. Methods: The retrospective study was performed by reviewing the adults with PHH treated by LPS from years 2014 to 2018. We included patients with CSF samples analyzed within 1 week prior to shunt insertion or at the time of shunt insertion. Baseline characteristics of each patient were collected. The primary outcomes were the incidence rate and associated factors of SO occurring within 3 months of shunt placement. The secondary outcomes included scores on the National Institute of Health Stroke Scale (NIHSS) and Evans Index at discharge. Results: A total of 76 eligible patients were analyzed, of whom 61 were obstruction-free and 15 were early SO. The overall rate of early SO was 15.6%. The RBCs count and nucleated cells count in preoperative CSF were actually higher in patients with early SO, compared to patients in the control group. Multivariate analysis identified RBC elevation (>0 × 106/L; OR: 10.629, 95% CI: 1.238-91.224, p = 0.031) as a dependent risk factor for early SO. NIHSS dramatically decreased at discharge while the alteration of ventricular size was not observed. Conclusions: This study suggested that the presence of RBCs in preoperative CSF was associated with early SO in patients with PHH treated by LPS.

6.
Front Med (Lausanne) ; 8: 704666, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34490296

RESUMO

Importance/Background: The coronavirus disease (COVID-19) pandemic is a critical public health issue. Evidence has shown that metformin favorably influences COVID-19 outcomes. This study aimed to assess the benefits and risks of metformin in COVID-19 patients. Methods: We searched the PubMed, Embase, Cochrane Library, and Chinese Biomedical Literature Database from inception to February 18, 2021. Observational studies assessing the association between metformin use and the outcomes of COVID-19 patients were included. The primary outcome was mortality, and the secondary outcomes included intubation, deterioration, and hospitalization. Random-effects weighted models were used to pool the specific effect sizes. Subgroup analyses were conducted by stratifying the meta-analysis by region, diabetic status, the adoption of multivariate model, age, risk of bias, and timing for adding metformin. Results: We identified 28 studies with 2,910,462 participants. Meta-analysis of 19 studies showed that metformin is associated with 34% lower COVID-19 mortality [odds ratio (OR), 0.66; 95% confidence interval (CI), 0.56-0.78; I 2 = 67.9%] and 27% lower hospitalization rate (pooled OR, 0.73; 95% CI, 0.53-1.00; I 2 = 16.8%). However, we did not identify any subgroup effects. The meta-analysis did not identify statistically significant association between metformin and intubation and deterioration of COVID-19 (OR, 0.94; 95% CI, 0.77-1.16; I 2 = 0.0% for intubation and OR, 2.04; 95% CI, 0.65-6.34; I 2 = 79.4% for deterioration of COVID-19), respectively. Conclusions: Metformin use among COVID-19 patients was associated with a reduced risk of mortality and hospitalization. Our findings suggest a relative benefit for metformin use in nursing home and hospitalized COVID-19 patients. However, randomized controlled trials are warranted to confirm the association between metformin use and COVID-19 outcomes. Study Registration: The study was registered on the PROSPERO on Feb 23, 2021 (CRD42021238722).

7.
Pharmgenomics Pers Med ; 14: 1107-1114, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34511981

RESUMO

Background: Deep vein thrombosis (DVT) is common among patients with stroke. However, the incidence of DVT in acute ischemic stroke patients treated with thrombolytic therapy and the risk factors associated with this condition are unknown. Objective: This study aimed to investigate the incidence and risk factors of DVT after thrombolysis in patients with acute ischemic stroke. Settings and Methods: We retrospectively reviewed the medical records of all patients with acute ischemic stroke who underwent ultrasonic examination after intravenous thrombolysis between April 2017 and December 2019 at the stroke center of the First Hospital of Jilin University, China. Color duplex ultrasound was used to diagnosis DVT in all patients within 72 h after intravenous thrombolysis. Univariate and multivariate logistic regression analyses were performed to identify the risk factors for DVT. Results: Overall, 474 patients were included in the study. Of these, 75 (15.8%) developed DVT (95% confidence interval 12.5-19.1). Older age was the risk factor that most significantly affected the development of DVT (p = 0.001). Compared to patients younger than 60 years old, those aged 60-69 years and ≥70 years had a higher risk of DVT, at rates of 2.201 (95% CI: 1.033-4.689; p < 0.05) and 4.241 (95% CI: 2.016-8.922; p < 0.001) times higher, respectively. Patients with higher triglyceride levels (odds ratio 0.545, 95% CI: 0.372-0.799, p = 0.002) and longer activated partial thromboplastin time (OR 0.927, 95% CI: 0.862-0.996, p = 0.040) were less likely to have DVT. Conclusion: DVT is a common complication among patients undergoing intravenous thrombolysis after acute ischemic stroke. Advanced age may increase the occurrence of DVT to some extent. For these patients, safe antiplatelet therapy should be explored and implemented as soon as possible.

8.
PLoS One ; 16(9): e0248796, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34499661

RESUMO

Ammonium toxicity in plants is considered a global phenomenon, but the primary mechanisms remain poorly characterized. Here, we show that although the addition of potassium or nitrate partially alleviated the inhibition of rice seedling root growth caused by ammonium toxicity, the combination of potassium and nitrate clearly improved the alleviation, probably via some synergistic mechanisms. The combined treatment with potassium and nitrate led to significantly improved alleviation effects on root biomass, root length, and embryonic crown root number. The aberrant cell morphology and the rhizosphere acidification level caused by ammonium toxicity, recovered only by the combined treatment. RNA sequencing analysis and weighted gene correlation network analysis (WGCNA) revealed that the transcriptional response generated from the combined treatment involved cellulose synthesis, auxin, and gibberellin metabolism. Our results point out that potassium and nitrate combined treatment effectively promotes cell wall formation in rice, and thus, effectively alleviates ammonium toxicity.

9.
Medicine (Baltimore) ; 100(31): e26691, 2021 Aug 06.
Artigo em Inglês | MEDLINE | ID: mdl-34397802

RESUMO

BACKGROUND: Ventriculoperitoneal shunt (VPS) and lumboperitoneal shunt (LPS) remain the mainstay of idiopathic normal pressure hydrocephalus (INPH). There are no randomized controlled trials completed to compare the efficacy of these 2 shunt techniques. METHODS/DESIGN: We will conduct a monocentric, assessor-blinded, and randomized controlled trial titled "Comparison of Ventriculoperitoneal Shunt to Lumboperitoneal Shunt for the treatment of Idiopathic Normal Pressure Hydrocephalus: Phase I (COVLINPH-1)" trial and recruit patients at West China Hospital of Sichuan University since June 2021. And this trial is expected to end in December 2030. Eligible participants will be randomly assigned into LPS group and VPS group at ratio of 1:1 followed by evaluation before surgery, 1 month, 12 months, and 5 years after surgery. The primary outcome is the rate of shunt failure within 5 years. The secondary outcomes include modified Rankin Scale (mRS), INPH grading scale (INPHGS), mini-mental state examination (MMSE), and Evans index. We will calculate the rate of favorable outcome, which is defined as shunt success and an improvement of more than 1 point in the mRS at evaluation point. We will also analyze the complications throughout the study within 5 years after shunt insertion. DISCUSSION: The results of this trial will provide state-of-the-art evidence on the treatment option for patients with INPH, and will also generate the discussion regarding this subject. TRIAL REGISTRATION NUMBER: ChiCTR2000031555; Pre-results.


Assuntos
Hidrocefalia de Pressão Normal/cirurgia , Peritônio/cirurgia , Espaço Subaracnóideo/cirurgia , Derivação Ventriculoperitoneal , Drenagem/efeitos adversos , Drenagem/métodos , Humanos , Vértebras Lombares , Ensaios Clínicos Controlados Aleatórios como Assunto , Método Simples-Cego , Derivação Ventriculoperitoneal/efeitos adversos
10.
BMJ Open ; 11(8): e051127, 2021 08 26.
Artigo em Inglês | MEDLINE | ID: mdl-34446499

RESUMO

INTRODUCTION: Ventriculoperitoneal shunt (VPS) remains the most widely used methods to treat communicating hydrocephalus. More recently, lumboperitoneal shunt (LPS) has been suggested as a reasonable option in some studies. However, there is lack of high-quality studies comparing these two techniques in order to certain the benefits and harms to use one of these two methods. The purpose of the current study is to determine the effectiveness and safety of the LPS versus the VPS in patients with communicating hydrocephalus. METHODS AND ANALYSIS: All eligible patients aged 18-90 years with communicating hydrocephalus will be recruited and then randomly allocated into LPS or VPS group in a ratio of 1:1. All patients will be analysed before shunt insertion, at the time of discharge, 1 month, 6 months, 12 months and 24 months postoperatively. The primary outcome measure is the rate of shunt failure at a 2-year follow-up term. The secondary outcomes include Keifer's Hydrocephalus Scale, National Institute of Health Stroke Scale, Glasgow Outcome Scale Extended, Evans index, safety endpoints and cost-effectiveness of hospital stay. ETHICS AND DISSEMINATION: The study will be performed in compliance with the Declaration of Helsinki (2002) of the World Medical Association. The study was approved by Institutional Review Board of West China Hospital. All patients will be fully informed the potential benefits, potential risks and responsibilities, those who will sign the informed consents once they are included. Preliminary and final results will be published in peer-reviewed journals and presented at national and international congresses. TRIAL REGISTRATION NUMBER: ChiCTR2100043839.


Assuntos
Hidrocefalia , Análise Custo-Benefício , Humanos , Hidrocefalia/cirurgia , Estudos Multicêntricos como Assunto , Ensaios Clínicos Controlados Aleatórios como Assunto , Resultado do Tratamento , Procedimentos Cirúrgicos Vasculares , Derivação Ventriculoperitoneal/efeitos adversos
11.
Int Arch Allergy Immunol ; 182(10): 1008-1016, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34375975

RESUMO

BACKGROUND: It is plausible that interleukin polymorphisms may affect predisposition of autoimmune disorders such as systemic lupus erythematosus (SLE), but the results of so far published studies remain controversial. OBJECTIVES: The authors conducted this meta-analysis to clarify relationships between interleukin-1 (IL-1)/interleukin-4 (IL-4)/interleukin-6 (IL-6)/interleukin-10 (IL-10) polymorphisms and SLE by pooling the findings of eligible studies. METHODS: A comprehensive search of PubMed, EMBASE, Web of Science, and CNKI was endorsed by the authors to identify already published studies. Fifty-seven studies were found to be eligible for meta-analyses. RESULTS: The overall pooled meta-analyses yielded positive findings for IL-1A -889 C/T, IL-1B -31 T/C, IL-6 -174 G/C, IL-4 -590 C/T, and IL-10 -1,082 A/G polymorphisms. In addition, we also detected similar positive findings for IL-1B -511 C/T, IL-4 -590 C/T, IL-10 -592 A/C, IL-10 -819 C/T, and IL-10 -1,082 A/G polymorphisms in Asians, and such positive findings were also observed for IL-1A -889 C/T, IL-6 -174 G/C, and IL-10 -1,082 A/G polymorphisms in Caucasians. CONCLUSIONS: The meta-analyses' results suggest that IL-1A -889 C/T, IL-1B -31 T/C, IL-6 -174 G/C, IL-4 -590 C/T, and IL-10 -1,082 A/G polymorphisms might affect predisposition of SLE.

12.
BMC Plant Biol ; 21(1): 364, 2021 Aug 10.
Artigo em Inglês | MEDLINE | ID: mdl-34376143

RESUMO

BACKGROUND: Improving the overall production of rice with high quality is a major target of breeders. Mining potential yield-related loci have been geared towards developing efficient rice breeding strategies. In this study, one single-locus genome-wide association studies (SL-GWAS) method (MLM) in conjunction with five multi-locus genome-wide association studies (ML-GWAS) approaches (mrMLM, FASTmrMLM, pLARmEB, pKWmEB, and ISIS EM-BLASSO) were conducted in a panel consisting of 529 rice core varieties with 607,201 SNPs. RESULTS: A total of 152, 106, 12, 111, and 64 SNPs were detected by the MLM model associated with the five yield-related traits, namely grain length (GL), grain width (GW), grain thickness (GT), thousand-grain weight (TGW), and yield per plant (YPP), respectively. Furthermore, 74 significant quantitative trait nucleotides (QTNs) were presented across at least two ML-GWAS methods to be associated with the above five traits successively. Finally, 20 common QTNs were simultaneously discovered by both SL-GWAS and ML-GWAS methods. Based on genome annotation, gene expression analysis, and previous studies, two candidate key genes (LOC_Os09g02830 and LOC_Os07g31450) were characterized to affect GW and TGW, separately. CONCLUSIONS: These outcomes will provide an indication for breeding high-yielding rice varieties in the immediate future.


Assuntos
Estudo de Associação Genômica Ampla , Oryza/crescimento & desenvolvimento , Oryza/genética , Desequilíbrio de Ligação , Fenótipo , Melhoramento Vegetal , Polimorfismo de Nucleotídeo Único , Locos de Características Quantitativas
13.
Prep Biochem Biotechnol ; : 1-11, 2021 Aug 02.
Artigo em Inglês | MEDLINE | ID: mdl-34339343

RESUMO

The optimization of extraction of Tetrastigma hemsleyanum Diels et Gilg polysaccharides (THP) using ultrasonic with enzyme method and its monosaccharide compositions and antioxidant activity were investigated in this work. Single-factor experiments and response surface methodology (RSM) were performed to optimize conditions for extraction, and the independent variables were (XA) dosage of cellulase, (XB) extraction time, (XC) ultrasonic power, and (XD) ratio of water to the material. The extraction rate of THP was increased effectively under the optimum conditions, and the maximum (4.692 ± 0.059%) was well-matched the predicted value from RSM. THP was consisted of mannose, glucuronic acid, rhamnose, galacturonic acid, glucose, galactose, and arabinose, while glucose was the dominant (26.749 ± 0.634%). According to the total antioxidant capacity assay with the FRAP method, DPPH, and hydroxyl radical scavenging assay, THP showed strong antioxidant activity with a dose-dependent behavior. The results indicated that THP has the potential to be a novel antioxidant and could expand its application in food and medicine.

14.
J Immunother Cancer ; 9(7)2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-34272308

RESUMO

BACKGROUND: Mesenteric lymph nodes (MLNs) are critical draining lymph nodes of the immune system that accommodate more than half of the body's lymphocytes, suggesting their potential value as a cancer immunotherapy target. Therefore, efficient delivery of immunomodulators to the MLNs holds great potential for activating immune responses and enhancing the efficacy of antitumor immunotherapy. Self-microemulsifying drug delivery systems (SMEDDS) have attracted increasing attention to improving oral bioavailability by taking advantage of the intestinal lymphatic transport pathway. Relatively little focus has been given to the lymphatic transport advantage of SMEDDS for efficient immunomodulators delivery to the MLNs. In the present study, we aimed to change the intestinal lymphatic transport paradigm from increasing bioavailability to delivering high concentrations of immunomodulators to the MLNs. METHODS: Chlorogenic acid (CHA)-encapsulated SMEDDS (CHA-SME) were developed for targeted delivery of CHA to the MLNs. The intestinal lymphatic transport, immunoregulatory effects on immune cells, and overall antitumor immune efficacy of CHA-SME were investigated through in vitro and in vivo experiments. RESULTS: CHA-SME enhanced drug permeation through intestinal epithelial cells and promoted drug accumulation within the MLNs via the lymphatic transport pathway. Furthermore, CHA-SME inhibited tumor growth in subcutaneous and orthotopic glioma models by promoting dendritic cell maturation, priming the naive T cells into effector T cells, and inhibiting the immunosuppressive component. Notably, CHA-SME induced a long-term immune memory effect for immunotherapy. CONCLUSIONS: These findings indicate that CHA-SME have great potential to enhance the immunotherapeutic efficacy of CHA by activating antitumor immune responses.

15.
Biochem Biophys Res Commun ; 568: 174-179, 2021 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-34246051

RESUMO

The aim of the study was to develop a model of coronary microembolization (CME) in rats at a lower cost. We developed a novel rat model without thoracotomy and ventilation under the guidance of echocardiography. Rats were sacrificed at 3 h, 24 h and 1 month postoperatively in both the Echo-CME and Open-chest CME groups for the comparison of the modeling accuracy, mortality, cardiopulmonary circulation, pleural adhesion and ventilation-induced lung injury (VILI). Results showed that the coronary microthrombus formed at 3 h and reached its peak at 24 h postoperatively, which included platelet aggregation and fibrin web. The Echo-group increases success rates, decreased mortality, postoperative complications including pleural adhesion, cardiopulmonary dysfunction and VILI postoperatively than the Open-chest group at 1month postoperatively. The ejection fraction of the CME group decreased to 50% and obvious cardiac fibrosis formed at 3 months postoperatively. Our unique surgical method provided a platform to study molecular mechanisms and potential new pathways for CME treatment.

16.
Analyst ; 146(15): 4811-4821, 2021 Aug 07.
Artigo em Inglês | MEDLINE | ID: mdl-34195717

RESUMO

Optical, and especially fiber-optic techniques for the sensing of pH have become very attractive and considerable research progress in this field has been made over recent years. The determination of the value of pH across a broad range of applications today, important for areas of study such as life sciences, environmental monitoring, manufacturing industry and widely in biological research is now accessible from such optical sensors. The need for such technology arises because familiar, commercial sensors are often limited in terms of their response time and the presence of drift, all of which emphasize the value of newer and rapidly developing technologies such as fiber-optic sensors, to address these wider applications. As a result, a new compact sensor design has been developed, designed around a specially-formed fiber-optic tip, coated with a pH-sensitive dye, and importantly covalently linked to a hydrogel matrix to provide high stability. The sensor developed was designed to have a very fast response time (to 90% of saturation, Δt90) of <5 s and a sensing uncertainty of ∼±0.04 pH units. Given the covalently bonded nature of the dye, the problem of leaching of the indicator dye is reduced, creating a probe which has been shown to be very stable over many days of use. Illustrating this through extended continuous use, over ∼12 h at pH 7, this stability was confirmed showing a drift of <0.05 pH h-1. In order to give an illustration of the value of the probe in an important biological application, the monitoring of pH levels between pH 7 to pH 8 in an AMES' medium, a substance which is important to maintain the metabolism of retinal cells is shown and the results as well as temperature stability of the probe discussed.


Assuntos
Monitoramento Ambiental , Tecnologia de Fibra Óptica , Hidrogéis , Concentração de Íons de Hidrogênio , Temperatura
17.
J Nanobiotechnology ; 19(1): 199, 2021 Jul 05.
Artigo em Inglês | MEDLINE | ID: mdl-34225762

RESUMO

BACKGROUND: Standard chemotherapy with taxanes, such as paclitaxel (PTX), remains the mainstay of systemic treatment of triple-negative breast cancer. Nanotechnology-based formulations have gradually replaced PTX injection and are widely used in China. However, no studies have compared the colloidal stability, antitumor efficacy, and safety of commercial PTX nanoformulations. Additionally, the desire to evaluate preclinical antitumor efficacy in human-derived tumor cells led to the widespread application of immunodeficient mouse models that likely contributed to the neglect of nanomedicines-immune system interactions. The present study investigated the colloidal stability, antitumor efficacy and safety, and nanomedicines-host immune system interactions of PTX nanoformulations. A further comparative analysis was performed to evaluate the clinical potential. RESULTS: Compared with liposome, PTX emulsion and PTX nanoparticle exhibited favorable colloidal stability. PTX emulsion was superior in inducing apoptosis and had a more pronounced inhibitory effect on 4T1-tumor spheroids compared with PTX liposome and PTX nanoparticle. Although PTX emulsion exhibited superior in vitro antitumor effect, no significant differences in the in vivo antitumor efficacy were found among the three types of PTX nanoformulations in an immunocompetent orthotopic 4T1 murine triple-negative breast cancer model. All PTX nanoformulations at maximum tolerated dose (MTD) induced lymphopenia and immunosuppression, as evidenced by the reduction of T cell subpopulations and inhibition of the dendritic cells maturation. CONCLUSIONS: The MTD PTX nanomedicines-induced lymphopenia and immunosuppression may weaken the lymphocyte-mediated antitumor cellular immune response and partly account for the lack of differences in the in vivo antitumor outcomes of PTX nanoformulations. Understanding of what impacts PTX nanomedicines has on the immune system may be critical to improve the design and conduct of translational research of PTX nanomedicines in monotherapy or combination therapy with immunotherapy.

18.
Int J Biol Macromol ; 184: 739-749, 2021 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-34174310

RESUMO

Polylactic acid (PLA) is a promising food packaging material with biocompatible, nontoxic and biodegradable. In order to reduce the deterioration of aquatic products caused by microorganisms, PLA coaxial nanofiber films with cinnamaldehyde (CMA), tea polyphenol (TP) and its composite as core materials were prepared by using coaxial electrospinning technology. Its microscopic morphology and structure were characterized separately, and its thermal stability, wettability and mechanical properties were determined. The antibacterial activity and antibacterial mechanism of nanofiber films were studied with Shewanella putrefaciens (S. putrefaciens) which is the dominant spoilage of aquatic products as the target of action. The results show that the CMA/TP (m/m = 2:5)-PLA coaxial nanofibers have small diameter, uniform distribution, smooth surface, no pores and fracture. At the same time, the film has strong hydrophobicity, good thermal stability and mechanical properties. Its antibacterial performance is better than that of single-core nanofiber films, which effectively destroys the cell membrane of S. putrefaciens, increases the permeability of cell membrane, and interferes with the synthesis and expression of its protein. The coaxial nanofiber films with CMA, TP and its composite as core material can be used as a fresh-keeping material with antibacterial properties, and has potential application value in the field of food preservation.


Assuntos
Acroleína/análogos & derivados , Antibacterianos/síntese química , Poliésteres/química , Polifenóis/síntese química , Shewanella putrefaciens/efeitos dos fármacos , Chá/química , Acroleína/química , Antibacterianos/química , Antibacterianos/farmacologia , Materiais Biocompatíveis/síntese química , Materiais Biocompatíveis/química , Materiais Biocompatíveis/farmacologia , Estabilidade de Medicamentos , Microbiologia de Alimentos , Embalagem de Alimentos , Temperatura Alta , Interações Hidrofóbicas e Hidrofílicas , Nanofibras , Polifenóis/química , Polifenóis/farmacologia
19.
Diabetologia ; 64(9): 2037-2051, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34117507

RESUMO

AIMS/HYPOTHESIS: Macrophage levels are elevated in pancreatic islets, and the resulting inflammatory response is a major contributor to beta cell failure during obesity and type 2 diabetes mellitus. Previous studies by us and others have reported that exosomes released by macrophages play important roles in mediating cell-to-cell communication, and represent a class of inflammatory factors involved in the inflammatory process associated with type 2 diabetes mellitus. However, to date, no reports have demonstrated the effect of macrophage-derived exosomes on beta cells, and little is known regarding their underlying mechanisms in beta cell injury. Thus, we aimed to study the impact of macrophage-derived exosomes on islet beta cell injury in vitro and in vivo. METHODS: The phenotypic profiles of islet-resident macrophages were analysed in C57BL/6J mice fed a high-fat diet (HFD). Exosomes were collected from the medium of cultured bone marrow-derived macrophages (BMDMs) and from isolated islet-resident macrophages of HFD-fed mice (HFD-Exos). The role of exosomes secreted by inflammatory M1 phenotype BMDMs (M1-Exos) and HFD-Exos on beta cell function was assessed. An miRNA microarray and quantitative real-time PCR (qPCR) were conducted to test the level of M1-Exos-derived miR-212-5p in beta cells. Then, miR-212-5p was overexpressed or inhibited in M1-Exos or beta cells to determine its molecular and functional impact. RESULTS: M1-polarised macrophages were enriched in the islets of obese mice. M1 macrophages and islet-resident macrophages of HFD-fed mice impaired beta cell insulin secretion in an exosome-dependent manner. miR-212-5p was notably upregulated in M1-Exos and HFD-Exos. Enhancing the expression of miR-212-5p impaired beta cell insulin secretion. Blocking miR-212-5p elicited a significant improvement in M1-Exos-mediated beta cell insulin secretion during injury. Mechanistically, M1-Exos mediated an intercellular transfer of the miR-212-5p, targeting the sirtuin 2 gene and regulating the Akt/GSK-3ß/ß-catenin pathway in recipient beta cells to restrict insulin secretion. CONCLUSIONS/INTERPRETATION: A novel exosome-modulated mechanism was delineated for macrophage-beta cell crosstalk that drove beta cell dysfunction and should be explored for its therapeutic utility.

20.
World J Emerg Med ; 12(3): 207-213, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34141036

RESUMO

BACKGROUND: There are conflicting results regarding whether corticosteroids have better efficacy than placebo in acute respiratory distress syndrome (ARDS) patients. Therefore, we aim to further evaluate the efficacy and safety of corticosteroids in adult ARDS patients. METHODS: The databases, including Medline, EMBASE, and Cochrane Central Register of Controlled Trials (CENTRAL) in the Cochrane Library, were searched from their inception to May 2, 2020. Randomized controlled trials (RCTs) and observational cohort studies were selected to assess the use of corticosteroids in adult ARDS patients. The quality of the results was judged by the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) methodology. The inverse-variance method with random or fixed effects modeling was used to compute pooled odds ratio (OR), standardized mean difference (SMD), and their 95% confidence interval (CI). RESULTS: Eight eligible RCTs and six cohort studies were included. The use of corticosteroids was associated with reduced mortality (OR 0.57, 95% CI 0.43-0.76, I2=35.1%, P=0.148) in ARDS patients, and the result was confirmed in the included cohort studies (OR 0.51, 95% CI 0.27-0.95, I2=66.7%, P=0.010). The subgroup analysis stratified by the initiation time and duration of corticosteroid use showed that early ARDS and prolonged corticosteroid use had significant survival benefits in the RCTs. The low-dose corticosteroid use was also associated with significantly more ventilator-free days and a reduced rate of new infections in ARDS patients. CONCLUSIONS: The low-dose corticosteroid therapy may be safe and reduce mortality, especially in patients with prolonged treatment and early ARDS.

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