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1.
J Hazard Mater ; 423(Pt B): 127114, 2022 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-34537638

RESUMO

Although selenium (Se) is an essential microelement for humans and animals, it is a potentially toxic element due to its bioaccumulation potential. In this study, Se fertilizer was supplied in a greenhouse vegetable (cucumber) plantation using an innovative system consisting of nanobubbles (NB_Se) and compared to that under conventional conditions of fertigation (C_Se) with six doses. The results revealed that NB_Se significantly reduced soil Se accumulation (38%-144%) and increased cucumber Se content compared with the C_Se treatments at the same Se dose. NB_Se significantly lowered the soil bacterial diversity, with an initial increase and then decrease with the Se doses. Bacterial associations and potential keystone taxa also differed between the NB_Se and C_Se. The greater abundance of oxidizing bacteria (indicated by the function composition of bacterial community) and the improved soil redox environment created by NBs sustained more available Se for plants, leading to a reduction in soil Se residual and an increase in the plant Se content. Our results highlight the feasibility and efficiency of NB_Se and demonstrate the important implications of Se for the maintenance of soil health and sustainability.

2.
Nanomaterials (Basel) ; 11(11)2021 Nov 02.
Artigo em Inglês | MEDLINE | ID: mdl-34835703

RESUMO

The photocatalysis technique has been proven to be a promising method to solve environmental pollution in situations of energy shortage, and has been intensively investigated in the field of pollutant degradation. In this work, a band structure-controlled solid solution of BiOBrXI1-X (x = 0.00, 0.05, 0.10, 0.15, 0.20, 1.00) with highly efficient light-driven photocatalytic activities was successfully synthesized via simple solvothermal methods. The phase composition, crystal structure, morphology, internal molecular vibration, optical properties, and energy band structure were characterized and analyzed by XRD, SEM, HRTEM, XPS, Raman, and UV Vis DRS. To evaluate the photocatalytic activity of BiOBrXI1-X, rhodamine B was selected as an organic pollutant. In particular, BiOBr0.15I0.85 displayed significantly enhanced photocatalytic activity by virtue of modulating the energy band position, optimizing redox potentials, and accelerating carrier separation. Moreover, the enhancement mechanism was elucidated on the basis of band structure engineering, which provides ideas for the design of highly active photocatalysts for practical application in the fields of environmental issues and energy conservation.

3.
Nat Commun ; 12(1): 6365, 2021 11 09.
Artigo em Inglês | MEDLINE | ID: mdl-34753899

RESUMO

The nucleolus is the organelle for ribosome biogenesis and sensing various types of stress. However, its role in regulating stem cell fate remains unclear. Here, we present evidence that nucleolar stress induced by interfering rRNA biogenesis can drive the 2-cell stage embryo-like (2C-like) program and induce an expanded 2C-like cell population in mouse embryonic stem (mES) cells. Mechanistically, nucleolar integrity maintains normal liquid-liquid phase separation (LLPS) of the nucleolus and the formation of peri-nucleolar heterochromatin (PNH). Upon defects in rRNA biogenesis, the natural state of nucleolus LLPS is disrupted, causing dissociation of the NCL/TRIM28 complex from PNH and changes in epigenetic state and reorganization of the 3D structure of PNH, which leads to release of Dux, a 2C program transcription factor, from PNH to activate a 2C-like program. Correspondingly, embryos with rRNA biogenesis defect are unable to develop from 2-cell (2C) to 4-cell embryos, with delayed repression of 2C/ERV genes and a transcriptome skewed toward earlier cleavage embryo signatures. Our results highlight that rRNA-mediated nucleolar integrity and 3D structure reshaping of the PNH compartment regulates the fate transition of mES cells to 2C-like cells, and that rRNA biogenesis is a critical regulator during the 2-cell to 4-cell transition of murine pre-implantation embryo development.

4.
J Integr Neurosci ; 20(3): 573-583, 2021 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-34645090

RESUMO

We investigated the anti-aging effects of velvet antler polypeptide on D-galactose (D-gal)-induced aging mice. D-gal-induced aging mice were established and randomly divided into five groups, the control, model, vitamin E (VE), velvet antler polypeptide low-dose and velvet antler polypeptide high-dose groups. The Morris water maze test was used to evaluate the learning and memory abilities of aging mice. Hippocampal neurons were observed via hematoxylin-eosin staining and transmission electron microscopy. Biochemical methods were used to detect the activities of superoxide dismutase, malonaldehyde and other enzymes and evaluate the influence of velvet antler polypeptide on the antioxidant capacity of aging mice. Using 16S rRNA gene sequencing and meristem technology, we assessed the effect of velvet antler polypeptide on aging mice's intestinal flora and fatty acid metabolism. The experimental results showed that velvet antler polypeptide could significantly improve aging mice's learning and cognitive abilities, increase the activities of superoxide dismutase, glutathione peroxidase, and catalase in the serum decrease the malonaldehyde content. Intestinal microecological analysis showed that velvet antler polypeptide could significantly increase the beneficial bacterial genus Lactobacillus abundance. Western blot analysis further demonstrated that velvet antler polypeptide could promote fatty acid metabolism by activating peroxisome proliferator-activated receptor α (PPARα) and upregulating the expression of the downstream enzymes carnitine-palmitoyl transferase-1 A and acyl-CoA oxidase 1 while downregulating that of apolipoprotein E4 (APOE4), thereby reducing fatty acid accumulation and increasing adenosine-triphosphate (ATP) production. Therefore, velvet antler polypeptide improves the intestinal microecology and activates the PPARα/APOE4 pathway to regulate fatty acid metabolism.

5.
Front Oncol ; 11: 721591, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34595115

RESUMO

Purpose: To find a suitable method for analyzing electronic portal imaging device (EPID) transmission fluence maps for the identification of position errors in the in vivo dose monitoring of patients with Graves' ophthalmopathy (GO). Methods: Position errors combining 0-, 2-, and 4-mm errors in the left-right (LR), anterior-posterior (AP), and superior-inferior (SI) directions in the delivery of 40 GO patient radiotherapy plans to a human head phantom were simulated and EPID transmission fluence maps were acquired. Dose difference (DD) and structural similarity (SSIM) maps were calculated to quantify changes in the fluence maps. Three types of machine learning (ML) models that utilize radiomics features of the DD maps (ML 1 models), features of the SSIM maps (ML 2 models), and features of both DD and SSIM maps (ML 3 models) as inputs were used to perform three types of position error classification, namely a binary classification of the isocenter error (type 1), three binary classifications of LR, SI, and AP direction errors (type 2), and an eight-element classification of the combined LR, SI, and AP direction errors (type 3). Convolutional neural network (CNN) was also used to classify position errors using the DD and SSIM maps as input. Results: The best-performing ML 1 model was XGBoost, which achieved accuracies of 0.889, 0.755, 0.778, 0.833, and 0.532 in the type 1, type 2-LR, type 2-AP, type 2-SI, and type 3 classification, respectively. The best ML 2 model was XGBoost, which achieved accuracies of 0.856, 0.731, 0.736, 0.949, and 0.491, respectively. The best ML 3 model was linear discriminant classifier (LDC), which achieved accuracies of 0.903, 0.792, 0.870, 0.931, and 0.671, respectively. The CNN achieved classification accuracies of 0.925, 0.833, 0.875, 0.949, and 0.689, respectively. Conclusion: ML models and CNN using combined DD and SSIM maps can analyze EPID transmission fluence maps to identify position errors in the treatment of GO patients. Further studies with large sample sizes are needed to improve the accuracy of CNN.

6.
Science ; 374(6564): 163, 2021 Oct 08.
Artigo em Inglês | MEDLINE | ID: mdl-34618593
7.
Sheng Li Xue Bao ; 73(5): 734-744, 2021 Oct 25.
Artigo em Chinês | MEDLINE | ID: mdl-34708230

RESUMO

Circadian clock is an internal autonomous time-keeping system, including central clocks located in the suprachiasmatic nucleus (SCN) and peripheral clocks. The molecular circadian clock consists of a set of interlocking transcriptional-translational feedback loops that take the clock-controlled genes 24 h to oscillate. The core mechanism of molecular circadian clock is that CLOCK/BMAL1 dimer activates the transcription of cryptochromes (CRYs) and Periods (PERs), which act as transcriptional repressors of further CLOCK/BMAL1-mediated transcription. In addition to this basic clock, there is an additional sub-loop of REV-ERBα and RORα regulating the transcription of BMAL1. Approximately 80% protein-coding genes demonstrate significant rhythmicity. The earth rotation is responsible for the generation of the daily circadian rhythms. To coordinate metabolic balance and energy availability, almost all organisms adapt to the rhythm. Studies have shown that circadian clock integrating with metabolic homeostasis increases the efficiency of energy usage and coordinates with different organs in order to adapt to internal physiology and external environment soon. As the central organ of metabolism, the liver performs various physiological activities nearly all controlled by the circadian clock. There are multiple interactive regulation mechanisms between the circadian clock and the regulation of liver metabolism. The misalignment of metabolism with tissue circadian is identified as a high-risk factor of metabolic diseases. This article reviews the recent studies on circadian physiological regulation of liver glucose, lipid and protein metabolism and emphasizes oscillation of mitochondrial function. We also take an outlook for new methods and application of circadian clock research in the future.


Assuntos
Relógios Circadianos , Proteínas CLOCK , Relógios Circadianos/genética , Ritmo Circadiano , Fígado , Núcleo Supraquiasmático
8.
Nature ; 599(7884): 290-295, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34671164

RESUMO

Mouse caspase-11 and human caspase-4 and caspase-5 recognize cytosolic lipopolysaccharide (LPS) to induce pyroptosis by cleaving the pore-forming protein GSDMD1-5. This non-canonical inflammasome defends against Gram-negative bacteria6,7. Shigella flexneri, which causes bacillary dysentery, lives freely within the host cytosol where these caspases reside. However, the role of caspase-11-mediated pyroptosis in S. flexneri infection is unknown. Here we show that caspase-11 did not protect mice from S. flexneri infection, in contrast to infection with another cytosolic bacterium, Burkholderia thailandensis8. S. flexneri evaded pyroptosis mediated by caspase-11 or caspase 4 (hereafter referred to as caspase-11/4) using a type III secretion system (T3SS) effector, OspC3. OspC3, but not its paralogues OspC1 and 2, covalently modified caspase-11/4; although it used the NAD+ donor, this modification was not ADP-ribosylation. Biochemical dissections uncovered an ADP-riboxanation modification on Arg314 and Arg310 in caspase-4 and caspase-11, respectively. The enzymatic activity was shared by OspC1 and 2, whose ankyrin-repeat domains, unlike that of OspC3, could not recognize caspase-11/4. ADP-riboxanation of the arginine blocked autoprocessing of caspase-4/11 as well as their recognition and cleavage of GSDMD. ADP-riboxanation of caspase-11 paralysed pyroptosis-mediated defence in Shigella-infected mice and mutation of ospC3 stimulated caspase-11- and GSDMD-dependent anti-Shigella humoral immunity, generating a vaccine-like protective effect. Our study establishes ADP-riboxanation of arginine as a bacterial virulence mechanism that prevents LPS-induced pyroptosis.

9.
J Exp Psychol Hum Percept Perform ; 47(9): 1247-1252, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34694853

RESUMO

Apparent motion is a robust perceptual phenomenon in which observers perceive a stimulus traversing the vacant visual space between two flashed stimuli. Although it is known that the "filling-in" of apparent motion favors the simplest and most economical path, the interpolative computations remain poorly understood. Here, we tested whether the perception of apparent motion is best characterized by Newtonian physics or kinematic geometry. Participants completed a target detection task while Pacmen-shaped objects were presented in succession to create the perception of apparent motion. We found that target detection was impaired when apparent motion, as predicted by kinematic geometry, not Newtonian physics, obstructed the target's location. Our findings shed light on the computations employed by the visual system, suggesting specifically that the "filling-in" perception of apparent motion may be dominated by kinematic geometry, not Newtonian physics. (PsycInfo Database Record (c) 2021 APA, all rights reserved).


Assuntos
Percepção de Movimento , Humanos , Movimento (Física) , Estimulação Luminosa , Percepção Visual
10.
Environ Sci Technol ; 55(19): 13122-13131, 2021 10 05.
Artigo em Inglês | MEDLINE | ID: mdl-34523920

RESUMO

Due to commercial uses and environmental degradation of aryl phosphate esters, diphenyl phosphate (DPhP) is frequently detected in environmental matrices and is thus of growing concern worldwide. However, information on potential adverse effects of chronic exposure to DPhP at environmentally realistic concentrations was lacking. Here, we investigated the effects of life cycle exposure to DPhP on zebrafish at environmentally relevant concentrations of 0.8, 3.9, or 35.6 µg/L and employed a dual-omics approach (metabolomics and transcriptomics) to characterize potential modes of action. Exposure to DPhP at 35.6 µg/L for 120 days resulted in significant reductions in body mass and length of male zebrafish, but did not cause those same effects to females. Predominant toxicological mechanisms, including inhibition of oxidative phosphorylation, down-regulation of fatty acid oxidation, and up-regulation of phosphatidylcholine degradation, were revealed by integrated dual-omics analysis and successfully linked to adverse outcomes. Activity of succinate dehydrogenase and protein content of carnitine O-palmitoyltransferase 1 were significantly decreased in livers of male fish exposed to DPhP, which further confirmed the proposed toxicological mechanisms. This study is the first to demonstrate that chronic, low-level exposure to DPhP can retard growth via inhibiting energy output in male zebrafish.


Assuntos
Retardadores de Chama , Peixe-Zebra , Animais , Compostos de Bifenilo , Metabolismo Energético , Feminino , Estágios do Ciclo de Vida , Masculino , Fosfatos
11.
Cancer Med ; 10(17): 6089-6098, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34346560

RESUMO

Bilateral breast cancer (BBC) is an uncommon subset of breast cancer (BC), and it may present as synchronous bilateral breast cancer (sBBC) or metachronous bilateral breast cancer (mBBC). Through this study, we aimed to evaluate the proportion of BBC in BC and compare the clinicopathological characteristics, treatment, and outcomes of sBBC and mBBC at an academic cancer center in China. Patients with BC consecutively treated between 2006 and 2016 were retrospectively reviewed. Patients with BBC were included. In total, 3924 patients with BC were analyzed and 127 patients with BBC (28 sBBC, 99 mBBC) with a median follow-up of 98 months were identified. The proportion of BBC was 3.2% (0.7%, sBBC; 2.5%, mBBC). The median age at the first diagnosis of mBBC was significantly younger than that at the first diagnosis of sBBC (p = 0.027). Patients diagnosed as having sBBC were more likely to have a positive family history (p = 0.047). The first tumors of mBBC were detected at a significantly earlier tumor stage compared with those of sBBC (p = 0.028). The concordance rates of histopathologic type in the first and second tumors were 60.7% and 58.0% in sBBC and mBBC, respectively. sBBC had a significantly poorer disease-free survival than mBBC did (p = 0.001). BBC is a rare disease affecting the Chinese population. sBBC is associated with a greater prevalence of a family history of breast cancer and poorer prognosis, compared with mBBC.

12.
Breast Cancer Res Treat ; 189(3): 725-736, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34392453

RESUMO

PURPOSE: To evaluate GT0918, a 2nd-generation AR antagonist, for its AR down-regulation activity among breast cancer patients. METHODS: The effect of GT0918 on AR protein expression was evaluated in AR expression breast cancer cells and in breast cancer xenograft model. A 3 + 3 phase I dose-escalation study was launched in Peking University Cancer Hospital. The endpoints included dose finding, safety, pharmacokinetics, and antitumor activity. RESULTS: GT0918 was demonstrated to effectively suppress the expression of AR protein and the growth of AR-positive breast cancer tumors in mouse xenograft tumor models. All patients treated with GT0918 were at a QD dose-escalation of five dose levels from 100 to 500 mg. The most common treatment-related AEs of any grade were asthenia, anemia, decreased appetite, increased blood cholesterol, increased blood triglycerides, decreased white blood cell count, and increased low-density lipoprotein. Grade 3 AEs were fatigue (2 of 18, 11.1%), aspartate aminotransferase increase (1 of 18, 5.6%), alanine aminotransferase increase (1 of 18, 5.6%), and neutrophil count decrease (1 of 18, 5.6%). Clinical benefit rate (CBR) in 16 weeks was 23.1% (3/13). Among 7 AR-positive patients, 6 can evaluate efficacy, and 2 completed 23.5- and 25-cycle treatment, respectively (as of 2020/1/20). PK parameters showed a fast absorption profile of GT0918 in the single-dose study. GT0918 and its major metabolite reached steady-state serum concentration levels at day 21 after multiple dosing. CONCLUSION: GT0918 can effectively inhibit AR-positive breast cancer tumor growth. GT0918 was demonstrated well tolerated with a favorable PK profile. The suitable dose of GT0918 was 500 mg QD and may provide clinical benefits for AR-positive mBC.


Assuntos
Antagonistas de Receptores de Andrógenos , Neoplasias da Mama , Animais , Neoplasias da Mama/tratamento farmacológico , Feminino , Humanos , Camundongos , Oxazóis , Receptores Androgênicos , Tioidantoínas
13.
Anatol J Cardiol ; 25(7): 476-483, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-34236322

RESUMO

OBJECTIVE: Severe right ventricular hypertrophy (SRVH) in hypertrophic cardiomyopathy (HCM) is rare. We studied the clinical characteristics and prognosis of 36 patients with HCM and SRVH in a Chinese cohort. METHODS: Patients with HCM and SRVH were enrolled between 2013 and 2017. The clinical characteristics, treatment therapies, and clinical outcomes of the 36 patients were retrospectively studied and compared with those of 128 patients without SRVH. RESULTS: Patients in the group with SRVH were younger than those in the group without SRVH (27.58±15.09 years vs 40.34±13.21 years, respectively; p<0.001). Patients with SRVH had more serious clinical symptoms and a higher New York Heart Association functional class than those without SRVH. Most patients in the group with SRVH exhibited diffuse RV hypertrophy, and 13 patients presented with biventricular outflow tract obstruction. Maximal left ventricular (LV) wall thickness (27.29±7.95 mm vs 24.33±5.85 mm, respectively; p=0.027) and LV outflow tract gradient (80.83±24.41 mm Hg vs 42.3±5.7 mm Hg, respectively; p=0.000) were significantly greater in patients with SRVH than in those without SRVH. A total of 30 patients in the group with SRVH underwent surgical correction. During a median follow-up period of 48 months, six patients with SRVH reached primary clinical endpoints (four sudden cardiac deaths, one heart failure-related death, and one heart transplantation), whereas only two deaths occurred in the patients without SRVH. CONCLUSION: We conclude that patients with HCM and SRVH exhibit serious symptoms and have complex surgical requirements and poor clinical outcomes.


Assuntos
Cardiomiopatia Hipertrófica , Obstrução do Fluxo Ventricular Externo , Cardiomiopatia Hipertrófica/complicações , Cardiomiopatia Hipertrófica/diagnóstico por imagem , Cardiomiopatia Hipertrófica/cirurgia , Hospitais , Humanos , Hipertrofia Ventricular Direita/diagnóstico por imagem , Prognóstico , Estudos Retrospectivos
14.
Am J Med Sci ; 362(3): 260-267, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34266644

RESUMO

BACKGROUND: The prevalence of Fabry disease (FD) in Chinese patients with hypertrophic cardiomyopathy (HCM) is unclear. We aimed to evaluate the prevalence, clinical characteristics, and outcomes of FD in Chinese patients with HCM. METHODS: Of 217 patients with HCM, FD probands were screened by next-generation sequencing at Fuwai Hospital. Medical data from α-galactosidase A activity, electrocardiography, echocardiography, coronary angiography, cardiac magnetic resonance, pathological examination, and follow up was analyzed. RESULTS: Two FD probands were observed (0.93% of patients with HCM), both of which were diagnosed with symptomatic obstructive HCM at 49 years of age. One proband had a GLA mutation (c.887T>C [p.M296T]) with a late-onset cardiac variant, which was characterized by dual ventricular hypertrophy and conduction disease with a permanent pacemaker. The other patient had a GLA mutation (c.758T>C [p.I253T]) with a classic phenotype and dual ventricular hypertrophy, atrioventricular block, renal failure, and recurrent cerebral infarction. Both probands had late gadolinium enhancement mainly in the basal segment of the inferolateral wall. Follow up revealed no exertional symptoms or outflow obstruction after surgical septal myectomy in the two probands, and stable renal function was observed after 6 months of migalastat therapy in the later one. A family study revealed six female carriers and three sudden cardiac deaths. CONCLUSIONS: FD is not uncommon in Chinese patients with HCM. Multiple organic involvement, dual ventricular hypertrophy, and conduction disease provide clinical clues for suspected FD, and early genetic screening is necessary. Surgical septal myectomy and migalastat improve the long-term prognosis of patients with FD.


Assuntos
Cardiomiopatia Hipertrófica/diagnóstico por imagem , Cardiomiopatia Hipertrófica/epidemiologia , Doença de Fabry/diagnóstico por imagem , Doença de Fabry/epidemiologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Cardiomiopatia Hipertrófica/genética , China/epidemiologia , Ecocardiografia/métodos , Eletrocardiografia/métodos , Doença de Fabry/genética , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Linhagem , Prevalência , Adulto Jovem
15.
Environ Int ; 155: 106691, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34146766

RESUMO

Over the course of the continual phase-outs of toxic halogenated flame retardants (HFRs), there has been an increasing demand for organophosphate esters (OPEs) in global FR markets. OPE-FRs have largely been identified as OP triesters, which have a basic chemical structure of O = P(OR)3. In addition to OP triesters, OPEs can refer to another class of related substances, namely, OP diesters that have a typical chemical structure of O = P(OR)2(OH)). OP diesters are known as biotic or abiotic degradation products of OP triesters. In recent years, environmental scientists have proven that OP diesters widely exist in a variety of environmental matrices and biotic samples around the world, implying the potential risks from OP diester exposure to biota and humans in the environment. Here, we have reviewed the scientific literature for studies involving OP diesters and up to the end of 2020. The aim of the present review is to assess the present understanding of the physicochemical properties, sources (industrial production and degradation), environmental occurrence of OP diesters, and adverse effects to exposed organisms. Based on the literature in the Web of Science core collection, we found that at least 23 OP diesters have been reported as contaminants in various environments or as degradation products of OP triesters. The physicochemical properties of OP diesters vary depending on their specific chemical structures. OP diesters containing halogen atoms and aryl groups seem to be more persistent (with greater estimated half-life (t1/2) values) in environmental matrices. There were multiple sources of OP diesters, including industrial production and biotic or abiotic degradation from OP triesters. Specifically, we found that ten OP diesters are produced somewhere in the world, and the total annual output was estimated to be 17,050 metric tons (this number is underestimated due to the limitation of the available information). In addition, the wide application of OP triesters worldwide makes the degradation of OP triesters another critical source of OP diesters to the environment and to organisms. Current monitoring studies have demonstrated that some OP diesters were detectable in the human body (via both blood and urine samples), indoor dust, wastewater, or sewage sludge worldwide. The highest concentrations of diphenyl phosphate (DPHP) in human urine have been reported as high as 727 ng/mL (children (aged 0-5 years) urine samples from Australia). In addition, adverse effects following direct or indirect exposure to 11 OP diesters in organisms (including animals, bacteria, and algae) have been reported, and the recorded adverse outcomes following exposure to OP diesters included developmental toxicity, alteration of gene expression, and disturbance of nuclear receptor activity. Biomonitoring studies regarding human samples have frequently reported statistically significant associations between the concentrations of OP diesters and markers of human health (mainly related to reproductive toxicity). Finally, on the basis of current knowledge on OP diesters, we propose prospects for related research directions in future studies.


Assuntos
Retardadores de Chama , Organofosfatos , Animais , Criança , Poeira/análise , Monitoramento Ambiental , Ésteres/análise , Retardadores de Chama/análise , Retardadores de Chama/toxicidade , Humanos , Organofosfatos/análise , Organofosfatos/toxicidade , Esgotos , Águas Residuárias
16.
Chin J Cancer Res ; 33(2): 243-255, 2021 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-34158743

RESUMO

Objective: Breast cancer (BC) with chest wall metastasis (CWM) usually shows rich neovascularization. This trial explored the clinical effect of apatinib on human epidermal growth factor receptor 2 (HER2)-negative advanced BC involving CWM. Methods: This trial involved four centers in China and was conducted from September 2016 to March 2020. Patients received apatinib 500 mg/d [either alone or with endocrine therapy if hormone receptor-positive (HR+)] until disease progression or unacceptable toxicity. Progression-free survival (PFS) was the primary endpoint. Results: We evaluated 26 patients for efficacy. The median PFS (mPFS) and median overall survival (mOS) were 4.9 [range: 2.0-28.5; 95% confidence interval (95% CI): 2.1-8.3] months and 18 (range: 3-55; 95% CI: 12.9-23.1) months, respectively. The objective response rate (ORR) was 42.3% (11/26), and the disease-control rate was 76.9% (20/26). In the subgroup analysis, HR+ patients compared with HR-negative patients had significantly improved mPFS of 7.0 (95% CI: 2.2-11.8) monthsvs. 2.3 (95% CI: 1.2-3.4) months, respectively (P=0.001); and mPFS in patients without or with chest wall radiotherapy was 6.4 (95% CI: 1.6-19.5) monthsvs. 3.0 (95% CI: 1.3-4.6) months, respectively (P=0.041). In the multivariate analysis, HR+ status was the only independent predictive factor for favorable PFS (P=0.014). Conclusions: Apatinib was highly effective for BC patients with CWM, especially when combined with endocrine therapy. PFS improved significantly in patients with HR+ status who did not receive chest wall radiotherapy. However, adverse events were serious and should be carefully monitored from the beginning of apatinib treatment.

17.
Front Oncol ; 11: 608781, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34012912

RESUMO

Purpose: To compare the efficacy and safety between pyrotinib (Pyr) and trastuzumab emtansine (T-DM1) in pre-treated human epidermal growth factor receptor 2-positive (HER2+) metastatic breast cancer (MBC) patients. Methods: A comprehensive literature search of the PubMed, EMBASE, and Web of Science was performed in August 2020. Randomized clinical trials comparing the efficacy and safety between different anti-HER2 regimens in patients pre-treated with trastuzumab (Tra) and a taxane in metastatic settings (≤second-line treatment) were included. A fixed effects network meta-analysis based on the Bayesian inferential framework was conducted for progression-free survival (PFS), overall survival (OS), overall response rate (ORR), and grade ≥3 adverse events (AEs). Values of surface under cumulative ranking probability curve (SUCRA) were calculated to offer a ranking of all regimens. Results: Twelve studies with 4,353 subjects were identified. Nine regimens were included into the network: T-DM1, lapatinib-capecitabine (Lap-Cap), Tra-Cap, Cap, neratinib (Ner), pertuzumab (Per)-Tra-Cap, Pyr-Cap, atezolizumab (Ate)-T-DM1, and Ner-Cap. For PFS, Pyr-Cap was more favorable than T-DM1 (hazard ratio, 95% confidence interval: 0.77, 0.70-0.86), Lap-Cap (0.64, 0.59-0.69), Tra-Cap (0.63, 0.56-0.70), Cap (0.50, 0.45-0.56), Ner (0.59, 0.51-0.69), Per-Tra-Cap (0.68, 0.59-0.79), and Ner-Cap (0.72, 0.64-0.81). For OS, Pyr-Cap showed further improvement than Lap-Cap (hazard ratio, 95% confidence interval: 0.71, 0.52-0.99), Cap (0.68, 0.49-0.96), and Ner (0.65, 0.45-0.94). For ORR, Pyr-Cap was significantly superior than Cap (odds ratio, 95% confidence interval: 7.87, 1.22-56.51). No significant difference was observed in grade ≥3 AEs among all the regimens. Pyr-Cap ranked in the highest in PFS, OS, ORR, and grade ≥3 AEs (SUCRA = 99.4, 89.7, 86.4, and 89.3%). Conclusions: These results indicate that Pyr may be more effective than T-DM1 in HER2+ MBC patients pre-treated with Tra and a taxane. However, it may be associated with more grade ≥3 AEs.

18.
Zhongguo Zhong Yao Za Zhi ; 46(8): 2037-2044, 2021 Apr.
Artigo em Chinês | MEDLINE | ID: mdl-33982517

RESUMO

As a traditional Chinese medicine, Chinese dragon's blood has multiple effects, such as activating blood to remove blood stasis, softening and dispelling stagnation, astringent and hemostasis, clearing swelling and relieving pain, regulating menstruation and rectifying the blood, so it is called "an effective medicine of promoting blood circulation". It has been widely used clinically to treat a variety of diseases. With the further research on Chinese dragon's blood, its anti-tumor medicinal value is gradually emerging. Modern pharmacological studies have shown that Chinese dragon's blood exerts anti-tumor effects mainly by inhibiting cell proliferation, inducing apoptosis, inducing DNA damage and cell cycle arrest, inducing senescence and autophagy of tumor cells, inhibiting metastasis and angiogenesis, as well as reversing multidrug resistance. This article focuses on the research progress on anti-tumor effects of Chinese dragon's blood extract and its chemical components, with a view to provide new references for the in-depth research and reasonable utilization of Chinese dragon's blood.


Assuntos
Dracaena , China , Feminino , Extratos Vegetais , Resinas Vegetais
19.
Biomed Pharmacother ; 139: 111568, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-33845374

RESUMO

Candida albicans (C. albicans) infection remains a challenge to clinicians due to the limited available antifungals. With the widespread use of antifungals in the clinic, the drug resistance has been emerging continuously, especially fluconazole. Therefore, searching for new antifungals, active constituents of natural or traditional medicines, and approaches to overcome antifungals resistance is needed. This study investigated the activity of Asiatic acid (AA) alone and in combination with fluconazole (FLC) against C. albicans in vitro and in vivo. The in vitro studies indicated that the drug combination had a synergistic effect on FLC-resistant C. albicans, with fractional inhibitory concentration index (FICI) of 0.25. And when AA at the dose of 32 µg/mL, the drug combination group could decrease the sessile minimum inhibitory concentration (sMIC) of FLC from > 1024 µg/mL to 0.125-0.25 µg/mL within 8 h against C. albicans biofilms, even with the FICI > 0.5. In vivo, the antifungal efficacy of AA used alone and in combination with FLC was evaluated by Galleria mellonella (G. mellonella) larvae. The drug combination group prolonged the survival rate and reduced tissue invasion of larvae infected with resistant C. albicans. Furthermore, mechanism studies indicated that the antifungal effects of AA in combination with FLC might be associated with the inhibition of drug efflux pump, the accumulation of reactive oxygen species (ROS) and the inhibition of hyphal growth. These findings might provide novel insights for overcoming drug resistance of C. albicans and bring new reference data for the development and application of AA in future.


Assuntos
Antifúngicos/farmacologia , Candida albicans/efeitos dos fármacos , Fluconazol/farmacologia , Triterpenos Pentacíclicos/farmacologia , Animais , Antifúngicos/uso terapêutico , Biofilmes/efeitos dos fármacos , Candidíase/tratamento farmacológico , Combinação de Medicamentos , Farmacorresistência Fúngica , Sinergismo Farmacológico , Fluconazol/uso terapêutico , Hifas/efeitos dos fármacos , Larva , Testes de Sensibilidade Microbiana , Mariposas , Triterpenos Pentacíclicos/uso terapêutico , Espécies Reativas de Oxigênio/metabolismo
20.
Environ Sci Pollut Res Int ; 28(32): 43815-43830, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-33840030

RESUMO

In this work, Co-Ce-Zr/γ-Al2O33 particle electrodes were prepared for the efficient degradation of ciprofloxacin (CIP). Co-Ce-Zr/γ-Al2O3 particle electrodes were analyzed with a scanning electron microscope (SEM), X-Ray Diffraction (XRD), X-Ray Fluorescence Spectrometer (XRF), X-ray photoelectron spectroscopy (XPS), and energy-dispersive X-ray spectroscopy (EDS). According to the results, significant amounts of Co3O4, CeO2, and ZrO2 were formed on the Co-Ce-Zr/γ-Al2O3 particle electrodes. It was shown that when the conditions of the reaction system were at pH=6, conductivity of 4 ms/cm, current of 0.2 A, initial pollutant concentration of 100 mg/L, and material dosage of 15 g, CIP could be completely degraded within 40 min, and the energy consumed in the reaction was 41.3 kWh/kg CIP. The rate of total organic carbon (TOC) removal by Co-Ce-Zr/γ-Al2O3 particle electrodes was recorded to be approximately 52.6%. Using a response surface methodology, we explored the optimal operating conditions. At the same time, we also explored the influence of inorganic anions in water and actual water medium on the rate of CIP removal. In addition, the ESR data proved that the main active substance in the reaction system was ·OH. The degradation intermediates were investigated, and the possible mechanism was proposed. Thus, this research provided a new solution for the treatment of antibiotic-containing wastewater.


Assuntos
Ciprofloxacina , Poluentes Químicos da Água , Ciprofloxacina/análise , Eletrodos , Oxirredução , Águas Residuárias , Poluentes Químicos da Água/análise
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