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1.
J Phys Chem A ; 2021 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-34470213

RESUMO

In order to resolve the existing discrepancies in the mechanism and key intermediates of oxadiazole thermolysis, the initial decomposition pathways of oxadiazoles have been studied comprehensively using the M062X method for optimization and CBS-QB3 and DLPNO-CCSD(T) methods for energies. The transformation from the furoxan ring to nitro group was suggested as a potential decay channel of furoxan compounds. Results of thermochemistry calculations showed that the preferred decomposition reaction of oxadiazoles is the ring-opening through the cleavage of the O-C or O-N bond. The introduction of the nitro group has little effect on the preferential path of oxadiazole thermal decomposition, but a great impact on the energy barrier. The lowest energy barrier and bond dissociation energy of NO2 loss of azoles were comprehensively studied based on the quantum chemistry calculations. The initial decay steps of 3,4-dinitrofurazanfuroxan and benzotrifuroxan were also studied to give insights into the mechanism of primary stages of thermal decomposition of oxadiazoles.

2.
Artigo em Inglês | MEDLINE | ID: mdl-34524259

RESUMO

ABSTRACT: The energy used by the heart is generated mainly by the metabolism of fatty acids and glucose. Trimetazidine (TMZ) inhibits fatty acid metabolism and is used for the treatment of heart diseases such as heart failure. 3-Bromopyruvate (3-BrPA) can suppress glucose metabolism, and it is considered a promising candidate agent for tumour therapy. As TMZ and 3-BrPA can separately inhibit the two main cardiac energy sources, it is necessary to investigate the effects of 3-BrPA combined with TMZ on the heart.Forty male Wistar rats were randomly divided into four groups: a control group, a TMZ group, a 3-BrPA group, and a 3-BrPA+TMZ group. Weight was recorded every day, and echocardiography was performed 14 days later. Heart function, the levels of ATP, oxidative stress-related factors (ROS, GSH, GSSG, MDA, SOD, and TAC) and apoptosis in heart tissues were assessed to evaluate the effects of 3-BrPA and TMZ on the heart. In our study, no obvious changes occurred in the 3-BrPA group or the TMZ group compared with the control group. The combination of 3-BrPA and TMZ worsened heart function, decreased ATP levels and increased oxidative stress and myocardial apoptosis. In conclusion, 3-BrPA and TMZ are not recommended for concurrent use.

4.
Trials ; 22(1): 619, 2021 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-34526079

RESUMO

BACKGROUND: Irritable bowel syndrome (IBS) is one of the most common functional gastrointestinal disorders in clinical practice. IBS diagnosis is based on symptoms defined by abdominal pain or discomfort associated with defecation or changes in bowel habits. Gut-brain interaction caused by stress or depressive emotion is one of the essential pathologies. Acupuncture has been used for the treatment of internal medicine, including digestive disorders and depressive disorders in Chinese medicine. This study aims to determine whether electro-acupuncture could have significant benefits than sham acupuncture for IBS. METHODS/DESIGN: This is a single-blinded randomized sham-controlled clinical trial with two arms. A total of 120 IBS patients will be recruited. After a 2-week run-in period, eligible subjects will be randomly assigned to one of two arms, acupuncture (AC) arm and sham acupuncture (SAC) arm. Each eligible subject will go through a 2-week run-in-period, 6-week treatment period, and 6-week follow-up period. Five visits in total were scheduled for each subject in week 0, week 2, week 5, week 8, and week 14. The outcomes would be measured with (1) IBS-SSS, (2) Hamilton Depression Rating Scale (HAMD-17), (3) Clinical Global Impression-Severity (CGI-S), (4) Self-Rating Depression Scale (SDS), and (5) IBS Quality of Life (IBS-QoL). DISCUSSION: The study will compare electro-acupuncture with sham acupuncture to explore the feasibility of electro-acupuncture in improving IBS symptoms. TRIAL REGISTRATION: ClinicalTrials.gov NCT04387383 . Registered on 13 May 2020.


Assuntos
Terapia por Acupuntura , Síndrome do Intestino Irritável , Dor Abdominal , Terapia por Acupuntura/efeitos adversos , Humanos , Síndrome do Intestino Irritável/diagnóstico , Síndrome do Intestino Irritável/terapia , Qualidade de Vida , Ensaios Clínicos Controlados Aleatórios como Assunto , Resultado do Tratamento
5.
J Plant Physiol ; 266: 153520, 2021 Sep 11.
Artigo em Inglês | MEDLINE | ID: mdl-34536904

RESUMO

Aluminum (Al) toxicity is one of the primary factors limiting crop production in acid soils worldwide. The cell wall is the major target of Al toxicity owing to the presence of many Al binding sites. Previous studies have found that XTH, encoding xyloglucan endohydrolase (XEH) and xyloglucan endotransglucosylase (XET), could participate in cell wall extension and affect the binding ability of the cell wall to Al by impeding the activities of these two enzymes. In this study, we found that ZmXTH, an XTH gene in maize, was involved in Al detoxification. The Al-induced up-regulation of ZmXTH occurred in the roots, prominently in the root tips. Additionally, the expression of ZmXTH was specifically induced by Al3+ but no other divalent or trivalent cations. Compared with the wild-type Arabidopsis, ZmXTH overexpressing plants grew more healthy and had decreased Al content in their root and root cell wall after Al stress. Overall, the results suggest that ZmXTH could confer the Al tolerance of transgenic Arabidopsis plants by reducing the Al accumulation in their roots and cell walls.

6.
Sci Rep ; 11(1): 17612, 2021 Sep 02.
Artigo em Inglês | MEDLINE | ID: mdl-34475503

RESUMO

Fine particulate matter (i.e. particles with diameters smaller than 2.5 microns, PM2.5) has become a critical environmental issue in China. Land use and land cover (LULC) is recognized as one of the most important influence factors, however very fewer investigations have focused on the impact of LULC on PM2.5. The influences of different LULC types and different land use and land cover change (LULCC) types on PM2.5 are discussed. A geographically weighted regression model is used for the general analysis, and a spatial analysis method based on the geographic information system is used for a detailed analysis. The results show that LULCC has a stable influence on PM2.5 concentration. For different LULC types, construction lands have the highest PM2.5 concentration and woodlands have the lowest. The order of PM2.5 concentration for the different LULC types is: construction lands > unused lands > water > farmlands >grasslands > woodlands. For different LULCC types, when high-grade land types are converted to low-grade types, the PM2.5 concentration decreases; otherwise, the PM2.5 concentration increases. The result of this study can provide a decision basis for regional environmental protection and regional ecological security agencies.

7.
J Nanobiotechnology ; 19(1): 272, 2021 Sep 08.
Artigo em Inglês | MEDLINE | ID: mdl-34496877

RESUMO

BACKGROUND: Retinol binding protein 4 (RBP4) has been regarded as an important serological biomarker for type 2 diabetes mellitus (T2DM). Hence, the construction of a highly sensitive detection method for RBP4 is the key to early prevention and multidisciplinary intervention of T2DM. In this work, a dual-quenched electrochemiluminescence (ECL) immunosensor has been fabricated for ultrasensitive detection of RBP4 by combining zeolitic imidazolate framework-67/AuPt-supported luminol (luminol@AuPt/ZIF-67) with MnO2 nanosheets-grown on carbon nanotubes (MnO2@CNTs). RESULTS: AuPt/ZIF-67 hybrids with high-efficiency peroxidase-like activity could provide multipoint binding sites for luminol and antibodies and significantly boost the amplified initial signal of the ECL immunosensor. Upon glutathione/H2O2 coreactants system, MnO2@CNTs composites could quench the initial signal by inhibiting mimic peroxidase activity of luminol@AuPt/ZIF-67. Moreover, the absorption spectrum of the MnO2@CNTs composites completely overlaps with the emission spectrum of luminol, which can further reduce initial signal by ECL resonance energy transfer (ECL-RET). CONCLUSIONS: Benefiting from the above-mentioned properties, the designed immunoassay sensitivity exhibited excellent sensitivity and relative stability for RBP4 detection range from 0.0001 to 100 ng mL-1 with a low detection limit of 43 fg mL-1. Therefore, our ECL immunosensor provides an alternative assaying strategy for early diagnosis of T2DM.

8.
World J Gastroenterol ; 27(31): 5232-5246, 2021 Aug 21.
Artigo em Inglês | MEDLINE | ID: mdl-34497447

RESUMO

BACKGROUND: Artificial intelligence in colonoscopy is an emerging field, and its application may help colonoscopists improve inspection quality and reduce the rate of missed polyps and adenomas. Several deep learning-based computer-assisted detection (CADe) techniques were established from small single-center datasets, and unrepresentative learning materials might confine their application and generalization in wide practice. Although CADes have been reported to identify polyps in colonoscopic images and videos in real time, their diagnostic performance deserves to be further validated in clinical practice. AIM: To train and test a CADe based on multicenter high-quality images of polyps and preliminarily validate it in clinical colonoscopies. METHODS: With high-quality screening and labeling from 55 qualified colonoscopists, a dataset consisting of over 71000 images from 20 centers was used to train and test a deep learning-based CADe. In addition, the real-time diagnostic performance of CADe was tested frame by frame in 47 unaltered full-ranged videos that contained 86 histologically confirmed polyps. Finally, we conducted a self-controlled observational study to validate the diagnostic performance of CADe in real-world colonoscopy with the main outcome measure of polyps per colonoscopy in Changhai Hospital. RESULTS: The CADe was able to identify polyps in the test dataset with 95.0% sensitivity and 99.1% specificity. For colonoscopy videos, all 86 polyps were detected with 92.2% sensitivity and 93.6% specificity in frame-by-frame analysis. In the prospective validation, the sensitivity of CAD in identifying polyps was 98.4% (185/188). Folds, reflections of light and fecal fluid were the main causes of false positives in both the test dataset and clinical colonoscopies. Colonoscopists can detect more polyps (0.90 vs 0.82, P < 0.001) and adenomas (0.32 vs 0.30, P = 0.045) with the aid of CADe, particularly polyps < 5 mm and flat polyps (0.65 vs 0.57, P < 0.001; 0.74 vs 0.67, P = 0.001, respectively). However, high efficacy is not realized in colonoscopies with inadequate bowel preparation and withdrawal time (P = 0.32; P = 0.16, respectively). CONCLUSION: CADe is feasible in the clinical setting and might help endoscopists detect more polyps and adenomas, and further confirmation is warranted.


Assuntos
Pólipos do Colo , Aprendizado Profundo , Inteligência Artificial , Pólipos do Colo/diagnóstico por imagem , Colonoscopia , Computadores , Humanos
9.
Ann Palliat Med ; 10(8): 9015-9024, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34488388

RESUMO

BACKGROUND: Tumor of the digestive system is a common malignancy with high morbidity and mortality. Although programmed cell death-1 (PD-1) inhibitors have become an effective treatment strategies for many kinds of tumors, there is still some uncertainty in digestive tumors, including: (I) therapeutic effects of PD-1 inhibitors are relatively limited; (II) responses of digestive system tumors to immunotherapies are highly heterogeneous. In the present study, we investigated the outcomes of PD-1 inhibitors for digestive system tumors in Chinese patients to analyze factors that may affect the effects of immunotherapies in digestive system tumors. METHODS: Data were obtained from the Hospital Information System (HIS) of the Department of Digestive Oncology (Henan Cancer Hospital) between January 2019 and December 2019. Inclusion criteria included patients receiving the same PD-1 inhibitor continuously for advanced or recurrent/metastatic digestive system tumors. Indicators including age, sex, clinical diagnosis, height, weight, gene status, PD-1 inhibitors, treatment regimen, medication cycle, efficacy evaluation results, and adverse reactions were analyzed retrospectively. The clinical outcomes were progression-free survival (PFS) and safety. RESULTS: A total of 2,767 patients were discharged from HIS, of which 64 (37 male/27 female) were included in this study. Thirty-eight (59.4%) of the patients were aged <60 years. Tumors included esophageal, gastric, liver, colorectal, and pancreatic cancer. Up until 30 June 2020, 51 patients were followed up to median progression-free survival (PFS), which was 5 months; the longest PFS was 18.5 months. There was no statistical significance in grouping according to sex, age and body mass index. Nevertheless, the median PFS differed statistically between monotherapy (9.4 months) versus combined therapy (4.7 months), and Cox regression analysis suggested that patients might benefit more from monotherapy than combined therapy. The incidence of adverse reactions was 47.7%, with thyroid dysfunction the most common adverse reaction. The incidence of grade 3-4 adverse reactions was 9.2% and mainly included pulmonary infection, immune-associated hepatitis, and severe oral ulcers. CONCLUSIONS: In digestive tumors, especially for second-line treatment and beyond, PD-1 monotherapy might be more beneficial than combined therapy. However, this might be related to the patient's tolerance. Large-sample prospective studies are needed for confirmation.


Assuntos
Neoplasias do Sistema Digestório , Inibidores de Checkpoint Imunológico/uso terapêutico , Receptor de Morte Celular Programada 1/antagonistas & inibidores , China , Neoplasias do Sistema Digestório/tratamento farmacológico , Feminino , Humanos , Masculino , Estudos Retrospectivos
10.
Ann Am Thorac Soc ; 2021 Sep 09.
Artigo em Inglês | MEDLINE | ID: mdl-34499590

RESUMO

RATIONALE: The effect of insulin resistance on left ventricular function is well documented, however less is known regarding its effect on the right ventricle (RV). OBJECTIVES: To evaluate the association between insulin resistance and RV function by echocardiography in a cohort of adults without baseline cardiovascular disease. METHODS: We performed a retrospective cohort study in the Multi-Ethnic Study of Atherosclerosis (MESA). Linear regression was used to examine the association between overall insulin resistance measured by the mean triglyceride to HDL cholesterol ratio (TG:HDL), and change in TG:HDL over time for each participant with echocardiographic RV function. Logistic regression was used to calculate the odds ratios of RV systolic and diastolic dysfunction. RESULTS: Among 3,032 participants, higher mean TG:HDL was associated with lower (worse) absolute RV longitudinal strain (ß -0.38; 95%CI -0.64, -0.13; p<0.01), tricuspid annular plane systolic excursion (TAPSE; ß -0.05; 95%CI -0.07, -0.04; p<0.001) and higher odds of abnormal RV strain (OR 1.26; 95%CI 1.08, 1.47; p<0.01) and abnormal TAPSE (OR 1.31; 95%CI 1.14, 1.51; p<0.001). TG:HDL was also associated with lower tricuspid E/A ratio (ß -0.03; 95%CI -0.04, -0.01; p<0.01), higher E/e' ratio (ß 0.15; 95%CI 0.07, 0.23; p<0.001), and higher odds of graded RV diastolic dysfunction (OR 1.19; 95%CI 1.03, 1.39; p<0.05). These associations remained following multivariable adjustment. CONCLUSIONS: Insulin resistance was associated with decreased RV systolic and diastolic function after adjusting for alternative causes of RV dysfunction, suggesting that insulin resistant individuals are at risk for early RV dysfunction, even in the absence of cardiovascular disease.

11.
Pharmacol Res ; : 105909, 2021 Sep 17.
Artigo em Inglês | MEDLINE | ID: mdl-34543739

RESUMO

Recently, increasing evidence has shown gut microbiota dysbiosis might be implicated in the physiological mechanisms of neuropsychiatric disorders. Altered microbial community composition, diversity and distribution traits have been reported in neuropsychiatric disorders. However, the exact pathways by which the intestinal microbiota contribute to neuropsychiatric disorders remain largely unknown. Given that the onset and progression of neuropsychiatric disorders are characterized with complicated alterations of neuroendocrine and immunology, both of which can be continually affected by gut microbiota via "microbiome-gut-brain axis". Thus, we assess the complicated crosstalk between neuroendocrine and immunological regulation might underlie the mechanisms of gut microbiota associated with neuropsychiatric disorders. In this review, we summarized clinical and preclinical evidence on the role of the gut microbiota in neuropsychiatry disorders, especially in mood disorders and neurodevelopmental disorders. This review may elaborate the potential mechanisms of gut microbiota implicating in neuroendocrine-immune regulation and provide a comprehensive understanding of physiological mechanisms for neuropsychiatric disorders.

12.
Acad Radiol ; 2021 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-34538550

RESUMO

RATIONALE AND OBJECTIVES: Synthesized mammography with digital breast tomosynthesis (SM+DBT) and full-field digital mammography with DBT were prospectively evaluated for recall rate (RR), cancer detection rate (CDR), positive predictive value 1 (PPV1), lesion recall differences, and disagreements in recall for additional imaging. MATERIALS AND METHODS: From December 15, 2015 to January 15, 2017, after informed consent was obtained for this Health Insurance Portability and Accountability Act compliant study, each enrolled patient's SM+DBT and FFDM+DBT were interpreted sequentially by one of eight radiologists. RR, CDR, PPV1, and imaging findings (asymmetry, focal asymmetry, mass, architectural distortion, and calcifications) recalled were reviewed. RESULTS: For SM+DBT and FFDM+DBT in 1022 patients, RR was 7.3% and 7.9% (SM+DBT vs. FFDM+DBT: diff= -0.6%; 90% CI= -1.4%, 0.1%); CDR was 6.8 and 7.8 per 1000 (SM+DBT vs. FFDM+DBT: diff= -1.0, 95% CI= -5.5, 2.8, p = 0.317); PPV1 was 9.3% and 9.9% (relative positive predictive value for SM+DBT vs. FFDM+DBT: 0.95, 95% CI: 0.73-1.22, p = 0.669). FFDM+DBT detected eight cancers; SM+DBT detected seven (missed 1 cancer with calcifications). SM+DBT and FFDM+DBT disagreed on patient recall for additional imaging in 19 patients, with majority (68%, 13/19 patients) in the recall of patients for calcifications. For calcifications, SM+DBT recalled six patients that FFDM+DBT did not recall, and FFDM+DBT recalled seven patients that SM+DBT did not recall, even though the total number of calcifications finding recalled was similar overall for both SM+DBT and FFDM+DBT. CONCLUSION: Disagreement in recall of patients for calcifications may impact cancer detection by SM+DBT, warranting further investigation.

13.
Chemosphere ; 287(Pt 1): 132074, 2021 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-34474384

RESUMO

Refractory organic pollutant effluent has led to severe water pollution. In this study, magnetic Co-N-doped carbon hybrid catalysts (Co-NC-x) were fabricated using a facile cation exchange combined pyrolysis and self-reduction technique to activate peroxymonosulfate (PMS) for rehabilitation of the water environment. Factors affecting the catalytic activity of the Co-NC-850 were comprehensively examined. 100% of RhB degradation efficiency within 20 min was achieved in the Co-NC-850/PMS system at the optimum conditions (C0 = 80 mg L-1, catalyst loading 0.025 g L-1, PMS concentration 0.8 mM, native pH and 25 °C). The electron paramagnetic resonance measurements and competitive quenching tests demonstrated that a sulfate radical (SO4•-) and singlet oxygen (1O2) account for RhB degradation in the Co-NC-850/PMS system, and 1O2 contributed ~86.2% to RhB removal. The synergistic effect of Co0 nanoparticles (NPs) and NC on Co-NC-850 might induce a predominant non-radical route to trigger PMS activation for RhB degradation. Direct oxidation of O2•- by a hydroxyl radical (•OH) might be the crucial process for forming 1O2. Magnetic response and successive cycles verified that Co-NC-850 has superior separable performance and reusability. This innovative magnetic Co-NC-850 hybrid catalyst for PMS activation delivered vast potential for disintegration of refractory organic contaminants.

14.
Front Immunol ; 12: 717496, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34484220

RESUMO

The antibody repertoire is a critical component of the adaptive immune system and is believed to reflect an individual's immune history and current immune status. Delineating the antibody repertoire has advanced our understanding of humoral immunity, facilitated antibody discovery, and showed great potential for improving the diagnosis and treatment of disease. However, no tool to date has effectively integrated big Rep-seq data and prior knowledge of functional antibodies to elucidate the remarkably diverse antibody repertoire. We developed a Rep-seq dataset Analysis Platform with an Integrated antibody Database (RAPID; https://rapid.zzhlab.org/), a free and web-based tool that allows researchers to process and analyse Rep-seq datasets. RAPID consolidates 521 WHO-recognized therapeutic antibodies, 88,059 antigen- or disease-specific antibodies, and 306 million clones extracted from 2,449 human IGH Rep-seq datasets generated from individuals with 29 different health conditions. RAPID also integrates a standardized Rep-seq dataset analysis pipeline to enable users to upload and analyse their datasets. In the process, users can also select set of existing repertoires for comparison. RAPID automatically annotates clones based on integrated therapeutic and known antibodies, and users can easily query antibodies or repertoires based on sequence or optional keywords. With its powerful analysis functions and rich set of antibody and antibody repertoire information, RAPID will benefit researchers in adaptive immune studies.

15.
Mikrochim Acta ; 188(10): 319, 2021 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-34476628

RESUMO

A novel cytosensor was constructed for the ultrasensitive detection and nondestructive release of circulating tumor cells (CTCs) by combining Au nanoparticles-loaded two-dimensional bimetallic PdMo (2D Au@PdMo) nanozymes and electrochemical reductive desorption. The 2D Au@PdMo nanozymes possessed high-efficiency peroxidase-like activity and were assembled with an aptamer composed of a thiol-modified epithelial specific cell adhesion molecule (EpCAM) to strengthen CTCs adhesion. Moreover, the electrode surface was decorated with highly fractal Au nanostructures (HFAuNSs) composites due to the similarity in fractal nanostructure with the CTCs membrane to enhance the CTCs anchoring efficiency and release capability. The captured CTCs could be further efficiently dissociated and nondestructively released from the modified electrodes upon electrochemical reductive desorption. The designed cytosensor showed an excellent analytical performance, with a wide linear range from 2 to 1 × 105 cells mL-1 and low limit of detection (LOD) of 2 cells mL-1 (S/N = 3) at the working potential in the range  -0.6 to 0.2 V. A satisfactory CTCs release reaching a range of 93.7-97.4% with acceptable RSD from 3.55 to 6.41% and good cell viability was obtained. Thus, the developed cytosensor might provide a potential alternative to perform CTC-based liquid biopsies, with promising applications in early diagnosis of tumors. Preparation and mechanism of desorption of the cytosensor based on 2D Au@PdMo nanozymes and electrochemical reductive desorption for the detection and release of CTCs. A Preparation procedure of the Apt/Au@PbMo bioconjugates. B Fabrication process of the sandwich-type cytosensor. C Electrochemical signal produced by the Au@PdMo nanozymes. D Mechanism of electrochemical reductive desorption for CTCs release.

16.
Zhongguo Zhong Yao Za Zhi ; 46(16): 4244-4251, 2021 Aug.
Artigo em Chinês | MEDLINE | ID: mdl-34467739

RESUMO

Coumarins are the main active components in Psoraleae Fructus. To study the multi-component pharmacokinetics of Psoraleae Fructus, this study established a sensitive and rapid ultra-pressure liquid chromatography coupled to tandem mass spectrometry(UPLC-MS/MS) method for simultaneous determination of psoralen, isopsoralen, psoralenoside, and isopsoralenoside in rat plasma. After validation, the method was applied to the investigation of pharmacokinetics of psoralen, isopsoralen, psoralenoside, and isopso-ralenoside in rats after single and multiple administration of Psoraleae Fructus extract. The results revealed that the exposure of psoralen and isopsoralen in rat plasma was high after a single intragastric administration of Psoraleae Fructus extract, with an AUC_(0-∞) of 443 619-582 680 and 167 314-276 903 ng·mL~(-1)·h~(-1), respectively. Compared with these two compounds, the exposure of psoralenoside and isopsoralenoside was lower with marked gender difference. After 7-day administration of Psoraleae Fructus extract to rats, the AUC_(0-∞) of psoralen and isopsoralen was 29 701-81 783 and 39 234-89 914 ng·mL~(-1)·h~(-1), respectively, which was significantly lower than that at the first day(P<0.05), and that of psoralenoside and isopsoralenoside was 7 360-19 342 and 8 823-45 501 ng·mL~(-1)·h~(-1), respectively. There was no significant gender difference in exposure of psoralenoside and isopsoralenoside in male and female rats. However, the exposure of psoralenoside and isopsoralenoside in male rats was reduced(P<0.05), and the t_(1/2) and mean residence time(MRT) were shortened, suggesting that the removal of these two compounds from the body was accelerated.


Assuntos
Medicamentos de Ervas Chinesas , Furocumarinas , Psoralea , Administração Oral , Animais , Benzofuranos , Cromatografia Líquida de Alta Pressão , Cromatografia Líquida , Ficusina , Furocumarinas/análise , Glicosídeos , Ratos , Espectrometria de Massas em Tandem
17.
Zhongguo Zhong Yao Za Zhi ; 46(16): 4274-4286, 2021 Aug.
Artigo em Chinês | MEDLINE | ID: mdl-34467742

RESUMO

This study evaluated the outcome indicators of the randomized controlled trials(RCTs) of traditional Chinese medicine(TCM) in the treatment of postmenopausal osteoporosis(PMOP) to provide a reference for the related research. Four Chinese databa-ses(CNKI, VIP, Wanfang and CBM) and three English databases(Cochrane Library, EMbase and PubMed) were searched syste-matically to screen RCTs of TCM in the treatment of PMOP according to the pre-set criteria, and the quality of the included trials was evaluated by the Cochrane risk-of-bias tool. A total of 29 627 articles were initially retrieved, and finally, 43 articles were included, including 34 in Chinese and 9 in English. As revealed by the results, the outcome indicators of 43 RCTs were mainly divided into six categories, with biochemical indicators accounting for 54.59%, bone mineral density(BMD) for 26.57%, quality of life for 6.28%, fracture for 1.94%, safety for 5.31%(including adverse reactions or events) and others for 5.31%. Biochemical indicators showed the maximum occurrence, followed by BMD. Many problems were found in the selection of outcome indicators of the TCM RCTs in the treatment of PMOP, such as the confusion of primary and secondary outcome indicators, the lack of endpoint criteria and vital clinical outcome indicators substituted by intermediate indicators, inconsistent evaluation standard of syndrome curative efficacy and neglected blinding in the measurement of subjective outcome indicators. The problems also included importance given to the efficacy indicators instead of the adverse outcome indicators, unnormalized indicator name, large quantitative range of the indicators, unconventional application of TCM efficacy criteria, seldom used confidence interval, relative effect indicator and absolute effect indicator.


Assuntos
Medicamentos de Ervas Chinesas , Osteoporose Pós-Menopausa , Densidade Óssea , Medicamentos de Ervas Chinesas/uso terapêutico , Feminino , Humanos , Medicina Tradicional Chinesa , Osteoporose Pós-Menopausa/tratamento farmacológico , Qualidade de Vida , Resultado do Tratamento
18.
Int J Nanomedicine ; 16: 6017-6034, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34511903

RESUMO

Background: The broader application of adoptive cell therapy (ACT) in cancer immunotherapies (particularly for solid tumors) has always been limited by the immunosuppressive tumor microenvironment (TME) and the insufficient targetability of effector T cells, resulting in unsatisfied therapeutic outcome. Here, we designed a new strategy by using aptamer-based immunoliposomes to modify PD-1-silencing T cells, which were activated by dendritic cell (DC)/tumor fusion cells (FCs) to improve the antitumor potency of cytotoxic T lymphocytes (CTLs/CD8+ T cells). Methods: PD-1 gene was knocked out from CD8+ T cells using CRISPR/Cas9 system to liberate T cell activity from immunosuppression. The PD-1- T cells were stimulated with DC/tumor FCs, followed by further functional modification of tumor-specific nanoliposomes (hEnd-Apt/CD3-Lipo) to generate FC/PD-1- CTLs. The activation and proliferation and specificity of the modified FC/PD-1- CTLs were measured. The antitumor activity of these CTLs against HepG2-tumors was evaluated in xenograft NOD/SCID mice, and the antitumor mechanism was investigated based on tissue immunohistochemistry and serum ELISA. Results: Our results indicated that the modification of hEnd-Apt/CD3-Lipo nanocomposites on the FC/PD-1- CTLs had a more substantial synergetic effect in inhibiting tumor growth and prolonging animal survival, rather than other control liposomes. Furthermore, the hEnd-Apt/CD3-Lipo-modified FC/PD-1- CTLs showed a stronger antitumor outcome in the tumor-bearing mouse model, through the mechanisms of suppressing tumor cell proliferation, promoting tumor apoptosis, reducing angiogenesis but increasing the infiltration of the FC/PD-1- CTLs in the tumor tissue, as well as upregulating the systemic levels of IFN-γ, IL-2, TNF-α and IL-6 cytokines, by comparison of the control settings. Conclusion: In sum, our investigation suggests an enhancement of antitumor effect by the surface modification of endoglin-targeting nanoliposomes upon DC/tumor FC-activated PD-1- CTLs, therefore, provides a new tumoral endoglin-targeted approach as a promising strategy to reduce immunosuppression of tumor microenvironment and improve the immunotherapeutic outcome of anticancer ACT.

20.
Aquat Toxicol ; 239: 105950, 2021 Aug 22.
Artigo em Inglês | MEDLINE | ID: mdl-34474269

RESUMO

Diarrheic shellfish poisoning toxins (DSP toxins) are a set of the most important phycotoxins produced by some dinoflagellates. Studies have shown that DSP toxins have various toxicities such as genotoxicity, cytotoxicity, and immunotoxicity to bivalve mollusks. However, these toxicities appear decreasing with exposure time and concentration of DSP toxins. The underlying mechanism involved remains unclear. In this study, small RNA sequencing was performed in the digestive gland of the mussel Perna viridis after exposure to DSP toxins-producing dinoflagellate Prorocentrum lima for different time periods. The potential roles of miRNAs in response and detoxification to DSP toxins in the mussel were analyzed. Small RNA sequencing of 12 samples from 72 individuals was conducted by BGISEQ-500. A total of 123 mature miRNAs were identified, including 90 conserved miRNAs and 33 potential novel miRNAs. After exposure to P. lima, multiple important miRNAs displayed some alterations. Further miRNA target prediction revealed some important genes involved in cytoskeleton, apoptosis, complement system and immune stress. qPCR demonstrated that miR-71_5, miR-750_1 and novel_mir4 were significantly up-regulated at 6 h after exposure to P. lima, while miR-100_2 was significantly down-regulated after 96 h of exposure. Accordingly, putative target genes of these differentially expressed miRNAs experienced some changes. After 6 h of DSP toxins exposure, NHLRC2 and C1q-like were significantly down-regulated. After 96 h of DSP toxins exposure, NHLRC2 was significantly up-regulated. It is reasonable to speculate that the mussel P. viridis might respond to DSP toxins through miR-750_1, novel_mir4 and miR-71_5 regulating the expression of relevant target genes involved in apoptosis, cytoskeleton, and immune response, etc. This study might provide new clues to uncover the toxic response of bivalve to DSP toxins and lay a foundation for revealing the roles of miRNAs in the environmental adaptation in shellfish.

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