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1.
ACS Omega ; 7(21): 17894-17906, 2022 May 31.
Artigo em Inglês | MEDLINE | ID: mdl-35664632

RESUMO

Aberrant glycosylation is a hallmark of cancer found during tumorigenesis and tumor progression. Lung cancer (LC) induced by oncogene mutations has been detected in the patient's saliva, and saliva glycosylation has been altered. Saliva contains highly glycosylated glycoproteins, the characteristics of which may be related to various diseases. Therefore, elucidating cancer-specific glycosylation in the saliva of healthy, non-cancer, and cancer patients can reveal whether tumor glycosylation has unique characteristics for early diagnosis. In this work, we used a solid-phase chemoenzymatic method to study the glycosylation of saliva glycoproteins in clinical specimens. The results showed that the α1,6-core fucosylation of glycoproteins was increased in cancer patients, whereas α1,2 or α1,3 fucosylation was significantly increased. We further analyzed the expression of fucosyltransferases responsible for α1,2, α1,3, and α1,6 fucosylation. The fucosylation of the saliva of cancer patients is drastically different from that of non-cancer or health controls. These results indicate that the glycoform of saliva fucosylation distinguishes LC from other diseases, and this feature has the potential to diagnose lung adenocarcinoma.

2.
Foods ; 11(11)2022 May 30.
Artigo em Inglês | MEDLINE | ID: mdl-35681360

RESUMO

Lactobacillus are normal inhabitants of the gastrointestinal tract and confer a variety of health effects. Lipoteichoic acid (LTA), an amphiphilic substance located in the cell membrane, is a key molecule in probiotic-host crosstalk. Through the characterization of structural characteristics of LTA molecules derived from Lactobacillus plantarum A3, Lactobacillus reuteri DMSZ 8533, and Lactobacillus acidophilus CICC 6074, there exists some heterogeneity in LTA molecules, which perhaps contributes to the distinguishable adhesion properties of Lactobacillus strains based on fluorescence microscopy observations. In LPS-induced RAW 264.7 cells, LTAs derived from three Lactobacillus strains obviously alleviated inflammatory responses as evidenced by the altered inflammatory cytokine levels of TNF-α, IL-6, and IL-10. Western blotting demonstrated that L. reuteri LTA blocked LPS-triggered expression of the MAPK and NF-κB pathways. The findings further validated that LTA is an important effector molecule and deserves further consideration as an alternative therapeutic for ulcerative colitis treatment.

3.
Huan Jing Ke Xue ; 43(6): 2996-3004, 2022 Jun 08.
Artigo em Chinês | MEDLINE | ID: mdl-35686769

RESUMO

The seasonal variation and spatial distribution of pharmaceuticals in typical drinking water sources in the middle reaches of the Yangtze River were analyzed using the solid-phase extraction and high-performance liquid chromatography-tandem mass spectrometry methods. Combined with the risk entropy method, the corresponding ecological risks for aquatic organisms were evaluated. The results showed that 80% of the target pharmaceuticals were detected in the drinking water sources, with average concentrations of 0.07-13.00 ng·L-1. The concentrations of the target pharmaceuticals were lower than or comparable with those in other drinking water sources reported in China. The spatiotemporal distribution of different pharmaceuticals varied. Generally, the detection level in winter was higher than that in summer, and there was no significant difference between that upstream and that downstream. This might be mainly attributed to seasonal/regional use and emissions of the pharmaceuticals, the impact of flow rate on dilution, and the impact of temperature on biodegradation. Compared with those before the COVID-19 epidemic, the detection concentrations of the target pharmaceuticals were relatively low. The reason for this might be that the prevention and control of the epidemic reduced the use and emission of the pharmaceuticals to a certain extent, and the high rainfall and runoff strengthened the dilution of water flow. The target pharmaceuticals, especially antibiotics, posed medium or low risks to aquatic organisms (especially algae). Considering the ecological risks and genotoxicity of pharmaceuticals and the potential risks of antibiotic-resistant genes, it is suggested to strengthen the investigation, evaluation, treatment, and control of pharmaceuticals in the water environment.


Assuntos
COVID-19 , Água Potável , Poluentes Químicos da Água , Antibacterianos/análise , Organismos Aquáticos , China , Água Potável/análise , Monitoramento Ambiental/métodos , Humanos , Preparações Farmacêuticas , Medição de Risco , Poluentes Químicos da Água/análise
4.
Food Res Int ; 156: 111339, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35651087

RESUMO

Milk-derived peptides have been identified as the essential ingredients in the food industry for the health-promoting properties. Some bioactive peptides in the milk product can be released by the specific protease system of lactic acid bacteria (LAB) during the fermentation processing. In this research, the bioactive peptides released from the casein and whey protein are investigated by the hydrolyzing ability of the Lactobacillus brevis CGMCC15954, Lactobacillus reuteri WQ-Y1 and Lactobacillus plantarum A3. Results found that the hydrolysates of casein/whey protein generated by L. reuteri WQ-Y1 have the potential antioxidant activity. Furthermore, milk-derived peptides identified by the liquid chromatography-mass spectrometry (LC-MS/MS) with the BIOPEP-UWM database showed the YLGYLEQLLR (αS1-casein), VKEAMAPK (ß-casein), YIPIQYVLSR (κ-casein) fragment had the promising antioxidant activity, especially VKEAMAPK, which exhibited IC50 of 0.63 and 0.86 mg/mL in DPPH and ABTS free radical scavenging activity. The finding of this study sheds some light of obtaining milk-derived peptides by using the Lactobacillus strains and proves the potential bioactive function of the LAB fermented milk products.


Assuntos
Antioxidantes , Proteínas do Leite , Antioxidantes/química , Caseínas/química , Cromatografia Líquida , Lactobacillus/metabolismo , Proteínas do Leite/análise , Peptídeos/química , Espectrometria de Massas em Tandem , Proteínas do Soro do Leite/análise
5.
Front Plant Sci ; 13: 891861, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35656008

RESUMO

Varieties of various crops with high resilience are urgently needed to feed the increased population in climate change conditions. Human activities and climate change have led to frequent and strong weather fluctuation, which cause various abiotic stresses to crops. The understanding of crops' responses to abiotic stresses in different aspects including genes, RNAs, proteins, metabolites, and phenotypes can facilitate crop breeding. Using multi-omics methods, mainly genomics, transcriptomics, proteomics, metabolomics, and phenomics, to study crops' responses to abiotic stresses will generate a better, deeper, and more comprehensive understanding. More importantly, multi-omics can provide multiple layers of information on biological data to understand plant biology, which will open windows for new opportunities to improve crop resilience and tolerance. However, the opportunities and challenges coexist. Interpretation of the multidimensional data from multi-omics and translation of the data into biological meaningful context remained a challenge. More reasonable experimental designs starting from sowing seed, cultivating the plant, and collecting and extracting samples were necessary for a multi-omics study as the first step. The normalization, transformation, and scaling of single-omics data should consider the integration of multi-omics. This review reports the current study of crops at abiotic stresses in particular heat stress using omics, which will help to accelerate crop improvement to better tolerate and adapt to climate change.

6.
Mar Pollut Bull ; 180: 113826, 2022 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-35696894

RESUMO

In this study, 214 surface sediment samples were collected from the offshore area of the Dongying coast and were analysed for heavy metals; particularly, their concentrations and pollution status were evaluated. The copper (Cu) and chromium (Cr) distributions were similar, their concentrations were the highest in the northeast areas and the Xiaoqing River estuary, where dominated by fine-grained sediments. Higher concentrations of lead (Pb), zinc (Zn), cadmium (Cd), and arsenic (As) were generally found in the offshore area of the study location, and the highest Cd concentration was observed in the Xiaoqing River estuary. The sediments were not polluted by Cu, Pb, Zn, and Cr; they were not polluted or moderately polluted by Cd and As. Results of the principal component analysis indicated that Cu, Pb, Zn, and Cr were derived from natural sources and Cd and As were derived from anthropogenic sources.


Assuntos
Arsênio , Metais Pesados , Poluentes Químicos da Água , Arsênio/análise , Cádmio/análise , China , Cromo/análise , Monitoramento Ambiental/métodos , Sedimentos Geológicos/análise , Chumbo/análise , Metais Pesados/análise , Medição de Risco , Rios , Poluentes Químicos da Água/análise , Zinco/análise
7.
FASEB J ; 36(7): e22417, 2022 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-35713934

RESUMO

Duck Tembusu virus (TMUV) is a serious avian pathogen causing a decline in egg production, but the mechanism of the virus that breaks through the innate immune system is poorly understood. Here, we show that TMUV inhibits poly(I:C)-induced interferon (IFN) production. Because poly(I:C) transfection can specifically activate the MDA5 pathway in duck primary cells, we found that infection with TMUV can specifically target MDA5 and lead to its degradation. MDA5 downregulation could be blocked by the autophagy inhibitor 3-methyladenine (3-MA) but not a proteasome inhibitor, strongly implicating MDA5 degradation as an autophagy-related degradation pathway. Pretreatment with 3-MA enhanced the expression of MDA5 and inhibited TMUV replication. To screen TMUV proteins that degraded MDA5, the TMUV replicon and MDA5-Flag were cotransfected into cells, and the western blot analysis showed that nonstructural 2B (NS2B) can degrade MDA5 in a dose-dependent manner. Dual-luciferase assays indicate that NS2B alone inhibits MDA5- or poly(I:C)-mediated IFN production. NS2B binds MDA5 in the presence of 3-MA. The deletion of the amino acids of NS2B from residues 51 to 92 (hydrophilic area) restored the expression of MDA5 and relieved the MDA5-mediated IFNß production inhibition by NS2B, indicating that the hydrophilic area of NS2B is important for its interaction with host innate immunity.


Assuntos
Flavivirus , Animais , Antivirais/metabolismo , Autofagia , Patos , Flavivirus/metabolismo , Imunidade Inata
8.
FASEB J ; 36(7): e22421, 2022 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-35713947

RESUMO

Lactobacillus species is one of the most commonly used probiotics with a wide range of health-promoting effects, and beneficial effects of the surface protein of the lactobacillus could potentially be involved in the action of probiotics in the gastrointestinal tract. In this study, the anti-inflammatory effect of LPxTG-motif surface protein (LMP) derived from Limosilactobacillus reuteri SH 23 was assessed using a mouse model of colitis induced by dextran sodium sulfate (DSS). The results showed that LMP has the inhibition properties upon the DSS-induced ulcerative colitis of mice via the MAPK-dependent NF-κB pathway. The inflammatory factors TNF-α and IL-6 were inhibited, and the IL-10 secretion was enhanced in the LMP treated DSS mice model. Furthermore, the diversity of the intestinal microbiota bacteria in this treated group was also influenced, including the increase in the abundance of Lactobacillus and Akkermansia genus in the LMP-treated mice groups, and there is a positive correlation between the IL-10 cytokines with the changes in the intestinal microbiota Lactobacillus and Akkermansia. Therefore, LMP derived from the L. reuteri SH 23 has the potential to alleviate inflammatory diseases through the balance of the intestinal flora with the inhibition of the inflammatory factors in the NF-κB pathway.


Assuntos
Colite Ulcerativa , Colite , Lactobacillus reuteri , Animais , Colite/metabolismo , Colite Ulcerativa/induzido quimicamente , Colite Ulcerativa/metabolismo , Colo/metabolismo , Sulfato de Dextrana/toxicidade , Modelos Animais de Doenças , Interleucina-10/metabolismo , Lactobacillus reuteri/metabolismo , Proteínas de Membrana/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , NF-kappa B/metabolismo
9.
Int J Breast Cancer ; 2022: 3359130, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35707316

RESUMO

Background and Aims: Regional anaesthesia reports to attenuate stress and inflammatory responses associated with surgical resection; however, the effectiveness of combined nerve blocks is less often investigated. We evaluated whether a combination of a pectoral nerve block (PNB) and stellate ganglion block (SGB) is more effective than a PNB alone in reducing these responses in women undergoing modified radical mastectomy (MRM). Methods: This is a prospective randomized controlled trial. Fifty patients with breast cancer were randomly allocated to receive an ultrasound-guided PNB (n = 25, PNB only group) or ultrasound-guided PNB combined with SGB (n = 25, combined blockade group). The primary outcome was perioperative plasma level of interleukin- (IL-) 6. Secondary outcomes included perioperative plasma levels of cortisol, glucose, IL-8, and tumour necrosis factor- (TNF-) α, pain scores, haemodynamic variables, sleep quality, and complications postsurgery. Results: The combined blockade group exhibited significantly lower IL-6 and TNF-α levels 24 h postsurgery. Cortisol levels were significantly lower in the combined blockade group at the end of the surgery. Glucose levels at the time of incision were lower in the combined blockade group. Pain scores up to 12 h postsurgery were significantly lower in the combined blockade group, which also exhibited better perioperative haemodynamic stability. Patients in the combined blockade group reported better sleep quality on the night of surgery. Conclusion: In patients undergoing MRM, PNB combined with SGB block effectively blunted perioperative inflammatory response than PNB alone. A combined block approach can also alleviate stress response and postoperative acute pain with stable perioperative haemodynamics and better postoperative sleep quality.

10.
Diabetes Ther ; 2022 Jun 11.
Artigo em Inglês | MEDLINE | ID: mdl-35689733

RESUMO

INTRODUCTION: Patients with diabetes mellitus and end-stage renal disease are at a high risk of developing coronary, cerebrovascular, and peripheral vascular diseases. This study aimed to characterize hypoglycemia and blood glucose fluctuations associated with maintenance hemodialysis in older adult patients with diabetes mellitus and end-stage renal disease using a continuous glucose monitoring system. METHODS: Seven patients were enrolled in this study, and 13 pairs of continuous glucose monitoring system data were collected. Each pair included data of 1 dialysis-on day and 1 dialysis-off day. Information on basic patient characteristics, including age, diabetes mellitus duration, hemodialysis duration, and proportions of hemoglobin A1c and glycated albumin, were collected. Differences in blood glucose fluctuation were compared between dialysis-on days and dialysis-off days. RESULTS: The mean blood glucose on dialysis-on days (6.96 ± 2.57 mmol/L) was significantly lower than that on dialysis-off days (7.68 ± 2.31 mmol/L; P < 0.05). In contrast, the following parameters had significantly higher values (all P < 0.05) on dialysis-on days compared to dialysis-off days: large amplitude of glycemic excursion level (5.82 ± 2.86 mmol/L versus 4.21 ± 1.71 mmol/L), large amplitude of glycemic excursion level from 8 a.m. to 2 p.m. (3.6 ± 1.74 mmol/L versus 2.8 ± 1.33 mmol/L), mean amplitude of glycemic excursion level (4.78 ± 1.68 mmol/L versus 3.89 ± 1.67 mmol/L), mean amplitude of glycemic excursion level from 8 a.m. to 2 p.m. (4.01 ± 1.03 mmol/L versus 3.12. ± 0.97 mmol/L), standard deviation of blood glucose (1.55 ± 0.89 mmol/L versus 1.03 ± 0.4 mmol/L), and time below a target glucose range of less than 3.9 mmol/L (8.27% versus 4.25%). CONCLUSION: Fluctuations in blood glucose levels were larger on dialysis-on days, particularly from the start of hemodialysis to 2 h post-hemodialysis, than on dialysis-off days. Hypoglycemia, as indicated by the time below a target glucose range of less than 3.9 mmol/L, occurred more frequently on dialysis-on days than on dialysis-off days.

11.
Fitoterapia ; 160: 105229, 2022 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-35662649

RESUMO

Eighteen stilbenes (1-18), including six previously undescribed ones (1-6), with diverse modification patterns were isolated from the leaves of edible and medicinal plant Cajanus cajan. Among the new isolates, compounds 1-3 were initially obtained as three racemic mixtures, which were further resolved into three pairs of optically pure enantiomers, respectively, by chiral HPLC. Besides, compounds 8, 10, 11, and 18 were obtained from C. cajan for the first time. The chemical structures and absolute configurations of the new stilbenes were elucidated unambiguously on the basis of extensive spectroscopic analyses, single crystal X-ray crystallographic study, and quantum chemical electronic circular dichroism (ECD) calculations. In addition, the in vitro anti-inflammatory activities of all isolated stilbenes were evaluated. Compounds 2, 9, 10, 11, and 14 exerted moderate suppression of nitric oxide (NO) secretion in lipopolysaccharide (LPS)-induced RAW264.7 cells without exhibiting substantial cytotoxicity.


Assuntos
Cajanus , Estilbenos , Anti-Inflamatórios/farmacologia , Cajanus/química , Estrutura Molecular , Folhas de Planta/química , Estilbenos/química , Estilbenos/farmacologia
12.
Dalton Trans ; 51(22): 8743-8748, 2022 Jun 07.
Artigo em Inglês | MEDLINE | ID: mdl-35612294

RESUMO

Photochemical reactions are vital synthetic means for the synthesis of natural products and highly strained molecules. However, it remains an immense challenge to control the chemo- and regioselectivity in the photoreactions of anthracene derivatives while maintaining high reactivity. Herein, we report the synthesis of two photoactive metallarectangles 1a and 1b by coordination-driven self-assembly of 2,6- and 2,7-bifunctionalized anthracenes with a half-sandwich rhodium template. By taking advantage of the rhodium template, the anthracene groups within the metallarectangles can be preorganized in a parallel fashion and exclusively undergo a photochemical [4 + 4] cycloaddition. As a result, the syn-photodimers were obtained in quantitative yields under irradiation at 365 nm. The photocycloaddition of metallarectangles 1a and 1b was found to be reversible via photo- and thermal cleavage reactions, even after repeating three times. Furthermore, pure organic photodimers 3a and 3b, which are difficult to synthesize by conventional organic methods, can be readily dissociated from the metalloassemblies in high yields.

13.
BMC Cardiovasc Disord ; 22(1): 213, 2022 May 11.
Artigo em Inglês | MEDLINE | ID: mdl-35546224

RESUMO

BACKGROUND: Bone-related proteins (such as sclerostin and osteoprotegerin [OPG]) are involved in the development of atherosclerosis. However, the relationship between bone-related proteins and acute myocardial infarction (AMI) has not been extensively evaluated. The purpose of this study was to assess the association of serum sclerostin and OPG with the presence, severity and prognosis in patients with AMI. METHODS: This study prospectively enrolled 152 patients attacked by acute chest pain. Serum sclerostin and OPG were detected within the first 24 h after AMI diagnosis by ELISA kits. The AMI predictive efficacy of sclerostin and OPG were analyzed by receiver operating characteristics (ROC) curve. Univariable and multivariable linear regression analyses were performed to determine the association between bone-related proteins and scores indicating the severity of coronary artery occlusion. Moreover, prognostic values were assessed by Kaplan-Meier curves and Cox regression analysis. RESULTS: There were 92 patients in AMI group, 60 in non-AMI group. Serum levels of sclerostin and OPG were significantly higher in AMI group than in non-AMI group (all p < 0.001), which showed predictive value for the presence of AMI (all p < 0.001). The area under the ROC curve values of sclerostin and OPG were 0.744 and 0.897, respectively. A multivariable linear regression analysis demonstrated that Ln-transformed sclerostin (ß = 0.288, p = 0.009) and Ln-transformed OPG (Ln-OPG: ß = 0.295, p = 0.019) levels were associated with GENISINI score, independently of conventional clinical parameters. In addition, Ln-OPG levels were still positively associated with GRACE score after adjustments (ß = 0.320, p = 0.001). During a 1-year follow-up, patients above the median of sclerostin levels had higher incidence of major adverse cardiac events (MACE) than those below the median (p = 0.028). It was also observed that the MACE rates were higher in patients above the median of OPG levels, though no statistic importance (p = 0.060). After adjusting conventional risk factors by multivariate Cox regression, Ln-OPG was associated with incident MACE (hazard ratio = 2.188 [95% confidence intervals 1.102-4.344], p = 0.025). CONCLUSIONS: Bone-related proteins could exert a potential role in early risk stratification and prognosis assessment in patients with AMI.


Assuntos
Infarto do Miocárdio , Osteoprotegerina , Proteínas Adaptadoras de Transdução de Sinal , Biomarcadores , Humanos , Infarto do Miocárdio/epidemiologia , Prognóstico , Curva ROC
14.
Phytomedicine ; 102: 154178, 2022 Jul 20.
Artigo em Inglês | MEDLINE | ID: mdl-35617889

RESUMO

BACKGROUND: Adriamycin (ADR), a high-efficiency, broad-spectrum anthraquinone chemotherapeutic agent, is currently used to treat various malignant tumors and can lead to cumulative, dose-dependent, and irreversible cardiotoxicity. Lycorine (LYC) is a benzyl phenethylamine alkaloid that exerts remarkable therapeutic effects on cancers and sepsis. PURPOSE: However, researchers have not yet elucidated whether LYC exerts protective effects against cardiotoxicity induced by ADR and the possible molecular mechanisms. DESIGN: This study established ADR injury models in vitro and in vivo to explore the effects of LYC against cardiotoxicity induced by ADR. The effects of LYC on blood biochemical parameters, cardiac parameters and structure, ADR-related pathophysiological processes, and the SIRT1/PPARγ signal pathway in ADR-injured models, were analyzed using a series of experimental methods. RESULTS: LYC significantly improved survival rate, blood biochemical parameters (LDH, CK, and BUN), cardiac parameters (SV and CO), mitochondrial dysfunction, and ameliorated oxidative stress, apoptosis, and myocardial fibrosis in ADR-injured mice (p<0.05). Moreover, LYC obviously increased cell viability and reduced oxidative stress, apoptosis, and mitochondrial dysfunction in ADR-injured cells (p<0.05). Furthermore, this study confirmed that the protective effect of LYC on ADR-induced cardiotoxicitymight be mediated by the SIRT1/PPARγ signaling pathway. These results revealed that the beneficial role of LYC on cardiotoxicity induced by ADR were mediated via regulating SIRT1/PPARγ signaling for the first time. CONCLUSION: These discoveries may provide a theoretical basis for the exploitation of LYC as a potential cardioprotective drug candidate due to its multiple biological functions to reduce ADR-induced cardiotoxicity, but further preclinical and clinical studies are still needed.


Assuntos
Cardiotoxicidade , Doxorrubicina , Alcaloides de Amaryllidaceae , Animais , Cardiotoxicidade/tratamento farmacológico , Camundongos , Estresse Oxidativo , PPAR gama , Fenantridinas , Sirtuína 1
15.
ACS Chem Neurosci ; 13(12): 1719-1726, 2022 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-35640092

RESUMO

It is urgently needed to find reliable biofluid biomarkers for early diagnosis of Parkinson's disease in order to achieve better treatment. Promising biomarkers can be found in Parkinson's disease-related glycoproteins as aberrant protein glycosylation plays an important role in disease progression. However, current information on serum N-glycoproteomic changes in Parkinson's disease is still limited. Here, we used glycoproteomics methods, which combine the solid-phase chemoenzymatic method, lectin affinity chromatography, and hydrophilic interaction chromatography with high-resolution mass spectrometry, to analyze the glycans, glycosites, and intact glycopeptides of serum. Increased abundance of glycans containing core fucose, sialic acid, and bisecting N-acetyl glucosamine was detected at the overall glycan level and also at specific glycosites of glycopeptides. Five Parkinson's disease-associated proteins with this type of N-glycosylation changes were also identified. We propose that the revealed site-specific N-glycosylation changes in serum can be potential biomarkers for Parkinson's disease.


Assuntos
Doença de Parkinson , Espectrometria de Massas em Tandem , Glicopeptídeos/química , Glicosilação , Humanos , Doença de Parkinson/diagnóstico , Polissacarídeos/química , Espectrometria de Massas em Tandem/métodos
16.
Phytother Res ; 36(6): 2628-2640, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35583809

RESUMO

Psoralidin (PSO) is a natural phenolic coumarin extracted from the seeds of Psoralea corylifolia L. Growing preclinical evidence indicates that PSO has anti-inflammatory, anti-vitiligo, anti-bacterial, and anti-viral effects. Growth arrest-specific gene 6 (GAS6) and its receptor, Axl, modulate cellular oxidative stress, apoptosis, survival, proliferation, migration, and mitogenesis. Notably, the neuroprotective role of the GAS6/Axl axis has been identified in previous studies. We hypothesize that PSO ameliorates cerebral hypoxia/reoxygenation (HR) injury via activating the GAS6/Axl signaling. We first confirmed that PSO was not toxic to the cells and upregulated GAS6 and Axl expression after HR injury. Moreover, PSO exerted a marked neuroprotective effect against HR injury, represented by restored cell viability and cell morphology, decreased lactate dehydrogenase (LDH) release, and reactive oxygen species (ROS) generation. Furthermore, PSO pretreatment also elevated the levels of nuclear factor-related factor 2 (Nrf-2), NAD(P)H dehydrogenase quinone-1 (NQO1), heme oxygenase-1 (HO-1), silent information regulator 1 (SIRT1), peroxisome proliferator-activated receptor coactivator 1α (PGC-1α), nuclear respiratory factor 1 (NRF1), uncoupling protein 2 (UCP2), and B-cell lymphoma 2 (BCl2) both in the condition of baseline and HR injury. However, GAS6 siRNA or Axl siRNA inhibited the neuroprotective effects of PSO. Our findings suggest that PSO pretreatment attenuated HR-induced oxidative stress, apoptosis, and mitochondrial dysfunction in neuroblastoma cells through the activation of GAS6/Axl signaling.


Assuntos
Hipóxia Encefálica , Fármacos Neuroprotetores , Benzofuranos , Cumarínicos/farmacologia , Humanos , Hipóxia , Peptídeos e Proteínas de Sinalização Intercelular , Fármacos Neuroprotetores/farmacologia , Proteínas Proto-Oncogênicas/metabolismo , RNA Interferente Pequeno , Receptores Proteína Tirosina Quinases/genética , Receptores Proteína Tirosina Quinases/metabolismo
17.
Clin Rheumatol ; 2022 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-35536414

RESUMO

OBJECTIVE: To evaluate the reliability and validity of the Chinese version of the eight-item Morisky Medication Adherence Scale (MMAS-8) in Chinese patients with systemic lupus erythematosus (SLE). METHODS: The survey was conducted with a consecutive sampling of 158 Chinese SLE patients attending public hospitals from January to March 2021. We used the translated Chinese version of the MMAS-8 to collect related data. Reliability, item, and factor analyses were used to test the reliability and validity of the MMAS-8 scale in the selected patients. The internal consistency reliability was evaluated using Cronbach's α coefficient. Test-retest reliability was assessed using intraclass correlation coefficients (ICCs) in a subset of 30 participants. Construct validity was evaluated using confirmatory factor analysis and correlations between the Self-efficacy for Appropriate Medication Use Scale (SEAMS) and related measures. RESULTS: The internal consistency reliability of the Chinese version of the MMAS-8 was high (Cronbach's α = 0.817), and the test-retest reliability was excellent (intraclass correlation = 0.947; P < 0.001). There were significant differences in the F test and t test between the two extreme groups before and after the ranking of 27% of the questionnaire scores (P < 0.001). The Kaiser-Meyer-Olkin (KMO) value of construct validity was 0.860. The spherical test value of Bartlettgers was 417.8822. Factor analysis yielded three components that accounted for 69.375% of the total variance. Exploratory factor analysis identified three dimensions of the Chinese version of the MMAS-8. In terms of criterion validity, the correlation of the MMAS-8 score in SEAMS indicated that the convergent validity was good (r = 0.926; P < 0.001). CONCLUSIONS: This study shows that the Chinese version of the Medication Adherence Scale-8 is a reliable and valid tool for assessing medication adherence in Chinese SLE patients. Key Points • Many factors affect medication adherence in SLE patients. • Many questionnaires measure medication adherence levels. • There is a lack of reliable validation of medication adherence questionnaires specifically for SLE patients.

18.
J Toxicol Pathol ; 35(2): 193-203, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35516842

RESUMO

Liver fibrosis results from liver inflammation and progresses to liver cirrhosis or liver cancer. It is known that nonalcoholic liver disease is mediated by the Toll-like receptor 4 (TLR4)/myeloid differentiation factor-2 (MD-2)-tumor necrosis factor-alpha (TNF-α) signaling pathway. This study aimed to investigate whether alcoholic liver disease is also mediated by this pathway. To this end, we first established rat models of liver fibrosis by administering alcohol. Next, the rats were injected with anti-TLR4 and anti-MD-2 antibodies. Real Time Quantitative PCR (RT-qPCR) and Western blotting were used to detect the activation of the TLR4/MD-2-TNF-α signaling pathway and hepatic stellate cells (HSCs). Moreover, the expression of molecules related to liver fibrosis was estimated. The morphology of rat liver tissue was observed through hematoxylin-eosin staining and Masson staining. For in vitro studies, Kupffer cells (KCs) isolated from the liver were transfected with si-TLR4 and si-MD-2 and co-cultured with HSCs to determine the activity of HSCs. It was found that alcohol treatment activated the TLR4/MD-2-TNF-α signaling pathway and upregulated the molecules associated with liver fibrosis. However, inhibition of TLR4 and MD-2 partially reversed this trend. Notably, in vitro studies indicated that knockdown of TLR4 and MD-2 in KCs partially inhibited LPS-induced activation of KCs and HSCs. Overall, this study showed that alcohol induces liver fibrosis via the LPS-TLR4/MD-2-TNF-α signaling pathway.

19.
Front Cardiovasc Med ; 9: 860059, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35557513

RESUMO

Introduction: Patients with incomplete revascularization (ICR) tend to develop refractory angina despite optimal medical therapy. The Compound Danshen Dripping Pills (CDDP) is a widely used antianginal drug in China and is shown to significantly alleviate myocardial ischemia. Previous studies showed dose-efficacy tendency when increasing doses of CDDP. This study aims to investigate the efficacy and safety of intensive doses of CDDP in patients with refractory angina with ICR. Methods and Analysis: The INCODER study is a multicenter, double-blind, randomized controlled, superiority trial. We plan to recruit 250 patients aged 18-85 years with a diagnosis of refractory angina with ICR. Patients will be randomized (1:1) to intensive treatment group (CDDP 20 pills three times per day) or standard treatment group (10 pills CDDP and 10 pills placebo three times per day). Patients will have a 6-week medication period and be followed up every 2 weeks. The primary endpoint is the change of total exercise time from baseline to week 6 as assessed by cardiopulmonary exercise testing (CPET). Secondary endpoints include changes in the frequency of angina, Canadian Cardiovascular Society angina class, nitroglycerin use, Seattle Angina Questionnaire scores, peak oxygen uptake (VO2 peak) and other parameters as measured by CPET, and the levels of plasma C-reactive protein, homocysteine, and N-terminal pro-B-type natriuretic peptide. Safety events related to CDDP use will be monitored. Ethics and Dissemination: The research had been approved by the Clinical research and laboratory animal ethics committee of the First Affiliated Hospital, Sun Yat-sen University ([2019]65). The results will be reported through peer-reviewed journals, seminars, and conference presentations. Trial Registration Number: www.chictr.org.cn (ChiCTR2000032384). Registered on 27 April 2020.

20.
Front Oncol ; 12: 836257, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35515130

RESUMO

Anaplastic meningioma is classified as a World Health Organization (WHO) grade III tumor and shows a strong tendency to recur. Although the incidence of anaplastic meningioma is low, the high rate of recurrence and death still makes treatment a challenge. A proteomics analysis was performed to investigate the differentially expressed proteins between anaplastic meningiomas and fibrous meningiomas by micro-LC-MS/MS. The key metabolic enzyme nicotinamide phosphoribosyltransferase (NAMPT) showed upregulated expression in anaplastic meningiomas. However, targeting NAMPT to treat anaplastic meningiomas has not been reported. In vitro, NAMPT inhibitor -FK866 reduced the viability of anaplastic meningiomas by inducing cell cycle arrest at the G2/M phase. Intriguingly, the NAMPT inhibitor -FK866 decreased the protein expression of immune checkpoints PD-L1 and B7-H3 by down-regulating the STAT1 and p-STAT1 expression in vitro. Furthermore, FK866 suppressed the growth of anaplastic meningiomas in an in vivo xenograft model. The expression of Ki-67 and immune checkpoint proteins (PD-L1 and B7-H3) showed significant differences between the group treated with FK866 and the control group treated with DMSO. In conclusion, the expression of NAMPT, which plays a crucial role in energy metabolism, was upregulated in anaplastic meningiomas. The NAMPT inhibitor -FK866 significantly suppressed the growth of anaplastic meningiomas in vitro and in vivo. More strikingly, FK866 potently inhibited immune checkpoint protein (PD-L1 and B7-H3) expression by regulating STAT1 in vitro and in vivo. Our results demonstrated that NAMPT inhibitors could potentially be an effective treatment method for patients suffering from anaplastic meningiomas.

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