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1.
Front Oncol ; 11: 712760, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34900669

RESUMO

Background: The clinical role of deficient DNA mismatch repair (dMMR)/microsatellite instability-high (MSI-H) in gastric cancer (GC) is still controversial. We aimed to analyze the relationship between dMMR/MSI-H and clinicopathological features along with survival. Methods: Patients who were diagnosed with GC at the three big cancer centers in China from 2015 to 2020 were evaluated retrospectively. MMR/MSI status was assessed using immunohistochemistry/PCR. Clinical and pathological data were collected from the medical record system. Results: A total of 196 patients with dMMR/MSI-H status were enrolled for analysis. The prevalence of MSI-H/dMMR in GC was 6.6%. Another 694 proficient MMR (pMMR) GC patients were enrolled for comparison. Compared with pMMR patients, dMMR/MSI-H patients were associated with older age, female predominance, distal location in the stomach, earlier TNM stage, intestinal subtype, better differentiation, and more negative HER2 status. The median overall survival (OS) of the dMMR/MSI-H group was better than that of the pMMR/microsatellite stability (MSS) group (not reached vs. 53.9 months, p = 0.014). Adjuvant chemotherapy had no impact in both disease-free survival (DFS) and OS of dMMR/MSI-H patients (p = 0.135 and 0.818, respectively). dMMR/MSI-H patients had poorer response and progression-free survival (PFS) of first-line chemotherapy, though they were statistically significant (p = 0.361 and 0.124, respectively). Conclusions: dMMR/MSI-H GC patients have specific clinicopathological characteristics and better prognosis than pMMR patients.

2.
Hu Li Za Zhi ; 68(6): 83-90, 2021 Dec.
Artigo em Chinês | MEDLINE | ID: mdl-34839494

RESUMO

BACKGROUND & PROBLEMS: Facilitated tucking (containment) is a strategy that has been demonstrated to improve insufficient muscle tone, reduce procedural pain, and stabilize vital signs in premature infants. PURPOSE: The aim of this study was to improve the accuracy and implementation rate of nursing staffs` facilitated tucking. METHODS: Formulate and standardize nursing care to reduce the burden on nursing staff and make staff implementation consistent. Decomposition diagrams of the production steps were posted in patient units, on-the-job education courses were held, and a short video was used to provide care guidelines to nursing staff. RESULTS: Compared to pretest levels, the rate of facilitated tucking implementation in the early, middle, and late invasive medical treatment periods, respectively, increased from 0% to 53.5%, 1.2% to 50%, and 6% to 48.8%, while the accuracy rate of facilitated tucking cognition increased from 61.1% to 91.9%. CONCLUSIONS: This project effectively promoted the standardization of facilitated tucking in our hospital, provided preterm infants with better care and neurological development, and improved mother-infant attachment.


Assuntos
Contenção Facilitada , Doenças do Prematuro , Criança , Humanos , Lactente , Recém-Nascido , Recém-Nascido Prematuro , Unidades de Terapia Intensiva Neonatal , Manejo da Dor
3.
Am J Cancer Res ; 11(10): 5006-5015, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34765307

RESUMO

Gastric cancer (GC) patients with Epstein-Barr virus (EBV) positivity have demonstrated promising response with immunotherapy. We assessed the efficacy and safety of camrelizumab as salvage treatment in EBV-positive mGC. In this single-arm, phase 2 prospective clinical trial (NCT03755440), stage IV EBV-positive GC patients who failed/could not tolerate previous lines of chemotherapy were given intravenous camrelizumab 200 mg every 2 weeks until disease progression or unacceptable toxicity. The primary endpoint was objective response rate. Secondary endpoints were progression-free survival (PFS), overall survival (OS), disease control rate (DCR), duration of response, and toxicity. Exploratory analysis included the associations between treatment response and tumor mutation burden (TMB), programmed cell death ligand-1 (PD-L1) expression. Six eligible patients were enrolled in the first stage of the study. No patient achieved an objective response; thus, the study did not proceed to the second stage. The DCR was 67% (4/6). The median PFS rate was 2.2 months (95% CI: 1.5-not reached [NR]) and median OS was 6.8 months (95% CI: 1.7-NR). All treatment-related adverse events were grade 1-2, with reactive cutaneous capillary endothelial proliferation (n=4 [67%]) being the most commonly observed event. The only patient with PD-L1 combined positive score >1 had disease progression. Two stable disease and one disease progression were observed in three patients with TMB >10 Mut/Mb. EBV positivity may not be a good predictor for response to camrelizumab in mGC. Newer biomarkers are needed to identify EBV-positive mGC respondents who might benefit from immunotherapy.

4.
Front Oncol ; 11: 698732, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34621668

RESUMO

Background: KEYNOTE-181, ATTRACTION-3, and ESCORT trials have opened the era of programmed death 1 (PD-1) inhibitors in the second-line therapy for esophageal squamous cell carcinoma (ESCC). There is no head-to-head comparison of pembrolizumab vs. nivolumab vs. camrelizumab in the second-line setting for ESCC. We performed an indirect comparison to explore the optimal choice of immune checkpoint inhibitor (ICI) for advanced ESCC. Methods: Patients in ATTRACTION-3 and ESCORT were all squamous carcinoma, while KEYNOTE-181 enrolled both adenocarcinoma and squamous carcinoma patients. We only extract information of patients with squamous carcinoma from KEYNOTE 181 study and all the patients from ATTRACTION-3 and ESCORT. The main clinical outcomes for this study were overall survival (OS), progression-free survival (PFS), objective response rate (ORR), and treatment-related adverse events (TRAEs). Results: Indirect analysis showed similar survival benefit among three PD-1 inhibitors. Nivolumab was comparable with pembrolizumab in most subgroups except that nivolumab was slightly better for patients with performance status (PS) score of 1 [HRnivo/pembro: 0.68 (95% confidence interval (CI): 0.45-1.02], p = 0.07). Compared with nivolumab indirectly, pembrolizumab and camrelizumab had better PFS [HRpembro/nivo: 0.85 (95% CI: 0.63-1.14), p = 0.29; HRcam/nivo: 0.64 (95% CI: 0.47-0.87), p = 0.004] and significantly higher ORR [RRpembro/nivo: 2.51 (95% CI: 1.22-5.15), p = 0.01; RRcam/nivo: 3.52 (95% CI: 1.73-7.18), p = 0.001]. Compared with camrelizumab indirectly, pembrolizumab had slightly worse PFS [HRpembro/cam: 1.33 (95% CI: 0.99-1.79), p = 0.057] and comparable ORR [RRpembro/cam: 0.71 (95% CI: 0.32-1.60; p = 0.41)]. Camrelizumab had a significantly higher rate of all grade TRAEs than both pembrolizumab and nivolumab. Conclusions: Combining the safety and potential survival benefit, we recommend nivolumab for ESCC patients with PS score of 1 and pembrolizumab or camrelizumab for patients with better PS and seeking for higher efficacy or longer PFS.

5.
Int Immunopharmacol ; 101(Pt B): 108236, 2021 Oct 12.
Artigo em Inglês | MEDLINE | ID: mdl-34653727

RESUMO

Diabetic nephropathy (DN) is a main complication of diabetes and often develops into end-stage nephropathy. Histologically, DN progresses as the gradual loss of podocytes with the loss of glomerular podocytes being the earliest sign of DN. Pyroptosis is a new type of programmed cell death and has been mechanistically correlated with podocyte injury in DN. The current study aimed to evaluate the protective effects of carnosine on glomerular podocytes in DN, both in vivo and in vitro. Using high glucose-treated cultured MPC5 cells and a streptozotocin (STZ)-induced diabetic mouse model, we evaluated the effects of carnosine on alleviating podocyte injury in DN. We found that carnosine significantly reversed albuminuria and histopathological lesions and alleviated renal inflammatory and pyroptosis responses in STZ-induced diabetic mice for 12 weeks. The results also showed that carnosine strongly inhibited podocyte inflammation and podocyte pyroptosis in vitro. Cellular Thermal Shift Assay (CETSA) and molecular docking results revealed that mechnaistically caspase-1 was the target of carnosine. We then found that silencing caspase-1 eliminated the protective effect of carnosine. Interestingly, we also found that caspase-1 and gasdermin D expression were increased in renal biopsy tissue of patients with DN. Our study is the first to demonstrate the novel role of carnosine in alleviating podocyte injury by inhibiting pyroptosis via the targeting of caspase-1. Carnosine may have potential as a therapeutic agent in treating DN by targeting caspase-1.

6.
Curr Opin Pharmacol ; 60: 281-290, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34500407

RESUMO

Nutraceuticals activating the Kelch-like epichlorohydrin (ECH)-associated protein 1 (Keap1)-nuclear factor erythroid-derived 2-related factor 2 (Nrf2)-antioxidant response element (ARE) pathway are widely used for nonalcoholic fatty liver disease (NAFLD) because no specific drugs are approved yet. The pathology of NAFLD is summarized as the 'two-hit' hypothesis. The 'first hit' includes insulin resistance and lipid accumulation. Oxidative stress, lipid peroxidation, and inflammation are regarded as the 'second hit'. Now there is controversial evidence about the roles of the Keap1-Nrf2-ARE pathway and its activators in NAFLD. When the 'first hit' occurs, the hepatocyte-specific Nrf2 deficiency reduces insulin resistance and significantly attenuates lipid accumulation. However, when the 'second hit' occurs, Nrf2 activation reduces oxidative stress and combats inflammation. We reviewed the roles of the Keap1-Nrf2-ARE pathway as a double-edged sword in the development of NAFLD, its inhibitors as a novel therapeutic approach for early NAFLD, and the nutraceutical character of its activators.


Assuntos
Hepatopatia Gordurosa não Alcoólica , Elementos de Resposta Antioxidante , Epicloroidrina , Humanos , Proteína 1 Associada a ECH Semelhante a Kelch/genética , Proteína 1 Associada a ECH Semelhante a Kelch/metabolismo , Fator 2 Relacionado a NF-E2/genética , Fator 2 Relacionado a NF-E2/metabolismo , Hepatopatia Gordurosa não Alcoólica/tratamento farmacológico , Estresse Oxidativo , Transdução de Sinais
7.
J Clin Transl Hepatol ; 9(3): 373-383, 2021 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-34221923

RESUMO

Background and Aims: Lipid accumulation is the major characteristic of non-alcoholic fatty liver disease, the prevalence of which continues to rise. We aimed to investigate the effects and mechanisms of icaritin on lipid accumulation. Methods: Cells were treated with icaritin at 0.7, 2.2, 6.7, or 20 µM for 24 h. The effects on lipid accumulation in L02 and Huh-7 cells were detected by Bodipy and oil red O staining, respectively. Mitochondria biogenesis of L02 cells was detected by MitoTracker Orange staining. Glucose uptake and adenosine triphosphate content of 3T3-L1 adipocytes and C2C12 myotubes were detected. The expression levels of proteins in the adenosine 5'-monophosphate-activated protein kinase (AMPK) signaling pathway, biomarkers of autophagy, and mitochondria biogenesis were measured by western blotting. LC3 puncta were detected by immunofluorescence. Results: Icaritin significantly attenuated lipid accumulation in L02 and Huh-7 cells and boosted the mitochondria biogenesis of L02 cells. Icaritin enhanced glucose uptake, decreased adenosine triphosphate content, and activated the AMPK signaling pathway in 3T3-L1 adipocytes and C2C12 myotubes. Icaritin boosted autophagy and also enhanced the initiation of autophagic flux in 3T3-L1 preadipocytes and C2C12 myoblasts. However, icaritin decreased autophagy and promoted mitochondria biogenesis in 3T3-L1 adipocytes and C2C12 myotubes. Conclusions: Icaritin attenuates lipid accumulation by increasing energy expenditure and regulating autophagy by activating the AMPK pathway.

8.
Chin Med ; 16(1): 3, 2021 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-33407692

RESUMO

BACKGROUND: OPD and OPD' are the two main active components of Ophiopogon japonicas in Shenmai injection (SMI). Being isomers of each other, they are supposed to have similar pharmacological activities, but the actual situation is complicated. The difference of hemolytic behavior between OPD and OPD' in vivo and in vitro was discovered and reported by our group for the first time. In vitro, only OPD' showed hemolysis reaction, while in vivo, both OPD and OPD' caused hemolysis. In vitro, the primary cause of hemolysis has been confirmed to be related to the difference between physical and chemical properties of OPD and OPD'. In vivo, although there is a possible explanation for this phenomenon, the one is that OPD is bio-transformed into OPD' or its analogues in vivo, the other one is that both OPD and OPD' were metabolized into more activated forms for hemolysis. However, the mechanism of hemolysis in vivo is still unclear, especially the existing literature are still difficult to explain why OPD shows the inconsistent hemolysis behavior in vivo and in vitro. Therefore, the study of hemolysis of OPD and OPD' in vivo is of great practical significance in response to the increase of adverse events of SMI. METHODS: Aiming at the hemolysis in vivo, this manuscript adopted untargeted metabolomics and lipidomics technology to preliminarily explore the changes of plasma metabolites and lipids of OPD- and OPD'-treated rats. Metabolomics and lipidomics analyses were performed on ultra-high performance liquid chromatography (UPLC) system tandem with different mass spectrometers (MS) and different columns respectively. Multivariate statistical approaches such as principal component analysis (PCA) and orthogonal partial least square-discriminant analysis (OPLS-DA) were applied to screen the differential metabolites and lipids. RESULTS: Both OPD and OPD' groups experienced hemolysis, Changes in endogenous differential metabolites and differential lipids, enrichment of differential metabolic pathways, and correlation analysis of differential metabolites and lipids all indicated that the causes of hemolysis by OPD and OPD' were closely related to the interference of phospholipid metabolism. CONCLUSIONS: This study provided a comprehensive description of metabolomics and lipidomics changes between OPD- and OPD'-treated rats, it would add to the knowledge base of the field, which also provided scientific guidance for the subsequent mechanism research. However, the underlying mechanism require further research.

9.
Stem Cells Dev ; 30(1): 39-48, 2021 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-33176587

RESUMO

A transgenic acute promyelocytic leukemia (APL) murine model established by Michael Bishop by cloning a human PML-RARα cDNA into the hMRP8 expression cassette has been widely used in the all-trans retinoid acid and arsenic preparations for the research of APL. However, in the existing literature, the data of regularity and characteristics of the pathogenesis of this model were still missing, which hinder the development of many studies, especially application of new technologies such as single-cell sequencing. Therefore, in this article, we have made up this part of the missing data using an improved APL murine model. We clarified the effects of different inoculation doses on the onset time, latency, morbidity, life span, and proportion of APL cells in peripheral blood (PB), spleen, bone marrow, and so on. The relationship between the proportion of APL cells in the bone marrow, spleen, and PB and organ histological changes was also revealed. These results were a supplement and refinement of this APL model. It would add to the knowledge base of the field and aid in ensuring that accurate models are used for directed interventions. It also provides a great convenience for the researchers who will carry out similar research.

10.
Oxid Med Cell Longev ; 2020: 8870656, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33381274

RESUMO

Ophiopogonin D (OPD) and Ophiopogonin D' (OPD') are two bioactive ingredients in Ophiopogon japonicus. Previously published studies have often focused on the therapeutic effects related to OPD's antioxidant capacity but underestimated the cytotoxicity-related side effects of OPD', which may result in unpredictable risks. In this study, we reported another side effect of OPD', hemolysis, and what was unexpected was that this side effect also appeared with OPD. Although hemolysis effects for saponins are familiar to researchers, the hemolytic behavior of OPD or OPD' and the interactions between these two isomers are unique. Therefore, we investigated the effects of OPD and OPD' alone or in combination on the hemolytic behavior in vitro and in vivo and adopted chemical compatibility and proteomics methods to explain the potential mechanism. Meanwhile, to explain the drug-drug interactions (DDIs), molecular modeling was applied to explore the possible common targets. In this study, we reported that OPD' caused hemolysis both in vitro and in vivo, while OPD only caused hemolysis in vivo. We clarified the differences and DDIs in the hemolytic behavior of the two isomers. An analysis of the underlying mechanism governing this phenomenon showed that hemolysis caused by OPD or OPD' was related to the destruction of the redox balance of erythrocytes. In vivo, in addition to the redox imbalance, the proteomics data demonstrated that lipid metabolic disorders and mitochondrial energy metabolism are extensively involved by hemolysis. We provided a comprehensive description of the hemolysis of two isomers in Ophiopogon japonicus, and risk warnings related to hemolysis were presented. Our research also provided a positive reference for the development and further research of such bioactive components.


Assuntos
Hemólise/efeitos dos fármacos , Ophiopogon/química , Saponinas/farmacologia , Espirostanos/farmacologia , Animais , Antioxidantes/efeitos adversos , Antioxidantes/química , Antioxidantes/isolamento & purificação , Antioxidantes/farmacologia , Células Sanguíneas/efeitos dos fármacos , Células Sanguíneas/metabolismo , Medicamentos de Ervas Chinesas/efeitos adversos , Medicamentos de Ervas Chinesas/química , Medicamentos de Ervas Chinesas/farmacologia , Isomerismo , Masculino , Camundongos , Oxirredução/efeitos dos fármacos , Proteoma/efeitos dos fármacos , Proteoma/metabolismo , Coelhos , Ratos , Ratos Wistar , Medição de Risco , Saponinas/efeitos adversos , Saponinas/química , Saponinas/isolamento & purificação , Espirostanos/efeitos adversos , Espirostanos/química , Espirostanos/isolamento & purificação , Testes de Toxicidade Aguda
11.
Phytomedicine ; 79: 153330, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32932202

RESUMO

BACKGROUND: Compound Dan Zhi tablet (DZT) is a commonly used traditional Chinese medicine formula. It has been used for the treatment of ischemic stroke for many years in clinical. However, its pharmacological mechanism is unclear. PURPOSE: The aim of the current study was to understand the protective effects and underlying mechanisms of DZT on ischemic stroke. METHODS: Fifteen representative chemical markers in DZT were determined by ultra-performance liquid chromatography coupled with tandem quadrupole time-of-flight mass spectrometry (UPLC-QTOF-MS). The protective effect of DZT against ischemic stroke was studied in a rat model of middle cerebral artery occlusion (MCAO), and the mechanism was further explored through a combination of network pharmacology and experimental verification. RESULTS: Quantitative analysis showed that the contents of phenolic acids, furan sulfonic acids, tanshinones, flavonoids, saponins and phthalides in DZT were calculated as 7.47, 0.788, 0.627, 0.531 and 0.256 mg/g, respectively. Phenolic acids were the most abundant constituents. Orally administered DZT (1.701 g kg-1) significantly alleviated the infarct size and neurological scores in MCAO rats. The network analysis predicted that 53 absorbed active compounds in DZT-treated plasma targeted 189 proteins and 47 pathways. Ten pathways were associated with anti-platelet activity. In further experiments, DZT (0.4 and 0.8 mg mL-1) markedly inhibited in vitro prostaglandin G/H synthase 1 (PTGS1) activity. DZT (0.4 and 0.8 mg mL-1) significantly inhibited in vitro platelet aggregation in response to ADP or AA. DZT (113 and 226 mg kg-1, p.o.) also produced a marked inhibition of ADP- or AA-induced ex vivo platelet aggregation with a short duration of action. DZT decreased the level of thromboxane A2 (TXA2) in MCAO rats. In the carrageenan-induced tail thrombosis model and ADP-induced acute pulmonary thromboembolism mice model, DZT (113 and 226 mg kg-1, p.o.) prevented thrombus formation. Importantly, DZT (113 and 226 mg kg-1, p.o.) exhibited a low bleeding liability. CONCLUSION: DZT protected against cerebral ischemic injury. The inhibition of TXA2 level, platelet aggregation and thrombosis formation might involve in the protective mechanism.


Assuntos
Medicamentos de Ervas Chinesas/química , Medicamentos de Ervas Chinesas/farmacologia , AVC Isquêmico/tratamento farmacológico , Ativação Plaquetária/efeitos dos fármacos , Trombose/tratamento farmacológico , Animais , Isquemia Encefálica/tratamento farmacológico , Isquemia Encefálica/patologia , Modelos Animais de Doenças , Medicamentos de Ervas Chinesas/farmacocinética , Infarto da Artéria Cerebral Média/tratamento farmacológico , Masculino , Camundongos Endogâmicos ICR , Agregação Plaquetária/efeitos dos fármacos , Inibidores da Agregação Plaquetária/farmacologia , Embolia Pulmonar/tratamento farmacológico , Coelhos , Ratos Sprague-Dawley , Comprimidos , Trombose/induzido quimicamente , Tromboxano A2/metabolismo
12.
Zhongguo Zhong Yao Za Zhi ; 45(1): 142-148, 2020 Jan.
Artigo em Chinês | MEDLINE | ID: mdl-32237423

RESUMO

The aim of this paper was to observe the effect of Realgar and arsenic trioxide on gut microbiota. The mice were divided into low-dose Realgar group(RL), medium-dose Realgar group(RM), high-dose Realgar group(RH), and arsenic trioxide group(ATO), in which ATO and RL groups had the same trivalent arsenic content. Realgar and arsenic trioxide toxicity models were established after intragastric administration for 1 week, and mice feces were collected 1 h after intragastric administration on day 8. The effects of Realgar on gut microbiota of mice were observed through bacterial 16 S rRNA gene sequences. The results showed that Lactobacillus was decreased in all groups, while Ruminococcus and Adlercreutzia were increased. The RL group and ATO group were consistent in the genera of Prevotella, Ruminococcus, and Adlercreutzia but different in the genera of Lactobacillus and Bacteroides. Therefore, the effects of Realgar and arsenic trioxide with the same amount of trivalent arsenic on gut microbiota were similar, but differences were still present. Protective bacteria such as Lactobacillus were reduced after Realgar administration, causing inflammation. At low doses, the number of anti-inflammatory bacteria, such as Ruminococcus, Adlercreutzia and Parabacteroides increased, which can offset the slight inflammation caused by the imbalance of bacterial flora. At high doses, the flora was disturbed and the number of Proteobacteria was increased, with aggravated intestinal inflammation, causing edema and other inflammatory reactions. Based on this, authors believe that the gastrointestinal reactions after clinical use of Realgar may be related to flora disorder. Realgar should be used at a small dose in combination with other drugs to reduce intestinal inflammation.


Assuntos
Trióxido de Arsênio/farmacologia , Arsenicais/farmacologia , Microbioma Gastrointestinal/efeitos dos fármacos , Sulfetos/farmacologia , Animais , Bactérias/classificação , Bactérias/efeitos dos fármacos , Camundongos
13.
Molecules ; 24(6)2019 Mar 20.
Artigo em Inglês | MEDLINE | ID: mdl-30897753

RESUMO

The Naoxinqing (NXQ) tablet is a standardised proprietary herbal product containing an extract of persimmon leaves (Diospyros kaki) for the management of cardio- and cerebrovascular diseases. Although previous reports suggested that the efficacy of NXQ is at least partly mediated by its anti-oxidative property, the anti-oxidative effect of the major components of NXQ has not been studied systematically. For quality control purposes, only analytical methods limited to 3 marker analytes have been reported, the extent to which the other components affect efficacy has not been explored. In this study, we developed an ultra-performance liquid chromatography-tandem mass spectrometry (UPLC MS/MS) method for the identification of seven analytes (kaempferol-3-O-glucoside (astragalin), quercetin-3-O-galactoside (hypericin), quercetin-3-O-glucoside (isoquercitin), kaempferol, 3,4-dihydroxybenzoic acid (protocatechuic acid), and furan-2-carboxylic acid (pyromucic acid) and quercetin) in the NXQ. This is the first method reported and validated for the quantification of the seven major secondary metabolites in NXQ. The results for the quantified analytes were then compared in 15 different batches of NXQ. The variation observed in the seven components highlights the need to quantify key bioactive components to ensure product consistency. Radical scavenging activity and abundance was used to rank the analytes. The anti-oxidative effects of NXQ were examined using cultured human vascular endothelial cells (EA.hy926). Corrected 2,2-di(4-tert-octylphenyl)-1-picrylhydrazyl (DPPH) activity results revealed that quercetin and kaempferol have the strongest anti-oxidant capacity in the extract. Both quercetin and kaempferol significantly inhibited the hydrogen peroxide (H2O2)-induced EA.hy926 cell injury and intracellular reactive oxygen species (ROS) generation. In conclusion, we established and validated an UPLC-MS/MC method for the analysis of major bioactive components in the NXQ and demonstrated that its anti-oxidative property may play a critical role in cerebrovascular protection.


Assuntos
Diospyros/química , Medicamentos de Ervas Chinesas/química , Extratos Vegetais/química , Folhas de Planta/química , Antracenos , Linhagem Celular , Cromatografia Líquida de Alta Pressão , Humanos , Hidroxibenzoatos/química , Quempferóis/química , Perileno/análogos & derivados , Perileno/química , Quercetina/análogos & derivados , Quercetina/química , Espécies Reativas de Oxigênio , Espectrometria de Massas em Tandem
14.
Haematologica ; 104(1): 102-112, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30076181

RESUMO

Fatty acid oxidation dependency of leukemia cells has been documented in recent studies. Pharmacologic inhibition of fatty acid oxidation, thereby, displays significant effects in suppressing leukemia. 2-Bromopalmitate, a palmitate analogue, was initially identified as an inhibitor of fatty acid oxidation, and recently recognized as an inhibitor of protein palmitoylation. However, the effects of 2-Bromopalmitate on leukemia and its cellular targets remain obscure. Herein, we discover in cultured cell lines, a transplantable mouse model, and primary blasts that 2-Bromopalmitate presents synergistic differentiation induction with all-trans retinoic acid in acute promyelocytic leukemia. Moreover, 2-Bromopalmitate overcomes all-trans retinoic acid resistance in all-trans retinoic acid-resistant cells and leukemic mice. Mechanistically, 2-Bromopalmitate covalently binds at cysteine 105 and cysteine 174 of retinoic acid receptor alpha (RARα) and stabilizes RARα protein in the presence of all-trans retinoic acid which is known to induce RARα degradation, leading to enhanced transcription of RARα-target genes. Mutation of both cysteines largely abrogates the synergistic effect of 2-Bromopalmitate on all-trans retinoic acid-induced differentiation, demonstrating that 2-Bromopalmitate promotes all-trans retinoic acid-induced differentiation through binding RARα. All-trans retinoic acid-based regimens including arsenic trioxide or chemotherapy, as preferred therapy for acute promyelocytic leukemia, induce adverse events and irreversible resistance. We expect that combining all-trans retinoic acid with 2-Bromopalmitate would be a promising therapeutic strategy for acute promyelocytic leukemia, especially for overcoming all-trans retinoic acid resistance of relapsed acute promyelocytic leukemia patients.


Assuntos
Sistemas de Liberação de Medicamentos , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Leucemia Promielocítica Aguda/tratamento farmacológico , Proteínas de Neoplasias/agonistas , Palmitatos/farmacologia , Receptor alfa de Ácido Retinoico/agonistas , Tretinoína/farmacologia , Humanos , Leucemia Promielocítica Aguda/metabolismo , Leucemia Promielocítica Aguda/patologia , Proteínas de Neoplasias/metabolismo , Receptor alfa de Ácido Retinoico/metabolismo , Ensaios Antitumorais Modelo de Xenoenxerto
15.
Eur J Pharmacol ; 768: 77-86, 2015 Dec 05.
Artigo em Inglês | MEDLINE | ID: mdl-26494630

RESUMO

The zebrafish (Danio rerio) has recently become a powerful animal model for cardiovascular research and drug discovery due to its ease of maintenance, genetic manipulability and ability for high-throughput screening. Recent advances in imaging techniques and generation of transgenic zebrafish have greatly facilitated in vivo analysis of cellular events of cardiovascular development and pathogenesis. More importantly, recent studies have demonstrated the functional similarity of drug metabolism systems between zebrafish and humans, highlighting the clinical relevance of employing zebrafish in identifying lead compounds in Chinese herbal medicine with potential beneficial cardiovascular effects. This paper seeks to summarise the scope of zebrafish models employed in cardiovascular studies and the application of these research models in Chinese herbal medicine to date.


Assuntos
Doenças Cardiovasculares/tratamento farmacológico , Descoberta de Drogas/métodos , Medicina Herbária/métodos , Peixe-Zebra , Animais , Doenças Cardiovasculares/fisiopatologia , Modelos Animais de Doenças , Humanos
16.
Clin Exp Hypertens ; 37(7): 594-8, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26114355

RESUMO

Increased blood pressure was associated with increased white blood cell count (adjusted p < 0.001) in a community-based health examination survey of adults in China (n = 39 282; aged 18-93 years). Adjusted odds ratios (95% confidence intervals) for hypertension across white blood cell count quintiles were 1.00, 0.99 (0.89-1.09), 1.11 (1.01-1.22), 1.09 (0.99-1.20), and 1.19 (1.08-1.31) (p for trend < 0.001). Body mass index and white blood cell count had an additive effect on systolic blood pressure (p for interaction = 0.047). Therefore, white blood cell count could independently predict hypertension in Chinese adults.


Assuntos
Pressão Sanguínea/fisiologia , Hipertensão , Leucócitos , Adulto , Índice de Massa Corporal , China/epidemiologia , Feminino , Inquéritos Epidemiológicos , Humanos , Hipertensão/sangue , Hipertensão/diagnóstico , Hipertensão/epidemiologia , Contagem de Leucócitos/métodos , Contagem de Leucócitos/estatística & dados numéricos , Masculino , Razão de Chances , Fatores de Risco
17.
Asian Pac J Cancer Prev ; 16(1): 125-31, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-25640339

RESUMO

Currently, taxol is mainly extracted from the bark of yews; however, this method can not meet its increasing demand on the market because yews grow very slowly and are a rare and endangered species belonging to first- level conservation plants. Recently, increasing efforts have been made to develop alternative means of taxol production; microbe fermentation would be a very promising method to increase the production scale of taxol. To determine the activities of the taxol extracted from endophytic fungus N. sylviforme HDFS4-26 in inhibiting the growth and causing the apoptosis of cancer cells, on comparison with the taxol extracted from the bark of yew, we used cellular morphology, cell counting kit (CCK-8) assay, staining (HO33258/PI and Giemsa), DNA agarose gel electrophoresis and flow cytometry (FCM) analyses to determine the apoptosis status of breast cancer MCF-7 cells, cervical cancer HeLa cells and ovarian cancer HO8910 cells. Our results showed that the fungal taxol inhibited the growth of MCF-7, HeLa and HO8910 cells in a dose-and time-dependent manner. IC50 values of fungal taxol for HeLa, MCF-7 and HO8910 cells were 0.1-1.0 µg/ml, 0.001-0.01 µg/ml and 0.01- 0.1 µg/ml, respectively. The fungal taxol induced these tumor cells to undergo apoptosis with typical apoptotic characteristics, including morphological changes for chromatin condensation, chromatin crescent formation, nucleus fragmentation, apoptotic body formation and G2/M cell cycle arrest. The fungal taxol at the 0.01-1.0 µg/ ml had significant effects of inducing apoptosis between 24-48 h, which was the same as that of taxol extracted from yews. This study offers important information and a new resource for the production of an important anticancer drug by endofungus fermentation.


Assuntos
Antineoplásicos/farmacologia , Neoplasias da Mama/tratamento farmacológico , Neoplasias Ovarianas/tratamento farmacológico , Paclitaxel/farmacologia , Neoplasias do Colo do Útero/tratamento farmacológico , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Feminino , Células HeLa , Humanos , Pontos de Checagem da Fase M do Ciclo Celular/efeitos dos fármacos , Células MCF-7 , Casca de Planta/metabolismo , Taxus/metabolismo , Árvores/metabolismo , Xylariales/metabolismo
18.
J Oral Maxillofac Surg ; 72(12): 2491-6, 2014 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-25216563

RESUMO

Sialolithiasis is defined as calcified stone(s) in the salivary duct or glands. Submandibular gland sialolithiasis is the most common (80 to 90%), followed by parotid gland sialolithiasis (5 to 15%). The typical clinical presentation is salivary gland swelling after eating. As the swelling persists, symptoms owing to local inflammation, such as pain and trismus, emerge. In severe cases, cellulitis and even abscess formation occur and subsequently lead to salivary gland atrophy or fistula formation if the sialolithiasis remains untreated. The most common treatment is complete excision of the affected gland together with the stone(s). In some cases, intraoral sialolithotomy is performed when the stone is solitary and easily palpable through the oral cavity. Sialendoscopy is increasingly performed because of its minimal invasiveness. The major limitation of endoscopic laser lithotripsy of the salivary glands is the size of the stone. Often, for a stone larger than 4 mm, multiple fragmentations of the stone into small pieces is necessary before the pieces can be removed by wire basket or grasping forceps. Recently, the holmium:YAG laser has been reported as quite effective in removing larger salivary gland stones. However, sialoendoscopic laser lithotripsy is a very time-consuming procedure and in most cases, when there are multiple large stones in a single gland, entire gland excision is recommended. This report describes a male patient diagnosed with multiple large stones in his left submandibular gland who was successfully treated under sialendoscopy with holmium:YAG laser lithotripsy.


Assuntos
Endoscopia/métodos , Ductos Salivares/cirurgia , Cálculos das Glândulas Salivares/cirurgia , Adulto , Humanos , Terapia a Laser , Masculino , Cálculos das Glândulas Salivares/diagnóstico por imagem , Tomografia Computadorizada por Raios X
19.
J Clin Hypertens (Greenwich) ; 16(10): 760-5, 2014 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-25113653

RESUMO

The authors aimed to investigate the relationship between serum gamma-glutamyltransferase (GGT) and prehypertension, as well as the modification of other metabolic risk factors in a large cohort of Chinese individuals. The data were collected via a community-based health examination survey in central China. Blood pressure, body mass index (BMI), and levels of GGT, fasting blood glucose, aspartate aminotransferase (AST), alanine aminotransferase (ALT), and lipid indicators were measured. In total, data from 18,302 patients with available biomarkers were included in the present study. Elevated blood pressure was associated with increased GGT concentration (P<.001). After adjusting for age, sex, BMI, fasting blood glucose, lipid indicators, AST, and family history of hypertension, the association between GGT levels and prehypertension remained significant (P=.021). The adjusted odds ratios (95% confidence interval) for prehypertension across quintiles of GGT level were 1.00, 1.057 (1.012-1.334), 1.068 (0.916-1.254), 1.024 (0.851-1.368), and 1.272 (1.027-1.593), respectively. In stratified analyses, the association between GGT levels and prehypertension was significant in women but was not significant in men. Moreover, additive effect of BMI and age on the effect of GGT levels on prehypertension (both P for interaction <.001) was observed. In summary, GGT levels were positively associated with prehypertension in women, independent of other metabolic factors. Furthermore, BMI and age may amplify the effects of GGT levels on prehypertension. These findings suggest that monitoring the levels of GGT could help in the diagnosis and monitoring of prehypertension.


Assuntos
Doenças Cardiovasculares/sangue , Doenças Cardiovasculares/diagnóstico , Síndrome Metabólica/sangue , Síndrome Metabólica/diagnóstico , Pré-Hipertensão/sangue , Pré-Hipertensão/diagnóstico , gama-Glutamiltransferase/sangue , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Alanina Transaminase/sangue , Aspartato Aminotransferases/sangue , Glicemia/metabolismo , Índice de Massa Corporal , China , Estudos de Coortes , Feminino , Predisposição Genética para Doença/genética , Inquéritos Epidemiológicos , Humanos , Lipídeos/sangue , Masculino , Pessoa de Meia-Idade , Pré-Hipertensão/genética , Distribuição Aleatória , Fatores de Risco , Adulto Jovem
20.
Gene ; 505(1): 114-20, 2012 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-22634102

RESUMO

The liver X receptor α (LXRα) is a nuclear receptor of the transcription factor and is known to play a crucial role in lipid metabolism processes such as bile acid and fatty acid synthesis in humans and rodents. However, very little information is available on the role of LXRα in the regulation of fatty acid synthesis in the goat mammary gland. In this investigation, a cDNA was isolated from the mammary gland of Xinong Saanen dairy goats and designated as goat LXRα. RT-PCR and RACE gave rise to the full-length cDNA of LXRα, which was comprised of 1654 bp and characterized by an ORF of 1344 bp and 5'- and 3'-UTR regions of 150 and 160 bp, respectively. The deduced amino acid sequence encodes 477 amino acids with a predicted molecular weight (MW) of 50.4kDa and a theoretical isoelectric point (pI) of 6.3. Additionally, homology search and sequence multi-alignment indicated that the putative goat LXRα amino acid sequence is very similar to those of cattle, mice, rats, swine, and humans. Bioinformatic predictions demonstrated that the LXRα protein is located in the nucleus, containing characteristic signatures of a nuclear receptor with DNA-binding domain (DBD) and ligand-binding domain (LBD). Real-time quantitative PCR suggested that LXRα was predominantly expressed in the small intestine, liver, spleen and mammary gland. Treatment of goat mammary gland epithelial cells (GMEC) with different concentrations (i.e., 0.01, 0.1, 1 µM) of T0901317, a synthetic agonist of LXRα, resulted in elevated sterol regulatory element binding protein 1 (SREBP1) and fatty acid synthase (FASN) mRNA levels in response to LXRα activation. The association between different T0901317 concentrations and fatty acid composition in GMEC also was examined using gas chromatography (GC). The results showed that activation of LXRα significantly increased GMEC C18:1 and C18:2 contents, but did not affect levels of saturated fatty acids (SFA). These discoveries are consistent with the notion that LXRα plays a key role in controlling lipogenesis and regulating synthesis of unsaturated fatty acids (UFA) in the mammary gland of goats, which may prove useful in regulation of milk fat production.


Assuntos
Ácidos Graxos , Cabras , Glândulas Mamárias Animais/metabolismo , Receptores Nucleares Órfãos , Animais , Bovinos , Clonagem Molecular , DNA Complementar/genética , Ácido Graxo Sintases/genética , Ácido Graxo Sintases/metabolismo , Ácidos Graxos/biossíntese , Ácidos Graxos/genética , Feminino , Cabras/genética , Cabras/metabolismo , Humanos , Ponto Isoelétrico , Receptores X do Fígado , Glândulas Mamárias Animais/citologia , Camundongos , Fases de Leitura Aberta/fisiologia , Especificidade de Órgãos/fisiologia , Receptores Nucleares Órfãos/genética , Receptores Nucleares Órfãos/metabolismo , Estrutura Terciária de Proteína , Ratos , Elementos de Resposta/fisiologia , Alinhamento de Sequência , Proteína de Ligação a Elemento Regulador de Esterol 1/genética , Proteína de Ligação a Elemento Regulador de Esterol 1/metabolismo
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