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1.
Signal Transduct Target Ther ; 6(1): 329, 2021 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-34471087

RESUMO

It's a challenge for detecting the therapeutic targets of a polypharmacological drug from variations in the responsed networks in the differentiated populations with complex diseases, as stable coronary heart disease. Here, in an adaptive, 31-center, randomized, double-blind trial involving 920 patients with moderate symptomatic stable angina treated by 14-day Danhong injection(DHI), a kind of polypharmacological drug with high quality control, or placebo (0.9% saline), with 76-day following-up, we firstly confirmed that DHI could increase the proportion of patients with clinically significant changes on angina-frequency assessed by Seattle Angina Questionnaire (ΔSAQ-AF ≥ 20) (12.78% at Day 30, 95% confidence interval [CI] 5.86-19.71%, P = 0.0003, 13.82% at Day 60, 95% CI 6.82-20.82%, P = 0.0001 and 8.95% at Day 90, 95% CI 2.06-15.85%, P = 0.01). We also found that there were no significant differences in new-onset major vascular events (P = 0.8502) and serious adverse events (P = 0.9105) between DHI and placebo. After performing the RNA sequencing in 62 selected patients, we developed a systemic modular approach to identify differentially expressed modules (DEMs) of DHI with the Zsummary value less than 0 compared with the control group, calculated by weighted gene co-expression network analysis (WGCNA), and sketched out the basic framework on a modular map with 25 functional modules targeted by DHI. Furthermore, the effective therapeutic module (ETM), defined as the highest correlation value with the phenotype alteration (ΔSAQ-AF, the change in SAQ-AF at Day 30 from baseline) calculated by WGCNA, was identified in the population with the best effect (ΔSAQ-AF ≥ 40), which is related to anticoagulation and regulation of cholesterol metabolism. We assessed the modular flexibility of this ETM using the global topological D value based on Euclidean distance, which is correlated with phenotype alteration (r2: 0.8204, P = 0.019) by linear regression. Our study identified the anti-angina therapeutic module in the effective population treated by the multi-target drug. Modular methods facilitate the discovery of network pharmacological mechanisms and the advancement of precision medicine. (ClinicalTrials.gov identifier: NCT01681316).

2.
Nanomedicine (Lond) ; 16(24): 2207-2242, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34533048

RESUMO

With the excellent ability to transform near-infrared light to localized visible or UV light, thereby achieving deep tissue penetration, lanthanide ion-doped upconversion nanoparticles (UCNP) have emerged as one of the most striking nanoscale materials for more effective and safer cancer treatment. Up to now, UCNPs combined with photosensitive components have been widely used in the delivery of chemotherapy drugs, photodynamic therapy and photothermal therapy. Applications in these directions are reviewed in this article. We also highlight microenvironmental tumor monitoring and precise targeted therapies. Then we briefly summarize some new trends and the existing challenges for UCNPs. We hope this review can provide new ideas for future cancer treatment based on UCNPs.


Assuntos
Elementos da Série dos Lantanídeos , Nanopartículas , Neoplasias , Fotoquimioterapia , Humanos , Raios Infravermelhos , Elementos da Série dos Lantanídeos/uso terapêutico , Neoplasias/tratamento farmacológico
3.
Cell Res ; 31(10): 1072-1087, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34239070

RESUMO

Glioblastoma (GBM) is a prevalent and highly lethal form of glioma, with rapid tumor progression and frequent recurrence. Excessive outgrowth of pericytes in GBM governs the ecology of the perivascular niche, but their function in mediating chemoresistance has not been fully explored. Herein, we uncovered that pericytes potentiate DNA damage repair (DDR) in GBM cells residing in the perivascular niche, which induces temozolomide (TMZ) chemoresistance. We found that increased pericyte proportion correlates with accelerated tumor recurrence and worse prognosis. Genetic depletion of pericytes in GBM xenografts enhances TMZ-induced cytotoxicity and prolongs survival of tumor-bearing mice. Mechanistically, C-C motif chemokine ligand 5 (CCL5) secreted by pericytes activates C-C motif chemokine receptor 5 (CCR5) on GBM cells to enable DNA-dependent protein kinase catalytic subunit (DNA-PKcs)-mediated DDR upon TMZ treatment. Disrupting CCL5-CCR5 paracrine signaling through the brain-penetrable CCR5 antagonist maraviroc (MVC) potently inhibits pericyte-promoted DDR and effectively improves the chemotherapeutic efficacy of TMZ. GBM patient-derived xenografts with high CCL5 expression benefit from combined treatment with TMZ and MVC. Our study reveals the role of pericytes as an extrinsic stimulator potentiating DDR signaling in GBM cells and suggests that targeting CCL5-CCR5 signaling could be an effective therapeutic strategy to improve chemotherapeutic efficacy against GBM.

4.
J Geriatr Cardiol ; 18(4): 261-270, 2021 Apr 28.
Artigo em Inglês | MEDLINE | ID: mdl-33995505

RESUMO

BACKGROUND: The efficacy and safety of proprotein convertase subtilisin/kexin type 9 (PCSK-9) inhibitors were confirmed by several clinical trials, but its effectiveness in routine clinical practice in China has not been evaluated. This study aims to describe the real world effectiveness of PCSK-9 inhibitors combined with statins compared with statins-based therapy among patients with very high risk of atherosclerotic cardiovascular disease (ASCVD). METHODS: This is a multi-center observational study, enrolled patients from 32 hospitals who underwent percutaneous coronary intervention (PCI) from January to June in 2019. There are 453 patients treated with PCSK-9 inhibitors combined with statins in PCSK-9 inhibitor group and 2,610 patients treated with statins-based lipid lowering therapies in statins-based group. The lipid control rate and incidence of major adverse cardiovascular events (MACE) over six months were compared between two groups. A propensity score-matched (PSM) analysis was used to balance two groups on confounding factors. Survival analysis using Kaplan-Meier methods was applied for MACE. RESULTS: In a total of 3,063 patients, 89.91% of patients had received moderate or high-intensity statins-based therapy before PCI, but only 9.47% of patients had low-density lipoprotein cholesterol (LDL-C) levels below 1.4 mmol/L at baseline. In the PSM selected patients, LDL-C level was reduced by 42.57% in PCSK-9 inhibitor group and 30.81% (P < 0.001) in statins-based group after six months. The proportion of LDL-C ≤ 1.0 mmol/L increased from 5.29% to 29.26% in PCSK-9 inhibitor group and 0.23% to 6.11% in statins-based group, and the proportion of LDL-C ≤ 1.4 mmol/L increased from 10.36% to 47.69% in PCSK-9 inhibitor group and 2.99% to 18.43% in statins-based group ( P < 0.001 for both). There was no significant difference between PCSK-9 inhibitor and statins-based treatment in reducing the risk of MACE (hazard ratio = 2.52, 95% CI: 0.49-12.97, P = 0.250). CONCLUSIONS: In the real world, PCSK-9 inhibitors combined with statins could significantly reduce LDL-C levels among patients with very high risk of ASCVD in China. The long-term clinical benefits for patients received PCSK-9 inhibitor to reduce the risk of MACE is still unclear and requires further study.

5.
BMC Cardiovasc Disord ; 20(1): 497, 2020 11 25.
Artigo em Inglês | MEDLINE | ID: mdl-33238890

RESUMO

BACKGROUND: Systematic investigation and analysis of cardiovascular health status (CVHS) of Chinese women is rare. This study aimed to assess CVHS and atherosclerotic cardiovascular disease (ASCVD) burden in the Chinese women physicians (CWP) and community-based non-physician cohort (NPC). METHODS: In this prospective, multicenter, observational study, CVHS using the American Heart Association (AHA) defined 7 metrics (such as smoking and fasting glucose) and ASCVD risk factors including hypertension, hyperlipidemia and type-2 diabetes were evaluated in CWP compared with NPC. RESULTS: Of 5832 CWP with a mean age of 44 ± 7 years, only 1.2% achieved the ideal CVHS and 90.1% showed at least 1 of the 7 AHA CVHS metrics at a poor level. Total CVHS score was significantly decreased and ASCVD risk burden was increased in postmenopausal subjects in CWP although ideal CVHS was not significantly influenced by menopause. Compared to 2596 NPC, fewer CWP had ≥ 2 risk factors (8% vs. 27%, P < 0.001); CWP scored significantly higher on healthy factors, a composite of total cholesterol, blood pressure, fasting glucose (P < 0.001), but, poorly on healthy behaviors (P < 0.001), specifically in the physical activity component; CWP also showed significantly higher levels of awareness and rates of treatment for hypertension and hyperlipidemia, but, not for type-2 diabetes. CONCLUSION: Chinese women's cardiovascular health is far from ideal and risk intervention is sub-optimal. Women physicians had lower ASCVD burden, scored higher in healthy factors, but, took part in less physical activity than the non-physician cohort. These results call for population-specific early and improved risk intervention.


Assuntos
Aterosclerose/epidemiologia , Nível de Saúde , Médicas , Saúde da Mulher , Mulheres Trabalhadoras , Adulto , Aterosclerose/diagnóstico , Aterosclerose/prevenção & controle , China/epidemiologia , Diabetes Mellitus Tipo 2/epidemiologia , Diabetes Mellitus Tipo 2/terapia , Dislipidemias/epidemiologia , Dislipidemias/terapia , Estilo de Vida Saudável , Fatores de Risco de Doenças Cardíacas , Humanos , Hipertensão/epidemiologia , Hipertensão/terapia , Masculino , Menopausa , Pessoa de Meia-Idade , Serviços Preventivos de Saúde , Estudos Prospectivos , Fatores de Proteção , Medição de Risco , Comportamento de Redução do Risco , Fatores Sexuais
6.
Oncol Lett ; 20(5): 221, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32963627

RESUMO

The present study analyzed the role of transforming growth factor-ß1 (TGF-ß1) and tissue transglutaminase (TG2) in breast cancer, as well as their protein levels in MCF-7 cells treated with cisplatin. In addition, the present study investigated the effects of TG2 and TGF-ß1 in MCF-7 cells following TGF-ß1 and TG2 inhibition or TGF-ß1 induction. The protein levels of TG2 and TGF-ß1 in breast cancer tissues and in MCF-7 cells treated with cisplatin, TG2 and TGF-ß1 inhibitors or 10 ng/ml TGF-ß1 were analyzed by immunohistochemical staining, immunofluorescence and western blotting. The results revealed that the expression levels of TG2 and TGF-ß1 in breast cancer tissues were significantly higher compared with those in paracancerous tissues. The fluorescence intensity of TG2 and TGF-ß1 in MCF-7 cells treated with cisplatin was lower compared with that in untreated MCF-7 cells. Using bioinformatics analysis, the present study predicted that TGF-ß1 may be associated with TG2. In addition, the expression levels of TGF-ß1 and TG2 in MCF-7 cells treated with inhibitors of TGF-ß1 and TG2 were lower compared with those in untreated MCF-7 cells. By contrast, the expression levels of TGF-ß1 and TG2 in MCF-7 cells treated with TGF-ß1 were higher compared with those in untreated MCF-7 cells. Therefore, the present study demonstrated that TGF-ß1 and TG2 may serve an important role in breast cancer tissues and in MCF-7 cells. In addition, it was revealed that TG2 and TGF-ß1 may have a synergistic role in MCF-7 cells.

7.
Talanta ; 212: 120749, 2020 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-32113532

RESUMO

Pb2+ is one of the major environmental pollutants, which can be visually detected by surface plasmon resonance of nanoparticles. Paper based analytical device, as a newly developed microfluidic detection platform, is featured in cost-effective and suitable for on-site analysis. In this paper, a sensitive and portable detection method for Pb2+ was proposed, in which Pb2+ was electrokinetically stacked on the paper fluidic channel by geometric field amplification effect and visualized online by glutathione-modified silver nanoparticles. Colorimetric quantification of the visualized stacking band was conducted by smart phone camera. To avoid unfavorable influence from pH change on the surface plasmon resonance visualization, field amplification effect was introduced by geometric design of the paper fluidic channel. The enriched Pb2+ was clearly visible on the paper substrate, and the stacking band intensity was about four orders of magnitude enhanced, comparing to the intensity without stacking. A linear response to Pb2+ was observed in the range of 0.3-7.0 µM (R2 = 0.997) with a limit of detection of 86 nM and a limit of quantity of 0.28 µM. The established method was used in the detection of Pb2+ from river and lake water samples, and the results were confirmed by atomic absorption spectroscopy method.

8.
Shock ; 54(4): 520-530, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32004183

RESUMO

Renal ischemia-reperfusion injury (IRI) is a major cause of acute kidney injury (AKI) and even induces remote organ damage. Accumulating proofs demonstrates that the endocannabinoid system may provide a promising access for treatment strategy of renal IRI associated AKI. In the current study, using the established renal IRI model of rat, we tested the hypothesis that pretreatment of URB602, 30 min before renal IRI, alleviates kidney injury and relevant distant organ damage via limiting oxidative stress and inflammation. Using Western blot analysis and LC-MS/MS, renal IRI showed to increase the levels of 2-arachidonoylglycerol (2-AG) in kidneys as well as COX-2, PGE2, TXA2, and decrease N-arachidonoylethanolamine (anandamide, AEA); the expressions of renal cannabinoid receptor 1 (CB1) and cannabinoid receptor 2 (CB2) were unchanged. The URB602 pretreatment in renal IRI, further enhanced renal 2-AG which is high affinity to both CB1 and CB2, and reduced renal COX-2 which is involved in the regulation of renal perfusion and inflammation. AM630 (CB2 antagonist) almost blocked all the antioxidant, anti-inflammatory and nephroprotective effects of URB602, whereas AM251 (CB1 antagonist) showed limited influence, and parecoxib (COX-2 inhibitor) slightly ameliorated renal function at the dose of 10 mg/kg. Taken together, our data indicate that URB602 acts as a reactive oxygen species scavenger and anti-inflammatory media in renal IRI mainly depending on the activation of CB2.

9.
Anal Chim Acta ; 1100: 149-155, 2020 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-31987135

RESUMO

Paper-based analytical device (PAD) has received more and more attention in the field of point-of-care test (POCT) due to its low cost, portability and simple operation. Sensitivity and selectivity are two important aspects in clinical diagnostic analysis. However, low sensitivity of a PAD limits its wider application for POCT. Here we introduced a PAD that can clean and enrich the protein content from salty media with both electric field (E) and pH gradient (double E/pH gradients), with which 100-fold enrichment effect could be achieved within 70 s as demonstrated by fluorescein isothiocyanate labeled bovine serum albumin (FITC-BSA) from artificial urine media. With post staining of the protein stacking band with bromophenol blue (BPB), selective colorimetric detection of human serum albumin (HSA) was achieved simply with smartphone camera in the clinically significant range of 10-300 mg‧L-1 (R2 = 0.99) with a limit of detection (LOD) of 4.9 mg‧L-1. Detection of microalbuminuria (MAU) of diabetic patients was demonstrated with this method without difference (ɑ = 0.01) to that by the clinical method (immunoturbidimetry). This work demonstrated the potential of this PAD method in online sample pretreatment and detection of target component from complex physiological samples.


Assuntos
Técnicas Analíticas Microfluídicas , Papel , Soroalbumina Bovina/isolamento & purificação , Albumina Sérica Humana/isolamento & purificação , Smartphone , Animais , Bovinos , Diabetes Mellitus/diagnóstico , Diabetes Mellitus/urina , Campos Eletromagnéticos , Humanos , Concentração de Íons de Hidrogênio , Técnicas Analíticas Microfluídicas/instrumentação , Sais/química , Soroalbumina Bovina/química , Soroalbumina Bovina/urina , Albumina Sérica Humana/química , Albumina Sérica Humana/urina
10.
Zhongguo Zhong Yao Za Zhi ; 44(16): 3512-3519, 2019 Aug.
Artigo em Chinês | MEDLINE | ID: mdl-31602916

RESUMO

The aim of this paper was to systematically evaluate the toxicity-reducing effect of Tripterygium-licorice in animal experiments,and also to provide evidence for basic research on the toxicity reduction of Tripterygium wilfordii. The PubMed,EMbase,Web of Science,CBM,CNKI and Wan Fang Databases from their establishment to August 31 th,2018 were searched. Two independent reviewers screened the papers,extracted the data,assessed the risk of bias using SYRCLE assessment tool and conducted Meta-analysis with Rev Man 5. 3 software. A total of 10 papers involving 31 studies were finally included,15 studies of which were used for Meta-analysis. Four studies were included for chronic hepatotoxicity animal model. In experimental group( 34 animals),Tripterygium was administered at dose of 0. 09-0. 1 mg·kg-1·d-1,and glycyrrhizic acid was administered at dose of 90-100 mg·kg-1,both for 2 weeks; in control group( 34 animals),glycyrrhizic acid was replaced with equal volume of normal saline. Eleven studies were included for acute hepatotoxicity animal model. In experimental group( 66 animals),glycyrrhizic acid was administered at dose of 75-480 mg·kg-1 for 7 days,then glycyrrhizic acid was stopped,and Tripterygium began to be administered at dose of 0. 6-1. 0 mg·kg-1 per 24 h or 48 h for a total of 1-2 times; in control group( 66 animals),glycyrrhizic acid was replaced with equal volume of normal saline or corresponding solvent. The results of Meta-analysis showed that in both chronic hepatotoxicity animal model and acute hepatotoxicity animal model,the transaminase levels in the experimental group were lower than those in the control group( P < 0. 05). Subgroup analysis of acute hepatotoxicity animal model showed that the transaminase levels in the experimental group were lower than those in the control group for every subgroup except " glycyrrhizic acid 75 mg·kg-1" subgroup. However,in terms of the mean difference( MD) and confidence interval( CI),there was no significant difference in transaminase decline between each subgroup. Low dose of glycyrrhizic acid( 90-100 mg·kg-1) has a toxicity-reduction effect on chronic hepatotoxicity induced by tripterygium( 0. 09-0. 10 mg·kg-1). Middle and high doses of glycyrrhizic acid( 120-480 mg·kg-1) have a toxicity-reduction effect on acute hepatotoxicity induced by tripterygium( 0. 6-1. 0 mg·kg-1),but with no significant dose-effect relationship.


Assuntos
Doença Hepática Induzida por Substâncias e Drogas/prevenção & controle , Medicamentos de Ervas Chinesas/toxicidade , Ácido Glicirrízico/administração & dosagem , Tripterygium/toxicidade , Animais , Medicamentos de Ervas Chinesas/administração & dosagem , Glycyrrhiza , Tripterygium/química
11.
Artigo em Inglês | MEDLINE | ID: mdl-31223331

RESUMO

Although deqi, the phenomenon whereby excitation of Qi in the meridians occurs with needling, is critical to the practice of acupuncture and its efficacy, it is poorly understood. So we investigate the influence of the deqi sensation on the analgesic effects of acupuncture in patients who were enrolled in a randomised controlled trial for the treatment of patients with primary dysmenorrhea, a painful and common condition, and cold and dampness stagnation. Two groups were assessed: a deqi group (undergoing deep needling with thick needles and manipulation, n=17) and a non-deqi group (undergoing shallow needling with thin needles and no manipulation, n=51). The Sanyinjiao (SP6) was needled for 30 min in both groups. Pain scores at baseline, upon needle removal, and at 10, 20, and 30 min after needle removal were evaluated by the Visual Analogue Scale for pain. The deqi sensation was evaluated by the Acupuncture Deqi Clinical Assessment Scale. Patients who experienced a genuine deqi sensation (n=39) were selected for further analysis. Compared with patients in the non-deqi group who experienced deqi (n=25), patients who self-reported deqi in the deqi group (n=14) felt a stronger deqi sensation, experienced soreness and fullness more frequently, felt a greater intensity of soreness, fullness, electric sensation, spreading, and radiating, and experienced larger spreading distances. In those who experienced the deqi sensation in the deqi group, the intensity of the sensation, as well as their degree of soreness and fullness, was negatively correlated with pain reduction. In patients who experienced the deqi sensation in the non-deqi group, deqi intensity was positively correlated with pain reduction, while soreness was negatively correlated with pain reduction. The distance of spreading was not correlated with pain reduction in either group. We found, in SP6 needling of patients with primary dysmenorrhea with cold and dampness stagnation, that a moderate deqi response predicted a prolonged analgesic effect better than a strong deqi response.

12.
Clin Sci (Lond) ; 133(7): 905-917, 2019 04 15.
Artigo em Inglês | MEDLINE | ID: mdl-30957778

RESUMO

Gut microbiota alterations manifest as intermittent hypoxia and fragmented sleep, thereby mimicking obstructive sleep apnea-hypopnea syndrome (OSAHS). Here, we sought to perform the first direct survey of gut microbial dysbiosis over a range of apnea-hypopnea indices (AHI) among patients with OSAHS. We obtained fecal samples from 93 patients with OSAHS [5 < AHI ≤ 15 (n=40), 15 < AHI ≤ 30 (n=23), and AHI ≥ 30 (n=30)] and 20 controls (AHI ≤ 5) and determined the microbiome composition via 16S rRNA pyrosequencing and bioinformatics analysis of variable regions 3-4. We measured fasting levels of homocysteine (HCY), interleukin-6 (IL-6), and tumor necrosis factor α (TNF-α). Results revealed gut microbial dysbiosis in several patients with varying severities of OSAHS, reliably separating them from controls with a receiver operating characteristic-area under the curve (ROC-AUC) of 0.789. Functional analysis in the microbiomes of patients revealed alterations; additionally, decreased in short-chain fatty acid (SCFA)-producing bacteria and increased pathogens, accompanied by elevated levels of IL-6. Lactobacillus levels correlated with HCY levels. Stratification analysis revealed that the Ruminococcus enterotype posed the highest risk for patients with OSAHS. Our results show that the presence of an altered microbiome is associated with HCY among OSAHS patients. These changes in the levels of SCFA affect the levels of pathogens that play a pathophysiological role in OSAHS and related metabolic comorbidities.


Assuntos
Bactérias/isolamento & purificação , Microbioma Gastrointestinal , Intestinos/microbiologia , Doenças Metabólicas/microbiologia , Apneia Obstrutiva do Sono/microbiologia , Adulto , Biomarcadores/sangue , Estudos de Casos e Controles , Comorbidade , Disbiose , Fezes/microbiologia , Feminino , Homocisteína/sangue , Interações Hospedeiro-Patógeno , Humanos , Masculino , Doenças Metabólicas/sangue , Doenças Metabólicas/diagnóstico , Doenças Metabólicas/epidemiologia , Pessoa de Meia-Idade , Apneia Obstrutiva do Sono/sangue , Apneia Obstrutiva do Sono/diagnóstico , Apneia Obstrutiva do Sono/epidemiologia
13.
Front Pharmacol ; 10: 29, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30804781

RESUMO

Background: Caesalpinia sappan L. (C. sappan) is a traditional Chinese medicinal plant. The dried heartwood of C. sappan (also known as Sappan wood) has been widely used for the folkloric medical treatment of ischemic cerebral stroke in China. However, the detailed underlying pharmacological mechanism still remains largely unexplored. Methods: In this study, a middle cerebral artery occlusion (MCAO) rat model was employed to elucidate the mechanism of the anti-cerebral ischemic effects of C. sappan ethanolic extract (CEE). Moreover, systemic multi-target identification coupled with gene ontology biological process (GO BP) and reactome pathway analysis was used to investigate the potential neuroprotective mechanism. Furthermore, the presumed mechanism was confirmed through biological analysis by determining the effects of CEE on the identified signaling pathways in PC12 cells model-induced by oxygen-glucose deprivation/reperfusion (OGD/R). Results: Our study demonstrates that CEE (both through in vivo administration at a dosage of 300 mg/kg and through in vitro incubation at a dosage of 2.4 µg/mL) is a neuroprotective agent that can effectively inhibit neuronal damage, promote synaptic generation, and suppress the activation of neutrophils, microglia, and astrocytes. Moreover, the neuroprotective mechanism of CEE is mediated via regulating 150 potential target proteins, which are associated with 6 biological processes and 10 pathways, including JAK-STAT, HSP90 and DNA damage/telomere stress. Conclusion: CEE can exert neuroprotective effect through multi-target pharmacological mechanisms to prevent ischemia/reperfusion-induced cerebral injury.

14.
Cell Death Dis ; 9(10): 988, 2018 09 24.
Artigo em Inglês | MEDLINE | ID: mdl-30250190

RESUMO

Plastic phenotype convention between glioma stem cells (GSCs) and non-stem tumor cells (NSTCs) significantly fuels glioblastoma heterogeneity that causes therapeutic failure. Recent progressions indicate that glucose metabolic reprogramming could drive cell fates. However, the metabolic pattern of GSCs and NSTCs and its association with tumor cell phenotypes remain largely unknown. Here we found that GSCs were more glycolytic than NSTCs, and voltage-dependent anion channel 2 (VDAC2), a mitochondrial membrane protein, was critical for metabolic switching between GSCs and NSTCs to affect their phenotypes. VDAC2 was highly expressed in NSTCs relative to GSCs and coupled a glycolytic rate-limiting enzyme platelet-type of phosphofructokinase (PFKP) on mitochondrion to inhibit PFKP-mediated glycolysis required for GSC maintenance. Disruption of VDAC2 induced dedifferentiation of NSTCs to acquire GSC features, including the enhanced self-renewal, preferential expression of GSC markers, and increased tumorigenicity. Inversely, enforced expression ofVDAC2 impaired the self-renewal and highly tumorigenic properties of GSCs. PFK inhibitor clotrimazole compromised the effect of VDAC2 disruption on glycolytic reprogramming and GSC phenotypic transition. Clinically, VDAC2 expression inversely correlated with glioma grades (Immunohistochemical staining scores of VDAC2 were 4.7 ± 2.8, 3.2 ± 1.9, and 1.9 ± 1.9 for grade II, grade III, and IV, respectively, p < 0.05 for all) and the patients with high expression of VDAC2 had longer overall survival than those with low expression of VDAC2 (p = 0.0008). In conclusion, we demonstrate that VDAC2 is a new glycolytic regulator controlling the phenotype transition between glioma stem cells and non-stem cells and may serves as a new prognostic indicator and a potential therapeutic target for glioma patients.


Assuntos
Neoplasias Encefálicas/metabolismo , Glioblastoma/metabolismo , Glucose/metabolismo , Células-Tronco Neoplásicas/metabolismo , Fenótipo , Fosfofrutoquinase-1 Tipo C/metabolismo , Canal de Ânion 2 Dependente de Voltagem/metabolismo , Animais , Neoplasias Encefálicas/patologia , Linhagem Celular Tumoral , Plasticidade Celular , Clotrimazol/farmacologia , Técnicas de Silenciamento de Genes , Glioblastoma/patologia , Glicólise , Humanos , Estimativa de Kaplan-Meier , Masculino , Camundongos SCID , Mitocôndrias/metabolismo , Gradação de Tumores , Fosfofrutoquinase-1/antagonistas & inibidores , Canal de Ânion 2 Dependente de Voltagem/genética , Ensaios Antitumorais Modelo de Xenoenxerto
15.
Int J Chron Obstruct Pulmon Dis ; 13: 1591-1597, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29805258

RESUMO

Purpose: It is unclear whether the effectiveness of pulmonary rehabilitation program (PRP) after cardiac surgery differs between patients with and without COPD. This study aimed to compare the effectiveness of PRP between patients with and without COPD undergoing coronary artery bypass graft (CABG) surgery. Patients and methods: We retrospectively included patients who underwent CABG surgery and received 3-week PRP from January 2009 to December 2013. We excluded patients who underwent emergency surgery, had an unstable hemodynamic status, were ventilator dependent or did not complete the PRP. Demographics, muscle strength, degree of dyspnea, pulmonary function and postoperative complications were compared. Results: Seventy-eight patients were enrolled (COPD group, n=40; non-COPD group, n=38). Maximal inspiratory pressure (MIP; -34.52 cmH2O vs -43.25 cmH2O, P<0.01; -34.67 cmH2O vs -48.18 cmH2O, P<0.01), maximal expiratory pressure (MEP; 32.15 cmH2O vs 46.05 cmH2O, P<0.01; 37.78 cmH2O vs 45.72 cmH2O, P<0.01) and respiratory rate (RR; 20.65 breath/minute vs 17.02 breath/minute, P<0.01; 20.65 breath/minute vs 17.34 breath/minute, P<0.01) in COPD and non-COPD groups, respectively, showed significant improvement, but were not significantly different between the two groups. Forced vital capacity (FVC; 0.85 L vs 1.25 L, P<0.01), forced expiratory volume in 1 second (FEV1; 0.75 L vs 1.08 L, P<0.01), peak expiratory flow (PEF; 0.99 L vs 1.79 L, P<0.01) and forced expiratory flow between 25% and 75% of vital capacity (FEF25-75; 0.68 L vs 1.15 L, P<0.01) showed significant improvement between postoperative Days 1 and 14 in the COPD group. FVC (1.11 L vs 1.36 L, P<0.05), FEV1 (96 L vs 1.09 L, P<0.05) and FEF25-75 (1.03 L vs 1.26 L, P<0.05) were significantly improved in the non-COPD group. However, only PEF (80.8% vs 10.1%, P<0.01) and FEF25-75 (67.6% vs 22.3%, P<0.05) were more significantly improved in the COPD group than in the non-COPD group. Conclusion: PRP significantly improved respiratory muscle strength and lung function in patients with and without COPD who underwent CABG surgery. However, PRP is more effective in improving PEF and FEF25-75 in COPD patients.


Assuntos
Ponte de Artéria Coronária , Doença da Artéria Coronariana/cirurgia , Pulmão/fisiopatologia , Doença Pulmonar Obstrutiva Crônica/reabilitação , Terapia Respiratória , Idoso , Pesquisa Comparativa da Efetividade , Ponte de Artéria Coronária/efeitos adversos , Doença da Artéria Coronariana/complicações , Doença da Artéria Coronariana/diagnóstico , Feminino , Volume Expiratório Forçado , Humanos , Masculino , Fluxo Máximo Médio Expiratório , Pessoa de Meia-Idade , Força Muscular , Pico do Fluxo Expiratório , Doença Pulmonar Obstrutiva Crônica/complicações , Doença Pulmonar Obstrutiva Crônica/diagnóstico , Doença Pulmonar Obstrutiva Crônica/fisiopatologia , Recuperação de Função Fisiológica , Músculos Respiratórios/fisiopatologia , Terapia Respiratória/efeitos adversos , Estudos Retrospectivos , Fatores de Tempo , Resultado do Tratamento , Capacidade Vital
16.
Chin J Integr Med ; 24(7): 545-550, 2018 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-27933511

RESUMO

OBJECTIVE: To evaluate the quality and consistency of recommendations in the clinical practice guidelines (CPGs) for hypertension in Chinese medicine (CM). METHODS: CM CPGs were identified from 5 electronic databases and hand searches through related handbooks published from January 1990 to December 2013. Three reviewers independently appraised the CPGs based on the Appraisal of Guidelines for Research and Evaluation (AGREE II) instrument, and compared the CPGs' recommendations on CM syndrome pattern classification and treatment. RESULTS: Five CM CPGs for hypertension were included. The quality score of the evidence-based (EB) guideline was higher than those of the consensus-based with no explicit consideration of evidence-based (CB-EB) and the consensus-based (CB) guidelines. Three out of five patterns in the CPGs were recommended by the EB guideline. Tianma Gouteng Formula () in the EB guideline was recommended mostly for hypertension patients with pattern of ascendant hyperactivity of Gan (Liver)-yang and pattern of yin deficiency with yang hyperactivity in the CPGs. Acupuncture and massage were recommended for Grade I and Grade II hypertension with severe symptoms weakening the quality of life in the EB guideline. For Grade I and Grade II hypertension, CM could be used alone, while for Grade III hypertension, they should be used in combination with Western medicines. CONCLUSION: The quality of EB guideline was higher than those of CB and CB-EB CPGs in CM for hypertension and CM should be prescribed alone or combined with Western medicines based on the grade of hypertension.


Assuntos
Hipertensão/terapia , Medicina Tradicional Chinesa/normas , Guias de Prática Clínica como Assunto/normas , Qualidade da Assistência à Saúde/normas , Humanos , Medicina Tradicional Chinesa/métodos , Garantia da Qualidade dos Cuidados de Saúde , Qualidade de Vida
17.
Zhongguo Zhong Yao Za Zhi ; 42(19): 3650-3655, 2017 Oct.
Artigo em Chinês | MEDLINE | ID: mdl-29235274

RESUMO

Baoyuan decoction (BYD) is a well-known traditional Chinese medicine formula for coronary heart disease with Qi deficiency. However, the detailed pharmacological mechanism of BYD is still unknown because of its complicated chemical compositions. In this study, we synthesized a kind of solid beads with benzophenone groups on its surface. Benzophenone can be activated and chemically cross-linked with the C-H bonds of the chemical compositions in BYD (BYD beads) under UV activation. We thus captured all the target proteins from mouse heart tissue lysates by using BYD beads. Based on proteomics analysis, we discovered totally 46 potential binding target proteins, most of which were located in mitochondria. KEGG analysis revealed that these target proteins were mainly associated with TCA cycle and amino acid metabolism signaling pathways, suggesting that the cardioprotection of BYD might be associated with regulating mitochondrial function and energy production. Moreover, JC-1 staining analysis also confirmed the protective effect of BYD on mitochondrial damage. In summary, our findings elucidated the potential mechanism of BYD on cardioprotection through "target fishing" strategy, and further explained its traditional efficacy in the molecular level. In addition, we also provide an approach for investigating the target group of complicated compositions in Chinese herbal formula. This novel method may provide a methodological reference for exploring the pharmacological mechanism of traditional Chinese formula in the future.


Assuntos
Benzofenonas/química , Cardiotônicos/farmacologia , Medicamentos de Ervas Chinesas/farmacologia , Mitocôndrias Cardíacas/efeitos dos fármacos , Animais , Camundongos , Proteínas Mitocondriais/química , Transdução de Sinais
18.
Zhongguo Zhong Yao Za Zhi ; 42(17): 3238-3242, 2017 Sep.
Artigo em Chinês | MEDLINE | ID: mdl-29192428

RESUMO

Clinical application evaluation research of Guidelines for the Diagnosis and Treatment of Common Diseases of Pediatrics in Traditional Chinese Medicine intends to evaluate the quality level and clinical application of the guideline. A questionnaire and prospective case survey methods were used to evaluate the applicability evaluation based on the clinician questionnaire and the application evaluation based on clinical case observation. The applicability evaluation, familiarity and utilization rate of doctors' guidelines were 85.06%, 62.76%; Sort by technical grade, intermediate grade doctors have a higher familiarity rate and utilization rate, while the junior grade doctor's is lower; Guide quality level of applicability evaluation, other items' rational percentage are better than 96% except the items of health preserving and prevention and other treatment is relatively low; Items' applicable percentage of applicability evaluation are more than 91% except the item of guide simplicity. Comprehensive applicability evaluation, The percentage of the guideline applicable to clinical practice accounted for 94.94%. The consistency rate of syndrome differentiation and clinical application is more than 96% in addition to prescription medication, other treatments and health preserving and prevention of the guidelines apply consistency of application evaluation. The percentage of good treatment effect accounted for 92.96% of application effect evaluation. The safety percentage is 99.89% and economy is 97.45%. The research shows that of Guidelines for the Diagnosis and Treatment of Common Diseases of Pediatrics in Traditional Chinese Medicine quality level is good and is basically applicable to pediatric clinical practice which can be used as a standardized recommendation of pediatric common diseases' treatment specification. A small part of the guidelines are not applicable and need to be further consummated. Health preserving and prevention and other treatment of the guideline need to be revised.


Assuntos
Medicina Tradicional Chinesa , Pediatria/normas , Guias de Prática Clínica como Assunto , Criança , Humanos , Médicos , Estudos Prospectivos , Inquéritos e Questionários
19.
Zhongguo Zhong Yao Za Zhi ; 42(17): 3243-3246, 2017 Sep.
Artigo em Chinês | MEDLINE | ID: mdl-29192429

RESUMO

This study is to assess the Guidelines for Diagnosis and Treatment of Common Diseases of Otolaryngology in Traditional Chinese Medicine in clinical application and provide evidence for further guideline revision. The assessment was divided into applicability assessment and practicability assessment. The applicability assessment based on questionnaire survey and the traditional Chinese medicine (TCM) practitioners were asked to independently fill the Questionnaire for Applicability Assessment on the Guidelines for Diagnosis and Treatment in Traditional Chinese Medicine. The practicability assessment was based on prospective case investigation and analysis method and the TCM practitioners-in-charge filled the Case Investigation Questionnaire for Practicability Assessment on the Guidelines for Diagnosis and Treatment in Traditional Chinese Medicine. The data were analyzed in descriptive statistics. 151 questionnaires were investigated for applicability assessment and 1 016 patients were included for practicability assessment. The results showed that 88.74% of them were familiar with the guidelines and 45.70% used them. The guidelines quality and related items were similar in applicability assessment and practicability assessment, and scored highly as more than 85.00% except the "recuperating and prevention". The results suggested that the quality of Guidelines for Diagnosis and Treatment of Common Diseases of Otolaryngology in Traditional Chinese Medicine was high and could better guide the clinical practice. The "recuperating and prevention" part should be improved and the evidence data should be included in future guideline revision, so that the clinical utilization rate could be increased.


Assuntos
Medicina Tradicional Chinesa , Otolaringologia , Guias de Prática Clínica como Assunto , Humanos , Estudos Prospectivos , Inquéritos e Questionários
20.
Zhongguo Zhong Yao Za Zhi ; 42(17): 3247-3251, 2017 Sep.
Artigo em Chinês | MEDLINE | ID: mdl-29192430

RESUMO

This study aims to evaluate the adaptability and applicability of Guidelines for the Diagnosis and Treatment of Cancer in Traditional Chinese Medicine. The assessment methods included adaptability assessment and applicability assessment. The adaptability assessment was based on the questionnaire survey to evaluate the familiarity, utilization, quality, and clinical application of the Guidelines; applicability assessment was based on the prospective observation of 853 clinical cases to investigate the applicability and effect of the Guidelines, including effectiveness, economy and safety. Statistical analysis for basic description, construction of different comparison groups for cross or hierarchical statistical test, multi-factor analysis, and confounding factors were used in the study. Adaptability assessment results showed that 63.03% of TCM doctors considered guidelines as good or very good applicability and 4.24% of TCM doctors considered guidelines with very poor applicability in clinical practice. For the applicability evaluation, TCM doctors considered that the "overall efficacy and technology level", "satisfactory degree" and "adaptability in clinical practice" of the guideline were 85.46%, 80.43% and 69.40% respectively. The results showed that guideline was well known among TCM doctors, especially junior TCM doctors. Adaptability and applicability of Guidelines were totally good but the quality and adaptability of the intervention schemes were still week, so the quality of Guidelines should be improved by revision.


Assuntos
Oncologia , Medicina Tradicional Chinesa , Neoplasias/terapia , Guias de Prática Clínica como Assunto , Humanos , Estudos Prospectivos
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