Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 37
Filtrar
1.
Biomed Pharmacother ; 174: 116486, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38520865

RESUMO

Recurrence and metastasis of gastric cancer is a major therapeutic challenge for treatment. The presence of cancer stem cells (CSCs) is a major obstacle to the success of current cancer therapy, often leading to treatment resistance and tumor recurrence and metastasis. Therefore, it is important to develop effective strategies to eradicate CSCs. In this study, we developed a combined therapeutic strategy of photothermal therapy (PTT) and gastric cancer stem cells (GCSCs) inhibition by successfully synthesizing nanoliposomes loaded with IR780 (photosensitizer) and EN4 (c-Myc inhibitor). The nanocomposites are biocompatible and exhibit superior photoacoustic (PA) imaging properties. Under laser irradiation, IR780-mediated PTT effectively and rapidly killed tumor cells, while EN4 synergistically inhibited the self-renewal and stemness of GCSCs by suppressing the expression and activity of the pluripotent transcription factor c-Myc, preventing the tumor progression of gastric cancer. This Nano-EN-IR@Lip is expected to be a novel clinical nanomedicine for the integration of gastric cancer diagnosis, treatment and prevention.


Assuntos
Lipossomos , Células-Tronco Neoplásicas , Fármacos Fotossensibilizantes , Terapia Fototérmica , Neoplasias Gástricas , Neoplasias Gástricas/patologia , Neoplasias Gástricas/terapia , Neoplasias Gástricas/tratamento farmacológico , Células-Tronco Neoplásicas/efeitos dos fármacos , Células-Tronco Neoplásicas/patologia , Humanos , Terapia Fototérmica/métodos , Animais , Linhagem Celular Tumoral , Fármacos Fotossensibilizantes/farmacologia , Fármacos Fotossensibilizantes/administração & dosagem , Indóis/farmacologia , Indóis/química , Nanopartículas/química , Camundongos Nus , Terapia Combinada , Camundongos , Camundongos Endogâmicos BALB C , Proteínas Proto-Oncogênicas c-myc/metabolismo , Proteínas Proto-Oncogênicas c-myc/genética , Nanocompostos/química
2.
ACS Appl Mater Interfaces ; 15(20): 24071-24083, 2023 May 24.
Artigo em Inglês | MEDLINE | ID: mdl-37159843

RESUMO

The rapid development of nanomedicine has brought hope and confidence to the precise treatment of tumors. However, the efficacy of nanoparticle-mediated therapy is severely limited due to phagocytosis and clearance by macrophages. CD47 is a well-documented ″don't eat me″ signaling molecule that binds to the SIRPα receptor on the macrophage surface, inhibiting the phagocytic behavior of the macrophages. In this study, CD47-overexpressing cancer cell membranes were used to coat hollow copper sulfide nanoparticles. The nanoparticles were shown to have an extended circulatory half-life and to actively target breast cancer, leading to increased accumulation in the tumor tissue. An excellent photothermal therapeutic effect was produced by near-infrared laser irradiation. At the same time, ß-lapachone within the nanoparticles generated large amounts of hydrogen peroxide in the tumor environment, which was then catalyzed by the copper sulfide nanozyme to cytotoxic hydroxyl radicals, exerting a chemodynamic therapeutic effect. This engineered biomimetic nanozyme, through the mediation of the ″don't eat me″ signal, achieved both photothermal and chemodynamic precision treatments of breast cancer, creating a new mode of safe and effective tumor treatment.


Assuntos
Neoplasias da Mama , Neoplasias , Humanos , Feminino , Neoplasias da Mama/patologia , Antígeno CD47/metabolismo , Cobre/metabolismo , Biomimética , Macrófagos/metabolismo , Fagocitose , Neoplasias/tratamento farmacológico
3.
Acta Pharmaceutica Sinica ; (12): 3572-3582, 2023.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-1004636

RESUMO

The natural products containing 3-acyl tetramic acid units have a large number of complex and diverse structures, showing a variety of biological activities such as antibacterial, antiviral, anti-tumor and so on, especially antibacterial activity which are regarded as a potential reservoir of new antibiotics. In this paper, the antibacterial activities of various natural products containing 3-acyl tetramic acids and the new research hotspots and directions are reviewed.

4.
J Nanobiotechnology ; 20(1): 213, 2022 May 06.
Artigo em Inglês | MEDLINE | ID: mdl-35524280

RESUMO

BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is a progressive fibrotic disease with pathophysiological characteristics of transforming growth factor-ß (TGF-ß), and reactive oxygen species (ROS)-induced excessive fibroblast-to-myofibroblast transition and extracellular matrix deposition. Macrophages are closely involved in the development of fibrosis. Nuclear factor erythroid 2 related factor 2 (Nrf2) is a key molecule regulating ROS and TGF-ß expression. Therefore, Nrf2 signaling modulation might be a promising therapy for fibrosis. The inhalation-based drug delivery can reduce systemic side effects and improve therapeutic effects, and is currently receiving increasing attention, but direct inhaled drugs are easily cleared and difficult to exert their efficacy. Therefore, we aimed to design a ROS-responsive liposome for the Nrf2 agonist dimethyl fumarate (DMF) delivery in the fibrotic lung. Moreover, we explored its therapeutic effect on pulmonary fibrosis and macrophage activation. RESULTS: We synthesized DMF-loaded ROS-responsive DSPE-TK-PEG@DMF liposomes (DTP@DMF NPs). DTP@DMF NPs had suitable size and negative zeta potential and excellent capability to rapidly release DMF in a high-ROS environment. We found that macrophage accumulation and polarization were closely related to fibrosis development, while DTP@DMF NPs could attenuate macrophage activity and fibrosis in mice. RAW264.7 and NIH-3T3 cells coculture revealed that DTP@DMF NPs could promote Nrf2 and downstream heme oxygenase-1 (HO-1) expression and suppress TGF-ß and ROS production in macrophages, thereby reducing fibroblast-to-myofibroblast transition and collagen production by NIH-3T3 cells. In vivo experiments confirmed the above findings. Compared with direct DMF instillation, DTP@DMF NPs treatment presented enhanced antifibrotic effect. DTP@DMF NPs also had a prolonged residence time in the lung as well as excellent biocompatibility. CONCLUSIONS: DTP@DMF NPs can reduce macrophage-mediated fibroblast-to-myofibroblast transition and extracellular matrix deposition to attenuate lung fibrosis by upregulating Nrf2 signaling. This ROS-responsive liposome is clinically promising as an ideal delivery system for inhaled drug delivery.


Assuntos
Fibrose Pulmonar Idiopática , Fator 2 Relacionado a NF-E2 , Animais , Fibrose , Fibrose Pulmonar Idiopática/tratamento farmacológico , Lipossomos , Camundongos , Camundongos Endogâmicos C57BL , Fator 2 Relacionado a NF-E2/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Fator de Crescimento Transformador beta/metabolismo , Fator de Crescimento Transformador beta/farmacologia
5.
World J Clin Cases ; 9(15): 3546-3558, 2021 May 26.
Artigo em Inglês | MEDLINE | ID: mdl-34046454

RESUMO

BACKGROUND: The effectiveness of adjunctive corticosteroid use in patients with coronavirus disease 2019 (COVID-19) remains inconclusive. AIM: To investigate the effectiveness of adjunctive corticosteroid therapy in patients with severe COVID-19. METHODS: We conducted a retrospective analysis of the difference in several outcomes between patients with severe COVID-19 who received corticosteroid therapy (the corticosteroid group) and patients with severe COVID-19 who did not receive corticosteroid therapy (the non-corticosteroid group). RESULTS: Seventy-five patients were included in this study. Of these, 47 patients were in the corticosteroid group and 28 patients were in the non-corticosteroid group. There were no differences between the two groups in the total length of hospital stay, the length of intensive care unit stay, high-flow oxygen days, non-invasive ventilator days, invasive ventilation days, and mortality rate. Total lesion volume ratio, consolidation volume ratio and ground-glass opacity volume ratio in the corticosteroid group decreased significantly on day 14, while those in the non-corticosteroid group did not show a significant decrease. CONCLUSION: Our results show that adjunctive corticosteroid use did not significantly improve clinical outcomes in severe COVID-19 patients, but might promote the absorption of pulmonary lesions. Larger multicenter randomized controlled studies may be needed to confirm this.

6.
JMIR Public Health Surveill ; 7(3): e24843, 2021 03 09.
Artigo em Inglês | MEDLINE | ID: mdl-33630743

RESUMO

BACKGROUND: Since the start of the COVID-19 pandemic, there have been over 2 million deaths globally. Acute respiratory distress syndrome (ARDS) may be the main cause of death. OBJECTIVE: This study aimed to describe the clinical features, outcomes, and ARDS characteristics of patients with COVID-19 admitted to the intensive care unit (ICU) in Chongqing, China. METHODS: The epidemiology of COVID-19 from January 21, 2020, to March 15, 2020, in Chongqing, China, was analyzed retrospectively, and 75 ICU patients from two hospitals were included in this study. On day 1, 56 patients with ARDS were selected for subgroup analysis, and a modified Poisson regression was performed to identify predictors for the early improvement of ARDS (eiARDS). RESULTS: Chongqing reported a 5.3% case fatality rate for the 75 ICU patients. The median age of these patients was 57 (IQR 25-75) years, and no bias was present in the sex ratio. A total of 93% (n=70) of patients developed ARDS during ICU stay, and more than half had moderate ARDS. However, most patients (n=41, 55%) underwent high-flow nasal cannula oxygen therapy, but not mechanical ventilation. Nearly one-third of patients with ARDS improved (arterial blood oxygen partial pressure/oxygen concentration >300 mm Hg) in 1 week, which was defined as eiARDS. Patients with eiARDS had a higher survival rate and a shorter length of ICU stay than those without eiARDS. Age (<55 years) was the only variable independently associated with eiARDS, with a risk ratio of 2.67 (95% CI 1.17-6.08). CONCLUSIONS: A new subphenotype of ARDS-eiARDS-in patients with COVID-19 was identified. As clinical outcomes differ, the stratified management of patients based on eiARDS or age is highly recommended.


Assuntos
COVID-19/complicações , Síndrome do Desconforto Respiratório/terapia , Síndrome do Desconforto Respiratório/virologia , Adulto , Idoso , COVID-19/mortalidade , China/epidemiologia , Feminino , Humanos , Unidades de Terapia Intensiva , Masculino , Pessoa de Meia-Idade , Síndrome do Desconforto Respiratório/mortalidade , Estudos Retrospectivos , Resultado do Tratamento
7.
Acta Pharmaceutica Sinica ; (12): 352-359, 2021.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-873759

RESUMO

Thiazolidinediones (TZDs) are currently the only recognized insulin sensitizers available for the clinical treatment of type 2 diabetes. Although their advantages are recognized, the profiles of numerous adverse effects hinder the continued use of these drugs. Peroxisome proliferator-activated receptor γ (PPARγ) is known as a receptor for TZDs, and its underlying mechanisms of pharmacological actions and adverse effects have been deeply explored. To maximally preserve the PPARγ-mediated insulin sensitizing effects and reduce the occurrence of related adverse effects, the concept of "selective PPARγ modulators (SPPARMs)" has been proposed and developed, guiding the development of new drugs. In this review, we summarize the recent research progress in the definition of SPPARMs, the candidate classification and the molecular underpinnings, as well as present the discovery of the YR series compounds as an example, and discuss the potential application prospects of SPPARMs.

8.
Acta Pharmaceutica Sinica ; (12): 1265-1278, 2021.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-887065

RESUMO

Indoleamine 2,3-dioxygenase 1 (IDO1) and tryptophan 2,3-dioxygenase (TDO) catalyze the initial and rate limiting step in the catabolism of tryptophan, which is related to tumor immune tolerance and poor prognosis in patients. In this regard, two enzymes have become important therapeutic targets for tumor immunotherapy. So far, nine IDO1 inhibitors and three IDO1/TDO dual inhibitors have entered clinical trials. This review summarizes the research progress of IDO1 inhibitors, TDO inhibitors and IDO1/TDO dual inhibitors from the perspective of medicinal chemistry.

9.
Am J Physiol Gastrointest Liver Physiol ; 318(2): G305-G312, 2020 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-31736338

RESUMO

Hepatocellular carcinoma (HCC) is the sixth common malignant tumor worldwide, but current efficient and convenient screening methods remain lacking. This study aimed to discover a diagnostic or a screening biomarker from the urine of hepatitis B virus (HBV)-related HCC patients. We used iTRAQ coupled with mass spectrometry to identify candidate urinary proteins in a discovery cohort (n = 40). The selected proteins were confirmed using ELISA in a validation cohort (n = 140). Diagnostic performance of the selected proteins was assessed using receiver operating characteristic (ROC) and qualitative diagnostic analysis. A total of 96 differentially expressed proteins were identified. Urinary α-fetoprotein (u-AFP) and orosomucoid 1 (u-ORM1) were selected as target proteins by bioinformatics analysis and were significantly higher in HCC than in non-HCC patients, as validated by Western blot analysis and ELISA. u-AFP had a strong correlation with serum AFP-L3 (Pearson's r = 0.944, P < 0.0001), indicating that u-AFP may be derived from circulating blood. The area under the curve (AUC) of u-AFP was 0.795 with a sensitivity of 62.5% and a specificity of 95.4%, which showed no significantly difference with serum AFP (se-AFP). The AUC was 0.864 as u-AFP and u-ORM1 were combined, and they performed much better than u-AFP or u-ORM1 alone. Qualitative diagnostic analysis showed that the positive predictive value of u-AFP was 90.1% and the diagnostic sensitivity of parallel combination of u-AFP and u-ORM1 was 85.1%. Taken together, AFP and ORM1 in the urine may be used as a diagnostic or screening biomarker of HCC, and studies on large samples are needed to validate the result.NEW & NOTEWORTHY This study provides a novel way to find biomarkers of hepatocellular carcinoma (HCC) and a new perspective of α-fetoprotein clinical application. The urine reagent strips may be helpful in high epidemic areas of HCC and in low-resource settings.


Assuntos
Biomarcadores/urina , Carcinoma Hepatocelular/etiologia , Carcinoma Hepatocelular/urina , Vírus da Hepatite B , Hepatite B Crônica/complicações , Neoplasias Hepáticas/etiologia , Neoplasias Hepáticas/urina , Orosomucoide/urina , alfa-Fetoproteínas/urina , Adulto , Idoso , Estudos de Coortes , Feminino , Humanos , Masculino , Programas de Rastreamento , Pessoa de Meia-Idade , Proteoma , Reprodutibilidade dos Testes , alfa-Fetoproteínas/genética
10.
PeerJ ; 7: e6645, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30923657

RESUMO

BACKGROUND: Liver fibrosis is often a consequence of chronic liver injury, and has the potential to progress to cirrhosis and liver cancer. Despite being an important human disease, there are currently no approved anti-fibrotic drugs. In this study, we aim to identify the key genes and pathways governing the pathophysiological processes of liver fibrosis, and to screen therapeutic anti-fibrotic agents. METHODS: Expression profiles were downloaded from the Gene Expression Omnibus (GEO), and differentially expressed genes (DEGs) were identified by R packages (Affy and limma). Gene functional enrichments of each dataset were performed on the DAVID database. Protein-protein interaction (PPI) network was constructed by STRING database and visualized in Cytoscape software. The hub genes were explored by the CytoHubba plugin app and validated in another GEO dataset and in a liver fibrosis cell model by quantitative real-time PCR assay. The Connectivity Map L1000 platform was used to identify potential anti-fibrotic agents. RESULTS: We integrated three fibrosis datasets of different disease etiologies, incorporating a total of 70 severe (F3-F4) and 116 mild (F0-F1) fibrotic tissue samples. Gene functional enrichment analyses revealed that cell cycle was a pathway uniquely enriched in a dataset from those patients infected by hepatitis B virus (HBV), while the immune-inflammatory response was enriched in both the HBV and hepatitis C virus (HCV) datasets, but not in the nonalcoholic fatty liver disease (NAFLD) dataset. There was overlap between these three datasets; 185 total shared DEGs that were enriched for pathways associated with extracellular matrix constitution, platelet-derived growth-factor binding, protein digestion and absorption, focal adhesion, and PI3K-Akt signaling. In the PPI network, 25 hub genes were extracted and deemed to be essential genes for fibrogenesis, and the expression trends were consistent with GSE14323 (an additional dataset) and liver fibrosis cell model, confirming the relevance of our findings. Among the 10 best matching anti-fibrotic agents, Zosuquidar and its corresponding gene target ABCB1 might be a novel anti-fibrotic agent or therapeutic target, but further work will be needed to verify its utility. CONCLUSIONS: Through this bioinformatics analysis, we identified that cell cycle is a pathway uniquely enriched in HBV related dataset and immune-inflammatory response is clearly enriched in the virus-related datasets. Zosuquidar and ABCB1 might be a novel anti-fibrotic agent or target.

11.
Orthopade ; 48(2): 119-124, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30574675

RESUMO

BACKGROUND: Several studies have suggested that excellent therapeutic outcomes can be achieved with conservative treatment of proximal humeral epiphyseal fractures in patients younger than 11 years old; however, the outcomes of conservative treatment for children older than 11 years are controversial. To address this problem, this study compared outcomes of conservative treatment for proximal humeral epiphyseal fractures in pediatric patients of different ages. METHODS: The patients were divided into two groups for comparative purposes based on age. Group I consisted of 34 patients who were less than 11 years old (average age: 5 years) and group II included 21 patients who were 11 years of age or older (average age: 14 years). Patients in both groups underwent conservative treatment and follow-up examination, where they first were examined with X­radiography for assessment of deformity, fracture union and loss of reduction. At the final follow-up after 2 years, patients were assessed by an interview and a detailed physical examination including the assessment of shoulder function using the Constant-Murley score. RESULTS: There were no significant differences in the grading scale of varus deformity between the two groups (P > 0.05) after immediate postreduction X­radiography; however, there were significant differences in the grading scale of varus deformity between group I and group II at the 2­year follow-up (P < 0.05). There were no significant differences between the two groups with respect to the Constant-Murley score and arm length discrepancy (P > 0.05) at final follow-up examinations. CONCLUSION: In general, the results suggested that the outcomes, as measured with radiographs, for both older and young children were comparable after immediate postreduction roentgenograms. For long-term follow-up there was a difference between the two groups and the degree of angulation and displacement might be associated with treatment outcomes for older children. Thus, these factors should be considered when treating and evaluating the outcomes for older children.


Assuntos
Tratamento Conservador , Fraturas do Ombro , Ombro , Atividades Cotidianas , Adolescente , Criança , Pré-Escolar , Epífises , Feminino , Fixação Interna de Fraturas , Humanos , Úmero , Masculino , Estudos Retrospectivos , Resultado do Tratamento
12.
Neural Regen Res ; 13(9): 1594-1601, 2018 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-30127120

RESUMO

Simple regulation of c-Jun N-terminal kinase (JNK) or p38 mitogen-activated protein kinase (MAPK) pathways is not enough to trigger cell apoptosis. However, activation of the stress activated pathway (JNK/p38 MAPK) together with inhibition of the growth factor activated extracellular signal-regulated kinase (ERK) pathway can promote cell apoptosis. We hypothesized that inhibition of the JNK or p38 pro-apoptotic pathway and activating the ERK pathway could be the mechanism of anti-apoptosis following cerebral ischemia/reperfusion injury. To investigate the mechanism of the protective effect of electroacupuncture on cerebral ischemia/reperfusion injury in JNK knockout mice, mouse models of cerebral ischemia/reperfusion injury were established by Longa's method. Electroacupuncture was conducted at acupoints Chize (LU5), Hegu (LI4), Sanyinjiao (SP6) and Zusanli (ST36) 1.5 hours after ischemia/reperfusion injury for 20 minutes, once a day. The neurological function was evaluated using neurological deficit scores. The expression of phospho-extracellular signal-regulated kinase (p-ERK) and phospho-p38 (p-p38) in JNK knockout mice was detected using double-labeling immunofluorescence and western blot assay. The mRNA expression of ERK and p38 was measured by quantitative real-time polymerase chain reaction. Electroacupuncture improved neurological function, increased the immunoreactivity and relative expression of p-ERK and reduced that of p-p38 in the cerebral cortex and hippocampus on the injured side. Electroacupuncture increased mRNA expression of ERK, but decreased that of p38 in the cerebral cortex and hippocampus on the injured side. In conclusion, electroacupuncture upregulated the protective ERK pathway and inhibited the pro-apoptotic p38 pathway, thereby exerting a neuroprotective effect and improving the neurological function in JNK knockout mice.

13.
Inflammation ; 41(2): 579-594, 2018 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-29234949

RESUMO

We previously demonstrated that a PEGylated curcumin (Curc-mPEG454) significantly inhibited cyclooxygenase 2 (COX-2) expression and improved the progression of liver fibrosis. The current study systematically evaluates its anti-inflammatory and antioxidant activities in vitro in a comparative study with curcumin, aspirin, NS-398, and vitamin C. RAW264.7 murine macrophages were pretreated with Curc-mPEG454, curcumin, aspirin, NS-398, or vitamin C at the indicated concentration for 2 h; then, the cells were stimulated with 1 µg/mL lipopolysaccharide (LPS) for 24 h. The levels of pro-inflammatory cytokines and mediators, including IL-6, TNF-α, PGE2, NO, and GSH, and the activities of COX-2, SOD, and CAT, and the transcription factors involved in inflammation, such as NF-κB, c-Jun, and Nrf2, were measured. Curc-mPEG454 showed lower cytotoxicity (IC50 57.8 µM) when compared with that of curcumin (IC50 32.6 µM) and inhibited the release of the inflammatory cytokines IL-6, TNF-α, IL-1ß, and MCP-1 in a concentration-dependent manner. At 16 µM, Curc-mPEG454 was most potent in the suppression of COX-2 expression at a transcriptional level rather than in the suppression of the catalytic activity of COX-2. Like curcumin, Curc-mPEG454 significantly reduced intracellular ROS production and enhanced the activities of SOD and CAT and the level of GSH to protect cells from LPS-induced oxidative injury. Further, its anti-inflammatory and antioxidation mechanisms are related to inhibition of NF-κB p65 nuclear translocation and c-Jun phosphorylation and to activation of Nrf2. Taken together, these findings indicate that PEGylation of curcumin not only improves its biological properties but also interferes with multiple targets involved in the inflammatory response. Curc-mPEG454 is a powerful and beneficial anti-inflammatory and antioxidant agent that merits further investigation. Graphical Abstract ᅟ.


Assuntos
Curcumina/análogos & derivados , Curcumina/farmacologia , Polietilenoglicóis/farmacologia , Animais , Anti-Inflamatórios/farmacologia , Antioxidantes/farmacologia , Lipopolissacarídeos/farmacologia , Camundongos , Fator 2 Relacionado a NF-E2/efeitos dos fármacos , Fator 2 Relacionado a NF-E2/metabolismo , Proteínas Proto-Oncogênicas c-jun/efeitos dos fármacos , Proteínas Proto-Oncogênicas c-jun/metabolismo , Células RAW 264.7 , Fator de Transcrição RelA/efeitos dos fármacos , Fator de Transcrição RelA/metabolismo
14.
Biomed Res Int ; 2017: 8234507, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28770225

RESUMO

Curcumin has the potential to cure dyslipidemia and nonalcoholic fatty liver disease (NAFLD). However, its therapeutic effects are curbed by poor bioavailability. Our previous work has shown that modification of curcumin with polyethylene glycol (PEG) improves blood concentration and tissue distribution. This study sought to investigate the role of a novel PEGylated curcumin derivative (Curc-mPEG454) in regulating hepatic lipid metabolism and to elucidate the underlying molecular mechanism in a high-fat-diet- (HFD-) fed C57BL/6J mouse model. Mice were fed either a control chow diet (D12450B), an HFD (D12492) as the NAFLD model, or an HFD with Curc-mPEG454 administered by intraperitoneal injection at 50 mg/kg or 100 mg/kg for 16 weeks. We found that Curc-mPEG454 significantly lowered the body weight and serum triglyceride (TG) levels and reduced liver lipid accumulation in HFD-induced NAFLD mice. It was also shown that Curc-mPEG454 suppressed the HFD-induced upregulated expression of CD36 and hepatic peroxisome proliferator activated receptor-γ (PPAR-γ), a positive regulator of CD36. Moreover, Curc-mPEG454 dramatically activated cAMP response element-binding (CREB) protein, which negatively controls hepatic PPAR-γ expression. These findings suggest that Curc-mPEG454 reverses HFD-induced hepatic steatosis via the activation of CREB inhibition of the hepatic PPAR-γ/CD36 pathway, which may be an effective therapeutic for high-fat-diet-induced NAFLD.


Assuntos
Antígenos CD36/metabolismo , Curcumina/farmacologia , Proteína de Ligação ao Elemento de Resposta ao AMP Cíclico/metabolismo , Fígado Gorduroso/tratamento farmacológico , PPAR gama/metabolismo , Transdução de Sinais/efeitos dos fármacos , Animais , Peso Corporal/efeitos dos fármacos , Dieta Hiperlipídica/efeitos adversos , Fígado Gorduroso/metabolismo , Metabolismo dos Lipídeos/efeitos dos fármacos , Fígado , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Hepatopatia Gordurosa não Alcoólica/tratamento farmacológico , Hepatopatia Gordurosa não Alcoólica/metabolismo , Obesidade/metabolismo
15.
Acta Anatomica Sinica ; (6): 43-47, 2017.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-844701

RESUMO

Objective To investigate the effect of lentivirus-stromal cell-derived factor-1α-green fluorescent protein(LV-SDF-1α-GFP) on the cardiac fibroblasts, the optimum conditions of infection, the expression and secretion of the target protein. Methods The cardiac fibroblasts of neonatal rats were primarily isolated and cultured by differential adherence methods, and were observed and identifi with immunofluorescence. LV-SDF-1α-GFP with different titers and conditions was transfected into cardiac fibroblasts. The expression of fluorescence and the optimal transfection conditions were observed. LV-SDF-1α-GFP target gene virus and negative control C0N145 virus were transfected into cardiac fibroblasts. The growth curve was drawn, and the effect of transfection on the proliferation of cardiac fibroblasts was explored. The cardiac fibroblasts were transfected with the optimum transfection dose, and the expression of SDF-1α was detected by Dot-blotting. The measurement data underwent statistical analysis. Results There was no statistical difference between the cardiac fibroblasts with SDF-1α transfected lentivirus and without no-transfected SDF-1α lentivirus. The peak of the expression of SDF-1α appeared in culture day 4 and statistical analysis showed significantly difference (P<0.05). Conclusion The LV-SDF-1α-GFP vector is of higher transfection efficiency to cardiac fibroblasts with the both low cytotoxicity and ability of secreting SDF-la protein.

16.
Zhonghua Gan Zang Bing Za Zhi ; 23(6): 428-32, 2015 Jun.
Artigo em Chinês | MEDLINE | ID: mdl-26236928

RESUMO

OBJECTIVE: To assess the clinical value ofprocalcitonin in cirrhotic patients with severe infection by comparing the serum procalcitonin levels in those patients with and without liver cirrhosis when suffering from sepsis. METHODS: A total of 225 septic patients were included in the study,including 91 patients without hepatopathy, 80 patients with cirrhosis, and 54 patients with chronic liver disease. The serum procalcitonin level was measured in all patients and statistically assessed for correlation with relevant clinical biochemistry indicators. The t-test, ANOVA test, Mann-Whitney U test, chi-square test and Spearman's correlation analysis were used for statistical analyses. RESULTS: The patients with cirrhosis showed significantly lower serum procalcitonin levels (0.84 (0.32-3.44) ng/ml) than the patients with no hepatopathy (2.17 (0.70-9.18) ng/ml) or the patients with chronic liver disease (2.12 (0.33-13.61) ng/ml) (both P less than 0.05); the patients in the no hepatopathy group and the chronic liver disease group showed statistically similar levels of serum procalcitonin (P=0.616). The patients with cirrhosis of Child-Pugh grade C showed significantly higher level of serum procalcitonin (1.25 (0.54-4.61) ng/ml) than those patients with Child-Pugh grade B (0.33 (0.14-1.31) ng/ml; P=0.026), suggesting that patients with Child-Pugh C stage cirrhosis may be more susceptible to gram-negative bacterial infection. In the cirrhosis group,serum procalcitonin level was positively correlated with white blood cell (WBC) count (r=0.312) and percentage of neutrophils (N%) (r=0.228) (both P less than 0.05). Correlation analysis of the no hepatopathy group and the chronic liver disease group showed no correlation between serum procalcitonin level and either WBC or N%. CONCLUSION: Under the sepsis condition, cirrhotic patients have lower serum procalcitonin level than patients without cirrhosis, and the serum procalcitonin level is positively correlated with WBC count and N%.


Assuntos
Cirrose Hepática , Sepse , Calcitonina , Peptídeo Relacionado com Gene de Calcitonina , Humanos , Precursores de Proteínas
17.
Yao Xue Xue Bao ; 49(4): 490-6, 2014 Apr.
Artigo em Chinês | MEDLINE | ID: mdl-24974466

RESUMO

A series of novel tetrahydrocarboline derivatives was designed and synthesized in order to discover more potent peroxisome proliferator-activated receptor (PPAR) alpha/gamma dual regulators. The structures of these compounds were confirmed by 1H NMR and HR-MS; their PPAR-regulating activities were evaluated in vitro. Compounds 6h, 6n, 6p and 6q exhibited more potent PPARalpha agonistic activities than the control drug WY14643, while compounds 60, 6g, 6i and 6q exhibited more potent PPARgamma agonistic activities than the control drug rosiglitazone. Compound 6q was discovered as a potent PPARalpha/gamma dual agonist and deserves further investigation.


Assuntos
Carbolinas/síntese química , Desenho de Fármacos , Hipoglicemiantes/síntese química , Receptores Ativados por Proliferador de Peroxissomo/agonistas , Animais , Carbolinas/química , Carbolinas/farmacologia , Células Cultivadas , Hipoglicemiantes/química , Hipoglicemiantes/farmacologia , Estrutura Molecular , PPAR alfa/agonistas , PPAR gama/agonistas , Pirimidinas/metabolismo , Rosiglitazona , Relação Estrutura-Atividade , Tiazolidinedionas/metabolismo , Transfecção
18.
J Asian Nat Prod Res ; 16(3): 296-303, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-24456252

RESUMO

A novel series of N-methyl-bisindolylmaleimides were synthesized and evaluated for their inhibitory activities against nine tumor cell lines. Some of the compounds showed an interesting activity against the tested cell lines. The most potent compounds 5e and 5j displayed antiproliferative activity with 50% inhibitory concentration values in the µM range against some tested cell lines.


Assuntos
Antineoplásicos/síntese química , Antineoplásicos/farmacologia , Indóis/síntese química , Indóis/farmacologia , Maleimidas/síntese química , Maleimidas/farmacologia , Antineoplásicos/química , Linhagem Celular Tumoral , Proliferação de Células , Ensaios de Seleção de Medicamentos Antitumorais , Células HeLa , Humanos , Indóis/química , Concentração Inibidora 50 , Células KB , Células MCF-7 , Maleimidas/química , Estrutura Molecular , Relação Estrutura-Atividade
19.
Acta Pharmaceutica Sinica ; (12): 490-496, 2014.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-245057

RESUMO

A series of novel tetrahydrocarboline derivatives was designed and synthesized in order to discover more potent peroxisome proliferator-activated receptor (PPAR) alpha/gamma dual regulators. The structures of these compounds were confirmed by 1H NMR and HR-MS; their PPAR-regulating activities were evaluated in vitro. Compounds 6h, 6n, 6p and 6q exhibited more potent PPARalpha agonistic activities than the control drug WY14643, while compounds 60, 6g, 6i and 6q exhibited more potent PPARgamma agonistic activities than the control drug rosiglitazone. Compound 6q was discovered as a potent PPARalpha/gamma dual agonist and deserves further investigation.


Assuntos
Animais , Carbolinas , Química , Farmacologia , Células Cultivadas , Desenho de Fármacos , Hipoglicemiantes , Química , Farmacologia , Estrutura Molecular , PPAR alfa , PPAR gama , Receptores Ativados por Proliferador de Peroxissomo , Pirimidinas , Metabolismo , Relação Estrutura-Atividade , Tiazolidinedionas , Metabolismo , Transfecção
20.
Artigo em Inglês | WPRIM (Pacífico Ocidental) | ID: wpr-264630

RESUMO

The effects of genetic factors on the noise-induced hearing loss (NIHL) are still unclear. In the present study, eight single-nucleotide polymorphisms (SNPs) included rs1227049 and rs3802711 (CDH23), rs1695 (GSTP1), rs137852540 (GJB2), rs2289274 (PMCA2), rs4880 (SOD2), rs7943316, and rs769214 within CAT that might associated with NIHL were further validated in Chinese workers. The results showed that the carriers of the T allele (AT+TT) of rs7943316 and A allele (GA+AA) of rs769214, were significantly associated with an increased risk of NIHL compared to those with AA genotype (P<0.05) and GG genotype (P<0.05). Moreover, a significant three-locus model (P=0.0107) involving rs2016520, rs9794, and rs1805192 were observed that might associated with NIHL, with 53.95% of testing accuracy. Thus, our present study provided the evidence that GJB2, SOD2, and CAT genes might account for the NIHL development in independently and/or in an interactive manner.


Assuntos
Humanos , Masculino , Povo Asiático , Genética , Estudos de Casos e Controles , Catalase , Genética , China , Conexina 26 , Conexinas , Genética , Predisposição Genética para Doença , Perda Auditiva Provocada por Ruído , Genética , Superóxido Dismutase , Genética
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...