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1.
Mol Biol Rep ; 2020 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-32415505

RESUMO

The improper usage of antibiotics is known to cause widespread antibiotic resistance. In this study, the antibacterial effects of a polypeptide-enriched extract from the skin of the amphibian Rana chensinensis (RCP) were evaluated against the Gram-negative bacteria Escherichia coli and Pseudomonas aeruginosa, the Gram-positive bacterium Staphylococcus aureus and the fungus Candida albicans. The mechanisms underlying these effects were also studied, and the minimum inhibitory concentration of RCP was determined for each species. Analyses of the levels of adenosine triphosphates (ATPases), including Na+/K+-ATPase and Ca2+-ATPase, and scanning electron microscopy confirmed that RCP damaged the microbial cell walls and membranes. RCP perturbed microbial metabolism and particularly affected the tricarboxylic acid cycle (TCA), suggesting that this agent downregulated the levels of succinate dehydrogenase, malate dehydrogenase and ATPase activity in cells. Furthermore, RCP caused the leakage of genetic material from all four microbial strains. In conclusion, RCP effectively inhibited the growth of Gram-negative and Gram-positive bacteria and a fungal species by disrupting energy metabolic processes.

2.
Clin Lab ; 66(5)2020 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-32390380

RESUMO

BACKGROUND: The aim of the study is to determine the effects of blood lead levels (BLLs) on spontaneous abortion. METHODS: A well-matched case-control study was performed at Peking Union Medical College Hospital from 2016 - 2018. Spontaneous abortion cases requiring suction and curettage within 12 weeks gestational age composed the case group. Control group includes pregnancies showing fetal cardiac activity with simultaneous requests for induced abortions matched to case group in age, gravidity, parity, and gestational age. RESULTS: Three hundred patients with 150 per group were included. Age, gravidity, parity, gestational age and the number of lead exposures, smokers, alcoholic beverage drinkers, and coffee drinkers were not significantly different between the two groups. The mean BLLs were 27.17 µg/L and 17.28 µg/L for the case and control group, respectively (p = 0.000). The odds ratios for spontaneous abortion comparing 5 - 9, 10 - 14, 15 - 24, 25 - 39, and ≥ 40 µg/L with a reference category of < 5 µg/L blood lead were 1.58 (0.23 - 10.90), 3.13 (2.11 - 9.08), 4.63 (1.45 - 14.83), 6.33 (1.95 - 20.56), and 22.56 (4.91 - 103.66), respectively, demonstrating a significant trend (P1 = 0.64, P2 = 0.02, P3 = 0.01, P4 = 0.02, and P5 = 0.00). CONCLUSIONS: Lead contamination and its effect on spontaneous abortion cannot be ignored. During early pregnancy, when BLL is above 10 µg/L, the chance of spontaneous abortion increases compared to BLLs below 5 µg/L. The higher the BLL is, the greater the risk of spontaneous abortion will be.

3.
BMC Neurol ; 20(1): 148, 2020 Apr 21.
Artigo em Inglês | MEDLINE | ID: mdl-32316912

RESUMO

BACKGROUND: Mild cognitive impairment (MCI) is an intermediate stage between normal aging and dementia. Studies on MCI progression are important for Alzheimer's disease (AD) prevention. 18F fluoro-deoxy-glucose positron emission tomography (FDG-PET) has been proven to be a powerful tool for measuring cerebral glucose metabolism. In this study, we proposed a classification framework for MCI prediction with both baseline and multiple follow-up FDG-PET scans as well as cognitive scores of 33 progressive MCI (pMCI) patients and 46 stable MCI (sMCI) patients from the Alzheimer's Disease Neuroimaging Initiative (ADNI). METHOD: First, PET images were normalized using the Yakushev normalization procedure and registered to the Brainnetome Atlas (BNA). The average metabolic intensities of brain regions were defined as static features. Dynamic features were the intensity variation between baseline and the other three time points and change ratios with the intensity obtained at baseline considered as reference. Mini-mental State Examination (MMSE) scores and Alzheimer's disease Assessment Scale-Cognitive section (ADAS-cog) scores of each time point were collected as cognitive features. And F-score was applied for feature selection. Finally, support vector machine (SVM) with radial basis function (RBF) kernel was used for the three above features. RESULTS: Dynamic features showed the best classification performance in accuracy of 88.61% than static features (accuracy of 78.48%). And the combination of cognitive features and dynamic features improved the classification performance in specificity of 95.65% and Area Under Curve (AUC) of 0.9308. CONCLUSION: Our results reported that dynamic features are more representative in longitudinal research for MCI prediction work. And dynamic features and cognitive scores complementarily enhance the classification performance in specificity and AUC. These findings may predict the disease course and clinical changes in individuals with mild cognitive impairment.

5.
Eur J Obstet Gynecol Reprod Biol ; 242: 109-113, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31580962

RESUMO

PURPOSE: To analyse the management of patients with placenta accreta spectrum (PAS) disorders who underwent 2nd trimester pregnancy terminations. METHOD: The records of patients with PAS disorders who underwent 2nd trimester pregnancy terminations were collected and analysed. RESULTS: Twenty-eight patients were included; 8 (28.6%) patients received prenatal diagnoses and 20 (71.4%) patients received postnatal diagnoses. In the prenatal diagnosis group, scheduling hysterotomy and placenta removal were performed in 5 patients with complete placenta previa and previous caesarean delivery without hysterectomy or postpartum haemorrhage, and medical termination was performed in 3 patients, 2 of whom retained the placenta in situ. In the postnatal diagnosis group, the placenta remained in situ in 11 patients, and in 13 (46.4%) patients overall, adjuvant treatments were applied to the patients, and the abnormally implanted placenta was passed 43.5 (range: 7-102) days after termination. A complication associated with the placenta left in situ included intrauterine infection in one case. Uterus preservation was achieved in all the patients. CONCLUSIONS: For patients with PAS disorders with complete placenta previa and previous caesarean delivery, hysterotomy is a safe choice for terminating a 2nd trimester pregnancy. When it is impossible to manually remove the placenta, leaving the placenta in situ with the administration of adjuvant treatment is a good choice for uterus preservation.

6.
Theranostics ; 9(18): 5282-5297, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31410215

RESUMO

Purpose: Methotrexate (MTX) is a first-line drug for rheumatoid arthritis (RA)therapy. However, MTX monotherapy often results in irreversible joint damage due to its slow onset of action and long duration. microRNA-124 (miR-124) has shown direct bone protection activity against RA. A co-delivery system for MTX and microRNA combination may provide therapeutic synergy. Methods: Methotrexate-conjugated polymer hybrid micelles (M-PHMs) were prepared by self-assembly of two functional amphiphilic polymers (MTX-PEI-LA and mPEG-LA) at an optimized weight ratio. Incorporation of microRNA was achieved through electrostatic interactions between microRNA and cationic polymer MTX-PEI-LA. Cellular uptake, endosome escape, biodistribution, and therapeutic efficacy of M-PHMs/miR-124 complexes were investigated and evaluated in RAW264.7 cells and a rat adjuvant-induced arthritis (AIA) model. Results: M-PHMs/miR-124 complexes exhibited folate receptor-mediated uptake in activated RAW264.7 cells. miR-124 was able to escape from the endosome and down-regulate nuclear factor of activated T cells cytoplasmic1 (NFATc1). M-PHMs/miR-124 complexes accumulated in inflamed joints of AIA rats and showed superior therapeutic efficacy through both anti-inflammatory effect and direct bone protective effect. Combination of miR-124 and MTX in these micelles induced disease remission. Conclusions: M-PHMs/miR-124 was highly effective against RA through therapeutic synergy. Additional studies are warranted to further investigate its therapeutic potential and delineate its mechanisms of action.

7.
J Clin Lab Anal ; 33(8): e22974, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31294919

RESUMO

BACKGROUND: With the development of industrialization, public exposure to toxic metals could occur everywhere, eventually affecting individuals' reproductive systems and even embryos and leading to early pregnancy loss. The aim of the study was to determine the profile of toxic metal levels in pregnant women in the general population and to identify biomarkers for metal toxicity in embryos. METHODS: A case-control study with pregnant women was conducted at Peking Union Medical College Hospital in 2016-2018. Women who experienced spontaneous abortion within 12 weeks of gestation comprised the case group, and women with pregnancies showing fetal cardiac activity who requested an induced abortion almost simultaneously were included in the control group. Blood and urine specimen were tested for concentrations of cadmium, chromium, selenium, arsenic, and mercury. RESULTS: A total of 195 patients were enrolled, with 95 in the case group and 100 in the control group. Significant differences in gravidity, parity, history of miscarriage, mean blood cadmium levels, and mean urine chromium levels were present between the two groups (P1 = 0.013, P2 = 0.000, P3 = 0.000, P4 = 0.002, P5 = 0.046); the odds ratios in the spontaneous abortion with blood cadmium >0.4 µg/L, urine chromium >2 µg/L, gravity <3, parity <2, and history of miscarriage >1 compared with the induced abortion group were 1.26 (1.09, 1.85), 1.56 (1.23, 2.53), 1.39 (1.17, 1.98), 1.72 (1.21, 4.62), and 1.18 (1.06, 1.65), with P-values of 0.003, 0.031, 0.003, 0.247, and 0.001, respectively. CONCLUSION: Blood cadmium and urine chromium levels are two possible biomarkers of toxic metal embryotoxicity in the general population, which means that in the general population, blood cadmium >0.4 µg/L or urine chromium >2 µg/L might indicate an increased risk of spontaneous abortion.

8.
Anticancer Res ; 39(3): 1169-1178, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30842146

RESUMO

BACKGROUND/AIM: Effective and targeted delivery of siRNA to tumor cells is a prerequisite to achieving their therapeutic effects. Survivin is up-regulated in tumor cells and is associated with resistance to therapy. Therefore, siRNA-mediated silencing of survivin is a potential therapeutic strategy for cancer. The aim of the study was to examine whether polymeric hybrid micelles can be used to effectively deliver siRNAs into cells. MATERIALS AND METHODS: First, linoleic acid (LA) was conjugated to polyethylenimine (PEI) and methoxy-polyethyleneglycol (mPEG) and two amphiphilic polymers (PEI-LA and mPEG-LA) were obtained. Polymeric hybrid micelle (PHM) was then prepared and characterized by self-assembly of PEI-LA and mPEG-LA at different percentages of the two amphiphilic polymers. A PHM/siRNA complex with optimized composition and good biocompatibility was then prepared and its cellular uptake, biodistribution, and antitumor effects were investigated. RESULTS: Survivin siRNA was efficiently delivered to the cells. It reduced survivin protein expression and greatly suppressed tumor growth. Moreover, siRNA loaded in PHM gathered in a solid tumor in mice and achieved an improved anticancer effect compared to naked siRNA. CONCLUSION: PHM is a promising and safe vehicle for siRNA delivery and may find utility in cancer therapy.


Assuntos
Micelas , Neoplasias/terapia , RNA Interferente Pequeno/administração & dosagem , Células A549 , Animais , Sobrevivência Celular/efeitos dos fármacos , Feminino , Humanos , Ácido Linoleico/administração & dosagem , Ácido Linoleico/química , Camundongos Endogâmicos BALB C , Camundongos Nus , Neoplasias/genética , Neoplasias/metabolismo , Neoplasias/patologia , Polietilenoglicóis/administração & dosagem , Polietilenoglicóis/química , Polietilenoimina/administração & dosagem , Polietilenoimina/química , RNA Interferente Pequeno/farmacocinética , Survivina/genética , Survivina/metabolismo , Carga Tumoral
9.
Pharmaceutics ; 11(2)2019 Feb 21.
Artigo em Inglês | MEDLINE | ID: mdl-30795589

RESUMO

A combination of chemotherapeutic drugs and siRNA is emerging as a new modality for cancer therapy. A safe and effective carrier platform is needed for combination drug delivery. Here, a functionalized mixed micelle-based delivery system was developed for targeted co-delivery of methotrexate (MTX) and survivin siRNA. Linolenic acid (LA) was separately conjugated to branched polyethlenimine (b-PEI) and methoxy-polyethyleneglycol (mPEG). MTX was then conjugated to LA-modified b-PEI (MTX-bPEI-LA) to form a functionalized polymer-drug conjugate. Functionalized mixed micelles (M-MTX) were obtained by the self-assembly of MTX-bPEI-LA and LA-modified mPEG (mPEG-LA). M-MTX had a narrow particle size distribution and could successfully condense siRNA at an N/P ratio of 16/1. M-MTX/siRNA was selectively taken up by HeLa cells overexpressing the folate receptor (FR) and facilitated the release of the siRNA into the cytoplasm. In vitro, M-MTX/siRNA produced a synergy between MTX and survivin siRNA and markedly suppressed survivin protein expression. In tumor-bearing mice, M-MTX/Cy5-siRNA showed an elevated tumor uptake. In addition, M-MTX/siRNA inhibited tumor growth. Immunohistochemistry and a western blot analysis showed a significant target gene downregulation. In conclusion, M-MTX/siRNA was highly effective as a delivery system and may serve as a model for the targeted co-delivery of therapeutic agents.

10.
Oxid Med Cell Longev ; 2018: 9140896, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30050662

RESUMO

Sarcodon imbricatus (SI), a precious edible fungus, contains 35.22% of total sugar, 18.33% of total protein, 24 types of fatty acid, 16 types of amino acid, and 8 types of minerals. Encouragingly, it is rich in potential antioxidants such as total polyphenols (0.41%), total sterols (3.16%), and vitamins (0.44%). In the present study, the antifatigue properties of SI and its potential mechanisms of action were explored by the experiments on acute excise-treated mice and chronic fatigue syndrome (CFS) mice. SI (0.25, 0.5, and 1 g/kg) significantly enhanced exercise tolerance in the weight-loaded forced swimming test (FST) and rota-rod test (RRT) and reduced the immobility in the tail suspension test on CFS mice. SI markedly increased the levels of glycogen in the liver and adenosine triphosphate (ATP) in the liver and muscle and decreased the lactic acid (LD) and blood urea nitrogen (BUN) content in both acute swimming-treated mice and CFS mice. SI improved the endogenous cellular antioxidant enzyme contents in the two mouse models by improving the activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) and reducing reactive oxygen species (ROS) and malondialdehyde (MDA) levels in serum, liver, and muscle, respectively. In CFS mice, the enhanced expression levels of nuclear factor erythroid-2-related factor 2 (Nrf2), SOD1, SOD2, heme oxygenase-1 (HO-1), and catalase (CAT) in the liver were observed after a 32-day SI administration. Our data indicated that SI possessed antifatigue activity, which may be related to its ability to normalize energy metabolism and Nrf2-mediated oxidative stress. Consequently, SI can be expected to serve as a novel natural antifatigue supplement in health foods.


Assuntos
Basidiomycota/fisiologia , Síndrome de Fadiga Crônica/dietoterapia , Síndrome de Fadiga Crônica/metabolismo , Fator 2 Relacionado a NF-E2/metabolismo , Estresse Oxidativo/fisiologia , Animais , Western Blotting , Catalase/metabolismo , Suplementos Nutricionais , Glutationa Peroxidase/metabolismo , Heme Oxigenase-1/metabolismo , Masculino , Malondialdeído/metabolismo , Camundongos , Espécies Reativas de Oxigênio/metabolismo , Superóxido Dismutase/metabolismo
11.
Cell Death Dis ; 9(6): 578, 2018 05 21.
Artigo em Inglês | MEDLINE | ID: mdl-29784961

RESUMO

Sarcodon imbricatus, a rare medicinal and edible fungus, has various pharmacological bioactivities. We investigated the effects of S. imbricatus polysaccharides (SIPS) on hematopoietic function and identified the underlying mechanisms using in vitro experiments with CHRF, K562, and bone marrow mononuclear cells (BMMNCs) and in vivo experiments with a mouse model of cyclophosphamide-induced hematopoietic dysfunction. We found that SIPS induced proliferation and differentiation of CHRF and K562 cells and upregulated the expression of hematopoietic-related proteins, including p90 ribosomal S6 kinases (RSK1p90), c-Myc, and ETS transcription factor, in the two cell lines. After 28 days of treatment, SIPS enhanced the bodyweight and thymus indices of the mice, alleviated enlargement of the spleen and liver, and contributed to the recovery of peripheral blood to normal levels. More importantly, the percentages of B lymphocytes and hematopoietic stem cells or hematopoietic progenitor cells were significantly elevated in bone marrow. Based on an antibody chip analysis and enzyme-linked immunosorbent assay, SIPS were found to successfully regulate 12 cytokines to healthy levels in serum and spleen. The cytokines included the following: interleukins 1Ra, 2, 3, 4, 5, and 6, tumor necrosis factor α, interferon-γ, granulocyte colony-stimulating factor (G-CSF) and macrophage colony-stimulating factor (M-CSF), C-C motif chemokine1, and monocyte chemoattractant protein-1. Moreover, SIPS upregulated the phosphorylation levels of janus kinase 2 (JAK2) and the signal transducer and activator of transcription 3 (STAT3) in the spleen, and similar results were validated in CHRF cells, K562 cells, and BMMNCs. The data indicate that SIPS activated the JAK2/STAT3 pathway, possibly by interactions among multiple cytokines, particularly G-CSF. We found that SIPS was remarkably beneficial to the bone marrow hematopoietic system, and we anticipate that it could improve myelosuppression induced by long-term radiotherapy or chemotherapy.


Assuntos
Ciclofosfamida/toxicidade , Fungos/química , Fator Estimulador de Colônias de Granulócitos/metabolismo , Células-Tronco Hematopoéticas/metabolismo , Janus Quinase 2/metabolismo , Polissacarídeos/farmacologia , Fator de Transcrição STAT3/metabolismo , Animais , Peso Corporal/efeitos dos fármacos , Células da Medula Óssea/citologia , Células da Medula Óssea/efeitos dos fármacos , Células da Medula Óssea/metabolismo , Diferenciação Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Citocinas/sangue , Hematopoese/efeitos dos fármacos , Células-Tronco Hematopoéticas/efeitos dos fármacos , Humanos , Células K562 , Masculino , Camundongos Endogâmicos BALB C , Transdução de Sinais/efeitos dos fármacos , Baço/metabolismo
12.
Int J Biol Macromol ; 116: 8-15, 2018 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-29730008

RESUMO

The objective of this study was to determine the ameliorative effects of Antrodia cinnamomea polysaccharide (ACPS) against cyclophosphamide (CTX)-induced immunosuppression in BALB/c mice. Four weeks of oral ACPS treatment successfully improved bodyweight and organ indexes and enhanced the function of T cells and the cytotoxicity of natural killer cells. CTX administration has been shown to notably decrease immunoglobulin A, G and M, interleukin 2, 6 and 12, and interferon α and γ levels in serum and in the spleen, and ACPS abolished these effects. Furthermore, ACPS effectively increased the total antioxidant capacity by stimulating superoxidase dismutase, catalase, and glutathione peroxidase activity in serum and in the spleen and by inhibiting the increases in reactive oxygen species and malondialdehyde levels. Notably, ACPS induced the activation of erythroid 2-related factor 2 (Nrf2) related to down-regulating Kelch-like ECH-associated protein 1 expression, which leads to enhanced levels of downstream antioxidative enzymes, including heme oxygenase-1 (HO-1), superoxide dismutase 2, and catalase in the spleen and thymus. Therefore, the protective effects of ACPS on CTX-induced immunosuppression in mice may be the result of a reduction in oxidative stress and involved in the Nrf2/HO-1 pathway. Our study suggests that ACPS has potential for development as an effective anti-immunosuppressive agent.


Assuntos
Ciclofosfamida/farmacologia , Heme Oxigenase-1/metabolismo , Imunossupressores/farmacologia , Proteínas de Membrana/metabolismo , Fator 2 Relacionado a NF-E2/metabolismo , Polissacarídeos/farmacologia , Animais , Antioxidantes/metabolismo , Antrodia , Catalase/metabolismo , Glutationa Peroxidase/metabolismo , Imunossupressão/métodos , Proteína 1 Associada a ECH Semelhante a Kelch/metabolismo , Malondialdeído/metabolismo , Camundongos , Camundongos Endogâmicos BALB C , Estresse Oxidativo/efeitos dos fármacos , Espécies Reativas de Oxigênio/metabolismo , Transdução de Sinais/efeitos dos fármacos , Baço/efeitos dos fármacos , Baço/metabolismo , Superóxido Dismutase/metabolismo
13.
Mol Med Rep ; 16(4): 4320-4326, 2017 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-28765877

RESUMO

Tricholoma matsutake, a popular food and biopharmaceutical resource in Asia, possesses various pharmacological activities. Although T. matsutake mycelium (TM) may enhance immunity, previous studies, to the best of our knowledge, have been performed on normal animals or cells alone. The present study aimed to evaluate the immunomodulatory activity of TM at doses of 0.3, 1.0 and 2.0 g/kg in cyclophosphamide (CTX)­induced immunosuppressed mouse models. TM treatment for 2 weeks markedly improved the gain in bodyweight, increased organ indices, reduced hind paw swelling and positively regulated the cytotoxicity of natural killer cells and the proliferation of lymphocytes. These effects are similar to that of thymosin α1 (0.16 mg/kg) which served as the positive control. In CTX­induced immunosuppressed mice, TM demonstrated marked effects on the modulation of the production of immunoglobulin (Ig)G and IgA, and the levels of interleukin­2, 6, 10 and 12, interferon­α and γ and tumor necrosis factor­α in serum. Compared with CTX mice, the reduced activity of nuclear factor (NF)­κB in serum and spleen, and phosphorylation of inhibitor of NF­κB kinase α/ß in spleen were observed in TM­treated mice. Taken together, TM effectively improved immune function in immunosuppressed mice via modulation of ILs and inflammatory factors associated with the NF­κB signaling pathway.


Assuntos
Ciclofosfamida/farmacologia , Fatores Imunológicos/farmacologia , Imunossupressão , Micélio/química , Tricholoma/química , Animais , Peso Corporal/efeitos dos fármacos , Morte Celular/efeitos dos fármacos , Citocinas/sangue , Feminino , Imunoglobulinas/sangue , Imunoglobulinas/metabolismo , Mediadores da Inflamação/metabolismo , Células Matadoras Naturais/efeitos dos fármacos , Células Matadoras Naturais/metabolismo , Masculino , Camundongos Endogâmicos BALB C , NF-kappa B/metabolismo , Transdução de Sinais/efeitos dos fármacos , Linfócitos T/efeitos dos fármacos , Linfócitos T/metabolismo , Regulação para Cima/efeitos dos fármacos
14.
Mol Med Rep ; 16(4): 5675-5682, 2017 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-28849191

RESUMO

Paecilomyces hepiali contains identical chemical constituents to Cordyceps sinensis, and it presents antidepressant­like activity via regulating noradrenergic and dopaminergic systems. Behavioral despair depression models serve important roles in scientific screening and evaluation of antidepressants. The present study aims to investigate the antidepressant­like activity of P. hepiali extract (PHC) in chronic unpredictable mild stress (CUMS)­induced rat model of depression. Following four weeks of treatment, similar to fluoxetine at 3 mg/kg (positive drug), PHC at doses from 0.08 to 2.0 g/kg strongly increased sucrose preference and reduced the immobility time of depression­like rats in forced swimming test. The hypo­level of adrenocorticotropic hormone, noradrenaline and glucocorticoid receptor in serum and hypothalamus of depression­like rats was enhanced by PHC. PHC normalized CUMS­induced disorders of dihydroxyphenylacetic acid, dopamine, 5­hydroxytryptamine (5­HT) and 5­hydroxyindoleacetic acid in serum and/or hypothalamus of depression­like rats. Moreover, PHC enhanced the expression of tyrosine hydroxylase and reduced the levels of dopamine D2 receptor and 5­HT2A receptor in hypothalamus. These results suggested that the antidepressant­like effects of PHC in CUMS­induced depression are associated with not only the modulation of dopamine, but also the regulation of 5-HT.


Assuntos
Transtorno Depressivo/etiologia , Transtorno Depressivo/metabolismo , Dopamina/metabolismo , Micoses/complicações , Paecilomyces/fisiologia , Serotonina/metabolismo , Estresse Psicológico , Animais , Comportamento Animal , Doença Crônica , Modelos Animais de Doenças , Hormônios/sangue , Hormônios/metabolismo , Masculino , Micoses/microbiologia , Neurotransmissores/sangue , Neurotransmissores/metabolismo , Ratos , Ratos Sprague-Dawley , Transdução de Sinais
15.
Saudi Pharm J ; 25(4): 460-463, 2017 May.
Artigo em Inglês | MEDLINE | ID: mdl-28579875

RESUMO

Aims: Sarcodon imbricatus, an edible fungus, is widely used in Asian medicine because of its significant pharmacological activities. In the present study, we investigated the immunomodulatory effects of polysaccharide-enriched S. imbricatus extracts (SP) in cyclophosphamide (CTX)-induced immunosuppressed mice. Results: Astragalus polysaccharide (AP) was used as a positive control. Compared with CTX-induced immunosuppressed mice, thirty-day SP treatment strongly enhanced the organ indexes of spleen and thymus and suppressed hind paw swelling. Both AP and SP increased the serum levels of immunoglobulin (IgA, IgG, and IgM), and suppressed the overproduction of interleukin-2 (IL-2). Moreover, SP reduced methane dicarboxylic aldehyde levels, and increased the total antioxidant capacity, superoxide dismutase, and glutathione peroxidase in both serum and liver tissues of CTX-induced immunosuppressed mice. Conclusion: S. imbricatus extracts significantly improved immune function in CTX-induced immunosuppressed mice via modulation of oxidative systems.

16.
PLoS One ; 12(6): e0180476, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28662169

RESUMO

This study evaluated the effects of Inonotus obliquus polysaccharides (IOs) on diabetes and other underlying mechanisms related to inflammatory factors and oxidative stress in a mouse model of streptozotocin (STZ)-induced diabetes. Four weeks administration of metformin (120 mg/kg) and IO1-4 (50%-80% alcohol precipitation), or IO5 (total 80% alcohol precipitation) at doses of 50 mg/kg reverses the abnormal changes of bodyweights and fasting blood glucose levels of diabetic mice. IOs significantly increased the insulin and pyruvate kinase levels in serum, and improved the synthesis of glycogen, especially for IO5. IOs restored the disturbed serum levels of superoxide dismutase, catalase, glutathione peroxidase, and malondialdehyde. The down-regulation of interleukin-2 receptor, matrix metalloproteinase-9, and the enhancement of interleukin-2 in serum of diabetic mice were significantly attenuated by IOs. Histologic and morphology examinations showed that IOs repaired the damage on kidney tissues, inhibited inflammatory infiltrate and extracellular matrix deposit injuries in diabetic mice. Compared with untreated diabetic mice, IOs decreased the expression of phosphor-NF-κB in the kidneys. These results show that IOs treatment attenuated diabetic and renal injure in STZ-induced diabetic mice, possibly through the modulation of oxidative stress and inflammatory factors. These results provide valuable evidences to support the use of I. obliquus as a hypoglycemic functional food and/or medicine.


Assuntos
Basidiomycota/química , Diabetes Mellitus Experimental/tratamento farmacológico , Hipoglicemiantes/farmacologia , Estresse Oxidativo/efeitos dos fármacos , Polissacarídeos/farmacologia , Animais , Hemoglobina A Glicada/metabolismo , Hipoglicemiantes/uso terapêutico , Insulina/sangue , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Polissacarídeos/uso terapêutico , Piruvato Quinase/sangue , Estreptozocina
17.
Biomed Res Int ; 2017: 9374026, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28424791

RESUMO

Antrodia cinnamomea, a folk medicinal mushroom, has numerous biological effects. In this study, we aim to assess whether the antifatigue effects of A. cinnamomea mycelia (AC) and its underlying mechanisms are related to oxidative stress signaling using behavioral mouse models and biochemical indices detection. Mice were orally treated with AC at doses of 0.1, 0.3, and 0.9 g/kg for three weeks. AC had no effect on the spontaneous activities of mice indicating its safety on central nervous system. Furthermore, results obtained from weight-loaded forced swimming test, rotary rod test, and exhausted running test confirmed that AC significantly enhanced exercise tolerance of mice. Biochemical indices levels showed that these effects were closely correlated with inhibiting the depletion of glycogen and adenosine triphosphate stores, regulating oxidative stress-related parameters (superoxide dismutase, glutathione peroxidase, reactive oxygen species, and malondialdehyde) in serum, skeletal muscle, and liver of mice. Moreover, the effects of AC may be related with its regulation on the activations of AMP-activated protein kinase, protein kinase B, and mammalian target of rapamycin in liver and skeletal muscle of mice. Altogether, our data suggest that the antifatigue properties of AC may be one such modulation mechanism via oxidative stress-related signaling in mice.


Assuntos
Antrodia/química , Fadiga/tratamento farmacológico , Fadiga/patologia , Micélio/química , Estresse Oxidativo , Transdução de Sinais , Proteínas Quinases Ativadas por AMP/metabolismo , Trifosfato de Adenosina/sangue , Animais , Modelos Animais de Doenças , Feminino , Glicogênio/metabolismo , Fígado/metabolismo , Testes de Função Hepática , Masculino , Camundongos , Músculo Esquelético/metabolismo , Oxirredução , Condicionamento Físico Animal , Proteínas Proto-Oncogênicas c-akt/metabolismo , Serina-Treonina Quinases TOR/metabolismo
18.
Oxid Med Cell Longev ; 2017: 7841823, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28337253

RESUMO

In the present study, the components of A. cinnamomea (AC) mycelia were systematically analyzed. Subsequently, its hepatoprotective effects and the underlying mechanisms were explored using a mouse model of acute alcohol-induced liver injury. AC contained 25 types of fatty acid, 16 types of amino acid, 3 types of nucleotide, and 8 types of mineral. The hepatoprotective effects were observed after 2 weeks of AC treatment at doses of 75 mg/kg, 225 mg/kg, and 675 mg/kg in the mouse model. These effects were indicated by the changes in the levels of aspartate aminotransferase, alanine aminotransferase, several oxidation-related factors, and inflammatory cytokines in serum and/or liver samples. AC reduced the incidence rate of necrosis, inflammatory infiltration, fatty droplets formation, and cell apoptosis in liver detecting via histological and TUNEL assay. In addition, AC reduced the expression of cleaved caspase-3, -8, and -9 and the levels of phosphor-protein kinase B (Akt) and phosphor-nuclear factor-κB (NF-κB) in the liver samples. Collectively, AC-mediated hepatoprotective effects in a mouse model of acute alcohol-induced liver injury are the result of reduction in oxidative stress. This may be associated with Akt/NF-κB signaling. These results provide valuable evidence to support the use of A. cinnamomea as a functional food and/or medicine.


Assuntos
Antrodia/química , Estresse Oxidativo/efeitos dos fármacos , Extratos Vegetais/farmacologia , Substâncias Protetoras/farmacologia , Transdução de Sinais/efeitos dos fármacos , Alanina Transaminase/sangue , Álcoois/toxicidade , Animais , Antioxidantes/metabolismo , Antrodia/metabolismo , Aspartato Aminotransferases/sangue , Caspase 3/metabolismo , Caspase 8/metabolismo , Caspase 9/metabolismo , Doença Hepática Induzida por Substâncias e Drogas/metabolismo , Doença Hepática Induzida por Substâncias e Drogas/patologia , Citocinas/sangue , Citocinas/metabolismo , Modelos Animais de Doenças , Fígado/metabolismo , Fígado/patologia , Camundongos , NF-kappa B/metabolismo , Extratos Vegetais/química , Substâncias Protetoras/química , Proteínas Proto-Oncogênicas c-akt/metabolismo , Espécies Reativas de Oxigênio/metabolismo
19.
Nanomedicine ; 13(2): 371-381, 2017 02.
Artigo em Inglês | MEDLINE | ID: mdl-27720989

RESUMO

Microfluidic systems can accelerate clinical translation of nanoparticles due to their ability to generate nanoparticles in a well-controlled and reproducible manner. In this study, a single-step process based on microfluidic focusing (MF) was employed to synthesize transferrin-conjugated lipid nanoparticles (Tf-LNPs) and the method was compared with a multi-steps bulk mixing (BM) method. The results indicate that this single-step MF process enables rapid and efficient synthesis of Tf-LNPs, which were named Tf-LNPs-MF. Tf-LNPs-MF was shown to have a smaller size and more uniform structures compared to LNPs produced by multi-steps BM method (Tf-LNPs-BM). Furthermore, efficient cellular uptake of Tf-LNPs-MF in vitro as well as greater tumor inhibition in vivo proved that Tf-LNPs-MF had higher siRNA delivery efficiency in vitro and in vivo. Taken together, this single-step microfluidic synthesis significantly simplified the Tf-LNPs production and improved their drug delivery properties and may serve as a valuable tool for developing new cancer therapies.


Assuntos
Microfluídica , Nanopartículas , RNA Interferente Pequeno , Humanos , Lipídeos , Transferrina
20.
Eur J Pharm Sci ; 96: 530-541, 2017 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-27789373

RESUMO

development, single-factor experiments were employed to evaluate the effect of adding different matrix, enhancers, 5-HMT, ethanol and glycerol on drug skin development, single-factor experiments were employed to evaluate the effect of adding different matrix, enhancers, 5-HMT, ethanol and glycerol on drug skin permeation. Finally, Carbopol 940 was selected as the gel matrix with N-methyl pyrrolidone (NMP) chosen as the enhancer. The relationship between time and the steady accumulative percutaneous amount (Q, µgcm-2) of optimized 5-HMT hydrogels was Q4-12h=1290.8t1/2-1227.7. The absolute bioavailability of 5-HMT hydrogels was 20.7% showed in pharmacokinetic study. No skin irritation was observed in 5-HMT hydrogels skin irritation study. In the pharmacodynamic study, the overactive bladder model was induced by 150µg/kg of pilocarpine in rats. The significant effects of 5-HMT hydrogels on the inhibition of urine output on rat model were last to 12h. The optimized 5-HMT hydrogels displayed prolonged pharmacological responses. 5-HMT hydrogels effectively avoided the metabolism difference of enzyme in bodies compared with tolterodine tablets, provided one single active compound in plasma to reduce the variability of having two active compounds. To further elucidate the transdermal mechanism, fourier transform infrared (FTIR) spectroscopy, differential scanning calorimeter (DSC) and activation energy measurements were used to study the transdermal routes and changes of stratum corneum during drug release.


Assuntos
Compostos Benzidrílicos/administração & dosagem , Compostos Benzidrílicos/farmacocinética , Cresóis/administração & dosagem , Cresóis/farmacocinética , Desenho de Fármacos , Hidrogéis/administração & dosagem , Hidrogéis/farmacocinética , Absorção Cutânea/efeitos dos fármacos , Administração Cutânea , Animais , Compostos Benzidrílicos/síntese química , Cresóis/síntese química , Feminino , Hidrogéis/síntese química , Masculino , Camundongos , Técnicas de Cultura de Órgãos , Coelhos , Ratos , Ratos Sprague-Dawley , Absorção Cutânea/fisiologia
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