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1.
PLoS One ; 19(2): e0287882, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38319940

RESUMO

The Chinese caterpillar mushroom, Ophiocordyceps sinensis (O. sinensis), is a rarely medicinal fungus in traditional chinese herbal medicine due to its unique medicinal values, and the expression stability of reference genes is essential to normalize its gene expression analysis. In this study, BestKeeper, NormFinder and geNorm, three authoritative statistical arithmetics, were applied to evaluate the expression stability of sixteen candidate reference genes (CRGs) in O. sinensis under different stress [low temperature (4°C), light treatment (300 lx), NaCl (3.8%)] and different development stages (mycelia, primordia and fruit bodies) and formation of morphologic mycelium (aeriasubstrate, hyphae knot mycelium). The paired variation values indicated that two genes could be enough to accurate standardization exposed to different conditions of O.sinensis. Among these sixteen CRGs, 18S ribosomal RNA (18S rRNA) and beta-Tubulin (ß-TUB) showed the topmost expression stability in O.sinensis exposed to all conditions, while glutathione hydrolase proenzym (GGT) and Phosphoglucose isomerase (PGI) showed the least expression stability. The optimal reference gene in different conditions was various. ß-TUB and Ubiquitin (UBQ) were identified as the two most stable genes in different primordia developmental stage, while phosphoglucomutase (PGM) with elongation factor 1-alpha (EF1-α) and 18S rRNA with UBQ were the most stably expressed for differentially morphologic mycelium stages and different stresses, respectively. These results will contribute to more accurate evaluation of the gene relative expression levels in O.sinensis under different conditions using the optimal reference gene in real-time quantitative PCR (RT-qPCR) analysis.


Assuntos
Cordyceps , Cordyceps/genética , RNA Ribossômico 18S/genética , Perfilação da Expressão Gênica/métodos , Genes de Plantas , Reação em Cadeia da Polimerase em Tempo Real/métodos , Padrões de Referência , Tubulina (Proteína)/genética , Ubiquitina/genética
2.
Int J Med Mushrooms ; 25(4): 75-92, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37075086

RESUMO

The asexual form of Ophiocordyceps sinensis has been controversial, but various morphologic mycelium appeared when O. sinensis was cultured under experimental conditions. To explore the generation mechanism of morphologic mycelium, developmental transcriptomes were analyzed from three kinds of mycelium (aerial mycelium, hyphae knot, and substrate mycelium). The results showed that diameter and morphology of these three kinds of mycelium were obviously different. KEGG functional enrichment analysis showed that the differential expressed genes (DEGs) of substrate mycelium were enriched in ribosomes and peroxisomes, indicating that prophase culture was rich in nutrients and the metabolism of substrate mycelium cells was vigorous in the stage of nutrient absorption. The up-DEGs of hyphae knot were mainly enriched in the oxidative phosphorylation pathway, indicating that oxidative phosphorylation was the main energy source for mycelium formation in the stage of nutrient accumulation and reproductive transformation. The up-DEGs of aerial mycelium were mainly enriched in the synthesis and degradation pathways of valine, leucine, and isoleucine, suggesting that the occurrence of aerial mycelium was related to amino acid metabolism at the later stage of culture, and nutritional stress accelerated the reproduction of asexual spores. In addition, the important roles of mycelium formation related genes were verified by combined analysis of qRT-PCR and transcriptome sequencing. Collectively, this study will provide theoretical guidance for inhibiting the occurrence of aerogenous mycelium and promoting the development of mycelium into pinhead primordia in the culture of O. sinensis in the future.


Assuntos
Cordyceps , Micélio , Cordyceps/genética , Perfilação da Expressão Gênica , Sequenciamento de Nucleotídeos em Larga Escala , Micélio/genética , Transcriptoma/genética
3.
Cells ; 11(19)2022 10 02.
Artigo em Inglês | MEDLINE | ID: mdl-36231074

RESUMO

Background: Retinal ischemia-reperfusion (I/R) injury often results in intractable visual impairments. The survival of retinal capillary endothelial cells is crucial for the treatment of retinal I/R injury. How to protect retinal endothelia from damage is a challenging work. Withaferin A, a small molecule derived from plants, has antibacterial and anti-inflammatory effects and has been used for about millennia in traditional medicine. The present study aimed to investigate the potential protective effect of withaferin A on retinal I/R injury. Methods: The drug-likeness of withaferin A was evaluated by the SwissADME web tool. The potential protective effect of withaferin A on the I/R-induced injury of human retinal microvascular endothelial cells (HRMECs) was investigated using multiple approaches. RNA sequencing was performed and associated mechanistic signaling pathways were analyzed based on the Kyoto Encyclopedia of Genes and Genomes data. The analytical results of RNA sequencing data were further validated by in vitro and in vivo experiments. Results: Withaferin A reduced the I/R injury-induced apoptotic death of HRMECs in vitro with a good drug-like property. RNA sequencing and experimental validation results indicated that withaferin A increased the production of the crucial antioxidant molecules heme oxygenase 1 (HO-1) and peroxiredoxin 1 (Prdx-1) during I/R. In addition, withaferin A activated the Akt signaling pathway and increased the expression of HO-1 and Prdx-1, thereby exerting an antioxidant effect, attenuated the retinal I/R injury, and decreased the apoptosis of HRMECs. The blockade of Akt completely abolished the effects of withaferin A. Conclusions: The study identified for the first time that withaferin A can protect against the I/R-induced apoptosis of human microvascular retinal endothelial cells via increasing the production of the antioxidants Prdx-1 and HO-1. Results suggest that withaferin A is a promising drug candidate for the treatment of retinal I/R injury.


Assuntos
Heme Oxigenase-1 , Traumatismo por Reperfusão , Animais , Antibacterianos/farmacologia , Anti-Inflamatórios/farmacologia , Antioxidantes/metabolismo , Células Endoteliais/metabolismo , Heme Oxigenase-1/metabolismo , Humanos , Estresse Oxidativo , Peroxirredoxinas/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Ratos , Ratos Sprague-Dawley , Traumatismo por Reperfusão/tratamento farmacológico , Traumatismo por Reperfusão/metabolismo , Vitanolídeos
4.
Ann Transl Med ; 10(18): 983, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-36267750

RESUMO

Background: Microvascular angina (MVA) is a group of clinical manifestations of angina pectoris or angina-like chest pain, positive exercise test, and exclusion of epicardial coronary artery spasm, wherein coronary angiography (CAG) does not present obvious epicardial vascular stenosis. Shexiang Tongxin dropping pill (STDP) has the effect of benefiting the Qi and opening the blood vessels, activating blood circulation, and resolving blood stasis. We explored the mechanism of STDP against MVA by network pharmacology and molecular docking. Methods: Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP), literature search, SwissTargetPrediction database, and high-throughput experiment- and reference-guided database of traditional Chinese medicine (HERB) were applied to identify the active ingredients and targets of STDP. The MVA targets were searched in the databases of GeneCards, Pharmacogenetics and Pharmacogenomics Knowledge Base (PharmGKB), DisGeNET, Online Mendelian Inheritance in Man (OMIM), and Therapeutic Target Database (TTD). The common targets of STDP and MVA were screened. The software RStudio 4.1.3 was used to analyze the enrichment of these targets using Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways. Protein-protein interaction (PPI) network analysis of the common targets was performed using the Search Tool for the Retrieval of Interacting Genes/Genomes (STRING) database. The cytoHubba plug-in of Cytoscape 3.9.1 software was employed to analyze the PPI network and obtain the core targets. Molecular docking was performed to verify the relationship between the core compounds and proteins with AutoDock Tools 1.5.7 and Pymol 2.4.0. Results: We identified 93 effective components of STDP, 310 potential targets, 981 MVA targets, and 138 intersectional targets. The potential anti-MVA mechanism of STDP may involve the advanced glycation end products/receptor for advanced glycation end products (AGE-RAGE) signaling pathway in diabetic complications; lipids and atherosclerosis; fluid shear stress; atherosclerosis; the tumor necrosis factor (TNF), interleukin (IL)-17, hypoxia-inducible factor (HIF)-1, and C-type lectin receptor signaling pathways. Further, STDP mainly acts on its targets IL-6, AKT1, STAT3, JUN, and IL-1ß to against MVA. Conclusions: The STDP may exert its therapeutic effects through processes, such as anti-inflammation, promotion of smooth muscle cell proliferation and differentiation, lipid metabolism, immunomodulation, and regulation of cellular autophagy.

5.
Int J Med Mushrooms ; 24(8): 81-97, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35997097

RESUMO

The Chinese caterpillar mushroom, Ophiocordyceps sinensis, is rare in traditional Chinese herbal medicine. It was reported that the development of ascospores in sexual stage of Chinese Cordyceps requires certain UV irradiation, but whether light has effect on the asexual stage of O. sinensis is unclear. It is important and necessary to identify the candidate genes involved in asexual stages (mycelium period) metabolism of O. sinensis exposed to light treatment. In this study, the isolated and purified monoascospore strains from O. sinensis were treated with 10 days light (L10) and dark as control. Transcriptome sequencing (RNA-seq) was conducted to investigate the effect of light treatment on O. sinensis at the gene level and the changes in various metabolic pathways. The results showed that the colony surface was covered with villous aerial hyphae with a yellow circular mycelium ribbon in the center of the colony, and the content of polysaccharides, urea, adenosine, and cordycepin were significantly enhanced by L10 treatment. Kyoto Encyclopedia of Genes and Genomes (KEGG) functional annotation analysis showed that cell structure and catalytic metabolism were the significant items classified, and crucial genes affecting the anabolic pathways of polysaccharides, urea, adenosine, and cordycepin were also identified. In addition, the important roles of photoreceptor genes CRYD, WC-1, and FRQ were verified by combined analysis of qRT-PCR and transcriptome sequencing. Collectively, this study would be helpful to better understand the influence of light on the asexual stage of Chinese Cordyceps and provide a preliminary light treatment reference for Cordyceps artificial cultivation.


Assuntos
Cordyceps , Adenosina/metabolismo , China , Micélio/genética , Transcriptoma , Ureia
6.
J Healthc Eng ; 2022: 9664078, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35368921

RESUMO

Objective: To investigate the clinical effect of the syndrome-position point selection method on the intervention of idiopathic tinnitus of the phlegm-fire stagnation pattern. Methods: One hundred patients with idiopathic tinnitus of phlegm-fire stagnation pattern who met the inclusion criteria were randomized into the treatment group and the control group by the random number table method, with 50 cases in each group. The treatment group (syndrome-position point selection method) was treated with acupuncture at the corresponding acupoints for tinnitus and associated symptoms and the corresponding acupoints located in Wernicke's area of scalp projection, while the control group (traditional acupuncture method) was treated with the combination of acupuncture points with the most frequent occurrence in the tinnitus research literature for acupuncture treatment. Both groups received acupuncture twice a week for 5 weeks. The efficacy was evaluated before and after treatment with the Tinnitus Severity Inventory (TSI), Sleep Spiegel Questionnaire, Self-Rating Anxiety Scale (SAS), and Self-Rating Depression Scale (SDS). Results: The 100 patients with idiopathic tinnitus of phlegm-fire stagnation pattern completed 5 weeks of clinical treatment and a month of follow-up with no loss of patients and no adverse event reports. Three patients recovered with the disappearance of the tinnitus symptoms in the treatment group after 5 weeks of treatment. After 5 weeks of treatment, obvious differences between the two groups were observed in the TSI scores (P < 0.05) and the Spiegel scores, with a better Spiegel score in the treatment group than in the control group (P < 0.05). Compared with the control group, the depression (SDS score) and anxiety (SAS score) of tinnitus patients in the treatment group were markedly improved (P < 0.05). Conclusion: In line with the principle of symptomatic treatment and based on the modern imaging data, the syndrome-position point selection method is more accurate and effective compared with the traditional acupoint selection method, which significantly improves the symptoms, sleep quality, and psychological state of patients with idiopathic tinnitus of the phlegm-fire stagnation pattern.


Assuntos
Terapia por Acupuntura , Zumbido , Pontos de Acupuntura , Ansiedade/tratamento farmacológico , Humanos , Projetos de Pesquisa , Zumbido/tratamento farmacológico , Zumbido/psicologia
7.
Contrast Media Mol Imaging ; 2021: 2135924, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34934408

RESUMO

Objective: To explore the clinical efficacy of combining early chemotherapy with Zhipu Liujunzi decoction under the concept of strengthening and consolidating body resistance for gastric cancer patients and nursing strategy. Methods: The clinical data of 100 patients undergoing radical gastrectomy in our hospital from July 2019 to July 2020 were selected for the retrospective analysis, and the patients were divided into the control group and experimental group according to different treatment methods, with 50 cases in each group. Early chemotherapy after surgery was given to patients in the control group, and on the basis of the aforesaid treatment and under the concept of strengthening and consolidating body resistance, patients in the experimental group took Zhipu Liujunzi decoction and received the nursing strategy, so as to compare their effective rate, adverse reaction rate (ARR), immune function indicators, KPS scores, and nursing satisfaction scores. Results: After treatment, the experimental group obtained significantly higher objective remission rate (ORR) and disease control rate (DCR) (P < 0.05), lower carcinoembryonic antigen (CEA) and carbohydrate antigen 19-9 (CA19-9) levels (P < 0.001), higher immune parameters levels (P < 0.001), higher KPS scores and lower TCM symptom scores (P < 0.001), lower PSQI scores, SAS scores, and SDS scores (P < 0.001) and higher nursing satisfaction scores (P < 0.001), and lower total accidence rate of toxic side effects (P < 0.05) than the control group. Conclusion: Under the concept of strengthening and consolidating body resistance, combining early chemotherapy with Zhipu Liujunzi decoction is a reliable method for improving the immune function and quality of life for gastric cancer patients with higher safety. Such a strategy greatly reduces the tumor marker levels in patients. Further research will be conducive to establishing a better solution for gastric cancer patients.


Assuntos
Medicamentos de Ervas Chinesas , Neoplasias Gástricas , Medicamentos de Ervas Chinesas/uso terapêutico , Humanos , Qualidade de Vida , Estudos Retrospectivos , Neoplasias Gástricas/tratamento farmacológico , Neoplasias Gástricas/patologia
8.
Nat Commun ; 12(1): 4871, 2021 08 11.
Artigo em Inglês | MEDLINE | ID: mdl-34381056

RESUMO

The heteromeric complex between PKD1L3, a member of the polycystic kidney disease (PKD) protein family, and PKD2L1, also known as TRPP2 or TRPP3, has been a prototype for mechanistic characterization of heterotetrametric TRP-like channels. Here we show that a truncated PKD1L3/PKD2L1 complex with the C-terminal TRP-fold fragment of PKD1L3 retains both Ca2+ and acid-induced channel activities. Cryo-EM structures of this core heterocomplex with or without supplemented Ca2+ were determined at resolutions of 3.1 Å and 3.4 Å, respectively. The heterotetramer, with a pseudo-symmetric TRP architecture of 1:3 stoichiometry, has an asymmetric selectivity filter (SF) guarded by Lys2069 from PKD1L3 and Asp523 from the three PKD2L1 subunits. Ca2+-entrance to the SF vestibule is accompanied by a swing motion of Lys2069 on PKD1L3. The S6 of PKD1L3 is pushed inward by the S4-S5 linker of the nearby PKD2L1 (PKD2L1-III), resulting in an elongated intracellular gate which seals the pore domain. Comparison of the apo and Ca2+-loaded complexes unveils an unprecedented Ca2+ binding site in the extracellular cleft of the voltage-sensing domain (VSD) of PKD2L1-III, but not the other three VSDs. Structure-guided mutagenic studies support this unconventional site to be responsible for Ca2+-induced channel activation through an allosteric mechanism.


Assuntos
Canais de Cálcio/química , Cálcio/metabolismo , Receptores de Superfície Celular/química , Canais de Cátion TRPP/química , Aminoácidos , Animais , Sítios de Ligação , Cálcio/química , Canais de Cálcio/genética , Canais de Cálcio/metabolismo , Microscopia Crioeletrônica , Ativação do Canal Iônico , Camundongos , Mutagênese , Conformação Proteica , Domínios Proteicos , Receptores de Superfície Celular/genética , Receptores de Superfície Celular/metabolismo , Canais de Cátion TRPP/genética , Canais de Cátion TRPP/metabolismo
9.
Chem Biodivers ; 17(9): e2000328, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32627416

RESUMO

The emodin anthraquinone derivatives are generally used in traditional Chinese medicine due to their various pharmacological activities. In the present study, a series of emodin anthraquinone derivatives have been designed and synthesized, among which 1,3-dihydroxy-6,8-dimethoxyanthracene-9,10-dione is a natural compound that has been synthesized for the very first time, and 1,3-dimethoxy-5,8-dimethylanthracene-9,10-dione is a compound that has never been reported earlier. Interestingly, while total seven of these compounds showed neuraminidase inhibitory activity in influenza virus with inhibition rate more than 50 %, specific four compounds exhibited significant inhibition of tumor cell proliferation. The further results demonstrate that 1,3-dimethoxy-5,8-dimethylanthracene-9,10-dione showed the best anticancer activity among all the synthesized compounds by inducing highest apoptosis rate to HCT116 cancer cells and arresting their G0/G1 cell cycle phase, through elevation of intracellular level of reactive oxygen species (ROS). Moreover, the binding of 1,3-dimethoxy-5,8-dimethylanthracene-9,10-dione with BSA protein has thoroughly been investigated. Altogether, this study suggests the neuraminidase inhibitory activity and antitumor potential of the new emodin anthraquinone derivatives.


Assuntos
Antraquinonas/farmacologia , Antineoplásicos/farmacologia , Desenho de Fármacos , Emodina/farmacologia , Simulação de Acoplamento Molecular , Antraquinonas/síntese química , Antraquinonas/química , Antineoplásicos/síntese química , Antineoplásicos/química , Ciclo Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Células Cultivadas , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Emodina/análogos & derivados , Emodina/química , Humanos , Estrutura Molecular , Espécies Reativas de Oxigênio/análise , Espécies Reativas de Oxigênio/metabolismo , Relação Estrutura-Atividade
10.
Int J Biol Macromol ; 160: 1252-1262, 2020 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-32485247

RESUMO

The present report represents the synthesis of a novel Pd NPs immobilized over a natural polysaccharide (pectin) coated Fe3O4 magnetic nanocomposite material (Fe3O4@pectin/Pd) for investigating the cardiovascular protective effects. The biomolecular functionalization not only stabilizes the ferrite nanoparticles from agglomeration but also provides an environment for the biogenic reduction of Pd2+ ions. This protocol is a promising breakthrough for the synthesis of a quasi-heterogeneous catalyst, a bridge between heterogeneous and homogeneous medium. The structure, morphology and physicochemical properties of the material were characterized utilizing various analytical techniques like FT-IR, FE-SEM, TEM, VSM, EDX-elemental mapping, ICP, EDX and XPS. The catalyst showed excellent reactivity in C-C and C-N cross coupling reactions via Suzuki and Buchwald-Hartwig reactions respectively. An array of different biphenyls and aryl amines were then procured by reactions of various aryl halides with phenylboronic acid or secondary amines over the catalyst affording good to excellent yields. The catalyst was easily recoverable using an external magnet and thereafter recycled for several trials with insignificant palladium leaching or loss in catalytic performance. To investigate the cardiovascular protective activities of catalyst, the MTT assay was done on Human Aortic Endothelial Cells (HAEC), Human Coronary Artery Endothelial Cells (HCAEC), and Human Pulmonary Artery Endothelial Cells (HPAEC) cell lines. Nanocatalyst-treated cell cutlers significantly (p ≤ 0.01) decreased the caspase-3 activity, and DNA fragmentation. It raised the cell viability and mitochondrial membrane potential in the high concentration of Mitoxantrone-treated HAEC, HCAEC, and HPAEC cells. According to the above findings, nanocatalyst can be administrated as a cardiovascular protective drug for the treatment of cardiovascular diseases after approving in the clinical trial studies in humans.


Assuntos
Cardiotônicos/síntese química , Compostos Férricos/química , Nanopartículas Metálicas/química , Paládio/química , Pectinas/química , Apoptose , Cardiotônicos/farmacologia , Catálise , Células Cultivadas , Células Endoteliais/efeitos dos fármacos , Células Endoteliais/metabolismo , Endotélio Vascular/citologia , Humanos
11.
ACS Nano ; 13(10): 11433-11442, 2019 Oct 22.
Artigo em Inglês | MEDLINE | ID: mdl-31539472

RESUMO

Quantum-dot light-emitting diodes (QLEDs) with high brightness have potential application in lighting and display. The high brightness is realized at high current density (J). However, at high J, the efficiency drops significantly, thereby limiting the achievable brightness. This notorious phenomenon has been known as efficiency roll-off, which is likely caused by the Auger- and/or thermal-induced emission quenching. In this work, we show that the Joule heat generated during device operation significantly affects the roll-off characteristics of QLEDs. To realize ultrabright and efficient QLEDs, the thermal stability of QDs is improved by replacing the conventional oleic acid ligands with 1-dodecanethiol. By further using a substrate with high thermal conductivity, the Joule heat generated at high J is effectively dissipated. Because of the effective thermal management, thermal-induced emission quenching is significantly suppressed, and consequently, the QLEDs exhibit a high external quantum efficiency (EQE) of 16.6%, which is virtually droop-free over a wide range of brightness (e.g., EQE = 16.1% @ 105 cd/m2 and 140 mA/cm2). Moreover, due to the reduced efficiency roll-off and enhanced heat dissipation, the demonstrated QLEDs can be operated at a very high J up to 3885 mA/cm2, thus enabling the devices to exhibit a record-high brightness of 1.6 × 106 cd/m2 and a lumen density of 500 lm/cm2. Our work demonstrates the significance of thermal management for the development of droop-free and ultrabright QLED devices for a wide variety of applications including lighting, transparent display, projection display, outdoor digital signage, and phototherapy.

12.
Onco Targets Ther ; 11: 2685-2698, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29785118

RESUMO

BACKGROUND: Traditional chemotherapy and molecular targeted therapy have shown modest effects on the survival of patients with pancreatic cancer. The current study aimed to investigate the antitumor effects of apatinib, Astragalus polysaccharide (APS), and the combination of both the drugs in pancreatic cancer cells and further explore the molecular mechanisms in vitro. MATERIALS AND METHODS: Expression of vascular endothelial growth factor receptor-2 (VEGFR-2) in human pancreatic cancer cell lines ASPC-1, PANC-1, and SW1990 was detected by Western blotting. Cell proliferation was measured by MTS, and migration and invasion were detected by wound-healing and Transwell assays, respectively. Cell apoptosis rate was determined by flow cytometry and cellular autophagy level affected by apatinib, and APS was analyzed by Western blotting. RESULTS: Human pancreatic cancer cell lines ASPC-1 and PANC-1 expressed VEGFR-2, but VEGFR-2 was not detected in SW1990. Either apatinib or APS inhibited cell proliferation in a dose-dependent manner in ASPC-1 and PANC-1. APS in combination with apatinib showed enhanced inhibitory effects on cell migration and invasion compared with apatinib monotherapy in ASPC-1 and PANC-1. Meanwhile, APS combined with apatinib strongly increased cell apoptosis percentage. Western blotting showed that the combination of APS and apatinib significantly enhanced the downregulation of phosphorylated protein kinase B (AKT) and extracellular signal-regulated kinase (ERK) (p-AKT and p-ERK) as well as matrix metalloproteinases-9 (MMP-9) expression. In addition, both apatinib and APS induced cellular autophagy. However, the expression of autophagy-related proteins was not further elevated in the combination group. CONCLUSION: The study first demonstrated that apatinib showed potentially inhibitory effects in pancreatic cancer cells and that APS enhanced the antitumor effects of apatinib through further downregulating the expression of phosphorylation of AKT and ERK as well as MMP-9.

13.
Oncotarget ; 8(34): 57149-57162, 2017 Aug 22.
Artigo em Inglês | MEDLINE | ID: mdl-28915661

RESUMO

Being a neurodegenerative disorder, Alzheimer's disease (AD) is the one of the most terrible diseases. And acetylcholinesterase (AChE) is considered as an important target for treating AD. Acetylcholinesterase inhibitors (AChEI) are considered to be one of the effective drugs for the treatment of AD. The aim of this study is to find a novel potential AChEI as a drug for the treatment of AD. In this study, instead of using the synthetic compounds, we used those extracted from plants to investigate the interaction between floribundiquinone B (FB) and AChE by means of both the experimental approach such as fluorescence spectra, ultraviolet-visible (UV-vis) absorption spectrometry, circular dichroism (CD) and the theoretical approaches such as molecular docking. The findings reported here have provided many useful clues and hints for designing more effective and less toxic drugs against Alzheimer's disease.

14.
Biochemistry ; 56(32): 4244-4255, 2017 08 15.
Artigo em Inglês | MEDLINE | ID: mdl-28763199

RESUMO

The histidine-rich salivary peptides of the histatin family are known to bind copper (Cu) and other metal ions in vitro; however, the details of these interactions are poorly understood, and their implications for in vivo antifungal activity have not been established. Here, we show that the availability of Cu during exposure of Candida albicans to histatin-5 (Hist-5) modulates its antifungal activity. Antifungal susceptibility testing revealed that co-treatment of Hist-5 with Cu improved the EC50 from ∼5 to ∼1 µM, whereas co-treatment with a high-affinity Cu-specific chelator abrogated antifungal activity. Spectrophotometric titrations revealed two previously unrecognized Cu(I)-binding sites with apparent Kd values at pH 7.4, ∼20 nM, and confirmed a high-affinity Cu(II)-binding site at the Hist-5 N-terminus with an apparent Kd of ∼8 pM. Evaluation of a series of His-to-Ala full-length and truncated Hist-5 peptides identified adjacent His residues (bis-His) as critical anchors for Cu(I) binding, with the presence of a third ligand revealed by X-ray absorption spectroscopy. On their own, the truncated peptides were ineffective at inhibiting the growth of C. albicans, but treatment with supplemental Cu resulted in EC50 values down to ∼5 µM, approaching that of full-length Hist-5. The efficacy of the peptides depended on an intact bis-His site and correlated with Cu(I) affinity. Together, these results establish new structure-function relationships linking specific histidine residues with Cu binding affinity and antifungal activity and provide further evidence of the involvement of metals in modulating the biological activity of these antifungal peptides.


Assuntos
Antifúngicos , Candida albicans/crescimento & desenvolvimento , Cobre , Histatinas , Antifúngicos/química , Antifúngicos/farmacologia , Cobre/química , Cobre/farmacologia , Histatinas/química , Histatinas/farmacologia , Humanos
15.
PLoS One ; 12(2): e0171682, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28231287

RESUMO

BACKGROUND: Acute coronary syndrome (ACS) is an important disease threatening human life and health. Many studies have shown that the loading dose of atorvastatin can significantly improve the prognosis of patients with ACS, and reduce the mortality. However, this conclusion is not consistent. Thus, we aimed to evaluate the effect of high-dose rosuvastatin loading before percutaneous coronary intervention (PCI) in Chinese patients with ACS using a meta-analysis based on a systematic review of published articles. METHODS: We systematically reviewed published studies, evaluating the effect of high-dose rosuvastatin loading before percutaneous coronary intervention in Chinese patients with ACS. The retrieval time is limited from inception to 2 November 2016, and the retrieved databases included PubMed, Embase, the Cochrane Library, Web of Science, CBM, CNKI, the VIP database and the Wang Fang database. Two researchers independently assessed the quality of the included studies and then extracted the data. Stata 11.0 was used for data analysis. RESULTS: In total, 11 articles, which included 802 patients, were included in our meta-analysis. Among these patients, 398 patients were in the high-dose group (20 mg/day) and 404 patients were in the conventional dose group (10 mg/day). Meta-analysis results showed that compared with the conventional dose group: 1) The loading dose of rosuvastatin can significantly reduce the hs-CRP level after PCI, including at 24 hours (SMD = -0.65, 95%CI -0.84 ~ -0.47, P = 0.000), 48 hours (SMD = -0.40, 95%CI -0.68 ~ -0.11, P = 0.006), and four weeks (SMD = -1.64, 95%CI -2.01 ~ -1.26, P = 0.000). 2) The loading dose of rosuvastatin can significantly reduce the levels of LDL-C and cTnT, including the level of LDL-C at 30 d after PCI (SMD = -0.89, 95%CI -1.10 ~ -0.69, P = 0.000), and the level of cTnT at 24 h after PCI (SMD = -1.93, 95%CI -2.28 ~ -1.59, P = 0.000), and increase the level of HDL-C at 48 h after PCI (SMD = 0.61, 95%CI 0.34 ~ 0.88, P = 0.000). 3) The loading dose of rosuvastatin can significantly reduce the levels of TG and TC, including the level of TG at 30 d after PCI (SMD = -0.94, 95%CI -1.17 ~ -0.71, P = 0.000), the level of TC at 48 h after PCI (SMD = -0.35, 95%CI -0.68 ~ -0.01, P = 0.043), and the level of TC at 30 d after PCI (SMD = -0.77, 95%CI -0.98 ~ -0.56, P = 0.000). CONCLUSIONS: Our systematic review and meta-analysis showed that, compared with the conventional dose, the loading dose of rosuvastatin was more beneficial to patients with ACS in China and is suitable for clinical application. Due to the limitations of the quality and quantity of included articles, this conclusion still needs to be confirmed by multicenter clinical trials.


Assuntos
Síndrome Coronariana Aguda/tratamento farmacológico , Síndrome Coronariana Aguda/cirurgia , Anticolesterolemiantes/uso terapêutico , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Intervenção Coronária Percutânea , Rosuvastatina Cálcica/uso terapêutico , Síndrome Coronariana Aguda/epidemiologia , Anticolesterolemiantes/administração & dosagem , China/epidemiologia , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/administração & dosagem , Intervenção Coronária Percutânea/métodos , Rosuvastatina Cálcica/administração & dosagem
16.
ACS Nano ; 10(12): 11076-11086, 2016 12 27.
Artigo em Inglês | MEDLINE | ID: mdl-28024346

RESUMO

Plasmonic scattering from metallic nanoparticles has been used for centuries to create the colorful appearance of stained glass. Besides their use as passive spectral filtering components, multifunctional optoelectronic applications can be achieved by integrating the nanoscatters with semiconductors that generate electricity using the complementary spectral components of plasmonic colors. To suppress the usual degradation of both efficiency and the gamut of plasmonic scattering coloration in highly asymmetric index configurations like a silicon host, aluminum nanodisks on indium tin oxide (ITO) coated silicon were experimentally studied and demonstrated color sorting in the full visible range along with photocurrent generation. Interestingly, the photocurrents were found to be comparable to the reference devices with only antireflection coatings in spite of the power loss for coloration. Detailed investigation shows that ITO serves as both the impedance matching layer for promoting the backward scattering and schottky contact with silicon, and moreover, plasmonic nanoscatters efficiently harvest the complement spectrum components for charge generation. The present approach combines the capacities of nanoscale color sorting and photoelectric converting at a negligible cost of efficiency, thus providing a broad flexibility of being utilized in various optoelectronic applications including self-powered display, filter-free imaging, and colorful photovoltaics.

17.
Psychiatry Res ; 240: 131-136, 2016 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-27107388

RESUMO

Liquiritigenin (Liq), the main active ingredient of traditional Chinese medicine licorice, possesses anti-inflammatory and neuroprotective properties. The current investigation was designed to explore whether liquiritigenin could relieve lipopolysaccharide (LPS)-induced depression-like behavior in mice and the underlying mechanism. Liquiritigenin (7.5mg/kg, 15mg/kg) and fluoxetine (20mg/kg) were pretreated intragastrically once daily for 7 consecutive days. LPS (0.5mg/kg) was injected subcutaneously to establish the depression model 30min after pretreatment on day 7. Interleukin (IL)-6 and tumor necrosis factor (TNF)-α levels in serum and hippocampus were detected by enzyme-linked immunosorbent assay (ELISA). Behavioral assessment was conduct 24h post LPS injection. The expressions of p65NF-κB, IκBα, brain-derived neurotrophic factor (BDNF) and tropomyosin-related kinase B (TrkB) in hippocampus were determined by western blot. The obtained results showed that liquiritigenin effectively reduced the levels of pro-inflammatory cytokines and the expressions of p-p65NF-κB and p-IκBα. Furthermore, liquiritigenin preconditioning could down-regulate the immobility time in tail suspension test (TST), forced swimming test (FST) and up-regulate BDNF and TrkB contents in hippocampus. Thus, it is assumed that the antidepressant activity of liquiritigenin might be attributed to its anti-inflammatory property and BDNF/TrkB signaling pathway.


Assuntos
Antidepressivos/farmacologia , Depressão/tratamento farmacológico , Flavanonas/farmacocinética , Lipopolissacarídeos/farmacologia , Glicoproteínas de Membrana/metabolismo , Proteínas Tirosina Quinases/metabolismo , Animais , Antidepressivos/administração & dosagem , Comportamento Animal/efeitos dos fármacos , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Citocinas/sangue , Depressão/induzido quimicamente , Depressão/psicologia , Transtorno Depressivo/tratamento farmacológico , Ensaio de Imunoadsorção Enzimática , Flavanonas/administração & dosagem , Elevação dos Membros Posteriores , Hipocampo/efeitos dos fármacos , Hipocampo/metabolismo , Interleucina-6/metabolismo , Lipopolissacarídeos/administração & dosagem , Masculino , Camundongos , Camundongos Endogâmicos ICR , Transdução de Sinais/efeitos dos fármacos , Natação , Fator de Necrose Tumoral alfa/metabolismo
18.
IUBMB Life ; 68(5): 403-9, 2016 05.
Artigo em Inglês | MEDLINE | ID: mdl-27027512

RESUMO

The aim of this study was to investigate whether umbelliferone (Umb) could attenuate insulin resistance in unpredictable chronic mild stress (CUMS)-induced rats. Behavioral changes were evaluated through sucrose preference test (SPT), open-field test, forced swimming test, and tail suspension test (TST), suggesting that Umb (20 and 40 mg/kg) could effectively improve depression symptoms. Oral glucose tolerance test and serum insulin indicated that Umb attributed to the control of blood glucose levels. The phosphorylation of insulin receptor, insulin receptor substrate (IRS)-1, glycogen synthase kinase-3ß, PI3K, and Akt was increased in Umb (20 and 40 mg/kg) treatment according to Western blot analysis. Taken together, the current results suggested the ameliorative effect of Umb against insulin resistance in the CUMS-induced rats. © 2016 IUBMB Life, 68(5):403-409, 2016.


Assuntos
Antidepressivos/farmacologia , Resistência à Insulina , Estresse Psicológico/sangue , Umbeliferonas/farmacologia , Animais , Antidepressivos/uso terapêutico , Avaliação Pré-Clínica de Medicamentos , Insulina/sangue , Locomoção/efeitos dos fármacos , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Ratos Sprague-Dawley , Estresse Psicológico/tratamento farmacológico , Umbeliferonas/uso terapêutico
19.
Biomed Mater Eng ; 26 Suppl 1: S2113-21, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26405990

RESUMO

Milkvetch root as a medicine has been used for more over 2000 years in China, can strengthen immune function, protect liver, promote urination, resist aging and stress, reduce blood pressure and extensively resist bacterium. This study explored the effects of milkvetch root on the immune function of patients with a definitive diagnosis of acute exacerbation of chronic obstructive pulmonary disease (COPD). The patients were randomly assigned to either the experimental or control group. All patients received conventional clinical therapy; those in the experimental group were also administered milkvetch root. The serum levels of cytokines including tumor necrosis factor alpha (TNF-α), interleukin-8 (IL-8), IL-1ß, and IL-32 and immunocytes including T helper (Th), cytotoxic T (Tc), natural killer (NK), regulatory T (Treg) and B cells were measured 1 day before treatment and 7 and 14 days post-treatment. After bronchodilator inhalation, pulmonary function was evaluated at these same time points. The serum TNF-α, IL-8, IL-1ß, and IL-32 levels were significantly lower in the experimental group than in the control group 14 days post-treatment. The Th/Tc ratio and NK cell ratio was significantly higher but the Treg cell ratio was significantly lower in the experimental group than in the control group. The forced expiratory volume in 1 second (FEV1) and FEV1/forced vital capacity (FVC) were significantly higher in the experimental group than in the control group 14 days post-treatment. These results indicate that milkvetch root can improve the immune function of patients with acute exacerbation of COPD.


Assuntos
Astrágalo/química , Medicamentos de Ervas Chinesas/uso terapêutico , Fatores Imunológicos/uso terapêutico , Pulmão/efeitos dos fármacos , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico , Idoso , Idoso de 80 Anos ou mais , Citocinas/sangue , Citocinas/imunologia , Medicamentos de Ervas Chinesas/química , Feminino , Humanos , Imunidade Celular/efeitos dos fármacos , Fatores Imunológicos/química , Pulmão/imunologia , Pulmão/fisiopatologia , Masculino , Pessoa de Meia-Idade , Raízes de Plantas/química , Doença Pulmonar Obstrutiva Crônica/sangue , Doença Pulmonar Obstrutiva Crônica/imunologia , Doença Pulmonar Obstrutiva Crônica/fisiopatologia , Testes de Função Respiratória
20.
Zhongguo Zhen Jiu ; 34(5): 517-20, 2014 May.
Artigo em Chinês | MEDLINE | ID: mdl-25022136

RESUMO

Literatures of study on acupoint functional effect of encephalic region with functional magnetic resonance imaging (fMRI) are collected from the database of China National Knowledge Information (CNKI) and Wan fang database. Analysis and comments are made respectively from the status quo of studies on combination of single acupoint, two acupoints and multiple acupoints under both physiological and pathological conditions. The results show that the corresponding encephalic regions can be specifically activated by acupuncture. And different regions can be activated by different acupoints. However, studies on single acupoint, two acupoints and three acupoints are the major researches carried out at present. It is still lack of observation on effect of commonly-used combinations in clinic. Moreover, the reliability of the research results are also affected by disunity of operations protocol, reinforcing or reducing manipulations, intensity or depth of stimulation and duration of needling retention. Therefore, it is necessary to establish a unified and standard operation protocol to strictly control the bias factors which may affect the result of research in the future, and take patients as the study target as much as possible, so as to further explore the central effect mechanism.


Assuntos
Pontos de Acupuntura , Encéfalo/diagnóstico por imagem , Encéfalo/fisiologia , Imageamento por Ressonância Magnética , Terapia por Acupuntura , Humanos , Radiografia
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