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1.
Int J Med Sci ; 21(5): 965-977, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38616996

RESUMO

Cardiac hypertrophy is the most prevalent compensatory heart disease that ultimately leads to spontaneous heart failure. Mounting evidence suggests that microRNAs (miRs) and endogenous hydrogen sulfide (H2S) play a crucial role in the regulation of cardiac hypertrophy. In this study, we aimed to investigate whether inhibition of miR-27a could protect against cardiac hypertrophy by modulating H2S signaling. We established a model of cardiac hypertrophy by obtaining hypertrophic tissue from mice subjected to transverse aortic constriction (TAC) and from cells treated with angiotensin-II. Molecular alterations in the myocardium were quantified using quantitative real time PCR (qRT-PCR), Western blotting, and ELISA. Morphological changes were characterized by hematoxylin and eosin (HE) staining and Masson's trichrome staining. Functional myocardial changes were assessed using echocardiography. Our results demonstrated that miR-27a levels were elevated, while H2S levels were reduced in TAC mice and myocardial hypertrophy. Further luciferase and target scan assays confirmed that cystathionine-γ-lyase (CSE) was a direct target of miR-27a and was negatively regulated by it. Notably, enhancement of H2S expression in the heart was observed in mice injected with recombinant adeno-associated virus vector 9 (rAAV9)-anti-miR-27a and in cells transfected with a miR-27a inhibitor during cardiac hypertrophy. However, this effect was abolished by co-transfection with CSE siRNA and the miR-27a inhibitor. Conversely, injecting rAAV9-miR-27a yielded opposite results. Interestingly, our findings demonstrated that glucagon-like peptide-1 (GLP-1) agonists could mitigate myocardial damage by down-regulating miR-27a and up-regulating CSE. In summary, our study suggests that inhibition of miR-27a holds therapeutic promise for the treatment of cardiac hypertrophy by increasing H2S levels. Furthermore, our findings unveil a novel mechanism of GLP-1 agonists involving the miR-27a/H2S pathway in the management of cardiac hypertrophy.


Assuntos
Estenose da Valva Aórtica , Insuficiência Cardíaca , MicroRNAs , Animais , Camundongos , Cardiomegalia/genética , Peptídeo 1 Semelhante ao Glucagon , MicroRNAs/genética , Cistationina gama-Liase
2.
J Neurophysiol ; 130(5): 1174-1182, 2023 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-37702542

RESUMO

Alzheimer's disease (AD) is a neurodegenerative disorder with insidious onset and progressive development. There is an urgent need to find drugs that prevent and slow AD progression. We focus our attention on 3,6'-disinapoyl sucrose (DISS), an oligosaccharide with antidepressant and antioxidant activities. In this work, APP/PS1 transgenic mice were used to explore the neuroprotective impact of DISS to provide new applications for prevention and therapy of AD. This study aims to assess DISS's neuroprotective impact on learning and memory deficits in APP/PS1 transgenic mice using behavioral tests (Morris water maze, novel object recognition test, and passive avoidance test). Morphological alterations of hippocampus neurons were observed by Nissl staining and neuronal apoptosis was assessed by TUNEL assay. By using ELISA, the expressions of inflammatory factors were evaluated, and Western blotting was used to measure the protein expressions of neuron-related regulators in the hippocampus. DISS significantly ameliorated the cognitive disorder in APP/PS1 transgenic mice, reduced apoptosis by decreasing the ratio of Bax/B-cell lymphoma/leukemia-2 (Bcl-2) in hippocampal neurons, and restored the abnormal secretion of inflammatory factors (IL-2, TNF-α, IL-1ß, and IL-6). Moreover, the gavage of high-dose DISS can boost the expressions of CREB/brain-derived neurotrophic factor (BDNF). Overall, our results indicate that DISS improves cognitive function in APP/PS1 transgenic mice by inhibiting neural apoptosis and activating the CREB/BDNF signal pathway.NEW & NOTEWORTHY In this study, for the first time, DISS was used in APP/PS1 transgenic mice to explore its neuroprotective effect. After gavage DISS for 1 mo, the impairment of learning and spatial memory ability and the loss of neurons in APP/PS1 mice were alleviated. DISS reduced a neuroprotective effect in AD mice via decreasing neuronal apoptosis, enhancing the expressions of CREB phosphorylation and BDNF, pointing to DISS as a new therapeutic target for AD.


Assuntos
Doença de Alzheimer , Disfunção Cognitiva , Fármacos Neuroprotetores , Camundongos , Animais , Camundongos Transgênicos , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Fármacos Neuroprotetores/farmacologia , Sacarose/farmacologia , Sacarose/uso terapêutico , Doença de Alzheimer/tratamento farmacológico , Doença de Alzheimer/metabolismo , Disfunção Cognitiva/tratamento farmacológico , Cognição , Modelos Animais de Doenças , Aprendizagem em Labirinto
3.
Small ; 19(32): e2300341, 2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-37029564

RESUMO

With the rapid development of nanotechnology and nanomedicine, there are great interests in employing nanomaterials to improve the efficiency of disease diagnosis and treatment. The clinical translation of hafnium oxide (HfO2 ), commercially namedas NBTXR3, as a new kind of nanoradiosensitizer for radiotherapy (RT) of cancers has aroused extensive interest in researches on Hf-based nanomaterials for biomedical application. In the past 20 years, Hf-based nanomaterials have emerged as potential and important nanomedicine for computed tomography (CT)-involved bioimaging and RT-associated cancer treatment due to their excellent electronic structures and intrinsic physiochemical properties. In this review, a bibliometric analysis method is employed to summarize the progress on the synthesis technology of various Hf-based nanomaterials, including HfO2 , HfO2 -based compounds, and Hf-organic ligand coordination hybrids, such as metal-organic frameworks or nanoscaled coordination polymers. Moreover, current states in the application of Hf-based CT-involved contrasts for tissue imaging or cancer diagnosis are reviewed in detail. Importantly, the recent advances in Hf-based nanomaterials-mediated radiosensitization and synergistic RT with other current mainstream treatments are also generalized. Finally, current challenges and future perspectives of Hf-based nanomaterials with a view to maximize their great potential in the research of translational medicine are also discussed.


Assuntos
Antineoplásicos , Nanoestruturas , Neoplasias , Humanos , Háfnio/química , Nanoestruturas/química , Neoplasias/diagnóstico por imagem , Neoplasias/terapia , Nanotecnologia/métodos
4.
J Asian Nat Prod Res ; 25(4): 387-402, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35672874

RESUMO

The aim of this study is to explore the effect and mechanism of 3,6'-disinapoylsucrose (DISS) on an Alzheimer's disease (AD) mice model induced by APPswe695 lentivirus (LV) and intraperitoneal injection of lipopolysaccharide (LPS). The results show that DISS improves cognitive ability, decreases the levels of IL-2, IL-6, IL-1ß, and TNF-α, reduces the expression of NF-κB p65, and alleviates Aß deposition and nerve cell damage. DISS can regulate tyrosine kinase B (TrkB)/brain-derived neurotrophic factor (BDNF) signaling in the hippocampus. In summary, DISS can significantly alleviate neuroinflammation, spatial learning and memory disorders in AD model mice.


Assuntos
Doença de Alzheimer , Disfunção Cognitiva , Camundongos , Animais , Proteínas Tirosina Quinases/metabolismo , Proteínas Tirosina Quinases/farmacologia , Precursor de Proteína beta-Amiloide/metabolismo , Precursor de Proteína beta-Amiloide/farmacologia , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Fator Neurotrófico Derivado do Encéfalo/farmacologia , Lipopolissacarídeos/farmacologia , Regulação para Cima , Disfunção Cognitiva/metabolismo , Doença de Alzheimer/metabolismo , Hipocampo/metabolismo , Peptídeos beta-Amiloides/metabolismo
5.
J Environ Manage ; 326(Pt A): 116841, 2023 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-36436439

RESUMO

Mesoporous carbon material (MCM) with rich ether surface group was prepared from sewage sludge hydrochar using Pluronic F127 as template under pyrolysis activation, which provided an energy-efficient method to promote the resource utilization of sewage sludge as adsorbents for phenols removal from water. The MCM possessed high surface area (549 m2/g), abundant mesopores (average width 3.81 nm) and well-developed graphite structure. Acidic conditions and low temperatures favored the adsorption of phenolic compounds. The quick adsorption process of reaching over 85% of the capacity in the first 10 min and intraparticle diffusion as primary rate-limiting step were observed for all phenolic compounds. Advanced statistical physics analysis was used successfully to interpret the adsorption mechanism of phenols onto MCM and revealed a multi-molecular monolayer adsorption process primarily through negative charge-assisted hydrogen bond interaction where the ether functional group contributed to the predominant active sites. The adsorption capacity of phenolic compounds depended upon the number of molecules adsorbed per ether active site and the available density of ether bond group on the surface of MCM. 2,4,6-trichlorophenol showed a highest adsorption priority to occupy the limited ether active sites and its adsorption capacity reached 0.49 mmol/g, while p-nitrophenol exhibited a maximum number of molecules adsorbed on the single ether active site, showing an adsorption capacity of 0.42 mmol/g. The synergistic effect of multi-interactions mechanisms resulted in phenolic compounds removal with adsorption energies lower than 30 kJ/mol. This prepared MCM adsorbent is promising for application in treatment of water polluted by phenols.


Assuntos
Carbono , Esgotos , Poloxâmero , Fenóis , Física , Éteres , Etil-Éteres , Água
6.
Appl Environ Microbiol ; 88(17): e0104622, 2022 09 13.
Artigo em Inglês | MEDLINE | ID: mdl-36000858

RESUMO

Exploring the potential functions of nonconserved residues on the outer side of α-helices and systematically optimizing them are pivotal for their application in protein engineering. Based on the evolutionary structural conservation analysis of GH5_5 cellulases, a practical molecular improvement strategy was developed. Highly variable sites on the outer side of the α-helices of the GH5_5 cellulase from Aspergillus niger (AnCel5A) were screened, and 14 out of the 34 highly variable sites were confirmed to exert a positive effect on the activity. After the modular combination of the positive mutations, the catalytic efficiency of the mutants was further improved. By using CMC-Na as the substrate, the catalytic efficiency and specific activity of variant AnCel5A_N193A/T300P/D307P were approximately 2.0-fold that of AnCel5A (227 ± 21 versus 451 ± 43 ml/s/mg and 1,726 ± 19 versus 3,472 ± 42 U/mg, respectively). The half-life (t1/2) of variant AnCel5A_N193A/T300P/D307P at 75°C was 2.36 times that of AnCel5A. The role of these sites was successfully validated in other GH5_5 cellulases. Computational analyses revealed that the flexibility of the loop 6-loop 7-loop 8 region was responsible for the increased catalytic performance. This work not only illustrated the important role of rapidly evolving positions on the outer side of the α-helices of GH5_5 cellulases but also revealed new insights into engineering the proteins that nature left as clues for us to find. IMPORTANCE A comprehensive understanding of the residues on the α-helices of the GH5_5 cellulases is important for catalytic efficiency and stability improvement. The main objective of this study was to use the evolutionary conservation and plasticity of the TIM-barrel fold to probe the relationship between nonconserved residues on the outer side of the α-helices and the catalytic efficiency of GH5_5 cellulases by conducting structure-guided protein engineering. By using a four-step nonconserved residue screening strategy, the functional role of nonconserved residues on the outer side of the α-helices was effectively identified, and a variant with superior performance and capability was constructed. Hence, this study proved the effectiveness of this strategy in engineering GH5_5 cellulases and provided a potential competitor for industrial applications. Furthermore, this study sheds new light on engineering TIM-barrel proteins.


Assuntos
Celulase , Celulases , Aspergillus niger/genética , Aspergillus niger/metabolismo , Catálise , Celulase/metabolismo , Celulases/metabolismo , Mutação
7.
J Am Chem Soc ; 143(4): 1846-1853, 2021 02 03.
Artigo em Inglês | MEDLINE | ID: mdl-33397097

RESUMO

Hypoxia is a common phenomenon among most solid tumors that significantly influences tumor response toward chemo- and radiotherapy. Understanding the distribution and extent of tumor hypoxia in patients will be very important to provide personalized therapies in the clinic. Without sufficient vessels, however, traditional contrast agents for clinical imaging techniques will have difficulty in accumulating in the hypoxic region of solid tumors, thus challenging the detection of hypoxia in vivo. To overcome this problem, herein we develop a novel hypoxia imaging probe, consisting of a hypoxia-triggered self-assembling ultrasmall iron oxide (UIO) nanoparticle and assembly-responding fluorescence dyes (NBD), to provide dual-mode imaging in vivo. In this strategy, we have employed nitroimidazole derivatives as the hypoxia-sensitive moiety to construct intermolecular cross-linking of UIO nanoparticles under hypoxia, which irreversibly form larger nanoparticle assemblies. The hypoxia-triggered performance of UIO self-assembly not only amplifies its T2-weighted MRI signal but also promotes the fluorescence intensity of NBD through its emerging hydrophobic environment incorporated into self-assemblies. In vivo results further confirm that our hypoxic imaging probe can display a prompt MRI signal for the tumor interior region, and its signal enhancement performs a long-term effective feature and gradually reaches 3.69 times amplification. Simultaneously, this probe also exhibits obvious green fluorescence in the hypoxic region of tumor sections. Accordingly, we also have developed a MRI difference value method to visualize the 3D distribution and describe the extent of the hypoxic tumor region within the whole bodies of mice. Due to its notable efficiency of penetration and accumulation inside a hypoxic tumor, our hypoxia imaging probe could also be considered as a potential candidate as a versatile platform for hypoxia-targeted drug delivery, and meanwhile its hypoxia-related therapeutic efficacy can be monitored.


Assuntos
Nanopartículas Magnéticas de Óxido de Ferro/química , Neoplasias/diagnóstico por imagem , Hipóxia Tumoral , Fluorescência , Humanos , Ligantes , Imageamento por Ressonância Magnética , Nanomedicina Teranóstica
8.
Biochem Biophys Res Commun ; 565: 21-28, 2021 08 06.
Artigo em Inglês | MEDLINE | ID: mdl-34090206

RESUMO

Preoperative anxiety is common and often comes with a higher probability of worse recovery. However, the neurological mechanism of the effect of preoperative anxiety on general anesthesia and subsequent awakening remains unknown. In this study, we report an anxious state results in delayed awakening in anxiety model mice from sevoflurane general anesthesia. More profound inhibition of DA neurons in the VTA contributes to delayed awakening. Optogenetic stimulation of VTA DA neurons can reverse the delay. The results indicate that VTA DA neurons may be involved in the delay in awakening from general anesthesia caused by anxiety.


Assuntos
Anestésicos Inalatórios/farmacologia , Ansiedade/tratamento farmacológico , Neurônios Dopaminérgicos/efeitos dos fármacos , Sevoflurano/farmacologia , Área Tegmentar Ventral/efeitos dos fármacos , Animais , Feminino , Camundongos , Camundongos Endogâmicos C57BL
9.
Molecules ; 27(1)2021 Dec 25.
Artigo em Inglês | MEDLINE | ID: mdl-35011346

RESUMO

Alzheimer's disease (AD) is a degenerative disease of the central nervous system characterized by the progressive impairment of neural activity. Studies have shown that 3,6'-disinapoyl sucrose (DISS) can alleviate the pathological symptoms of AD through the activation of the cAMP/CREB/BDNF signaling pathway. However, the exact biochemical mechanisms of action of DISS are not clear. This study explores metabolism of DISS in an AD mouse model, induced by the microinjection of a lentiviral expression plasmid of the APPswe695 gene into CA1 of the hippocampus. After gavage administration of DISS (200 mg/kg), the kidneys, livers, brains, plasma, urine, and feces were collected for UHPLC-Orbitrap mass spectrometry analysis. Twenty metabolites, including the prototype drug of DISS, were positively or tentatively identified based on accurate mass measurements, characteristic fragmentation behaviors, and retention times. Thus, the metabolic pathways of DISS in AD mice were preliminarily elucidated through the identification of metabolites, such as ester bond cleavage, demethoxylation, demethylation, and sinapic acid-related products. Furthermore, differences in the in vivo distribution of several metabolites were observed between the model and sham control groups. These findings can provide a valuable reference for the pharmacological mechanisms and biosafety of DISS.


Assuntos
Doença de Alzheimer , Região CA1 Hipocampal/metabolismo , Ácidos Cumáricos , Sacarose/análogos & derivados , Doença de Alzheimer/tratamento farmacológico , Doença de Alzheimer/metabolismo , Animais , Cromatografia Líquida de Alta Pressão , Ácidos Cumáricos/farmacocinética , Ácidos Cumáricos/farmacologia , Modelos Animais de Doenças , Masculino , Espectrometria de Massas , Camundongos , Camundongos Endogâmicos ICR , Sacarose/farmacocinética , Sacarose/farmacologia
10.
Prep Biochem Biotechnol ; 51(9): 842-851, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-32795109

RESUMO

Cr(VI) is one of the most common environmental pollutants. The non-biodegradable Cr(VI) in aqueous solution accumulates along the food chain and damages the health of plant, animal, and human. In this study, solid-state fermentation technology was used to treat Caulis lonicerae residue to improve its adsorption capacity for Cr(VI). Caulis lonicerae can be used to extract the active ingredients such as organic acids, flavonoids, and triterpenoid saponins that have various effects including anti-oxidation and immune boosting. However, there is no proper treatment for large amount of residue left after extraction. The Phanerochaete chrysosporium was inoculated into the residue for solid-state fermentation, and the adsorption capacity of C. lonicerae residue before (CLr) and after fermentation (FCLr) regarding Cr(VI) adsorption was compared. In the range of 40-120 mg/L Cr(VI), the adsorption capacity of FCLr was significantly higher than that of CLr. The scanning electron microscopy (SEM) results exhibited a rougher surface of FCLr. The Fourier-transform infrared spectroscopy (FTIR) results revealed that the structure of FCLr was affected by the combination of Cr(VI), and the multiple functional groups interacted with Cr(VI) (such as -OH, C-H, C = O, C-O-C, and C-O). The adsorption capacity could reach 48.91 mg/g and the Cr(VI) removal percentage may reach 98.07% for FCLr increased by 28.24% through fermentation.


Assuntos
Cromo/metabolismo , Lonicera/química , Phanerochaete/crescimento & desenvolvimento , Poluentes Químicos da Água/metabolismo
11.
Molecules ; 26(9)2021 May 08.
Artigo em Inglês | MEDLINE | ID: mdl-34066799

RESUMO

Honey has good antimicrobial properties and can be used for medical treatment. The antimicrobial properties of unifloral honey varieties are different. In this study, we evaluated the antimicrobial and antioxidant activities of nine kinds of Chinese monofloral honeys. In addition, headspace gas chromatography-ion mobility spectrometry (HS-GC-IMS) technology was used to detect their volatile components. The relevant results are as follows: 1. The agar diffusion test showed that the diameter of inhibition zone against Staphylococcus aureus of Fennel honey (21.50 ± 0.41 mm), Agastache honey (20.74 ± 0.37 mm), and Pomegranate honey (18.16 ± 0.11 mm) was larger than that of Manuka 12+ honey (14.27 ± 0.10 mm) and Manuka 20+ honey (16.52 ± 0.12 mm). The antimicrobial activity of Chinese honey depends on hydrogen peroxide. 2. The total antioxidant capacity of Fennel honey, Agastache honey, and Pomegranate honey was higher than that of other Chinese honeys. There was a significant positive correlation between the total antioxidant capacity and the total phenol content of Chinese honey (r = 0.958). The correlation coefficient between the chroma value of Chinese honey and the total antioxidant and the diameter of inhibition zone was 0.940 and 0.746, respectively. The analyzed dark honeys had better antimicrobial and antioxidant activities. 3. There were significant differences in volatile components among Fennel honey, Agastache honey, Pomegranate honey, and Manuka honey. Hexanal-D and Heptanol were the characteristic components of Fennel honey and Pomegranate honey, respectively. Ethyl 2-methylbutyrate and 3-methylpentanoic acids were the unique compounds of Agastache honey. The flavor fingerprints of the honey samples from different plants can be successfully built using HS-GC-IMS and principal component analysis (PCA) based on their volatile compounds. Fennel honey, Agastache honey, and Pomegranate honey are Chinese honey varieties with excellent antimicrobial properties, and have the potential to be developed into medical grade honey.


Assuntos
Antibacterianos/farmacologia , Antioxidantes/farmacologia , Mel/análise , Mel/classificação , Staphylococcus aureus/efeitos dos fármacos , Agastache/química , Antibacterianos/química , Antioxidantes/química , China , Cromatografia Gasosa , Foeniculum/química , Peróxido de Hidrogênio/farmacologia , Espectrometria de Mobilidade Iônica , Leptospermum/química , Testes de Sensibilidade Microbiana , Fenóis/farmacologia , Punica granatum/química
12.
AAPS PharmSciTech ; 22(3): 132, 2021 Apr 13.
Artigo em Inglês | MEDLINE | ID: mdl-33851275

RESUMO

The main objective of this study was to develop an in vivo predictive dissolution (IVPD) model for topiroxostat immediate-release (IR) formulation by the combination of mechanistic absorption model (MAM) deconvolution method with time shifting factor (TSF) adjustment. The in vitro dissolution profiles in different biorelevant dissolution media containing different concentrations of sodium lauryl sulfate (SLS) were obtained from dissolution testing with the paddle method of the US Pharmacopeia, while the human pharmacokinetic profile was taken from the published experimental results. The GastroPlus™ software was used to observe the linear relationship between in vitro drug dissolution and in vivo absorption. The pharmacokinetic profile of topiroxostat IR tablet was first deconvoluted through the MAM method to obtain the fraction absorbed in vivo. Next, Levy plot was constructed to estimate the TSF, and the time scale for both processes of dissolution and absorption was then adjusted to be superimposable. The IVPD modelling was subsequently established with data between in vitro dissolution profiles and fraction absorbed in vivo. Finally, the dissolution profiles of topiroxostat IR tablet were translated into a pharmacokinetic curve in terms of convolution method. The comparison between translated and observed pharmacokinetic data will validate the performance of the developed IVPD model. This new linear IVPD model with high predictive power for the tablet can predict the in vivo pharmacokinetic differences through in vitro dissolution data, and it can be utilized as a risk-control tool for the formulation development of the topiroxostat IR tablet and the quality control of product batches.


Assuntos
Simulação por Computador , Modelos Biológicos , Nitrilas/química , Nitrilas/farmacocinética , Piridinas/química , Piridinas/farmacocinética , Adulto , Liberação Controlada de Fármacos/fisiologia , Inibidores Enzimáticos/química , Inibidores Enzimáticos/farmacocinética , Feminino , Previsões , Humanos , Modelos Lineares , Masculino , Pessoa de Meia-Idade , Comprimidos , Adulto Jovem
13.
Zhongguo Zhong Yao Za Zhi ; 46(24): 6465-6473, 2021 Dec.
Artigo em Zh | MEDLINE | ID: mdl-34994139

RESUMO

In this study, the molecular mechanism of astragaloside Ⅳ(AS-Ⅳ) in the treatment of Parkinson's disease(PD) was explored based on network pharmacology, and the potential value of AS-Ⅳ in alleviating neuronal injury in PD by activating the PI3 K/AKT signaling pathway was verified through molecular docking and in vitro experiments. Such databases as SwissTargetPrediction, BTMAN-TAM, and GeneCards were used to predict the targets of AS-Ⅳ for the treatment of PD. The Search Tool for the Retrieval of Interacting Genes/Proteins(STRING) was employed to analyze protein-protein interaction(PPI) and construct a PPI network, and the Database for Annotation, Visualization and Integrated Discovery(DAVID) was used for Gene Ontology(GO) term enrichment and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment analysis. Based on the results of GO enrichment analysis and KEGG pathway analysis, the PI3 K/AKT signaling pathway was selected for further molecular docking and in vitro experiments in this study. The in vitro cell model of PD was established by MPP~+. The cell viability was measured by MTT assay and effect of AS-Ⅳ on the expression of the PI3 K/AKT signaling pathway-related genes and proteins by real-time polymerase chain reaction(RT-PCR) and Western blot. Network pharmacology revealed totally 122 targets of AS-Ⅳ for the treatment of PD, and GO enrichment analysis yielded 504 GO terms, most of which were biological processes and molecular functions. Totally 20 related signaling pathways were screened out by KEGG pathway analysis, including neuroactive ligand-receptor interaction, PI3 K/AKT signaling pathway, GABAergic synapse, and calcium signaling pathway. Molecular docking demonstrated high affinity of AS-Ⅳ to serine/threonine-protein kinases(AKT1, AKT2), phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit gamma(PIK3 CG), and phosphoinositide-3-kinase, catalytic, alpha polypeptide(PIK3 CA) on the PI3 K/AKT signaling pathway. In vitro experiments showed that AS-Ⅳ could effectively inhibit the decrease of the viability of PC12 induced by MPP~+ and up-regulate the mRNA expression levels of AKT1 and PI3 K as well as the phosphorylation levels of AKT and PI3 K. As an active component of Astragali Radix, AS-Ⅳ acts on PD through multiple targets and pathways. Furthermore, it inhibits neuronal apoptosis and protects neurons by activating the PI3 K/AKT signaling pathway, thereby providing reliable theoretical and experimental supports for the treatment of PD with AS-Ⅳ.


Assuntos
Medicamentos de Ervas Chinesas , Fosfatidilinositol 3-Quinases , Animais , Medicamentos de Ervas Chinesas/farmacologia , Simulação de Acoplamento Molecular , Farmacologia em Rede , Células PC12 , Fosfatidilinositol 3-Quinases/genética , Proteínas Proto-Oncogênicas c-akt/genética , Ratos , Saponinas , Transdução de Sinais , Triterpenos
14.
Curr Genomics ; 20(1): 61-68, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31015792

RESUMO

BACKGROUND: Hepatitis B Viral (HBV) infection is one of the major causes of Hepatocellular Carcinoma (HCC). Mounting evidence had provided that the HBV integration might be a critical con-tributor of HCC carcinogenesis. OBJECTIVE AND METHODS: To explore the profile of HBV integration in the plasma DNA, the method of next-generation sequencing, HBV capture and bioinformatics had been employed to screen for HBV in-tegration sites in the plasma samples. RESULTS: In the initial experiment, a total of 87 breakpoints were detected in the 20 plasma samples. The distribution of breakpoints showed that there was significant enrichment of breakpoints in the region of intron. Furthermore, the HBV breakpoints were prone to occur in the region of X protein (1,700-2,000bp) in the plasma samples. The pathway analysis had revealed that the HBV integrations sites were specifically enriched in the cancer pathway. CONCLUSION: Altogether, our results had provided direct evidence for the HBV integration in plasma DNA, and they might be potentially useful for future HCC prognosis and diagnosis.

15.
Molecules ; 24(2)2019 Jan 14.
Artigo em Inglês | MEDLINE | ID: mdl-30646615

RESUMO

In Asia, honey is mainly produced by Apis mellifera and Apis cerana. However, the price of A. cerana honey is usually much higher than A. mellifera honey. Seeing considerable profits, some dishonest companies and beekeepers mislabel A. mellifera honey as A. cerana honey or incorporate A. mellifera honey into A. cerana honey. In the present study, we developed methods to discriminate A. cerana honey from A. mellifera honey based on the MRJP2 (major royal jelly protein 2) gene. Two pairs of species-specific primers were designed. The amplification products of A. cerana and A. mellifera were 212 and 560 bp, respectively. As little as one percent incorporation of A. mellifera honey in the mixture can be detected by duplex PCR. Additionally, another method based on the melt curve analysis using the same primers was also developed, allowing a rapid discrimination of real-time PCR product of different species. Our study shows that the entomological authentication of honey samples can be identified by nuclear genes other than mitochondrial genes and this extends the possibility of gene selection in identification. The authentication system we proposed could be a useful tool for discriminating A. cerana honey from A. mellifera honey.


Assuntos
Abelhas/genética , Mel/análise , Mel/normas , Proteínas de Insetos/genética , Animais , Valor Nutritivo , Reação em Cadeia da Polimerase , Especificidade da Espécie
16.
Pak J Pharm Sci ; 31(4(Special)): 1633-1638, 2018 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-30203751

RESUMO

In order to conceal the unpleasant smell of pharmaceutical raw materials of Penicillin V potassium, we use ß-cyclodextrin (ß-CD) as a drug carrier. The Penicillin V potassium ß-CD inclusion complex was prepared by saturated aqueous solution method; the characterization of penicillin V potassium ß-CD inclusion complex is determined by scanning electron microscopy, Differential Scanning Calorimeter (DSC) and X-ray Diffraction (XRD), the formation constants of the complexes were determined by UV spectrophotometry; based on the results obtained from the orthogonal experimental design, the optimum preparation process are summarized as follow: ß-CD: Penicillin V potassium = 4: 1 (molar ratio), stirring temperature 50 centigrade, stirring time 12h, the encapsulation efficiency is 29.40%.


Assuntos
Cristalização/métodos , Portadores de Fármacos/química , Penicilina V/química , beta-Ciclodextrinas/química , Temperatura , Fatores de Tempo
17.
PLoS Pathog ; 10(7): e1004261, 2014 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-25079600

RESUMO

Israeli acute paralysis virus (IAPV) is a widespread RNA virus of honey bees that has been linked with colony losses. Here we describe the transmission, prevalence, and genetic traits of this virus, along with host transcriptional responses to infections. Further, we present RNAi-based strategies for limiting an important mechanism used by IAPV to subvert host defenses. Our study shows that IAPV is established as a persistent infection in honey bee populations, likely enabled by both horizontal and vertical transmission pathways. The phenotypic differences in pathology among different strains of IAPV found globally may be due to high levels of standing genetic variation. Microarray profiles of host responses to IAPV infection revealed that mitochondrial function is the most significantly affected biological process, suggesting that viral infection causes significant disturbance in energy-related host processes. The expression of genes involved in immune pathways in adult bees indicates that IAPV infection triggers active immune responses. The evidence that silencing an IAPV-encoded putative suppressor of RNAi reduces IAPV replication suggests a functional assignment for a particular genomic region of IAPV and closely related viruses from the Family Dicistroviridae, and indicates a novel therapeutic strategy for limiting multiple honey bee viruses simultaneously and reducing colony losses due to viral diseases. We believe that the knowledge and insights gained from this study will provide a new platform for continuing studies of the IAPV-host interactions and have positive implications for disease management that will lead to mitigation of escalating honey bee colony losses worldwide.


Assuntos
Abelhas/virologia , Colapso da Colônia/epidemiologia , Dicistroviridae/patogenicidade , Viroses/epidemiologia , Viroses/patologia , Animais , Biomarcadores/metabolismo , Colapso da Colônia/genética , Colapso da Colônia/virologia , Dicistroviridae/genética , Perfilação da Expressão Gênica , Genoma Viral , Interações Hospedeiro-Patógeno , Hibridização In Situ , Análise de Sequência com Séries de Oligonucleotídeos , RNA Mensageiro/genética , RNA Interferente Pequeno/genética , RNA Viral/genética , Reação em Cadeia da Polimerase em Tempo Real , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Proteínas Virais/antagonistas & inibidores , Proteínas Virais/genética , Proteínas Virais/metabolismo , Viroses/genética , Viroses/virologia
18.
Appl Environ Microbiol ; 82(8): 2256-62, 2016 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-26801569

RESUMO

Sacbrood virus(SBV) is one of the most destructive viruses in the Asian honeybee Apis cerana but is much less destructive in Apis mellifera In previous studies, SBV isolates infecting A. cerana(AcSBV) and SBV isolates infecting A. mellifera(AmSBV) were identified as different serotypes, suggesting a species barrier in SBV infection. In order to investigate this species isolation, we examined the presence of SBV infection in 318A. mellifera colonies and 64A. cerana colonies, and we identified the genotypes of SBV isolates. We also performed artificial infection experiments under both laboratory and field conditions. The results showed that 38A. mellifera colonies and 37A. cerana colonies were positive for SBV infection. Phylogenetic analysis based on RNA-dependent RNA polymerase (RdRp) gene sequences indicated that A. cerana isolates and most A. mellifera isolates formed two distinct clades but two strains isolated fromA. mellifera were clustered with theA. cerana isolates. In the artificial-infection experiments, AcSBV negative-strand RNA could be detected in both adult bees and larvae ofA. mellifera, although there were no obvious signs of the disease, demonstrating the replication of AcSBV inA. mellifera Our results suggest that AcSBV is able to infectA. melliferacolonies with low prevalence (0.63% in this study) and pathogenicity. This work will help explain the different susceptibilities ofA. cerana and A. melliferato sacbrood disease and is potentially useful for guiding beekeeping practices.


Assuntos
Abelhas/virologia , Genótipo , Vírus de RNA/classificação , Vírus de RNA/isolamento & purificação , Animais , Análise por Conglomerados , Filogenia , Vírus de RNA/genética , RNA Polimerase Dependente de RNA/genética , Análise de Sequência de DNA
19.
Int J Syst Evol Microbiol ; 66(2): 1088-1094, 2016 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-26652178

RESUMO

A novel haloalkalitolerant, rod-shaped bacterium, designated strain YIM 4-4T, was isolated from the surface water of the Dugerno lake, a haloalkaline lake in Inner Mongolia. The taxonomy of strain YIM 4-4T was investigated by a polyphasic approach. Strain YIM 4-4T was Gram-stain-negative, strictly aerobic, non-motile and formed red colonies. Optimal growth conditions were 28 °C, pH 8.0-11.0 and 0.5-2 % NaCl. The major respiratory quinone was menaquinone-7 (MK-7). The polar lipid profile was composed predominantly of phosphatidylethanolamine, six unidentified polar lipids, one phospholipid and one aminolipid. The predominant cellular fatty acids (>5 %) were iso-C15 : 0, iso-C17 : 1I/anteiso-C17 : 1B, iso-C16 : 1G, iso-C17 : 0 3-OH, C16 : 1ω7c/C16 : 1ω6c and iso-C16 : 1. The genomic DNA G+C content was 43.0 mol%. 16S rRNA gene sequence analysis indicated that the members of the genera Cecembia, Fontibacter, Aquiflexum and Indibacter of the family Cyclobacteriaceae (phylum Bacteroidetes) were the most closely related, with 16S rRNA gene sequence similarities ranging from 93.6 to 94.2 %. Other members of the family Cyclobacteriaceae showed sequence similarities < 93.0 %. On the basis of phenotypic, chemotaxonomic and phylogenetic properties, strain YIM 4-4T represents a novel species of a new genus, for which the name Mongoliibacter ruber gen. nov., sp. nov. is proposed. The type strain is YIM 4-4T ( = CCTCC AB 2012966T = DSM 27929T).

20.
Appl Microbiol Biotechnol ; 100(15): 6927-6934, 2016 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-27260287

RESUMO

In order to study the role of sufficient phosphorus (P) in biodiesel production by microalgae, Phaeodactylum tricornutum were cultivated in six different media treatments with combination of nitrogen (N) sufficiency/deprivation and phosphorus sufficiency/limitation/deprivation. Profiles of N and P, biomass, and fatty acids (FAs) content and compositions were measured during a 7-day cultivation period. The results showed that the FA content in microalgae biomass was promoted by P deprivation. However, statistical analysis showed that FA productivity had no significant difference (p = 0.63, >0.05) under the treatments of N deprivation with P sufficiency (N-P) and N deprivation with P deprivation (N-P-), indicating P sufficiency in N deprivation medium has little effect on increasing biodiesel productivity from P. triornutum. It was also found that the P absorption in N-P medium was 1.41 times higher than that in N sufficiency and P sufficiency (NP) medium. N deprivation with P limitation (N-P-l) was the optimal treatment for producing biodiesel from P. triornutum because of both the highest FA productivity and good biodiesel quality.


Assuntos
Biocombustíveis/análise , Diatomáceas/metabolismo , Ácidos Graxos/metabolismo , Microalgas/metabolismo , Nitrogênio/análise , Fósforo/análise , Biomassa , Ácidos Graxos/análise , Análise de Componente Principal
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