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1.
J Food Sci ; 2019 Nov 21.
Artigo em Inglês | MEDLINE | ID: mdl-31750940

RESUMO

Aroma assessment remains difficult and uncertain in the present sensory assessment system. It is highly desirable to develop a new assessment method to discriminate the quality of various teas in the tea market. In the present work, based on linear discriminant analysis and principal component analysis, the aroma of dry and wet samples of different Xi-hu Longjing and Pu-erh teas were tested and differentiated by electronic noses (e-nose). The results confirm that e-nose can discriminate different priced Xi-hu Longjing tea samples in the range of 80-800 RMB/500 g and varying storage years of Pu-erh tea samples. Furthermore, for the detection of both dry and wet samples of Longjing and Pu-erh teas, the results reveal that all samples have specific aroma characteristics that e-nose can recognize. More importantly, contribution analysis in sensors indicates that nitrogen oxides, methane and alcohols are the characteristic components that contribute to the fragrances of different priced Xi-hu Longjing teas, while nitrogen oxides, aromatic benzene and amines make the fragrances of Pu-erh teas with different storage years disparate. PRACTICAL APPLICATION: This work demonstrates that e-nose can rapidly distinguish tea products with different price levels and varying storage years. With the advantages of ease of use, high portability and flexibility, e-nose will be widely expanded and applied in refined processing and the development of flavored foods.

2.
Oncol Rep ; 2019 Oct 30.
Artigo em Inglês | MEDLINE | ID: mdl-31746412

RESUMO

The present study aimed to assess the performance of positron emission tomography­magnetic resonance imaging (PET/MR) for the visualization and characterization of lesions. In addition, the present study investigated whether the apparent diffusion coefficient (ADC) and intravoxel incoherent motion parameters exhibited any significant correlation with standardized uptake values (SUV) in patients with nasopharyngeal carcinoma (NPC). A total of 35 patients with NPC underwent whole body PET­computed tomography (CT) and head and neck MR imaging (MRI) scans using the PET/CT­MRI system. Image quality, lesion conspicuity and the diagnostic confidence of PET/CT, T1 weighted (T1w) PET/MR and T2w PET/MR imaging were assessed. The true diffusion coefficient (D), the pseudo­diffusion coefficient or diffusion within the microcirculation (D*), and the perfusion fraction or the contribution of water moving in the capillaries (f), and ADC, were calculated. The correlation between the ADC, D*, D and f values and the SUV were analyzed using Pearson's correlation analysis. Similar image quality was obtained using PET/CT, T1w PET/MR and T2w PET/MR imaging. However, the T1w PET/MR and T2w PET/MR imaging were more effective than PET/CT in analyzing the lesion conspicuity of the primary tumors and lymph nodes. In addition, T2w PET/MR imaging was more efficient than T1w PET/MR imaging in analyzing primary tumors and lymph nodes. Pearson's correlation analysis showed no significant correlation between the SUV and ADC, and D*, D and f values in NPC. The present results suggested that the application of PET/MR is feasible and could serve as a reliable alternative to PET/CT, while SUV and ADC, D*, D and f values were identified as independent biomarkers in NPC.

3.
Nat Prod Res ; : 1-7, 2019 Nov 19.
Artigo em Inglês | MEDLINE | ID: mdl-31741407

RESUMO

Two new mertoterpenoids, australins A (1) and B (2), and a new alkaloid, australine (4), together with five known compounds (3, 5-8) were isolated from the fruiting bodies of Ganoderma australe. Their structures including absolute configurations were assigned by using spectroscopic methods and electronic circular dichroism (ECD) calculations. Racemic australin A was further purified by chiral HPLC. Biological assessments reveal that compounds (+)-1 and 7 could significantly protect SH-SY5Y cells from glutamate-induced neural excitotoxicity.

4.
Nucl Med Commun ; 2019 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-31764594

RESUMO

OBJECTIVES: To evaluate the utility of sequential F-18 fluorodeoxyglucose PET/diffusion-weighted imaging in assessing myocardial perfusion and viability in coronary artery disease. METHODS: Fourteen coronary artery disease patients and five non-coronary artery disease subjects underwent sequential cardiac F-18 fluorodeoxyglucose PET/diffusion-weighted imaging using a trimodality PET/computed tomography-MRI system. The perfusion data were acquired by measuring low b-values apparent diffusion coefficient using diffusion-weighted imaging. Regional myocardial viability was determined by perfusion/metabolism patterns. The perfusion/metabolism patterns obtained by low b-values apparent diffusion coefficient/fluorodeoxyglucose uptake were analyzed and compared with the results from the combination of rest methoxyisobutylisonitrile (Tc-MIBI) myocardial perfusion single-photon emission computed tomography with F-18 fluorodeoxyglucose PET/computed tomography. RESULTS: Ten coronary artery disease patients and five non-coronary artery disease subjects were included in the final analysis. Low b-values apparent diffusion coefficient defects involved with 25 myocardial regions were demonstrated in nine coronary artery disease patients, while Tc-MIBI defects involved with 21 myocardial regions were shown in the same patients. The agreement between low b-values apparent diffusion coefficient and MIBI uptake was good in coronary artery disease patients (κ = 0.627, P < 0.001) and was better still in the whole subjects (κ = 0.733, P < 0.001). Low b-values apparent diffusion coefficient/fluorodeoxyglucose uptake demonstrated mismatch patterns in six coronary artery disease patients and MIBI/fluorodeoxyglucose uptake revealed mismatch patterns in seven coronary artery disease patients. Agreement in the evaluation of regional myocardial viability between low b-values apparent diffusion coefficient/fluorodeoxyglucose uptake and MIBI/fluorodeoxyglucose uptake was high in coronary artery disease patients (κ = 0.627, P < 0.001) and all subjects (κ = 0.728, P < 0.001). CONCLUSIONS: Low b-values apparent diffusion coefficient/fluorodeoxyglucose uptake is comparable to MIBI/fluorodeoxyglucose uptake in assessing perfusion/metabolism patterns, indicating that microperfusion might dominate the diffusion signal at low b-values and sequential PET/diffusion-weighted imaging might be useful to evaluate myocardial viability in coronary artery disease patients.

5.
Artigo em Inglês | MEDLINE | ID: mdl-31758622

RESUMO

The chemical nanospace confinement effect on the physicochemical properties of host-guest systems is of pivotal interest to enzyme-mimicking study. Herein we demonstrate a nanocage coupling effect from a redox Ru(II)-Pd(II) metal-organic cage (MOC-16) for efficient photochemical H 2 production by virtue of redox-guest modulation of the photo-induced electron transfer (PET) process. Through coupling with photoredox cycle of MOC-16, tetrathiafulvalene (TTF) guests act as electron relay mediator to improve the overall electron transfer efficiency in the host-guest system in a long-time scale, leading to significant promotion of visible-light driven H 2 evolution. By contrast, the presence of larger TTF-derivatives in bulk solution without host-guest interactions results in interference with PET process of MOC-16, leading to inefficient H 2 evolution. Such interaction protocol provides an example to understand the interplay between redox active nanocage and guest for optimization of redox events and photocatalytic activities in a spatially confined chemical nanoenvironment, which might be extendable to other enzyme-mimicking photochemical molecular device (PMD) at a supramolecular level.

6.
Nat Commun ; 10(1): 5048, 2019 Nov 06.
Artigo em Inglês | MEDLINE | ID: mdl-31695122

RESUMO

Metal-organic frameworks (MOFs) have been recognized as compelling platforms for the development of miscellaneous applications because of their structural diversity and functional tunability. Here, we propose that the electrocatalytic properties could be well modified by incorporating missing linkers into the MOF. Theoretical calculations suggest the electronic structure of MOFs can be tuned by introducing missing linkers, which improves oxygen evolution reaction (OER) performance of the MOF. Inspired by these aspects, we introduced various missing linkers into a layered-pillared MOF Co2(OH)2(C8H4O4) (termed as CoBDC) to prepare missing-linker MOFs. Transmission electron microscope and synchrotron X-ray measurements confirmed that the missing linkers in the MOF could be introduced and well controlled by our strategy. The self-supported MOF nanoarrays with missing linkers of carboxyferrocene exhibit excellent OER performance with ultralow overpotential of 241 mV at 100 mA cm-2. This work opens a new prospect to develop efficient MOF-based electrocatalysts by introducing missing linkers.

7.
Neurosci Lett ; : 134618, 2019 Nov 08.
Artigo em Inglês | MEDLINE | ID: mdl-31711978

RESUMO

Brain-derived neurotrophic factor (BDNF) has been implicated in the pathogenesis of psychiatric disorders, and studies have shown BDNF aberrations in major psychiatric diseases including schizophrenia (SCZ) and major depressive disorder (MDD). However, data from clinical studies were inconsistent. In this study, we recruited 34 patients with MDD, 77 patients with SCZ and 65 healthy control (HC) subjects to clarify the circulating BDNF levels in MDD and SCZ patients, and to assess whether serum BDNF levels were associated with the disease severity. Our results showed that serum BDNF levels were significantly decreased in the patients with SCZ (Mean difference = -4.517, 95%CI of difference = -7.854 to -1.180, p < 0.01) and MDD (Mean difference = -5.699, 95%CI of difference = -9.892 to -1.506, p < 0.01) when compared with HC subjects. Sub-group analyses suggested that BDNF levels were significantly reduced in the female SCZ (Mean difference = -5.700, 95%CI of difference = -10.21 to -1.189, p < 0.01) and MDD (Mean difference = -5.840, 95%CI of difference = -10.66 to -1.019, p < 0.05) patients, but not in male patients. Further analyses indicated that serum BDNF levels were not correlated with disease severity of MDD and SCZ. In addition, the transcriptional expression of TrkB was significantly down-regulated in the blood of MDD patients, but not in SCZ patients. However, there was no significant correlation between BDNF concentrations and TrkB mRNA levels. Taken together, our results revealed differential changes of BDNF-TrkB signaling in MDD and SCZ patients, therefore contributed to a better understanding of MDD and SCZ pathophysiology.

8.
Schizophr Bull ; 2019 Nov 18.
Artigo em Inglês | MEDLINE | ID: mdl-31738422

RESUMO

Prenatal administration of mitotoxin methylazoxymethanol acetate (MAM) in rats produces behavioral, pharmacological, and anatomical abnormalities once offspring reach adulthood, thus establishing a widely used neurodevelopmental model of schizophrenia. However, the molecular aspects underlying this disease model are not well understood. Therefore, this study examines epigenetic and transcriptional dysregulation in the prefrontal cortex and hippocampus of MAM rats as these are brain regions closely associated with schizophrenia pathogenesis. Upon sequencing messenger and microRNA (mRNA and miRNA, respectively), differential expression was revealed in the prefrontal cortex and hippocampus between MAM- and saline-treated rats; sequencing data were validated by qualitative real-time polymerase chain reaction. Bioinformatic analyses demonstrated that the differentially expressed (DE) genes were strongly enriched in interactive pathways related to schizophrenia, including chemical synaptic transmission, cognition, and inflammatory responses; also, the potential target genes of the DE miRNAs were enriched in pathways related to synapses and inflammation. The blood of schizophrenia patients and healthy controls was further analyzed for several top DE mRNAs: DOPA decarboxylase, ret proto-oncogene, Fc receptor-like 2, interferon lambda receptor 1, and myxovirus (influenza virus) resistance 2. The results demonstrated that the expression of these genes was dysregulated in patients with schizophrenia; combining these mRNAs sufficiently differentiated schizophrenia patients from controls. Taken together, this study suggests that the MAM model has the potential to reproduce hippocampus and prefrontal cortex abnormalities, relevant to schizophrenia, at the epigenetic and transcriptional levels. These data also provide novel targets for schizophrenia diagnoses and treatments.

9.
Int J Mol Sci ; 20(21)2019 Oct 28.
Artigo em Inglês | MEDLINE | ID: mdl-31661818

RESUMO

Salt stress inhibits the production of all crop species, including rapeseed (Brassica napus L.), the second most widely planted oil crop species. Although melatonin was confirmed to alleviate salt stress in rapeseed seedlings recently, the mechanism governing the expression levels remains unknown. Therefore, the melatonin-induced transcriptome variation of salt-stressed seedlings was explored. In this study, the transcriptomes of leaves and roots under control (CK), salt (125 mM NaCl, ST) and melatonin (125 mM NaCl plus 50 µM melatonin, MS) treatments were evaluated by using next-generation sequencing techniques. After conducting comparisons of gene expression in the roots and leaves between MS and ST, the differentially expressed gene (DEG) pools were screened. Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses highlighted the significant pathways, which were mainly related to plant hormone synthesis and signal transduction, lignin and fatty acid metabolism. The functional genes in the objective KEGG pathways were identified. Furthermore, members of several transcription factor (TF) families participated in the response process. Combined with the hormone (campesterol (CS), jasmonic acid (JA), and gibberellic acid 3 (GA3)) contents measured in the seedlings, it could be concluded that melatonin induced changes in the intrinsic hormone metabolic network, which promoted seedling growth. Thus, this study identified new candidate genes and pathways active during the interactions between melatonin and salt stress, which provide clues for disclosing melatonin's function in resistance to salt injury. Our results contribute to developing a practical method for sustainable agriculture on saline lands.

10.
J Cell Mol Med ; 23(12): 7974-7984, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31568662

RESUMO

Thyroid cancer is maintaining at a high incidence level and its carcinogenesis is mainly affected by a complex gene interaction. By analysis of the next-generation resequencing of paired papillary thyroid cancer (PTC) and adjacent thyroid tissues, we found that Growth Associated Protein 43 (GAP43), a phosphoprotein activated by protein kinase C, might be novel markers associated with PTC. However, its function in thyroid carcinoma has been poorly understood. We discovered that GAP43 was significantly overexpressed in thyroid carcinoma and these results were consistent with that in The Cancer Genome Atlas (TCGA) cohort. In addition, some clinicopathological features of GAP43 in TCGA database showed that up-regulated GAP43 is significantly connected to lymph node metastasis (P < 0.001) and tumour size (P = 0.038). In vitro experiments, loss of function experiments was performed to investigate GAP43 in PTC cell lines (TPC-1 and BCPAP). The results proved that GAP43 knockdown in PTC cell significantly decreased the function of cell proliferation, colony formation, migration, and invasion and induced cell apoptosis. Furthermore, we also indicated that GAP43 could modulate the expression of epithelial-mesenchymal transition-related proteins, which could influence invasion and migration. Put those results together, GAP43 is a gene which was associated with PTC and might be a potential therapeutic target.

11.
Inorg Chem ; 58(21): 14652-14659, 2019 Nov 04.
Artigo em Inglês | MEDLINE | ID: mdl-31603662

RESUMO

The development of cost-effective, high-performance, and robust bifunctional electrocatalysts for overall water splitting remains highly desirable yet quite challenging. Here, by selecting appreciate precursors of dopamine and a Co-containing metal-organic framework of ZIF-67, we subtly couple their reaction processes to develop a facile approach for the synthesis of a hollow CoP nanostructure with N-doped carbon skeleton (H-CoP@NC). Benefiting from the highly porous nanostructure and conductive carbon skeleton, H-CoP@NC is capable of working as highly active and durable bifunctional electrocatalyst for both hydrogen and oxygen evolution reaction. When further used as the electrocatalyst for overall water splitting, H-CoP@NC delivers excellent activity (cell voltage of 1.72 V at a current density of 10 mA cm-2), close to that of the noble-metal-based benchmark catalyst couple of Pt/C||RuO2. Our work thus provides new insights into the development of transitional metal phosphides based hollow hybrid nanostructures, particularly those with multiple functionalities in sustainable energy conversion technologies and systems.

12.
Arch Toxicol ; 93(11): 3305-3320, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31612242

RESUMO

Aflatoxin B1 (AFB1), a food contaminant derived from Aspergillus fungi, has been reported to cause hepatic immunotoxicity via inflammatory infiltration and cytokines release. As a pro-inflammatory factor, cyclooxygenase-2 (COX-2) is widely involved in liver inflammation induced by xenobiotics. However, the mechanism by which AFB1-induced COX-2 regulates liver inflammatory injury via hepatocytes-Kupffer cells (KCs) crosstalk remains unclear and requires further elucidation. Here, we established a COX-2 upregulated model with AFB1 treatment in vivo (C57BL/6 mice, 1 mg/kg body weight, i.g, 4 weeks) and in vitro (human liver HepaRG cells, 1 µM for 24 h). In vivo, AFB1-treated mice exhibited NLRP3 inflammasome activation, inflammatory infiltration, and increased recruitment of KCs. In vitro, dephosphorylated COX-2 by protein phosphatase 2A (PP2A)-B55δ promoted NLRP3 inflammasome activation, including mitochondrial translocation of NLRP3, caspase 1 cleavage, and IL-1ß release. Moreover, phosphorylated COX-2 at serine 601 (p-COX-2Ser601) underwent endoplasmic reticulum (ER) retention for proteasome degradation. Furthermore, pyroptosis and inflammatory response induced by AFB1 were relieved with COX-2 genetic (siPTGS2) intervention or pharmaceutic (celecoxib, 30 mg/kg body weight, i.g, 4 weeks) inhibition of COX-2 via NLRP3 inflammasome suppression in vivo and in vitro. Ex vivo, in a co-culture system with murine primary hepatocytes and KCs, activated KCs induced by damaged signals from pyroptotic hepatocytes, formed a feedback loop to amplify NLRP3-dependent pyroptosis of hepatocytes via pro-inflammatory signaling, leading to liver inflammatory injury. Taken together, our data suggest a novel mechanism that protein quality control of COX-2 determines the intracellular distribution and activation of NLRP3 inflammasome, which promotes liver inflammatory injury via hepatocytes-KCs crosstalk.

13.
Int J Mol Med ; 44(6): 2057-2064, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31661123

RESUMO

There is growing interest in the application of lactoferrin (LF) as a drug or food additive for animals and humans. The objective of this study was to produce transgenic cloned goats that would serve as living bioreactors, expressing high levels of recombinant human LF (rhLF) in their milk. We designed a pCL25 expression vector containing goat ß­casein/CMV chimeric promoter in order to facilitate rhLF expression. This pCL25­rhLF­Neo vector was microinjected into goat fetal fibroblasts. G418 selection and PCR analysis were used to identify transgenic donor cells suitable for somatic cell nuclear transfer (SCNT). After SCNT and embryo transplantation, goats harboring the hLF gene were produced, as confirmed via PCR and southern blotting. The average rhLF concentration in milk from this transgenic goat was 3.89 mg/ml as determined via ELISA. We also used an optimized buffer in order to effectively elute high­purity (95.8%) rhLF from a cation­exchange column, with the recovered rhLF exhibiting high biological activity. Findings from this study demonstrated that it is possible to generate a transgenic goat harboring the hLF transgene driven by the goat ß­casein/CMV chimeric promoter. It represents an initial step towards the production of rhLF, potentially allowing for industrialized purification in the future.

14.
Cell Signal ; : 109436, 2019 Oct 22.
Artigo em Inglês | MEDLINE | ID: mdl-31654716

RESUMO

BACKGROUND: Severe acute pancreatitis (SAP) is associated with high morbidity and mortality. Bone marrow mesenchymal stem cells (BMSCs) have shown obvious protective effect on SAP. However, little is known about the underlying mechanism. The objective of this study is to unravel the role and regulatory mechanism of miR-181a-5p in BMSCs-mediated pancreatic repair. METHODS: BMSCs were isolated from Sprague-Dawley rats and characterized by flow cytometry and Oil Red O staining. Sodium taurocholate- and caerulein-induced models were used as SAP models in vivo and in vitro, respectively. Pancreatic injury were evaluated by H&E and histopathological analysis, as well as by measuring levels of amylase, lipase and cytokines. qRT-PCR and western blotting were performed to detect the level of miR-181a-5p and the protein levels of PTEN/Akt, respectively. ELISA was conducted to detect the levels of TNF-α, IL-1ß, IL-6, angiopoietin, IL-4, IL-10 and TGF-ß1. The apoptotic rate of AR42 J cells was quantitated by concurrent staining with Annexin-V-FITC and PI. RESULTS: BMSCs significantly attenuated pancreatic injury in SAP rats by reducing inflammatory infiltration and necrosis, and this effect was abolished by CXCR4 agonist AMD3100. ADM3100 exhibited more severe pancreatic injury and decreased miR-181a-5p levels in the pancreas and serum compared to SAP group. Overexpression of miR-181a-5p in BMSCs (BMSCs-miR-181a-5p) markedly potentiated the protective effect of BMSCs by reducing histological damage and levels of amylase and lipase. Moreover, BMSCs-miR-181a-5p dramatically reduced levels of angiopoietin, TNF-α, IL-1ß and IL-6, but induced the levels of IL-4 and IL-10. In caerulein-treated AR42 J cells, co-culturing of BMSCs-miR-181a-5p alleviated caerulein-induced increase of amylase and lipase, and apoptosis via PTEN/Akt/TGF-ß1 signaling. CONCLUSION: BMSCs alleviate SAP and reduce inflammatory responses and apoptosis by secreting miR-181a-5p to target PTEN/Akt/TGF-ß1 signaling. Hence, BMSCs-miR-181a-5p could serve as potential therapeutic target for SAP.

15.
Chem Biodivers ; 16(11): e1900416, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31631505

RESUMO

The frequent disease of Panax notoginseng caused by the pathogenic fungi in field cultivation has become the major threaten to the sustainable development of it. The present study was conducted to find natural agent with potential inhibition against pathogen. Therefore, the inhibitory effects of Cinnamomum cassia (L.) J.Presl essential oils (EOs) against P. notoginseng associated pathogenic fungi were conducted both in vitro and in vivo experiments. The results of the Oxford cup test revealed that C. cassia dry bark EO (50 mg/mL) had significant inhibitory activity on the growth of all tested fungi, and the growth of various pathogens was completely inhibited, except for that of Fusarium solani. Therefore, the constituents of C. cassia EOs were analyzed by GC/MS, and the research demonstrated that the main constituents of C. cassia dry bark EO were trans-cinnamaldehyde (75.65 %), (E)-2-methoxycinnamaldehyde (6.08 %), cinnamaldehyde (3.47 %) and cinnamyl acetate (1.02 %). The MIC results showed that C. cassia dry bark EO and the main compounds had good antifungal effect on the tested strains, and the inhibitory effect was similar to that of hymexazol (chemical pesticide). By analyzing the value of the fraction inhibitory concentration index (FICI), additive effects, irrelevant effects and synergistic effects were observed after the mixture of hymexazol against various pathogens. Moreover, in vivo model showed that C. cassia dry bark EO could reduce the occurrence of anthrax in P. notoginseng. To widen the resources of C. cassia available, the compositions of both C. cassia fresh bark and leaf EOs were also tested and many common compositions existed among them. Taken together, it was concluded that C. cassia EO had the potential use in the field to reduce the pathogenic disease.

16.
ACS Chem Neurosci ; 10(11): 4502-4510, 2019 Nov 20.
Artigo em Inglês | MEDLINE | ID: mdl-31642670

RESUMO

The Chinese mitten crab (Eriocheir sinensis) is a commercially important crab in China and is usually managed at high stocking densities. Agonistic behavior directly impacts crab integrity, survival, and growth and results in economic losses. In the present study, we evaluated the modulatory effects of serotonin (5-HT) and dopamine (DA) though the 5-HT2 and DA2 receptor-cyclic adenosine monophosphate (cAMP)-protein kinase A (PKA) pathway on agonistic behavior. The results showed that injection of either 10-6 mol/crab 5-HT or DA reduced the agonistic behavior of E. sinensis (P < 0.05), as did 10-10 mol/crab DA and 10-8 mol/crab 5-HT and DA (P < 0.05); however, a dose of 10-10 mol/crab 5-HT promoted agonistic behavior. 5-HT significantly increased the mRNA expression level of 5-HT7 receptor and reduced that of the DA2 receptor in the cerebral ganglion (P < 0.05). In contrast to 5-HT, DA significantly decreased 5-HT2B mRNA levels and increased 5-HT7 and DA2 receptor levels in the thoracic ganglia (P < 0.05). In addition, injections of either 5-HT or DA increased the cAMP and PKA levels in hemolymph (P < 0.05). By using in vitro culture of the thoracic ganglia, the current study showed that ketanserin (5-HT2 antagonist) and [R(-)-TNPA] (DA2 agonist) had obvious effects on the expression levels of the two receptors (P < 0.05). In vivo experiments further demonstrated that ketanserin and [R(-)-TNPA] could both significantly reduce the agonistic behavior of the crabs (P < 0.05). Furthermore, both ketanserin and [R(-)-TNPA] promoted the cAMP and PKA levels (P < 0.05). The injection of CPT-cAMP (cAMP analogue) elevated the PKA levels and inhibited agonistic behavior. In summary, this study showed that 5HT-2B and DA2 receptors were involved in the agonistic behavior that 5-HT/DA induced through the cAMP-PKA pathway in E. sinensis.

18.
CNS Neurosci Ther ; 2019 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-31503421

RESUMO

Alzheimer's disease (AD) is characterized by ß-amyloid (Aß) deposition and Tau phosphorylation, in which its pathogenesis has not been cleared so far. The metabolism of Aß and Tau is critically affected by the autophagy. Abnormal autophagy is thought to be involved in the pathogenesis of AD, regulating autophagy may become a new strategy for AD treatment. In the early stage of AD, the presence of Aß and Tau can induce autophagy to promote their clearance by means of mTOR-dependent and independent manners. As AD progress, the autophagy goes aberrant. As a result, Aß and Tau generate continually, which aggravates both autophagy dysfunction and AD. Besides, several related genes and proteins of AD can also adapt autophagy to make an effect on the AD development. There seems to be a bi-directional relationship between AD pathology and autophagy. At present, this article reviews this relationship from these aspects: (a) the signaling pathways of regulating autophagy; (b) the relationships between the autophagy and the processing of Aß; (c) Aß and Tau cause autophagy dysfunction; (d) normal autophagy promotes the clearance of Aß and Tau; (e) the relationships between the autophagy and both genes and proteins related to AD: TFEB, miRNAs, Beclin-1, Presenilin, and Nrf2; and (f) the small molecules regulating autophagy on AD therapy. All of the above may help to further elucidate the pathogenesis of AD and provide a theoretical basis for clinical treatment of AD.

19.
Org Lett ; 21(21): 8523-8527, 2019 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-31556302

RESUMO

(±)-Lucidumone (1), an enantiomeric meroterpenoid possessing an unprecedented skeleton comprising a fused 6/5/6/6/5 polycyclic system, was isolated from Ganoderma lucidum and structurally identified. The absolute configuration of (-)-1 was assigned by single-crystal X-ray crystallography. A plausible biosynthetic pathway for 1 is proposed. A chemical biology approach reveals that (-)-1 selectively inhibits COX-2 by directly binding with an amino acid residue of Tyr385, representing a new structure scaffold of COX-2 inhibitors.

20.
J Biochem Mol Toxicol ; 33(11): e22392, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31503386

RESUMO

Ganoderic acid A (GA-A), recognized as a lanostanetriterpene isolated from Ganoderma lucidum, demonstrates an efficient antitumor activity in multiple cancers. To date, it is unclear whether and how GA-A functions on human glioblastoma (GBM). To unravel the functional significance of GA-A on human glioblastoma (GBM), the cell-counting kit-8 and transwell assays were used to detect proliferation, migration, and invasion of human GBM cell after GA-A treatment. Then, we utilized the flow cytometry and western blot to further evaluate the effect of GA-A on GBM cell. Further, activities of autophagy and PI3K/AKT signaling were assessed by Western blot assay. We found that GA-A significantly inhibited proliferation, migration, and invasion of GBM cell. Additionally, GA-A markedly triggered cell apoptosis, which incarnated an elevation trend in apoptotic percentage, simultaneously, an increased level of proapoptosis protein (Bax and active caspase-3) and a decreased level of antiapoptosis protein (Bcl-2), induced by GA-A treatment. Meanwhile, levels of two well-known autophagy markers (beclin 1 and LC3 II) increased while another autophagic substrate (P-62) was reduced. Moreover, the expressions levels of phosphorylated AKT, mTOR, p-P70S6K, and cyclin D1 in the PI3K/AKT pathway were significantly reduced, which revealed GA-A repressed the activation of PI3K/AKT signaling pathway. Collectively, these results indicate that GA-A may encourage U251 cell growth and invasion/migration inhibition, apoptosis, and autophagy through the inactivation of PI3K/AKT signaling pathway in human GBM. Hence, GA-A may be a potent antitumorigenic agent for human GBM in future clinical practice.

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