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1.
Front Pharmacol ; 12: 748658, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34776966

RESUMO

Cytochrome P450 (CYP) is the most important phase I drug-metabolizing enzyme, and the effect of drugs on CYP enzymes can lead to decreased pharmacological efficacy or enhanced toxicity of drugs, but there are many deficiencies in the evaluation models of CYP enzymes in vitro. Human-induced hepatocytes (hiHeps) derived from human fibroblasts by transdifferentiation have mature hepatocyte characteristics. The aim was to establish a novel evaluation system for the effect of drugs on CYP3A4, 1A2, 2B6, 2C9, and 2C19 in vitro based on hiHeps. Curcumin can inhibit many CYP enzymes in vitro, and so the inhibition of curcumin on CYP enzymes was compared by human liver microsomes, human hepatocytes, and hiHeps using UPLC-MS and the cocktail method. The results showed that the IC50 values of CYP enzymes in the hiHeps group were similar to those in the hepatocytes group, which proved the effectiveness and stability of the novel evaluation system in vitro. Subsequently, the evaluation system was applied to study the inhibitory activity of notoginseng total saponins (NS), safflower total flavonoids (SF), and the herb pair of NS-SF on five CYP enzymes. The mechanism of improving efficacy after NS and SF combined based on CYP enzymes was elucidated in vitro. The established evaluation system will become a powerful tool for the research of the effect of drugs on the activity of CYP enzymes in vitro, which has broad application prospects in drug research.

2.
Huan Jing Ke Xue ; 42(11): 5424-5432, 2021 Nov 08.
Artigo em Chinês | MEDLINE | ID: mdl-34708981

RESUMO

As the bridge of pollutant exchange between sediments and aquatic ecosystems, microorganisms play an important role in material circulation. However, there are few comparative studies of microorganisms in water and sediment of urban rivers with unconventional water supply, sluice dam, and lining closure. The highly artificial area of Beijing-Tianjin-Hebei section of the North Canal was chosen for this study. We analyze the differences of microbial community composition in water and sediment using high-throughput sequencing. The results show that the microbial communities in the sediments of the North Canal have higher α-diversity than those in the water. With regards to ß-diversity, the similarity of microbial communities in the water is higher than that in the sediment. There is no significant difference in the abundance of Proteobacteria between water and sediments. The abundance of α-Proteobacteria, Actinobacteria, Cyanobacteria, and Verrucomicrobia was higher in water than that of sediment, while the abundance of γ-Proteobacteria, δ-Proteobacteria, Chloroflexi, Firmicutes, and Acidobacteria was higher in sediments than that of water. Aerobic or facultative anaerobes dominated the microbial aquatic system, while anaerobes dominated the sediments. The risk of bacteria releasing pathogens from the sediment into the water habitat is high. The research results provide a scientific basis for revealing the mechanism of microbial community change under river pollution risk in highly artificial reclaimed water.


Assuntos
Cianobactérias , Microbiota , Sedimentos Geológicos , Sequenciamento de Nucleotídeos em Larga Escala , Microbiota/genética , RNA Ribossômico 16S/genética , Água
3.
Neuromodulation ; 2021 Aug 26.
Artigo em Inglês | MEDLINE | ID: mdl-34435730

RESUMO

BACKGROUND: Transcutaneous auricular vagus nerve stimulation (taVNS) may modulate cardiac autonomic function. However, the response rate of the traditional tonic paradigm is low, and the results remain inconsistent. A recent pilot study presented a novel burst paradigm to activate the cardiac parasympathetic system, which might offer a new approach to treat cardiac autonomic function. The present study reassessed the effect of burst taVNS on modulating heart rate variability and explored the difference between burst and traditional tonic paradigms. MATERIALS AND METHODS: Forty-two young adults were recruited for this study. Each participant underwent three types of taVNS with sham (30 sec of stimulation), tonic (25 Hz, 500 µsec), and burst (five pulses at 500 Hz every 200 msec) paradigms, respectively, with simultaneous electrocardiogram recording. One-way analysis of variance, multivariate analysis of variance, and linear regression were used for analysis. Multiple testing was performed using Bonferroni correction. RESULTS: Both burst and tonic paradigms induced a significant decrease in heart rate, which continued until poststimulation, and increased cardiac parasympathetic activity. Moreover, two parasympathetic system indicators showed significant increase only in burst taVNS. The response rates during burst (35.7%) and tonic (38.1%) stimulations were both higher than that during sham stimulation (11.9%). The response to taVNS showed parameter specificity with few nonresponders to the tonic paradigm responding to the burst paradigm. The overall response rate increased from 38.1% in tonic taVNS to 54.8% in taVNS using both burst and tonic paradigms. For both burst and tonic responders, baseline cardiac parasympathetic activity was found to be significantly negatively correlated with changes during stimulation. CONCLUSION: The burst parameter could be used as an alternative strategy for regulating cardiac parasympathetic function by taVNS, which has the potential to be used as a complementary paradigm to traditional tonic taVNS for promoting clinical treatment efficacy.

4.
J Pharm Biomed Anal ; 204: 114229, 2021 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-34252820

RESUMO

Quinoline alkaloids are the main bioactive and potentially toxic constituents in the root bark of Dictamnus dasycarpus Turcz. (BXP), a widely used traditional Chinese medicine for the treatment of skin inflammation, eczema and rubella. However, the comprehensive analysis of the chemical components and metabolites of quinoline alkaloids remain unclear. In this study, an integrated strategy by combining UPLC/Q-TOF-MS and UPLC/Qtrap-MS was established to comprehensively profile the quinoline alkaloids from BXP and their metabolites in rat plasma, urine and feces. Q-TOF-MS (MSE mode), Qtrap-MS (EMS, MIM, pMRM and NL mode) were performed for acquiring more precursor ions and clearer precursor product ions. A step-by-step manner based on the diagnostic fragment ions (DFIs), in-house database, ClogP value and dipole moment (µ) was proposed to overcome the complexities due to the similar fragmentation behaviors of the quinoline alkaloids. As a result, a total of 73 quinoline alkaloids were unambiguously or tentatively identified. Among them, 4 furoquinolines, 10 dihydrofuroquinolines, 2 pyranoquinolinones, 4 dihydropyranoquinolinones and 9 quinol-2-ones were characterized in BXP for the first time. Moreover, a total of 98 BXP-related constituents (including 57 prototypes and 41 metabolites) were detected in rat plasma, urine and feces. The metabolic pathways included phase I reactions (O-demethylation, hydroxylation and 2,3-olefinic epoxidation) and phase II reactions (conjugation with glucuronide, sulfate and N-acetylcysteine). In conclusion, the integrated strategy with the proposed stepwise manner is suitable for rapid identifying and characterizing more extensive quinoline alkaloids of BXP in vitro and in vivo. Moreover, the results will be helpful for revealing the pharmacological effective substances or toxic substances of BXP and provide a solid basis for further research.


Assuntos
Alcaloides , Dictamnus , Medicamentos de Ervas Chinesas , Quinolinas , Animais , Cromatografia Líquida de Alta Pressão , Fezes , Casca de Planta , Ratos , Espectrometria de Massas em Tandem
5.
Biomed Chromatogr ; 35(10): e5171, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34010455

RESUMO

Notoginseng total saponins (NS), safflower total flavonoids (SF), and the combination of NS and SF, namely CNS, are used for the treatment of cardiovascular diseases in clinic. This study developed a cocktail assay involving seven cytochrome P450 (CYP) enzymes to elucidate the effect of NS, SF, and CNS on CYP enzymes and to explore the synergistic effect of CNS in terms of CYP enzymes. Ultra-performance liquid chromatography-MS and reverse-transcription polymerase chain reaction were applied to detect the activities and mRNA expression levels of CYP enzymes. SF exhibited inhibitory effects on CYP1A2, 2B1, 2E1, and 2C11 and induction effects on CYP2C19 and 2D4. NS exhibited induction effects on CYP1A2, 2B1, 2E1, 2C11, 2C19, and 2D4. CNS exhibited induction effects on CYP1A2, 2B1, 2E1, 2C19, and 2D4 and inhibitory effects on CYP3A1 in vivo. Moreover, mRNA expression results were consistent with pharmacokinetic results. Potential herb-drug interactions should be studied closely when SF, NS, or CNS with clinical drugs are metabolized by CYP1A2, 2B1, 2E1, 2C11, 2C19, 2D4, and 3A1. CNS could change the inhibition or induction effects of CYP compared to the NS group, which might be one of the causes for the synergistic effects of the combination of NS and SF.


Assuntos
Carthamus tinctorius/química , Sistema Enzimático do Citocromo P-450 , Flavonoides/farmacologia , Panax notoginseng/química , Saponinas/farmacologia , Animais , Cromatografia Líquida de Alta Pressão , Sistema Enzimático do Citocromo P-450/efeitos dos fármacos , Sistema Enzimático do Citocromo P-450/metabolismo , Flavonoides/análise , Interações Ervas-Drogas , Masculino , Ratos , Ratos Sprague-Dawley , Saponinas/análise
6.
J Pharm Biomed Anal ; 200: 114079, 2021 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-33901755

RESUMO

A total of 49 limonoids derivatives were rapidly identified by UNIFI software and three new limonoids derivatives, named dasycarinone (1, DAS), isodictamdiol C (2) and dasycarinone A (3), along with nineteen known compounds, were isolated from the root bark of Dictamnus dasycarpus, named as "Baixianpi" in Chinese. Their structures were elucidated on the basis of spectroscopic data (UV, IR, HR-ESI-MS, NMR, CD spectra and OR). All the compounds were tested for anti-inflammatory activities by suppressing the nitric oxide (NO) production in lipopolysaccharide (LPS) induced BV-2 cells. DAS exhibited a strong anti-inflammatory activity with IC50 value of 1.8 µM. Nuclear Factor kappa B (NF-κB) luciferase assay and enzyme-linked immune sorbent assay indicated that DAS can suppress the release of inflammatory cytokines such as Tumor Necrosis Factor α (TNF-α), interleukin 6 (IL-6) via inactivating NF-κB signaling pathways. Moreover, we found that anti-inflammatory activities of obacunone-class are better than those of limonin-class by analyzing structure-activity relationship. Our results suggested that obacunone derivatives play an important role on anti-inflammation of Baixianpi. As a representative among them, DAS showed a strong anti-inflammatory activity via suppressing NF-κB signaling pathways.


Assuntos
Dictamnus , Limoninas , Anti-Inflamatórios/farmacologia , Limoninas/farmacologia , Lipopolissacarídeos , Casca de Planta , Extratos Vegetais/farmacologia
7.
Huan Jing Ke Xue ; 42(5): 2287-2295, 2021 May 08.
Artigo em Chinês | MEDLINE | ID: mdl-33884798

RESUMO

Sediment bacteria have attracted much attention because of their important roles in energy flow and pollutant cycle transformation. The changes in the spatial distribution pattern of bacteria are the basis for research on the biodiversity generation and maintenance mechanisms. However, there are few studies on the spatial variation in benthic microorganisms and its biogeographic models. The highly artificial North Canal River across the Beijing-Tianjin-Hebei area was chosen as the research area in this study. The spatial variation in the different classification levels of the Kingdom, Phylum, Class, Order, Family, Genus, Species, and operational taxonomic units and their diversity formation mechanisms were analyzed. The results showed that the samples at different classification levels had a more homogeneous distribution pattern. There were clearer distribution boundaries at the low classification levels than at the high classification levels. The significance of the bacterial community variation increased as the classification level of the bacterial community decreased. Furthermore, the difference between groups increased and the similarities within groups decreased as the classification level of the bacterial community decreased. The typical rhizosphere microorganisms represented by Frankiales and Rhodobacterales showed significant enrichment in the upstream samples, followed by the midstream samples and a significant decrease in the downstream samples. Microorganisms related to the carbon, nitrogen, and sulfur cycles represented by Anaerolineales and Desulfobacterales showed significant enrichment in the midstream, followed by the downstream and a significant reduction in the upstream. The genus Phenylobacterium was significantly enriched in the upstream followed by the midstream, and was significantly reduced in the downstream. The pathogenic bacteria represented by Clostridium_gasigenes and Moraxella_osloensis showed a significant enrichment pattern in the midstream. The contents of Ca2+, SO42-, and total organic carbon (TOC) in the downstream samples were significantly higher than those in the upstream and midstream samples. The discharge of untreated wastewater downstream increased the salt and TOC contents in the sediment. The ecological restoration project in the sediment of the riparian zone decreased the salt and TOC contents in the upstream and midstream samples. Environmental selection was the main driving factor of the pattern of spatial variation in the bacterial communities in the sediments of the North Canal River.


Assuntos
Aquaporinas , Rios , Bactérias/genética , Pequim , Biodiversidade , China , Monitoramento Ambiental , Sedimentos Geológicos
8.
Front Genet ; 12: 633812, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33815468

RESUMO

Enhancer RNAs, a type of long non-coding RNAs (lncRNAs), play a critical role in the occurrence and development of glioma. RNA-seq data from 161 glioblastoma multiforme (GBM) samples were acquired from The Cancer Genome Atlas database. Then, 70 eRNAs were identified as prognosis-related genes, which had significant relations with overall survival (log-rank test, p < 0.05). AC003092.1 was demonstrated as an immune-related eRNA by functional enrichment analysis. We divided samples into two groups based on AC003092.1 expression: AC003092.1 High (AC003092.1_H) and AC003092.1 Low (AC003092.1_L) and systematically analyzed the influence of AC003092.1 on the immune microenvironment by single-sample gene-set enrichment analysis and CIBERSORTx. We quantified AC003092.1 and TFPI2 levels in 11 high-grade gliomas, 5 low-grade gliomas, and 7 GBM cell lines. Our study indicates that AC003092.1 is related to glioma-immunosuppressive microenvironment, and these results offer innovative sights into GBM immune therapy.

9.
Aging (Albany NY) ; 13(3): 3501-3517, 2021 01 10.
Artigo em Inglês | MEDLINE | ID: mdl-33429364

RESUMO

Foxp3+ regulatory T cells (Treg) play an important part in the glioma immunosuppressive microenvironment. This study analyzed the effect of Foxsp3 on the immune microenvironment and constructed a Foxp3-related immune prognostic signature (IPS)for predicting prognosis in glioblastoma multiforme (GBM). Immunohistochemistry (IHC) staining for Foxp3 was performed in 72 high-grade glioma specimens. RNA-seq data from 152 GBM samples were obtained from The Cancer Genome Atlas database (TCGA) and divided into two groups, Foxp3 High (Foxp3_H) and Foxp3 Low (Foxp3_L), based on Foxp3 expression. We systematically analyzed the influence of Foxp3 on the immune microenvironment. Least Absolute Shrinkage and Selection Operator (LASSO) Cox analysis was conducted for immune-related genes that were differentially expressed between Foxp3_H and Foxp3_L GBM patients. We found a differential expression of Foxp3 in high-grade glioma tissues. The presence of Foxp3 was significantly associated with poor OS. From the four-gene IPS developed, GBM patients were stratified into low-risk and high-risk groups in both the training set and validation sets. Furthermore, we developed a novel nomogram to evaluate the overall survival in GBM patients. This study offers innovative insights into the GBM immune microenvironment and these findings contribute to individualized treatment and improvement in the prognosis for GBM patients.


Assuntos
Neoplasias Encefálicas/genética , Fatores de Transcrição Forkhead/genética , Glioblastoma/genética , Microambiente Tumoral/genética , Neoplasias Encefálicas/imunologia , Feminino , Fatores de Transcrição Forkhead/imunologia , Perfilação da Expressão Gênica , Glioblastoma/imunologia , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , RNA-Seq , Taxa de Sobrevida , Transcriptoma , Microambiente Tumoral/imunologia
10.
In Vivo ; 35(1): 249-257, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33402471

RESUMO

BACKGROUND/AIM: Curcumin is a polyphenol that exerts a variety of pharmacological activities and plays an anti-cancer role in many cancer cells. It was recently reported that gasdermin E (GSDME) is involved in the progression of pyroptosis. MATERIALS AND METHODS: HepG2 cells were treated with various concentrations of curcumin and cell viability was examined using MTT assay, apoptosis was analysed using flow cytometry, reactive oxygen species (ROS) levels using dihydroethidium, LDH release using an LDH cytotoxicity assay, and protein expression using western blot. RESULTS: Curcumin increased the expression of the GSDME N-terminus and proteins involved in pyrolysis, promoted HspG2 cell pyrolysis and increased intracellular ROS levels. Moreover, inhibition of the production of intracellular ROS with n-acetylcysteine (NAC) improved the degree of apoptosis and pyrolysis induced by curcumin. CONCLUSION: Curcumin induces HspG2 cell death by increasing apoptosis and pyroptosis, and ROS play a key role in this process. This study improves our understanding of the potential anti-cancer properties of curcumin in liver cancer.


Assuntos
Carcinoma Hepatocelular , Curcumina , Neoplasias Hepáticas , Apoptose , Carcinoma Hepatocelular/tratamento farmacológico , Carcinoma Hepatocelular/genética , Curcumina/farmacologia , Células Hep G2 , Humanos , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/genética , Piroptose , Espécies Reativas de Oxigênio
11.
Am J Transl Res ; 12(10): 6235-6249, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33194026

RESUMO

Mounting lines of evidence indicated that the "colony stimulating factor-1 (CSF-1)/tumor-associated macrophage (TAM)" signature plays an important role in the progression, invasion and metastasis of multiple tumors. However, the potential role of CSF-1/TAM in oral squamous cell carcinoma (OSCC) remains largely unknown. In the present study, the expression of CSF-1 from 99 OSCC specimens and its correlation with clinicopathological features and patient outcomes were investigated. Meanwhile, the correlation between CSF-1 expression and TAM infiltration was also explored. To investigate the potential effect of CSF-1 on tumor growth, nude mice were subcutaneously injected with Cal27 cell line and a small molecule inhibitor of CSF-1 (BZL945). The results showed that the high expression rate of CSF-1 (52%) was found in OSCC, and the upregulation of CSF-1 was closely correlated with lymph node metastasis and clinical stage. Additionally, there was a positive correlation between a high CSF-1 level and elevated TAM infiltration. The xenograft model study showed that CSF-1 signal blockade inhibited tumor growth, with a significant synchronous decrease in CSF-1 expression and TAM infiltration. Overall, our findings indicated that CSF-1 plays a crucial role in TAMs-mediated OSCC tumor progression and invasion. The "CSF-1/TAM" signaling axis may serve as a prospective target for anti-tumor therapy of OSCC.

12.
Chin Med J (Engl) ; 133(12): 1415-1421, 2020 Jun 20.
Artigo em Inglês | MEDLINE | ID: mdl-32558704

RESUMO

BACKGROUND: Cerebrospinal fluid (CSF) has been demonstrated as a better source of circulating tumor DNA (ctDNA) than plasma for brain tumors. However, it is unclear whether whole exome sequencing (WES) is qualified for detection of ctDNA in CSF. The aim of this study was to determine if assessment of ctDNA in CSF by WES is a feasible approach to detect genomic alterations of glioblastoma. METHODS: CSFs of ten glioblastoma patients were collected pre-operatively at the Department of Neurosurgery, Sun Yat-sen University Cancer Center. ctDNA in CSF and genome DNA in the resected tumor were extracted and subjected to WES. The identified glioblastoma-associated mutations from ctDNA in CSF and genome DNA in the resected tumor were compared. RESULTS: Due to the ctDNA in CSF was unqualified for exome sequencing for one patient, nine patients were included into the final analysis. More glioblastoma-associated mutations tended to be detected in CSF compared with the corresponding tumor tissue samples (3.56 ±â€Š0.75 vs. 2.22 ±â€Š0.32, P = 0.097), while the statistical significance was limited by the small sample size. The average mutation frequencies were similar in CSF and tumor tissue samples (74.1% ±â€Š6.0% vs. 73.8% ±â€Š6.0%, P = 0.924). The R132H mutation of isocitrate dehydrogenase 1 and the G34V mutation of H3 histone, family 3A (H3F3A) which had been reported in the pathological diagnoses were also detected from ctDNA in CSF by WES. Patients who received temozolomide chemotherapy previously or those whose tumor involved subventricular zone tended to harbor more mutations in their CSF. CONCLUSION: Assessment of ctDNA in CSF by WES is a feasible approach to detect genomic alterations of glioblastoma, which may provide useful information for the decision of treatment strategy.


Assuntos
DNA Tumoral Circulante , Glioblastoma , Biomarcadores Tumorais/genética , DNA Tumoral Circulante/genética , Genômica , Glioblastoma/genética , Humanos , Mutação/genética , Sequenciamento Completo do Exoma
13.
Ann Transl Med ; 8(6): 370, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32355814

RESUMO

Background: Skull base meningioma surgery is often difficult and complicated to perform. Therefore, this study aims to investigate the effectiveness of 3-dimensional (3D)-printed models of skull base meningioma in the representation of anatomical structures, the simulation of surgical plans, and patient education on surgical outcomes. Methods: A retrospective study of 35 patients (3D group: 19 patients and non-3D group: 16 patients) with skull base meningioma was conducted. Mimics software was used to create 3D reconstructions (with the skull, blood vessels, nerves, and tumors set to different colors), and 3D solid models were printed to determine the surgical protocols and communication pathways with the patient. Results: The 3D-printed model can visually display the relationship of different structures, including the skull, blood vessels, cranial nerves, and tumors. The surgeon should select the proper surgical approaches before surgery through the model and pay attention to protecting the important structures during the operation. According to the models, the surgeon should cut off the blood supply to the tumor to reduce intraoperative bleeding. For patients with skull base bone destruction, the skull base repair should be prepared in advance. Patients and their families should have a thorough understanding of the disease through the model, and there should be effective communication between doctors and patients. Conclusions: The 3D-printed model of a skull base meningioma can present the structures in a detailed manner and facilitate in helping the surgeon to develop a surgical plan. At the same time, it helps patients and their families to understand the condition and the surgical plan, which is conducive to better patient education.

14.
Phytochemistry ; 172: 112260, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31982646

RESUMO

Six undescribed quinoline alkaloids, named dasycarines A-E, and 18 known ones were isolated from the root bark of Dictamnus dasycarpus. All the structures were elucidated on the basis of comprehensive analysis of UV, IR, NMR, and HRMS spectroscopic data, and the absolute configurations were assigned via comparison of the calculated and experimental ECD data. (+)-Dasycarine A (1a) and (-)-Dasycarine A (1b) are a pair of enantiomers of dimeric furoquinoline alkaloid, which are the first dimeric via [2 + 2] cycloaddition of furan. The structure and absolute configuration of (-)-dasycarine A was determined via X-ray crystallography. Additionally, all the isolated compounds were tested for their inhibitory effects on NO production stimulated by LPS in BV-2 microglial cells. Three compounds showed strong inhibition with IC50 values below 5.0 µM; nine compounds exhibited inhibition with IC50 values in the range of 7.8-28.4 µM. Furthermore, we demonstrated that preskimmianine suppressed the levels of pro-inflammatory cytokines such as tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and nuclear factor kappa B (NF-κB) in LPS-induced BV-2 microglial cells.


Assuntos
Alcaloides , Dictamnus , Quinolinas , Anti-Inflamatórios , Casca de Planta
15.
J Asian Nat Prod Res ; 22(8): 716-723, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31144510

RESUMO

Three new compounds (1-3), named dasycarine G (1), dasycarether (2), and dasycarester (3), along with seven known compounds (4-10) obtained from the genus Dictamnus for the first time, were isolated from the root bark of Dictamnus dasycarpus. Their structures were elucidated on the basis of spectroscopic data (UV, IR, HR-ESI-MS, 1D and 2D NMR, and CD). In the in vitro assay, compounds 1, 5, 6, 9, and 10 exhibited NO inhibitory effects of LPS-induced BV-2 cells with IC50 values in the range of 10.4 µM to 27.2 µM.


Assuntos
Dictamnus , Anti-Inflamatórios , Espectroscopia de Ressonância Magnética , Estrutura Molecular , Casca de Planta
16.
J Pharm Biomed Anal ; 178: 112936, 2020 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-31672581

RESUMO

The combination of notoginseng total saponins (NS) and safflower total flavonoids (SF), namely CNS, presents a synergistic protection effect on the myocardial ischemia rats. The aim of this study was to find the clues for their synergistic actions by comparing the biliary metabolism and excretion profiles after oral administration of CNS and its individual extracts. An ultra-performance liquid chromatography coupled with hybrid triple quadrupole-linear ion trap mass spectrometer (UPLC-QTRAP-MS/MS) platform was used to identify and quantify the CNS-derived components in bile. The neutral losses, precursor ions, and predictive multiple reaction monitoring (pMRM) scans were firstly used to detect the CNS-derived ingredients in vivo. A total of 43 components, including 38 flavonoids and 5 ginsenosides were tentatively identified according to the previously established chemical and metabolic profiles of NS and SF. Afterwards, the primary circulating and biological components, hydroxysafflor yellow A (HSYA), ginsenosides Rg1 (GRg1), Re (GRe), and Rd (GRd) were chosen to compare the bile excretion between CNS and its individual extract groups, by using a validated LC-MRM-MS/MS method. The approach was proved to be well satisfied the related requirements from the guidelines of FDA (specificity, calibration curve, sensitivity, precision, accuracy, matrix effect, recovery, and stability). Comparing with the SF and NS groups, the combination group did not affect the metabolic pathways of the CNS-related components, however, it decreased the cumulative excretion ratios of HSYA, GRg1, GRe, and GRd. In conclusion, the compatibility of SF and NS could reduce the bile excretion of the CNS-derived compounds, which may be one of the reasons for the enhancement of anti-myocardial ischemia after combination.


Assuntos
Bile/metabolismo , Carthamus tinctorius/química , Flavonoides/química , Panax notoginseng/química , Saponinas/química , Animais , Cromatografia Líquida de Alta Pressão/métodos , Medicamentos de Ervas Chinesas/química , Ginsenosídeos/química , Masculino , Metaboloma , Ratos , Ratos Sprague-Dawley , Sensibilidade e Especificidade , Espectrometria de Massas em Tandem/métodos
17.
Zhongguo Zhong Yao Za Zhi ; 44(21): 4720-4727, 2019 Nov.
Artigo em Chinês | MEDLINE | ID: mdl-31872670

RESUMO

An ultra-performance liquid chromatography hybrid triple quadrupole-linear ion trap mass spectrometry(UPLC-QtrapMS) method was established to identify the metabolites in rat plasma,bile,urine and feces after oral administration of Cinnamomi Cortex(CC) aqueous extract. Several survey experiments,such as enhanced mass spectrum scan(EMS),precursor ion scan(PI),neutral loss scan(NL) and multiple ions monitoring(MIM) were applied to search target components,and two separate enhanced product ion(EPI) scans were triggered via information-dependent acquisition(IDA) method to generate the MS/MS spectra. According to the mass spectrometric data collected from reference standards and reported literature,the structures of metabolites were deduced. A total of76 metabolites and 5 original compounds were tentatively identified in rats after oral administration of CC aqueous extract. Deglycosylation,methylation,sulfonation,and glucuronidation were observed as the primary metabolic pathways for the chemical constituents of CC. These data are able to benefit the clarification of the therapeutic material basis,the clinical usage and further R&D of CC.


Assuntos
Bile , Medicamentos de Ervas Chinesas/metabolismo , Espectrometria de Massas em Tandem , Administração Oral , Animais , Cromatografia Líquida de Alta Pressão , Fezes , Ratos
18.
Int J Biol Sci ; 15(9): 1846-1860, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31523187

RESUMO

Pancreatic disease, including pathologies such as acute pancreatitis (AP), chronic pancreatitis (CP), and pancreatic cancer (PC), is a complicated and dangerous clinical condition involving the disruption of exocrine or endocrine function. PC has one of the highest mortality rates among cancers due to insufficient diagnosis in early stages. Furthermore, efficient treatment options for the disease etiologies of AP and CP are lacking. Thus, the identification of new therapeutic targets and reliable biomarkers is required. As essential couriers in intercellular communication, exosomes have recently been confirmed to play an important role in pancreatic disease, but the specific underlying mechanisms are unknown. Herein, we summarize the current knowledge of exosomes in pancreatic disease with respect to diagnosis, molecular mechanisms, and treatment, proposing new ideas for the study of pancreatic disease.


Assuntos
Exossomos/metabolismo , Pancreatopatias/metabolismo , Neoplasias Pancreáticas/metabolismo , Doença Aguda , Animais , Exossomos/genética , Humanos , Pancreatopatias/genética , Pancreatopatias/patologia , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/patologia , Pancreatite Crônica/genética , Pancreatite Crônica/metabolismo , Pancreatite Crônica/patologia , RNA não Traduzido/genética
19.
Exp Mol Med ; 51(8): 1-17, 2019 08 02.
Artigo em Inglês | MEDLINE | ID: mdl-31375658

RESUMO

Currently, preliminary results have confirmed the existence of receptor-interacting protein kinase 3 (RIPK3) and mixed lineage kinase domain-like protein (MLKL)-dependent necroptosis of pancreatic acinar cells during early acute pancreatitis (AP), which might be a potential target for the effective regulation of necroinflammatory injury. However, the exact effect of receptor-interacting protein kinase 1 (RIPK1)-dependent regulated acinar cell necrosis on AP is still uncertain. In our study, we first explored the changes in the degree of local and systemic inflammation in AP rats when the activation of acinar cell RIPK1 was inhibited. The RIPK1 inhibitor Nec-1 was used to treat rats, and the levels of related inflammatory markers, necrosis indicators and apoptotic indicators were measured. Changes in pancreatic nuclear factor κB (NF-κB) and aquaporin 8 (AQP8) expression were noted. Next, the expression of AQP8 in AR42J cells was inhibited, and the degree of cell necrosis and inflammatory damage was found to be significantly reduced. Most importantly, we demonstrated that the RIPK1/NF-ĸB/AQP8 axis might be a potential regulatory pathway mediating RIPK1-dependent regulated acinar cell necrosis in early AP. Finally, we used the NF-κB inhibitor PDTC and Nec-1 to treat rats in different groups and measured the degree of pathological pancreatic injury, the activation of RIPK1, and the expression of NF-κB and AQP8. In summary, we hypothesized that there might be a RIPK1/NF-ĸB/AQP8 pathway controlling RIPK1-dependent regulated necrosis of acinar cells in AP, which might be a promising therapeutic target against AP-related injury.


Assuntos
Células Acinares/efeitos dos fármacos , Células Acinares/patologia , Imidazóis/farmacologia , Indóis/farmacologia , Pancreatite/prevenção & controle , Proteínas Serina-Treonina Quinases/antagonistas & inibidores , Animais , Aquaporinas/antagonistas & inibidores , Aquaporinas/genética , Aquaporinas/metabolismo , Linhagem Celular , Masculino , NF-kappa B/antagonistas & inibidores , NF-kappa B/metabolismo , Necrose/prevenção & controle , Pâncreas/efeitos dos fármacos , Pâncreas/patologia , Pancreatite/patologia , Prolina/análogos & derivados , Prolina/farmacologia , Proteínas Serina-Treonina Quinases/metabolismo , RNA Interferente Pequeno/farmacologia , Ratos , Ratos Wistar , Transdução de Sinais/efeitos dos fármacos , Tiocarbamatos/farmacologia
20.
New Phytol ; 223(3): 1478-1488, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31004497

RESUMO

Improvement of crop drought resistance and water-use efficiency (WUE) has been a major endeavor in agriculture. Arabidopsis ENHANCED DROUGHT TOLERANCE1/HOMEODOMAIN GLABROUS11 (AtEDT1/HDG11), a homeodomain-START transcription factor we previously identified from the enhanced drought tolerance1 mutant (edt1), has been demonstrated to improve drought tolerance and WUE significantly in multiple plant species when constitutively overexpressed. Here, we report the genetic evidence suggesting a genetic pathway, which consists of EDT1/HDG11, ERECTA, and E2Fa loci, and regulates WUE by modulating stomatal density. AtEDT1/HDG11 transcriptionally activates ERECTA by binding to homeodomain-binding (HD) cis-elements in the ERECTA promoter. ERECTA, in turn, depends on E2Fa to modulate the expression of cell cycle-related genes. This modulation affects the transition from mitosis to endocycle, leading to increased ploidy levels in leaf cells, and therefore increased cell size and decreased stomatal density. Our results suggest a possible EDT1/HDG11-ERECTA-E2Fa genetic pathway that reduces stomatal density by increasing cell size and provide a new avenue to improve WUE of crops.


Assuntos
Proteínas de Arabidopsis/metabolismo , Arabidopsis/fisiologia , Fatores de Transcrição E2F/metabolismo , Estômatos de Plantas/fisiologia , Proteínas Serina-Treonina Quinases/metabolismo , Receptores de Superfície Celular/metabolismo , Fatores de Transcrição/metabolismo , Água , Arabidopsis/genética , Tamanho Celular , Regulação da Expressão Gênica de Plantas , Mutação/genética , Poliploidia , Regiões Promotoras Genéticas/genética , Ligação Proteica , Regulação para Cima
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