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OBJECTIVE: This study aimed to compare the efficacy of enhanced 3D T1-weighted black-blood fast-spin-echo vessel wall magnetic resonance imaging (eVW-MRI) and time-of-flight magnetic resonance angiography (TOF MRA) for follow-up evaluation of aneurysms treated with flow diversion (FD). METHODS: Our study enrolled 77 patients harboring 84 aneurysms treated with FD. Follow-up was by MRI (eVW-MRI and TOF MRA) and digital subtraction angiography (DSA). Two radiologists, blinded to DSA examination results, independently evaluated the images of aneurysm occlusion and parent artery patency using the Kamran-Byrne Scale. Interobserver diagnostic agreement and intermodality diagnostic agreement were acquired. Pretreatment and follow-up aneurysm wall enhancement (AWE) patterns were collected. RESULTS: Based on the Kamran-Byrne Scale, the intermodality agreement between eVW-MRI and DSA was better than TOF MRA versus DSA for aneurysm remnant detection (weighted ĸ = 0.891 v. 0.553) and parent artery patency (ĸ = 0.950 v. 0.221). Even with the coil artifact, the consistency of eVW-MRI with DSA for aneurysm remnant detection was better than that of TOF MRA (weighted ĸ = 0.891 v. 0.511). The artifact of adjunctive coils might be more likely to affect the accuracy in evaluating parent artery patency with TOF MRA than with eVW-MRI (ĸ = 0.077 v. 0.788). The follow-up AWE patterns were not significantly associated with pretreatment AWE patterns and aneurysm occlusion. CONCLUSIONS: The eVW-MRI outperforms TOF MRA as a reliable noninvasive and nonionizing radioactive imaging method for evaluating aneurysm remnants and parent artery patency after FD. The significance of enhancement patterns on eVW-MRI sequences needs more exploration. CLINICAL RELEVANCE STATEMENT: The application of enhanced vessel wall magnetic resonance imaging has proven to be a promising tool to depict aneurysm remnant and parent artery stenosis in order to tailor the antiplatelet therapy strategy in patients after flow diversion. KEY POINTS: ⢠Enhanced vessel wall magnetic resonance imaging has an emerging role in depicting aneurysm remnant and parent artery patency after flow diversion. ⢠With or without the artifact from adjunctive coils, enhanced vessel wall magnetic resonance imaging was better than TOF MRA in detecting aneurysm residual and parent artery stenosis by using DSA imaging as the standard. ⢠Enhanced vessel wall magnetic resonance imaging holds potential to be used as an alternative to DSA for routine aneurysm follow-up after flow diversion.
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Embolização Terapêutica , Aneurisma Intracraniano , Humanos , Aneurisma Intracraniano/diagnóstico por imagem , Aneurisma Intracraniano/cirurgia , Seguimentos , Resultado do Tratamento , Constrição Patológica/terapia , Embolização Terapêutica/métodos , Imageamento por Ressonância Magnética , Angiografia por Ressonância Magnética/métodos , Angiografia Digital/métodosRESUMO
Research into traditional Chinese medicine metabolism in feces is one of the key avenues to understanding the fate of traditional Chinese medicines in vivo. In this study, we used ultraperformance liquid chromatography-quadrupole time-of-flight MS in combination with a post-targeted screening strategy to identify the prototype components and metabolites in rat feces after oral administration. Based on our group's previous research, the component database of Qi-Yu-San-Long decoction (QYSLD) was established. Prototype components were screened from the fecal samples based on summarized chromatographic and MS behaviors. According to the chemical structure characteristics of related compounds, the possible metabolic pathways were inferred, and the metabolites related to QYSLD were predicted. We extracted ion chromatograms by predicting the m/z values of metabolite excimer ions and identified related metabolites based on their retention time and fragmentation behavior. A total of 93 QYSLD-related xenobiotics were confirmed or tentatively identified in rat fecal samples, and the results indicated that the main metabolic pathways of QYSLD were hydrolysis, deglycosylation, oxidation, reduction, decarboxylation, methylation and acetylation. This study presents a rapid method for identifying the prototype components and metabolites, and offers valuable insights into the biotransformation profiling of QYSLD in rat feces.
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Medicamentos de Ervas Chinesas , Ratos , Animais , Ratos Sprague-Dawley , Cromatografia Líquida de Alta Pressão/métodos , Medicamentos de Ervas Chinesas/química , Cromatografia Líquida/métodos , Espectrometria de Massas/métodos , Fezes/química , Administração OralRESUMO
Panax ginseng (P. ginseng), the dried root and rhizome of P. ginseng C. A. Meyer, is widely used in many fields as dietary supplements and medicine. To characterize the chemical constituents in P. ginseng cultivated in different growth environments, a UPLC-TOF-MS method was established for qualitative analysis. Four hundred and eight ginsenosides, including 81 new compounds, were characterized in P. ginseng from different regions. Among the detected compounds, 361 ginsenosides were recognized in P. ginseng cultivated in the region of Monsoon Climate of Medium Latitudes, possessing the largest amount of ginsenosides in all samples. Furthermore, 41 ginsenosides in 12 batches of P. ginsengs were quantified with a UPLC-MRM-MS method, and P. ginsengs from different regions were distinguished via chemometric analysis. This study showed that the different environments have a greater influence on P. ginseng, which laid a foundation for further quality control of the herb.
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Ginsenosídeos , Panax , Cromatografia Líquida de Alta Pressão/métodos , Cromatografia Líquida , Espectrometria de Massas em Tandem/métodos , Raízes de Plantas/química , Panax/química , Ginsenosídeos/química , Metabolômica/métodosRESUMO
To compare the chemical distinctions of Panax ginseng Meyer in different growth environments and explore the effects of growth-environment factors on P. ginseng growth, an ultra-performance liquid chromatography-tandem triple quadrupole time-of-flight mass spectrometry (UPLC-Triple-TOF-MS/MS) was used to characterize the ginsenosides obtained by ultrasonic extraction from P. ginseng grown in different growing environments. Sixty-three ginsenosides were used as reference standards for accurate qualitative analysis. Cluster analysis was used to analyze the differences in main components and clarified the influence of growth environment factors on P. ginseng compounds. A total of 312 ginsenosides were identified in four types of P. ginseng, among which 75 were potential new ginsenosides. The number of ginsenosides in L15 was the highest, and the number of ginsenosides in the other three groups was similar, but it was a great difference in specie of ginsenosides. The study confirmed that different growing environments had a great influence on the constituents of P. ginseng, and provided a new breakthrough for the further study of the potential compounds in P. ginseng.
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Ginsenosídeos , Panax , Ginsenosídeos/química , Espectrometria de Massas em Tandem/métodos , Cromatografia Líquida de Alta Pressão/métodos , Panax/química , Cromatografia LíquidaRESUMO
PURPOSE: Venous thromboembolism (VTE) is a major health issue among hip fracture patients. This study aimed to develop an information platform based on a mobile application and then evaluate whether information platform-based nursing could improve patient's drug compliance and reduce the incidence of VTE in hip fracture patients. METHODS: This study retrospectively analyzed hip fracture patients who were treated with conventional prevention and intervention methods for VTE (control group) between January 2008 and November 2012, and prospectively analyzed hip fracture patients who were treated with nursing intervention based on the information platform (study group) between January 2016 and September 2017. All the patients included in the both groups were hip fracture patients who had an age over 50 years, treated with surgery, and hospitalized ≥ 48 h. Patients were excluded if they admitted to hospital due to old fractures, had a severe bleeding after 72 h of admission, diagnosed with any type of VTE, or refused to participate in the study. The information platform was divided into medical, nursing, and patient interface. Based on the information platform, medical practitioners and nurses could perform risk assessments, monitoring management and early warnings, preventions and treatments, health educations, follow-up, and other aspects of nursing interventions for patients. This study compared essential characteristics, drug compliance, VTE occurrence, and mean length of hospitalization between the two groups. Besides, a subgroup analysis was performed in the study group according to different drug compliances. SPSS 18.0 software (IBM Corp., NY, and USA) was used for statistical analysis. RESULTS: Altogether 1177 patients were included in the control group, and 491 patients in the study group. Regarding baseline data, patients in the study group had more morbidities than those in the control group (p < 0.05). The difference of drug compliance between the two groups was statistically significant (p < 0.001): 761 (64.7%) of the patients in the control group and only 30 (6.1%) patients in the study group had poor drug compliance. In terms of VTE, 10.7% patients (126/1177) in the control group had VTE, and the rate in the study group was 7.1% (35/491), showing a statistically significant difference (p = 0.02). Moreover, the average length of hospitalization in the study group was also significantly lower than that in the control group (10.4 days vs. 13.7 days, p < 0.001). Subgroup analyses of the study group showed that the incidence of VTE in patients with poor, partial, and good compliances were 56.7% (17/30), 5.8% (10/171), and 2.8% (8/290), respectively, revealing a significantly huge difference (p < 0.001). CONCLUSIONS: Poor drug compliance leads to higher VTE occurrence. The information platform-based nursing can effectively improve the compliance of hip fracture patients and thus considerably reduce the incidence of VTE. The mobile application may be an effective tool to prevent VTE in hip fracture patients.
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Fraturas do Quadril , Tromboembolia Venosa , Humanos , Pessoa de Meia-Idade , Tromboembolia Venosa/etiologia , Tromboembolia Venosa/prevenção & controle , Tromboembolia Venosa/epidemiologia , Estudos Retrospectivos , Fatores de Risco , Fraturas do Quadril/cirurgia , IncidênciaRESUMO
In this paper, magnetic cotton textile wastes pyrolyzed by ferric cerium oxide (FexCey oxide/PC) were synthesized for degradation of p-nitrophenol by catalytic ozonation, and the optimal Fe-Ce ratio was 10:1. Compared to Fe10Ce1 oxide, the Fe10Ce1 oxide/PC not only greatly improved the degradation efficiency of PNP, but also reduced the dosage of catalyst. Through the BET test, the Fe10Ce1 oxide/PC has a high specific surface area to absorb part of the pollutants. VSM test shows that the material is magnetic and easy to recycle. Response surface methodology (RSM) was applied to optimize the experimental condition, and the optimal removal rate was 90% when the initial pH was 9, the catalyst dosage was 0.4 g/L, and the ozone addition was 1.77 L/min (5.9 mg/L). Finally, the mechanism of PNP degradation was explored utilizing inhibitor and ESR free radical detection. The adsorption capacity of the material and electron-absorbing property of PNP jointly determined the high catalytic efficiency with Fe10Ce1 oxide/PC in catalytic ozonation.
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Cério , Ozônio , Poluentes Químicos da Água , Catálise , Fenômenos Magnéticos , Nitrofenóis , TêxteisRESUMO
BACKGROUND: At low levels, carbon monoxide (CO) has been shown to have beneficial effects on multiple organs and tissues through its potential anti-inflammatory, anti-apoptotic, and anti-proliferative properties. However, the effect of CO-releasing molecule (CORM)-3, a water-soluble CORM, on ischemic stroke and its mechanism of action are still unclear. METHODS: We investigated the role of CORM-3 in the mouse model of transient middle cerebral artery occlusion (tMCAO). CORM-3 or saline was administered to mice by retro-orbital injection at the time of reperfusion after 1-h tMCAO or at 1 h after sham surgery. We assessed infarct volume and brain water content at 24 and 72 h after ischemia, blood-brain barrier permeability at 6 and 72 h after ischemia, and neurologic deficits on days 1, 3, 7, and 14. RESULTS: Among mice that underwent tMCAO, those that received CORM-3 had significantly smaller infarct volume and greater expression of neuronal nuclear antigen (NeuN) and microtubule-associated protein 2 than did saline-treated mice. CORM-3-treated mice had significantly fewer activated microglia in the peri-infarction zone than did control mice and exhibited downregulated expression of ionized calcium-binding adapter molecule (Iba)-1, tumor necrosis factor-α, and interleukin 1ß. CORM-3-treated mice had significantly lower brain water content and enhanced neurologic outcomes on days 3, 7, and 14 post-tMCAO. Lastly, CORM-3 treatment reduced Evans blue leakage; increased expression of platelet-derived growth factor receptor-ß, tight junction protein ZO-1, and matrix protein laminin; and decreased protein level of matrix metalloproteinase-9. CONCLUSION: CORM-3 treatment at the time of reperfusion reduces ischemia-reperfusion-induced brain injury by suppressing neuroinflammation and alleviating blood-brain barrier disruption. Our data suggest that CORM-3 may provide an effective therapy for ischemic stroke.
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Anti-Inflamatórios/uso terapêutico , Barreira Hematoencefálica/efeitos dos fármacos , Encefalite/etiologia , Encefalite/prevenção & controle , Infarto da Artéria Cerebral Média , Compostos Organometálicos/uso terapêutico , Acetiltransferases/metabolismo , Animais , Barreira Hematoencefálica/fisiopatologia , Edema Encefálico/tratamento farmacológico , Edema Encefálico/etiologia , Proteínas de Ligação ao Cálcio/metabolismo , Infarto Cerebral/tratamento farmacológico , Infarto Cerebral/etiologia , Citocinas/metabolismo , Modelos Animais de Doenças , Regulação da Expressão Gênica/efeitos dos fármacos , Infarto da Artéria Cerebral Média/complicações , Infarto da Artéria Cerebral Média/tratamento farmacológico , Infarto da Artéria Cerebral Média/patologia , Laminina/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Proteínas dos Microfilamentos/metabolismo , Microglia/efeitos dos fármacos , Fosfopiruvato Hidratase/metabolismo , Receptor beta de Fator de Crescimento Derivado de Plaquetas/metabolismo , Proteína da Zônula de Oclusão-1/metabolismoRESUMO
Cell-based therapy is considered to be a promising therapeutic strategy for stroke treatment. Although unfractionated bone marrow mononuclear cells (BMMNCs) have been tried in both preclinical and clinical trials, the effective subpopulations need to be identified. In this study, we used fluorescence-activated cell sorting to harvest the CXCR4(+)CD45(+) and CXCR4(+)CD45(-) BMMNC subpopulations from transgenic mice that express enhanced green fluorescent protein. We then allogeneically grafted unfractionated BMMNCs or a subpopulation into mice subjected to transient middle cerebral artery occlusion (tMCAO) and compared the effects on stroke outcomes. We found that CXCR4(+)CD45(-) BMMNCs, but not CXCR4(+)CD45(+) BMMNCs, more effectively reduced infarction volume and neurologic deficits than did unfractionated BMMNCs. Brain tissue from the ischemic hemisphere of mice treated with CXCR4(+)CD45(-) BMMNCs had higher levels of vascular endothelial growth factor and lower levels of TNF-α than did tissue from mice treated with unfractionated BMMNCs. In contrast, CXCR4(+)CD45(+) BMMNCs showed an increase in TNF-α. Additionally, CXCR4(+)CD45(+) and CXCR4(+)CD45(-) populations exhibited more robust migration into the lesion areas and were better able to express cell-specific markers of different linages than were the unfractionated BMMNCs. Endothelial and astrocyte cell markers did not colocalize with eGFP(+) cells in the brains of tMCAO mice that received CXCR4(+)CD45(+) BMMNCs. In vitro, the CXCR4(+)CD45(-) BMMNCs expressed significantly more Oct-4 and Nanog mRNA than did the unfractionated BMMNCs. However, we did not detect gene expression of these two pluripotent markers in CXCR4(+)CD45(+) BMMNCs. Taken together, our study shows for the first time that the CXCR4(+)CD45(-) BMMNC subpopulation is superior to unfractionated BMMNCs in ameliorating cerebral damage in a mouse model of tMCAO and could represent a new therapeutic approach for stroke treatment.
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Células da Medula Óssea/imunologia , Transplante de Medula Óssea , Encéfalo/imunologia , Infarto da Artéria Cerebral Média/imunologia , Leucócitos Mononucleares/imunologia , Animais , Células da Medula Óssea/citologia , Encéfalo/patologia , Encéfalo/fisiologia , Isquemia Encefálica/imunologia , Isquemia Encefálica/patologia , Ensaios de Migração Celular , Citometria de Fluxo , Proteínas de Fluorescência Verde , Infarto da Artéria Cerebral Média/patologia , Antígenos Comuns de Leucócito/imunologia , Leucócitos Mononucleares/citologia , Leucócitos Mononucleares/transplante , Camundongos , Camundongos Transgênicos , Receptores CXCR4/imunologia , Regeneração , Acidente Vascular Cerebral/imunologia , Acidente Vascular Cerebral/patologia , Fator de Necrose Tumoral alfa/imunologia , Fator A de Crescimento do Endotélio Vascular/imunologiaRESUMO
Recent evidence has shown that an increase in CD4(+)CD25(+)FoxP3(+) regulatory T (Treg) cells may contribute to stroke-induced immunosuppression. However, the molecular mechanisms that underlie this increase in Treg cells remain unclear. Here, we used a transient middle cerebral artery occlusion model in mice and specific pathway inhibitors to demonstrate that stroke activates the sympathetic nervous system, which was abolished by 6-OHDA. The consequent activation of ß2-adrenergic receptor (AR) signaling increased prostaglandin E2 (PGE2) level in bone marrow. ß2-AR antagonist prevented the upregulation of PGE2. PGE2, which acts on prostaglandin E receptor subtype 4 (EP4), upregulated the expression of receptor activator for NF-κB ligand (RANKL) in CD4(+) T cells and mediated the increase in Treg cells in bone marrow. Treatment of MCAO mice with RANKL antagonist OPG inhibited the increase in percent of bone marrow Treg cells. PGE2 also elevated the expression of indoleamine 2,3 dioxygenase in CD11C(+) dendritic cells and promoted the development of functional Treg cells. The effect was neutralized by treatment with indomethacin. Concurrently, stroke reduced production of stromal cell-derived factor-1 (SDF-1) via ß3-AR signals in bone marrow but increased the expression of C-X-C chemokine receptor (CXCR) 4 in Treg and other bone marrow cells. Treatment of MCAO mice with ß3-AR antagonist SR-59230A reduced the percent of Treg cells in peripheral blood after stroke. The disruption of the CXCR4-SDF-1 axis may facilitate mobilization of Treg cells and other CXCR4(+) cells into peripheral blood. This mechanism could account for the increase in Treg cells, hematopoietic stem cells, and progenitor cells in peripheral blood after stroke. We conclude that cerebral ischemia can increase bone marrow CD4(+)CD25(+)FoxP3(+) regulatory T cells via signals from the sympathetic nervous system.
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Células da Medula Óssea/imunologia , Isquemia Encefálica/imunologia , Transdução de Sinais/imunologia , Sistema Nervoso Simpático/imunologia , Linfócitos T Reguladores/imunologia , Animais , Células da Medula Óssea/metabolismo , Isquemia Encefálica/metabolismo , Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD4-Positivos/metabolismo , Dinoprostona/metabolismo , Fatores de Transcrição Forkhead/metabolismo , Tolerância Imunológica/imunologia , Masculino , Camundongos , Receptores de Prostaglandina E Subtipo EP4/metabolismo , Sistema Nervoso Simpático/metabolismo , Linfócitos T Reguladores/metabolismoRESUMO
Ochratoxin A (OTA) is a toxic secondary metabolite that widely contaminates agro-products and poses a significant dietary risk to human health. Previously, a carboxypeptidase CP4 was characterized for OTA degradation in Lysobacter sp. CW239, but the degradation activity was much lower than its host strain CW239. In this study, an amidohydrolase ADH2 was screened for OTA hydrolysis in this strain. The result showed that 50 µg/L OTA was completely degraded by 1.0 µg/mL rADH2 within 5 min, indicating ultra-efficient activity. Meanwhile, the two hydrolases (i.e., CP4 and ADH2) in the strain CW239 showed the same degradation manner, which transformed the OTA to ochratoxin α (OTα) and l-ß-phenylalanine. Gene mutants (Δcp4, Δadh2 and Δcp4-adh2) testing result showed that OTA was co-degraded by carboxypeptidase CP4 and amidohydrolase ADH2, and the two hydrolases are sole agents in strain CW239 for OTA degradation. Hereinto, the ADH2 was the overwhelming efficient hydrolase, and the two types of hydrolases co-degraded OTA in CW239 by synergistic effect. The results of this study are highly significant to ochratoxin A contamination control during agro-products production and postharvest.
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Lysobacter , Ocratoxinas , Ocratoxinas/metabolismo , Ocratoxinas/toxicidade , Lysobacter/metabolismo , Lysobacter/genética , Amidoidrolases/metabolismo , Amidoidrolases/genética , Carboxipeptidases/metabolismo , Carboxipeptidases/genética , Hidrolases/metabolismo , Hidrolases/genéticaRESUMO
The contamination of microplastics in terrestrial geoenvironment (CMTG) is widespread and severe and has, received considerable attention. However, studies on CMTG are in their initial stages. The literature on CMTG published in the past decade was analyzed through bibliometric analysis, such as the annual publications, countries with the highest contributions, prolific authors, and author keywords. The sources, compositions, migrations and environmental impacts of CMTG are summarized, and possible future directions are proposed. This study analyzed the annual publications, countries with the highest contributions, prolific authors, and author keywords related to microplastics. The results demonstrated that 15,306 articles were published between 2014 and 2023. China is the leading country in terms of the total number of publications. The main sources of CMTG include landfills, agricultural non-point sources, sewage treatment systems and transportation systems. The composition of the CMTG exhibits significantly temporal and spatial variability from different sources. The migration paths of the CMTG were within the soil, groundwater seepage and wind transportation of suspended particles. Microplastics increase soil cohesion, decrease porosity, reduce pore scale, decrease air circulation, and increase water retention capacity, and the exudation of highly water-soluble additives in microplastics can cause secondary contamination of geological entities. Microplastics have an adverse effect on plant growth, animal digestion, microbial activity, energy and lipid metabolism, oxidative stress, and respiratory diseases in humans. It is recommended to develop more efficient and convenient quantitative testing methods for microplastics, formulate globally harmonized testing and evaluation standards, include microplastic testing in testing programs for contaminated soils, and develop efficient methods for the remediation of microplastic contaminated geological bodies.
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Huachansu (HCS) tablets, classified as well-known traditional Chinese medicine (TCM) preparation, have been proved to be effective in the treatment of hepatocellular carcinoma (HCC) in clinical studies. However, the underlying mechanism of HCS tablets against HCC has not been comprehensively elucidated. In this study, a rat model of HCC was established with diethylnitrosamine (DEN) inducer. The efficacy of HCS tablets against HCC was assessed through liver histopathological examination and evaluation of biochemical indicators. A metabolomics method based on UPLC-Q-TOF/MS combined with multivariate data analysis was established to identify differential metabolites related to the inhibition effect of HCS tablets on HCC, and then the relevant metabolic pathway analysis was performed to investigate the anti-HCC mechanisms of HCS tablets. The results showed that compared to the control group, the HCC model group showed a significant increase in the values of HCC-related biochemical indicators and the number of tumor nodules, indicating the successful establishment of the HCC rat model. Upon treatment with HCS tablets, the values of HCC-related biochemical indicators decreased, liver fibrosis and nuclear deformation were also significantly alleviated. A total of 15 differential metabolites associated with the anti-tumor effect of HCS tablets on HCC were screened and annotated through hepatic tissue metabolomics studies. Analysis of metabolic pathways revealed that the therapeutic effects of HCS tablets on HCC mainly involved the pentose and glucuronate interconversions and arachidonic acid metabolism. Further western blotting corroborated that the alteration in arachidonic acid (AA) level after the intervention of HCS tablets was related to the inhibition of cPLA2α expression in rat liver tissues. In conclusion, HCS tablets exhibit a certain anti-tumor effect on HCC, and the metabolomics method based on UPLC-Q-TOF/MS combined with further verification at the biochemical level is a promising way to reveal its underlying mechanism.
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Carcinoma Hepatocelular , Medicamentos de Ervas Chinesas , Neoplasias Hepáticas , Ratos , Animais , Carcinoma Hepatocelular/induzido quimicamente , Carcinoma Hepatocelular/tratamento farmacológico , Cromatografia Líquida de Alta Pressão/métodos , Ácido Araquidônico , Medicamentos de Ervas Chinesas/farmacologia , Medicamentos de Ervas Chinesas/uso terapêutico , Neoplasias Hepáticas/tratamento farmacológico , Metabolômica/métodos , Comprimidos , Biomarcadores/metabolismoRESUMO
Shenqi-Tiaoshen formula (SQTSF) is a traditional Chinese medicine (TCM) prescription that has been employed in the treatment of chronic obstructive pulmonary disease (COPD). Clinical practice has demonstrated that SQTSF is an effective prescription for stable COPD. However, owing to the complexity of TCM prescription, there is a lack of in-depth understanding of the chemical components of SQTSF and its in vivo metabolism studies. In this study, a comprehensive analytical strategy based on ultra-performance liquid chromatography coupled with quadrupole-time-of-flight mass spectrometry (UPLC-Q-TOF/MS) was established to identify the chemical components, the absorbed components, and the metabolites of SQTSF given by gavage in rats, and analyze their dynamic changes. As a result, 86 chemical components of SQTSF were characterized, which were mainly categorized into flavonoids, saponins, organic acids, terpenoids, etc. Among them, 13 compounds were confirmed unambiguously by reference standards. Furthermore, 20 prototype components and 46 metabolites were detected in rat plasma at different time points. It was found that one prototype component and thirteen metabolites could be detected during the entire 24 h, indicating that these compounds were slowly eliminated and thus accumulated in vivo over a prolonged duration. Interestingly, the phenomenon that three prototype components and fourteen metabolites reappeared after a period of disappearance from the plasma was found. It was also observed that different prototype components may generate the same metabolite. The metabolic processes of SQTSF in rats mainly included oxidation, reduction, hydration, demethylation, deglycosylation, methylation, acetylation, glucuronidation, glutathionylation, and associated combination reactions. Overall, the present study identified the chemical components of SQTSF and their dynamic metabolic profile in rat plasma, which provided a systematic and applicable strategy for screening and characterization of the prototype components and metabolites of TCM compound preparations.
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Medicamentos de Ervas Chinesas , Doença Pulmonar Obstrutiva Crônica , Ratos , Animais , Ratos Sprague-Dawley , Espectrometria de Massas em Tandem/métodos , Cromatografia Líquida de Alta Pressão/métodos , Metaboloma , Medicamentos de Ervas Chinesas/químicaRESUMO
Introduction: Lung cancer, one of the most frequent malignancies, has a high death rate and an increased number of new cases globally. Ginkgo biloba has been used for many years in the treatment of lung cancer. Ginkgetin is the key active ingredient extracted from Ginkgo biloba. However, the mechanism by which ginkgetin inhibits the invasive metastasis of lung cancer is unclear. Methods: We used a network pharmacology approach to obtain the molecular mechanism by which ginkgetin inhibits lung cancer metastasis. Then we analyzed potential target proteins between ginkgetin and lung cancer. Finally, we validated with molecular docking and experimental validation. Results: By analyzing the intersecting genes of lung cancer and ginkgetin, there were 79 intersecting genes, which were mainly involved in the positive regulation of cell migration, with the cancer pathway being one of the most enriched pathways. The results of in vitro experiments showed that GK had a large inhibitory effect on cell invasion and metastasis of A549 and H1299. In vivo animals GK had a great inhibitory effect on metastasis of LLC. Conclusion: This study identified the potential related GK molecular targets and signaling pathways in treating human lung cancer using network pharmacological approaches. Experiments confirmed that GK inhibits the Akt/GSK-3ß/Snail and Wnt/ß-catenin cascade initiation in A549, H1299 and LLC cells, preventing metastasis. This study's results align with the hypotheses derived from the network pharmacology analysis.
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Robotic systems have revolutionized various industries, and dentistry is no exception. Recently, due to the robust advancements in artificial intelligence and technology, there has been a significant evolution of dental robotic systems, ranging from surgeon controlled, robot-assisted operations, to more autonomous processes. The present clinical case report describes a 1-year follow-up of the successful use of an autonomous dental implant robot system with an osseodensification (OD) protocol for implant osteotomy preparation, maxillary sinus elevation, and simultaneous implant placement at the maxillary second premolar site. A prefabricated provisional prosthesis was delivered immediately after implant placement, with final prosthesis delivery at 3 months. The findings from this report demonstrate the integration and clinical augmentation of more autonomous protocols in the field of implant dentistry using dental robots.
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- Seven previously undescribed ent-eudesmane sesquiterpenoids (1-7), as well as seven known analogs (8-14), were isolated from the Chinese liverwort Chiloscyphus polyanthus var. rivularis. Their structures were established based on comprehensive spectroscopy analysis, electronic circular dichroism calculations, as well as biosynthetic considerations. The cytotoxicity against HepG2 (Human hepatocellular carcinomas) cancer cell line, and antifungal activity against Candida albicans SC5314 of all isolated ent-eudesmane sesquiterpenoids were preliminarily tested, results showed that the tested compounds did not display obvious cytotoxicity and antifungal activities under the tested concentration.
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Antifúngicos , Antineoplásicos , Hepatófitas , Sesquiterpenos de Eudesmano , Sesquiterpenos , Antifúngicos/farmacologia , Antifúngicos/química , China , Hepatófitas/química , Estrutura Molecular , Sesquiterpenos/química , Sesquiterpenos de Eudesmano/farmacologia , Sesquiterpenos de Eudesmano/química , Células Hep G2/efeitos dos fármacos , Humanos , Antineoplásicos/química , Antineoplásicos/farmacologiaRESUMO
The homotypic fusion and vacuole protein sorting (HOPS) complex mediates membrane trafficking involved in endocytosis, autophagy, lysosome biogenesis, and phagocytosis. Defects in HOPS subunits are associated with various forms of cancer, but their potential as drug targets has rarely been examined. Here, we identified vacuolar protein sorting-associated protein 41 homolog (VPS41), a subunit of the HOPS complex, as a target of methyl 2,4-dihydroxy-3-(3-methyl-2-butenyl)-6-phenethylbenzoate (DMBP), a natural small molecule with preferable anticancer activity. DMBP induced methuosis and inhibited autophagic flux in cancer cells by inhibiting the function of VPS41, leading to the restrained fusion of late endosomes and autophagosomes with lysosomes. Moreover, DMBP effectively inhibited metastasis in a mouse metastatic melanoma model. Collectively, the current work revealed that targeting VPS41 would provide a valuable method of inhibiting cancer proliferation through methuosis.
Assuntos
Endossomos , Neoplasias , Camundongos , Animais , Transporte Proteico , Endossomos/metabolismo , Autofagia , Endocitose , Lisossomos/metabolismo , Neoplasias/metabolismo , Proteínas de Transporte Vesicular/metabolismoRESUMO
In this study, the removals of sodium p-toluenesulfonate (NaTSA) by catalytic ozonation with two different cobalt-iron compounds, CoxFe oxides prepared by co-precipitation/calcination (CPO) and CoxFe oxides prepared by direct calcination (DCO), as the catalysts, had a difference of about 12%. It was found that the CPO surface contained active type c water, which was generally adsorbed on the oxygen vacancy. The test of oxygen temperature-programmed desorption (O2-TPD) showed that the surface of CPO was rich in oxygen vacancy. Through the electrochemical oxygen evolution reaction (OER) detection, a pair of Co valence redox peaks were detected from the CV curves, and the results of XPS test showed the replacement of octahedral Co3+ with Fe3 + in the Co3O4 during preparation of CPO. The enriched oxygen vacancy could be used as active sites for ozone adsorption and improve the charge transfer capacity. The number of hydroxyl radicals was detected by electron spin resonance (EPR) and it indicated that CPO contained more hydroxyl radicals, so it had higher effect in catalytic ozonation for organic pollutant degradation. In this paper, the relationship between oxygen vacancy and reactive center in the microstructure of the catalysts was established to discuss their working mechanism. The influence of the initial pH value, catalyst dosage, and ozone concentration on the removal of NaTSA was investigated by response surface design, and the optimal experimental conditions were predicted and verified.