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2.
Crit Care ; 28(1): 115, 2024 04 09.
Artigo em Inglês | MEDLINE | ID: mdl-38594724

RESUMO

BACKGROUND: Sepsis-induced myocardial injury is a serious complication of sepsis. QT prolongation is a proarrhythmic state which reflects myocardial injury in a group of heterogeneous disorders. However, the study on the clinical value of QT prolongation in sepsis is limited. METHODS: We aimed to investigate the clinical characteristics and predictors of new-onset QT prolongation in sepsis and its impact on the outcome in a multicenter retrospective cohort study. Electrocardiographic and clinical data were collected from patients with sepsis from the wards and intensive care units of four centers after exclusion of QT-influencing medications and electrolyte abnormalities. Clinical outcomes were compared between patients with and without QT prolongation (QTc > 450 ms). Multivariate analysis was performed to ascertain whether QT prolongation was an independent predictor for 30-day mortality. The factors predicting QT prolongation in sepsis were also analyzed. RESULTS: New-onset QT prolongation occurred in 235/1024 (22.9%) patients. The majority demonstrated similar pattern as type 1 long QT syndrome. Patients with QT prolongation had a higher 30-day in-hospital mortality (P < 0.001), which was also associated with increased tachyarrhythmias including paroxysmal atrial fibrillation or tachycardia (P < 0.001) and ventricular arrhythmia (P < 0.001) during hospitalization. QT prolongation independently predicted 30-day mortality (P = 0.044) after multivariate analysis. History of coronary artery disease (P = 0.001), septic shock (P = 0.008), acute respiratory (P < 0.001), heart (P = 0.021) and renal dysfunction (P = 0.013) were independent predictors of QT prolongation in sepsis. CONCLUSIONS: New-onset QT prolongation in sepsis was associated with increased mortality as well as atrial and ventricular arrhythmias, which was predicted by disease severity and organ dysfunction.


Assuntos
Síndrome do QT Longo , Sepse , Humanos , Estudos Retrospectivos , Fatores de Risco , Hospitalização , Eletrocardiografia , Síndrome do QT Longo/etiologia , Síndrome do QT Longo/tratamento farmacológico , Sepse/complicações
3.
ACS Appl Bio Mater ; 7(3): 1362-1380, 2024 03 18.
Artigo em Inglês | MEDLINE | ID: mdl-38373393

RESUMO

Untimely or improper treatment of traumatic bleeding may cause secondary injuries and even death. The traditional hemostatic modes can no longer meet requirements of coping with complicated bleeding emergencies. With scientific and technological advancements, a variety of topical hemostatic materials have been investigated involving inorganic, biological, polysaccharide, and carbon-based hemostatic materials. These materials have their respective merits and defects. In this work, the application and mechanism of the major hemostatic materials, especially some hemostatic nanomaterials with excellent adhesion, good biocompatibility, low toxicity, and high adsorption capacity, are summarized. In the future, it is the prospect to develop multifunctional hemostatic materials with hemostasis and antibacterial and anti-inflammatory properties for promoting wound healing.


Assuntos
Hemostáticos , Humanos , Hemostáticos/farmacologia , Hemostáticos/uso terapêutico , Coagulação Sanguínea , Hemostasia , Hemorragia , Cicatrização
4.
J Ethnopharmacol ; 301: 115746, 2023 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-36179951

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Shixiao San (SXS) is a traditional Chinese formula that has been widely used in clinical practice to treat blood stasis syndromes, such as hyperlipidemia, atherosclerotic, thrombosis and coronary heart disease. However, the effectiveness and mechanism of SXS have not been studied in detail yet. AIM OF THE STUDY: Current study aimed to identify the compounds in SXS, evaluate the formula efficacies using network pharmacology, molecular docking, and verify the pharmacological effects by in vivo and in vitro experiments. MATERIALS AND METHODS: The compounds in SXS were analyzed using UPLC-QTOF-MS. Potential target genes for identified compounds were obtained from three databases. DAVID database was used to perform GO and KEGG pathway enrichment analyses. PPI network was constructed to screen core targets. Molecular docking was used to examine interactions between active compounds and potential targets. The mechanism was also verified by model of acute blood stasis rats and human umbilical vein cells. RESULTS: In total, 45 compounds were identified from SXS. Among the detected phytochemicals, quercetin, isorhamnetin, kaempferol, D-catechin, naringenin and amentoflavone were identified as the active constituents. SXS is primarily involved in the modulation of hypoxic state, vascular regulation, and inflammation response, according to GO and KGG pathway enrichment analysis. A network of protein-protein interactions (PPIs) was constructed and five core targets were identified as VEGFA, AKT1, EGFR, PTGS2, and MMP9. Molecular docking simulation revealed good binding affinity of the five putative targets with the corresponding compounds. SXS reduced HIF-1α and COX-2 levels and increased the eNOS expression levels in hypoxic HUVECs. SXS can reduce the whole blood viscosity in adrenaline induced acute blood stasis rats and relieve blood stasis. CONCLUSIONS: SXS removes blood stasis might through VEGFA/AKT/eNOS/COX-2 pathway and flavonoids are the main active components in the formula.


Assuntos
Medicamentos de Ervas Chinesas , Humanos , Ratos , Animais , Simulação de Acoplamento Molecular , Medicamentos de Ervas Chinesas/farmacologia , Medicamentos de Ervas Chinesas/uso terapêutico , Medicamentos de Ervas Chinesas/química , Ciclo-Oxigenase 2 , Farmacologia em Rede
5.
Int J Biol Macromol ; 222(Pt B): 2028-2040, 2022 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-36209909

RESUMO

Four fractions of polysaccharides (TPP-1, TPP-2, TPP-3, and TPP-4) were isolated and purified from the pollen of Typha angustifolia L., and the structure of TPP-3 was furtherly determined by HPGPC (High Performance Gel Permeation Chromatography), monosaccharide composition analysis, methylation analysis and NMR (Nuclear Magnetic Resonance). TPP-3 was found to be a homogeneous heteropolysaccharide with an average molecular weight of 5.5 × 104 Da and composed of eight types of monosaccharides. The pro-angiogenic activities of TPP-3 were verified on HUVECs and VEGFR tyrosine kinase inhibitor II (VRI)-induced vascular defect zebrafish model. Furthermore, the underlying mechanism investigation showed that its pro-angiogenic activities were closely related with the activation of VEGF/PI3K/Akt signaling pathway.


Assuntos
Typhaceae , Peixe-Zebra , Animais , Peixe-Zebra/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Indutores da Angiogênese/farmacologia , Polissacarídeos/química , Monossacarídeos/análise , Pólen/química
6.
Phytomedicine ; 102: 154152, 2022 Jul 20.
Artigo em Inglês | MEDLINE | ID: mdl-35636167

RESUMO

BACKGROUND: Carbonized traditional Chinese medicine (TCM) is a kind of distinctive traditional medicine, which has been widely used to cure various bleeding syndromes in clinic for over 2000 years. However, there are no effective quality control methods developed on carbonized TCM so far. PURPOSE: This study aimed at developing a processing-associated quality marker (Q-marker) discovery strategy, which would enable to promote the quality control study of carbonized TCM. METHODS: Carbonized Typhae Pollen (CTP), a typical carbonized TCM with fantastic efficacy of stanching bleeding and removing blood stasis, was used as an example. First, a ultraperformance liquid chromatography with quadrupole time-of-flight mass spectrometry (UPLC-QTOF-MS) method was established to characterize four types of CTP in different processing degrees. Second, chemometric method was applied to screen candidate Q-markers. Third, peak area changes and Aratio changes of each candidate markers in 57 batches samples were described (Traceability and Transitivity). Fourth, systems pharmacology and two high-throughput zebrafish models: cerebral hemorrhage model and thrombus model were used to furtherly screen Q-markers (Effectiveness). Finally, a ultraperformance liquid chromatographic coupled with triple quadrupole tandem mass spectrometry (UPLC-TQ-MS) method was established and applied to quantify Q-markers in additional 10 batches of CTP samples (Measurability). RESULTS: The chemical profiles of Typhae Pollen during the carbonized process were investigated. Then, 12 candidate compounds were screened in chemometric part. Six Q-markers (isorhamnetin-3-O-neohesperidoside, isorhamnetin-3-O-rutinoside, kaempferol-3-O-neohesperidoside, naringenin, quercetin and isorhamnetin) were subsequently screened out using three principles of Q-markers combined with content changes and two in vivo zebrafish models. Their average contents in additional 10 batches of CTP were 316.8 µg/g, 13.7 µg/g, 6.1 µg/g, 197.8 µg/g, 12.9 µg/g and 199.3 µg/g, respectively. Their content proportion was about 25: 1: 0.5: 15: 1: 15. CONCLUSION: A processing-associated Q-marker discovery strategy was developed for carbonized TCM. It might provide a novel insight to solve the problem of 'Chao Tan Cun Xing' in carbonized process.


Assuntos
Medicamentos de Ervas Chinesas , Medicina Tradicional Chinesa , Animais , Biomarcadores/análise , Cromatografia Líquida de Alta Pressão/métodos , Medicamentos de Ervas Chinesas/química , Ensaios de Triagem em Larga Escala , Metabolômica/métodos , Farmacologia em Rede , Espectrometria de Massas em Tandem/métodos , Peixe-Zebra
7.
Carbohydr Polym ; 289: 119433, 2022 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-35483846

RESUMO

Oxidative stress is closely associated with the initiation and progression of aging. Considerable interest centers in the potential application of natural polysaccharides in oxidative stress alleviation and senescence delay. Herein, LFP-05S, an acidic heteropolysaccharide from Lycii fructus, was purified and structurally characterized based on a combination strategy of molecular weight (MW) distribution, monosaccharide composition, methylation and NMR spectroscopy analysis. The dominant population of LFP-05S was composed of long homogalacturonan (HG) backbone interspersed with alternating sequences of intra-rhamnogalacturonans-I (RG-I) domains and branched arabinogalactan and arabinan. Orally supplied LFP-05S exhibited defensive modulation in paraquat (PQ)-damaged oxidative stress Caenorhabditis elegans by strengthening the internal defense systems. Under normal conditions, LFP-05S extended the lifespan without significant impairment of propagation. Overall, these results suggested LFP-05S and L. fructus are worth further exploration as promising redox-based candidates for the prevention and management of aging and related disorders.


Assuntos
Caenorhabditis elegans , Estresse Oxidativo , Animais , Carboidratos da Dieta , Frutas , Longevidade , Polissacarídeos/química , Polissacarídeos/farmacologia
8.
Mitochondrial DNA B Resour ; 7(2): 331-332, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35141412

RESUMO

The complete plastome of G. subelliptica, Merr. 1909. The complete length is 158,356 bp, with the typical structure and gene content of angiosperm plastomes, including a large single-copy region (LSC) of 86,220 bp, a repeat region (IRB), and a reverse repeat region (IRA) of 27,399 bp, respectively, and a small single-copy region (SSC) of 17,338 bp. The plastome contains 130 genes, including 85 protein-coding genes, 37 tRNA genes, and 8 rRNA genes. The total G/C content of the plastome is 36.1%.

9.
Rheumatology (Oxford) ; 61(6): 2644-2651, 2022 05 30.
Artigo em Inglês | MEDLINE | ID: mdl-34599805

RESUMO

OBJECTIVES: This study aimed to characterize the systemic lipid profile of patients with asymptomatic hyperuricemia (HUA) and gout using lipidomics, and to find potential underlying pathological mechanisms therefrom. METHODS: Sera were collected from Affiliated Hospital of Nanjing University of Chinese Medicine as centre 1 (discovery and internal validation sets) and Suzhou Hospital of Traditional Chinese Medicine as centre 2 (external validation set), including 88 normal subjects, 157 HUA and 183 gout patients. Lipidomics was performed by ultra high performance liquid chromatography plus Q-Exactive mass spectrometry (UHPLC-Q Exactive MS). Differential metabolites were identifed by both variable importance in the projection ≥1 in orthogonal partial least-squares discriminant analysis mode and false discovery rate adjusted P ≤ 0.05. Biomarkers were found by logistic regression and receiver operating characteristic (ROC) analysis. RESULTS: In the discovery set, a total of 245 and 150 metabolites, respectively, were found for normal subjects vs HUA and normal subjects vs gout. The disturbed metabolites included diacylglycerol, triacylglycerol (TAG), phosphatidylcholine, phosphatidylethanolamine, phosphatidylinositol, etc. We also found 116 differential metabolites for HUA vs gout. Among them, the biomarker panel of TAG 18:1-20:0-22:1 and TAG 14:0-16:0-16:1 could differentiate well between HUA and gout. The area under the receiver operating characteristic ROC curve was 0.8288, the sensitivity was 82% and the specificity was 78%, at a 95% CI 0.747, 0.9106. In the internal validation set, the predictive accuracy of TAG 18:1-20:0-22:1 and TAG 14:0-16:0-16:1 panel for differentiation of HUA and gout reached 74.38%, while it was 84.03% in external validation set. CONCLUSION: We identified serum biomarkers panel that have the potential to predict and diagnose HUA and gout patients.


Assuntos
Gota , Hiperuricemia , Biomarcadores , Humanos , Lipidômica , Metaboloma , Triglicerídeos
10.
Biomed Pharmacother ; 138: 111521, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-34311525

RESUMO

Euphorbiae pekinensis Radix (EP) is effective in treating various diseases, but it's toxicity is a major obstacle in use in clinical. Although EP was processed with vinegar to reduce it's toxicity, the detailed mechanism of toxicity in EP have not been clearly delineated. This study investigate the toxicity attenuation-mechanism of Euphorbiae pekinensis after being processed with vinegar (VEP) and the toxic mechanism of four compounds from EP on zebrafish embryos. The contents of four compounds decreased obviously in VEP. Correspondingly, slower development on embryos can be seen as some symptoms like reduction of heart rate, liver area and gastrointestinal peristalsis after exposed to the compounds. Some obvious pathological signals such as pericardial edema and yolk sac edema were observed. Furthermore, the compounds could increase the contents of MDA and GSH-PX and induce oxidative damage by inhibiting the activity of SOD. Also, four compounds could provoke apoptosis by up-regulating the expression level of p53, MDM2, Bax, Bcl-2 and activating the activity of caspase-3, caspase-9. In conclusion, the four compounds play an important role in the toxicity attenuation effects of VEP, which may be related to the apoptosis induction and oxidative damage. This would contribute to the clinical application and further toxicity-reduction mechanism research.


Assuntos
Euphorbia/toxicidade , Trato Gastrointestinal/efeitos dos fármacos , Coração/efeitos dos fármacos , Fígado/efeitos dos fármacos , Compostos Fitoquímicos/toxicidade , Extratos Vegetais/toxicidade , Peixe-Zebra/embriologia , Animais , Apoptose/efeitos dos fármacos , Proteínas Reguladoras de Apoptose/genética , Proteínas Reguladoras de Apoptose/metabolismo , Cardiotoxicidade , Embrião não Mamífero/efeitos dos fármacos , Embrião não Mamífero/metabolismo , Embrião não Mamífero/patologia , Euphorbia/química , Trato Gastrointestinal/embriologia , Trato Gastrointestinal/metabolismo , Coração/embriologia , Fígado/embriologia , Fígado/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Compostos Fitoquímicos/isolamento & purificação , Extratos Vegetais/isolamento & purificação , Proteínas de Peixe-Zebra/genética , Proteínas de Peixe-Zebra/metabolismo
11.
Front Aging Neurosci ; 13: 618690, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33815088

RESUMO

A correlation between the abnormal cerebral glucose metabolism and the progression of Alzheimer's disease (AD) has been found in previous studies, suggesting that glucose alterations may be used to predict the histopathological diagnosis in AD. In this study, we investigated the dynamic changes of cerebral glucose uptake in vivo using MR glucose chemical exchange saturation transfer (glucoCEST) imaging in a rat model of AD with an intracerebroventricular (i.c.v) injection of amyloid Aß-protein (25-35), confirmed by Morris water maze and Nissl staining. In total, 6 rats in the AD group and 6 rats in the control group that were given an injection of sterile normal saline were included. At 28 days after injection, all rats performed a 7.0 T MR exanimation, including glucoCEST, diffusion tensor imaging (DTI) and hippocampus magnetic resonance spectra (MRS), to detect the possible metabolic and structural changes in the rat brain. A significantly elevated brain glucoCEST signal in the brain of AD rats was observed, and a decreased brain glucose uptake was also explored during the progression of glucose infusion compared with those in rats of the control group. In addition, there is a significant positive correlation between glucoCEST enhancement (GCE) and myo-Inosito (Ins) in the AD group and the control group (P < 0.05). A significantly reduced number of neurons in the cortex and hippocampus in AD rats combined with the significantly longer escape and a decreased number of crossings were verified at 28 days after Aß25-35 injection by Nissl staining and Morris water maze, respectively. Our results indicated that an abnormal brain glucose mechanism in AD rats could be detected by glucoCEST imaging, suggesting a new method to explore the occurrence and progress of diabetes-related AD or dementia.

12.
J Ethnopharmacol ; 270: 113774, 2021 Apr 24.
Artigo em Inglês | MEDLINE | ID: mdl-33388428

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Carbonized Typhae Pollen (CTP), a processed product of Typhae Pollen after stir-fried, is a well-known Traditional Chinese Medicine (TCM) with functions of removing blood stasis and hemostasis. AIM OF REVIEW: The aim of this study is to summarize and discuss up-to-date information on quality control of CTP, and effects of carbonized process on phytochemistry and biological activities. We hope this review could provide feasible insights for further studies of CTP on its material basis and pharmacological effect mechanism. MATERIAL AND METHODS: The information of TP before and after carbonized process was collected from online databases (PubMed, CNKI, Google Scholar, Baidu Xueshu, Web of Science, SpringerLink, Wiley Online Library, SciFinder and Chemical book). Meanwhile local books, published and unpublished Ph.D., MSc. dissertations were also taken into consideration. RESULTS: A total of 27 Ph.D., MSc. dissertations and 208 articles were collected from online database, from which 122 compounds of TP were collected, but only two researches focused on the chemical compositions of CTP. Introductions of new technologies and intelligent processing equipment developments are considered as two main solutions to the quality control of CTP. CTP is a well-known ethnic medicine in China with a fantastic efficacy in curing bleeding caused by blood stasis. Flavonoids were reported as the main active compounds for removing blood stasis while the enhanced hemostatic activity were consistent with flavonoid aglycones. Modern pharmacological researches showed that CTP has wound healing activity, effects on blood vessels, antithrombotic activity, hemostatic activity, antioxidant activity and immunomodulatory activity. CONCLUSIONS: Although CTP has been widely used in clinic, there are some problems blocking its further development. Unknown mechanism and uncertain active compounds might be the main reasons for few rules on controlling the quality of CTP. It is necessary to investigate the mechanisms and the relationship between carbonized process and the changes in constituents as well as pharmacological effects. This is essential to promote the safe clinical use of CTP.


Assuntos
Medicamentos de Ervas Chinesas/normas , Medicamentos de Ervas Chinesas/uso terapêutico , Pólen/química , Typhaceae/química , Animais , Carbono/química , Medicamentos de Ervas Chinesas/química , Medicamentos de Ervas Chinesas/farmacologia , Humanos , Medicina Tradicional Chinesa , Controle de Qualidade
13.
J Ethnopharmacol ; 268: 113591, 2021 Mar 25.
Artigo em Inglês | MEDLINE | ID: mdl-33212176

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Typhae Pollen (TP) is a well-known Traditional Chinese Medicine (TCM) to remove blood stasis. Carbonized Typhae Pollen (CTP), a processed product of TP after being stir-fried, has been widely applied to clinical practice with its capability of hemostasis. However, the underlying mechanism of TP and CTP are still not fully elucidated and discrimination against TP and CTP remains a challenge. AIM OF STUDY: The aim of this study is to investigate whether TP could remove blood stasis by promoting angiogenesis and the process of carbonizing it could enhance hemostatic effect. Meanwhile, some chemical markers for quality control of CTP had better to be found. MATERIAL AND METHODS: The changes of constituents between TP and CTP were analyzed by UPLC-QTOF-MS/MS. We investigated pro-angiogenic and hemostatic effects of TP and CTP in two zebrafish models: VRI-induced ISV insufficiency model and Ator-induced cerebral hemorrhage model. Subsequently, quantitative real-time PCR (qRT-PCR) was applied to investigate the mechanism of pharmacological effects. Finally, chemometric method was applied to find chemical markers. RESULTS: A total of 19 compounds were identified in qualitative analysis. The loss rate of each compound was calculated and compared. Two compounds (huaicarbon A/B) could only be detected in CTP and the content of flavonoid glycosides in CTP was significantly decreased compared with TP. The average content of the three identified flavonoid aglycones (quercetin, isorhamnetin and kaempferol) was increased about 30 percent in CTP. TP promoted pro-angiogenesis by up-regulating the expression of VEGFA, flt1 and kdr. After heating process, the pro-angiogenic activity was reduced and hemostatic activity was enhanced in CTP. Then qRT-PCR analysis found that CTP could significantly up-regulate the expression of VEGFA and vWF. In the discovery of markers, 6 chemical markers for discrimination of TP and CTP were obtained by chemometric method. CONCLUSION: Our research indicated that the pro-angiogenic activity of TP was involved in VEGF signaling pathway. After processing, hemostatic activity of CTP has been enhanced by up-regulating the expression of VEGFA and vWF. A chemical marker database was established to provide a scientific evidence for quality control, mechanism and the clinical application of TP and CTP.


Assuntos
Indutores da Angiogênese/farmacologia , Medicamentos de Ervas Chinesas/farmacologia , Hemostáticos/farmacologia , Pólen , Typhaceae , Fator A de Crescimento do Endotélio Vascular/biossíntese , Indutores da Angiogênese/isolamento & purificação , Animais , Animais Geneticamente Modificados , Biomarcadores/metabolismo , Relação Dose-Resposta a Droga , Avaliação Pré-Clínica de Medicamentos/métodos , Medicamentos de Ervas Chinesas/isolamento & purificação , Hemostáticos/isolamento & purificação , Fator A de Crescimento do Endotélio Vascular/genética , Peixe-Zebra
14.
Chin J Integr Med ; 27(3): 192-197, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31065990

RESUMO

OBJECTIVE: To investigate the mechanism of Radix Kansui (RK) stir-fried with vinegar (VRK) decreased hepatotoxicity in mice. METHODS: According to a random number table, 40 mice were randomly divided into negative control group (0.5% carboxymethylcellulose sodium, 20 mL/kg), positive control group (0.1% mixture of carbon tetrachloride in soybean oil, 20 mL/kg), RK group (the ethyl acetate extracts of RK, 250 g crude drug/kg) and VRK group (the ethyl acetate extracts of VRK, 250 g crude drug/kg) with 10 mice per group. All mice were administered orally by gavage daily for 7 continuous days. The morphology of liver tissues was examined to assess the liver injury by a transmission electron microscope. Hepatocyte apoptosis in vivo was determined by terminal deoxynucleotidyltransferase-mediated dUTP-biotin nickend labeling (TUNEL) assay. Immunohistochemical technique was adopted to detect the expression of particular antiapoptotic and proapoptotic proteins in the mitochondrial pathways, including B-cell lymphoma (Bcl-2) and caspase-3, as well as the expression of inflammatory mediators, including nuclear factor kappa B (NF- κ B) and intercellular adhesion molecule-1 (ICAM-1). RESULTS: Liver injury and hepatocyte apoptosis were observed in RK mice, and the liver injury were significantly reduced in VRK-treated mice. In immunohistochemistry study, compared with the negative control group, RK inhibited dramatically the Bcl-2 protein expression and significantly increased the expression of caspase-3, NF- κ B and ICAM-1 (all P<0.01). Compared with the RK group, VRK group induced significant increase on Bcl-2 protein expression, and decreased the caspase-3, NF- κ B and ICAM-1 protein expression (P<0.05 or P<0.01). CONCLUSION: The mechanism of reduced hepatotoxicity of VRK may be associated with the reduced inflammation, regulation of antiapoptotic and proapoptotic mediators in the mitochondrial pathway.


Assuntos
Doença Hepática Induzida por Substâncias e Drogas , Medicamentos de Ervas Chinesas , Euphorbia , Ácido Acético , Animais , Apoptose , Doença Hepática Induzida por Substâncias e Drogas/tratamento farmacológico , Medicamentos de Ervas Chinesas/farmacologia , Camundongos , Mitocôndrias , NF-kappa B , Raízes de Plantas
15.
J Ethnopharmacol ; 267: 113507, 2021 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-33098970

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Malignant ascites (MA) effusion is mainly caused by hepatocellular, ovarian, and breast cancer etc. It has been reported that Euphorbia kansui (EK), the root of Euphorbia kansui S.L.Liou ex S.B.Ho, possessing a therapeutic effect on MA. However, the clinical applications of EK are seriously restricted for its severe toxicity. Although studies demonstrated that vinegar-processing can reduce the toxicity and retain the water expelling effect of EK, its specific mechanism remains unknown. AIM OF THE STUDY: This study aims to explore the underlying mechanisms of toxicity reduction without compromising the pharmacological effects of EK stir-fried with vinegar (VEK). MATERIALS AND METHODS: 3-O-(2'E,4'Z-decadienoyl)-20-O-acetylingenol (3-O-EZ), a major diterpenoid of EK, could convert into ingenol after processing EK with vinegar. The H22 mouse hepatoma ascites model was replicated, and were given 3-O-EZ and ingenol seven days (110.14, 50.07 and 27.54 mg/kg). The histopathological observation, serum liver enzymes, serum Renin-Angiotensin-Aldosterone System (RAAS) levels, ascites volumes, pro-inflammatory cytokines levels and H22 cells apoptosis in ascites were examined. Then the intestine (Aquaporin 8, AQP8) and kidney (Aquaporin 2, AQP2; Vasopressin type 2 receptor, V2R) protein expression were detected, as well as the metabolomics of serum were analyzed. Finally, the content of 3-O-EZ and ingenol in EK and VEK were investigated. RESULTS: 3-O-EZ and ingenol can relieve hepatic and gastrointestinal injuries, reduce ascites volumes, enhance the H22 cells apoptosis, ameliorate abnormal pro-inflammatory cytokines and RAAS levels, and down-regulate the expression of AQP8, AQP2, V2R. The involved metabolic pathways mainly included glycerophospholipid metabolism and arachidonic acid metabolism. And the decreasing rate of 3-O-EZ in VEK was 19.14%, the increasing rate of ingenol in VEK was 92.31%. CONCLUSION: 3-O-EZ and ingenol possess significant effect in treating MA effusion, while ingenol has lower toxicity compared with 3-O-EZ. And provide evidence for the mechanism of attenuation in toxicity without compromising the pharmacological effects of VEK.


Assuntos
Ácido Acético/química , Antineoplásicos Fitogênicos/farmacologia , Ascite/prevenção & controle , Carcinoma Hepatocelular/tratamento farmacológico , Cromatografia Líquida de Alta Pressão , Culinária , Diterpenos/farmacologia , Euphorbia , Neoplasias Hepáticas/tratamento farmacológico , Extratos Vegetais/farmacologia , Animais , Antineoplásicos Fitogênicos/isolamento & purificação , Apoptose/efeitos dos fármacos , Aquaporina 2/metabolismo , Aquaporinas/metabolismo , Ascite/metabolismo , Ascite/patologia , Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/patologia , Linhagem Celular Tumoral , Citocinas/metabolismo , Diterpenos/isolamento & purificação , Euphorbia/química , Feminino , Temperatura Alta , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/patologia , Masculino , Camundongos , Camundongos Endogâmicos ICR , Extratos Vegetais/isolamento & purificação , Receptores de Vasopressinas/metabolismo , Sistema Renina-Angiotensina/efeitos dos fármacos , Transdução de Sinais
16.
Carbohydr Polym ; 249: 116894, 2020 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-32933702

RESUMO

Regeneration of neurites network constitutes a neurotrophic and therapeutic strategy for Parkinson's disease (PD). Increasing evidence is supporting the potential application of natural polysaccharides in prevention or treatment of PD. In this study, an acidic heteropolysaccharide LFP-1 was isolated from Lycii fructus, and purified by ion-exchange and gel filtration chromatography. Structural features of LFP-1 were analyzed with molecular weight (MW) distribution, monosaccharide composition, methylation and nuclear magnetic resonance (NMR) spectra. LFP-1 was a complicated structured polysaccharide with an average MW of 1.78 × 104 Da and composed of highly branched arabinogalactans, homogalacturonan and rhamnogalacturonan moieties. LFP-1 promoted neuronal differentiation and neurite outgrowth in vitro in PC12 cell models. Furthermore, LFP-1 had a significantly protective effect against 1-methyl-4-phenylpyridiniumion (MPP+)-induced neurotoxicity in PD model PC12 cells. These observations unambiguously indicated the neurotrophic and neuroprotective activities of LFP-1, which may be developed for prevention or treatment of neurodegeneration in PD.


Assuntos
1-Metil-4-fenilpiridínio/toxicidade , Ácidos/química , Lycium/química , Fármacos Neuroprotetores/farmacologia , Síndromes Neurotóxicas/tratamento farmacológico , Transtornos Parkinsonianos/tratamento farmacológico , Polissacarídeos/farmacologia , Animais , Síndromes Neurotóxicas/etiologia , Síndromes Neurotóxicas/patologia , Células PC12 , Transtornos Parkinsonianos/induzido quimicamente , Transtornos Parkinsonianos/patologia , Extratos Vegetais/farmacologia , Polissacarídeos/isolamento & purificação , Ratos
17.
J Pharm Biomed Anal ; 191: 113638, 2020 Nov 30.
Artigo em Inglês | MEDLINE | ID: mdl-32980794

RESUMO

Rubiae Radix et Rhizoma (called "Qiancao", QC), the root and rhizome of Rubia cordifolia L., has been widely used in clinical practice for its excellent performance in removing blood stasis and haemostasis. However, after carbonization processing, significant changes occurred in chemical components of the charcoal of Rubiae Radix et Rhizoma (called "Qiancaotan", QCT), which enhanced the performance in haemostasis and weakened the performance in removing blood stasis in clinic. In order to study the material basis of function variation during processing, a rapid, reliable, accurate and validated UPLC-MS/MS approach was established to determine twelve quinones in QC and QCT simultaneously. Meanwhile, the antithrombotic effect of target components on zebrafish thrombus model induced by phenylhydrazine (PHZ) was investigated. Chromatographic separation was accomplished on an ACQUITY UPLC C18column with acetonitrile-water containing 0.2 % (v/v) formic acid as mobile phase, at a flow rate of 0.30 mL/min. Quantitation was performed using multiple reaction monitoring (MRM) in positive and negative ion electrospray ionization (ESI). Furthermore, the activity evaluation studies showed that the reduction of removing blood stasis effect of QCT was due to the decrease of dehydro-α-lapachone, lapachol, rubioncolin C and mollugin. This study demonstrated that the method has been successfully applied to determine the content of twelve quinones responsible for the function variation of QCT, and provided a new insight into the material basis and the effect of eliminating stasis before and after processing of QC.


Assuntos
Medicamentos de Ervas Chinesas , Rizoma , Animais , Cromatografia Líquida de Alta Pressão , Cromatografia Líquida , Medicamentos de Ervas Chinesas/farmacologia , Fibrinolíticos , Quinonas , Espectrometria de Massas em Tandem , Peixe-Zebra
18.
J Ind Microbiol Biotechnol ; 47(6-7): 485-495, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32535763

RESUMO

L-Leucine is an essential amino acid that has wide and expanding applications in the industry. It is currently fast-growing market demand that provides a powerful impetus to further increase its bioconversion productivity and production stability. In this study, we rationally engineered the metabolic flux from pyruvate to L-leucine synthesis in Corynebacterium glutamicum to enhance both pyruvate availability and L-leucine synthesis. First, the pyc (encoding pyruvate carboxylase) and avtA (encoding alanine-valine aminotransferase) genes were deleted to weaken the metabolic flux of the tricarboxylic acid cycle and reduce the competitive consumption of pyruvate. Next, the transcriptional level of the alaT gene (encoding alanine aminotransferase) was down regulated by inserting a terminator to balance L-leucine production and cell growth. Subsequently, the genes involved in L-leucine biosynthesis were overexpressed by replacing the native promoters PleuA and PilvBNC of the leuA gene and ilvBNC operon, respectively, with the promoter Ptuf of eftu (encoding elongation factor Tu) and using a shuttle expression vector. The resulting strain WL-14 produced 28.47 ± 0.36 g/L L-leucine in shake flask fermentation.


Assuntos
Carbono/metabolismo , Corynebacterium glutamicum/metabolismo , Leucina/biossíntese , Alanina/biossíntese , Ciclo do Ácido Cítrico , Corynebacterium glutamicum/genética , Fermentação , Microbiologia Industrial , Engenharia Metabólica , Plasmídeos/metabolismo , Ácido Pirúvico/metabolismo , Transaminases/metabolismo , Valina/biossíntese
19.
Sensors (Basel) ; 20(9)2020 May 06.
Artigo em Inglês | MEDLINE | ID: mdl-32384807

RESUMO

Within the framework of Internet of Things or when constrained in limited space, lensless imaging technology provides effective imaging solutions with low cost and reduced size prototypes. In this paper, we proposed a method combining deep learning with lensless coded mask imaging technology. After replacing lenses with the coded mask and using the inverse matrix optimization method to reconstruct the original scene images, we applied FCN-8s, U-Net, and our modified version of U-Net, which is called Dense-U-Net, for post-processing of reconstructed images. The proposed approach showed supreme performance compared to the classical method, where a deep convolutional network leads to critical improvements of the quality of reconstruction.

20.
Anal Chim Acta ; 1107: 74-84, 2020 Apr 22.
Artigo em Inglês | MEDLINE | ID: mdl-32200904

RESUMO

A sensitive, rapid, precise and specific analytical method of hydrophilic interaction ultra-performance liquid chromatography coupled with triple-quadrupole linear ion-trap tandem mass spectrometry (HILIC-UHPLC-QTRAP®/MS2) combined with a high-efficiency and easy sample preparation technology of ultrasound-assisted ionic liquid dispersive liquid-liquid microextraction (UA-IL-DLLME) was developed to investigate neurotransmitters (NTs) in mild cognitive impairment, mild dementia and moderate dementia patients' urine samples. Firstly, the UA-IL-DLLME parameters were optimized using Plackett-Burman screening and rotatable central composite design, and the main optimal conditions were obtained: ultrasound power of 307 W, ultrasound time of 4.3 min and agitation time of 4.8 min. Secondly, HILIC-UHPLC-QTRAP®/MS2 method was developed to simultaneously determine 15 underivatized NTs in urine samples. The analysis results of clinical samples showed that some NTs such as γ-aminobutyric acid (GABA), acetylcholine (Ach) and glutamic acid (Glu) presented significant differences in different dementia stages. Finally, multivariate analysis based on the combination of principal component analysis and supervised counter propagation artificial neural network was developed for comprehensive analysis of the obtained clinical data sets. As a result, GABA and Glu were simultaneously presented meaningful contribution for classification of samples, and might be considered as potential differential compounds to the urine samples from cluster patients with different dementia stages. In summary, the presented strategy of preparation, analysis and statistics might be used to investigate NTs in different clinical biological fluids.


Assuntos
Cromatografia Líquida de Alta Pressão/métodos , Demência/urina , Líquidos Iônicos/química , Microextração em Fase Líquida/métodos , Neurotransmissores/urina , Espectrometria de Massas em Tandem/métodos , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/urina , Feminino , Humanos , Limite de Detecção , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Ondas Ultrassônicas
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