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1.
Bioprocess Biosyst Eng ; 47(7): 1071-1080, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38811469

ABSTRACT

This study investigates the immobilization of cellulase on zeolitic imidazolate frameworks (ZIFs) by physical adsorption, specifically the ZIF-8-NH2 and Fe3O4@ZIF-8-NH2, to enhance enzymatic hydrolysis efficiency. The immobilization process was thoroughly analyzed, including optimization of conditions and characterization of ZIF carriers and immobilized enzymes. The impacts on the catalytic activity of cellulase under various temperatures, pH levels, and storage conditions were examined. Additionally, the reusability of the immobilized enzyme was assessed. Results showed the cellulase immobilized on Fe3O4@ZIF-8-NH2 exhibited a high loading capacity of 339.64 mg/g, surpassing previous studies. Its relative enzymatic activity was found to be 71.39%. Additionally, this immobilized enzyme system demonstrates robust reusability, retaining 68.42% of its initial activity even after 10 cycles. These findings underscore the potential of Fe3O4@ZIF-8-NH2 as a highly efficient platform for cellulase immobilization, with promising implications for lignocellulosic biorefinery.


Subject(s)
Cellulase , Cellulose , Enzymes, Immobilized , Zeolites , Enzymes, Immobilized/chemistry , Cellulase/chemistry , Zeolites/chemistry , Adsorption , Hydrolysis , Cellulose/chemistry , Imidazoles/chemistry , Hydrogen-Ion Concentration , Temperature
2.
BMC Anesthesiol ; 22(1): 389, 2022 12 15.
Article in English | MEDLINE | ID: mdl-36522711

ABSTRACT

BACKGROUND: Postpartum depression (PPD) is a serious complication commonly seen in postnatal women. In this paper, an investigation was conducted to see if obstetric anesthesia clinic childbirth course combined with labor epidural analgesia (LEA) was associated with a decreased risk of PPD. METHODS: Six hundred fifty-five nulliparous women were enrolled in this prospective cohort study. The parturients were divided into 4 groups, with Group C being the control group, Group AC received the obstetric anesthesia clinic childbirth course only, Group LEA received LEA only, and Group AC + LEA received both the obstetric anesthesia clinic childbirth course and LEA. Maternal and neonatal variables in the perinatal period were recorded. PPD at 6 weeks was assessed using the Chinese version of the Edinburgh Postpartum Depression Scale (EPDS), where a score ≥ 10 is the threshold for PPD. Multivariate logistic regression analysis was performed to assess the association between obstetric anesthesia clinic childbirth course combined with LEA and postpartum depression. RESULTS: A total of 124 maternities had EPDS ≥10 points, the incidence of PPD was 18.9%。The incidence of PPD and EPDS scores were significantly lower in Group AC + LEA than in Group C (12.1% vs 26.8%, P <  0.05; 6 (5, 7) vs 7 (5, 11), P <  0.05). Received an anesthesia clinic childbirth course combined with LEA was associated with a decreased risk of PPD (OR 0.273, 95% CI, 0.100-0.743, P = 0.013). Multivariate logistic regression analysis identified 5 other independent factors for PPD, including maternal SAS score in the delivery room, W-DEQ score in the delivery room, living in a confinement center, EPDS score at 1st week postpartum and perinatal care satisfaction . CONCLUSIONS: Received an obstetrics anesthesia clinic childbirth course combined with LEA for nulliparous women with a single term cephalic pregnancy was associated with a decreased risk of PPD at 6 weeks. TRIAL REGISTRATION: Chinese Clinical Trial Registry, ChiCTR2000039163. Registered on 20/10/2020.


Subject(s)
Analgesia, Epidural , Anesthesia, Obstetrical , Depression, Postpartum , Labor, Obstetric , Pregnancy , Infant, Newborn , Female , Humans , Depression, Postpartum/epidemiology , Depression, Postpartum/prevention & control , Prospective Studies , Analgesics
3.
J Am Pharm Assoc (2003) ; 62(2): 481-486, 2022.
Article in English | MEDLINE | ID: mdl-34776338

ABSTRACT

BACKGROUND: There is a lack of research on the nature of drug-related problems (DRPs) in older adult communities in China and the impact of home medication review on DRP reduction and health-related quality-of-life (HRQoL) improvement. OBJECTIVES: To identify and categorize DRPs in older adults in China and to assess the impact of home medication review. METHODS: The prospective study was conducted in 2 community health service centers in Shanghai, China from December 2018 to December 2019. Eligible patients received a home medication review by a clinical pharmacist to assess for DRPs and adherence, propose pharmaceutical interventions, and measure outcomes of HRQoL. All enrolled patients were followed up for 3 months. RESULTS: Medication use in 412 patients was analyzed. A total of 362 DRPs were identified, an average of 0.88 per patient. Treatment effectiveness was the primary DRP type (249; 68.8%). The most common causes of DRPs were patient-related (35.1%) and drug selection (31.0%). Pharmacists made 733 interventions, an average of 2 per DRP. A total of 82.1% of these interventions were accepted. At a 3-month follow-up, home medication review led to a statistically significant reduction in the mean number of DRPs (0.4 vs. 0.88, P < 0.001) and an increase in medication adherence (1.42 vs. 0.85, P < 0.001). Both HRQoL indicators also improved, EuroQol 5 Dimension scale (0.75 vs. 0.78, P < 0.001) and EuroQol-visual analog scale (70 vs. 77.65, P < 0.001). CONCLUSION: Home medication review is a practical means to optimize drug therapy and improve patients' HRQoL in community settings.


Subject(s)
Drug-Related Side Effects and Adverse Reactions , Quality of Life , Aged , China , Humans , Independent Living , Medication Review , Pharmacists , Prospective Studies
4.
J Environ Sci (China) ; 111: 38-50, 2022 Jan.
Article in English | MEDLINE | ID: mdl-34949366

ABSTRACT

Toxic heavy metal ions, valuable noble metal ions and organic dyes are significant concerns in wastewater treatment. In this work, MoO3 nanobelts (MoO3 NBs) prepared by solvothermal method and MoS2 nanoarrays (MoS2 NAs) constructed using MoO3 NBs precursor were proposed to effectively remove heavy/noble metal ions and organic dyes, such as Pb(II), Au(III) and Methylene Blue (MB). The two adsorbents exhibited the excellent adsorption capacity towards Pb(II), Au(III) and MB. The maximum removal capacity of Pb(II) and MB on MoO3 NBs was 684.93 mg/g and 1408 mg/g, respectively, whereas that of Au(III) and MB on MoS2 NAs was 1280.2 mg/g and 768 mg/g, respectively. Furthermore, the thermodynamic parameters were calculated from the temperature-dependent curves, suggesting that the removal of Pb(II) and Au(III) on both adsorbents was spontaneous and endothermic. The new adsorbents introduced here were high adsorption activity, ease of fabrication, high scalability, good chemical stability, great repeatability and abundant and cheap supply, which were highly attractive for wastewater treatment.


Subject(s)
Methylene Blue , Water Pollutants, Chemical , Adsorption , Hydrogen-Ion Concentration , Kinetics , Lead , Molybdenum , Water Pollutants, Chemical/analysis
5.
Zhongguo Zhong Yao Za Zhi ; 44(1): 40-47, 2019 Jan.
Article in Zh | MEDLINE | ID: mdl-30868810

ABSTRACT

Affinity chromatography is characterized by its high specificity,high recovery rate and sensitivity,and it has been widely used in the selection of active ingredients of traditional Chinese medicine,separation and enrichment of low molecular weight sugars and protein peptides,research on mechanism of action and discovery of targets.This paper reviewed the application of affinity chromatography and its adsorption isotherm model,kinetic model and adsorption thermodynamic mechanism in the field of traditional Chinese medicine.This summarizes and provides thinking for comprehensive applications of affinity chromatography theory in the field of active ingredient screening,purification and medicine interaction.


Subject(s)
Chromatography, Affinity , Drugs, Chinese Herbal/chemistry , Medicine, Chinese Traditional , Models, Theoretical , Adsorption
6.
Chemistry ; 24(5): 1080-1087, 2018 Jan 24.
Article in English | MEDLINE | ID: mdl-29027272

ABSTRACT

A novel MoS2 -based flower-like nanohybrid for hydrogen evolution was fabricated through coating the Cu-containing metal-organic framework (HKUST-1) onto MoS2 nanosheets. It is the first time that MoS2 @HKUST-1 nanohybrids have been reported for the enhanced electrochemical performance of HER. The morphologies and components of the MoS2 @HKUST-1 flower-like nanohybrids were characterized by scanning electron microscopy, X-ray diffraction analysis and Fourier transform infrared spectroscopy. Compared with pure MoS2 , the MoS2 @HKUST-1 hybrids exhibit enhanced performance on hydrogen evolution reaction with an onset potential of -99 mV, a smaller Tafel slope of 69 mV dec-1 , and a Faradaic efficiency of nearly 100 %. The MoS2 @HKUST-1 flower-like nanohybrids exhibit excellent stability in acidic media. This design opens new possibilities to effectively synthesize non-noble metal catalysts with high performance for the hydrogen evolution reaction (HER).

7.
Xenobiotica ; 48(4): 368-375, 2018 Apr.
Article in English | MEDLINE | ID: mdl-28532263

ABSTRACT

1. A novel bio-pharmacokinetic/pharmacodynamic (PK/PD) system was established and assessed in predicting the PK parameters and PD effects of the model drug cyclophosphamide (CP) considering the interrelationships between drug metabolism, pharmacological effects and dynamic blood circulation processes in vitro. 2. The system contains a peristaltic pump, a reaction chamber with rat liver microsomes (RLMs) encapsulated in pluronic F127-acrylamide-bisacrylamide (FAB) hydrogels, an effector cell chamber and a recirculating pipeline. The metabolism and pharmacological effects of CP (5, 10 and 20 mM) were measured by HPLC and MTT assay. A mathematical model based on mass balance was used to predict the in vitro clearance of CP. In vivo clearance of CP was estimated by in vitro to in vivo extrapolations (IVIVE) and simulations using Simcyp® software. 3. The predicted in vivo clearance of CP at concentrations of 5, 10 and 20 mM was 11.36, 10.12 and 10.68 mL/min/kg, respectively, within two-fold differences compared with the reported 11.1 mL/min/kg. The survival ratio of effector cells during the metabolism and circulation of CP was significantly enhanced. 4. This system may serve as an alternative approach to predict in vivo metabolism, pharmacological effects and toxicity of drugs, ensuring an efficient drug screening process.


Subject(s)
Bioreactors , Cyclophosphamide/pharmacokinetics , Microsomes, Liver/metabolism , Animals , Cyclophosphamide/pharmacology , Drug Evaluation, Preclinical/methods , Humans , MCF-7 Cells , Rats
8.
Zhongguo Zhong Yao Za Zhi ; 43(20): 4011-4018, 2018 Oct.
Article in Zh | MEDLINE | ID: mdl-30486524

ABSTRACT

Hypolipidemic polysaccharides have notable activity and safety with a range of diverse sources. In this paper, the classification of hypolipidemic polysaccharides was carried out into polysaccharide sulfate, glycosaminoglycan, homopolysaccharide and heteropolysaccharide. The hypolipidemic activity mechanism and structure-activity relationship hypothesis of those polysaccharides in recent years were briefly reviewed therefore to provide references for the study and product development of polysaccharides.


Subject(s)
Hypolipidemic Agents/chemistry , Hypolipidemic Agents/pharmacology , Polysaccharides/chemistry , Polysaccharides/pharmacology , Structure-Activity Relationship
9.
Drug Metab Dispos ; 44(1): 40-9, 2016 Jan.
Article in English | MEDLINE | ID: mdl-26467766

ABSTRACT

Currently used in vitro models for estimating liver metabolism do not take into account the physiologic structure and blood circulation process of liver tissue. The Bio-PK metabolic system was established as an alternative approach to determine the in vitro intrinsic clearance of the model drug tolbutamide. The system contained a peristaltic pump, recirculating pipeline, reaction chamber, and rat liver microsomes (RLMs) encapsulated in pluronic F127-acrylamide-bisacrylamide (FAB) hydrogel. The metabolism of tolbutamide at initial concentrations of 100, 150, and 200 µM was measured in both the FAB hydrogel and the circular medium. The data from the FAB hydrogel and the circular medium were fitted to a mathematical model to obtain the predicted intrinsic clearance of tolbutamide after different periods of preincubation. The in vitro clearance value for tolbutamide was incorporated into Simcyp software and used to predict both the in vivo clearance value and the dynamic process of elimination. The predicted in vivo clearance of tolbutamide was 0.107, 0.087, and 0.095 L/h/kg for i.v. injection and 0.113, 0.095, and 0.107 L/h/kg for oral administration. Compared with the reported in vivo clearance of 0.09 L/h/kg (i.v.) and 0.10 L/h/kg (oral), all the predicted values differed by less than twofold. Thus, the Bio-PK metabolic system is a reliable and general in vitro model, characterized by three-dimensional structured RLM and circulation and perfusion processes for predicting the in vivo intrinsic clearance of low-extraction compounds, making the system more analogous with the rat in terms of both morphology and physiology.


Subject(s)
Hydrogels/chemistry , Hypoglycemic Agents/metabolism , Microsomes, Liver/enzymology , Models, Biological , Tolbutamide/metabolism , Administration, Oral , Animals , Diffusion , Hypoglycemic Agents/administration & dosage , Infusion Pumps , Injections, Intravenous , Kinetics , Metabolic Clearance Rate , Microsomes, Liver/metabolism , Rats , Reproducibility of Results , Tolbutamide/administration & dosage
10.
Pharmacol Res ; 110: 101-110, 2016 08.
Article in English | MEDLINE | ID: mdl-27180010

ABSTRACT

Segetoside I is a plant-derived bisdesmosidic saponin from Vaccaria segetalis (Neck) with reported anticancer activities. This development has raised an interest in the therapeutic potential of segetoside I. Here, we report the in vitro and in vivo antitumor activities of segetoside I against some selected cancer cell lines (HepG2, human hepatoma; H22, mouse hepatoma; MCF-7, breast cancer; U251, gliocoma; BGC, HGC & SGC, gastric cancinoma; Lovo-1,colon cancer). MTT bioassay analysis showed that HepG2 cells were the most sensitive to segetoside I compared with other cancer cell lines, with lower toxicity in healthy mouse embryonic fibroblast cells. Segetoside I pretreatment of HepG2 resulted in apoptotic induction, dose-dependent DNA fragmentation, inhibition of cell migration, up-regulation of Bax and down-regulation of Bcl-2, which indicated that an apoptotic signaling event could have been initiated. The segetoside I also suppressed hepato-tumour growth in mice with virtually no cytotoxicity and prolonged animal survival, making it a strong oncology drug agent. These findings showed that segetoside I exhibited its antitumor activity via apoptotic induction and significantly support the possible application of the antitumor agent as a potential chemotherapeutic candidate worthy of further investigations.


Subject(s)
Antineoplastic Agents, Phytogenic/pharmacology , Apoptosis/drug effects , Carcinoma, Hepatocellular/drug therapy , Cell Proliferation/drug effects , Liver Neoplasms/drug therapy , Oleanolic Acid/analogs & derivatives , Saponins/pharmacology , Animals , Antineoplastic Agents, Phytogenic/toxicity , Carcinoma, Hepatocellular/metabolism , Carcinoma, Hepatocellular/pathology , Cell Movement/drug effects , Dose-Response Relationship, Drug , Hep G2 Cells , Humans , Inhibitory Concentration 50 , Lethal Dose 50 , Liver Neoplasms/metabolism , Liver Neoplasms/pathology , MCF-7 Cells , Mice , Oleanolic Acid/pharmacology , Oleanolic Acid/toxicity , Proto-Oncogene Proteins c-bcl-2/metabolism , Rats, Sprague-Dawley , Saponins/toxicity , Signal Transduction/drug effects , Tumor Burden/drug effects , Xenograft Model Antitumor Assays , bcl-2-Associated X Protein/metabolism
11.
Acta Pharmacol Sin ; 37(6): 834-44, 2016 Jun.
Article in English | MEDLINE | ID: mdl-27133301

ABSTRACT

AIM: Ergosterol is a plant sterol with anti-tumor and anti-angiogenic activities, but is poorly soluble. In this study, we attempted to enhance its anti-tumor action and oral bioavailability via poly(lactide-co-glycolide) (PLGA) nanoparticle encapsulation. METHODS: Ergosterol-loaded PLGA nanoparticles (NPs/Erg) were prepared using the emulsion/solvent evaporation technique. Their physicochemical properties were characterized, and their cytotoxicity against human cancer cell lines was evaluated with MTT assay. The pharmacokinetics and tissue distribution of NPs/Erg were investigated in rats and mice, respectively. RESULTS: NPs/Erg were spherical in shape with a particle size of 156.9±4.8 nm and a Zeta potential of -19.27±1.13 mV, and had acceptable encapsulation efficiency and loading capacity. NPs/Erg exerted much stronger cytotoxicity against human cancer cells than the free ergosterol, and showed significantly reduced IC50 values (14.69±0.48 µg/mL in glioma U251 cells; 9.43±0.52 µg/mL in breast cancer MCF-7 cells; 4.70±0.41 µg/mL in hepatoma HepG2 cells). After oral administration of a single dose in rats, NPs/Erg displayed a prolonged plasma circulation with a 4.9-fold increase of oral bioavailability compared with the free ergosterol. After mice received NPs/Erg, the ergosterol in NPs/Erg was rapidly distributed in stomach, kidneys, liver, brain, spleen, and virtually non-existent in heart and lungs. The presence of NPs/Erg in brain was particularly improved compared with the free ergosterol. CONCLUSION: The PLGA nanoparticles serve as a promising carrier for the poorly soluble ergosterol and significantly improve its bioavailability, biodistribution and in vitro anti-tumor activities.


Subject(s)
Antineoplastic Agents/administration & dosage , Antineoplastic Agents/pharmacokinetics , Drug Carriers/chemistry , Ergosterol/administration & dosage , Ergosterol/pharmacokinetics , Nanoparticles/chemistry , Polyglactin 910/chemistry , Administration, Oral , Animals , Antineoplastic Agents/pharmacology , Biological Availability , Cell Line, Tumor , Cell Survival/drug effects , Ergosterol/pharmacology , Humans , Male , Mice , Neoplasms/drug therapy , Neoplasms/metabolism , Neoplasms/pathology , Rats, Sprague-Dawley
12.
Biomed Chromatogr ; 30(3): 432-9, 2016 Mar.
Article in English | MEDLINE | ID: mdl-26184450

ABSTRACT

For quantitative and other related bioactive studies of hydnocarpin, there is a need to establish an efficient, specific and sensitive analytical method (in vitro and in vivo). In this paper, an efficient HPLC method has been established and validated to analyze hydnocarpin in a nanomicelle formulation for the first time. Various chromatographic conditions for in vitro and in vivo determinations were investigated, with the application examined by pharmacokinetics and tissue distribution studies. The analysis was carried out using an HPLC system with a Waters symmetry C18 column (4.6 × 150 mm, 5 µm) at 25°C with a detecting wavelength of 342 nm. Eluting at a rate of 1.0 mL/min, a 65% methanol and 35% acetic acid solution (0.1%) served as the mobile phase for the in vitro determinations while a 62% methanol and 38% acetic acid solution (0.1%) was used for in vivo analysis with isoliquiritigenin as internal standard. The established in vitro linearity range for hydnocarpin was 0.2-20 µg/mL (R(2) = 0.9996), with the biological (in vivo) samples following the same trend. The accuracy of the method was >99% (in vitro) and 92.4-105.3% (in vivo). Also, the precision met the acceptance criterion. These results indicate that the established method exhibited high specificity, accuracy, linearity and precision. Additionally, this efficient HPLC method was applied to pharmacokinetics and tissue distribution studies.


Subject(s)
Flavonolignans/blood , Micelles , Nanostructures/analysis , Animals , Chromatography, High Pressure Liquid/methods , Drug Stability , Flavonolignans/pharmacokinetics , Linear Models , Male , Mice , Rats , Rats, Sprague-Dawley , Reproducibility of Results , Sensitivity and Specificity , Tissue Distribution
13.
J Sci Food Agric ; 95(13): 2678-85, 2015 Oct.
Article in English | MEDLINE | ID: mdl-25400282

ABSTRACT

BACKGROUND: Capsaicin, as a food additive, has attracted worldwide concern owing to its pungency and multiple pharmacological effects. However, poor water solubility and low bioavailability have limited its application. This study aims to develop a capsaicin-loaded microemulsion to enhance the oral bioavailability of the anti-neuropathic-pain component, capsaicin, which is poorly water soluble. RESULTS: In this study, the microemulsion consisting of Cremophor EL, ethanol, medium-chain triglycerides (oil phase) and water (external phase) was prepared and characterized (particle size, morphology, stability and encapsulation efficiency). The gastric mucosa irritation test of formulated capsaicin was performed in rats to evaluate its oral feasibility, followed by the pharmacokinetic study in vivo. Under these conditions, the encapsulated capsaicin revealed a faster capsaicin release in vitro coupled with a greater absorption in vivo when compared to the free capsaicin. The oral bioavailability of the formulated capsaicin-loaded microemulsions was 2.64-fold faster than that of free capsaicin. No significant irritation was observed on the mucosa from the pathological section of capsaicin-loaded microemulsion treated stomach. CONCLUSION: These results indicate that the developed microemulsion represents a safe and orally effective carrier for poorly soluble substances. The formulation could be used for clinical trials and expand the application of capsaicin.


Subject(s)
Capsaicin/administration & dosage , Capsicum/chemistry , Emulsions , Plant Extracts/administration & dosage , Administration, Oral , Analgesics/administration & dosage , Analgesics/pharmacokinetics , Animals , Biological Availability , Capsaicin/pharmacokinetics , Chemistry, Pharmaceutical , Gastric Mucosa/drug effects , Male , Particle Size , Plant Extracts/pharmacokinetics , Rats, Sprague-Dawley , Solubility
14.
Zhongguo Zhong Yao Za Zhi ; 40(6): 1032-7, 2015 Mar.
Article in Zh | MEDLINE | ID: mdl-26226740

ABSTRACT

Affinity chromatography is a chromatographic method for separating molecules using the binding characteristics of the stationary phase with potential drug molecules. This method can be performed as a high throughput screening method and a chromatographic separation method to screen a variety of active drugs. This paper summarizes the history of affinity chromatography, screening technology of affinity chromatography, and application of affinity chromatography in screening bio-active compounds in herbal medicines, and then discusses its application prospects, in order to broaden applications of the affinity chromatography in drug screening.


Subject(s)
Chromatography, Affinity/methods , Drug Evaluation, Preclinical/methods , Drugs, Chinese Herbal/chemistry , Plants, Medicinal/chemistry , Animals , Chromatography, Affinity/trends , Drug Evaluation, Preclinical/trends , Drugs, Chinese Herbal/isolation & purification , Drugs, Chinese Herbal/pharmacology , Humans
15.
Biomed Chromatogr ; 28(2): 247-54, 2014 Feb.
Article in English | MEDLINE | ID: mdl-23996456

ABSTRACT

An efficient HPLC method was developed and validated for the simultaneous determination of ergosterol and 22,23-dihydroergosterol in Flammulina velutipes sterol-loaded microemulsions (FVSMs). The different chromatographic conditions for in vitro and in vivo determinations were investigated, with the application examined by tissue distribution. Chromatographic separation was achieved on an Inertsil ODS-SP (250 × 4.6 mm, 5 µm) analytical column using a mobile phase of 98% methanol (in vitro), and 93% methanol for stomach samples and 96% methanol for other samples (in vivo) at 1.0 mL/min. The sterol content was detected at 282 nm. The established in vitro linearity ranges for ergosterol and 22,23-dihydroergosterol were 0.58-72.77 µg/mL (r1 = 0.9999) and 0.59-73.25 µg/mL (r2 = 0.9999), respectively, with the biological (in vivo) samples following the same trend. The accuracy of the method was >99% (in vitro) and between 93%-108% (in vivo). The LOQ was 2.15 µg/L for ergosterol and 2.41 µg/L for 22,23-dihydroergosterol in the in vitro studies. Also, the precisions met the acceptance criterion. These results indicate that the established HPLC method was specific, linear, accurate, precise and sensitive for the separation and simultaneous determination of ergosterol and 22,23-dihydroergosterol.


Subject(s)
Chromatography, High Pressure Liquid/methods , Ergosterol/analogs & derivatives , Ergosterol/analysis , Flammulina/chemistry , Animals , Drug Stability , Emulsions , Ergosterol/blood , Ergosterol/chemistry , Ergosterol/pharmacokinetics , Linear Models , Mice , Reproducibility of Results , Sensitivity and Specificity
16.
Biomed Chromatogr ; 28(12): 1615-23, 2014 Dec.
Article in English | MEDLINE | ID: mdl-24706535

ABSTRACT

Novel lipid raft stationary phase chromatography (LRSC), with lipid rafts that contain abundant tropomyosin-related tyrosine kinase A receptors immobilized on the stationary phase, was developed for a high-throughput screening of potentially active antitumor agents. Lestaurtinib was used as a model compound to determine the operational parameters of the LRSC. Of all the factors considered, the particle size of column packing, the column temperature and the flow rate were of immense importance in determining the performance of the established LRSC system. In order to profoundly comprehend the binding interaction between the model drug and the receptors on the column, thermodynamic studies were employed. The results revealed that the interaction was spontaneous and exothermic, a typical enthalpy-driven process. Additionally, the primary forces were hydrogen bonding and van der Waals forces. In evaluating the applicability of the method, active extracts from Albizziae Cortex were screened out using the LRSC system under the optimized conditions. The bioactive components were successfully confirmed by the MTT assay. In conclusion, it could be said that the LRSC is a good model for screening potential antitumor agents because of its viability, rapid response and scalable features.


Subject(s)
Antineoplastic Agents/analysis , Antineoplastic Agents/metabolism , Chromatography, High Pressure Liquid/instrumentation , Chromatography, High Pressure Liquid/methods , Drug Discovery/methods , Membrane Microdomains/metabolism , Albizzia/chemistry , Antineoplastic Agents/chemistry , Carbazoles/analysis , Carbazoles/chemistry , Carbazoles/metabolism , Cell Line, Tumor , Furans , Humans , Membrane Microdomains/chemistry , Models, Chemical , Particle Size , Plant Extracts/chemistry , Thermodynamics
17.
Int J Clin Pharm ; 46(2): 471-479, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38245664

ABSTRACT

BACKGROUND: Teprotumumab was approved by the US Food and Drug Administration (FDA) for the treatment of thyroid eye disease in 2020. However, its adverse events (AEs) have not been investigated in real-world settings. AIM: This study aimed to detect and evaluate AEs associated with teprotumumab in the real-world setting by conducting a pharmacovigilance analysis of the FDA Adverse Event Reporting System (FAERS) database. METHOD: Reporting odds ratio (ROR) was used to detect risk signals from the data from January 2020 to March 2023 in the FAERS database. RESULTS: A total of 3,707,269 cases were retrieved, of which 1542 were related to teprotumumab. The FAERS analysis identified 99 teprotumumab-related AE signals in 14 System Organ Classes (SOCs). The most frequent AEs were muscle spasms (n = 287), fatigue (n = 174), blood glucose increase (n = 121), alopecia (n = 120), nausea (n = 118), hyperacusis (n = 117), and headache (n = 117). The AEs with strongest signal strengths were autophony (ROR = 14,475.49), deafness permanent (ROR = 1853.35), gingival recession (ROR = 190.74), deafness neurosensory (ROR = 129.89), nail growth abnormal (ROR = 103.67), onychoclasis (ROR = 73.58), ear discomfort (ROR = 72.88), and deafness bilateral (ROR = 62.46). Eleven positive AE signals were found at the standardized MedDRA queries (SMQs) level, of which the top five SMQs were hyperglycemia/new-onset diabetes mellitus, hearing impairment, gastrointestinal nonspecific symptoms and therapeutic procedures, noninfectious diarrhea, and hypertension. Age significantly increased the risk of hearing impairment. CONCLUSION: This study identified potential new and unexpected AE signals of teprotumumab. Our findings emphasize the importance of pharmacovigilance analysis in the real world to identify and manage AEs effectively, ultimately improving patient safety during teprotumumab treatment.


Subject(s)
Antibodies, Monoclonal, Humanized , Drug-Related Side Effects and Adverse Reactions , Hearing Loss , United States/epidemiology , Humans , United States Food and Drug Administration , Drug-Related Side Effects and Adverse Reactions/epidemiology , Data Mining , Pharmacovigilance , Adverse Drug Reaction Reporting Systems
18.
Mol Neurobiol ; 61(1): 252-265, 2024 Jan.
Article in English | MEDLINE | ID: mdl-37603153

ABSTRACT

The increased α-synuclein (α-syn)-dependent activation of CD4 T cells leads to the progressive loss of dopaminergic (DA) neurons in the substantia nigra (SN) in Parkinson's disease (PD). Astragaloside IV (AS-IV) protects DA neurons against neuroinflammation. The effects of AS-IV on CD4 T-cell-mediated immune responses in PD remain unknown. Rotenone (ROT) injected unilaterally into the substantia nigra pars compacta (SNc) of rats induced PD. AS-IV (20 mg/kg) was intraperitoneally injected once a day for 14 days. The limb hanging test and rotarod test were performed to evaluate the alteration of behavior at 4 and 6 weeks. Total gastrointestinal transit tests were performed at 4 weeks. Western blotting was used to detect the expression of proinflammatory cytokine proteins. Immunofluorescence staining was conducted to test the expression and localization of major histocompatibility complex class II (MHCII), cleaved caspase-1 and α-syn in astrocytes. Flow cytometry analysis, immunohistochemistry and immunofluorescence staining were used to measure the expression of CD4 T-cell subsets in the SN. The application of AS-IV protected against the loss of DA neurons and behavioral deficits in ROT-induced PD rat models. AS-IV administration inhibited the aggregation of α-syn in DA neurons and the expression of proinflammatory cytokines such as TNF-α, IL-18, IL-6 and IL-1ß. AS-IV decreased the activation of CD4 T cells and three CD4 T-cell subsets: Tfh, Treg and Th1. AS-IV interrupted the ROT-induced interaction between astrocytes and CD4 T cells and the colocalization of MHCII and α-syn in astrocytes. AS-IV inhibited the expression of α-syn in astrocytes and the colocalization of α-syn and cleaved caspase-1 in astrocytes. AS-IV prevents the loss of DA neurons in PD by inhibiting the activation of α-syn-specific CD4 T cells, which is regulated by MHCII-mediated antigen presentation in astrocytes.


Subject(s)
Parkinson Disease , Saponins , Triterpenes , alpha-Synuclein , Rats , Animals , alpha-Synuclein/metabolism , Rotenone/pharmacology , CD4-Positive T-Lymphocytes/metabolism , Parkinson Disease/metabolism , Dopaminergic Neurons/metabolism , Immunity , Caspases/metabolism
19.
Analyst ; 138(5): 1549-57, 2013 Mar 07.
Article in English | MEDLINE | ID: mdl-23350066

ABSTRACT

Graphene oxide (GO)/graphene (GN) nanosheets were coated onto the poly(glycidyl methacrylate-ethylene dimethacrylate) monolithic bed synthesized inside the capillary in order to prepare a promising polymer monolith microextraction (PMME) material (GO/GN@poly(GMA-EDMA)). Various techniques, including Fourier transform infrared spectroscopy, atomic force microscopy, transmission electron microscopy, X-ray photoelectron spectroscopy, and scanning electron microscopy, were employed to characterize the synthesized GO/GN@poly(GMA-EDMA) monoliths, confirming that GO/GN was effectively functionalized on the poly(GMA-EDMA) monolithic materials. Furthermore, a new method was developed for the analysis of sarcosine (identified as a potential prostate cancer biomarker) using PMME coupled with liquid chromatography-tandem mass spectrometry (LC-MS/MS). Under the preoptimized conditions, the monolithic column afforded satisfactory enhancement factor (32-fold) and low limits of detection (1.0 ng mL(-1)) were obtained. In comparison to several other commercialized solid phase extraction adsorbents, GN@poly(GMA-EDMA) monoliths exhibited excellent performance with recoveries of sarcosine approaching 93% with relative standard deviations less than 11.5%.

20.
Zhongguo Zhong Yao Za Zhi ; 38(20): 3409-12, 2013 Oct.
Article in Zh | MEDLINE | ID: mdl-24490544

ABSTRACT

Matrine is one of the main active components extracted from Sophora flavescens, S. subprostrata and S. alopecuroides. In recent years, its anti-tumor activity has attracted wide attention. According to studies, matrine shows the anti-tumor effect through multiple channels such as inducing apoptosis and autophagy of cancer cells, arresting cell cycle, inhibiting tumor cell migration, angiogenesis and NF-kappaB, as well as the synergistic effect with chemotherapeutics. Along with the further studies on matrine's anti-tumor mechanism, it has a broad prospect for development and application in tumor clinical treatment.


Subject(s)
Alkaloids/pharmacology , Antineoplastic Agents, Phytogenic/pharmacology , Neoplasms/drug therapy , Quinolizines/pharmacology , Animals , Cell Cycle/drug effects , Cell Proliferation/drug effects , Gene Expression Regulation, Neoplastic/drug effects , Humans , Neoplasms/genetics , Neoplasms/metabolism , Matrines
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