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ETHNOPHARMACOLOGICAL RELEVANCE: XBJ injection is approved by the China Food and Drug Administration for the adjunctive treatment of sepsis, and it is derived from the traditional Chinese medicine (TCM) prescription XuefuZhuyu Decoction. It consists of five Chinese herbal extracts: Carthamus tinctorius, Paeonia lactiflora, Salvia miltiorrhiza, Conioselinum anthriscoides 'Chuanxiong' and Angelica sinensis. AIM OF THE STUDY: The purpose of this study was to explore the relationship between ferroptosis and acute septic lung injury, and to evaluate the improvement effect of XBJ injection on acute lung injury in sepsis. MATERIALS AND METHODS: Acute lung injury was induced in rats by cecum ligation and puncture, and these rats were treated with XBJ injection. Oxidative stress and inflammation levels were assessed in serum and lung tissue, and tissue samples were collected for histological and protein analyses. To illustrate the mechanism of the improvement effect of XBJ on acute lung injury in sepsis, serum lipidomics was carried out to investigate whether XBJ prevents oxidative stress-induced lipid metabolism disorders. Furthermore, protein expression of ferroptosis-related genes was also examined. RESULTS: XBJ was shown to be effective in alleviating sepsis-induced ALI. XBJ also improves sepsis-induced acute lung injury by reducing lipid peroxidation and inflammation and modulating ferroptosis pathways. Specifically, compared with the sham group, XBJ downregulated the levels of Fe2+, MDA and GSSG, and reversed the decrease in the levels of GSH and GSH/GSSH in lung tissue. Metabolic pathways such as glycerophospholipid metabolism, phospholipid metabolism, and lipid metabolism associated with ferroptosis were obtained by lipidomic analysis of differential lipid metabolite enrichment, suggesting that ferroptosis occurs in septic rats, and that XBJ inhibits ferroptosis and thereby improves sepsis-induced ALI. Furthermore, XBJ optimises iron metabolism and lipid oxide metabolism by regulating the expression of a series of proteins that are closely related to ferroptosis, such as GPX4, ACSL4, x-CT, and FTH1. CONCLUSIONS: Our findings, initially, indicated that XBJ ameliorates sepsis-induced ALI by reducing oxidative stress and ferroptosis, revealing a previously unrecognised mechanism by which XBJ ameliorates sepsis-induced ALI.
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Therapeutic drug monitoring is essential for ensuring the efficacy and safety of medications. This study introduces a streamlined approach that combines pipette-tip solid-phase extraction (PT-SPE) with matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS), facilitating rapid and high-throughput monitoring of drug concentrations. As a demonstration, this method was applied to the extraction and quantification of antidepressants in serum. Utilizing Zip-Tip C18, the method enabled the extraction of antidepressants from complex biological matrices in less than 2 min, with the subsequent MALDI-MS analysis yielding results in just 1 min. Optimal extraction recoveries were achieved using a sampling solution at pH 9.0 and a 10 µL ethanol desorption solution containing 0.1% phosphoric acid. For MALDI analysis, 2,5-dihydroxybenzoic acid was identified as the most effective matrix for producing the highest signal intensity. The quantification strategy exhibited robust linearities (R2 ≥ 0.997) and satisfactory limits of quantification, ranging from 0.05 to 0.5 µg/mL for a suite of antidepressants. The application for monitoring dynamic concentration changes of antidepressants in rat serum emphasized the method's efficacy. This strategy offers the advantages of high throughput, minimal sample usage, environmental sustainability, and simplicity, providing ideas and a reference basis for the subsequent development of methods for therapeutic drug monitoring.
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Antidepressivos , Extração em Fase Sólida , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz , Extração em Fase Sólida/métodos , Animais , Antidepressivos/sangue , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz/métodos , Ratos , Limite de Detecção , Ensaios de Triagem em Larga Escala/métodos , Ratos Sprague-Dawley , Monitoramento de Medicamentos/métodos , MasculinoRESUMO
AIMS: Sodium tanshinone IIA sulfonate (STS) injection has been widely used as adjunctive therapy for pulmonary heart disease (PHD) in China. Nevertheless, the efficacy of STS injection has not been systematically evaluated so far. Hence, the efficacy of STS injection as adjunctive therapy for PHD was explored in this study. METHODS: Randomized controlled trials (RCTs) were screened from China Science and Technology Journal Database, China National Knowledge Infrastructure, Wanfang Database, PubMed, Sino-Med, Google Scholar, Medline, Chinese Biomedical Literature Database, Cochrane Library, Embase and Chinese Science Citation Database until 20 January 2024. Literature searching, data collection and quality assessment were independently performed by two investigators. The extracted data was analyzed with RevMan 5.4 and STATA 14.0. Basing on the methodological quality, dosage of STS injection, control group measures and intervention time, sensitivity analysis and subgroup analysis were performed. RESULTS: 19 RCTs with 1739 patients were included in this study. Results showed that as adjunctive therapy, STS injection combined with Western medicine showed better therapeutic efficacy than Western medicine alone for PHD by increasing the clinical effective rate (RR = 1.22; 95% CI, 1.17 to 1.27; p < 0.001), partial pressure of oxygen (MD = 10.16; 95% CI, 5.07 to 15.24; p < 0.001), left ventricular ejection fraction (MD = 8.66; 95% CI, 6.14 to 11.18; p < 0.001) and stroke volume (MD = 13.10; 95% CI, 11.83 to 14.38; p < 0.001), meanwhile decreasing the low shear blood viscosity (MD = -1.16; 95% CI, -1.57 to -0.74; p < 0.001), high shear blood viscosity (MD = -0.64; 95% CI, -0.86 to -0.42; p < 0.001), plasma viscosity (MD = -0.23; 95% CI, -0.30 to -0.17; p < 0.001), hematokrit (MD = -8.52; 95% CI, -11.06 to -5.98; p < 0.001), fibrinogen (MD = -0.62; 95% CI, -0.87 to -0.37; p < 0.001) and partial pressure of carbon dioxide (MD = -8.56; 95% CI, -12.09 to -5.02; p < 0.001). CONCLUSION: STS injection as adjunctive therapy seemed to be more effective than Western medicine alone for PHD. However, due to low quality of the included RCTs, more well-designed RCTs were necessary to verify the efficacy of STS injection.
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Medicamentos de Ervas Chinesas , Fenantrenos , Doença Cardiopulmonar , Humanos , Doença Cardiopulmonar/tratamento farmacológico , Injeções , Fenantrenos/uso terapêutico , Medicamentos de Ervas Chinesas/uso terapêuticoRESUMO
Bongkrekic acid (BA) poisoning can progress rapidly and lead to the failure of multiple organs, such as brain, liver and kidney. The mortality of BA poisoning is 40-100%. Little information is available on the toxicokinetic parameters of BA in human. Although hemodialysis is widely utilized for patients with severe BA poisoning, the exact amount of BA removed by hemodialysis is poorly documented. We analyzed toxicokinetic parameters, endogenous clearance and hemodialysis clearance in a patient with BA poisoning. A 27-year-old male developed symptoms of severe diarrhea, nausea, vomiting and weakness after eating rice noodles for more than one day. The patient developed multiple organ failures, especially the liver. Initial serum BA concentration was 0.5µg/mL. He received plasmapheresis, routing, and Oxiris-based Continuous Renal Replacement Therapy (CRRT). The whole blood, serum, urine and dialysate BA concentrations were collected and analyzed hourly. Toxicokinetic parameters relationships were determined using noncompartmental analysis. The clearances were determined using standard pharmacokinetic calculations. The disposition of BA was characterized by a long half-life (t1/2 of 102) and high max plasma (CL of 129,000 L/h/kg) following ingestion of contaminated food. The average serum clearance of BA during PE is remarkable higher than CRRT and the endogenous clearance. In contrast, the rates of decline in blood levels during the CRRT treatments were similar to the natural rate of decline. The total amount of BA removed by Plasmapheresis was 5.51mg. However, most CRRT failed to eliminate BA. We report a rare case of BA poisoning with a complication of liver failure and acute kidney damage. The patient expired, even with supportive care, plasmapheresis and hemodialysis. Analysis of whole blood, serum, urine and dialysate concentrations showed limited efficacy of CRRT in removing BA from blood. In contrast, there was significant extraction of BA from Plasmapheresis.
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Rim , Fígado , Masculino , Humanos , Adulto , Ácido Bongcréquico , Toxicocinética , Soluções para DiáliseRESUMO
BACKGROUND: During the last 40 years, Danshen injection has been widely used as an adjunctive therapy for angina pectoris in China, but its efficacy is not yet well defined. The objective of this study was to verify the efficacy of Danshen injection as adjunctive therapy in treating angina pectoris. METHODS: The major databases including PubMed, Cochrane Library, Sino-Med, Medline, Embase, Google Scholar, China National Knowledge Infrastructure, Wanfang Databases, Chinese Scientific Journal Database, Chinese Biomedical Literature Database and the Chinese Science Citation Database were systematically searched for the published randomised controlled trials (RCTs) on Danshen injection until April 2016. Meta-analysis was conducted on the primary outcomes (i.e., the improvements in symptoms and electrocardiography (ECG)). The quality of the included RCTs was evaluated with the M scoring system (the refined Jadad scale). Based on the quality, year of publication and sample size of RCTs, sensitivity analysis and subgroup analysis were performed in this study. RESULTS: Ten RCTs, including 944 anginal patients, were identified in this meta-analysis. Compared with using antianginal agents (ß-blockers, calcium antagonists, nitrates, etc.) alone, Danshen injection combined with antianginal agents had a better therapeutic effect in symptom improvement (odds ratio [OR], 3.66; 95% confidence interval [CI]: 2.50-5.36) and in ECG improvement (OR, 3.25; 95% CI: 1.74-6.08). CONCLUSIONS: This study showed that Danshen injection as adjunctive therapy seemed to be more effective than antianginal agents alone in treating angina pectoris. However, more evidence is needed to accurately evaluate the efficacy of Danshen injection because of the low methodological quality of the included RCTs.
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Angina Pectoris/tratamento farmacológico , Medicamentos de Ervas Chinesas/administração & dosagem , Inibidores da Agregação Plaquetária/administração & dosagem , Salvia miltiorrhiza , Angina Pectoris/diagnóstico , Animais , Quimioterapia Adjuvante , Eletrocardiografia , Humanos , Injeções IntravenosasRESUMO
BACKGROUND In the past decades, a large number of randomized controlled trials (RCTs) on the efficacy of ligustrazine injection combined with conventional antianginal drugs for angina pectoris have been reported. However, these RCTs have not been evaluated in accordance with PRISMA systematic review standards. The aim of this study was to evaluate the efficacy of ligustrazine injection as adjunctive therapy for angina pectoris. MATERIAL AND METHODS The databases PubMed, Medline, Cochrane Library, Embase, Sino-Med, Wanfang Databases, Chinese Scientific Journal Database, Google Scholar, Chinese Biomedical Literature Database, China National Knowledge Infrastructure, and the Chinese Science Citation Database were searched for published RCTs. Meta-analysis was performed on the primary outcome measures, including the improvements of electrocardiography (ECG) and the reductions in angina symptoms. Sensitivity and subgroup analysis based on the M score (the refined Jadad scores) were also used to evaluate the effect of quality, sample size, and publication year of the included RCTs on the overall effect of ligustrazine injection. RESULTS Eleven RCTs involving 870 patients with angina pectoris were selected in this study. Compared with conventional antianginal drugs alone, ligustrazine injection combined with antianginal drugs significantly increased the efficacy in symptom improvement (odds ratio [OR], 3.59; 95% confidence interval [CI]: 2.39 to 5.40) and in ECG improvement (OR, 3.42; 95% CI: 2.33 to 5.01). Sensitivity and subgroup analysis also confirmed that ligustrazine injection had better effect in the treatment of angina pectoris as adjunctive therapy. CONCLUSIONS The 11 eligible RCTs indicated that ligustrazine injection as adjunctive therapy was more effective than antianginal drugs alone. However, due to the low quality of included RCTs, more rigorously designed RCTs were still needed to verify the effects of ligustrazine injection as adjunctive therapy for angina pectoris.
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Angina Pectoris/tratamento farmacológico , Pirazinas/uso terapêutico , Quimioterapia Adjuvante , Medicamentos de Ervas Chinesas , Humanos , Inibidores da Agregação Plaquetária/uso terapêutico , Ensaios Clínicos Controlados Aleatórios como AssuntoRESUMO
The molecularly imprinted solid-phase extraction (MISPE) monolithic column coupled with high-performance liquid chromatography (HPLC) was firstly developed for the extraction of hesperetin in the flesh of Citrus reticulata cv. Chachiensis, which is a traditional Chinese medicine (TCM). The molecularly imprinted polymers (MIPs) have been prepared by a thermal polymerization method using hesperetin as the template, acrylamide (AM) as functional monomer and ethylene glycol dimethacrylamide (EGDMA) as cross-linker in the mixed porogen of methanol, toluene and dodecanol. The prepared MIPs were characterized in detail by SEM and FTIR. The results confirmed the uniform and open structure of network skeleton with large flow-through pores. The influence of synthesis conditions on the specific recognition properties of hesperetin MIPs were also investigated systematically. The results showed that high adsorption capacity and good selectivity of MIPs were achieved when using non-imprinted polymer monolith (NIP) and structure similarly compound rutin as references. Furthermore, several parameters of the MISPE method have been optimized, and then it was successfully applied to the extraction of hesperetin from the flesh of Citrus reticulata cv. Chachiensis. Good gathering and impurity removing ability of prepared MIP were demonstrated. The MISPE method was proven to be a potentially competitive technique for separation and cleanup of hesperetin in complex TCM with satisfied recovery (90.8 ± 3.2%) and good precision (RSD = 6.48%).
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Hesperidina/química , Extratos Vegetais/química , Acrilamida/química , Adsorção , Cromatografia Líquida de Alta Pressão/métodos , Citrus/química , Medicina Tradicional Chinesa/métodos , Metanol/química , Impressão Molecular/métodos , Polimerização , Polímeros/química , Rutina/química , Extração em Fase Sólida/métodosRESUMO
Gold nanoparticles (Au NPs) were synthesized and stabilized by using water-soluble quaternized cellulose (QC) as support matrix through a straightforward and environmentally friendly aqueous-phase approach. The structure and morphology of QC-supported Au NPs (QC-Au NPs) were investigated systematically by UV-visible, FT-IR, x-ray diffraction and TEM measurement. The Au NPs with mean diameter of about 7nm were shown to efficiently redisperse in water due to the strong interaction between QC and Au NPs, and the solutions were quite stable after storage for nearly 4 months at room temperature. QC-Au NPs were subsequently used as novel physically adsorbed coatings for protein separation by CE. The separation performance was significantly improved in the capillary coated by QC-Au NPs compared with that of the uncoated capillary or QC coated capillary. A small quantity of Au NPs (Au content of 4.6%) was adequate for the obvious improvement of coating ability. The theoretical plate number of lysozyme in QC-Au1 NPs coated capillary was 2.9 times as much as that in QC coated capillary. We have demonstrated the separation of six model proteins with RSD of migration time less than 2.79% and RSD of peak area less than 4.81%. Furthermore, QC-Au NPs was applied to the analysis of closely related proteins and biological samples. With simplicity, high resolution and reproducibility, the proposed method shows potential for applications in proteomics and clinical diagnosis.
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Celulose/química , Eletroforese Capilar/métodos , Ouro/química , Nanopartículas Metálicas/química , Proteínas/análise , Animais , Microscopia Eletrônica de Transmissão , Leite/química , Reprodutibilidade dos Testes , Espectroscopia de Infravermelho com Transformada de FourierRESUMO
Hydrophobically modified quaternized celluloses (HMQCs), containing the quaternary ammonium groups and hexadecyl groups, were homogeneously synthesized as novel dynamic coatings for CE. Compared with quaternized cellulose coating, HMQC coating is able to generate stronger reversed EOF (ca. 10% increase) and has better efficiency in suppressing protein adsorption. The effects of the polymer concentration, the degree of hydrophobic substitution, and the buffer pH on the EOF mobility as well as on the separation of basic proteins were investigated in detail. It was shown that the use of HMQC coating could obviously improve the separation performance of basic proteins within a broad pH range. Five basic proteins (lysozyme, ribonuclease A, cytochrome c, bovine pancreatic trypsin inhibitor, and chymotrypsinogen) could be completely separated at pH 8.0. The successful performance of HMQC was further demonstrated by the analyses of lysozyme in tear and urine samples.
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Celulose/química , Eletroforese Capilar/métodos , Proteínas/isolamento & purificação , Adulto , Animais , Bovinos , Feminino , Humanos , Concentração de Íons de Hidrogênio , Interações Hidrofóbicas e Hidrofílicas , Masculino , Muramidase/análise , Muramidase/isolamento & purificação , Muramidase/urina , Proteínas/análise , Reprodutibilidade dos Testes , Propriedades de Superfície , Lágrimas/químicaRESUMO
In this work, a series of quaternized celluloses (QCs), homogeneously synthesized in the NaOH/urea aqueous solutions, were studied as dynamic coatings for capillary electrophoresis. Capillaries coated with these cationic cellulose derivatives at the concentration as low as 3 µg/mL were able to generate a stable, reversed electroosmotic flow. The effects of QC molecular parameters, such as the degree of cationic substitution and molecular weight, and the effect of buffer pH on the EOF mobility as well as the separation of basic proteins were investigated in detail. It was shown that the use of QC coatings in CE could drastically reduce the analysis time and improve the separation performance within a broad pH range. Five basic proteins, that is, lysozyme, ribonuclease A, cytochrome C, bovine pancreatic trypsin inhibitor, and chymotrypsinogen were baselinely separated even at pH 8.0. The separation efficiency and analysis reproducibility demonstrated that the QC coatings were efficient in minimizing the adsorption of basic proteins on the fused silica capillary. The successful performance was further demonstrated for biosample analysis.