Multiomics profiling of the therapeutic effect of Dan-deng-tong-nao capsule on cerebral ischemia-reperfusion injury.

BACKGROUND: Stroke is a complex physiological process associated with intestinal flora dysbiosis and metabolic disorders. Dan-deng-tong-nao capsule (DDTN) is a traditional Chinese medicine used clinically to treat cerebral ischemia-reperfusion injury (CIRI) for many years. However, little is known about the effects of DDTN in the treatment of CIRI from the perspective of gut microbiota and metabolites. PURPOSE: This study aimed to investigate the regulatory roles of DDTN in endogenous metabolism and gut microbiota in CIRI rats, thus providing a basis for clinical rational drug use and discovering natural products with potential physiological activities in DDTN for the treatment of CIRI. METHODS: The chemical composition of DDTN in vitro and in vivo was investigated using ultra-high performance liquid chromatography-high resolution mass spectrometry (UHPLCHRMS), followed by target prediction using reverse molecular docking. Secondly, a biological evaluation of DDTN ameliorating neural damage in CIRI was performed at the whole animal level. Then, an integrated omics approach based on UHPLCHRMS and 16S rRNA sequencing was proposed to reveal the anti-CIRI effect and possible mechanism of DDTN. Finally, exploring the intrinsic link between changes in metabolite profiles, changes in the intestinal flora, and targets of components to reveal DDTN for the treatment of CIRI. RESULTS: A total of 112 chemical components of DDTN were identified in vitro and 10 absorbed constituents in vivo. The efficacy of DDTN in the treatment of CIRI was confirmed by alleviating cerebral infarction and neurological deficits. After the DDTN intervention, 21 and 26 metabolites were significantly altered in plasma and fecal, respectively. Based on the fecal microbiome, a total of 36 genera were enriched among the different groups. Finally, the results of the network integration analysis showed that the 10 potential active ingredients of DDTN could mediate the differential expression of 24 metabolites and 6 gut microbes by targeting 25 target proteins. CONCLUSION: This study was the first to outline the landscapes of metabolites as well as gut microbiota regulated by DDTN in CIRI rats using multi-omics data, and comprehensively revealed the systematic relationships among ingredients, targets, metabolites, and gut microbiota, thus providing new perspectives on the mechanism of DDTN in the treatment of CIRI.

Mn Single-Atom Nanozyme Functionalized 3D-Printed Bioceramic Scaffolds for Enhanced Antibacterial Activity and Bone Regeneration.

Infective bone defect is increasingly threatening human health. How to achieve the optimal antibacterial activity and regenerative repair of infective bone defect simultaneously is a huge challenge in clinic. Herein, this work reports a rational integration of Mn single-atom nanozyme into the 3D-printed bioceramic scaffolds (Mn/HSAE@BCP scaffolds). The integrated Mn/HSAE@BCP scaffolds can catalyze the conversion of H2O2 to produce hydroxyl radical (•OH) and superoxide anion (O2 •-) through cascade reaction. Besides, the prominent thermal conversion efficiency of Mn/HSAE@BCP scaffolds can be utilized for sonodynamic therapy (SDT). The synergetic strategy of chemodynamic therapy (CDT)/SDT enables the sufficient generation of reactive oxygen species (ROS) to kill Staphylococcus aureus (S. aureus) or Escherichia coli (E. coli). Furthermore, the enhanced antibacterial efficacy of Mn/HSAE@BCP scaffolds is beneficial to upregulate the expression of osteogenesis-related markers (such as collagen 1(COL1), Runt-related transcription factor 2 (Runx2), osteocalcin (OCN), and osteoprotegerin (OPG)) in vitro and further promote bone regeneration in vivo. The results demonstrate the good potential of Mn/HSAE@BCP scaffolds for the enhanced antibacterial activity and bone regeneration, which provide an effective method for the treatment of clinical infective bone defect.

Pseudo-allergic reactions induced by Chinese medicine injections: a review.

Traditional Chinese medicine injections (TCMIs) is a new dosage form of Chinese medicine, which plays a unique role in rescuing patients with critical illnesses that are difficult to replace. With the rapid development and widespread application of TCMIs in recent years, their adverse events have emerged and attracted much attention. Among them, pseudo-allergic reactions, i.e., the most significant adverse reactions occurring with the first dose without immunoglobulin E mediated conditions. Currently, studies on the types of TCMIs and antibiotic mechanisms that cause pseudo-allergic reactions are incomplete, and standard models and technical guidelines for assessing TCMIs have not been established. First, this review describes the causes of pseudo-allergic reactions, in which the components and structures responsible for pseudo-allergic reactions are summarized. Second, the mechanisms by which pseudo-allergic reactions are discussed, including direct stimulation of mast cells and complement activation. Then, research models of pseudo-allergic reaction diseases are reviewed, including animal models and cellular models. Finally, the outlook and future challenges for the development of pseudo-allergic reactions in traditional Chinese medicine (TCM) are outlined. This shed new light on the assessment and risk prevention of pseudo-allergic reactions in TCM and the prevention of clinical adverse reactions in TCM.

UHPLC-HRMS-based metabolomic and lipidomic characterization of glioma cells in response to anlotinib.

Anlotinib, as a promising oral small-molecule antitumor drug, its role in glioma has been only reported in a small number of case reports. Therefore, anlotinib has been considered as a promising candidate in glioma. The aim of this study was to investigate the metabolic network of C6 cells after exposure to anlotinib and to identify anti-glioma mechanism from the perspective of metabolic reprogramming. Firstly, CCK8 method was used to evaluate the effects of anlotinib on cell proliferation and apoptosis. Secondly, ultra-high performance liquid chromatography-high resolution mass spectrometry (UHPLC-HRMS)-based metabolomic and lipidomic were developed to characterize the metabolite and lipid changes in cell and cell culture medium (CCM) caused by anlotinib in the treatment of glioma. As a result, anlotinib had concentration-dependent inhibitory effect with the concentration range. In total, twenty-four and twenty-three disturbed metabolites in cell and CCM responsible for the intervention effect of anlotinib were screened and annotated using UHPLC-HRMS. Altogether, seventeen differential lipids in cell were identified between anlotinib exposure and untreated groups. Metabolic pathways, including amino acid metabolism, energy metabolism, ceramide metabolism, and glycerophospholipid metabolism, were modulated by anlotinib in glioma cell. Overall, anlotinib has an effective treatment against the development and progression of glioma, and these remarkable pathways can generate the key molecular events in cells treated with anlotinib. Future research into the mechanisms underlying the metabolic changes is expected to provide new strategies for treating glioma.

Study of the effects of Au@ZIF-8 on metabolism in mouse RAW 264.7 macrophages.

Mass spectrometry-based metabolomics plays a vital role in discovering new markers and revealing the unpredictable biological effects of external stimuli. However, the current metabolomics research on materials is still in its infancy, and in-depth research on possible toxic mechanisms is lacking. In this study, a nanocomposite of gold nanoparticles (AuNPs)-zeolite-imidazole framework-8 (ZIF-8) (Au@ZIF-8) was designed to investigate its effects on metabolism in mouse RAW 264.7 macrophages. The successful synthesis of Au@ZIF-8 was confirmed by transmission electron microscopy (TEM) and elemental analysis. The changes in the metabolic activity of mouse RAW 264.7 macrophages at different concentrations of Au@ZIF-8 and different treatment times were investigated, and their influence on the morphological changes and behavior of RAW 264.7 cells was discussed. In addition, ultrahigh-performance liquid chromatography quadrupole-orbital high-resolution mass spectrometry (UHPLC/Q-Orbitrap HRMS) was used to study the metabolic effects of Au@ZIF-8 on RAW 264.7 cells, and the results showed different metabolites being expressed at different reaction times. After 4, 8 and 24 h of treatment, the differential expression of 14, 16, and 16 metabolites, respectively, was detected. Twenty-five candidate key metabolites were identified from the results of the expression patterns and metabolic pathways. These metabolites are related to glutamine metabolism, the tricarboxylic acid cycle and glycolytic metabolic pathways, which may provide insight into the treatment of diseases caused and progressed by glutamine metabolism. This study also indicates the effectiveness of high-resolution LC-MS in revealing the nanotoxicity mechanism of Au@ZIF-8.

Surface molecularly imprinted polymers fabricated by differential UV-vis spectra and reverse prediction method for the enrichment and determination of sterigmatocystin.

A novel magnetic molecularly imprinted polymers (MMIPs) with a new functional monomer Triallyl isocyanurate was synthesized successfully to enrich and detect sterigmatocystin (STG) in wheat samples. The differential UV-vis spectra and the reverse prediction method were selected to achieve the optimal synthesis conditions of the MMIPs, which were characterized well. The adsorption experiment showed that MMIPs have high selectivity and sensitivity. A magnetic solid phase extraction combined with high performance liquid chromatography (MSPE-HPLC) method based on the MMIPs was successfully established with the optimal extraction condition. The linear range and RSD were 1.8-25 ng·g-1 and 2.6-4.1%, respectively. The recovery of this method was 87.6-96.9% and the limit of detection (LOD) was 0.63 ng·g-1. The excellent sensitivity and selectivity of this method were confirmed by experiment of the extraction and detection of STG in wheat extracts. This work extends the use of molecular imprinting in mycotoxins applications.

Metabolomics and Transcriptomics Analysis on Metabolic Characteristics of Oral Lichen Planus.

OBJECTIVE: To explore metabolic biomarkers related to erosive and reticulated oral lichen planus (OLP) by non-targeted metabolomics methods and correlate metabolites with gene expression, and to investigate the pathological network pathways of OLP from the perspective of metabolism. METHODS: A total of 153 individuals were enrolled in this study, including 50 patients with erosive oral lichen planus (EOLP), 51 patients with reticulated oral lichen planus (ROLP), and 52 healthy controls (HC). The ultra-high-performance liquid chromatography quadrupole-Orbitrap high-resolution accurate mass spectrometry (UHPLC/Q-Orbitrap HRMS) was used to analyze the metabolites of 40 EOLP, 40 ROLP, and 40 HC samples, and the differential metabolic biomarkers were screened and identified. The regulatory genes were further screened through the shared metabolites between EOLP and ROLP, and cross-correlated with the OLP-related differential genes in the network database. A "gene-metabolite" network was constructed after finding the key differential genes. Finally, the diagnostic efficiency of the biomarkers was verified in the validation set and a diagnostic model was constructed. RESULT: Compared with HC group, a total of 19 and 25 differential metabolites were identified in the EOLP group and the ROLP group, respectively. A total of 14 different metabolites were identified between EOLP and ROLP. Two diagnostic models were constructed based on these differential metabolites. There are 14 differential metabolites shared by EOLP and ROLP. The transcriptomics data showed 756 differentially expressed genes, and the final crossover network showed that 19 differential genes were associated with 12 metabolites. Enrichment analysis showed that alanine, aspartate and glutamate metabolism were closely associated with the pathogenesis of OLP. CONCLUSION: The metabolic change of different types of OLP were clarified. The potential gene perturbation of OLP was provided. This study provided a strong support for further exploration of the pathogenic mechanism of OLP.

Association of Coronary Artery Disease and Metabolic Syndrome: Usefulness of Serum Metabolomics Approach.

Introduction: Individuals with metabolic syndrome (MetS) are at increasing risk of coronary artery disease (CAD). We investigated the common metabolic perturbations of CAD and MetS via serum metabolomics to provide insight into potential associations. Methods: Non-targeted serum metabolomics analyses were performed using ultra high-performance liquid chromatography coupled with Q Exactive hybrid quadrupole-orbitrap high-resolution accurate mass spectrometry (UHPLC-Q-Orbitrap HRMS) in samples from 492 participants (272 CAD vs. 121 healthy controls (HCs) as cohort 1, 55 MetS vs. 44 HCs as cohort 2). Cross-sectional data were obtained when the participants were recruited from the First Affiliated Hospital of Zhengzhou University. Multivariate statistics and Student's t test were applied to obtain the significant metabolites [with variable importance in the projection (VIP) values >1.0 and p values <0.05] for CAD and MetS. Logistic regression was performed to investigate the association of identified metabolites with clinical cardiac risk factors, and the association of significant metabolic perturbations between CAD and MetS was visualized by Cytoscape software 3.6.1. Finally, the receiver operating characteristic (ROC) analysis was evaluated for the risk prediction values of common changed metabolites. Results: Thirty metabolites were identified for CAD, mainly including amino acids, lipid, fatty acids, pseudouridine, niacinamide; 26 metabolites were identified for MetS, mainly including amino acids, lipid, fatty acids, steroid hormone, and paraxanthine. The logistic regression results showed that all of the 30 metabolites for CAD, and 15 metabolites for MetS remained significant after adjustments of clinical risk factors. In the common metabolic signature association analysis between CAD and MetS, 11 serum metabolites were significant and common to CAD and MetS outcomes. Out of this, nine followed similar trends while two had differing directionalities. The nine common metabolites exhibiting same change trend improved risk prediction for CAD (86.4%) and MetS (90.9%) using the ROC analysis. Conclusion: Serum metabolomics analysis might provide a new insight into the potential mechanisms underlying the common metabolic perturbations of CAD and MetS.

Visual Recognition and Detection of Clindamycin by Au@Ag Core-Shell Nanoparticles.

The work described a new colorimetric sensor for the quantitative detection of clindamycin based on Au@Ag core-shell nanoparticles (Au@Ag NPs). The obtained Au@Ag NPs were characterized by transmission electron microscopy (TEM) and ultraviolet and visible spectrophotometry (UV-vis). When Au@Ag NPs were added to a clindamycin solution, it can be observed that the color immediately changed from bright yellow to gray-blue and the absorption spectrum also changed, realizing the visual detection of clindamycin. Under optimal conditions, the absorption ratio (A 546/A 400) of the UV-vis spectra increased linearly with the concentration of clindamycin ranging from 6.25 × 10-7 to 7.50 × 10-6 mol/L (R 2 = 0.9945), with a limit of detection (LOD) of 2.00 × 10-7 mol/L and good recovery of 100.0-102.0% (relative standard deviation (RSD) < 2%). The detection process was convenient without complicated instruments. Compared with other analytes, the Au@Ag NPs detection system has good selectivity for clindamycin. In addition, the Au@Ag NPs colorimetric sensor was successfully used to determine clindamycin in human urine samples. This study provides a simple, rapid, intuitive, and low-cost visualization analysis method of clindamycin, which was helpful for the visualization detection of other targets.

Integrative Analysis of Metabolomic and Transcriptomic Data Reveals Metabolic Alterations in Glioma Patients.

Glioma is a malignant brain tumor. There is growing evidence that its progression involves altered metabolism. This study's objective was to understand how those metabolic perturbations were manifested in plasma and urine. Metabolic signatures in blood and urine were characterized by liquid chromatography-tandem mass spectrometry. The results were linked to gene expression using data from the Gene Expression Omnibus database. Genes and pathways associated with the disease were thus identified. Forty metabolites were identified, which were differentially expressed in the plasma of glioma patients, and 61 were identified in their urine. Twenty-two metabolites and five disturbed pathways were found both in plasma and urine. Twelve metabolites in plasma and three in urine exhibited good diagnostic potential for glioma. Transcriptomic analyses revealed specific changes in the expression of 1437 genes associated with glioma. Seventeen differentially expressed genes were found to be correlated with four of the metabolites. Enrichment analysis indicated that dysregulation of glutamatergic synapse pathway might affect the pathology of glioma. Integration of metabolomics with transcriptomics can provide both a broad picture of novel cancer signatures and preliminary information about the molecular perturbations underlying glioma. These results may suggest promising targets for developing effective therapies.

Human Saliva Metabolome for Oral Lichen Planus Biomarker Identification.

BACKGROUND: Oral Lichen Planus (OLP) is one of the most common oral mucosal diseases. However, the current diagnostic method for OLP has limitations, and sometimes it is easy to be misdiagnosed. Salivary metabolomics may provide new ideas for the diagnosis of OLP. OBJECTIVE: To identify the biomarkers for the early detection of OLP. METHODS: A non-targeted metabolomic analysis method was established based on UHPLC-Q-Orbitrap HRMS (Ultra-performance liquid chromatography-quadrupole/orbitrap high resolution mass spectrometry) to analyze the differential metabolites in saliva samples of patients with OLP and healthy subjects. Saliva samples were collected from 120 OLP patients and 125 healthy subjects. RESULTS: A total of 19 differential metabolites were identified, including 6 amino acid metabolites, 2 carnitines, 2 lipid metabolites and 9 other metabolites. The integrated biomarkers were constructed by 3 metabolites according to Receiver Operating Characteristic (ROC). Meanwhile, multiple metabolic pathways were found to be involved in the occurrence and development of OLP. CONCLUSION: Metabolomics can be used to characterize the characteristics of metabolic disorders in patients with OLP, which is also helpful to the early diagnosis of OLP and reveal the pathological process of OLP.

Fluorescence determination of quercetin in food samples using polyhedron-shaped MOF@MOF(NUZ-8) based on NH2-UiO-66 and ZIF-8.

A new metal-organic framework compound (MOF@MOF, NUZ-8) comprised of NH2-UiO-66 and ZIF-8 under the polyvinylpyrrolidone (PVP) as the structure modifier was synthesized through an internal extended growth method (IEGM). The resulting NUZ-8 emerged the unreported unique polyhedron shape and showed considerable specific surface area (1466.1862 m2/g), excellent adsorption capacity, and fluorescence. NUZ-8 was used as a probe for the rapid optical detection of natural antioxidant quercetin (QCT). Its outstanding selectivity and sensitivity to QCT are derived from the fact that NH2-UiO-66 acted as an optical tentacle to perceive QCT in virtue of its luminescence advantages, and ZIF-8 realized the selective enrichment of the QCT through its electron-rich framework structure. The experiments were carried out at an excitation wavelength of 335 nm and an emission wavelength range of 370-530 nm. Under conditions of the investigation, this probe realized the rapid detection of QCT and considerable adsorption capacity with wide linearity (0.3-80 µM), a low detection limit (0.14 µM), and acceptable recoveries (84.0-97.0%) in red wine samples, properties which were superior to many other detection platforms. The synthesis and the use of the above polyhedral composite provide guidance for the application of the IEGM in enhancing chemical sensing and instant determination of drugs.Graphical abstract Flow chart of this paper.

Alpiniae oxyphyllae Fructus and Alzheimer's disease: An update and current perspective on this traditional Chinese medicine.

Alzheimer's disease (AD) is a common progressive neuro-degenerative disease, and the morbidity and mortality are still on the rise. In spite of recent advances in AD treatment, their clinical efficacy has been limited, non-curative and easy to drug resistance. Alpiniae oxyphyllae Fructus (AOF), derived from the dried and mature fruits of the Zingiberaceae plant Alpinia oxyphylla Miq, is a choice in traditional Chinese medicine to treat AD, which has a good effect and has been used for a long time. Recent studies have demonstrated its potent activities in modulating multiple signaling pathways associated with ß-amyloid deposition, tau protein phosphorylation, chronic inflammation, oxidative stress. The neuropharmacological mechanism of AOF in AD have been fully illustrated in numerous studies. In this review, we first briefly described the active components of AOF and related mechanism for treating AD. And we also provide a systematic overview of recent progress on the pharmacokinetic characteristics of the active ingredients of AOF and analyzed their bioavailability differences in the development of AD. Thus, AOF hold a great therapeutic potential in the treatment of AD and is worthy of further research and promotion.

Pharmacokinetic Research Progress of Anti-tumor Drugs Targeting for Pulmonary Administration.

BACKGROUND: Cancer is a major problem that threatens human survival and has a high mortality rate. The traditional chemotherapy methods are mainly intravenous injection and oral administration, but have obvious toxic and side effects. Anti-tumor drugs for pulmonary administration can enhance drug targeting, increase local drug concentration, and reduce the damage to systemic organs, especially for the treatment of lung cancer. METHODS: The articles on the pharmacokinetics of anti-tumor drugs targeting pulmonary administration were retrieved from the Pub Med database. This article mainly took lung cancer as an example and summarized the pharmacokinetic characteristics of anti-tumor drugs targeting for pulmonary administration contained in nanoparticles, dendrimers, liposomes and micelles. RESULTS: The review shows that the pharmacokinetics process of pulmonary administration is associated with a drug carrier by increasing the deposition and release of drugs in the lung, and retarding the lung clearance rate. Among them, the surface of dendrimers could be readily modified, and polymer micelles have favorable loading efficiency. In the case of inhalation administration, liposomes exhibit more excellent lung retention properties compared to other non-lipid carriers. Therefore, the appropriate drug carrier is instrumental to increase the curative effect of anti-tumor drugs and reduce the toxic effect on surrounding healthy tissues or organs. CONCLUSION: In the process of pulmonary administration, the carrier-embedded antitumor drugs have the characteristics of targeted and sustained release compared with non-packaging drugs, which provides a theoretical basis for the clinical rational formulation of chemotherapy regimens. However, there is currently a lack of comparative research between drug packaging materials, and more importantly, the development of safe and effective anti-tumor drugs targeting for pulmonary administration requires more data.

Metabolism and Distribution of Novel Tumor Targeting Drugs In Vivo.

BACKGROUND: As a new tumor therapy, targeted therapy is becoming a hot topic due to its high efficiency and low toxicity. Drug effects of targeted tumor drugs are closely related to pharmacokinetics, so it is important to understand their distribution and metabolism in vivo. METHODS: A systematic review of the literature on the metabolism and distribution of targeted drugs over the past 20 years was conducted, and the pharmacokinetic parameters of approved targeted drugs were summarized in combination with the FDA's drug instructions. Targeting drugs are divided into two categories: small molecule inhibitors and monoclonal antibodies. Novel targeting drugs and their mechanisms of action, which have been developed in recent years, are summarized. The distribution and metabolic processes of each drug in the human body are reviewed. RESULTS: In this review, we found that the distribution and metabolism of small molecule kinase inhibitors (TKI) and monoclonal antibodies (mAb) showed different characteristics based on the differences of action mechanism and molecular characteristics. TKI absorbed rapidly (Tmax ≈ 1-4 h) and distributed in large amounts (Vd > 100 L). It was mainly oxidized and reduced by cytochrome P450 CYP3A4. However, due to the large molecular diameter, mAb was distributed to tissues slowly, and the volume of distribution was usually very low (Vd < 10 L). It was mainly hydrolyzed and metabolized into peptides and amino acids by protease hydrolysis. In addition, some of the latest drugs are still in clinical trials, and the in vivo process still needs further study. CONCLUSION: According to the summary of the research progress of the existing targeting drugs, it is found that they have high specificity, but there are still deficiencies in drug resistance and safety. Therefore, the development of safer and more effective targeted drugs is the future research direction. Meanwhile, this study also provides a theoretical basis for clinical accurate drug delivery.

Potential Metabolic Biomarkers for Early Detection of Oral Lichen Planus, a Precancerous Lesion.

Background: Oral lichen planus (OLP) is a T-cell-mediated chronic inflammatory disorder and precancerous oral lesion with high incidence. The current diagnostic method of OLP is very limited and metabolomics may provide a new approach for quantitative evaluation. Methods: The Ultra-Performance Liquid Chromatography-Quadrupole/Orbitrap High Resolution Mass Spectrometry (UHPLC-Q-Orbitrap HRMS) was applied to analyze the change of metabolites in serum of patients with OLP. A total of 115 OLP patients and 124 healthy controls were assigned to either a training set (n = 160) or a test set (n = 79). The potential biomarkers and the change of serum metabolites were profiled and evaluated by multivariate analysis. Results: Totally, 23 differential metabolites were identified in the training set between OLP group and healthy group. Three prominent metabolites in receiver operating characteristic (ROC) were selected as a panel to distinguish OLP or healthy individuals in the test set, and the diagnostic accuracy was 86.1%. Conclusions: This study established a new method for the early detection of OLP by analyzing serum metabolomics using UHPLC-Q-Orbitrap HRMS, which will help in understanding the pathological processes of OLP and identifying precancerous lesions in oral cavity.

Metabolomic Insights Into the Synergistic Effect of Biapenem in Combination With Xuebijing Injection Against Sepsis.

The drug combination of biapenem (BIPM) and xuebijing injection (XBJ) is commonly applied for the treatment of sepsis in China. However, the potential synergistic mechanism is still enigmatic. There have been no studies focused on the plasma metabolome alterations in sepsis after the intervention of this combination. In this work, an untargeted metabolomics approach was performed by liquid chromatography-mass spectrometry coupled with multivariate statistical analysis to provide new insights into the synergistic effect of BIPM in combination with XBJ. We characterized the metabolic phenotype of sepsis and described metabolic footprint changes in septic rats responding to XBJ and BIPM individually and in combination, in addition to histopathological and survival evaluation. A total of 91 potential biomarkers of sepsis were identified and 32 disturbed metabolic pathways were constructed. Among these biomarkers, 36 metabolites were reversely regulated by XBJ, mainly including glycerophospholipids, sphingolipids, free fatty acids (FFAs), bile acids and acylcarnitines; 42 metabolites were regulated by BIPM, mainly including amino acids, glycerophospholipids, and acylcarnitines; 72 metabolites were regulated after XBJ-BIPM combination treatment, including most of the 91 potential biomarkers. The results showed that the interaction between XBJ and BIPM indeed exhibited a synergistic effect by affecting some key endogenous metabolites, 15 metabolites of which could not be regulated when XBJ or BIPM was used alone. Compared with Model group, 13, 22, and 27 metabolic pathways were regulated by XBJ, BIPM, and XBJ-BIPM combination, respectively. It suggested that many more endogenous metabolites and metabolic pathways were significantly regulated after combination treatment compared with XBJ or BIPM monotherapy. Metabolisms of lipids, amino acids, acylcarnitines, and bile acids were common pathways involved in the synergistic action of XBJ and BIPM. This study was the first to employ metabolomics to elucidate the synergistic effect and decipher the underlying mechanisms of BIPM in combination with XBJ against sepsis. The results provide some support for clinical application of antibiotics in combination with traditional Chinese medicines and have important implications for the treatment of sepsis in clinic.

Selective recognition and enrichment of carbamazepine in biological samples by magnetic imprinted polymer based on reversible addition-fragmentation chain transfer polymerization.

A well-defined molecularly imprinted polymer (Fe3O4@CS@MIP) was synthesized via reversible addition-fragmentation chain transfer polymerization for magnetic solid-phase extraction coupled with high-performance liquid chromatography-diode array detector to detect carbamazepine (CBZ) in biological samples. The composition of Fe3O4@CS@MIP was selected by a two-step screening method. 4-vinyl pyridine, divinylbenzene and dimethylformamide were chosen as the functional monomer, cross-linker and porogen, respectively. The imprinted layer was coated on the surface of the chain transfer agent-modified magnetic chitosan nanoparticles. The prepared Fe3O4@CS@MIP was characterized by scanning electron microscopy, transmission electron microscopy, Fourier transform infrared spectroscopy, Brunauer-Emmett-Teller measurement and vibrating sample magnetometer. The results indicated that Fe3O4@CS@MIP had a large surface area (265.8 m2/g), high saturation magnetization (19.88 emu/g) and uniform structure. Besides, the binding property of the Fe3O4@CS@MIP was studied in detail. The Fe3O4@CS@MIP showed high imprinting factor (IF = 4.83) and desirable adsorption capacity (323.10 µmol/g) to CBZ. Under the optimum conditions, the developed method exhibited excellent linearity (R2>0.999) in the range of 0.01-0.5 mg/L and 1.0-30.0 mg/L, and the limits of detection were 1.0 µg/L and 9.6 µg/L for the urine and serum samples, respectively. Good recoveries (88.22%-101.18%) were obtained with relative standard deviations less than 4.83%. This work provided a practical approach for the selective extraction and detection of CBZ in real samples.

A regenerable sorbent composed of a zeolite imidazolate framework (ZIF-8), Fe3O4 and graphene oxide for enrichment of atorvastatin and simvastatin prior to their determination by HPLC.

Graphene oxide (GO), nanosized Fe3O4 and zeolite imidazolate framework-8 (ZIF-8) were hybridized as a multifunctional sorbent for use in microextraction. The sorbent was characterized by SEM, TEM, XRD and FTIR. The composite is porous, has a high specific surface (> 600 m2·g-1) and is paramagnetic. The GO sheets are shown to act as carriers for the Fe3O4 nanoparticles and ZIF-8. The composite is a viable material for the preconcentration of atorvastatin and simvastatin from urine prior to their determination by HPLC with PDA detection. The limits of detection are 116 and 387 pg·mL-1, respectively. Recoveries from spiked urine samples range between 84.7 and 95.7%, with relative standard deviation of ≤4.5%. Enrichment factors range from 169 to 191. The method was successfully applied to the determination of atorvastatin in urine. Moreover, this sorbent is regenerable and recyclable for at least seven times without obvious decrease in performance. Graphical abstract A composite sorbent composed of a zeolite imidazolate framework, Fe3O4 and graphene oxide was applied to the extraction of statins in urine prior their determination by HPLC.