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Introduction: Ganshu Nuodan is a liver-protecting dietary supplement composed of Ganoderma lucidum (G. lucidum) spore powder, Pueraria montana (Lour.) Merr. (P. montana), Salvia miltiorrhiza Bunge (S. miltiorrhiza) and Astragalus membranaceus (Fisch.) Bunge. (A. membranaceus). However, its pharmacodynamic material basis and mechanism of action remain unknown. Methods: A mouse model of acute alcohol liver disease (ALD) induced by intragastric administration of 50% alcohol was used to evaluate the hepatoprotective effect of Ganshu Nuodan. The chemical constituents of Ganshu Nuodan were comprehensively identified by UPLC-QTOF/MS, and then its pharmacodynamic material basis and potential mechanism of action were explored by proteomics and network pharmacology. Results: Ganshu Nuodan could ameliorate acute ALD, which is mainly manifested in the significant reduction of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) in serum and malondialdehyde (MDA) content in liver and the remarkably increase of glutathione (GSH) content and superoxide dismutase (SOD) activity in liver. Totally 76 chemical constituents were identified from Ganshu Nuodan by UPLC-QTOF/MS, including 21 quinones, 18 flavonoids, 11 organic acids, 7 terpenoids, 5 ketones, 4 sterols, 3 coumarins and 7 others. Three key signaling pathways were identified via proteomics studies, namely Arachidonic acid metabolism, Retinol metabolism, and HIF-1 signaling pathway respectively. Combined with network pharmacology and molecular docking, six key targets were subsequently obtained, including Ephx2, Lta4h, Map2k1, Stat3, Mtor and Dgat1. Finally, these six key targets and their related components were verified by molecular docking, which could explain the material basis of the hepatoprotective effect of Ganshu Nuodan. Conclusion: Ganshu Nuodan can protect acute alcohol-induced liver injury in mice by inhibiting oxidative stress, lipid accumulation and apoptosis. Our study provides a scientific basis for the hepatoprotective effect of Ganshu Nuodan in acute ALD mice and supports its traditional application.
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Enfermedad Hepática Inducida por Sustancias y Drogas , Hepatopatías Alcohólicas , Ratones , Animales , Simulación del Acoplamiento Molecular , Farmacología en Red , Proteómica , Hepatopatías Alcohólicas/tratamiento farmacológico , Hepatopatías Alcohólicas/prevención & control , Etanol/metabolismo , Etanol/uso terapéutico , Glutatión/metabolismoRESUMEN
Introduction: Xuanhuang Pill (XHP) is a traditional Chinese medicine oral formula composed of 10 herbs. This study aims to verify the hepatoprotective activity of XHP and explain its possible mechanism. Methods: The hepatoprotective activity of XHP was evaluated by constructing a mouse model of alcoholic liver disease, and the mechanism of XHP was preliminarily explained by utilizing ultra-performance liquid chromatography/time-of-flight mass spectrometry (UPLC-QTOF/MS), proteomics and network pharmacology. Results: The current study demonstrated that treatment with XHP ameliorated acute alcohol-induced liver injury in mice by significantly reducing alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels and triglycerides (TGs) and malondialdehyde (MDA) content. Remarkably, treatment also increased superoxide dismutase (SOD) activity and glutathione (GSH) content. UPLC-QTOF/MS, 199 compounds were identified as within the make-up of the XHP. Network pharmacology analysis showed that 103 targets regulated by 163 chemical components may play an important role in the protective liver effect mediated by XHP. Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis suggest that the HIF-1, FoxO, PI3K-Akt, insulin, and thyroid hormone signaling pathways are key modulators of XHP's effects. Finally, eight key targets including Mapk1, Mapk3, Akt1, Map2k1, Pik3ca, Pik3cg, Raf1, and Prkca were verified by molecular docking and proteomics analysis, which provide insight into the hepatoprotective effect observed with XHP treatment. Conclusion: In summary, these results improved upon knowledge of the chemical composition and the potential mechanisms of hepatoprotective action of oral XHP treatment, providing foundational support for this formulation as a viable therapeutic option for alcoholic liver disease.
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Hepatopatías Alcohólicas , Farmacología en Red , Animales , Ratones , Simulación del Acoplamiento Molecular , Fosfatidilinositol 3-Quinasas , Hepatopatías Alcohólicas/tratamiento farmacológico , Hepatopatías Alcohólicas/prevención & control , Cromatografía LiquidaRESUMEN
Renal tubular injury in patients with diabetic kidney disease(DKD) may be accompanied by glomerular and microvascular diseases. It plays a critical role in the progression of renal damage in DKD, and is now known as diabetic tubulopathy(DT). To explore the multi-targeted therapeutic effects and pharmacological mechanisms in vivo of total flavones of Abelmoschus manihot(TFA), an extract from traditional Chinese medicine for treating kidney disease, in attenuating DT, the authors randomly divided all rats into four groups: a normal control group(normal group), a DT model group(model group), a DT model+TFA-treated group(TFA group) and a DT model+rosiglitazone(ROS)-treated group(ROS group). The DT rat model was established based on the DKD rat model by means of integrated measures. After successful modeling, the rats in the four groups were continuously given double-distilled water, TFA suspension, and ROS suspension, respectively by gavage every day. After 6 weeks of treatment, all rats were sacrificed, and the samples of their urine, blood, and kidneys were collected. The effects of TFA and ROS on various indicators related to urine and blood biochemistry, renal tubular injury, renal tubular epithelial cell apoptosis and endoplasmic reticulum stress(ERS), as well as the activation of the protein kinase R-like endoplasmic reticulum kinase(PERK)-eukaryotic translation initiation factor 2α(eIF2α)-activating transcription factor 4(ATF4)-C/EBP homologous protein(CHOP) signaling pathway in the kidney of the DT model rats were investigated. The results indicated that hypertrophy of renal tubular epithelial cells, renal tubular hyperplasia and occlusion, as well as interstitial extracellular matrix and collagen deposition occurred in the DT model rats. Moreover, significant changes were found in the expression degree and the protein expression level of renal tubular injury markers. In addition, there was an abnormal increase in tubular urine proteins. After TFA or ROS treatment, urine protein, the characteristics of renal tubular injury, renal tubular epithelial cell apoptosis and ERS, as well as the activation of the PERK-eIF2α-ATF4-CHOP signaling pathway in the kidney of the DT model rats were improved to varying degrees. Therein, TFA was superior to ROS in affecting the pathological changes in renal tubule/interstitium. In short, with the DT model rats, this study demonstrated that TFA could attenuate DT by multiple targets through inhibiting renal tubular ERS-induced cell apoptosis in vivo, and its effect and mechanism were related to suppressing the activation of the PERK-eIF2α-ATF4-CHOP signaling pathway in the kidney. These findings provided preliminary pharmacological evidence for the application of TFA in the clinical treatment of DT.
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Ratas , Animales , Abelmoschus , Especies Reactivas de Oxígeno/metabolismo , Flavonas/farmacología , Estrés del Retículo Endoplásmico , Nefropatías Diabéticas/tratamiento farmacológico , Apoptosis , Diabetes MellitusRESUMEN
The rapid development of nanotechnology has triggered the emerging of tremendous theranostic nanoplatforms for combating cancers. Silicene, as an emerging two-dimensional (2D) material, has been recently explored as therapeutic agent due to their desirable biodegradation and strong photothermal-conversion performance. However, the rational design of silicene-based composites for further exerting multifunctional medical applications is still highly challenging. Herein, we report on the construction of silicene-based silicene@Pt composite nanosheets for computed tomography (CT)/photoacoustic (PA) imaging-guided dual-sensitized radiotherapy combined with photonic tumor hyperthermia, which has been achieved by a seed-growth approach to in situ grow Pt components onto silicene nanosheets' surface. Especially, by functionalization of Pt components, these nanosheets could act as both contrast agents for CT imaging and dual radio-sensitizing agents for radiotherapy, which could deposit Pt-involved radiation energy (sensitized therapeutic process I) and overcome hypoxia-associated radio-resistance by Pt-catalytic O2 generation from overexpressed H2O2 within the tumor microenvironment (sensitized therapeutic process II). The strong photothermal-conversion performance of silicene nanosheets not only endowed silicene@Pt composite nanosheets with photoacoustic imaging property, but also realized the photonic tumor hyperthermia and achieved a combined therapeutic effect with radiotherapy. This work not only broadens the biomedical applications of silicene, but also develops functionalization strategies of silicene for versatile biomedical applications.
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Hipertermia Inducida , Neoplasias , Técnicas Fotoacústicas , Línea Celular Tumoral , Humanos , Peróxido de Hidrógeno , Hipertermia , Fototerapia , Nanomedicina TeranósticaRESUMEN
PURPOSE: To compare Lipiodol uptake and tumor response in intermediate-stage hepatocellular carcinoma (HCC) with and without pre-embolization vascular lake phenomenon (VLP) and to identify the incidence and predictive factors of this phenomenon, in patients treated by conventional transarterial chemoembolization (cTACE). MATERIALS AND METHODS: This retrospective study included 151 consecutive patients with intermediate HCC totaling 232 nodules, who underwent cTACE from June 2015 to October 2018. Patients were divided into two groups according to the presence of VLP before embolization. Initial Lipiodol uptake was assessed using post-cTACE computed tomography (CT) within 1-1.5 months after cTACE. Enhanced CT or magnetic resonance imaging was performed at 6 months after the procedure to assess local recurrence and distant metastasis. RESULTS: The VLP was demonstrated in 21.85% (33/151) patients and 16.81% (39/232) nodules on the super-selective angiography. On nodule-based analysis, significantly better Lipiodol uptake (p < 0.001) and higher ORR (60.61% vs. 26.49%, p < 0.001) and DCR (87.88% vs. 51.66%, p < 0.001) were observed in the VLP group compared to the non-VLP group. The multivariate logistic regression analysis showed that the presence of VLP (OR 6.431, 95% CI 2.495-16.579) might be a predictive factor for better Lipiodol uptake. Univariate and multivariate logistic regression analysis showed that poor differentiation of tumor (OR 6.397, 95% CI 2.804-19.635) remained predictive for the VLP. CONCLUSION: The incidence of VLP before embolization is 21.19%. The presence of VLP is well correlated with tumor Lipiodol uptake after cTACE and may be a new predictive factor for evaluation of cTACE efficacy and prognosis of intermediate HCC.
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Antineoplásicos/administración & dosificación , Carcinoma Hepatocelular/terapia , Quimioembolización Terapéutica , Medios de Contraste/farmacocinética , Aceite Etiodizado/farmacocinética , Neoplasias Hepáticas/terapia , Adulto , Anciano , Carcinoma Hepatocelular/diagnóstico por imagen , Carcinoma Hepatocelular/metabolismo , Quimioembolización Terapéutica/métodos , Femenino , Humanos , Neoplasias Hepáticas/diagnóstico por imagen , Neoplasias Hepáticas/metabolismo , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Pronóstico , Estudios Retrospectivos , Tomografía Computarizada por Rayos XRESUMEN
Photothermal therapy (PTT) is an emerging technology as a noninvasive therapeutic modality for inducing photonic cancer hyperthermia. However, current photothermal conversion agents suffer from low therapeutic efficiency and single functionality. Engineering crystal defects on the surface or substrate of semiconductors can substantially enhance their optical absorption capability as well as improve their photothermal effects in theranostic nanomedicines. In this study, a specific defect engineering strategy was developed to endow two-dimensional (2D) BiOCl nanosheets with intriguing photothermal conversion performance by creating oxygen vacancies on the surface (O-BiOCl). Importantly, the photothermal performance and photoacoustic imaging capability of the 2D O-BiOCl nanosheets could be precisely controlled by modulating the amounts of oxygen vacancies. The strong Bi-based X-ray attenuation coefficient endowed these nanosheets with the contrast-enhanced computed tomography imaging capability. The high near-infrared-triggered photonic hyperthermia for tumor ablation was systematically demonstrated both in vitro at the cellular level and in vivo for tumor breast cancer mice xenograft models. Based on the demonstrated high biocompatibility of these 2D O-BiOCl nanosheets, this work not only formulates an intriguing 2D photothermal nanoagent for tumor ablation, but also provides an efficient strategy to control the photothermal performance of nanoagents by defect engineering.
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Nanopartículas/química , Fototerapia/métodos , Nanomedicina Teranóstica/métodos , Ingeniería de Tejidos/métodos , Tomografía Computarizada por Rayos X/métodos , Animales , Humanos , RatonesRESUMEN
Pulmonary fibrosis (PF) is a crippling disease characterized by progressive dyspnea and associated with a high mortality rate, but its origin is unknown and there is no effective treatment. Yifei Sanjie formula (YFSJF) is a Chinese medicine that is widely used for treatment of respiratory systems disease. However, the molecular basis for the function of YFSJF has not been determined. Here we investigate the contribution of YFSJF in BLM-induced PF mice. Administration with YFSJF significantly alleviated the degree of BLM-induced collagen I and III deposition and the inflammatory injuring in the lungs and suppressed hydroxyproline release in PF animals. The active components of YFSJF are comprised with flavonoid, amino acids, saponins, oligosaccharide, organic acid, vitamin, esters, purine nucleosides. Additionally, there was a significant increase in autophagosomes, after treatment with YFSJF in PF animals. Interestingly, autophagy dysfunction by the blocker chloroquine (CQ) resulted in collagen deposition and inducing the expression of fibrosis-related genes. In addition, YFSJF-induced autophagy is mediated by the PI3K-AKT-mTOR pathway, and knockdown of PI3K by siRNA up-regulated the expression of autophagy-related genes and down-regulated the expression of collagen in human lung fibroblasts (HLF). Our findings provide a detailed understanding that YFSJF-antifibrotic effects are mainly mediated by triggering autophagy, and suppressing phosphorylation of the PI3K-AKT-mTOR pathway is required for YFSJF-curative effect.
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Autofagia , Fosfatidilinositol 3-Quinasas/metabolismo , Proteínas Proto-Oncogénicas c-akt/metabolismo , Fibrosis Pulmonar/tratamiento farmacológico , Fibrosis Pulmonar/patología , Transducción de Señal , Serina-Treonina Quinasas TOR/metabolismo , Animales , Autofagosomas/metabolismo , Autofagosomas/ultraestructura , Autofagia/efectos de los fármacos , Colágeno/metabolismo , Modelos Animales de Enfermedad , Medicamentos Herbarios Chinos , Humanos , Inflamación/complicaciones , Inflamación/patología , Pulmón/patología , Masculino , Fosforilación/efectos de los fármacos , Fibrosis Pulmonar/complicaciones , Fibrosis Pulmonar/metabolismo , Factor de Crecimiento Transformador beta1/metabolismoRESUMEN
Traditional cancer-therapeutic modalities such as chemotherapy suffer from the low therapeutic efficiency and severe side effects. The emerging nanocatalytic therapy could in-situ catalyze the endogenous substances into highly toxic species and then efficiently kill the cancer cells, but the lack of high-performance nanocatalysts hinders their broad clinical translation. In this work, we have successfully developed, for the first time, nanosized zero-valence crystalized iron nanoparticles for in-situ triggering nanocatalytic Fenton reaction within tumor microenvironment to produce large amounts of hydroxyl radicals and subsequently kill the cancer cells, which could be further synergistically enhanced by either photonic hyperthermia or magnetic hyperthermia as assisted by these iron nanoparticles acting as photothermal-conversion or magnetothermal-conversion nanoagents, respectively. Especially, the excellent magnetic performance of these zero-valence crystallized iron nanoparticles has achieved both in vitro and in vivo contrast-enhance magnetic resonance imaging for potentially guiding the photonic/magnetic hyperthermia-synergistic nanocatalytic cancer therapy. This work not only provides the new type of iron-based nanoparticles for biomedical application, but also demonstrates the high efficiency of nanocatalytic cancer therapy as assisted by both photonic and magnetic hyperthermia.
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Hipertermia Inducida , Hierro/química , Fenómenos Magnéticos , Nanopartículas/química , Neoplasias/terapia , Fotones , Animales , Materiales Biocompatibles/química , Catálisis , Línea Celular Tumoral , Medios de Contraste/química , Femenino , Humanos , Peróxido de Hidrógeno/química , Imagen por Resonancia Magnética , Ratones Endogámicos BALB C , Ratones Desnudos , Nanopartículas/ultraestructura , Fototerapia , Povidona/química , Especies Reactivas de Oxígeno/metabolismoRESUMEN
Gubenfangxiao decoction (GBFXD) is a traditional Chinese medicine based on a combination of Yu-Ping-Feng-San and Erchen decoctions. GBFXD has been widely used for decades in treating asthma at the Affiliated Hospital of Nanjing University of Chinese Medicine. Previously, GBFXD was found to reduce lung inflammation and airway remodeling; however, the underlying mechanism remains unknown. In this study, the effects of GBFXD on asthmatic mice were evaluated based on pathology and lung function; airway hyperresponsiveness (AHR) and pathology were compared among the two different mouse models utilized. Furthermore, the mechanism of action of GBFXD on asthmatic mice was analyzed using iTRAQ labeling technology combined with ingenuity pathway analysis (IPA). Modeling analysis of pre- and post-treatment proteins identified 75 differentially expressed proteins. These proteins were related to B-cell development, calcium-induced lymphocyte apoptosis, antigen presentation, and Th1 and Th2 activation pathways. Moreover, 68 differentially expressed proteins were identified in the GBFXD treatment group compared with the model group. Upstream regulatory factors predicted that interleukin (IL)-4 (necessary for inducing polarization of type 2 [M2] macrophages), cyclooxygenase, and prostaglandin E2 are significantly elevated in the model group. Based on IPA analysis, it was concluded that several pathways, including mitochondrial dysfunction and oxidative phosphorylation, are closely associated with the therapeutic effects of GBFXD in asthma. Moreover, the differential expression of several proteins, including the M2 markers, MRC1, ARG1, Retnla, Chil3, and CHIA, were validated by western blotting, confirming that GBFXD can reduce airway inflammation, which fits the pattern of an alternative M2 activation state, and attenuate AHR. Overall, our findings indicate that GBFXD significantly suppresses M2 macrophage polarization, providing further insights into the mechanism underlying the protective effects of GBFXD.
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Benign prostatic hyperplasia (BPH) patients experience complications after surgery. We studied oxidative stress scavenging by porous Se@SiO2 nanospheres in prostatic urethra wound healing after transurethral resection of the prostate (TURP). Beagle dogs were randomly distributed into two groups after establishing TURP models. Wound recovery and oxidative stress levels were evaluated. Re-epithelialization and the macrophage distribution at the wound site were assessed by histology. The mechanism by which porous Se@SiO2 nanospheres regulated macrophage polarization was investigated by qRT-PCR, western blotting, flow cytometry, immunofluorescence and dual luciferase reporter gene assays. Our results demonstrated that Porous Se@SiO2 nanosphere-coated catheters advance re-epithelization of the prostatic urethra, accelerating wound healing in beagle dogs after TURP, and improve the antioxidant capacity to inhibit oxidative stress and induced an M2 phenotype transition of macrophages at the wound. By restraining the function of reactive oxygen species (ROS), porous Se@SiO2 nanospheres downregulated Ikk, IκB and p65 phosphorylation to block the downstream NF-κB pathway in macrophages in vitro. Since activation of NF-κB signaling cascades drives macrophage polarization, porous Se@SiO2 nanospheres promoted macrophage phenotype conversion from M1 to M2. Our findings suggest that porous Se@SiO2 nanosphere-coated catheters promote postoperative wound recovery in the prostatic urethra by promoting macrophage polarization toward the M2 phenotype through suppression of the ROS-NF-κB pathway, attenuating the inflammatory response. STATEMENT OF SIGNIFICANCE: The inability to effectively control post-operative inflammatory responses after surgical treatment of benign prostatic hyperplasia (BPH) remains a challenge to researchers and surgeons, as it can lead to indirect cell death and ultimately delay wound healing. Macrophages at the wound site work as pivotal regulators of local inflammatory response. Here, we designed and produced a new type of catheter with a coating of porous Se@SiO2 nanosphere and demonstrated its role in promoting prostatic urethra wound repair by shifting macrophage polarization toward the anti-inflammatory M2 phenotype via suppressing ROS-NF-κB pathway. These results indicate that the use of porous Se@SiO2 nanosphere-coated catheter may provide a therapeutic strategy for postoperative complications during prostatic urethra wound healing to improve patient quality of life.
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Catéteres , Materiales Biocompatibles Revestidos/farmacología , Macrófagos/patología , Nanosferas/química , Transducción de Señal , Dióxido de Silicio/química , Uretra/patología , Cicatrización de Heridas/efectos de los fármacos , Animales , Polaridad Celular , Perros , Humanos , Macrófagos/efectos de los fármacos , Macrófagos/metabolismo , Masculino , FN-kappa B/metabolismo , Nanosferas/ultraestructura , Estrés Oxidativo/efectos de los fármacos , Porosidad , Próstata/patología , Próstata/cirugía , Repitelización/efectos de los fármacos , Especies Reactivas de Oxígeno/metabolismo , Selenio/química , Células THP-1 , Resección Transuretral de la Próstata , Uretra/efectos de los fármacosRESUMEN
Light-activated photoacoustic imaging (PAI) and photothermal therapy (PTT) using the second near-infrared biowindow (NIR-II, 1000-1350 nm) hold great promise for efficient tumor detection and diagnostic imaging-guided photonic nanomedicine. In this work, we report on the construction of titanium nitride (TiN) nanoparticles, with a high photothermal-conversion efficiency and desirable biocompatibility, as an alternative theranostic agent for NIR-II laser-excited photoacoustic (PA) imaging-guided photothermal tumor hyperthermia. Working within the NIR-II biowindow provides a larger maximum permissible exposure (MPE) and desirable penetration depth of the light, which then allows detection of the tumor to the full extent using PA imaging and complete tumor ablation using photothermal ablation, especially in deeper regions. After further surface polyvinyl-pyrrolidone (PVP) modification, the TiN-PVP photothermal nanoagents exhibited a high photothermal conversion efficiency of 22.8% in the NIR-II biowindow, and we further verified their high penetration depth using the NIR-II biowindow and their corresponding therapeutic effect on the viability of tumor cells in vitro. Furthermore, these TiN-PVP nanoparticles were developed as a contrast agent for NIR-II-activated PA imaging both in vitro and in vivo for the first time and realized efficient photothermal ablation of the tumor in vivo within both the NIR-I and NIR-II biowindows. This work not only provides a paradigm for TiN-PVP photothermal nanoagents working in the NIR-II biowindow both in vitro and in vivo, but also proves the feasibility of PAI and PTT cancer theranostics using NIR-II laser excitation.
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Neoplasias de la Mama/terapia , Hipertermia Inducida/métodos , Nanomedicina/métodos , Nanopartículas/uso terapéutico , Nanomedicina Teranóstica/métodos , Titanio/uso terapéutico , Técnicas de Ablación/métodos , Animales , Línea Celular Tumoral , Medios de Contraste/efectos de la radiación , Medios de Contraste/uso terapéutico , Medios de Contraste/toxicidad , Femenino , Rayos Infrarrojos , Ratones Endogámicos BALB C , Nanopartículas/efectos de la radiación , Nanopartículas/toxicidad , Técnicas Fotoacústicas/métodos , Fototerapia/métodos , Titanio/efectos de la radiación , Titanio/toxicidadRESUMEN
Respiratory syncytial virus (RSV) is a leading cause of acute lower respiratory tract infections. Qingfei oral liquid (QFOL), a traditional Chinese medicine, is widely used in clinical treatment for RSV-induced pneumonia. The present study was designed to reveal the potential targets and mechanism of action for QFOL by exploring its influence on the host cellular network following RSV infection. We investigated the serum proteomic changes and potential biomarkers in an RSV-infected mouse pneumonia model treated with QFOL. Eighteen BALB/c mice were randomly divided into three groups: RSV pneumonia model group (M), QFOL-treated group (Q) and the control group (C). Serum proteomes were analyzed and compared using a label-free quantitative LC-MS/MS approach. A total of 172 protein groups, 1009 proteins, and 1073 unique peptides were successfully identified. 51 differentially expressed proteins (DEPs) were identified (15 DEPs when M/C and 43 DEPs when Q/M; 7 DEPs in common). Classification and interaction network showed that these proteins participated in various biological processes including immune response, blood coagulation, complement activation, and so forth. Particularly, fibrinopeptide B (FpB) and heparin cofactor II (HCII) were evaluated as important nodes in the interaction network, which was closely involved in coagulation and inflammation. Further, the FpB level was increased in Group M but decreased in Group Q, while the HCII level exhibited the opposite trend. These findings not only indicated FpB and HCII as potential biomarkers and targets of QFOL in the treatment of RSV pneumonia, but also suggested a regulatory role of QFOL in the RSV-induced disturbance of coagulation and inflammation-coagulation interactions.
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Biomarcadores/sangre , Medicamentos Herbarios Chinos/farmacología , Fibrinopéptido B/análisis , Cofactor II de Heparina/análisis , Proteoma/efectos de los fármacos , Proteómica , Infecciones por Virus Sincitial Respiratorio/sangre , Virus Sincitiales Respiratorios/efectos de los fármacos , Animales , Cromatografía Liquida , Modelos Animales de Enfermedad , Medicamentos Herbarios Chinos/uso terapéutico , Fibrinopéptido B/genética , Regulación de la Expresión Génica/efectos de los fármacos , Cofactor II de Heparina/genética , Pulmón/patología , Ratones Endogámicos BALB C , Infecciones por Virus Sincitial Respiratorio/tratamiento farmacológico , Espectrometría de Masas en TándemRESUMEN
ETHNOPHARMACOLOGICAL RELEVANCE: Banxia (BX) is the dried tuber of Pinellia ternata (Thunb.) Breit., a commonly prescribed Chinese medicinal herb for the treatment of cough, phlegm, and vomiting in pregnant women. However, raw BX has been demonstrated to exert toxic effects on reproduction and the precise and comprehensive mechanisms remain elusive. AIM OF THE STUDY: We applied an iTRAQ (isobaric tags for relative and absolute quantitation, iTRAQ)-based proteomic method to explore the mechanisms of raw BX-induced fetal toxicity in mice. MATERIALS AND METHODS: The mice were separated into two groups, control mice and BX-treated mice. From gestation days 6-8, the control group was treated with normal saline and the BX group was exposed to BX suspension (2.275g/kg/day). Gastrulae were obtained and analyzed using the quantitative proteomic approach of iTRAQ coupled to liquid chromatography-tandem mass spectrometry (LC-MS/MS). A multi-omics data analysis tool, OmicsBean (http://www.omicsbean.cn), was employed to conduct bioinformatic analysis of differentially abundant proteins (DAPs). Quantitative real-time PCR (qRT-PCR) and western blotting methods were applied to detect the protein expression levels and validate the quality of the proteomics. RESULTS: A total of 1245 proteins were identified with < 1% false discovery rate (FDR) and 583 protein abundance changes were confidently assessed. Moreover, 153 proteins identified in BX-treated samples showed significant differences in abundance. Bioinformatics analysis showed that the functions of 37 DAPs were predominantly related to nervous system development. The expression levels of the selected proteins for quantification by qRT-PCR or western blotting were consistent with the results in iTRAQ-labeled proteomics data. CONCLUSION: The results suggested that oral administration of BX in mice may cause fetal abnormality of the nervous system. The findings may be helpful to elucidate the underlying mechanisms of BX-induced embryotoxicity.
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Medicamentos Herbarios Chinos/toxicidad , Sistema Nervioso/efectos de los fármacos , Sistema Nervioso/crecimiento & desarrollo , Pinellia/química , Proteómica/estadística & datos numéricos , Animales , Femenino , Gástrula/efectos de los fármacos , Gástrula/metabolismo , Ratones , Sistema Nervioso/metabolismo , Tubérculos de la Planta/toxicidadRESUMEN
MXenes, an emerging family of graphene-analogues two-dimensional (2D) materials, have attracted continuous and tremendous attention in many application fields because of their intrinsic physiochemical properties and high performance in versatile applications. In this work, we report on the construction of tantalum carbide (Ta4C3) MXene-based composite nanosheets for multiple imaging-guided photothermal tumor ablation, which has been achieved by rational choice of the composition of MXenes and their surface functionalization. A redox reaction was activated on the surface of tantalum carbide (Ta4C3) MXene for in situ growth of manganese oxide nanoparticles (MnOx/Ta4C3) based on the reducing surface of the nanosheets. The tantalum components of MnOx/Ta4C3 acted as the high-performance contrast agents for contrast-enhanced computed tomography, and the integrated MnOx component functionalized as the tumor microenvironment-responsive contrast agents for T1-weighted magnetic resonance imaging. The photothermal-conversion performance of MnOx/Ta4C3 composite nanosheets not only has achieved contrast-enhanced photoacoustic imaging, but also realized the significant tumor-growth suppression by photothermal hyperthermia. This work broadens the biomedical applications of MXenes, not only by the fabrication of family members of biocompatible MXenes, but also by the development of functionalization strategies of MXenes for cancer-theranostic applications.
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Grafito/química , Nanocompuestos/química , Neoplasias/diagnóstico por imagen , Neoplasias/terapia , Fototerapia , Tantalio/química , Animales , Línea Celular Tumoral , Medios de Contraste/química , Hipertermia Inducida , Imagen por Resonancia Magnética , Masculino , Compuestos de Manganeso , Ratones , Ratones Endogámicos BALB C , Ratones Desnudos , Nanopartículas , Neoplasias/patología , Óxidos , Tamaño de la Partícula , Propiedades de Superficie , Tomografía Computarizada por Rayos X , Microambiente Tumoral/efectos de los fármacosRESUMEN
Conventionally, ceramics-based materials, fabricated by high-temperature solid-phase reaction and sintering, are preferred as bone scaffolds in hard-tissue engineering because of their tunable biocompatibility and mechanical properties. However, their possible biomedical applications have rarely been considered, especially the cancer phototherapeutic applications in both the first and second near-infrared light (NIR-I and NIR-II) biowindows. In this work, we explore, for the first time as far as we know, a novel kind of 2D niobium carbide (Nb2C), MXene, with highly efficient in vivo photothermal ablation of mouse tumor xenografts in both NIR-I and NIR-II windows. The 2D Nb2C nanosheets (NSs) were fabricated by a facile and scalable two-step liquid exfoliation method combining stepwise delamination and intercalation procedures. The ultrathin, lateral-nanosized Nb2C NSs exhibited extraordinarily high photothermal conversion efficiency (36.4% at NIR-I and 45.65% at NIR-II), as well as high photothermal stability. The Nb2C NSs intrinsically feature unique enzyme-responsive biodegradability to human myeloperoxidase, low phototoxicity, and high biocompatibility. Especially, these surface-engineered Nb2C NSs present highly efficient in vivo photothermal ablation and eradication of tumor in both NIR-I and NIR-II biowindows. This work significantly broadens the application prospects of 2D MXenes by rationally designing their compositions and exploring related physiochemical properties, especially on phototherapy of cancer.
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Materiales Biocompatibles/uso terapéutico , Hipertermia Inducida/métodos , Neoplasias/terapia , Niobio/uso terapéutico , Fototerapia/métodos , Animales , Línea Celular Tumoral , Femenino , Humanos , Rayos Infrarrojos , Ratones , Ratones Endogámicos BALB C , Ratones Desnudos , Nanoestructuras/uso terapéutico , Nanoestructuras/ultraestructura , Neoplasias/patologíaRESUMEN
Rapid and reliable identification of non-target components in herbal preparations remains a primary challenge, especially when corresponding reference substances are inaccessible. In this work, an efficient post-experiment data processing methodology, named reference substance free diagnostic fragment ion (RSFDFI), was developed based on ultra-high-performance liquid chromatography coupled with linear ion trap-Orbitrap tandem mass spectrometry (UHPLC/LTQ-Orbitrap). The first step of this approach was to cluster the components that share common fragment ions into several groups. After querying the database using a predicted chemical formula, the component with the fewest primary hits was preferentially deduced based on its MS/MS spectrum. Once the structure was characterized, its common fragment ions could be used as the prior structural information to select the possible candidates that would facilitate the subsequent identification for each group. Taking Pudilan Xiaoyan oral liquid (PDL) as a model herbal preparation, which has been extensively used for the treatment of epidemic parotitis and children with hand-foot-mouth diseases, this strategy enables a nearly eight-fold narrowing of the database hits, with fifty-two components, including lignans, flavonoids, alkaloids and steroids, being rapidly identified. In conclusion, our work clearly demonstrates that integrating RSFDFI with high-resolution mass spectrometry is a powerful methodology for rapid identification of non-target components from herbal prescriptions and may open new avenues for chemical analysis in other complex mixtures.
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Medicamentos Herbarios Chinos , Espectrometría de Masas/métodos , Cromatografía Líquida de Alta Presión , Estándares de ReferenciaRESUMEN
Using the absorbent resin, silica gel and ODS column chromatography as well as semi-preparative HPLC, ten compounds were isolated from 70% ethanol extract of tubers of Dioscorea zingiberensis C. H. Wright, and their structures were elucidated as trigoneoside XIIIa (1), parvifloside (2), trigoneoside IVa (3), deltoside (4), protobioside (5), lilioglycoside k (6), zingiberensis newsaponin I (7), deltonin (8), prosapogenin A of dioscin (9), and trillin (10) on the basis of NMR and MS spectral data analysis. Among these compounds, 1, 3, 5 and 6 were isolated from this plant for the first time. In the screening test on platelet aggregation, compounds 7 and 8 exhibited induction effect on platelet aggregation, while compound 9 exhibited significant inhibitory effect on platelet aggregation in vitro.
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Animales , Masculino , Ratas , Dioscorea , Química , Medicamentos Herbarios Chinos , Química , Farmacología , Espectrometría de Masas , Estructura Molecular , Agregación Plaquetaria , Ratas Wistar , Saponinas , Química , FarmacologíaRESUMEN
Yunnan Baiyao is a widely used herbal prescription in traditional medicine for the treatment of bleeding and hematological diseases, while its chemical profile remains elusive. In this work, a novel methodology combining polarity-directed extraction technique with a diagnostic ion filtering strategy based on LC hybrid ion trap TOF-MS analysis was developed for global, efficient, and rapid characterization of components in Yunnan Baiyao. Di-ethyl ether, n-butanol, and ethanol/water (70:30, v/v) covering low-to-high polarity ranges were chosen as the extraction solvent, respectively. The results clearly showed that, compared with conventional single extraction solvent, collaboratively using extraction solvents with different polarities can effectively increase the number of detected peaks and enrich the product ions information in multistage mass spectra analysis. By further matching diagnostic ions and fragmental pathways, a total of 34 components were successfully identified. Our work clearly demonstrates that integrating polarity-directed extraction and diagnostic ion filtering techniques is a powerful and reliable strategy for global detection and identification of complex chemicalome from herbal prescriptions, and may open new avenues for chemical analysis in other complex mixtures.
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Cromatografía Liquida/métodos , Medicamentos Herbarios Chinos/química , Espectrometría de Masas/métodos , China , Estructura MolecularRESUMEN
The main objective of the current study was to develop a universal method for a protein binding assay of complicated herbal components, and to investigate the possible relationship between compound polarity and protein binding using Schisadra lignans as an example. Firstly, the rat, dog and human plasma were spiked with three different concentrations of Schisandra chinensis extract (SLE), and ultramicrofiltration was used to obtain the unbound ingredients. Secondly, thirty-one Schisandra lignans in total plasma and ultrafiltered fluid were measured by LC-IT-TOFMS. Lastly, a relative exposure approach, which entailed calculating the relative concentrations of each Schisandra lignan from the corresponding calibration equation created from the calibration samples spiked with the stock solution of SLE, was applied in order to overcome the absence of authentic standards. The results showed that Schisandra lignans exhibited a high capability to bind with plasma protein, furthermore, the protein binding ratio of the lignan components increased proportionally with their individual chromatographic retention time, which indicated that the ratio of protein binding of lignans might increase accordingly with decreasing polarity. This study suggested that the compound polarity might be an important factor affecting the plasma protein binding of herbal components.
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Proteínas Sanguíneas/metabolismo , Cromatografía Líquida de Alta Presión/métodos , Medicamentos Herbarios Chinos/química , Lignanos/química , Espectrometría de Masas/métodos , Schisandra/química , Animales , Proteínas Sanguíneas/química , Perros , Humanos , Cinética , Lignanos/sangre , Masculino , Unión Proteica , RatasRESUMEN
This study was to develop and evaluate a practical approach of mass defect filtering (MDF), a post-acquisition data processing technique, for the rapid classification of complicated peaks into well-known chemical families based on the exact mass acquired by high resolution mass spectrometry. The full-scan LC-MS/MS data of the Ophiopogon japonicus extract was acquired using high performance liquid chromatography coupled with hybrid quadrupole-time of flight (LCMS-Q-TOF) system which features high resolution, mass accuracy, and sensitivity. To remove the interferences of the complex matrix, MDF approach was developed and employed to rapidly pick out the peaks of ophiopogonins and ophiopogonones from full-scan mass chromatograms. The accuracy of MDF was evaluated in reference to the result of structural identification. After the MDF based classification, both target and non-target components in Ophiopogon japonicus extract were characterized based on the detailed fragment ions analysis in the hybrid ion trap and time-of-flight mass spectrometry (LCMS-IT-TOF). By this approach, more than 50 ophiopogonins and 27 ophiopogonones were structurally characterized. The present results of rapid detection and identification of ophiopogonins and ophiopogonones suggest that the proposed MDF approach based on the high-resolution mass spectrometry data would be expected adaptable to the analysis of other herbal components.