ABSTRACT
Hyperbaric oxygen therapy (HBOT) has been used in patients with diabetic foot ulcers (DFU) for many years, but its clinical efficacy is still controversial. Therefore, this study explored the efficacy of HBOT applied to DFU by means of meta-analysis. PubMed, Cochrane Library, Embase, CNKI and Wanfang databases were searched, from database inception to October 2023, and published randomised controlled trials (RCTs) of HBOT in DFU were collected. Two investigators independently screened the collected literature, extracted relevant data and assessed the quality of the literature. Review Manager 5.4 software was applied for data analysis. Twenty-nine RCTs with 1764 patients were included. According to the combined results, when compared with conventional treatment, HBOT significantly increased the complete healing rate of DFUs (46.76% vs. 24.46%, odds ratio [OR]: 2.83, 95% CI: 2.29-3.51, p < 0.00001) and decreased the amputation rate (26.03% vs. 45.00%, OR: 0.41, 95% CI: 0.18-0.95, p = 0.04), but the incidence of adverse events was significantly higher in patients (17.37% vs. 8.27%, OR: 2.49, 95% CI: 1.35-4.57, p = 0.003), whereas there was no significant difference in the mortality (6.96% vs. 12.71%, OR: 0.52, 95% CI: 0.21-1.28, p = 0.16). Our results suggest that HBOT is effective in increasing the complete healing rate and decreasing the amputation rate in patients with DFUs, but increases the incidence of adverse events, while it has no significant effect on mortality.
Subject(s)
Diabetic Foot , Hyperbaric Oxygenation , Wound Healing , Humans , Diabetic Foot/therapy , Hyperbaric Oxygenation/methods , Randomized Controlled Trials as Topic , Treatment OutcomeABSTRACT
Guhong injection (GHI) has been applied in the therapy of cardio-cerebrovascular disease in clinic, but there is no report about the pharmacokinetic/pharmacodynamic (PK/PD) research on GHI treating myocardial ischemia/reperfusion (MI/R) injury in rats. In this study, eight compounds of GHI in plasma, including N-acetyl-L-glutamine (NAG), chlorogenic acid (CGA), hydroxysafflor yellow A (HSYA), p-coumaric acid ( pCA), rutin, hyperoside, kaempferol-3-O-rutinoside, and kaempferol-3-O-glucoside, were quantified by LC-MS/MS. We discovered that the values of t1/2ß, k12, V2, and CL2 were larger than those of t1/2α, k21, V1, and CL1 for all compounds. The levels of four biomarkers, creatine kinase-MB (CK-MB), cardiac troponin I (cTn I), ischemia-modified albumin (IMA), and alpha-hydroxybutyrate dehydrogenase (α-HBDH) in plasma were determined by ELISA. The elevated level of these biomarkers induced by MI/R was declined to different degrees via administrating GHI and verapamil hydrochloride (positive control). The weighted regression coefficients of NAG, HSYA, CGA, and pCA in PLSR equations generated from The Unscrambler X software (version 11) were mostly minus, suggesting these four ingredients were positively correlated to the diminution of the level of four biomarkers. Emax and ED50, two parameters in PK/PD equations that were obtained by adopting Drug and Statistics software (version 3.2.6), were almost enlarged with the rise of GHI dosage. Obviously, all analytes were dominantly distributed and eliminated in the peripheral compartment with features of rapid distribution and slow elimination. With the enhancement of GHI dosage, the ingredients only filled in the central compartment if the peripheral compartment was replete. Meanwhile, high-dose of GHI generated the optimum intrinsic activity, but the affinity of compounds with receptors was the worst, which may be caused by the saturation of receptors. Among the eight analytes, NAG, HSYA, CGA, and pCA exhibited superior cardioprotection, which probably served as the pharmacodynamic substance basis of GHI in treating MI/R injury.
Subject(s)
Glutamine/analogs & derivatives , Myocardial Reperfusion Injury , Plant Extracts , Animals , Rats , Myocardial Reperfusion Injury/drug therapy , Biomarkers , Chromatography, Liquid , Least-Squares Analysis , Serum Albumin , Tandem Mass SpectrometryABSTRACT
Fourteen sesquiterpenes, including one undescribed sesquiterpene lactone, were isolated from Youngia japonica, and their structures were identified by NMR, HRESIMS, ECD and calculated ECD. Cytotoxic activities of all isolates against A549, HeLa, and 4 T1 cell lines were detected by CCK8 assay. Among them, 2 showed obvious cytotoxic activity against A549 cells. Subsequently, the production of ROS, and apoptosis of A549 cells treated with 2 were evaluated. The result showed that 2 distinctly increased the ROS level, and induced the apoptosis of A549 cells. Further anticancer mechanism studies showed that 2 increased the expression of cleaved caspase 3. Taken together, our results demonstrated that 2 might become potential leading compounds for the treatment of lung cancer.
Subject(s)
Antineoplastic Agents , Asteraceae , Sesquiterpenes , Humans , Cell Line, Tumor , Molecular Structure , Reactive Oxygen Species , Antineoplastic Agents/pharmacology , Apoptosis , Sesquiterpenes/pharmacology , Sesquiterpenes/chemistryABSTRACT
The importance of virtual reality (VR) has been emphasized by many medical studies, yet it has been relatively under-applied to surgical operation. This study characterized how VR has been applied in clinical education and evaluated its tutorial utility by designing a surgical model of tumorous resection as a simulator for preoperative planning and medical tutorial. A 36-year-old male patient with a femoral tumor who was admitted to the Affiliated Jiangmen Traditional Chinese Medicine Hospital was randomly selected and scanned by computed tomography (CT). The data in digital imaging and communications in medicine (*.DICOM) format were imported into Mimics to reconstruct a femoral model, and were generated to the format of *.stl executing in the computer-aided design (CAD) software SenSable FreeForm Modeling (SFM). A bony tumor was simulated by adding clay to the femur, the procedure of tumorous resection was virtually performed with a toolkit called Phantom, and its bony defect was filled with virtual cement. A 3D workspace was created to enable the individual multimodality manipulation, and a virtual operation of tumorous excision was successfully carried out with indefinitely repeated running. The precise delineation of surgical margins was shown to be achieved with expert proficiency and inexperienced hands among 43 of 50 participants. This simulative educator presented an imitation of high definition, those trained by VR models achieved a higher success rate of 86% than the rate of 74% achieved by those trained by conventional methods. This tumorous resection was repeatably handled by SFM, including the establishment of surgical strategy, whereby participants felt that respondent force feedback was beneficial to surgical teaching programs, enabling engagement of learning experiences by immersive events which mimic real-world circumstances to reinforce didactic and clinical concepts.
ABSTRACT
A method based on ultra-high performance liquid chromatography coupled with triple quadrupole linear ion trap-tandem mass spectrometry(UHPLC-QTRAP-MS/MS) was developed for the simultaneous determination of 41 bioactive constituents of flavonoids, organic acids, nucleosides, and amino acids in Lysimachiae Herba. The content of multiple bioactive constituents was compared among the samples from different habitats. The chromatographic separation was performed in a Waters XBridge®C_(18) column(4.6 mm×100 mm, 3.5 µm) at 30 â. The gradient elution was performed with 0.4% methanol(A)-formic acid water(B) as the mobile phase at a flow rate of 0.8 mL·min~(-1), and the multiple-reaction monitoring(MRM) mode was adopted. According to the content of 41 constituents, hierarchical cluster analysis(HCA), orthogonal partial least squares discriminant analysis(OPLS-DA), and gray relational analysis(GRA) were perfomed to comprehensively evaluate the samples from different habitats. The results showed that the 41 constituents exhibited good linear relationship within the tested concentration ranges, with the correlation coefficients(r) greater than 0.999 4. The method featured good precision, repeatability, and stability with the relative standard deviations(RSDs) less than 5.0%. The average recoveries of the 41 constituents ranged from 98.06% to 101.9%, with the RSDs of 0.62%-4.6%. HCA and OPLS-DA separated 48 batches of Lysimachiae Herba samples from different habitats into three categories: the producing areas in Sichuan and Chongqing, the producing areas in Jiangsu, Zhejiang, and Jiangxi, and the producing areas in Guizhou. The content of 41 constituents varied among the Lysimachiae Herba samples from different habitats. The GRA results revealed that the Lysimachiae Herba sample from Nanchong City, Sichuan Province had the best comprehensive quality. The method developed in this study was accurate and reliable and thus can be used for comprehensive evaluation of Lysimachiae Herba quality and provide basic information for the selection of habitats.
Subject(s)
Drugs, Chinese Herbal , Tandem Mass Spectrometry , Tandem Mass Spectrometry/methods , Multivariate Analysis , Chromatography, High Pressure Liquid/methods , Drugs, Chinese Herbal/chemistry , Amino Acids/analysisABSTRACT
Ovalbumin (OVA) is a major allergen in hen eggs. Enzymolysis has been demonstrated as an efficient method for reducing OVA allergenicity. This study demonstrates that microwave pretreatment (MP) at 400 W for 20 s assisting bromelain enzymolysis further decreases the allergenicity of OVA, which was attributed to the increase in the degree of hydrolysis and promoted the destruction of IgE-binding epitopes. The results showed that MP could promote OVA unfolding, expose hydrophobic domains, and disrupt tightly packed α-helical structures and disulfide bonds, which increased the degree of hydrolysis by 7.28% and the contents of peptides below 1 kDa from 43.55 to 85.06% in hydrolysates compared with that for untreated OVA. Biological mass spectrometry demonstrated that the number of intact IgE-binding epitope peptides in MP-assisted OVA hydrolysates decreased by 533 compared to that in hydrolysis without MP; consequently, their IgG/IgE binding rates decreased more significantly. Therefore, MP-assisted enzymolysis may provide an alternative method for decreasing the OVA allergenicity.
Subject(s)
Allergens , Chickens , Animals , Female , Ovalbumin/chemistry , Allergens/chemistry , Chickens/metabolism , Microwaves , Peptides , Mass Spectrometry , Epitopes , Immunoglobulin E/metabolismABSTRACT
BACKGROUND: Selenium, a natural microelement with both nutritional and toxicological properties, is intertwined with tumorigenesis and progression. However, it is not fully understood how selenium metabolism affects immune response and cancer biology. METHODS: We estimated selenium metabolism by Gene Set Enrichment Analysis (GSEA) to delineate the selenium metabolism landscape using The Cancer Genome Atlas (TCGA), Genotype-Tissue Expression (GTEx), Cancer Cell Line Encyclopedia (CCLE) and a integrated pan-cancer single-cell dataset. We systematically explored the prognostic implications of selenium metabolism and selenium-related regulatory patterns. The therapeutic value of selenium metabolism was explored through machine learning and examined in several immunotherapy cohorts. The heterogeneity and underlying mechanism of selenium metabolism were investigated by cellâcell communication analysis at the single-cell level. RESULTS: A GSEA analysis based on 86 genes was used to evaluate the selenium metabolism landscape. The selenium metabolism score exhibited prognostic value in predicting the lower risk of mortality, possibly due to its correlation with multiple cancer hallmarks, including a positive correlation with complement (R = 0.761, P < 0.001), inflammatory response (R = 0.663, P < 0.001), apoptosis (R = 0.626, P < 0.001), hypoxia (R = 0.587, P < 0.001), reactive oxygen species (ROS) (R = 0.558, P < 0.001), and interferon gamma response (R = 0.539, P < 0.001). We also observed heterogeneity in the relationship between selenium metabolism and immunity across different cancers. Based on selenium-related genes, we constructed a machine learning model with area under the ROC curve (AUC) of 0.82 in predicting immune checkpoint inhibitor (ICI)-based immunotherapy response. Single-cell selenium metabolism quantification revealed that adjacent and tumor tissues had higher selenium metabolism compared with normal tissues, especially in epithelial cells, fibroblasts and macrophages. The communication between high-selenium epithelium and high-selenium fibroblast was significantly higher than other cells, especially in cytokines, chemokines, collagen, Wnt, VEGF, IGF and FGF pathways. CONCLUSION: Our study provides a comprehensive landscape of selenium metabolism levels and diverse regulatory patterns in different cancers, deepening the understanding of selenium's roles in tumorigenesis and immunity.
Subject(s)
Neoplasms , Selenium , Humans , Neoplasms/genetics , Carcinogenesis , Apoptosis , Sequence Analysis, RNAABSTRACT
Background: Disordered gut microbiota (GM) structure and function may contribute to osteoporosis (OP). This study explores how traditional Chinese medicine (TCM) intervention affects the structure and function of the GM in patients with OP. Method: In a 3-month clinical study, 43 patients were randomly divided into two groups receiving conventional treatment and combined TCM (Yigu decoction, YGD) treatment. The correlation between the intestinal flora and its metabolites was analyzed using 16S rDNA and untargeted metabolomics and the combination of the two. Results: After three months of treatment, patients in the treatment group had better bone mineral density (BMD) than those in the control group (P < 0.05). Patients in the treatment group had obvious abundance changes in GM microbes, such as Bacteroides, Escherichia-Shigella, Faecalibacterium, Megamonas, Blautia, Klebsiella, Romboutsia, Akkermansia, and Prevotella_9. The functional changes observed in the GM mainly involved changes in metabolic function, genetic information processing and cellular processes. The metabolites for which major changes were observed were capsazepine, Phe-Tyr, dichlorprop, D-pyroglutamic acid and tamsulosin. These metabolites may act through metabolic pathways, the citrate cycle (TCA cycle) and beta alanine metabolism. Combined analysis showed that the main acting metabolites were dichlorprop, capsazepine, D-pyroglutamic acid and tamsulosin. Conclusion: This study showed that TCM influenced the structure and function of the GM in patients with OP, which may be one mechanism by which TCM promotes the rehabilitation of patients with OP through the GM.
Subject(s)
Gastrointestinal Microbiome , Humans , Pyrrolidonecarboxylic Acid , Tamsulosin , RNA, Ribosomal, 16S/geneticsABSTRACT
A comprehensive analytical method based on ultra-fast liquid chromatography coupled with triple quadrupole/linear ion trap tandem mass spectrometry(UFLC-QTRAP-MS/MS) was established for simultaneous determination of the content of 45 bioactive constituents including flavonoids, alkaloids, amino acids, phenolic acids, and nucleosides in Epimedium brevicornum. The multiple bioactive constituents in leaves, petioles, stems and rhizomes of E. brevicornum were analyzed. The gradient elution was performed at 30 â in an XBridge~® C_(18) column(4.6 mm×100 mm, 3.5 µm) with 0.4% formic acid aqueous solution-acetonitrile as the mobile phase at a flow rate of 0.8 mL·min~(-1). Single factor experiment and response surface methodology were employed to optimize the extraction conditions. Multivariate statistical analyses including systematic cluster analysis(SCA), principal component analysis(PCA), partial least squares discriminant analysis(PLS-DA), and one-way analysis of variance(One-way ANOVA) were carried out to classify the samples from different parts and identify different constituents. Grey relation analysis(GRA) and entropy weight-TOPSIS analysis were performed to build a multi-index comprehensive evaluation model for different parts of E. brevicornum. The results showed that there was a good relationship between the mass concentrations of 45 constituents and the corresponding peak areas, with the correlation coefficients(r) not less than 0.999 0. The precision, repeatability, and stability of the established method were good for all the target constituents in this study, with the relative standard deviations(RSDs) less than 5.0%(0.62%-4.9%) and the average recovery of 94.51%-105.7%. The above results indicated that the bioactive constituents varied in different parts of E. brevicornum, and the overall quality followed the trend of leaves > petioles > rhizomes > stems. This study verified the rationality of the Chinese Pharmacopoeia(2020 edition) stipulating that the medicinal part of E. brevicornum is the leaf. Moreover, our study indicated that the rhizome had the potential for medicinal development. The established method was accurate and reliable, which can be used to comprehensive evaluate and control the quality of E. brevicornum. This study provides data reference for clarifying the medicinal parts and rationally utilizing the resources of E. brevicornum.
Subject(s)
Epimedium , Chromatography, High Pressure Liquid , Tandem Mass Spectrometry , Chromatography, Liquid , Multivariate AnalysisABSTRACT
Purpose: Cervical spondylotic radiculopathy (CSR) is a common neurologic condition that causes chronic neck pain and motor functions, with neuropathic pain (NP) being the primary symptom. Although it has been established that electroacupuncture (EA) can yield an analgesic effect in clinics and synaptic plasticity plays a critical role in the development and maintenance of NP, the underlying mechanisms have not been fully elucidated. In this study, we explored the potential mechanisms underlying EA's effect on synaptic plasticity in CSR rat models. Materials and Methods: The CSR rat model was established by spinal cord compression (SCC). Electroacupuncture stimulation was applied to LI4 (Hegu) and LR3 (Taichong) acupoints for 20 min once a day for 7 days. Pressure pain threshold (PPT) and mechanical pain threshold (MPT) were utilized to detect the pain response of rats. A gait score was used to evaluate the motor function of rats. Enzyme-linked immunosorbent assay (ELISA), Western blot (WB), immunohistochemistry (IHC), immunofluorescence (IF), and transmission electron microscopy (TEM) were performed to investigate the effects of EA. Results: Our results showed that EA alleviated SCC-induced spontaneous pain and gait disturbance. ELISA showed that EA could decrease the concentration of pain mediators in the cervical nerve root. WB, IHC, and IF results showed that EA could downregulate the expression of synaptic proteins in spinal cord tissues and promote synaptic plasticity. TEM revealed that the EA could reverse the synaptic ultrastructural changes induced by CSR. Conclusion: Our findings reveal that EA can inhibit SCC-induced NP by modulating the synaptic plasticity in the spinal cord and provide the foothold for the clinical treatment of CSR with EA.
ABSTRACT
The incidence of major depressive disorder (MDD) is increasing all over the world. There is a great need for complementary or alternative therapies with high safety, few side effects, and precise efficacy to care for MDD. In China, acupuncture has significant laboratory data and clinical trials to demonstrate its antidepressant efficacy. However, there is no clear answer as to how it works. Exosomes are membranous vesicles that rely on cellular multivesicular bodies (MVBs) fused to the cell membrane for release into the extracellular matrix. Almost all cell types are capable of producing and releasing exosomes. As a result, exosomes contain complex RNAs and proteins from their relatives (Cells that secretes exosomes). They can cross biological barriers and participate in biological activities, such as cell migration, angiogenesis, and immune regulation. These properties have made them a popular research topic. Some experts have suggested that exosomes may serve as delivery vehicles for acupuncture to work. This presents both an opportunity and a new challenge for improving the protocols of acupuncture as a treatment for MDD. To better define the relationship between MDD, exosomes, and acupuncture, we reviewed the literature from the last few years. Inclusion criteria included randomized controlled trials and basic trials evaluating acupuncture in the treatment or prevention of MDD, the role of exosomes in the development and progression of MDD, and the role of exosomes in acupuncture. We believe that acupuncture may affect the distribution of exosomes in vivo, and exosomes may be a new carrier for acupuncture treatment of MDD in the future.
ABSTRACT
Natural holoferritin, containing average 2000 Fe3+/ferritin, has been considered as promising iron supplementary in food and medical science. However, the low extraction yields highly limited its practical application. Herein, we provided a facile strategy for holoferritin preparation through in vivo microorganism-directed biosynthesis, and the structure, iron content, and the composition of iron core have been investigated. The results revealed that in vivo biosynthesized holoferritin possesses great monodispersity and water-solubility. In addition, the in vivo biosynthesized holoferritin contains a comparative iron content as compared to natural holoferritin, giving the ratio of â¼ 2500 iron/ferritin. Besides, the composition of iron core has been identified as ferrihydrite and FeOOH, and three steps might be involved in iron core formation. This work highlighted that the microorganism-directed biosynthesis could be an efficient strategy for preparation of holoferritin, which might be beneficial for its practical application for iron supplementation.
Subject(s)
Iron , Nanoparticles , Iron/metabolism , Ferritins/chemistry , Food , SolubilityABSTRACT
The Pickering emulsions containing cinnamon essential oil (CEO) stabilized by lignocellulose nanocrystals-tannic acid (LCNC-TA) complexes were used to improve properties of gelatin film. The influences of various volume proportion mixed oil (sunflower oil/CEO 1:0, 5:1, 2:1 and 1:1) were investigated. Introducing CEO reduced the droplet size approximately from 57 to 30 µm, facilitating droplet distribution in film matrix. With increasing CEO proportion, the surface structure of emulsion films became uniform without micropores or cavities, showing good compatibility with film matrix during film-forming process. Furthermore, increasing CEO proportion improved tensile strength (TS, 3.75-4.61 MPa) and water vapor permeability (WVP, 9.16 × 10-12-7.61 × 10-12 g·cm-1s-1Pa-1) of emulsion films. Besides, the UV blocking, antioxidant and antibacterial properties of emulsion films improved as CEO proportion increased. Compared with the control gelatin film, the loss of CEO in emulsion films effectively decreased through pre-embedding approach by Pickering emulsion method.
Subject(s)
Nanoparticles , Oils, Volatile , Emulsions/chemistry , Cinnamomum zeylanicum , Oils, Volatile/chemistry , Tannins , Sunflower Oil , Steam , Antioxidants , Gelatin/chemistry , Nanoparticles/chemistry , Anti-Bacterial AgentsABSTRACT
ETHNOPHARMACOLOGICAL RELEVANCE: The plant Erigeron breviscapus (Vant.) Hand.-Mazz.,a Chinese herbal medicine with multiple pharmacological effects and clinical applications, has been traditionally used in the treatment of paralysis caused by stroke and joint pain from rheumatism by the Yi minority people of Southwest China for generations.However, its mechanism involves many factors and has not been fully clarified. AIM OF THE STUDY: Taking intestinal flora as the target, the protective effect of extract(breviscapine) of E. breviscapus on cerebral ischemia and its possible mechanism were discussed from the perspective of brain inflammatory pathway and intestinal CYP3A4, which depends on intestinal flora. MATERIALS AND METHODS: In this study, we first verified the binding ability between major active ingredient of Erigeron breviscapus and the core target TLR4 protein by molecular docking using Vina software.We established a rat model of cerebral ischemia-reperfusion injury in vivo.The neurological function of rats was scored by Bederson score table, the cerebral infarction volume was detected by TTC staining, and the serum NSE level was detected by ELASA. 16S rRNA sequencing was used to detect the intestinal flora of rats in each group.The expression levels of cerebral TLR4/MyD88/NF-κB and CYP3A4 mRNA and protein in different intestinal segments were detected by qRT-PCR and Western blot. RESULTS: Compared with the model group, the neurological injury score, infarct volume and serum NSE concentration of breviscapine low, medium and high dose groups and nimodipine groups decreased significantly. Meanwhile, breviscapine could significantly reduce the expression level of the TLR4/MyD88/NF-κB in brain tissue and CYP3A4 in different intestinal segments of rats with cerebral ischemia-reperfusion injury. In addition, breviscapine also significantly ameliorated intestinal flora dysbiosis of rats with cerebral ischemia-reperfusion injury. CONCLUSIONS: Breviscapine can protect rats from cerebral ischemia-reperfusion injury by regulating intestinal flora, inhibiting brain TLR4/MyD88/NF-κB inflammatory pathway and intestinal CYP3A4 expression.
Subject(s)
Brain Ischemia , Drugs, Chinese Herbal , Erigeron , Gastrointestinal Microbiome , Reperfusion Injury , Animals , Brain Ischemia/drug therapy , Brain Ischemia/metabolism , Cytochrome P-450 CYP3A/genetics , Cytochrome P-450 CYP3A/metabolism , Drugs, Chinese Herbal/pharmacology , Drugs, Chinese Herbal/therapeutic use , Erigeron/genetics , Erigeron/metabolism , Flavonoids , Molecular Docking Simulation , Myeloid Differentiation Factor 88/genetics , Myeloid Differentiation Factor 88/metabolism , NF-kappa B/metabolism , Nimodipine/pharmacology , RNA, Messenger/metabolism , RNA, Ribosomal, 16S , Rats , Rats, Sprague-Dawley , Reperfusion Injury/drug therapy , Reperfusion Injury/metabolism , Signal Transduction , Toll-Like Receptor 4/genetics , Toll-Like Receptor 4/metabolismABSTRACT
Hernandezine (Her) is a bisbenzylisoquinoline alkaloid extracted from the traditional Chinese herbal medicine Thalictrum glandulosissimum. Evidence shows that Her is a natural agonist of adenosine monophosphate (AMP)-activated protein kinase (AMPK) and induces apoptosis and autophagy in tumor cells. In this study, we investigated the role of autophagy in Her-induced cell death in human pancreatic cancer cell lines. We showed that Her dose-dependently suppressed cell proliferation, promoted autophagy and induced autophagic death in pancreatic ductal adenocarcinoma (PDAC) cell lines Capan-1 and SW1990. The IC50 values of Her in inhibition of Capan-1 and SW1990 cells were 47.7 µM and 40.1 µM, respectively. Immunoblotting showed that Her (1-40 µM) promoted the conversion of LC3-I to LC3-II, and Her exerted concentration-dependent and time-dependent effects on autophagy activation in PDAC cells. In transmission electron microscopy and fluorescence image analysis, we found that autophagic vacuoles were significantly increased in Her-treated cells. Knockdown of ATG5, a key gene in the autophagy pathway, alleviated the activation of autophagy by Her. These results demonstrated that Her induced autophagy in PDAC cells. Intensely activated autophagy could promote cell death. The autophagy inhibitors, BafA1 and HCQ significantly inhibited Her-induced cell death, implying that Her induced autophagic cell death in PDAC cells. Moreover, we showed that Her activated autophagy by increasing the phosphorylation of AMPK and decreasing the phosphorylation of mTOR/p70S6K. Knockdown of AMPKα relieves the autophagic cell death induced by Her. Furthermore, Her concentration-dependently enhanced reactive oxygen species (ROS) generation in PDAC cells. Antioxidants could reduce the phosphorylation of AMPK and suppress autophagic cell death induced by Her. Our study provides evidence for the development of Her as a therapeutic agent for the treatment of pancreatic cancer.
Subject(s)
Autophagic Cell Death , Benzylisoquinolines , Pancreatic Neoplasms , Female , Humans , AMP-Activated Protein Kinases/metabolism , Apoptosis , Autophagic Cell Death/drug effects , Autophagy , Benzylisoquinolines/pharmacology , Cell Line, Tumor , Pancreatic Neoplasms/drug therapy , Reactive Oxygen Species/metabolism , Signal Transduction , Pancreatic NeoplasmsABSTRACT
To explore the common questions of acupuncture translational medicine study and the development strategy of its translational application. It is believed that the research on the individual and common mechanisms of acupuncture effects, and the common molecule of acupoint and parameter research for the effect onset of acupuncture may promote clinical translation and instrument research and development. The study of meridian theory should be fully applied to clinical practice to build a meridian diagnostic system with clinical significance. Using evidence-based medicine, the clinical research of acupuncture can be transformed into clinical guidelines to provide the effective regimens for clinical practice. The communication and cooperation should be enhanced between the basic research and clinical application in the field of acupuncture. It is suggested that the promotion of acupuncture translational medicine research is contribute to the overall development of acupuncture discipline, and to better service for the human health engineering.
Subject(s)
Meridians , Research Design , Humans , Translational Science, BiomedicalABSTRACT
Considering the impact of oxidative stress on the development of many diseases, together with the role of natural antioxidants in maintaining physiological balance in humans, medicinal mushrooms are potential sources of bioactive compounds against many diseases. In the present work, in vitro evaluation of the biological activities of the alcoholic extracts of two wild tree mushrooms, namely, Ganoderma applanatum and Fomitopsis pinicola, has been performed. Extraction of G. applanatum (GAE) and F. pinicola (FPE) was conducted with 60% ethanol and 100% ethanol sequentially. UPLC-MS/MS identification was conducted on the two mushrooms extracts. A total of 15 substances were identified in GAE, including 3 spiro meroterpenoids and 12 triterpenoids; a total of 14 chemical constituents were iden¬tified in FPE, including 8 triterpenoids, 4 triterpene glycosides, 1 lanosterol, and 1 lanostanoid. The resulting extracts were examined for their in vitro antioxidative and cytoprotective effects against AAPH-induced oxidative damage. Our results demonstrated that both extracts have potent antioxidative activities, when GAE was 0.2 mg/mL, the clearance rates of DPPH and ABTS have reached 93.34% and 99.93%, respectively. When FPE was 1.4 mg/mL and 0.6 mg/mL, the scavenging rates of DPPH and ABTS have reached 91.76% and 100%, respectively. Both the alcoholic extracts of G. applanatum and F. pinicola were able to protect the AAPH-induced damage and could effectively inhibit cell aging via ß-galactosidase (SA ß-gal) staining activity test and scanning electron microscopy analysis.
Subject(s)
Adrenal Gland Neoplasms , Agaricales , Ganoderma , Pheochromocytoma , Triterpenes , Humans , Antioxidants/chemistry , Chromatography, Liquid , Tandem Mass Spectrometry , Agaricales/chemistry , Triterpenes/chemistry , EthanolABSTRACT
BACKGROUND: Recent studies have demonstrated that dysfunction of the intestinal barrier is a significant contributing factor to the development of severe acute pancreatitis (SAP). A stable intestinal mucosa barrier functions as a major anatomic and functional barrier, owing to the balance between intestinal epithelial cell (IEC) proliferation and apoptosis. There is some evidence that calcium overload may trigger IEC apoptosis and that calcineurin (CaN)/nuclear factor of activated T-cells (NFAT) signaling might play an important role in calcium-mediated apoptosis. AIM: To investigate the potential mechanisms underlying the therapeutic effect of Qingyi decoction (QYD) in SAP. METHODS: A rat model of SAP was created via retrograde infusion of sodium deoxycholate. Serum levels of amylase, tumor necrosis factor (TNF-α), interleukin (IL)-6, D-lactic acid, and diamine oxidase (DAO); histological changes; and apoptosis of IECs were examined in rats with or without QYD treatment. The expression of the two subunits of CaN and NFAT in intestinal tissue was measured via quantitative real-time polymerase chain reaction and western blotting. For in vitro studies, Caco-2 cells were treated with lipopolysaccharide (LPS) and QYD serum, and then cell viability and intracellular calcium levels were detected. RESULTS: Retrograde infusion of sodium deoxycholate increased the severity of pancreatic and intestinal pathology and the levels of serum amylase, TNF-α, and IL-6. Both the indicators of intestinal mucosa damage (D-lactic acid and DAO) and the levels of IEC apoptosis were elevated in the SAP group. QYD treatment reduced the serum levels of amylase, TNF-α, IL-6, D-lactic acid, and DAO and attenuated the histological findings. IEC apoptosis associated with SAP was ameliorated under QYD treatment. In addition, the protein expression levels of the two subunits of CaN were remarkably elevated in the SAP group, and the NFATc3 gene was significantly upregulated at both the transcript and protein levels in the SAP group compared with the control group. QYD significantly restrained CaN and NFATc3 gene expression in the intestine, which was upregulated in the SAP group. Furthermore, QYD serum significantly decreased the LPS-induced elevation in intracellular free Ca2+ levels and inhibited cell death. CONCLUSION: QYD can exert protective effects against intestinal mucosa damage caused by SAP and the protective effects are mediated, at least partially, by restraining IEC apoptosis via the CaN/NFATc3 pathway.
Subject(s)
Amine Oxidase (Copper-Containing) , Pancreatitis , Acute Disease , Amine Oxidase (Copper-Containing)/metabolism , Amine Oxidase (Copper-Containing)/pharmacology , Amylases , Animals , Caco-2 Cells , Calcineurin/adverse effects , Calcineurin/metabolism , Calcium/metabolism , Deoxycholic Acid/metabolism , Deoxycholic Acid/pharmacology , Deoxycholic Acid/therapeutic use , Drugs, Chinese Herbal , Epithelial Cells/pathology , Humans , Interleukin-6/metabolism , Intestinal Mucosa/pathology , Lactic Acid/metabolism , Lipopolysaccharides/pharmacology , Pancreatitis/pathology , Rats , Rats, Sprague-Dawley , T-Lymphocytes/metabolism , Tumor Necrosis Factor-alpha/metabolismABSTRACT
Bioactive or nutraceutical ingredients have been widely used in pursuit of health and well-being. However, the environmental instability, poor solubility and bioavailability, and unspecific delivery highly limited their practical values. By virtue of the unique shell-like structure, definite disassembly/reassembly behavior, and excellent safety profile of ferritin protein, it stands out among of various nano-materials and is emerging as one of the most promising vehicles for the encapsulation and delivery of bioactive ingredients or drugs. In this review, we present a systematic overview of recent advances of ferritin-based delivery systems from single-encapsulation, co-encapsulation, to compartmentalized-encapsulation of bioactive ingredients or drugs. Different encapsulation strategies for cargo loading as well as their advantages and drawbacks have been critically reviewed. This study emphasized the importance of the construction of compartmentalized delivery systems through the usage of ferritin nanocages, which exhibit great potential for facilitating the synergistic functionality of different types of cargos. Lastly, the applications of ferritin nanocages for physicochemical improvements and functionality achievements of loaded cargos are summarized. In conclusion, ferritin protein nanocages not only are excellent nanocarriers, but also can act as"multi-seated" vehicles for co-encapsulation and compartmentalized encapsulation of different cargos simultaneously.
Subject(s)
Dietary Supplements , Ferritins , Biological Availability , Excipients , Ferritins/chemistry , Ferritins/metabolism , Solubility , Systematic Reviews as TopicABSTRACT
Spinal cord injury (SCI) is a highly disabling disorder for which few effective treatments are available. Grape seed proanthocyanidins (GSPs) are polyphenolic compounds with various biological activities. In our preliminary experiment, GSP promoted functional recovery in rats with SCI, but the mechanism remains unclear. Therefore, we explored the protective effects of GSP on SCI and its possible underlying mechanisms. We found that GSP promoted locomotor recovery, reduced neuronal apoptosis, increased neuronal preservation, and regulated microglial polarisation in vivo. We also performed in vitro studies to verify the effects of GSP on neuronal protection and microglial polarisation and their potential mechanisms. We found that GSP regulated microglial polarisation and inhibited apoptosis in PC12 cells induced by M1-BV2 cells through the Toll-like receptor 4- (TLR4-) mediated nuclear factor kappa B (NF-κB) and phosphatidylinositol 3-kinase/serine threonine kinase (PI3K/AKT) signaling pathways. This suggests that GSP regulates microglial polarisation and prevents neuronal apoptosis, possibly by the TLR4-mediated NF-κB and PI3K/AKT signaling pathways.