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BACKGROUND:The traditional view is that proximal fibular fractures do not require fixation.Others and our research suggest that the proximal fibular structure plays an important role in the stability of the posterolateral structure of the knee joint,and its mechanism of action is worth studying. OBJECTIVE:To investigate the biomechanical effects of proximal fibular fractures on various structures of the knee joint in an extended state. METHODS:Finite element method was used to conduct simulated biomechanical experiments.A healthy young male volunteer was selected to establish a finite element model of the knee joint in an extended state using MRI and CT image data,and four proximal fibular shapes were simulated(Model A:intact,Model B:1 cm fracture below the fibular head,Model C:1 cm tip defect fracture from the proximal end of the fibula to the distal end,and Model D:2 cm bone defect from the proximal end of the fibula).A longitudinal concentrated load of 1 500 N was applied to the femoral shaft to compare and analyze the distribution and changing trend of the maximum equivalent stress and maximum first principal stress of each structure of the knee joint in an extended state under four working conditions. RESULTS AND CONCLUSION:(1)In Model A,the maximum equivalent stress in the tibial cartilage and lateral compartment of the meniscus was greater than that in the medial compartment,while the maximum first principal stress in the tibial plateau and medial compartment of the meniscus was greater than that in the lateral compartment.The maximum equivalent stress of the medial condyle of the femoral cartilage was greater than that of the lateral condyle,and the maximum first principal stress of the medial condyle of the femoral cartilage was greater than that of the medial condyle.(2)Compared to Model A,there was no significant difference in the magnitude and distribution of the maximum equivalent stress and maximum first principal stress in the cartilage and meniscus of Model C.(3)Compared to Model A,the maximum equivalent stress increase amplitude of Model B was in the order of medial tibial cartilage(14.9%),medial condyle of femoral cartilage(13.6%),and medial meniscus(6.6%).The maximum first principal stress increase amplitude was the medial meniscus(11.06%),the medial tibial cartilage(8.65%),and the medial condyle of the femoral cartilage(7.46%).The maximum equivalent stress increase amplitude of the ligament was as follows:popliteal arch ligament(33.2%)>anterior cruciate ligament(21.3%)>fibular collateral ligament(17%)>posterior cruciate ligament(14.3%)>anterior lateral collateral ligament(13.2%)>medial collateral ligament(10.1%).(4)Compared to Model A,the maximum equivalent stress increasing trend of Model D followed the medial tibial cartilage(19.5%),femoral cartilage medial condyle(17.9%),and medial meniscus(9.9%).The maximum first principal stress in sequence was the medial meniscus(14.04%),the medial tibial cartilage(13.03%),and the medial condyle of the femoral cartilage(11.37%).The increasing trend of maximum equivalent stress in ligaments was as follows:anterior cruciate ligament(25.2%)>posterior cruciate ligament(18.9%)>medial collateral ligament(18.5%)>anterior lateral collateral ligament(12.7%).(5)It is suggested that when the knee joint is extended,a 1 cm fracture below the fibular head and a 2 cm fibular tip bone defect have a significant impact on the structure of the medial ventricular cartilage,anterior cruciate ligament,and posterior lateral ligament complex.
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Objective To explore the effect of lidocaine(LID)on ischemia-reperfusion injury in orthotopic liver transplantation(OLT)rats and to analyze its mechanism of action.Methods Sixty rats were randomly divided into Verteporfin group,high-dose LID(High LID),medium-dose LID(Medium LID),low-dose LID(Low LID),Model and Control groups,on average.The rest of the rats except the control rats were used to establish OLT models.Observe the pathological changes in liver tissue were with hematoxylin-eosin staining.Serum aspartate transaminase(AST),total bilirubin(TBIL),lactate dehydrogenase(LDH)activities and alanine transaminase(ALT)were detected.Measure liver tissue levels of proinflammatory factors tumor necrosis factor-α(TNF-α),interleukin(IL)-6,IL-1β,and IL-10 with enzyme-linked immunosorbent assays.Reactive oxygen species(ROS)was detected by a fluorescence probe.Malondialdehyde(MDA)was detected by the thiobarbituric acid colorimetric method.Superoxide dismutase(SOD)was detected by nitrogen blue tetrazole colorimetry.Glutathione peroxidase(GSH-Px)was detected by a spectrophotometry method.Apoptosis of liver histiocytes was detected by in situ end labeling.Detect the expression of mammalian STE20 like protein kinase(MST1),phosphorylation(p)-MST1,large tumor suppressor factor 1(LATS1),p-LATS1,Yes associated protein(YAP),p-YAP,and apoptosis-related proteins B-cell lymphoma 2(Bcl-2)and Bcl-2 related X protein(Bax)with Western blot.Results Compared with the Control group,liver tissue in Model group rats showed injury,liver cell necrosis,and a large degree of inflammatory cell infiltration.Moreover,the cell apoptosis rate;serum AST,ALT,TBIL,and LDH activities;and liver tissue levels of TNF-α,IL-6,IL-1β,MDA,ROS,and Bax were significantly increased.Furthermore,liver tissue levels of IL-10,SOD,GSH-Px,Bcl-2,p-MST1/MST1,p-LATS1/LATS1,and p-YAP/YAP proteins were significantly reduced(P<0.05).Compared with the Model group,liver tissue injury was reduced in Low LID,Medium LID,and High LID groups.The cell apoptosis rate;serum AST,ALT,TBIL,and LDH activities;and liver tissue levels of TNF-α,IL-6,1L-1β,MDA,ROS,and Bax were significantly reduced.Moreover,liver tissue levels of IL-10,SOD,GSH-Px,Bcl-2,p-MST1/MST1,p-LATS1/LATS1,and p-YAP/YAP proteins were significantly increased(P<0.05).Hippo-YAP signaling pathway inhibitor verteporfin reversed the improving effect of LID on ischemia-reperfusion injury in OLT rats(P<0.05).Conclusions LID may activate the Hippo-YAP pathway,which reduces the inflammatory response,oxidative stress,and liver cell apoptosis,and improves liver ischemia-reperfusion injury in OLT rats.
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Objective To investigate the correlation between brain injury and spleen damage in a rat model of acute ischemic stroke and stasis interaction,and its effect on the MCP-1/CCR2 axis,and to provide an experimental basis for the mechanism of brain-spleen inflammatory coupling in spleen lesions caused by acute ischemic stroke.Methods Forty male SD rats were randomly divided into a sham group,carrageenan/yeast stasis syndrome group(carrageenan/yeast,CA/Y),middle cerebral artery occlusion group(MCAO),and middle cerebral artery stasis syndrome group(MCAO CA/Y)with 10 rats in each group.CA/Y and MCAO CA/Y groups were injected with 10 mg/kg carrageenan and 10 mg/kg intraperitoneally on the first day of modeling.2 mg/kg of dry yeast suspension were injected subcutaneously on the second day.MCAO and MCAO CA/Y groups were established by wire embolism on the second day.At 24 h after cerebral infarction modeling,the neurological deficit score was calculated in each group,the percentage of the cerebral infarction area was determined by TTC staining,the spleen weight was measured,and the correlation between the percentage of the cerebral infarction area and spleen weight was analyzed by the Spearman correlation coefficient.Furthermore,the pathological morphology of brain and spleen tissues was observed by hematoxylin-eosin(HE)staining,and chemotactic protein 1(MCP-1)and interferon-γ(IFN-γ)contents were measured in rat plasma by enzyme-linked immunosorbent assays.Western blot was used to detect chemokine C-C-motif receptor 2(CCR2)protein expression in the ischemic side of brain tissue.Results Compared with the sham group,the neurological deficit score,cerebral infarction area,and MCP-1 and IFN-γ contents in plasma were significantly increased(P<0.01),spleen weight was decreased significantly(P<0.01),and CCR2 protein expression in brain tissue was significantly upregulated(P<0.05)in MCAO and MCAO CA/Y groups.Moreover,the area of cerebral infarction was increased significantly(P<0.01),the spleen weight was decreased significantly(P<0.01),and CCR2 protein expression in brain and spleen tissues was significantly upregulated(P<0.05)Compared with the MCAO group,the area of cerebral infarction in the MCAO CA/Y group was significantly increased(P<0.01)and the spleen weight was decreased significantly(P<0.05).Spearman correlation analysis showed that the spleen weight was negatively correlated to the percentage of the cerebral infarction area(P<0.01,r=-0.9711).Pathological morphology observation revealed that the pathological changes in the MCAO CA/Y group were the most serious,cerebral liquefaction necrosis foci were seen in the brain tissue cortex,arrangement of neuronal cells in the lesions was sparse and disordered with volume atrophy and a small number of vacuoles and nuclear solidification,most neuronal cells were degenerated and necrotic,microglia hyperplasia was obvious,small blood vessels were significantly increased,and interstitial lipid degeneration was severe.The density of periarterial lymph sheath cells in some of the spleen tissue was reduced and the marginal area is widened.Conclusions A correlation between brain and spleen injury was found after acute ischemic stroke with stasis and toxin syndrome,and the chemokine signaling axis of MCP-1/CCR2 might be involved in the mechanism of brain-spleen inflammation coupling.
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Interferon γ-inducible protein 16(IFI16)is one member of human pyrin and HIN domain-containing protein(PYHIN)family(also known as interferon-inducible p200 pro-tein family),which is widely present in human organs and tis-sues,and is involved in cell cycle regulation,senescence and ap-optosis,even in immune reaction.The content and localization of IFI16 may change under different physiological and pathological conditions,and recent studies have revealed that it may play an important role in the development of antiviral,tumor,inflammato-ry diseases and other diseases.In this paper,we review its mechanism and the current status of its research in diseases,with the aim of providing a reference for the in-depth study of IFI16.
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Objective To study the medication law of Professor Zhang Yunling in the treatment of headache based on data mining technology;To provide ideas for the clinical treatment of headache.Methods Professor Zhang Yunling's outpatient TCM prescription data for the treatment of headache from Sep.2017 to Dec.2020 were collected,and the Ancient and Modern Medical Record Cloud Platform 2.3.5 was used to mine the selected TCM prescriptions for herbal medicine frequency statistics,property,taste and meridian tropism statistics,herbal medicine efficacy statistics,correlation analysis,clustering analysis,complex network analysis,etc.Results Through collection and screening,totally 332 prescriptions were included,involving 178 kinds of Chinese materia medica,with a total frequency of 5 380 times.The top 10 kinds of Chinese materia medica were Chuanxiaong Rhizoma,Paeoniae Radix alba,Atractyodis Macrocephalae Rhizoma,Testudinis Carapax et Plastrum,Bambusae Caulis in Taenia,Glycyrrhizae Radix et Rhizoma,Astragali Radix,Amomi Fructus Rotundus,Pinelliae Rhizoma Praeparatum,and Polygalae Radix.They were mainly warm,mild and slightly cold in properties,sweet,pungent and bitter in tastes,and liver,lung,spleen meridian in meridian tropism.In the statistics of herbal medicine efficacy,expelling wind and relieving pain,suppressing liver yang,promoting blood circulation and qi,clearing heart and relieving restlessness,clearing heat and detoxifying,softening liver and relieving pain were used more frequently.The combinations in herbal medicines association included"Atractyodis Macrocephalae Rhizoma-Chuanxiaong Rhizoma","Testudinis Carapax et Plastrum-Paeoniae Radix alba","Glycyrrhizae Radix et Rhizoma-Paeoniae Radix alba","Testudinis Carapax et Plastrum-Chuanxiaong Rhizoma","Bambusae Caulis in Taenia-Chuanxiaong Rhizoma".Herbal medicines clustering clustered 32 kinds of high-frequency herbal medicines used more than 60 times into 6 categories.Complex network analysis screened out the core formula for the treatment of headache:Chuanxiaong Rhizoma,Paeoniae Radix alba,Atractyodis Macrocephalae Rhizoma,Bambusae Caulis in Taenia,Pinelliae Rhizoma Praeparatum,Testudinis Carapax et Plastrum,Astragali Radix,Amomi Fructus Rotundus,and Glycyrrhizae Radix et Rhizoma.Conclusion In the treatment of headache,Professor Zhang Yunling holds that the pathogenesis of headache is deficiency in origin and excess in superficiality,deficiency of qi and blood,loss of nourishment of brain collaterals,stagnation of phlegm and dampness,disturbance of wind pathogen,obstruction of brain collaterals,and the location of the disease is related to the five viscera and involves the stomach.Focuses on tonifying deficiency and reducing excess,treats exterior and interior separately,and gives consideration to both the symptoms and the root causes,which often uses drugs to treat headache,such as dispelling wind and relieving pain,promoting blood circulation and relieving pain,relieving spasm and relieving pains,eliminating phlegm and dampness,invigorating qi and spleen,nourishing blood and yin,eliminating dampness and regulating stomach,relieving depression and restlessness,which can provide some reference for the clinical treatment of headache.
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@#Objective The potential mechanism of curcumin(CUR)combined with berberine(BBR)in improving drug-induced liver injury(DILI)was preliminarily predicted by a method of in vivo experiment in combination with network pharmacology.Methods The animal model was established by acetaminophen(APAP)-induced DILI and the levels of alanine aminotransferase(ALT)and aspartate aminotransferase(AST)were detected in serum of mice.The network pharmacological approach was used to collect related targets of CUR,BBR,and DILI;Wayne mapping was carried out to screen intersection targets,followed by establishment of a protein-protein interaction(PPI)network of CUR-BBR-DILI.Functional enrichment analysis of gene ontology(GO)and pathway enrichment analysis of Kyoto Encyclopedia of Genes and Genomes(KEGG)were conducted finally.Results The in vivo experimental results showed that the combination of CUR and BBR can significantly reduce the serum ALT and AST levels in mice,which is better than administration alone;Network pharmacology experiment results exhibited that 291 related targets of CUR and 208 related targets of BBR were collected by PharmMapper database,and 904 related targets of DILI were collected by Genecards database;77 intersection targets were screened by Venny 2.1.0 database;52 gene functions and 20 signal pathways possibly in connection with the improvement of DILI via drug combination were obtained by GO and KEGG analysis,respectively;nine of the top ten core targets according to degree in PPI network were enriched to PI3K/AKT signaling pathway,which were in order as follows:SRC,EGFR,HSP90AA1,IGF1,HRAS,MAPK14,ESR1,CASP3,and PTK2.Conclusion DILI might be synergistically improved by CUR combined BBR through multi-target and multi-pathway manner,providing a theoretical basis for the elucidation of the mechanism of drug combination against DILI.
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ObjectiveThe differential expression of microRNAs (miRNAs) between the active stage and the remission stage of ulcerative colitis (UC) was analyzed by bioinformatics method, and the regulatory relationship was constructed by screening the differentially expressed genes (DEGs). The mechanism of Xizhuo Jiedu recipe in the treatment of UC was speculated and verified by animal experiments. MethodThe miRNAs data set of colonic mucosa tissue of UC patients was obtained from the gene expression database (GEO), and the most differentially expressed miRNAs were screened by GEO2R, Excel, and other tools as research objects. TargetScan, miRTarbase, miRDB, STRING, TRRUST, and Matescape databases were used to screen key DEGs, predict downstream transcription factors (TFs), gene ontology (GO), and conduct Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis. The key signaling pathways were selected for animal experiments. In animal experiments, the UC mouse model was prepared by making the mouse freely drink 2.5% dextran sodium sulfate (DSS). Xiezhu Jiedu recipe and mesalazine were given by gavage for seven days, and the inflammatory infiltration of colonic mucosa was observed by hematoxylin-eosin (HE) staining. Real-time fluorescence quantitative polymerase chain reaction (Real-time PCR) was used to detect the mRNA expression of miR-155-5p in colon tissue. Immunohistochemistry and Western blot were used to detect the protein expression levels of cytokine signal transduction inhibitor (SOCS1), phosphorylated transcriptional signal transductor and activator 3 (p-STAT3), phosphorylated Janus kinase 2 (p-JAK2), and retinoic acid-associated orphan receptor-γt (ROR-γt). The expression levels of transforming growth factor-β (TGF-β), interleukin-17 (IL-17), interleukin-6 (IL-6), and interleukin-10 (IL-10) in serum were detected by enzyme linked immunosorbent assay (ELISA). ResultThe GSE48957 dataset was screened from the GEO database, and miR-155-5p was selected as the research object from the samples in the active and remission stages. 131 DEGs were screened. The GO/KEGG enrichment analysis was closely related to biological processes such as positive regulation of miRNA transcription and protein phosphorylation, as well as signaling pathways such as stem cell signaling pathway, IL-17 signaling pathway, and helper T cell 17 (Th17) cell differentiation. The Matescape database was used to screen out 10 key DEGs, among which SOCS1 was one of the key DEGs of miR-155-5p. Further screening of the TFS of key DEGs revealed that STAT3 was one of the main TFs of SOCS1. The results of animal experiments showed that Xiezhu Jiedu Recipe could effectively down-regulate the mRNA expression of miR-155-5p and protein expression of p-STAT3, p-JAK2, and ROR-γt in colon tissue of UC mice and the expression of IL-17 and IL-6 in serum of UC mice, up-regulate the protein expression of SOCS1 and the expression of TGF-β and IL-10, increase the level of anti-inflammatory factors, and reduce inflammatory cell infiltration. ConclusionIt is speculated that Xizhuo Jiedu recipe may interfere with SOCS1 by regulating the expression of miR-155-5p in UC mice, inhibit the phosphorylation of STAT3, inhibit the differentiation of CD4+ T cells into Th17 cells, reduce the levels of pro-inflammatory factors (IL-17 and IL-6), and increase the levels of anti-inflammatory factors (TGF-β and IL-10). As a result, the inflammation of colon mucosa in UC mice was alleviated.
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ObjectiveTo observe and compare the electrocardiogram index, myocardial morphology, and connexin 43 (Cx43) expression of two rat models of acute cerebral infarction (ACI) due to stasis combined with toxin complicated with cerebral-cardiac syndrome (CCS), and to provide experimental evidence for the research on the occurrence mechanism of cardiac diseases induced by ACI and the clinical diagnosis and treatment of CCS. MethodSixty SPF-grade male SD rats were randomized into six groups (n=10): normal , syndrome of stasis combined with toxin induced by carrageenin combined with dry yeast (CA/Y), multi-infarct induced by micro-embolism (ME), middle cerebral artery occlusion (MCAO), CA/Y+ME, and CA/Y+MCAO groups. The model of syndrome of stasis combined with toxin was established by intraperitoneal injection with carrageenan (CA) at 10 mg·kg-1 on the first day and subcutaneous injection with dry yeast (Y) suspension (2 mg·kg-1) on the second day of modeling. Twenty-four hours after the modeling of ACI, the electrocardiograms (ECGs) of rats in each group were collected and the number/percentage (%) of abnormal ECG was calculated. The infarct area of the brain was evaluated by 2,3,5-triphenyltetrazolium chloride (TTC) staining, and myocardial injury was assessed by hematoxylin-eosin (HE) staining. Immumohistochemical staining and Western blot were employed to determine the expression of Cx43 in the myocardium. ResultA certain number of rats in each model group presented abnormal ECG. Compared with the normal group and CA/Y group, CA/Y+MCAO group had the highest rate of abnormal ECG (P<0.01). Compared with the normal, CA/Y, ME, and CA/Y+ME groups, the CA/Y+ME and CA/Y+MCAO groups showed decreased amplitudes of P-wave and T-wave, shortened P-R interval, and extended Q-T interval, which were particularly obvious in the CA/Y+MCAO group (P<0.05, P<0.01) and in accordance with the cerebral infarction area and pathological changes. The expression of Cx43 was up-regulated in both CA/Y+ME and CA/Y+MCAO groups, especially in the CA/Y+MCAO group (P<0.01). ConclusionThe two rat models of ACI due to stasis combined with toxin complicated with CCS can be used to study the mechanism of heart diseases caused by cerebrovascular diseases and the therapeutic effects of Chinese medicines with the functions of resolving stasis and detoxifying. Moreover, the CA/Y+MCAO method has higher abnormal electrocardiogram rate, severer myocardial pathological injury, and higher expression of Cx43 protein. The models can be chosen according to specific experimental purpose.
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Diabetic retinopathy(DR) and coronary heart disease(CHD) are both major chronic vascular complications that seriously jeopardize the health of the population and often occur together in clinical practice, it is of great clinical value to actively explore the association between the two in the process of disease development and methods of prevention and treatment of modern medicine and traditional Chinese medicine(TCM). According to TCM, the heart and eyes physiologically communicate with each other by taking Qi, blood and veins as bridges, blood stasis obstructing collaterals is the common TCM etiology of DR and CHD, whose mechanism involves inflammation, oxidative stress and endothelial dysfunction. Promoting blood circulation and removing blood stasis plays an important role in the same treatment for different diseases and prevention and treatment of comorbidities, possibly by inhibiting the expression of interleukin-1β(IL-1β), endothelin-1(ET-1) and hypoxia inducible factor-1α/vascular endothelial growth factor(HIF-1α/VEGF), regulating phosphatidylinositol 3-kinases/protein kinase B/mammalian target of rapamycin(PI3K/Akt/mTOR) pathway, initiating adenosine monophosphate(AMP)-activated protein kinase/silent information regulator 1(AMPK/SIRT1) and nuclear transcription factor erythroid 2-related factor 2/heme oxygenase-1(Nrf2/HO-1) signaling pathways, inhibiting Hippo/Yes-associated protein(Hippo/YAP) signaling pathway, inhibiting mitochondrial permeability transition pore and anti-platelet agglutination for treating DR and CHD, which provides a multi-component, multi-pathway and multi-target selection strategies and ideas for the prevention and treatment of DR and CHD by TCM from a biological perspective. Based on this, subsequent studies should focus on constructing clinically relevant comorbidity models, conducting multicenter prospective studies, and fully utilizing artificial intelligence technology to gain a deeper understanding of the relationship between the two diseases, so as to elucidate the mechanism of promoting blood circulation and removing blood stasis in preventing and treating panvascular diseases.
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Fatty acids(FAs),which were initially recognized as energy sources and essential building blocks of biomembranes,serve as the precursors of important signaling molecules.Tracing FA metabolism is essential to understanding the biochemical activity and role of FAs in physiological and pathological events.Inspired by the advances in click chemistry for protein enrichment,we herein established a click chemistry-based enrichment(CCBE)strategy for tracing the cellular metabolism of eicosapentaenoic acid(EPA,20:5 n-3)in neural cells.Terminal alkyne-labeled EPA(EPAA)used as a surrogate was incubated with N2a,mouse neuroblastoma cells,and alkyne-labeled metabolites(ALMs)were selectively captured by an azide-modified resin via a Cu(I)-catalyzed azide-alkyne cycloaddition reaction for enrichment.After removing unlabeled metabolites,ALMs containing a triazole moiety were cleaved from solid-phase resins and subjected to liquid chromatography mass spectrometry(LC-MS)analysis.The proposed CCBE strategy is highly selective for capturing and enriching alkyne-labeled metabolites from the complicated matrices.In addition,this method can overcome current detection limits by enhancing MS sensitivity of targets,improving the chromatographic separation of sn-position glycerophospholipid regioisomers,facilitating structural characterization of ALMs by a specific MS/MS fragmentation signature,and providing versatile fluorescence detection of ALMs for cellular distribution.This CCBE strategy might be expanded to trace the metabolism of other FAs,small molecules,or drugs.
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Objective To optimize the microwave-assisted extraction process of green tea polyphenols. Methods The extraction yield of tea polyphenols was figured up by building the standard curve of gallic acid and examining the concentration of tea polyphenols in green tea extract with the introduction of a correction factor. The effects of four single factor levels of microwave extraction time, microwave output power, liquid-to-material yield, and ethanol volume fraction on the extraction yield of tea polyphenols were primarily studied in this experiment. The response surface was applied to further optimize the extraction process of green tea polyphenols after exploring the appropriate range of four single factor levels. Results The optimal extraction process was as follows: extraction time 37 s, microwave output power 350 w, material - liquid yield 1∶45 (g/ml), ethanol volume fraction 55%, and the actual extraction yield of tea polyphenols was 25.65%, which was not much different from the theoretical value. Conclusion The microwave-assisted green tea polyphenol extraction process optimized by response surface methodology is time-saving and practicable, and the extraction yield is high.
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Breast cancer is a kind of malignant tumor discovered lately, with a high incidence and a poor prognosis. The shortage of relevant biological biomarkers lead to the unsatisfactory treatment efficacy and the early diagnosis in breast cancer. Metabolomics is a new discipline that uses high-throughput analysis techniques to study the dynamic changes of endogenous metabolites under the influence of different pathological physiological stimulation or gene mutations, which has provided a novel way for biomarker screening and disease diagnosis and treatment. The overview of metabolomics and its applications in breast cancer early diagnosis, drug efficacy evaluation, and disease prognosis were summarized in this review.
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Objective To construct a cardiovascular chip model for evaluating the damage of vascular glycocalyx induced by four marine toxins: okadaic acid (OA), conotoxin (CTX), tetrodotoxin (TTX) and gymnodimine (GYM), and explore the protective effect of triptolide on toxin-induced injury. Methods Human umbilical vein endothelial cells(HUVEC) were inoculated into a three-channel microfluidic chip. CCK-8 method and immunofluorescence staining were used to analyze the damage of cell viability and glycocalyx tissue induced by low, middle and high concentrations of marine toxin, as well as the protective effect of triptolide on toxin-induced injury. Results The cells in the cardiovascular chip grew well and had structurally intact glycocalyx. Compared with the control group, the activity of HUVEC cells were inhibited in group of the medium and high concentration of OA and high concentration of GYM (P<0.05). The activity of cells had not been inhibited by CTX and TTX significantly , but all the four toxins caused serious damage to the glycocalyx tissue (P<0.01). After pre-protection with triptolide, the toxicity of the four toxins to HUVEC cells and the damage rate of glycocalyx decreased significantly. Conclusion The four marine biotoxins could damage the activity and glycocalyx of HUVEC cells in a dose-dependent manner, while triptolide has a protective effect on HUVEC cells injured by toxin.
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As a highly malignant tumor, the diagnosis of cholangiocarcinoma (CCA) is often late and the prognosis is poor for which the early symptoms are atypical and the lack of accurate biomarkers. Metabolomics is an emerging science that researches the alterations of all endogenous small molecule metabolites in an organism under the influence of pathological, physiological or genetic modification. The development and progress of CCA is closely related to metabolism. Metabolomic is characterized by global analysis, high throughput and reflects real-time alterations in biology system, providing a new avenue for biomarker screening and diseases diagnosis and treatment. The advances of metabolomics studies on CCA in the recent years were reviewed in this paper which could provide the reference for further research.
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Gypenosides, structurally analogous to ginsenosides and derived from a sustainable source, are recognized as the principal active compounds found in Gynostemma pentaphyllum, a Chinese medicinal plant used in the treatment of the metabolic syndrome. By bioactive tracking isolation of the plants collected from different regions across China, we obtained four new gypenosides (1-4), together with nine known gypenosides (5-13), from the methanol extract of the plant. The structures of new gypenosides were elucidated by one-dimensional (1D) and two-dimensional (2D) nuclear magnetic resonance (NMR) spectra, complemented by chemical degradation experiments. Through comprehensive evaluation involving COL1A1 promoter assays and PP2Cα activity assays, we established a definitive structure-activity relationship for these dammarane-type triterpenoids, affirming the indispensability of the C-3 saccharide chain and C-17 lactone ring in effectively impeding extracellular matrix (ECM) deposition within hepatic stellate cells. Further in vivo study on the CCl4-induced liver damage mouse model corroborated that compound 5 significantly ameliorated the process of hepatic fibrosis by oral administration. These results underscore the potential of dammarane-type triterpenoids as prospective anti-fibrotic leads and highlight their prevalence as key molecular frameworks in the therapeutic intervention of chronic hepatic disorders.
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Animals , Mice , Gynostemma , Liver Cirrhosis/drug therapy , Triterpenes/pharmacology , Ginsenosides , Extracellular Matrix , DammaranesABSTRACT
Methods The model of heart failure after myocardial infarction was established by left coronary artery liga-tion in rats. Two weeks after modeling, all rats were randomly divided into model group, LGZGD group, and captopril group. Meanwhile sham operation group was set up. The rats were given continuous intragastric administration with drug or distilled water for 28 days, once a day. The behavioral signs of rats in each group were observed. The cardiac function of rats in each group was examined by echocardiography. Serum BNP and NT-ProBNP content were detected by enzyme-linked immunoassay; The changes of myocardial his-topathological and collagen fibers in rats were detected using sirius staining. The contents of oxidative stress index including ROS, SOD in myocardial tissue of rats in each group were observed by DCFH-DA fluorescent probe and Enzyme-linked immunoassay. The ultra-structure of mitochondria was observed by transmission electron microscopy. Expressions of apoptotic proteins ( mitochondrial CytC, cytoplasmic CytC) were detec- ted by Western blot. Expression of proteins related to the Nrf2/BNIP3 pathway were examined by immunoflu-orescence and Western blot. Results LGZGD could significantly improve the cardiac function of rats, reduce the contents of BNP and NT-ProBNP, inhibit the excessive deposition of collagen in myocardial interstiti-um, reduce ROS, increase the content of SOD, improve mitochondrial structure damage, up-regulate the expression of Nrf2 and nuclear translocation, and reduce the expression of BNIP3. Conclusions LGZGD can inhibit the ventricular remodeling and prevent the occurrence of heart failure after myocardial infarction. Its pharmacological effects are mainly related to regulating the Nrf2/BNIP3 pathway, activating Nrf2, promoting its nuclear transfer, and further down-regulating BNIP3 , protecting mitochondrial function, and reducing cardiomyocyte apoptosis.
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Aim To study the effect of Rubus irritans Focke extract on adipogenic differentiation of 3T3-L1 preadipocytes, and to further explore the potential mechanism of Rubus irritans Focke on adipocyte metabolism, so as to provide a new basis for the prevention and treatment of obesity. Methods Rubus irritans Focke extract was separated and prepared by MCI medium pressure chromatographic column. MTT method was used to detect cell proliferation, and oil red 0 staining and kit test was used to to detect the level of lipid accumulation. Western blot was employed to detect the expressions of peroxisome proliferator-activated receptor ¦y (PPAR7), CCAAT enhancer binding protein a (C/ EBPa), adenosine 5'-monophosphate activated protein kinase (AMPK) and phosphorylated AMPK (p-AMPK) protein. Results When the concentration of Rubus irritans Focke extract was less than 100 mg •L
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Aim To discuss the mechanism of Lurong Dabu Decoction on cough variant asthma. Methods Guinea pigs were divided into normal group(CON), model group(OVA), Lurong Dabu Decoction high-dose group(HIGH),low-dose group(LOW), and dexamethasone group(DEX)at random. The CVA model was established by smoking plus injection of OVA, aluminum hydroxide solution and nebulized inhalation to stimulate cough. Gguinea pigs were dissected 24 hours after the last challenge to obtain alveolar lavage fluid(BALF)and lung tissues. Immunoadsorption(ELISA)method was applied to detect the types of inflammatory cells and the content of inflammatory cytokines in BALF; HE and Masson staining of the middle lobe of the left lung were used to observe the pathological changes in lung tissues; immunohistochemical staining was used to observe TLR4 and WNT-5A protein expression and distribution of lung tissues; the protein extracted from the upper lobe of the left lung was used to measure the level of TLR4 and WNT-5A protein in lung tissues by Western blot; immunofluorescence was employed to measure the fluorescence intensity of TLR4 and WNT-5A in lung tissues; flow cytometry was used to detect IL-4 and IFN-γ in guinea pig lung tissues. Results Lurong Dabu Decoction could improve guinea pig airway inflammation, inhibit collagen fiber deposition, reduce the content of IL-4, IL-5, and IL-13 in BALF, and inhibit the protein expression of TLR4 and WNT-5A in lung tissues and increase IFN-γ levels in lung tissues while decreasing IL-4 levels. Conclusion Lurong Dabu Decoction may inhibit the occurrence of CVA through TLR4/WNT-5A signaling pathway.
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To investigate the regulation of N6- methyladenosine ( m6A ) modification on L-type calcium channels in atrial myocytes under high hydrostatic pressure, mediated by methyltransferase-like protein 3 ( METTL3 ). Methods C57BL/6J mice were randomly assigned to the control group and the hypertension group ( treated with continuous administration of angiotensin for four weeks ). Masson staining was used to observe the fibrosis of mouse atrial tissue, while dot blot assay and Western blot were used to detect the levels of m6A, METTL3, and Cavi1 2 in the atrial tissue. A high hydrostatic pressure model was constructed using the HL-1 cell line cultured in vitro, and METTL3 was intervened to observe changes in m6A expression levels, METTL3 and Cavi1 2 levels in cells,and action potential duration ( APD ) and L-type calcium current ( I
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OBJECTIVE@#To explore the technical aspects of the accuracy of cervical pedicle screw placement with O-arm guidance.@*METHODS@#The clinical data of 21 patients who underwent cervical pedicle screw fixation by O-arm real-time guidance from December 2015 to January 2020 were analyzed retrospectively. There were 15 males and 6 females, aged from 29 to 76 years old with an average of (45.3±11.5) years. The postoperative CT scan was utilized to evaluate the placement of the pedicle screw and classified according to the Gertzbein and Robbins classification.@*RESULTS@#A total of 132 pedicle screws were implanted in 21 patients, 116 at C3-C6 and 16 at C1 and C2. According to Gertzbein & Robbins classification, the overall breach rates were found to be 11.36% (15/132) with 73.33% (11 screws) Grade B, 26.67% (4 screws) Grade C, and no Grade D or E screw breaches. There were no pedicle screw placement related complications at final follow-up.@*CONCLUSION@#The application of O-arm real-time guidance technology can make cervical pedicle screw placement reliable. High accuracy and better intra-operative control can increase surgeon's confidence in using cervical pedicle instrumentation. Considering the high-risk nature of anatomical area around cervical pedicle and the possibility of catastrophic complications, the spine surgeon should have sufficient surgical skills, experience, ensures stringent verification of the system, and never relies solely on the navigation system.