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A BBB co-culture cell model consisting of rat brain microvascular endothelial cells (BMEC) and astrocytes (AS) was established to study the effect of Angelica dahurica coumarins on the transport behavior of puerarin across blood-brain barrier (BBB) in vitro and in vivo. The barrier function of this model was evaluated by measuring the transendothelial resistance, phenol red permeability and BBB related protein expression. The permeability assay and western blot methods were performed to study the effects of Angelica dahurica coumarins on the BBB permeability and the expression of BBB related protein. The animal experiment protocols in this study were approved by the Animal Ethics Committee of Xi'an Jiaotong University (Animal Ethics No.: 2021-1329). The results showed that the established BMEC/AS co-culture model could be used to evaluate drug transport across BBB in vitro. After combined with Angelica dahurica coumarins, the transport capacity of puerarin was significantly increased in vitro and in vivo. Additionally, Angelica dahurica coumarins enhanced BBB permeability and inhibited the protein expression of P-glycoprotein (P-gp), zonula occludens-1 (ZO-1) and occludin. Angelica dahurica coumarins might increase BBB permeability by inhibiting the expression of P-gp and tight junction protein, thereby increasing the content of puerarin in brain tissue.
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OBJECTIVES@#To investigate the change in the distribution of memory B cell subsets in children with frequently relapsing nephrotic syndrome (FRNS) during the course of the disease.@*METHODS@#A total of 35 children with primary nephrotic syndrome (PNS) who attended the Department of Pediatrics of the Affiliated Hospital of Xuzhou Medical University from October 2020 to October 2021 were enrolled as subjects in this prospective study. According to the response to glucocorticoid (GC) therapy and frequency of recurrence, the children were divided into two groups: FRNS (n=20) and non-FRNS (NFRNS; n=15). Fifteen children who underwent physical examination were enrolled as the control group. The change in memory B cells after GC therapy was compared between groups, and its correlation with clinical indicators was analyzed.@*RESULTS@#Before treatment, the FRNS and NFRNS groups had significantly increased percentages of total B cells, total memory B cells, IgD+ memory B cells, and IgE+ memory B cells compared with the control group, and the FRNS group had significantly greater increases than the NFRNS group (P<0.05); the FRNS group had a significantly lower percentage of class-switched memory B cells than the NFRNS and control groups (P<0.05). After treatment, the FRNS and NFRNS groups had significant reductions in the percentages of total B cells, total memory B cells, IgM+IgD+ memory B cells, IgM+ memory B cells, IgE+ memory B cells, IgD+ memory B cells, and IgG+ memory B cells (P<0.05) and a significant increase in the percentage of class-switched memory B cells (P<0.05). The FRNS group had a significantly higher urinary protein quantification than the NFRNS and control groups (P<0.05) and a significantly lower level of albumin than the control group (P<0.05). In the FRNS group, urinary protein quantification was negatively correlated with the percentage of class-switched memory B cells and was positively correlated with the percentage of IgE+ memory B cells (P<0.05).@*CONCLUSIONS@#Abnormal distribution of memory B cell subsets may be observed in children with FRNS, and the percentages of IgE+ memory B cells and class-switched memory B cells can be used as positive and negative correlation factors for predicting recurrence after GC therapy in these children.
Subject(s)
Child , Humans , B-Lymphocyte Subsets/metabolism , Immunoglobulin E , Immunoglobulin M , Nephrotic Syndrome/immunology , Prospective Studies , Glucocorticoids/therapeutic useABSTRACT
In recent years, immunotherapy has made great progress in clinical cancer therapy. However, the poor tumor specificity, low intra-tumoral penetration, and low cellular uptake in the systemic delivery of immunotherapeutic drugs lead to low efficacy and poor safety, limiting the development of immunotherapy. Active tumor-targeting nano drug delivery systems (aNDDS) can enhance the concentration of drugs in target cells through the interaction between surface-conjugated antibodies or ligands and the receptors on target cell membranes, providing a viable strategy for specific and efficient drug delivery. In addition, some specific types of cell membranes with the natural targeting ability have been exploited for the construction of biomimetic nanocarriers to improve the drug delivery efficiency. In view of the many advantages of active tumor-targeting nanocarriers, researchers also have designed a series of aNDDS for promoting antitumor immune responses and proved that they improved the efficacy and safety of immunotherapy. In this review, we summarize the recent progress on aNDDS for improving the tumor immunotherapy and look forward to the main challenges and future directions in this field.
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ObjectiveMetabolomics was used to identify biomarkers of chronic alcoholism， and to evaluate the neuroprotective effect of geniposide， providing reference for the diagnosis and treatment of chronic alcoholism. MethodThe rat model of chronic alcoholism was established by intragastric administration of 50% ethanol with 8 mL·kg-1 for 14 days， and then increased to 12 mL·kg-1 for 21 days. Meanwhile， the intervention was performed by continuous gavage of geniposide （15 mg·kg-1） for 35 days. At the end of the experiment， the biochemical indexes and histopathological morphology of liver and brain tissues of rats were detected. Ultra performance liquid chromatography-quadrupole-time-of-flight tandem mass spectrometry （UPLC-Q-TOF-MS） was used for urine metabonomics. The chromatographic conditions was as follows：ACQUITY UPLC™ HSS T3 column （2.1 mm×100 mm， 1.8 μm）， mobile phase of 0.1% formic acid acetonitrile solution （A）-0.1% formic acid aqueous solution （B） for gradient elution （0-2.5 min， 1%-11%A； 2.5-4.5 min， 11%-21%A； 4.5-7.0 min， 21%-40%A； 7.0-8.5 min， 40%-99%A； 8.5-10.5 min， 99%A； 10.5-10.6 min， 99%-1%A； 10.6-13.0 min， 1%A）， the flow rate of 0.4 mL·min-1. The conditions of mass spectrometry were electrospray ionization （ESI）， positive and negative ion modes， scanning range of m/z 50-1 200. Progenesis QI 2.0 and MassLynx 4.1 were used for data analysis， and biomarkers were identified by matching element composition and secondary fragments with Human Metabolome Database （HMDB）. ResultThe pathological results showed that on the 35th day of model replication， compared with the model group， the cortical neurons in the geniposide group showed a significantly improved state of disorder， nuclear pyknosis， hyperchromatism and cell membrane boundary blurred necrosis. The biochemical results showed that geniposide could significantly increase the activities of glutathione peroxidase （GSH-Px） and superoxide dismutase （SOD）， decrease the activity of acetylcholinesterase （AChE）， decrease the levels of β-endorphin （β-EP） and malondialdehyde （MDA）. A total of 48 biomarkers of chronic alcoholism were identified by metabonomics， involving seven metabolic pathways of tryptophan metabolism， phenylalanine metabolism， pentose and glucuronate interconversions， pyrimidine metabolism， ascorbate and aldarate metabolism， steroid hormone biosynthesis and purine metabolism. The main pathway is 5-hydroxytryptamine pathway of tryptophan metabolism. ConclusionBiomarkers related to nerve injury in chronic alcoholism are mainly derived from the 5-hydroxytryptamine metabolic pathway. Geniposide can regulate this pathway so as to improve oxidative stress in the brain and play a neuroprotective role.
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Objective:To investigate the clinicopathological characteristics and influencing factors of kidney prognosis in primary IgA nephropathy (IgAN) patients.Methods:The data of primary IgAN patients diagnosed with renal biopsy in the First Affiliated Hospital of Anhui Medical University from January 2015 to September 2019 were retrospective analyzed. According to the level of baseline estimated glomerular filtration rate (eGFR) when performing renal biopsy, the patients were divided into group A[eGFR≥90 ml·min -1·(1.73 m 2) -1], group B[eGFR 61-89 ml·min -1·(1.73 m 2) -1] and group C[eGFR≤60 ml·min -1·(1.73 m 2) -1]. The clinical and pathological data were collected and compared among the three groups. Kaplan-Meier method was conducted for renal results, whereas the Cox proportional-hazards regression model was exploited to analyze the influencing factors of kidney prognosis in IgAN patients. Results:A total of 742 patients were included in the study, including 394 cases (53.1%) in group A, 203 cases (27.4%) in group B, and 145 cases (19.5%) in group C. There were 325 males (43.8%) and 417 females (56.2%). The median duration of renal biopsy was 6 (1, 24) months, and the median age was 36 years old (18-68 years old). As the baseline level of renal function decreased, the proportion of patients with nephrotic syndrome, hypertension, anemia and hyperuricemia and the levels of 24 h urinary protein, serum triglyceride and total cholesterol increased significantly (all P<0.05), while the proportion of gross hematuria episodes and the ratio of serum albumin to globulin significantly decreased (all P<0.05). For the aspect of pathological manifestations, the proportions of cell proliferation in capillaries (E1), segmental sclerosis or adhesion (S1), renal tubular atrophy or interstitial fibrosis (T1/2), globular sclerosis, renal arteriole wall thickening and vitreous degeneration, Lee's grade Ⅳ and Ⅴ increased with the decrease of baseline renal function (all P<0.05). Kaplan-Meier analysis showed that the cumulative renal survival rate decreased with the decline of baseline renal function (Log-rank χ2=88.510, P<0.001). As a result of multivariate Cox regression analysis, nephrotic syndrome ( HR=2.399, 95% CI 1.054-5.459, P=0.037), hypertension ( HR=1.806, 95% CI 1.071-3.048, P=0.027), low baseline eGFR (taking group A as the reference, group B: HR=2.383, 95% CI 1.053-5.392, P=0.037; group C: HR=6.878, 95% CI 3.074-15.393, P<0.001), IgG deposition ( HR=2.224, 95% CI 1.384-3.574, P=0.001) and globular sclerosis ( HR=2.075, 95% CI 1.230-3.501, P=0.006) were the independent influencing factors for renal progression in primary IgAN patients. Conclusions:The level of baseline renal function in primary IgAN patients can be used to predict the extent of clinic-pathological damage. Nephrotic syndrome, hypertension, low baseline eGFR, IgG deposition and globular sclerosis are the independent influencing factors for renal progression in primary IgAN patients.
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Nature has endowed gaseous molecules such as O
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OBJECTIVE@#To investigate the protective effect of electroacupuncture (EA) at "Zusanli" (ST 36) in pregnant rats on lung dysplasia of newborn rats with intrauterine growth restriction (IUGR) induced by maternal food restriction.@*METHODS@#Twenty-four female SD rats were randomly divided into a control group, a control+EA group, a model group and a model+EA group, 6 rats in each group. From the 10th day into pregnancy to the time of delivery, the rats in the model group and the model+EA group were given with 50% dietary restriction to prepare IUGR model. From the 10th day into pregnancy to the time of delivery, the rats in the control+EA group and the model+EA group were treated with EA at bilateral "Zusanli" (ST 36), once a day. The body weight of offspring rats was measured at birth, and the body weight and lung weight of offspring rats were measured on the 21st day after birth. The lung function was measured by small animal lung function detection system; the lung tissue morphology was observed by HE staining; the content of peroxisome proliferator activated receptor γ (PPARγ) in lung tissue was detected by ELISA.@*RESULTS@#Compared with the control group, the body weight at birth as well as the body weight, lung weight, lung dynamic compliance (Cdyn) and PPARγ at 21 days after birth in the model group were significantly decreased (@*CONCLUSION@#EA at "Zusanli" (ST 36) may protect the lung function and lung histomorphology changes by regulating the level of PPARγ of lung in IUGR rats induced by maternal food restriction.
Subject(s)
Animals , Female , Pregnancy , Rats , Acupuncture Points , Electroacupuncture , Fetal Growth Retardation/therapy , Lung , Rats, Sprague-DawleyABSTRACT
In this study, ultra-high performance liquid chromatography-linear ion trap/electrostatic field orbit trap combined-type mass spectrometry(UPLC-LTQ-Orbitrap-MS) was used to analyze the main active components of Huangqi Guizhi Wuwu Decoction(HQGZ). A total of 50 active components were identified from HQGZ and 108 potential targets of the components related to the treatment of rheumatoid arthritis were retrieved based on network pharmacology, including 87 key targets, followed by Gene Ontology(GO) term enrichment and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment of the targets. The result indicated that HQGZ may exert therapeutic effects mainly through the sphingolipid signaling pathway, tumor necrosis factor(TNF) signaling pathway, as well as the positive regulation of ribonucleic acid(RNA) polymerase Ⅱ promoter transcription, inflammatory response and other biological processes. At the same time, cell experiment was performed to verify the key proteins in the TNF signaling pathway. The results demonstrated that HQGZ significantly reduced the expression of caspase-3(CASP3), TNF, relaxed(RELA) protein, and IkappaB kinase beta(IKBKB) in fibroblast-like synoviocytes induced by TNF-α. The results of UPLC-LTQ-Orbitrap-MS, network pharmacology and cell experiment showed that the active components in HQGZ may inhibit inflammatory response and regulate immune function and cell apoptosis by modulating key proteins in TNF signaling pathway to treat rheumatoid arthritis.
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Humans , Arthritis, Rheumatoid/genetics , Chromatography, High Pressure Liquid , Drugs, Chinese Herbal/pharmacology , Network Pharmacology , SynoviocytesABSTRACT
Objective: To explore the mechanism of Jingfang Granule in treatment of corona virus infection through biological information technology based on network pharmacology and molecular docking. Methods: The databases of TCMIP and TCMSP were used to summarize the flavor and meridian tropism and active compounds of Jingfang Granule, and the potential targets of active compounds were searched by PubChem and SwissTargetPrediction. The corona virus targets were collected from the GeneCards database. And common targets were enriched and analyzed by DAVID database after the intersection of the compounds targets and the disease targets. Then the network of "TCM-Ingredients-Common targets" was established by Cytoscape 3.7.2, the main active components and key targets were screened for molecular docking. Results: Totally 139 active components of Jingfang Granule and 27 common targets were obtained. GO enrichment analysis and KEGG enrichment analysis found that the pathways in cancer, MAPK signaling pathway, PI3K-Akt signaling pathway, TNF signaling pathway were the main pathways of Jingfang Granule in treatment of corona virus infection. The network of "TCM-Ingredients-Common targets" was successfully constructed, and results of molecular docking showed that the main components in this network such as β-sitosterol, cerevisterol, isorhamnetin, hesperetin, and luteolin etc., have good affinity with key targets of VEGFA, IL6, TNF, PPARγ, APP, ACE2, and SARS-CoV-2 3CL hydrolase. Conclusion: Jingfang Granule treats corona virus infectious diseases through the compatibility of multiple traditional Chinese medicine. Its resistance to corona virus infection may be through the β-sitosterol, cerevisterol, isorhamnetin, hesperetin, and luteolin act on the VEGFA, IL6, TNF, PPARγ, APP and other targets, and then affects the pathways in cancer, MAPK signal pathway, PI3K-Akt signal pathway, TNF signal pathways to achieve.
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Objective:To investigate the expression of long-chain noncoding RNA (lncRNA) CTA-796E4.4 in bladder cancer tissues and cell lines, and to observe its effect on the proliferation and invasion of bladder cancer cells and to explore its possible molecular mechanism.Methods:The expression of CTA-796E4.4 in 73 bladder cancer tissues and adjacent tissues, 4 kinds of bladder cancer cell lines (UM-UC-3, BIU-87, 5637, T24) and normal bladder epithelial cells in the First People′s Hospital of Tianmen City from November 2016 to January 2019 were detected by qPCR. UM-UC-3 cells infected with recombinant lentivirus (LV-CTA-796E4.4) carrying the CTA-796E4.4 gene were taken as an experimental group, and UM-UC-3 cells infected with negative control lentivirus (LV-NC) were as a control group. The effect of over expression of CTA-796E4.4 on the expression of Forkhead box transcription factor O1 (FOXO1) mRNA was detected by qPCR. The expression of FOXO1 protein was detected by Western blotting, Thiazolyl blue (MTT) method Transwell invasion assay was respectively used to examine the effect of high expression of CTA-796E4.4 on proliferation and invasion of UM-UC-3 cells.Results:The expression level of CTA-796E4.4 in bladder cancer tissue was lower than that in para cancerous tissue (1.22 ± 0.33 vs. 4.30 ± 0.64) and the difference was statistically significant ( P < 0.01). The expression of CTA-796E4.4 in bladder cancer cells was lower than that in bladder cancer epithelial cells (0.11 ± 0.03, 0.61 ± 0.03, 0.33 ± 0.03, 0.73 ± 0.04 vs.1.01 ± 0.10) ( P < 0.01). After LV-CTA-796E4.4 infection, the expression of CTA-796E4.4 was significantly increased ( P < 0.01) and the expression of FOXO1 gene was increased ( P < 0.01). High expression of CTA-796E4.4 significantly inhibited cell proliferation and invasion of UM-UC-3 cells ( P < 0.05). Conclusions:The expression of lncRNA CTA-796E4.4 is decreased in bladder cancer and cell lines. High expression of CTA-796E4.4 inhibites the proliferation and invasion of UM-UC-3 cells. The molecular mechanism may be that up-regulation of CTA-796E4.4 can promote the expression of FOXO1.
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Myocardial substrate metabolism is severely impaired after heart failure, and the selection and utilization of substrates, such as glucose and fatty acids, are remodeled, resulting in insufficient myocardial productivity, cardiac dysfunction and progressive left ventricular remodeling. It is believed traditionally that the heart changes from fatty acid metabolism to glucose metabolism during heart failure, which however is contradictory with some findings in recent years. No consistent conclusion can be drawn from studies on the changes of myocardial energy substrate metabolism and its regulatory mechanism after heart failure. Metabolic treatment for heart failure has developed slowly. Therefore, it is necessary to explore the reasons for heterogeneity of these conclusions for defining the metabolic patterns of heart failure substrates and developing metabolically targeted drugs. This review summarizes the metabolic patterns and regulatory mechanisms of normal myocardium under physiological conditions, focuses on the elaboration and comparison of myocardial substrates metabolic abnormalities in heart failure induced by ischemic heart disease, pressure load, volume load and dilated cardiomyopathy in such aspects as etiology, severity, duration of heart failure, species studied, animal models and metabolic detection methods, and makes a preliminary analysis on the consistency and differences of relevant conclusions in various studies, and discusses the future trend of metabolic treatment, with the aim to summarize the rules and molecular mechanism of glucose metabolism and fatty acid metabolism after heart failure and provide clues for the research of metabolic targeted therapy.
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Objective To observe the expression of long non-coding RNA (LncRNA-NEAT1) in renal cell carcinoma and cell lines,and to explore its influence on the malignant biological behavior of renal cell carcinoma and its possible molecular mechanism.Methods The expression of NEAT1 was detected by quantitative polymerase chain reaction (qPCR) in l0 cases of renal cell carcinoma and paracancerous tissues,and in 4 types of renal cell carcinoma cells and normal renal tubular epithelial cells.ACHN cells infected with negative control lentivirus (LV-NC) were used as control group,and ACHN cells infected with recombinant lentivirus carrying NEAT1 gene (LV-NEAT1) were used as experimental group.Bioinformatics predicts targeted miRNA and downstream genes of NEAT1.The effect of overexpression of NEAT1 on the mRNA expression of miR-342-3p and cell adhesion molecule 1 (CADM1) was detected by qPCR.The protein expression of CADM1 was detected by Western blot.The proliferation and invasion of ACHN cells were detected by methyl thiazolyl tetrazolium (MTT) method and Transwell invasion assay.Results The expression level of NEAT1 in renal cell carcinoma was lower than that in paracancerous tissue (P ＜ 0.01).The expression of NEAT1 in renal carcinoma cell lines was lower than that in renal tubular epithelial cells (P ＜0.01).After LV-NEAT1 infection,the expression of NEAT1 and CADM1 gene were significantly increased (P ＜0.01),while the expression of miR-342-3p decreased (P ＜0.01).Overexpression of NEAT1 significantly inhibited cell proliferation and invasion of ACHN cells (P ＜ 0.05).Conclusions LncRNA NEAT1 was down-regulated in renal cell carcinoma and cell lines.Overexpression of NEAT1 inhibited the proliferation and invasion of ACHN cells.The molecular mechanism may be that NEAT1 up-regulates the expression of CADM1 gene through complementary binding to miR-342-3p.
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Objective@#To investigate the etiology, characteristics and prevention of severe facial deformity in patients with uremia entering the dialysis stage.@*Methods@#Four cases with uremia in the dialysis stage who presented with severe facial deformity between October 2011 and November 2018 were reviewed, including 3 males and 1 female. The ages were 31, 15, 51 and 61, respectively. The general information, clinical symptoms, biochemical indicators, relevant imaging indicators, diagnoses, treatments and efficacies of the 4 patients admitted to the First Affiliated Hospital of Anhui Medical University were collected.@*Results@#All the 4 patients appeared obviously shorter, accompanied by a certain degree of decline in self-care ability, multiple bone and joint pain and severe facial deformity. They presented with significantly increased serum levels of alkaline phosphatase, calcium, phosphorus and parathyroid hormone, and parathyroid hormone level>2 500 pg/ml.Ultrasonography and 99Tcm radionuclide scan showed in situ or ectopic hyperplasia of parathyroid tissue. Bone radiography showed local decrease of bone mineral density and cystic changes.After parathyroidectomy, the serum levels of alkaline phosphatase, parathyroid hormone, calciumand phosphorus decreased significantly, while bone pain symptoms and facial deformities gradually improved.@*Conclusion@#Secondary hyperparathyroidism is a serious complication in patients with dialysis and few of patients may have severe facial deformity (Sagliker syndrome) affecting their normal life and social activities. Parathyroidectomy can improve the facial deformity and the quality of life of patients.
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Objective@#To explore the role of comprehensive nursing intervention in improving medication compliance of prostate cancer patients undergoing endocrine therapy.@*METHODS@#We practiced comprehensive nursing intervention in 43 prostate cancer patients undergoing endocrine therapy in our hospital from January 2016 to December 2018. Using the 8-item Morisky Medication Adherence Scale (MMAS-8), we investigated the medication compliance of the patients at 1, 3 and 6 months after treatment.@*RESULTS@#The MMAS-8 score of the patients was 7.8 ± 1.1 at 1 month after medication, decreased to 6.2 ± 1.9 at 3 months (P < 0.05), and increased to 7.9 ± 1.2 at 6 months (P < 0.05).@*CONCLUSIONS@#Comprehensive nursing intervention can improve the medication compliance of prostate cancer patients undergoing endocrine therapy and the outcomes of treatment as well.
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Acupuncture is widely used in the treatment of ischemic diseases of the central nervous system in different clinical stages and has achieved a good clinical effect. The current research showed that acupuncture can improve cerebral blood flow perfusion via increasing blood flow volume, blood flow velocity, the levels of vasomotor substances and reduction of blood viscosity and erythrocyte aggregation index. In recent years, many studies focused on the pathophysiological mechanism of acupuncture in improving cerebral ischemia via triggering the cholinergic vasodilatation, up-regulation of expression of vascular-related proteins and genes，attenuation of inflammatory reaction, etc. Currently, the methods for evaluating the effect of acupuncture are mostly noninvasive functional magnetic resonance imaging in healthy subjects. Future studies should include united selection of acupoints and acupuncture needle manipulations, more reasonable combination of different acupoints, united outcome evaluative standards, better repeatability, employment of big data, etc.
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OBJECTIVE@#To compare the effects of electroacupuncture (EA) at "Zusanli" (ST 36) versus "Yanglingquan" (GB 34) in the pregnant rats on perinatal nicotineexposureinduced lung function and morphology of newborn rats and explore the rule of acupoint effect in EA for the prevention from lung dysplasia in newborn rats.@*METHODS@#A total of 24 female SD rats were randomized into a normal saline group (S group), a nicotine group (N group), a nicotineST 36 group (N + ST 36 group) and a nicotineGB 34 group (N+GB 34 group), 6 rats in each one. Starting at the 6th day of pregnancy, 0.9% sodium chloride solution was injected subcutaneously in the S group, 1 mg/kg; and in the rest 3 groups, nicotine of the same dose was injected through to the 21st postnatal day to establish the perinatal nicotineexposure model. Simultaneously, during model preparation, EA was applied at "Zusanli" (ST 36) and "Yanglingquan" (GB 34) in the N+ST 36 group and the N+GB 34 group respectively, once a day, through to the 21st postnatal day. The lung function analytic system for small animal was adopted to observe the changes in lung function indicators in newborn rats, such as peak inspiratory flow (PIF), peak expiratory flow (PEF), expiratory resistance (RE), inspiratory resistance (RI) and dynamic compliance (Cdyn). HE staining was used to observe the morphological changes of lung, such as alveolar fusion and rupture.@*RESULTS@#Compared with the S group, PEF and Cdyn were lower and PIF, RI and RE higher in the N group (all 0.05).@*CONCLUSION@#Electroacupuncture at "Zusanli" (ST 36) in the pregnant rats significantly improves the perinatal nicotineexposureinduced lung function and morphology of newborn rats than electroacupuncture at "Yanglingquan" (GB 34).
Subject(s)
Animals , Female , Pregnancy , Rats , Acupuncture Points , Animals, Newborn , Electroacupuncture , Lung , Nicotine , Toxicity , Random Allocation , Rats, Sprague-DawleyABSTRACT
Two new polyketides, chinoketides A and B (1 – 2) with a known compound xylarphthalide A (3), were isolated from the solid medium of the endophytes from the leaves of the relic plant Distylium chinense with the “black-box” co-culture method, and the structures of two new compounds were elucidated by NMR, MS and CD spectra. And the absolute configurations of chinoketides A (1) and B (2) were determined as 2R,3R,8S and 5R,6S by calculating their ECD spectra to compare with the experimental CD spectra. Finally, the antimicrobial activities were evaluated to Erwinia carotovora sub sp. Carotovora (Jones) Bersey et al, and the results showed that compounds 1 – 3 displayed the antimicrobial activities with MIC value at 20.5, 30.4 and 10.2 µg/mL.
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Coculture Techniques , Endophytes , Methods , Pectobacterium carotovorum , Plants , PolyketidesABSTRACT
The aim of this paper was to study the curative effect of Huotan Jiedu Tongluo (HTJDTL) decoction on a rabbit model with early atherosclerosis (AS),and furtherly to explore whether it could inhibit the BH4/eNOS uncoupling ROS or not. Twenty-four Japanese white rabbits were randomly divided into sham operation group, model group, HTJDTL decoction group and atorvastatin group. Rabbit models with early atherosclerosis were established by high fat diet, nitrogen drying and carotid artery balloon injury. The rabbits were sacrificed at 7th days after balloon injury and several parameters were measured. The pathological morphology of the common carotid artery was observed by HE staining. The blood lipids were detected by peroxidase method. The ratio of vascular eNOS dimer and monomer was measured by Western blot. The ELISA and biochemical technology were respectively used for testing BH4 and ROS levels in serum. The results showed that compared with the sham operation group, the model group had mild stenosis of the common carotid artery lumen, uneven intimal hyperplasia, lipid deposition in the intima and media, and obvious hyperplasia of the adventitia with inflammatory cell infiltration. The HTJDTL decoction could significantly inhibit the intimal hyperplasia compared with the model group, meanwhile, reduce the lipid deposition of the media and the infiltration of the adventitial cells. Compared with the sham operation group, the blood lipids and ROS of the model animals significantly increased, but BH4 and the ratio of eNOS dimer/monomer decreased. Compared with the model group, HTJDTL decoction significantly reduced the TC, ox-LDL and ROS levels, and also up-regulated eNOS dimer/monomer ratio, but it increased BH4 trend without statistical difference. According to the results, it was found that HTJDTL decoction couldsignificantly prevent and improve the vascular remodeling of rabbits model with early atherosclerosis. The mechanism of decoction may largely be related to the inhibition of BH4/eNOS uncoupling and the reduction of oxidative stress.
Subject(s)
Animals , Rabbits , Atherosclerosis , Drug Therapy , Carotid Arteries , Pathology , Drugs, Chinese Herbal , Pharmacology , Nitric Oxide Synthase Type III , Metabolism , Oxidative Stress , Random Allocation , Signal TransductionABSTRACT
Cardiovascular disease (CVD) is the most common cause of death in patients with non-alcoholic fatty liver disease (NAFLD). New therapeutic strategies which have the potential for slowing down the evolution of NAFLD and reducing CVD-related mortality are urgently needed. Statins are well recognized in the treatment of dyslipidemia, but their use in the treatment of NAFLD is limited due to the safety concerns. Ilexgenin A (IA) is one of the main bioactive compounds in 'Shan-lv-cha', an herbal tea commonly used in China. In the present study, we investigated the possible synergistic therapeutic effects of IA and simvastatin (SV) on NAFLD. IA or SV showed beneficial effects on the rats with NAFLD by lowering the liver weight, liver index and plasma levels of alanine aminotransferase and aspartate aminotransferase, regulating abnormal metabolism of lipids and ameliorating steatosis in liver. IA significantly enhanced the hypolipidemic and anti-inflammation effects of SV. Furthermore, a sensitive, accurate, convenient and reproducible LC-MS method was developed to investigate the effects of IA on the pharmacokinetics of SV. No significant changes were observed in pharmacokinetic parameters of SV and simvastatin hydroxy acid in the IA plus SV co-treated group in comparison with those in the group treated with SV alone. The mRNA levels and activity of CYP3A1 were not altered by IA. In conclusion, the results obtained from the present study should be helpful for further clinical application of SV and IA alone or in combination.
Subject(s)
Animals , Male , Rats , Alanine Transaminase , Metabolism , Aspartate Aminotransferases , Metabolism , Cytochrome P-450 CYP3A , Genetics , Metabolism , Diet, High-Fat , Disease Models, Animal , Drug Synergism , Drug Therapy, Combination , Lipids , Blood , Liver , Metabolism , Pathology , Molecular Structure , Non-alcoholic Fatty Liver Disease , Blood , Drug Therapy , Rats, Sprague-Dawley , Simvastatin , Pharmacokinetics , Therapeutic Uses , Transcription, Genetic , Triterpenes , Chemistry , Therapeutic UsesABSTRACT
Cardiovascular disease (CVD) is the most common cause of death in patients with non-alcoholic fatty liver disease (NAFLD). New therapeutic strategies which have the potential for slowing down the evolution of NAFLD and reducing CVD-related mortality are urgently needed. Statins are well recognized in the treatment of dyslipidemia, but their use in the treatment of NAFLD is limited due to the safety concerns. Ilexgenin A (IA) is one of the main bioactive compounds in 'Shan-lv-cha', an herbal tea commonly used in China. In the present study, we investigated the possible synergistic therapeutic effects of IA and simvastatin (SV) on NAFLD. IA or SV showed beneficial effects on the rats with NAFLD by lowering the liver weight, liver index and plasma levels of alanine aminotransferase and aspartate aminotransferase, regulating abnormal metabolism of lipids and ameliorating steatosis in liver. IA significantly enhanced the hypolipidemic and anti-inflammation effects of SV. Furthermore, a sensitive, accurate, convenient and reproducible LC-MS method was developed to investigate the effects of IA on the pharmacokinetics of SV. No significant changes were observed in pharmacokinetic parameters of SV and simvastatin hydroxy acid in the IA plus SV co-treated group in comparison with those in the group treated with SV alone. The mRNA levels and activity of CYP3A1 were not altered by IA. In conclusion, the results obtained from the present study should be helpful for further clinical application of SV and IA alone or in combination.