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Aim To predict the mechanism of Fufang Congrong Yizhi Capsules (FCYC) in the treatment of mild cognitive impairment (MCI) by network pharmacology method, and further validate it in combination with cellular experiments. Methods TCMSP, Gene-Cards, OMIM and TTD databases, Chinese Pharmacopoeia and related literature were used to screen the active ingredients of FCYC and the targets of MCI treatment. The TCM-compound-target-disease network and PPI of intersection targets were constructed, and the GO and KEGG analysis were performed by the Ehamb bioinformation platform. GO and KEGG analysis were performed through Yihanbo biological information platform. Cell model of MCI was established by PC-12 injury induced by Aβ
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It is of great significance to apply the nanocrystals self-stabilized Pickering emulsion (NSSPE) to traditional Chinese medicine (TCM) compounds, and to study the effect of NSSPE on the oral absorption of various components with different solubility and permeability. In the study, NSSPE of Tongmai prescription was prepared by the high pressure homogenization method with nanocrystals of main active components (puerarin, ferulic acid, salvianolic acid B and tanshinone IIA) of Tongmai prescription as solid particle stabilizers and a mixture of Ligusticum chuanxiong essential oil and Labrafil M 1944 CS as oil phase. The NSSPE had better physical stability than nanocrystals suspension and blank emulsion. The adsorption of nanocrystals on the surface of oil droplets was confirmed by scanning electron microscopy and fluorescence microscopy. The surface adsorption rates of puerarin, ferulic acid, salvianolic acid B and tanshinone ⅡA in NSSPE were 15.40% ± 3.19%, 15.39% ± 5.07%, 10.97% ± 3.70% and 31.51% ± 1.60%, respectively. When solid active components were prepared into nanocrystals suspension, the cellular uptake and transport across Caco-2 cells were increased significantly for puerarin and tanshinone IIA. The uptake rates of ferulic acid, ligustilide and tanshinone IIA in NSSPE were further increased compared with the physical mixture of nanocrystals suspension and oil, and the transports of ligustilide and tanshinone IIA were also significantly improved. The main absorption mechanisms of NSSPE were passive diffusion and caveolin-mediated endocytosis, which were determined mainly by the microstructure of NSSPE. In conclusion, NSSPE could be applied to complicated TCM. The "micro" and "nano" synergistic microstructure with drug nanocrystals adsorbed on the surface of micron-sized oil droplets could not only improve the physical stability of NSSPE, but also promote the absorption of various components in NSSPE, which made NSSPE a promising oral drug delivery system for TCM.
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OBJECTIVES@#To establish a rapid and nondestructive identification method for human body fluid stains and non-biological stains using three-dimensional fluorescence spectroscopy.@*METHODS@#The collected three-dimensional fluorescence spectrum data of human saliva, 3% blood, coffee and Fanta® stains were processed with dimensionality reduction. After wavelet transform, spectral denoising and feature extraction, the classification formula was established. The Fisher discriminant was used for spectrum matching and recognition to establish the analysis method to distinguish stain types.@*RESULTS@#According to the results of data training and comparison, all the recognition accuracies of Fanta®, coffee, saliva and blood were more than 91.39%. Among them, saliva reached 100% recognition accuracy.@*CONCLUSIONS@#Three-dimensional fluorescence spectroscopy is a potential method for rapid and nondestructive identification of biological and non-biological stains.
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Humanos , Medicina Legal/métodos , Corantes/análise , Café , Espectrometria de Fluorescência , Líquidos Corporais/químicaRESUMO
BackgroundThe significant morbidity and mortality resulted from the infection of a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) call for urgent development of effective and safe vaccines. We report the immunogenicity and safety of a SARS-CoV-2 inactivated vaccine, KCONVAC, in healthy adults. MethodsTwo phase 1 and phase 2 randomized, double-blind, and placebo-controlled trials of KCONVAC were conducted in Chinese healthy adults aged 18 through 59 years. The phase 1 trial was conducted in a manner of dosage escalation. The first 30 participants were randomized in a ratio of 4:1 to receive two doses of either KCONVAC at 5 g per dose or placebo on Day 0 and Day 14, and the second 30 participants were randomized to receive either KCONVAC at 10 g per dose or placebo following the same procedures. The participants in the phase 2 trial were randomized in a ratio of 2:2:1 to receive either KCONVAC at 5 g or 10 g per dose, or placebo on Day 0 and Day 14, or Day 0 and Day 28. In the phase 1 trial, the primary safety endpoint was the proportion of participants experiencing adverse reactions/events within 28 days following each vaccination. Antibody response and cellular response were assayed in the phase 1 trial. In the phase 2 trial, the primary immunogenicity endpoint was the seroconversion and titre of neutralization antibody, and the seroconversion of receptor binding domain (RBD)-IgG 28 days after the second dose. FindingsIn the phase 1 trial, 60 participants were enrolled and received at least one dose of 5-g vaccine (N=24), 10-g vaccine (N=24), or placebo (N=12). In the phase 2 trial, 500 participants were enrolled and received at least one dose of 5-g vaccine (N=100 for 0/14 or 0/28 regimens), 10-g vaccine (N=100 for each regimen), or placebo (N=50 for each regimen). In the phase 1 trial, 13 (54%), 11(46%), and 7 (58%) participants reported at least one adverse event (AE), of whom 10 (42%), 6 (25%), and 6 (50%) participants reported at least one vaccination-related AE after receiving 5-g vaccine, 10-g vaccine, or placebo, respectively. In the phase 2 trial, 16 (16%), 19 (19%), and 9 (18%) participants reported at least one AE, of whom 13 (13%), 17 (17%), and 6 (12%) participants reported at least one vaccination-related AE after receiving 5-g vaccine, 10-g vaccine, or placebo at the regimen of Day 0/14, respectively. Similar results were observed in the three treatment groups of Day 0/28 regimen. All the AEs were grade 1 or 2 in intensity. No AE of grade 3 or more was reported. One SAE (foot fracture) was reported in the phase 1 trial. KCONVAC induced significant antibody response. 87{middle dot}5% (21/24) to 100% (24/24) of participants in the phase 1 trial and 83{middle dot}0% (83/100) to 100% (99/99) of participants in the phase 2 trial seroconverted for neutralising antibody to live virus, neutralising antibody to pseudovirus, and RBD-IgG after receiving two doses. Across the treatment groups in the two trials, the geometric mean titres (GMTs) of neutralising antibody to live virus ranged from 29{middle dot}3 to 49{middle dot}1 at Day 0/14 regimen and from 100{middle dot}2 to 131{middle dot}7 at Day 0/28 regimen, neutralising antibody to pseudovirus ranged from 69{middle dot}4 to 118{middle dot}7 at Day 0/14 regimen and from 153{middle dot}6 to 276{middle dot}6 at Day 0/28 regimen, and RBD-IgG ranged from 605{middle dot}3 to 1169{middle dot}8 at Day 0/14 regimen and from 1496{middle dot}8 to 2485{middle dot}5 at Day 0/28 regimen. RBD-IgG subtyping assay showed that a significant part of RBD-IgG was IgG1. The vaccine induced obvious T-cell response with 56{middle dot}5% (13/23) and 62{middle dot}5% (15/24) of participants in 5-g and 10-g vaccine groups showed positive interferon-{gamma} enzyme-linked immunospot responses 14 days after the second dose in the phase 1 trial, respectively. InterpretationKCONVAC is well tolerated and able to induce robust antibody response and cellular response in adults aged 18 to 59 years, which warrants further evaluation with this vaccine in the upcoming phase 3 efficacy trial. FundingGuandong Emergency Program for Prevention and Control of COVID-19 (2020A1111340002) and Shenzhen Key Research Project for Prevention and Control of COVID-19.
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BACKGROUND@#The significant morbidity and mortality resulted from the infection of a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) call for urgent development of effective and safe vaccines. We report the immunogenicity and safety of an inactivated SARS-CoV-2 vaccine, KCONVAC, in healthy adults.@*METHODS@#Phase 1 and phase 2 randomized, double-blind, and placebo-controlled trials of KCONVAC were conducted in healthy Chinese adults aged 18 to 59 years. The participants in the phase 1 trial were randomized to receive two doses, one each on Days 0 and 14, of either KCONVAC (5 or 10 μg/dose) or placebo. The participants in the phase 2 trial were randomized to receive either KCONVAC (at 5 or 10 μg/dose) or placebo on Days 0 and 14 (0/14 regimen) or Days 0 and 28 (0/28 regimen). In the phase 1 trial, the primary safety endpoint was the proportion of participants experiencing adverse reactions/events within 28 days following the administration of each dose. In the phase 2 trial, the primary immunogenicity endpoints were neutralization antibody seroconversion and titer and anti-receptor-binding domain immunoglobulin G seroconversion at 28 days after the second dose.@*RESULTS@#In the phase 1 trial, 60 participants were enrolled and received at least one dose of 5-μg vaccine (n = 24), 10-μg vaccine (n = 24), or placebo (n = 12). In the phase 2 trial, 500 participants were enrolled and received at least one dose of 5-μg vaccine (n = 100 for 0/14 or 0/28 regimens), 10-μg vaccine (n = 100 for each regimen), or placebo (n = 50 for each regimen). In the phase 1 trial, 13 (54%), 11 (46%), and seven (7/12) participants reported at least one adverse event (AE) after receiving 5-, 10-μg vaccine, or placebo, respectively. In the phase 2 trial, 16 (16%), 19 (19%), and nine (18%) 0/14-regimen participants reported at least one AE after receiving 5-, 10-μg vaccine, or placebo, respectively. Similar AE incidences were observed in the three 0/28-regimen treatment groups. No AEs with an intensity of grade 3+ were reported, expect for one vaccine-unrelated serious AE (foot fracture) reported in the phase 1 trial. KCONVAC induced significant antibody responses; 0/28 regimen showed a higher immune responses than that did 0/14 regimen after receiving two vaccine doses.@*CONCLUSIONS@#Both doses of KCONVAC are well tolerated and able to induce robust immune responses in healthy adults. These results support testing 5-μg vaccine in the 0/28 regimen in an upcoming phase 3 efficacy trial.@*TRIAL REGISTRATION@#http://www.chictr.org.cn/index.aspx (No. ChiCTR2000038804, http://www.chictr.org.cn/showproj.aspx?proj=62350; No. ChiCTR2000039462, http://www.chictr.org.cn/showproj.aspx?proj=63353).
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Adulto , Humanos , COVID-19 , Vacinas contra COVID-19 , Método Duplo-Cego , SARS-CoV-2 , Vacinas de Produtos Inativados/efeitos adversosRESUMO
Based on the serum medicinal method, this study aims to investigate the migrating components of Yougui Yin in the blood after intragastric administration, and to provide reference for the basic research of its pharmacodynamics. The kidney deficiency rat model was replicated by adenine method. Normal rats and model rats were administered orally for a single gavage of Yougui Yin. The components in blood were rapidly analyzed and identified by ultra-high performance liquid chromatography/quadrupole time-of-flight mass spectrometry(UPLC-Q-TOF-MS) and multiple reaction monitoring(MRM), and the migrating components in blood of Yougui Yin were explored by multivariate statistical analysis. The results showed that there were 42 characteristic peaks in the plasma of normal rats by UPLC-Q-TOF-MS technology and 13 chemical components were identified, including 6 alkaloids, 2 flavonoids, 2 triterpenoid saponins, 1 iridoid, 1 phenylpropanoid and 1 monoterpenoid. There were 22 characteristic peaks in the plasma of kidney-deficiency rats, and 12 chemical components were identified, including 2 iridoids, 6 alkaloids, 2 flavonoids, 1 monoterpenoid and 1 triterpenoid saponin. Verbascoside, isoacteoside, acteoside, pinoresinoldiglucoside, loganin and morroniside were identified by MRM both in the plasma of normal rats and kidney-deficiency rats. Compared with 85 monomer components in Yougui Yin, 17 common prototype components were found by UPLC-MS in the plasma of normal rats and kidney deficiency rats, including verbascoside, isoacteoside, acteoside, rehmapicrogenin derived from Rehmanniae Radix Praeparata, pinoresinol diglucoside and geniposidic acid from Eucommiea Cortex, loganin and morroniside derived from Corni Fructus, mesaconine, benzoylmesaconine, benzoylaconitine, benzoylhypacoitine, mesaconitine, aconitine derived from Aconiti Lateralis Radix Praeparata, liquiritin, isoliquiritin and glycyrrhizic acid derived from Glycyrrhizae Radix et Rhizoma. Thirty-one metabolites of medicinal ingredients not found in the plasma of adenine-induced kidney deficiency rats were also detected in the plasma of normal rats. Twelve metabolites of medicinal materials not found in the plasma of normal rats were detected in the plasma of kidney deficiency rats. The results of the study provide reference for explaining the material basis and mechanism of Yougui Yin in the treatment of kidney deficiency.
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Animais , Ratos , Adenina , Cromatografia Líquida de Alta Pressão , Cromatografia Líquida , Medicamentos de Ervas Chinesas/toxicidade , Rim , Espectrometria de Massas em Tandem , TecnologiaRESUMO
"Kidney essence" is a profound concept in the theory of traditional Chinese medicine. But its biological basis is unknown until now, resulting in the therapeutic effects of traditional Chinese drugs on reinforcing kidney for supplementing essence hard to be evaluated. This study aimed, to explore the potential biological basis and mechanism of traditional Chinese drugs of reinforcing kidney for supplementing essence on diseases related to deficiency of kidney essence through network pharmacology analysis on the intersection of targets of drugs and diseases. The targets for ingredients in Rehmanniae radix praeparata (RRP), Polygoni multiflori radix praeparata (PMRP) and Polygonati rhizome (PR) were gathered from TCMSP and TCMID database. Osteoporosis, Alzheimer's disease, anemia, infertility and oligospermia targets were collected from OMIM and DisGeNET database. Drug-compound-target-disease (DCTD) network was established with Cytoscape 3.6.1 software, then Clue GO and DAVID database was used to acquire the annotation about GO terms and signaling pathways. Natural aging mice, an acknowledged syndrome model of deficiency of kidney essence, and RRP were used to verify the predictive targets by Western blot analysis. All animal experiments were conducted in accordance with the international guidelines and regulations for the care and use of animals. DCTD network showed that the intersection of drugs and diseases included 175 common targets. After topology analysis, 71 key were screened out targets which were associated with GO annotation exhibited that biological processes (including transcription regulation, RNA metabolism regulation, and DNA-dependent transcription regulation), cell composition (including nuclear lumen, organelle lumen, and membrane closure lumen), molecular function (including transcription regulation, transcription factor activity, and enzyme binding), and signaling pathway (including peroxisome proliferator-activated receptor alpha (PPARα), mitogen-activated protein kinase (MAPK), hypoxia-inducible factor 1 (HIF-1), erythropoietin (EPO) and other signaling pathways. In natural aging mice, the expressions of HIF-1α, growth factor receptor-bound protein 2 (GRB2), MAPK3, signal transducer and activator of transcription 5A (STAT5A), transcription factor AP-1 (JUN) and proto-oncogene c-Fos (FOS) in EPO pathway were significantly decreased. RRP significantly reversed the decrease of the above targets. Above all, these results indicated that the therapeutic effects of traditional Chinese drugs of reinforcing kidney for supplementing essence on deficiency of kidney essence may be related to the regulation of nuclear transcriptional activity and EPO signaling pathway.
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This study aimed to evaluate the effects of Jiawei Foshou San capsule (JWFSSC) on CYP1A2, CYP2C6, CYP2D2, CYP2E1 and CYP3A1/2 enzyme activities in rat liver microsomes in vitro and in vivo, and to provide pharmacokinetic data for its combined use with other medicines. After incubating liver microsomes with a cocktail of probe drugs, the metabolites were quantitated with LC-MS/MS to assess the CYP enzyme activity. The hepatic pathological changes were evaluated by histology after hematoxylin and eosin (HE) staining. With the dose range up to 3 200 mg·L-1, the IC50 of JWFSSC for CYP2D2, CYP2E1 and CYP3A1/2 in vitro was 229.3 mg·L-1, 361.9 mg·L-1 and 274.6 mg·L-1 respectively. Compared with the vehicle control group, the enzyme activities of CYP1A2, CYP2C6 and CYP3A1/2 showed a significant increase in animals given JWFSSC 180 mg·kg-1·d-1 (P<0.01). Based on histology, several pathological changes were observed in JWFSSC groups: there was less inflammatory infiltration compared to the tetrahydropalmatine (THP) group. These results of inhibition in vitro and induction in vivo suggest a strengthened efficacy and a prolonged effective time of drugs metabolized by CYP2D2 and CYP2E1 enzymes when combined with JWFSSC in use. The dosage of parent drugs should be appropriately reduced when used in combination with JWFSSC. However, if a drug is metabolized by CYP1A2 and CYP2C6 when used in combination with JWFSSC, the effect of the drug is likely reduced and the dosage should be increased appropriately. In addition, the combination of ferulic acid (FA), ligustrazine (LZ) and THP can significantly reduce the toxicity of THP in rat livers. In this study, the program of animal testing had been approved by Committee on the management and usage of experimental animal in the College of Pharmaceutical Sciences, Southwest University.
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The aim of this paper was to observe the changes of EPO in rats with chronic renal failure and low immunity induced by adenine and to investigate the reversal effect of Yougui Yin(YGY)and exogenous EPO.SD rats were randomly divided into normal control group(n=20)and adenine-model group(n=90).The adenine-model group rats were given with adenine 150 mg·kg~(-1)for 14days by gavage administration,and then randomly divided into 8 groups as follows:model group(n=20),YGY groups(10,20,40 g·kg~(-1),10 in each group),rh EPO group(500,1 000,1 500 IU·kg~(-1),10 in each group),and Guilu Erxian Gao 10 g·kg~(-1)group(positive control group,n=10).From the 15th day,every group except normal control group received 150 mg·kg~(-1)adenine by gavage administration once every two days to maintain the model.Meanwhile,the rats in each YGY group and Guilu Erxian Gao group received corresponding drugs by gavage administration once a day for 30 days.The rats in rh EPO groups were subcutaneously injected with rh E-PO once every 3 days for 30 days.On day 46,rats were anesthetized to take blood and then sacrificed.The serum levels of creatinine,urea,glandular hormone,immunoglobulin,complement and interleukin,the proportion of T cells in the spleen,the killing rate of NKcells and the proliferative capacity of spleen cells were measured.Western blot was used to detect the key proteins in JAK2-STAT5 and NF-κB pathways mediated by EPO in kidney and spleen.As compared with the normal control group,the serum levels of CREA and UREA were increased significantly and the serum levels of ACTH,T and T3 were decreased significantly in the model group rats,indicating that the functions of kidney,adrenal gland,gonad and thyroid in rats were decreased.At the same time,the serum levels of Ig A,Ig G,Ig M,C3,C4,IL-2 and IL-6 were significantly decreased,the proportion of CD4~+,CD4~+/CD8~+T cell subsets,the killing rate of NK cell and the proliferation ability of spleen lymphocyte in spleen of the model group rats were significantly declined,indicating that the immune function of model group rats was decreased,and the model of kidney deficiency immunodeficiency was successfully constructed.As compared with the model group,both YGY and rh EPO significantly reduced serum levels of CREA and UREA,significantly increased serum levels of ACTH,T,T3,T4,Ig A,Ig G,Ig M,C3,C4,IL-2,and IL-6,increased the proportion of CD4~+,CD4~+/CD8~+T cell subsets,the killing rate of NK cell and the proliferation ability of spleen lymphocyte in spleen.YGY could significantly increase the content of EPO in serum.Both YGY and rh EPO could regulate the expression of EPOR,p-JAK2/JAK2,STAT5,NF-κB p50,NF-κB p65 and NF-κB IκB of EPO-mediated JAK2-STAT5 and NF-κB pathways in kidney and spleen.EPO is an important factor in the chronic renal failure and low immunity induced by adenine in rats.Exogenous EPO and YGY have significant reversal effects for the model rats.The mechanism of YGY may be related to the up-regulation of EPO in serum and regulating the expression of key proteins in EPO-mediated JAK2-STAT5 and NF-κB pathways in kidney and spleen.The mechanism of exogenous EPO may be related to regulating the expression of the key proteins in EPO-mediated JAK2-STAT5 and NF-κB pathways in kidney and spleen.
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Animais , Ratos , Medicamentos de Ervas Chinesas , Falência Renal Crônica , Ratos Sprague-Dawley , Insuficiência Renal Crônica , Transdução de SinaisRESUMO
@#【Objective】To evaluate the efficacy of early filtering surgery in newborns with primary congenital glaucoma(NPCG).【Methods】A total of 70 eyes of 39 patients with NPCG,who underwent trabeculotomy or combined trabeculotomy-trabeculectomy within 3 years old were retrospectively studied. Preoperative and postoperative intraocular pressure(IOP),corneal clarity and diameter,optic disc cupping and visual acuity were evaluated. Kaplan-Meier survival analysis of the success rates were studied. Success rates of the patients who underwent surgery within 1 month old(22 eyes)and older than 1 month old(48 eyes)were compared by Log- Rank.【Results】The postoperative IOP(mmHg;16.9 ± 5.2) were significantly lower than the preoperative IOP(28.7±5.8 ,P<0.001). At the last visit ,the cornea became clearer , C/D(cup/disc)ratio decreased significantly,while the horizontal corneal diameter did not change significantly in all the children. The success rates for all eyes at 1,2,3,6 and 9 years after operation were 94.3%(63 eyes),90.6%(52 eyes),85.9%(40 eyes),85.9%(23 eyes),and 85.9%(15 eyes),respectively. The success rates and visual acuity at last visit of patients who underwent surgery within 1 month old were better than those older than 1 month old(P=0.033; P=0.01). There were no severe intraoperative or postoperative complications.【Conclusions】Early surgery such as trabeculotomy or combined trabeculotomy-trabeculectomy is a safe and effective treatment for NPCG.
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The treatment effect and signaling pathway regulation effects of kidney-tonifying traditional Chinese medicine on osteoporosis have been widely studied, but there is no systematic summary currently. This review comprehensively collected and analyzed the traditional Chinese medicines on the treatment and signaling pathway regulation of osteoporosis in recent ten years, such as Epimedii Folium, Drynariae Rhizoma, Cnidii Fructus, Eucommiae Cortex, Psoraleae Fructus and Dipsaci Radix. Based on the existing findings, the following conclusions were obtained: ①kidney-tonifying traditional Chinese medicine treated osteoporosis mainly through BMP-Smads, Wnt/-catenin, MAPK, PI3K/AKT signaling pathway to promote osteoblast bone formation and through OPG/RANKL/ RANK, estrogen, CTSK signaling pathway to inhibit osteoclasts of bone resorption. Epimedii Folium, Drynariae Rhizoma, Cnidii Fructus and Psoraleae Fructus up-regulated the expression of key proteins and genes of BMP-Smads and Wnt/-catenin signaling pathways to promote bone formation. Epimedii Folium, Drynariae Rhizoma, Cnidii Fructus, Eucommiae Cortex, Psoraleae Fructus and Dipsaci Radix inhibited the bone resorption by mediating the OPG/RANKL/RANK signaling pathway. ②Kidney-tonifying traditional Chinese medicine prevented and treated osteoporosis through a variety of ways: icariin in Epimedii Folium, naringin in Drynariae Rhizoma, osthole in Cnidii Fructus and psoralen in Psoraleae Fructus can regulate BMP-Smads, Wnt/-catenin signaling pathway to promote bone formation, but also activate OPG/RANKL/RANK, CTSK and other signaling pathways to inhibit bone resorption. ③The crosstalk of the signaling pathways and the animal experiments of the traditional Chinese medicine on the prevention and treatment of osteoporosis as well as their multi-target mechanism and comprehensive regulation need further clarification.
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Animais , Humanos , Medicamentos de Ervas Chinesas , Usos Terapêuticos , Medicina Tradicional Chinesa , Osteoporose , Tratamento Farmacológico , Transdução de SinaisRESUMO
Jiawei Foshou San is a new Chinese medicine compound consisting of ligustrazine, ferulic acid and fumarate. Previously Jiawei Foshou San inhibited the growth of endometriosis with unclear mechanism, especially in metastasis and invasion. In this study, network pharmacology analysis was performed to explore potential mechanism of Jiawei Foshou San on endometriosis. Jiawei Foshou San compound targets were purchase from TCMID, TCMSP and SEA database. Endometriosis targets were collected from OMIM, DisGeNET and GEO database. Networks of Jiawei Foshou San compound-compound targets and compound target-endometriosis target were established with Cytoscape 3.5.0 software. Key targets were analyzed for pathway enrichment through DAVID database. It was found that Jiawei Foshou San regulated 66 core targets (MMP2, MMP9, TIMP1, ICAM1, VEGFA, et al.) and affected 115 pathways, such as estrogen, HIF-1, TNF and GnRH signaling pathways. MMP-TIMP were uncovered as one cluster of the core targets. Furthermore, Jiawei Foshou San significantly suppressed the growth of ectopic endometrium. Meanwhile, invasion and metastasis were restrained after treating with Jiawei Foshou San through decreasing MMP-2 and MMP-9, increasing TIMP-1. In brief, these results provide a pharmacodynamic basis for the study of Jiawei Foshou San.
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Since the discovery of neural stem cells(NSCs) in embryonic and adult mammalian central nervous systems, new approaches for proliferation and differentiation of NSCs have been put forward. One of the approaches to promote the clinical application of NSCs is to search effective methods to regulate the proliferation and differentiation. This problem is urgently to be solved in the medical field. Previous studies have shown that traditional Chinese medicine could promote the proliferation and differentiation of NSCs by regulating the relevant signaling pathway in vivo and in vitro. Domestic and foreign literatures for regulating the proliferation and differentiation of neural stem cells in recent 10 years and the reports for their target and signaling pathways were analyzed in this paper. Traditional Chinese medicine could regulate the proliferation and differentiation of NSCs through signaling pathways of Notch, PI3K/Akt, Wnt/β-catenin and GFs. However, studies about NSCs and traditional Chinese medicine should be further deepened; the mechanism of multiple targets and the comprehensive regulation function of traditional Chinese medicine should be clarified.
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In recent twenty years, there are a lot of studies about the effect of borneol on permeability of blood-brain barrier(BBB); however, it isDODOrt of regular conclusions of effect factors and in-depth analysis of functional mechanisms. The current researching data were collected and analyzed in this paper for illuminating the effect factors and mechanisms of borneol on permeability of BBB.The following conclusions were obtained: five factors about borneol influencing the permeability of BBB. First, opticity activity of borneol had no significant effect on action effects. Second, dose of borneol in the range of 50.00-200.00 mg•kg⁻¹, did not affect the effect direction, but only affect its action intensity either with use alone or combination use. Third, the borneol can increase the permeability of physiological BBB, and decrease the permeability of pathological BBB. Fourth, regardless of using singly or using compatibility with musk, borneol can decrease the permeability of BBB in different brain disease models. Fifth, when used with astragalus, catalpol or puerarin, borneol can increase the permeability of BBB and promote the drugs through BBB in pathological conditions. The target spots and mechanisms of borneol's bidirectional regulation on the permeability of BBB are related to the structure and function of cerebral endothelial cells, the exocytosis effects of P-gp and low pinocytosis internal transport effects. On one hand,borneol can down-regulate P-gp by inhibiting NF-κB to reduce the exocytosis effects of P-gp and promote the blood brain barrier pinocytosis to increase the permeability of BBB; On the other hand,borneol can reduce the degradation of basement membrane of blood vessel and tight junctions by inhibiting the expression of IL-1β, MMP-9 to decrease the permeability of BBB;moreover,borneol has bidirectional regulation effects on blood-brain barrier permeability by influencing the signaling pathways of Ca2+-eNOS-NO, VEGF-eNOS-NO. However, the detailed mechanisms that borneol regulates and controls the permeability of BBB are so complicated, so they shall be further proved and clarified.
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To investigate the effect of Siwu decoction on improving iron deficiency anemia in infant rats and observe its regulatory effects on iron metabolism. SD rats were fed with low iron fodder for 2 weeks, and then the rats with hemoglobin level less than 75 g•L ⁻¹ were screened out and randomly divided into model group, Ferrous succinate 50 mg•kg ⁻¹ group, Siwu decoction 4 g•kg ⁻¹, 8 g•kg ⁻¹ and 16 g•kg ⁻¹ groups. After 4 weeks' gavage administration, Wright-Giemsa's staining of blood smear and HE staining of the livers were conducted, and all rats were tested for blood routine, serum iron, total iron binding capacity, serum ferritin, serum hepcidin and liver hepcidin. The expression levels of liver ferritin, transferrin and transferrin receptor 1 were also detected. The results showed that as compared with normal group, the activity level of model group was decreased, and the color and lustre of auricles and toes were pale white; the number of red blood cells was decreased; the volume was smaller, with an increased zone of central pallor; the body weight and blood routine parameters were decreased significantly; the livers were pale red, and the hepatic cords around thecentral veins were unclear and misaligned; the serum iron, serum ferritin, liver iron levels and the expression of liver ferritin were decreased significantly; the total iron binding capacity, serum hepcidin, liver hepcidin, the expression levels of liver transferrin and transferrin receptor 1 were significantly increased, indicating successful establishment of models. As compared with the model group, activity was increased in Siwu decoction group; the color and lustre of auricles and toes were ruddy; the number of red blood cells was increased; the volume was larger, with a decreased zone of central pallor; the body weight and blood routine parameters were increased significantly; the livers were red, hepatic cords around the central veins were clear and aligned;the serum iron, serum ferritin, liver iron levels and the expression of liver ferritin were significantly increased, the total iron binding capacity, serum hepcidin, liver hepcidin, the expression of liver transferrin and transferrin receptor 1 were decreased significantly. The results demonstrated that Siwu decoction had a certain effect on improving iron deficiency anemia in infant rats, and the mechanism may be associated with the regulatory effect of hepcidin iron metabolism.
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The study of central nervous system disease is dependent on in vitro culture of neuronal cells. However, it is hard to determine the interaction between cells in culture of single type of neuronal cells. The co-culture system is able to mimic the cell-cell interaction in the brain and to facilitate investigation into the interaction between different types of cells, as well as cell-environment interaction. The co-culture of neurocytes is more and more popular in the disease study of central nervous system in vitro, such as stroke, Parkinson's disease, Alzheimer's disease, amyotrophic lateral sclerosis, etc. Neurovascular unit (NVU), which is composed of neurons, brain microvascular endothelial cells and astrocytes, can reflect the structure and function of brain in state of the art. Establishment of NVU in vitro is important in the study of the brain diseases. In this paper, several co-culture models of the central nervous system are reviewed in techniques for two-dimensional and three-dimensional culturing. Cell contact and non-contact methods are compared. Moreover, their application in the relevant research and the future direction are explored.
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This study was designed to investigate the inhibitory effects of Jiawei Foshou San (JWFSS) capsule in vitro on five major human liver microsomes CYP1A2, CYP2C9, CYP2D6, CYP2E1, CYP3A4, as well as on rat liver microsomes CYP1A2, CYP2C9, CYP2D2, CYP2E1, CYP3A1/2. The test groups included a negative control group, an inhibitor positive control group, an ferulic acid (FA) group, a ligustrazine (LZ) group, a tetrahydropalmatine (THP) group, and an JWFSS capsule group. After incubating the liver microsomes with a cocktail of probe drugs, the metabolites were quantitated with LC-MS/MS, and IC 50 values were calculated to assess the inhibitory effect of JWFSS capsule and its components on five rat/human CYP450 enzymes. All of the IC50 values for the FA and the LZ for the five CYPs could not be determined. The IC50 of the THP for rat CYP3A1/2 and for human CYP2D6 was 7.46 and 9.24 μmol·L-1, respectively. The IC50 of the JWFSS capsule for rat CYP2D2, CYP2E1 and CYP3A1/2 was 241.3, 369.8 and 293.0 mg ·L-1, for human CYP2D6, CYP2E1 and CYP3A4 was 123.9, 189.9 and 171.3 mg·L-1 respectively. The results indicated there were little probability that FA and LZ inhibited the activity of rat and human liver five CYPs; THP was identified as moderate-intensity inhibitor of rat liver CYP3A1/2 and human liver CYP2D6; JWFSS capsule might have a inhibitory effect on the activity of rat and human liver CYP2D, CYP2E1 and CYP3A in vitro, showing that there was a strengthened efficacy and a prolonged effective time for drugs metabolized by CYP2D, CYP2E1, CYP3A and combined with JWFSS capsule.
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<p><b>BACKGROUND</b>Early surgical intervention is required for the primary congenital glaucoma (PCG). There are currently few reports on the surgical outcomes in infants with PCG. This study aimed to evaluate the efficacy and safety of trabeculotomy and the postoperative visual outcomes in Chinese newborns with PCG within 4 weeks of birth.</p><p><b>METHODS</b>A total of 21 eyes of 12 patients with PCG who underwent primary trabeculotomy within 4 weeks of birth were retrospectively studied. Preoperative and postoperative intraocular pressure (IOP), corneal clarity and diameter, axial length and optic disc cupping, visual acuity and postoperative refractive error, success rates, and complications were evaluated. Kaplan-Meier survival analysis was applied to evaluate the success rates.</p><p><b>RESULTS</b>The mean follow-up time was 46.9 ± 34.4 months (range: 12-122 months). The postoperative IOP was significantly lower than the preoperative IOP at all of the follow-up visits (P < 0.001). The complete success rates for all eyes at 1, 2, 3, and 5 years postoperatively were 90.5%, 85.7%, 85.7%, and 85.7%, respectively. The IOPs of the three patients who needed antiglaucomatous medications postoperatively were also well controlled. At the last visit, the cornea became clear, and the cup-to-disc ratio decreased significantly (P = 0.01) although the horizontal corneal diameter did not change significantly (P = 0.11). Visual acuities were able to be recorded in eight eyes at the last visit, among which six eyes had a best-corrected visual acuity of 20/40 or better. There were no severe intraoperative or postoperative complications.</p><p><b>CONCLUSIONS</b>Trabeculotomy proves to be a safe and effective treatment in reducing IOP in this group of Chinese newborns with PCG. The outcomes of vision function were satisfactory in most of the patients.</p>
Assuntos
Criança , Pré-Escolar , Feminino , Humanos , Lactente , Masculino , Anormalidades Congênitas , Cirurgia Geral , Glaucoma , Cirurgia Geral , Complicações Pós-Operatórias , Estudos Retrospectivos , Trabeculectomia , Resultado do TratamentoRESUMO
To compare the effects of different preparation technologies on the concentrations of puerarin and catalpol in plasma and brain of rats after oral administration, in order to lay an experimental basis for developing new oral Zige preparations. The nanocrystal, self-microemulsions (tween-80 and Cremophor RH-40 as emulsifiers) and inclusion complex of HP-β-CD containing puerarin and catalpol were prepared. The concentrations of puerarin and catalpol in plasma and brain of rats after oral administration were determined by HPLC-MS/MS method. The pharmacokinetic parameters and brain target index were compared. The results showed that preparation technologies had different influences on the concentrations of puerarin and catalpol in plasma and brain. The self-microemulsion (tween-80) could significantly increase the oral absorption of puerarin than other technologies(P<0.05), and inclusion complex could remarkably increase the oral absorption of catalpol than nanocrystal(P<0.01). For puerarin, the brain targeting index of inclusion complex was the highest (P<0.05); but for catalpol, the brain targeting index of inclusion complex and self-microemulsions were both higher than nanocrystal (P<0.05). The self-microemulsion(tween-80) had the highest AUCbrain of puerarin than other groups (P<0.01); the inclusion complex had the highest AUCbrain for catalpol, but there was no significant difference compared with self-microemulsions. In conclusion, the self-microemulsion (tween-80) technology could increase the amount of puerarin and catalpol in brain, and was expected to be used in new oral Zige preparations.
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The sedative traditional Chinese medicine has a long history of clinical experience in treating insomnia. The main pharmacological effects of sedative agents are sedation, hypnosis, antianxiety and antidepression which might be related to certain neurotransmitters and cytokines and so on. This review summarized the mechanism of sedative traditional Chinese medicine and its active monomers based on neurotransmitters, including GABA, Glu, 5-HT, DA, NE and their metabolites 5-HIAA, HVA, DOPAC. The results showed that the most research about the sedative medicine at present was throught serotonergic and GABA ergic system. Study on Ziziphi Spinosae Semen was the most extensive, including its monomers, extracts and traditional Chinese patent medicines. It involved many sedative traditional Chinese medicine, such as Schisandrae Chinensis Fructus, Albiziae Flos, Polygalae Radix, Longan Arillus, Ganoderma, etc. It also systematically summarized the information which was useful for the further applications and research on sedative drugs and their active components.