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1.
Journal of Clinical Hepatology ; (12): 334-341, 2022.
Article in Chinese | WPRIM | ID: wpr-920880

ABSTRACT

Objective To investigate the intervention effect of GDC-0449, a hedgehog signaling pathway inhibitor, on rats with liver fibrosis induced by carbon tetrachloride (CCl 4 ) combined with 2-acetylaminofluorene (2-AAF). Methods A total of 18 female Fisher344 rats were randomly divided into normal group, CCl 4 /2-AAF group, and GDC-0449 group, with 6 rats in each group. The rats in the CCl 4 /2-AAF group and the GDC-0449 group were given subcutaneously injected 30% CCl 4 -olive oil solution at a dose of 2 mL/kg twice a week for 6 weeks to induce liver fibrosis; since week 7, in addition to the injection of CCl 4 -olive oil solution, the rats in these two groups were given 2-AAF (100 mg/kg/d) by gavage, and the rats in the GDC-0449 group were given GDC-0449 (25 mg/kg/d) by gavage, while those in the normal group were given an equal volume of olive oil solution by injection and normal saline by gavage. All rats were sacrificed at the end of week 9, and related samples were collected. HE staining and sirius red (SR) staining were used to observe the changes in liver histopathology and collagen deposition, and the semi-quantitative analysis of SR-positive area and Ishak score were used to evaluate fibrosis degree; the alkaline hydrolysis method was used to measure the level of hydroxyproline (Hyp) in liver tissue; immunohistochemistry, Western blot, and qRT-PCR were used to measure the expression of α-smooth muscle actin (α-SMA), type Ⅰ collagen (Col-Ⅰ), type Ⅳ collagen (Col-Ⅳ), cytokeratin 19 (CK19), cytokeratin 7 (CK7), the epithelial cell adhesion molecule Epcam, and the hedgehog signaling pathway in liver tissue; double immunofluorescence staining was used to observe the colocalization of CK19 and the oval cell marker OV6. A one-way analysis of variance was used for comparison of continuous data between multiple groups, and the least significant difference t -test was used for further comparison between two groups. Results Compared with the normal group, the CCl 4 /2-AAF group had marked inflammatory cell aggregation and collagen deposition in liver tissue, with the formation of a pseudolobular structure, as well as significant increases in Hyp level and collagen positive area ratio in liver tissue ( P < 0.05), Ishak score ( P < 0.05), and the expression of α-SMA, Col-Ⅰ, Col-Ⅳ, Epcam, CK19, CK7, the transmembrane transporter Smoothened (Smo), Hedgehog ligand Desert Hedgehog (Dhh), the Indian Hedgehog membrane-binding receptor Patched (Ptch2), and glioma-related oncogenes Gli1, Gli2, and Gli3 (all P < 0.05); double immunofluorescence staining showed that CK19-positive cells also expressed OV6 in the liver tissue of rats in the CCl 4 /2-AAF group, with a significant increase compared with the normal group. Compared with the CCl 4 /2-AAF group, the GDC-0449 group had significant reductions in inflammatory cell aggregation and collagen deposition in liver tissue, Hyp level and collagen positive area ratio in liver tissue ( P < 0.05), Ishak score ( P < 0.05), and the expression of α-SMA, Epcam, CK19, CK7, Smo, Ptch2, Gli1, Gli2, and Gli3 (all P < 0.05); double immunofluorescence staining showed a significant reduction in the number of cells with co-expression of OV6 and CK19 in liver tissue. Conclusion The Hedgehog signaling pathway inhibitor GDC-0449 can significantly inhibit the progression of liver fibrosis induced by CCl 4 /2-AAF in rats, possibly by inhibiting hepatic stellate cell activation, collagen deposition, activation and proliferation of hepatic progenitor cells, and differentiation of hepatic progenitor cells into biliary epithelial cells.

2.
Article in Chinese | WPRIM | ID: wpr-928745

ABSTRACT

OBJECTIVE@#To identify the key genes and explore mechanisms in the development of myelodysplastic syndrome (MDS) by bioinformatics analysis.@*METHODS@#Two cohorts profile datasets of MDS were downloaded from Gene Expression Omnibus (GEO) database. Differentially expressed gene (DEG) was screened by GEO2R, functional annotation of DEG was gained from GO database, gene ontology (GO) enrichment analysis was performed via Kyoto Encyclopedia of Genes and Genomes (KEGG) database, and key genes were screened by Matthews correlation coefficient (MCC) based on STRING database.@*RESULTS@#There were 112 DEGs identified, including 85 up-regulated genes and 27 down-regulated genes. GO enrichment analysis showed that biological processes were mainly enriched in immune response, etc, cellular component in cell membrane, etc, and molecular function in protein binding, etc. KEGG signaling pathway analysis showed that main gene enrichment pathways were primary immunodeficiency, hematopoietic cell lineage, B cell receptor signaling pathway, Hippo signaling pathway, and asthma. Three significant modules were screened by Cytoscape software MCODE plug-in, while 10 key node genes (CD19, CD79A, CD79B, EBF1, VPREB1, IRF4, BLNK, RAG1, POU2AF1, IRF8) in protein-protein interaction (PPI) network were screened based on STRING database.@*CONCLUSION@#These screened key genes and signaling pathways are helpful to better understand molecular mechanism of MDS, and provide theoretical basis for clinical targeted therapy.


Subject(s)
Computational Biology , Gene Expression , Gene Expression Profiling , Humans , Microarray Analysis , Myelodysplastic Syndromes/genetics , Protein Interaction Maps
3.
Article in Chinese | WPRIM | ID: wpr-928645

ABSTRACT

OBJECTIVES@#To investigate the levels of fat-soluble vitamins A, D, and E in children with obesity and their influencing factors.@*METHODS@#A total of 273 children with obesity who attended the Department of Clinical Nutrition, Xi'an Children's Hospital, from January 2019 to April 2021 were enrolled as the obesity group. A total of 226 children with normal body weight who underwent physical examination during the same period were enrolled as the control group. Anthropometric parameters and body composition were measured for both groups, and the serum concentrations of vitamins A, D, and E were also measured.@*RESULTS@#Compared with the control group, the obesity group had significantly higher serum levels of vitamin A [(1.32±0.21) μmol/L vs (1.16±0.21) μmol/L, P<0.001] and vitamin E [(9.3±1.4) mg/L vs (8.3±1.2) mg/L, P<0.001] and a significant reduction in the level of 25-hydroxyvitamin D [(49±22) nmol/L vs (62±24) nmol/L, P<0.001]. In the obesity group, the prevalence rates of marginal vitamin A deficiency, vitamin D deficiency/insufficiency, and vitamin E insufficiency were 5.5% (15/273), 56.8% (155/273), and 4.0% (11/273), respectively. After adjustment for body mass index Z-score and waist-to-height ratio, serum vitamin A level was positively correlated with age (P<0.001), while vitamins E and 25-hydroxyvitamin D levels were negatively correlated with age in children with obesity (P<0.001). After adjustment for age, the serum levels of vitamin A, vitamin E and 25-hydroxyvitamin D were not correlated with degree of obesity, percentage of body fat, and duration of obesity in children with obesity, while the serum levels of vitamins A and E were positively correlated with waist-to-height ratio (P<0.001).@*CONCLUSIONS@#There are higher serum levels of vitamins A and E in children with obesity, especially in those with abdominal obesity, while serum vitamin D nutritional status is poor and worsens with age. Therefore, vitamin D nutritional status should be taken seriously for children with obesity, and vitamin D supplementation should be performed when necessary.


Subject(s)
Calcifediol , Child , Humans , Pediatric Obesity , Vitamin A , Vitamin D , Vitamin E , Vitamins
4.
Article in Chinese | WPRIM | ID: wpr-928368

ABSTRACT

OBJECTIVE@#To determine the origin of a mosaicism small supernumerary marker chromosome (sSMC) by cytogenetic and molecular analysis.@*METHODS@#Karyotype analysis, fluorescence in situ hybridization (FISH) and SNP-array were carried out.@*RESULTS@#The karyotype of the patient was mos47,XX,+mar[45]/48,XX,+2mar[3]/46,XX[52]; the SNP-array result was arr[hg19]15q11.1q11.2 (20 161 372-24 314 675)×3, and the repeat fragment was about 4.15 Mb. FISH showed that approximately 50% of the cells have contained a sSMC with double D15Z1 probe site segments derived from abnormal idic(15). This sSMC did not contain SNRPN and PML probe fragments of Prader-Willi syndrome/Angelman syndrome.@*CONCLUSION@#When the patient's karyotype and phenotype are inconsistent, cytogenetic and molecular biology technologies should be combined to clarify the karyotype and gene location, so as to provide more accurate genetic consultation for the follow-up treatments.


Subject(s)
Chromosome Disorders , Chromosomes, Human, Pair 15 , Comparative Genomic Hybridization , Humans , In Situ Hybridization, Fluorescence , Karyotype , Mosaicism
5.
Article in Chinese | WPRIM | ID: wpr-928190

ABSTRACT

This study aims to explore the toxicity mechanism of Rhododendri Mollis Flos(RMF) based on serum metabolomics and network toxicology. The toxic effect of RMF on normal rats was evaluated according to the symptoms, serum biochemical indexes, and histopathology. Serum metabolomics was combined with multivariate statistical analysis to search endogenous differential metabolites and related metabolic pathways. The toxic components, targets, and signaling pathways of RMF were screened by network toxicology technique, and the component-target-metabolite-metabolic pathway network was established with the help of serum metabolomics. The result suggested the neurotoxicity, hepatotoxicity, and cardiotoxicity of RMF. A total of 31 differential metabolites and 10 main metabolic pathways were identified by serum metabolomics, and 11 toxic components, 332 related target genes and 141 main signaling pathways were screened out by network toxicology. Further analysis yielded 7 key toxic components: grayanotoxin Ⅲ,grayanotoxinⅠ, rhodojaponin Ⅱ, rhodojaponin Ⅴ, rhodojaponin Ⅵ, rhodojaponin Ⅶ, and kalmanol, which acted on the following 12 key targets: androgen receptor(AR), albumin(ALB), estrogen receptor β(ESR2), sex-hormone binding globulin(SHBG), type 11 hydroxysteroid(17-beta) dehydrogenase(HSD17 B11), estrogen receptor α(ESR1), retinoic X receptor-gamma(RXRG), lactate dehydrogenase type C(LDHC), Aldo-keto reductase(AKR) 1 C family member 3(AKR1 C3), ATP binding cassette subfamily B member 1(ABCB1), UDP-glucuronosyltransferase 2 B7(UGT2 B7), and glutamate-ammonia ligase(GLUL). These targets interfered with the metabolism of gamma-aminobutyric acid, estriol, testosterone, retinoic acid, 2-oxobutyric acid, and affected 4 key metabolic pathways of alanine, aspartate and glutamate metabolism, cysteine and methionine metabolism, steroid hormone biosynthesis, and retinol metabolism. RMF exerts toxic effect on multiple systems through multiple components, targets, and pathways. Through the analysis of key toxic components, target genes, metabolites, and metabolic pathways, this study unveiled the mechanism of potential neurotoxicity, cardiotoxicity, and hepatotoxicity of RMF, which is expected to provide a clue for the basic research on toxic Chinese medicinals.


Subject(s)
Animals , Cardiotoxicity , Chemical and Drug Induced Liver Injury , Drugs, Chinese Herbal/toxicity , Hormones , Metabolomics , Rats
6.
Article in Chinese | WPRIM | ID: wpr-927976

ABSTRACT

A UHPLC-Q Exactive Orbitrap MS method was used to analyze the chemical constituents of the classical prescription Qianghuo Shengshi Standard Decoction(QHSS). UHPL conditions were as follows: Waters~(TM) UPLC~(TM) HSS T3 C_(18) column(2.1 mm×100 mm, 1.7 μm) and mobile phase of acetonitrile-0.1% formic acid aqueous solution. Mass spectrometry data of QHSS, each herb extract, and negative sample were collected in both positive and negative ion modes. The chemical constituents of QHSS were identified or tentatively identified based on the accurate molecular weight, retention time, MS fragmentation, comparison with reference substances, and literature reports. A total of 141 compounds were identified, including 18 amino acids, oligosaccharides, oligopeptides, and their derivatives, 19 phenolic acids, 44 coumarins, 18 flavonoids and chromones, 13 saponins, 17 phthalides, and 12 other components. This study comprehensively characterized the chemical constituents of QHSS, laying an experimental basis for the in-depth research on the material basis and quality control of QHSS.


Subject(s)
Chromatography, High Pressure Liquid , Drugs, Chinese Herbal/chemistry , Gas Chromatography-Mass Spectrometry , Mass Spectrometry , Quality Control
7.
Article in Chinese | WPRIM | ID: wpr-927339

ABSTRACT

Heat-sensitive moxibustion is the appropriate technique of the external treatment in traditional Chinese medicine and it is widely used in community because of its "easy learning, simple operation and clear curative effect". Pragmatic randomized controlled trial is a main intervention design in the real world study, which provides a high-level evidence for the effectiveness assessment of heat-sensitive moxibustion in community management. Focusing on the key links of randomization, e.g. block randomization, stratified randomization, cluster randomization, sample size allocation, allocation concealment and blinding, the paper elaborates the advantages, disadvantages and technical details of two-stage randomization with consideration of patient preference in pragmatic randomized controlled trials of heat-sensitive moxibustion in community. It facilitates improving the quality of evidence, reproducibility and methodological homogeneity among different trials.


Subject(s)
Hot Temperature , Humans , Moxibustion , Patient Preference , Random Allocation , Reproducibility of Results
8.
Article in English | WPRIM | ID: wpr-926756

ABSTRACT

Objective@#To evaluate the performance of baseline clinical characteristics and pretherapeutic histogram parameters derived from T2 mapping of the extraocular muscles (EOMs) in the prediction of treatment response to intravenous glucocorticoid (IVGC) therapy for active and moderate-to-severe thyroid-associated ophthalmopathy (TAO) and to investigate the effect of fat-suppression (FS) in T2 mapping in this prediction. @*Materials and Methods@#A total of 79 patients clinically diagnosed with active, moderate-to-severe TAO (47 female, 32 male;mean age ± standard deviation, 46.1 ± 10 years), including 43 patients with a total of 86 orbits in the responsive group and 36 patients with a total of 72 orbits in the unresponsive group, were enrolled. Baseline clinical characteristics and pretherapeutic histogram parameters derived from T2 mapping with FS (i.e., FS T2 mapping) or without FS (i.e., conventional T2 mapping) of EOMs were compared between the two groups. Independent predictors of treatment response to IVGC were identified using multivariable analysis. Receiver operating characteristic (ROC) curve analysis was performed to evaluate the predictive performance of the prediction models. Differences between the models were examined using the DeLong test. @*Results@#Compared to the unresponsive group, the responsive group had a shorter disease duration, lower kurtosis (FSkurtosis), lower standard deviation, larger 75th, 90th, and 95th (FS-95th) T2 relaxation times in FS mapping and lower kurtosis in conventional T2 mapping. Multivariable analysis revealed that disease duration, FS-95th percentile, and FS-kurtosis were independent predictors of treatment response. The combined model, integrating all identified predictors, had an optimized area under the ROC curve of 0.797, 88.4% sensitivity, and 62.5% specificity, which were significantly superior to those of the imaging model (p = 0.013). @*Conclusion@#An integrated combination of disease duration, FS-95th percentile, and FS-kurtosis was a potential predictor of treatment response to IVGC in patients with active and moderate-to-severe TAO. FS T2 mapping was superior to conventional T2 mapping in terms of prediction.

9.
Journal of Clinical Hepatology ; (12): 1075-1080, 2022.
Article in Chinese | WPRIM | ID: wpr-924779

ABSTRACT

Objective To investigate the efficacy of endoscopic ligation combined with traditional Chinese medicine (TCM) syndrome differentiation-based treatment in the secondary prevention of esophageal variceal bleeding (EVB) in patients with liver cirrhosis. Methods A total of 108 EVB patients who were admitted to Department of Liver Cirrhosis, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine from April 2015 to February 2021 and underwent endoscopic ligation were enrolled, among whom 59 patients with TCM treatment were enrolled as Chinese and Western medicine group, and 49 patients without TCM treatment were enrolled as Western medicine group. The two groups were compared in terms of the incidence rate of rebleeding, mortality rate, and the improvement rate of portal hypertensive gastropathy. The t -test was used for comparison of normally distributed continuous data between groups, and the Mann-Whitney U rank sum test was used for comparison of non-normally distributed continuous data between groups; the chi-square test or the Fisher's exact test was used for comparison of categorical data between two groups; a Cox regression analysis was used to evaluate the risk factors for rebleeding. Results Compared with the Western medicine group, the Chinese and Western medicine group had a significantly lower rebleeding rate within 13-24 months after ligation (2% vs 12%, P =0.045), a significantly lower mortality rate of rebleeding (2% vs 12%, P =0.045), and a significantly higher overall response rate of portal hypertensive gastropathy (90% vs 77%, P =0.04). Underlying diseases (mainly including diabetes, hypertension, and heart disease) and Child-Pugh class for liver function were significant risk factors for rebleeding (all P < 0.05). Conclusion Ligation combined with TCM treatment can significantly reduce the incidence rate of delayed rebleeding and the mortality rate of EVB and improve the degree of portal hypertensive gastropathy, which provides a new strategy for ligation combined with TCM treatment to improve the overall response of EVB secondary prevention.

10.
China Pharmacy ; (12): 987-991, 2022.
Article in Chinese | WPRIM | ID: wpr-923603

ABSTRACT

OBJECT IVE To e stablish the method for simultaneous determination of levetiracetam and carbamazepine concentrations in human plasma. METHODS After plasma samples were precipitated with methanol ,using carbamazepine-D 10 as the internal standard ,the concentrations of levetiracetam and carbamazepine were determined by high performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS). The determination was performed on XBridge BEH C 18 column with methanol-0.1% formic acid as mobile phase (gradient elution )at the flow rate of 0.35 mL/min. The column temperature was set at 40℃,and sample size was 2 μL. With electrospray ion source,a multiple reaction monitoring mode was used for positive ion scanning;the detected ion pairs for quantitative analysis were m/z 171.3→126.3(levetiracetam),m/z 237.1→194.1(carbamazepine), 247.1→204.1(internal standard ). RESULTS The linear range of the concentrations of levetiracetam and carbamazepine were 0.5-50 and 0.2-20 μg/mL(r=0.997 3 and 0.998 5),respectively;the lower quantitative limits were 0.5 and 0.2 μg/mL,respectively. RSDs of intra-day and inter-day were all no more than 10.00%. RE of intra-day and inter-day were within ±4.00%;the average extraction recoveries rate were 95.60%-105.00%;the average internal standard correction matrix factors were 98.40%-110.00%; RSDs of stability tests were all not higher than 5.60%. The concentrations of levetiracetam and carbamazepine in the plasma of 22 patients measured by this method were 3.36-40.90 and 3.64-9.93 μg/mL,respectively. CONCLUSIONS The established method for determining the concentration of levetiracetam and carbamazepine in human plasma is f ast,sensitive,accurate and stable ,and can be used for the monitoring of plasma concentration and pharmacokinetic study in epilepsy patients.

11.
Article in Chinese | WPRIM | ID: wpr-923385

ABSTRACT

@#Objective    To observe the status of thrombocytopenia in adult patients after cardiac surgery, and to explore its mechanism and clinical significance. Methods    Retrospective analysis of 240 patients after cardiac surgery in the 2nd ward of surgical intensive care unit (ICU) of Fuwai Hospital from May to June 2020 was conducted, including 137 males and 103 females with a mean age of 56.0±12.0 years. According to postoperative platelet status, the patients were divided into a thrombocytopenia group and a non-thrombocytopenia group. The clinical baseline data, preoperative platelet count, postoperative minimum platelet count, volume of drainage, transfusion of blood products, mechanical ventilator time, ICU stay, hospital stay and complications were compared between the two groups. Results    The mean preoperative platelet count was 199×109/L±55×109/L and the mean postoperative platelet nadir was 109×109/L±37×109/L, with a mean reduction rate of 44.1%±15.8%. The platelet count of 235 (97.9%) patients after operation was lower than that before operation. Among them, 98 (40.8%) patients had platelet count<100×109/L, 46 (19.2%)<75×109/L and 8 (3.3%)<50×109/L. Results of multivariable logistic analysis showed that cardiopulmonary bypass time>120 min (OR=2.576, 95%CI 1.313-5.053, P<0.05) was an independent risk factor for postoperative thrombocytopenia. Mechanical ventilator time (25.5± 16.8 h vs. 17.3±8.5 h, P<0.05), ICU stay (85.2±54.7 h vs. 60.0±33.9 h, P<0.05) and hospital stay (15.8±6.2 d vs. 14.2±3.9 d, P<0.05) were longer in the thrombocytopenia group (<100×109/L) compared with the non-thrombocytopenia group (>100×109/L). More drainage volume [685 (510, 930) mL vs. 560 (440, 790) mL, P<0.05] and complications occurred in the thrombocytopenia group. In multivariable analysis, thrombocytopenia was significantly inversely associated with prolonged ICU stay (OR=2.993, 95%CI 1.622-5.524, P<0.05). Conclusion    Thrombocytopenia occurs commonly after adult cardiac surgery, and the incidence in different types of surgery varies. Postoperative thrombocytopenia is related to the prolonged recovery. Extracorporeal circulation may be a contributing factor to thrombocytopenia, and further studies investigating mechanism and strategies to reduce postoperative thrombocytopenia are needed.

12.
Article in English | WPRIM | ID: wpr-881076

ABSTRACT

Digestive system cancers, including liver, gastric, colon, esophageal and pancreatic cancers, are the leading cause of cancers with high morbidity and mortality, and the question of their clinical treatment is still open. Previous studies have indicated that Ziyuglycoside II (ZYG II), the major bioactive ingredient extract from Sanguisorba officinalis L., significantly inhibits the growth of various cancer cells. However, the selective anti-tumor effects of ZYG II against digestive system cancers are not systemically investigated. In this study, we reported the anti-cancer effect of ZYG II on esophageal cancer cells (OE21), cholangiocarcinoma cells (HuCCT1), gastric cancer cells (BGC-823), liver cancer cells (HepG2), human colonic cancer cells (HCT116), and pancreatic cancer cells (PANC-1). We also found that ZYG II induced cell cycle arrest, oxidative stress and mitochondrial apoptosis. Network pharmacology analysis suggested that UBC, EGFR and IKBKG are predicted targets of ZYG II. EGFR signaling was suggested as the critical pathway underlying the anti-cancer effects of ZYG II and both docking simulation and western blot analysis demonstrated that ZYG II was a potential EGFR inhibitor. Furthermore, our results showed synergistic inhibitory effects of ZYG II and chemotherapy 5-FU on the growth of cancer cells. In summary, ZYG II are effective anti-tumor agents against digestive cancers. Further systemic evaluation of the anti-cancer activities in vitro and in vivo and characterization of underlying mechanism will promote the development of novel supplementary therapeutic strategies based on ZYG II for the treatment of digestive system cancers.

13.
Article in English | WPRIM | ID: wpr-881073

ABSTRACT

Qing-Fei-Pai-Du decoction (QFPDD) is a Chinese medicine compound formula recommended for combating corona virus disease 2019 (COVID-19) by National Health Commission of the People's Republic of China. The latest clinical study showed that early treatment with QFPDD was associated with favorable outcomes for patient recovery, viral shedding, hospital stay, and course of the disease. However, the effective constituents of QFPDD remain unclear. In this study, an UHPLC-Q-Orbitrap HRMS based method was developed to identify the chemical constituents in QFPDD and the absorbed prototypes as well as the metabolites in mice serum and tissues following oral administration of QFPDD. A total of 405 chemicals, including 40 kinds of alkaloids, 162 kinds of flavonoids, 44 kinds of organic acids, 71 kinds of triterpene saponins and 88 kinds of other compounds in the water extract of QFPDD were tentatively identified via comparison with the retention times and MS/MS spectra of the standards or refereed by literature. With the help of the standards and in vitro metabolites, 195 chemical components (including 104 prototypes and 91 metabolites) were identified in mice serum after oral administration of QFPDD. In addition, 165, 177, 112, 120, 44, 53 constituents were identified in the lung, liver, heart, kidney, brain, and spleen of QFPDD-treated mice, respectively. These findings provided key information and guidance for further investigation on the pharmacologically active substances and clinical applications of QFPDD.


Subject(s)
Administration, Oral , Alkaloids/analysis , Animals , COVID-19 , Chromatography, High Pressure Liquid , Drugs, Chinese Herbal/pharmacokinetics , Flavonoids/analysis , Mice , SARS-CoV-2 , Saponins/analysis , Triterpenes/analysis
14.
Article in English | WPRIM | ID: wpr-881068

ABSTRACT

Angelicae Sinensis Radix (Danggui) and Ligusticum Chuanxiong Rhizoma (Chuan Xiong) herb-pair (DC) have been frequently used in Traditional Chinese medicine (TCM) prescriptions for hundreds of years to prevent vascular diseases and alleviate pain. However, the mechanism of DC herb-pair in the prevention of liver fibrosis development was still unclear. In the present study, the effects and mechanisms of DC herb-pair on liver fibrosis were examined using network pharmacology and mouse fibrotic model. Based on the network pharmacological analysis of 13 bioactive ingredients found in DC, a total of 46 targets and 71 pathways related to anti-fibrosis effects were obtained, which was associated with mitogen-activated protein kinase (MAPK) signal pathway, hepatic inflammation and fibrotic response. Furthermore, this hypothesis was verified using carbon tetrachloride (CCl

15.
Frontiers of Medicine ; (4): 302-312, 2021.
Article in English | WPRIM | ID: wpr-880973

ABSTRACT

Cullin-RING E3 ubiquitin ligase (CRL)-4 is a member of the large CRL family in eukaryotes. It plays important roles in a wide range of cellular processes, organismal development, and physiological and pathological conditions. DDB1- and CUL4-associated factor 8 (DCAF8) is a WD40 repeat-containing protein, which serves as a substrate receptor for CRL4. The physiological role of DCAF8 is unknown. In this study, we constructed Dcaf8 knockout mice. Homozygous mice were viable with no noticeable abnormalities. However, the fertility of Dcaf8-deficient male mice was markedly impaired, consistent with the high expression of DCAF8 in adult mouse testis. Sperm movement characteristics, including progressive motility, path velocity, progressive velocity, and track speed, were significantly lower in Dcaf8 knockout mice than in wild-type (WT) mice. However, the total motility was similar between WT and Dcaf8 knockout sperm. More than 40% of spermatids in Dcaf8 knockout mice showed pronounced morphological abnormalities with typical bent head malformation. The acrosome and nucleus of Dcaf8 knockout sperm looked similar to those of WT sperm. In vitro tests showed that the fertilization rate of Dcaf8 knockout mice was significantly reduced. The results demonstrated that DCAF8 plays a critical role in spermatogenesis, and DCAF8 is a key component of CRL4 function in the reproductive system.


Subject(s)
Animals , Cullin Proteins/genetics , DNA-Binding Proteins/genetics , Factor VIII , Male , Mice , Mice, Knockout , Spermatogenesis/genetics , Ubiquitin-Protein Ligases
16.
Frontiers of Medicine ; (4): 144-154, 2021.
Article in English | WPRIM | ID: wpr-880953

ABSTRACT

Oocyte cryopreservation is widely used for clinical and social reasons. Previous studies have demonstrated that conventional slow-freezing cryopreservation procedures, but not storage time, can alter the gene expression profiles of frozen oocytes. Whether vitrification procedures and the related frozen storage durations have any effects on the transcriptomes of human metaphase II oocytes remain unknown. Four women (30-32 years old) who had undergone IVF treatment were recruited for this study. RNA-Seq profiles of 3 fresh oocytes and 13 surviving vitrified-thawed oocytes (3, 3, 4, and 3 oocytes were cryostored for 1,2, 3, and 12 months) were analyzed at a single-cell resolution. A total of 1987 genes were differentially expressed in the 13 vitrified-thawed oocytes. However, no differentially expressed genes were found between any two groups among the 1-, 2-, 3-, and 12-month storage groups. Further analysis revealed that the aberrant genes in the vitrified oocytes were closely related to oogenesis and development. Our findings indicated that the effects of vitrification on the transcriptomes of mature human oocytes are induced by the procedure itself, suggesting that long-term cryostorage of human oocytes is safe.


Subject(s)
Adult , Cryopreservation , Female , Humans , Metaphase , Oocytes , RNA-Seq , Vitrification
17.
Article in English | WPRIM | ID: wpr-880677

ABSTRACT

Rotator cuff injuries are the most common cause of shoulder pain and dysfunction. Ideal animal shoulder models should have similar shoulder anatomy and function as human, and are able to replicate the microenvironment change after tendon injury. At present, a variety of animal models including rat, mouse, rabbit, sheep, canine, bovine, and primate have been used to study the mechanism of rotator cuff injury, effects of different repair techniques, and factors affecting tendon to bone healing. Although large animal models are more anatomically similar to humans, small animal models are more convenient in revealing the biological mechanism of rotator cuff injury and healing. Choosing appropriate animal models based on research objectives and establishing new small animal models play a critical role in revealing the mechanism of rotator cuff diseases and developing novel treating strategies.


Subject(s)
Animals , Cattle , Disease Models, Animal , Dogs , Mice , Rabbits , Rats , Rotator Cuff , Rotator Cuff Injuries , Sheep , Tendon Injuries , Wound Healing
18.
Neuroscience Bulletin ; (6): 1381-1396, 2021.
Article in English | WPRIM | ID: wpr-922639

ABSTRACT

Mechanosensitive ion channels (MSCs) are key molecules in the mechano-electrical transduction of arterial baroreceptors. Among them, acid-sensing ion channel 2 (ASIC2) and transient receptor potential vanilloid subfamily member 1 (TRPV1) have been studied extensively and documented to play important roles. In this study, experiments using aortic arch-aortic nerve preparations isolated from rats revealed that both ASIC2 and TRPV1 are functionally necessary, as blocking either abrogated nearly all pressure-dependent neural discharge. However, whether ASIC2 and TRPV1 work in coordination remained unclear. So we carried out cell-attached patch-clamp recordings in HEK293T cells co-expressing ASIC2 and TRPV1 and found that inhibition of ASIC2 completely blocked stretch-activated currents while inhibition of TRPV1 only partially blocked these currents. Immunofluorescence staining of aortic arch-aortic adventitia from rats showed that ASIC2 and TRPV1 are co-localized in the aortic nerve endings, and co-immunoprecipitation assays confirmed that the two proteins form a compact complex in HEK293T cells and in baroreceptors. Moreover, protein modeling analysis, exogenous co-immunoprecipitation assays, and biotin pull-down assays indicated that ASIC2 and TRPV1 interact directly. In summary, our research suggests that ASIC2 and TRPV1 form a compact complex and function synergistically in the mechano-electrical transduction of arterial baroreceptors. The model of synergism between MSCs may have important biological significance beyond ASIC2 and TRPV1.


Subject(s)
Acid Sensing Ion Channels/physiology , Animals , HEK293 Cells , Humans , Pressoreceptors/physiology , Rats , TRPV Cation Channels/physiology
19.
Acta Pharmaceutica Sinica ; (12): 778-785, 2021.
Article in Chinese | WPRIM | ID: wpr-876510

ABSTRACT

This study investigated the mechanism by which icaritin (ICT) inhibits exosomes-induced lung metastasis of B16BL6 mouse melanoma cells. The culture supernatant of B16BL6 cells was collected for extraction of exosomes by ultracentrifugation and their characterization by transmission electron microscopy and Western blotting. Exosomal protein was quantified by BCA. A wound-healing assay was used to determine the effect of ICT on the migratory ability of B16BL6 cells induced by exosomes. After establishing an experimental melanoma lung metastasis model in C57BL/6 mice, we used H&E staining to study the ability of ICT to inhibit exosomes-induced melanoma metastasis. Animal experiments were approved by the Ethics Committee of Nanjing University of Chinese Medicine. ELISA and immunofluorescence were used to detect pro-inflammatory factors interleukin 6 (IL-6), S100 calcium-binding protein A8/A9 complex (S100A8/A9), serum amyloid A (SAA) and fibronectin in metastatic tumors. The expression of metastatic tissue-related proteins stimulator of interferon gene (STING), phospho-STING (p-STING), TANK-binding kinase 1 (TBK1) and phospho-TBK1 (p-TBK1) was detected by immunohistochemistry or Western blotting. The results showed that the particle size of exosomes was 149.33 ± 2.68 nm, the polydispersity index (PDI) was 0.192 ± 0.02, the zeta potential was -32.22 ± 0.50 mV, and the particles had classic tea tray-like membrane structure under TEM. The protein concentration of exosomes was measured to be 838.66 ± 62.14 μg·mL-1. The results of the cell scratch test showed that ICT can inhibit exosomes-induced migration of B16BL6 cells at a concentration of 5, 10, and 20 μmol·L-1. In vivo experimental results also showed that ICT can inhibit exosomes-induced metastasis of melanoma to the lungs and can significantly inhibit the expression of pro-inflammatory factors S100A8/A9, SAA and IL-6 in lung tissue, and inhibit the expression of p-STING and p-TBK1 in metastatic lung tissue. Taken together, these results indicated that ICT can significantly inhibit exosomes-induced tumor metastasis, and the inhibition is related to the inactivation of STING in metastatic foci.

20.
Journal of Clinical Hepatology ; (12): 169-172, 2021.
Article in Chinese | WPRIM | ID: wpr-862562

ABSTRACT

Liver fibrosis is the only way for various chronic liver diseases to develop into liver cirrhosis and is a reversible pathological state. However, how to prevent or reverse the development and progression of liver fibrosis is still an important scientific problem to be solved in clinical practice. As an important cell fate determinant, Numb has been shown to be closely associated with the development of many diseases. In the fibrotic environment, different subtypes of Numb protein are translated due to the selective shear action of the Numb gene, which have different regulatory effects on the activation of different signaling pathways and the differentiation of liver stem cells. At present, there are few reports on the role of Numb protein subtypes in liver fibrosis. This article reviews the regulatory effect of different Numb protein subtypes on the Notch, Hedgehog, and P53 signaling pathways and liver stem cells and elaborates on their potential application prospects in the treatment of liver fibrosis.

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