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1.
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.

2.
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.

3.
Article in Chinese | WPRIM | ID: wpr-879592

ABSTRACT

OBJECTIVE@#To analyze a patient with infertility and a fragile site found at 16q22 by using cytogenetic methods.@*METHODS@#Peripheral blood sample was taken from the patient and subjected to chromosomal karyotyping and single nucleotide polymorphism microarray (SNP-array) analysis.@*RESULTS@#The patient was found to be a mosaicism for a fragile site at 16q22, which has a variable morphology and cannot be induced by folic acid treatment. No abnormality was found by SNP-array analysis.@*CONCLUSION@#A rare fragile site, which can be induced without folic acid treatment, has been identified at 16q22. The strategy of assisted reproduction for such individuals is yet to be explored.


Subject(s)
Chromosome Fragile Sites , Chromosome Fragility , Chromosomes, Human, Pair 16 , Genetic Testing , Humans , Karyotyping , Mosaicism
4.
Article in Chinese | WPRIM | ID: wpr-879141

ABSTRACT

To investigate the potential molecular mechanism of the combination of Platycodonis Radix and Lilii Bulbus with the homology of medicine and food in the treatment of pneumonia by means of network pharmacology and in vitro verification experiment. Under the condition of bioavailability(OB)≥30% and drug-like(DL)≥0.18, the active components of Platycodonis Radix and Lilii Bulbus were screened in TCMSP database; the prediction targets of active components were searched from TCMSP, DrugBank and other databases, and the potential targets of pneumonia were obtained through GeneCards and OMIM database. The common targets were obtained by the intersection of drug and disease targets. The PPI network of common targets was constructed by STRING 11.0, and the core targets were obtained by topological analysis. Then the core targets received GO and KEGG analysis with use of WebGestalt and Metascape. The "component-target-pathway" network was constructed with the help of Cytoscape 3.7.1 software, and the component-target molecular docking verification was carried out with Discovery Studio 2016 software. Finally, the core targets and pathways were preliminarily verified in vitro. In this study, 12 active components were screened, 225 drug prediction targets and 420 potential diseases targets were obtained based on data mining method, and 14 core targets were obtained by topological analysis, including TNF, MMP9, AKT1, IL4 and IL2. The enrichment results of GO and KEGG showed that "Platycodonis Radix and Lilii Bulbus" drug pair may regulate inflammation, cell growth and metabolism by acting on 20 key signaling pathways such as TNF and IL-17, thereby exerting anti-pneumonia effects. The results of molecular docking showed that 12 active components had good binding ability with 14 core targets. In vitro experiment results showed that the core components of "Platycodonis Radix and Lilii Bulbus" drug pair could inhibit the expression of MMP9 and TNF-α by regulating TNF signal pathway. This study confirmed the scientificity and reliability of the prediction results of network pharmacology, and preliminarily revealed the potential molecular mechanism of the compatibility of Platycodonis Radix and Lilii Bulbus in the treatment of pneumonia. It provides a novel insight on systematically exploring the mechanism of the compatible use of Platycodonis Radix and Lilii Bulbus, and has a certain reference value for the research, development and application of new drugs.


Subject(s)
Drugs, Chinese Herbal , Humans , Medicine, Chinese Traditional , Molecular Docking Simulation , Pneumonia/drug therapy , Reproducibility of Results
5.
Article in Chinese | WPRIM | ID: wpr-878948

ABSTRACT

Network pharmacology and liver fibrosis(LF) model in vitro were used to analyze the underly mechanism of anti-liver fibrosis effect that induced by Piperis Longi Fructus and its major active compounds. TCMSP and TCMIP were used to search for the chemical constituents of Piperis Longi Fructus, as well as the oral bioavailability(OB), drug-likeness(DL), intercellular permeability of intestinal epithelial cells(Caco-2) and Drug-likeness grading were set as limiting conditions. The related target genes of Piperis Longi Fructus were queried by TCMSP database, while related targets of LF were screened by GeneCards databases. Interaction network was constructed using Cytoscape 3.7.1. These above data were imported into STRING database for PPI network analysis. Enrichment of gene ontology(GO) and pathway analysis(KEGG) within Bioconductor database were utilized to note functions of related targets of Piperis Longi Fructus. Finally, the core targets and pathways were preliminarily verified by in vitro experiments. The effects of piperlongumine(PL), the major active component of Piperis Longi Fructus, on proliferation of rat liver stellate cells(HSC-T6) and expression of α smooth muscle actin(α-SMA) and collagen Ⅰ were investigated. The major factors TNF-α of tumor necrosis factor(TNF) pathway and NF-κB p65, IL-6 protein expressions of LF process were examined. A total of 12 active compounds such as PL were obtained by analyzing the bioavailability and drug-like properties, which inferred to 48 targets. The functional enrichment analysis of GO obtained 1 240 GO items, mainly involving in process of biology and molecular function. A total of 99 signaling pathways were enriched in the KEGG pathway enrichment analysis, including TNF signaling pathway, cGMP-PKG signaling pathway, calcium signaling pathways. CCK-8 assay showed that PL inhibited proliferation of HSC-T6 induced by transforming growth factor-β1(TGF-β1). Western blot analysis found that treated with PL suppressed the protein expressions of α-SMA, collagen Ⅰ, TNF-α and p65 in HSC-T6. Enzyme linked immunosorbent assay(ELISA) showed that PL inhibited the expressions of TNF-α and IL-6 in the cluture supertant of HSC-T6 cells. In conclusion, PL could play an anti-liver fibrosis role by regulating TNF/NF-κB signaling pathway. This study provided the mechanism basis of anti-LF effects induced by Piperis Longi Fructus and its major active compounds, which might help for the further study of the mechanism and key targets of Piperis Longi Fructus.


Subject(s)
Animals , Caco-2 Cells , Hepatic Stellate Cells/metabolism , Humans , Liver Cirrhosis/genetics , NF-kappa B/metabolism , Rats , Signal Transduction
6.
Article in English | WPRIM | ID: wpr-878330

ABSTRACT

Objective@#Prior pulmonary tuberculosis (PTB) on chest X-ray (CXR) was commonly found in infertile patients receiving examinations before @*Method@#We conducted a retrospective cohort study of 14,254 infertile patients who had received IVF-ET at Peking University Third Hospital in 2017. Prior PTB was defined as the presence of signs suggestive of old or inactive PTB on CXR, with or without a clinical TB history. Patients who had prior PTB on CXR but had not received a clinical diagnosis and anti-TB therapy were included for analysis. Live birth, clinical pregnancy, and miscarriage rates were compared between the untreated PTB and non-PTB groups.@*Results@#The untreated PTB group had significantly lower clinical pregnancy (31.7% @*Conclusions@#Untreated PTB was associated with adverse pregnancy outcomes after IVF-ET, especially in patients with unexplained infertility, highlighting the clinical significance of PTB in this specific patient population.


Subject(s)
Abortion, Spontaneous/epidemiology , Adult , China/epidemiology , Embryo Transfer/statistics & numerical data , Female , Fertilization in Vitro/statistics & numerical data , Humans , Infertility, Female/etiology , Live Birth/epidemiology , Middle Aged , Pregnancy , Pregnancy Complications, Infectious/epidemiology , Pregnancy Outcome/epidemiology , Radiography, Thoracic , Retrospective Studies , Tuberculosis, Pulmonary/epidemiology , Young Adult
7.
Chinese Medical Journal ; (24): 1405-1415, 2021.
Article in English | WPRIM | ID: wpr-878190

ABSTRACT

BACKGROUND@#More and more scholars have called for the cumulative live birth rate (CLBR) of a complete ovarian stimulation cycle as a key indicator for assisted reproductive technology. This research aims to study the CLBR of the first ovarian hyperstimulation cycles and analyze the related prognosis factors that might affect the CLBR.@*METHODS@#Our retrospective study included first in vitro fertilization or intracytoplasmic sperm injection (IVF/ICSI) cycles performed between January 2013 to December 2014. A total of 17,978 couples of first ovarian hyperstimulation IVF/ICSI cycles were included. The study was followed up for 4 years to observe the CLBR. The multivariable logistic regression model was used to analyze the prognosis factor, P value of <0.05 was considered statistically significant.@*RESULTS@#The cumulative pregnancy rate was 58.14% (10,452/17,978), and the CLBR was 49.66% (8928/17,978). The female age was younger in the live birth group when compared with the non-live birth group (30.81 ± 4.05 vs. 33.09 ± 5.13, P < 0.001). The average duration of infertility was shorter than the non-live birth cohort (4.22 ± 3.11 vs. 5.06 ± 4.08, P < 0.001). The preliminary gonadotropin used and the total number of gonadotropin used were lower in the live birth group when compared with the non-live birth group (both P < 0.001). Meanwhile, the number of oocytes retrieved and transferrable embryos were both significantly higher in the live birth group (15.35 ± 7.98 vs. 11.35 ± 7.60, P < 0.001; 6.66 ± 5.19 vs. 3.62 ± 3.51, P < 0.001, respectively).@*CONCLUSIONS@#The women's age, body mass index, duration of infertility years, infertility factors, controlled ovarian hyperstimulation protocol, the number of acquired oocytes, and number of transferrable embryos are the prognosis factors that significantly affected the CLBR.


Subject(s)
Birth Rate , China , Female , Fertilization in Vitro , Humans , Live Birth , Ovulation Induction , Pregnancy , Pregnancy Rate , Retrospective Studies , Sperm Injections, Intracytoplasmic
8.
Article in Chinese | WPRIM | ID: wpr-877598

ABSTRACT

OBJECTIVE@#To observe the clinical therapeutic effect of electroacupuncture (EA) combined with tamsulosin hydrochloride sustained release capsule on chronic prostatitis (CP) of damp and heat stasis.@*METHODS@#A total of 70 patients with CP of damp and heat stasis were randomized into an acupuncture plus medication group (35 cases, 4 cases dropped off) and a medication group (35 cases, 5 cases dropped off). In the medication group, tamsulosin hydrochloride sustained release capsule was given orally, 0.2 mg a time, once each night. On the basis of treatment in the medication group, EA was applied at Guanyuan (CV 4), Sanyinjiao (SP 6) and Yinglingquan (SP 9), with disperse-dense wave, 5 mA in intensity for 30 min. Treatment for 30 days was as one course, and totally 3 courses were required in both groups. Before treatment, 1, 2, 3 months into treatment and at the follow-up of 2 months after treatment, the TCM syndrome score and National Institutes of Health chronic prostatitis symptom index (NIH-CPSI) score were observed, and the clinical efficacy was evaluated in both groups.@*RESULTS@#Compared before treatment, the TCM syndrome scores of 3 months into treatment and follow-up were decreased in the acupuncture plus medication group (@*CONCLUSION@#Acupuncture combined with medication can improve the clinical symptoms in patients with CP of damp and heat stasis, and its therapeutic effect is superior to simple western medication.


Subject(s)
Acupuncture Points , Acupuncture Therapy , Chronic Disease , Hot Temperature , Humans , Male , Prostatitis/drug therapy , Treatment Outcome
9.
Journal of Clinical Hepatology ; (12): 1449-1453, 2021.
Article | WPRIM | ID: wpr-877336

ABSTRACT

Fuzheng Huayu prescription is developed by Shanghai University of Traditional Chinese Medicine and has the functions of promoting blood circulation, removing blood stasis, nourishing essence, and tonifying the liver, and it is an effective empirical prescription for the treatment of chronic liver diseases including chronic viral hepatitis, nonalcoholic fatty liver disease, liver fibrosis, liver cirrhosis, and liver cancer. This prescription has been used in clinical practice for many years and has a marked clinical effect in alleviating clinical symptoms and improving liver fibrosis and complications. In recent years, many scholars have conducted in-depth studies on the clinical effect and mechanism of action of Fuzheng Huayu prescription in the treatment of chronic liver diseases and achieved satisfactory results. This article summarizes related research findings in order to provide a reference for subsequent studies.

10.
Chinese Journal of Neurology ; (12): 267-271, 2021.
Article in Chinese | WPRIM | ID: wpr-885414

ABSTRACT

The term of vascular cognitive impairment (VCI) has been constantly evolved and updated. The latest definition refers to the contribution of stroke and subclinical vascular brain injury that resulted from vascular pathology and its risk factors, to the cognitive impairment syndrome involving at least one domain, ranging from mild cognitive impairment to dementia, as well as mixed cognitive impairment, including Alzheimer′s disease. This article presents the epidemiology, etiology, pathogenesis, classification, clinical manifestations, auxiliary examination, diagnosis, prevention and treatment of VCI.

11.
Article in Chinese | WPRIM | ID: wpr-883269

ABSTRACT

Objective:To investigate the clinicopathological characteristics and treatment strategies of undifferentiated carcinoma with osteoclast-like giant cells of pancreas (UCOGCP).Methods:The retrospective and descriptive study was conducted. The clinicopathological data of 5 patients with UCOGCP who were admitted to Peking University First Hospital from January 2004 to January 2019 were collected. There were 1 male and 4 females, aged from 33 to 71 years, with a median age of 56 years. Patients underwent preoperative laboratory test, imaging and histopatho-logical examinations. Patients with pancreatic head tumors underwent pancreaticoduodenectomy, and those with tumors in the body or tail of pancreas underwent distal pancreatectomy combined with splenectomy. All patients underwent standard lymph node dissection. Postoperative adjuvant therapy was individually decided by a multidisciplinary team. Observation indicators: (1) preopera-tive examination and treatment; (2) postoperative histopathological situations; (3) follow-up. Follow-up using outpatient examination and telephone interview was performed to detect tumor recurrence of patients up to January 2020. Measurement data with normal distribution were represented as Mean± SD. Measurement data with skewed distribution were described as M (range). Count data were described as absolute numbers. Results:(1) Preoperative examination and treatment: of the 5 UCOGCP patients, CA19-9 was elevated as 65.43 U/mL in only 1 patient preoperatively, while the CA19-9 was normal in other 4 patients. Four patients showed a solid cystic mass on preoperative contrast-enhanced computed tomography (CT) scan, and 1 patient showed a delayed peripheral enhancement of the solid tumor with central necrosis. The magnetic resonance imaging (MRI) scan showed hypointense signals on T1, T2 and weighted diffusion sequences in all 5 patients. Three of the 5 patients were resectable according to imaging data, 1 patient had locally advanced tumor, infiltrating the transverse colon, stomach, and partial small intestine, with the portal vein thrombus, and 1 patient had pancreatic head tumor with a liver metastatic lesion of 0.4 cm diameter which was detected on position emission tomography CT and was diagnosed as UCOGCP by endoscopic ultrasound-guided fine-needle aspiration biopsy. All patients underwent radical resection. Of the 3 patients with resectable tumors, 2 patients underwent pancreaticoduo-denectomy and 1 patient underwent distal pancreatectomy combined with splenectomy. One patient with locally advanced tumor in the body and tail of pancreas underwent distal pancreatectomy + transverse colostomy + partial gastrectomy + portal vein thrombectomy, and 1 patient with pancreatic head tumor and liver metastasis underwent pancreatoduodenectomy combined with left lateral hepatectomy. Of the 5 patients, 2 received postoperative adjuvant chemotherapy with single-agent gemcitabine, 1 received albumin-paclitaxel+gemcitabine combination chemotherapy, 1 received S1 as single agent chemotherapy, and 1 did not receive adjuvant chemotherapy. (2) Postoperative histopathological situations: of the 5 patients, 4 cases showed a cystic solid appearance of gross specimens, and 1 case had a solid appearance with central hemorrhagic necrosis. The tumor diameter was 5.2 cm(range, 2.0?14.0 cm). All the 5 patients achieved negative margins. Of the 5 patients, there was 1 case with portal vein invasion, 2 cases with vascular invasion, 3 cases with perineural invasion, and 2 cases with regional lymph node metastasis. One patient may had multiple tumor invasion and metastasis. Four of 5 patients had paraffin specimens available for immuno-histochemical staining. Four patients were positive for both CD68 and vimentin stains, while 3 patients were positive for programmed death ligand-1 (PD-L1), including 2 samples with 5% positive cells and 1 sample with 25% positive cells. Postoperative pathological examination showed a large number of spindle histiocytoid sarcoma cells scattered with osteoclast like giant cells and pleomorphic carcinoma giant cells. The tumor mutation burden in the 4 patients was 3.23 Muts/Mb(range, 2.61?21.77 Muts/Mb). Microsatellite status was stable in 4 patients. The next generation sequencing of 4 patients showed that all patients had KRAS mutation which was the most frequently mutation in pancreatic ductal adenocarcinoma. Of the 4 patients, 1 case had germline pathogenic mutation in TP53, 1case had somatic mutation in TP53, 1 case had somatic mutation in TP53, BLM, CDKN2A, and 1 case had somatic mutation in ARID1A. (3) Follow-up: 5 patients were followed up for 14?173 months, with a median follow-up time of 46 months. During the follow-up, 4 patients achieved disease-free survival and 1 patient had local recurrence at postoperative 11 months.Conclusions:UCOGCP is a rare variant of pancreatic tumor that exhibits a cystic solid mass in imaging examinations. High expression of PD-L1 is common in UCOGCP. The prognosis for UCOGCP is favorable following radical surgery. Patients may benefit from extended radical surgery even if the tumor has locally progression or distant metastasis.

12.
Article in Chinese | WPRIM | ID: wpr-882660

ABSTRACT

Objective:To investigate the role and mechanism of high mobility group box 1(HMGB1) in the injury of Caco-2 intestinal epithelial barrier induced by lipopolysaccharide (LPS).Methods:The Caco-2 cellular monolayer barrier was established with Transwell chamber. After the Caco-2 monolayer model was established, the transepithelial electrical resistance (TEER) values were measured. When the TEER value reached 500 Ω·cm 2, the cells were divided into 3 groups: control group, LPS treatment group, and LPS+ ethyl pyruvate (EP) treatment group. The concentration of LPS and EP were 100 μg/mL, 50 μg/mL, separately. Then TEER values were measured at 12, 24, 48 and 72 h, and FITC-dextran permeability was detected at 24 h. The cells were seeded on 6-well plates. After cell density reached 80%, treatments were given as the above. The real-time polymerase chain reaction (RT-PCR) and Western blot were used to measure the changes in the protein and mRNA expressions of Occludin, HMGB1, and nuclear factor-κB (NF-κB). Results:Compared with the control group, the TEER values (Ω·cm 2) reduced at 12, 24, 48 and 72 h in the LPS treatment group [(514.22±12.59) vs (304.96±9.69), (521.65±13.35) vs (276.21±7.82), (523.99±8.18) vs (206.64±15.85), (491.21±6.72) vs (156.33±10.83), all P<0.05]. The FITC-dextran permeability increased significantly at 24 h [(2.58±0.07) vs (1.04±0.06), P<0.05]. The expression levels of Occludin protein and mRNA were decreased (all P<0.05), while the expression levels of HMGB1 and NF-κB protein and mRNA were significantly increased (all P<0.05). Compared with the LPS treatment group, the TEER values (Ω·cm 2) increased significantly at 12, 24, 48 and 72 h in the EP treatment group [(519.00±5.66) vs (304.96±9.69), (504.69±8.57) vs (276.21±7.82), (453.65±10.74) vs (206.64±15.85), (385.28±7.57) vs (156.33±10.83), all P<0.05]. The FITC-dextran permeability decreased at 24 h [(1.23±0.11) vs (2.58±0.07), P<0.05]. The expression level of Occludin protein and mRNA were increased ( P<0.05), while the expression levels of HMGB1 and NF-κB protein and mRNA were significantly decreased (all P<0.05). Conclusions:LPS can injure intestinal barrier directly in vitro and reduces the expression of tight junction proteins between cells. The mechanism may be related to the increased expression of HMGB1 and NF-κB protein.

13.
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.

14.
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
15.
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

16.
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
17.
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
18.
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
19.
Article in Chinese | WPRIM | ID: wpr-879892

ABSTRACT

OBJECTIVE@#To study the association between maternal reduced folate carrier (@*METHODS@#A hospital-based case-control study was conducted. The mothers of 683 infants with CHD who attended the Department of Cardiothoracic Surgery, Hunan Children's Hospital, from November 2017 to March 2020 were enrolled as the case group. The mothers of 740 healthy infants without any deformity who attended the hospital during the same period of time were enrolled as the control group. A questionnaire survey was performed to collect the exposure data of subjects. Venous blood samples of 5 mL were collected from the mothers for genetic polymorphism detection. A multivariate logistic regression analysis was used to evaluate the association of @*RESULTS@#After control for confounding factors, the multivariate logistic regression analysis showed that maternal @*CONCLUSIONS@#Maternal


Subject(s)
Case-Control Studies , Child , Female , Genetic Predisposition to Disease , Genotype , Heart Defects, Congenital/genetics , Humans , Infant , Polymorphism, Single Nucleotide , Reduced Folate Carrier Protein/genetics , Risk Factors
20.
Journal of Leukemia & Lymphoma ; (12): 236-239, 2020.
Article in Chinese | WPRIM | ID: wpr-862826

ABSTRACT

Objective:To observe the clinical efficacy and adverse reactions of bortezomib once-weekly therapy for newly diagnosed multiple myeloma (MM).Methods:The clinical data of 50 patients with newly diagnosed MM who received bortezomib combined with chemotherapy in Heze Municipal Hospital of Shandong Province from June 2016 to June 2019 were retrospectively analyzed. The patients were divided into once-weekly medication regimen (the observation group, 21 cases) and twice-weekly medication regimen (the control group, 29 cases). The efficacy and adverse reactions of both groups were compared.Results:The total effective rate of the former 2 treatment courses in the observation group was lower than that in the control group, and the difference was statistically significant [23.8% (5/21) vs. 55.2% (16/29), χ 2 = 4.918, P = 0.027]. After treatment of 4 and 6 courses, there were no statistically significant differences in the total effective rate between the observation group and the control group [66.7% (14/21) vs. 72.4% (21/29); 81.0% (17/21) vs. 86.2% (25/29), all P > 0.05]. The incidence of peripheral neuropathy in the observation group was lower than that in the control group, and the difference was statistically significant [14.3% (3/21) vs. 41.4% (12/29), χ 2 = 4.416, P = 0.036]. There was no statistically significant difference in the incidence of other adverse reactions of both groups (both P < 0.05). Conclusions:The therapeutic effect of once-weekly medication regimen is similar to that of twice-weekly medication regimen for the treatment of newly diagnosed MM. The incidence of peripheral neuropathy in the once-weekly therapy is low and the patients can have better tolerance.

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