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1.
Chinese Journal of Cardiology ; (12): 759-768, 2023.
Article in Chinese | WPRIM | ID: wpr-984714

ABSTRACT

Objective: Bioinformatics analysis was used to screen differentially expressed genes (DEGs) in macrophages of sepsis myocardial injury and to verify key genes. Methods: Experiment 1 (gene chip and bioinformatics analysis): The gene chip data GSE104342 of cardiac macrophages in septic mice was downloaded from Gene Expression Omnibus database. DEGs were obtained by R language analysis. DAVID online database was used to obtain gene ontology and kyoto encyclopedia of genes and genomes (KEGG) enrichment analysis of DEGs. STRING online database was used for protein-protein interaction network analysis of DEGs, and then key genes were screened by using Cytoscape software and molecular complex detection (MCODE) plug-ins. Experiment 2 (sepsis model construction and related protein verification): Ten male C57BL/6 mice, aged 8-14 weeks. Five mice were randomly selected as control group, and 5 mice were selected as the sepsis group by building a mice sepsis model in vivo. Echocardiography was used to detect the cardiac function. Hematoxylin-eosin staining was used to assess the cardiac morphology. TUNEL staining was used to evaluate cardiomyocyte apoptosis. Immunofluorescence staining was used to detect the expression of differentiation antigen cluster 206 (CD206),inducible nitric oxide synthases (iNOS),F4/80,suppressor of cytokine signaling 3 (Socs3) ,interleukin 1 receptor antagonist (Il1rn) and chemokine C-C motif ligand 7 (Ccl7) protein. RAW264.7 macrophages were cultured in vitro and divided into 2 groups: LPS groupstimulated by lipopolysaccharide (LPS, 1 mg/L) and blank control group treated with equal-volume phosphate buffer solution. Reverse transcription-polymerase chain reaction (RT-PCR) was used to evaluate the expression of Socs3, Il1rn and Ccl7 in vitro. Results: Experiment 1: 24 647 genes were screened in GSE104342 dataset and 177 genes (0.72%) were differential expression, including 120 up-regulated genes and 57 down-regulated genes. Gene ontology enrichment analysis showed that DEGs were mainly involved in inflammatory response, immune response, apoptosis regulation and antigen processing and presentation. KEGG signaling pathway analysis showed that DEGs in cardiac macrophages of septic mice were mainly enriched in cytokine-cytokine receptor interaction, tumor necrosis factor signaling pathway, NOD like receptor signaling pathway. Three hub genes were obtained by STRING and Cytoscape analysis, including Socs3, Il1rn and Ccl7. Experiment 2: In vivo, it was found that compared with the control group, the cardiac function of the sepsis mice decreased significantly, the myocardial cells were significantly edema, inflammatory cell infiltration, myocardial fiber rupture, some myocardial nuclei dissolved and disappeared, and the cardiomyocyte apoptosis increased, suggesting that the sepsis myocardial injury model of mice was successfully constructed. Compared with the control group, the expression of CD206 in the myocardium of septic mice was down-regulated, the expression of iNOS, F4/80, Socs3, Il1rn and Ccl7 were up-regulated. In addition, there was co-localization between Socs3, Il1rn, Ccl7 and F4/80 protein. Compared with the blank control group, the expression of Socs3, Il1rn and Ccl7 significantly upregulated after LPS intervention in vitro by RT-PCR. Conclusions: The selected key genes Socs3, Il1rn and Ccl7 were up-regulated in myocardial macrophages of septic mice. Socs3, Il1rn and Ccl7 are expected to become new targets for the diagnosis and treatment of sepsis cardiac injury.


Subject(s)
Male , Mice , Animals , Lipopolysaccharides , Mice, Inbred C57BL , Myocardium , Computational Biology , Sepsis , Macrophages , Cytokines , Gene Expression Profiling
2.
Acta Pharmaceutica Sinica ; (12): 2226-2238, 2023.
Article in Chinese | WPRIM | ID: wpr-999153

ABSTRACT

Src homology phosphotyrosyl phosphatase 2 (SHP2) is a protein tyrosine phosphatase encoded by PTPN11, which catalyzes the dephosphorylation of protein tyrosine. As a convergence node, SHP2 mediates multiple signaling pathways such as rat sarcoma (RAS)-rapidly accelerated fibrosarcoma (RAF)-mitogen-activated extracellular signal-regulated kinase (MEK)-extracellular regulated protein kinases (ERK), phosphatidylinositol 3-kinase (PI3K)-serine/threonine kinase (AKT), janus kinase (JAK)-signal transducer and activator of transcription (STAT) and programmed death-1 (PD-1)/programmed cell death-ligand 1 (PD-L1). It can not only regulate the growth and proliferation of tumor cells, but also mediate the immune escape of tumor cells by influencing the tumor microenvironment. Given its dual biological functions in tumor immune regulation, SHP2 is a promising target for cancer immunotherapy. To date, several SHP2 allosteric inhibitors have been advanced into clinical trials for tumor immunotherapy with single or combination therapeutic strategies. Additionally, SHP2 activators also showed therapeutic potential in the field of tumor immune modulation. In this paper, we reviewed the dual function of SHP2 in both tumor and immune cells. Besides, the challenges and prospects of SHP2 modulators in cancer immunotherapy were also briefly discussed, aiming to explore new horizon of SHP2 modulators for tumor immunotherapy.

3.
Journal of Southern Medical University ; (12): 552-559, 2023.
Article in Chinese | WPRIM | ID: wpr-986961

ABSTRACT

OBJECTIVE@#To evaluate the regulatory effect of berberine on autophagy and apoptosis balance of fibroblast-like synoviocytes (FLSs) from patients with in rheumatoid arthritis (RA) and explore the mechanism.@*METHODS@#The inhibitory effect of 10, 20, 30, 40, 50, 60, 70, and 80 μmol/L berberine on RA-FLS proliferation was assessed using CCK-8 method. Annexin V/PI and JC-1 immunofluorescence staining was used to analyze the effect of berberine (30 μmol/L) on apoptosis of 25 ng/mL TNF-α- induced RA-FLSs, and Western blotting was performed to detect the changes in the expression levels of autophagy- and apoptosis-related proteins. The cells were further treated with the autophagy inducer RAPA and the autophagy inhibitor chloroquine to observe the changes in autophagic flow by laser confocal detection of mCherry-EGFP-LC3B. RA-FLSs were treated with the reactive oxygen species (ROS) mimic H2O2 or the ROS inhibitor NAC, and the effects of berberine on ROS, mTOR and p-mTOR levels were observed.@*RESULTS@#The results of CCK-8 assay showed that berberine significantly inhibited the proliferation of RA-FLSs in a time- and concentration-dependent manner. Flow cytometry and JC-1 staining showed that berberine (30 μmol/L) significantly increased apoptosis rate (P < 0.01) and reduced the mitochondrial membrane potential of RA-FLSs (P < 0.05). Berberine treatment obviously decreased the ratios of Bcl-2/Bax (P < 0.05) and LC3B-II/I (P < 0.01) and increased the expression of p62 protein in the cells (P < 0.05). Detection of mCherry-EGFP-LC3B autophagy flow revealed obvious autophagy flow block in berberine-treated RA-FLSs. Berberine significantly reduced the level of ROS in TNF-α-induced RA-FLSs and upregulated the expression level of autophagy-related protein p-mTOR (P < 0.01); this effect was regulated by ROS level, and the combined use of RAPA significantly reduced the pro-apoptotic effect of berberine in RA-FLSs (P < 0.01).@*CONCLUSION@#Berberine can inhibit autophagy and promote apoptosis of RA-FLSs by regulating the ROS-mTOR pathway.


Subject(s)
Humans , Synoviocytes , Berberine/metabolism , Reactive Oxygen Species/metabolism , Tumor Necrosis Factor-alpha/metabolism , Hydrogen Peroxide/metabolism , Sincalide/metabolism , Cell Proliferation , Arthritis, Rheumatoid/metabolism , Signal Transduction , TOR Serine-Threonine Kinases/metabolism , Apoptosis , Fibroblasts , Autophagy , Cells, Cultured
4.
Chinese Medical Sciences Journal ; (4): 97-108, 2023.
Article in English | WPRIM | ID: wpr-981588

ABSTRACT

Objective To investigate the effects of propofol and sevoflurane on neurological recovery of traumatic brain injury (TBI) patients in the early postoperative stage.Methods We retrospectively analyzed the clinical data of TBI patients who underwent craniotomy or decompressive craniectomy. Generalized additive mixed model (GAMM) was used to analyze effects of propofol and sevoflurane on Glasgow Coma Scale (GCS) on postoperative days 1, 3, and 7. Multivariate regression analysis was used to analyze effects of the two anesthetics on Glasgow Outcome Scale (GOS) at discharge.Results A total of 340 TBI patients were enrolled in this study. There were 110 TBI patients who underwent craniotomy including 75 in the propofol group and 35 in the sevoflurane group, and 134 patients who underwent decompressive craniectomy including 63 in the propofol group and 71 in the sevoflurane group. It showed no significant difference in GCS at admission between the propofol and the sevoflurane groups among craniotomy patients (β = 0.75, 95%CI: -0.55 to 2.05, P = 0.260). However, elevation in GCS from baseline was 1.73 points (95%CI: -2.81 to -0.66, P = 0.002) less in the sevoflurane group than that in the propofol group on postoperative day 1, 2.03 points (95%CI: -3.14 to -0.91, P < 0.001) less on day 3, and 1.31 points (95%CI: -2.43 to -0.19, P = 0.022) less on day 7. The risk of unfavorable GOS (GOS 1, 2, and 3) at discharge was higher in the sevoflurane group (OR = 4.93, 95%CI: 1.05 to 23.03, P = 0.043). No significant difference was observed among two-group decompressive craniectomy patients in GCS and GOS.Conclusions Compared to propofol, sevoflurane was associated with worse neurological recovery during the hospital stay in TBI patients undergoing craniotomy. This difference was not detected in TBI patients undergoing decompressive craniectomy.

5.
China Tropical Medicine ; (12): 832-2022.
Article in Chinese | WPRIM | ID: wpr-980024

ABSTRACT

@#Abstract: Objective To analyze the epidemiological characteristics of late diagnosed HIV/AIDS cases (LD) in Sanya from 2010 to 2021, and to provide evidence for reducing the LD rate. Methods The database was downloaded from the AIDS Prevention and Control Information System of China's Disease Prevention and Control Information System and newly reported HIV/AIDS cases between 2010 and 2021 in Sanya were included, identified LD according to the LD criteria proposed by Chinese Center for Disease Control and Prevention in 2014 and analyzed the relevant factors of LD. Results From 2010 to 2021, a total of 710 research objects were included in this study. The proportion of LD was 33.4% (237/710), and decreased from 95.5% to 22.4% between 2010 and 2021 (χ2trend=34.777, P<0.001). Ethnic groups, educational level, sample sources and confirmed date were the relevant factors of LD of HIV/AIDS in Sanya City. The proportion of LD was 56.8% in Li ethnic group, which was higher than that in Han ethnic (OR=2.253, 95%CI=1.361-3.670). The proportion of LD of patients who were middle school and less was 55.5%, which were more likely to be LD than high school or above (OR=1.722, 95%CI=1.072-2.765). The proportion of LD was 56.8% in patients whose samples were from medical institutions or testing consultation were more likely to be LD than MSM (OR=5.564, 95%CI=3.278-9.444; OR=2.204, 95%CI=1.239-3.923). Compared with patients who were confirmed between 2018-2021, the patients derived from 2010 to 2013 had higher LD (OR=2.246, 95%CI=1.311-4.488). Conclusion The LD of HIV/AIDS in Sanya cannot be ignored, especially the HIV/AIDS from counseling and testing and medical institutions. We should strengthen HIV testing, strengthen health education.

6.
Chinese Journal of Physical Medicine and Rehabilitation ; (12): 233-237, 2022.
Article in Chinese | WPRIM | ID: wpr-933971

ABSTRACT

Objective:To analyze the effect of transtracheal pressure (TTP) on the application of a speaking valve in critically ill patients after tracheostomy.Methods:A retrospective analysis was conducted of 50 patients wearing a speaking valve after tracheostomy. Patients who had been wearing a speaking valve for 30min or more were the tolerance group, while those with less than 30min were the intolerance group. Transtracheal pressure was monitored during resting breathing, forced expiration and speaking. Linear regression models were evaluated to isolate the factors best predicting tolerance. The changes in respiratory muscle contraction before and after wearing a speaking valvs were evaluated using ultrasound. The patients′ satisfaction with wearing a speaking valve was also recorded.Results:TTP during speaking significantly predicted tolerance. The baseline values of diaphragmatic thickening fraction and physical functioning also positively predicted tolerance. Acute physiology and chronic health (APACHE II) score was a significant negative predictor. After wearing the speaking valve, the average contraction of the rectus abdominis, external oblique, internal oblique and transverse abdominis muscles increased significantly. Both groups expressed high satisfaction with the speaking valves.Conclusions:Transtracheal pressure during speaking can help predict the tolerance for wearing a speaking valve among critically ill patients after a tracheostomy. Baseline diaphragmatic thickening fraction, physical functioning and APACHE II score can predict the duration of speaking valve tolerance.

7.
Acta Pharmaceutica Sinica ; (12): 1565-1573, 2022.
Article in Chinese | WPRIM | ID: wpr-929449

ABSTRACT

Immune checkpoints (ICs) are immunosuppressive molecules expressed on immune cells, which can regulate immune cells' activation. Immune checkpoint inhibitors (ICIs) which can block the interaction of immune checkpoints and their ligands, improve the cytotoxic effect of the immune system on tumor cells. Immunotherapy such as employing ICIs has gradually become a conventional therapeutic strategy for cancer treatment. However, the low response rate and the emergence of drug resistance have seriously affected the clinical efficacy of ICIs. Reactive oxygen species (ROS) are electronic reduction products of active oxygen, as well as natural by-products of cell metabolism, which can be used as regulators of intercellular signals. Tumor microenvironment (TME) is often in the state of oxidative stress (OS), which is the imbalance between oxidative system and antioxidant system. ROS can affect the interaction with its ligands by regulating the expression and activity of immune checkpoints in TME, thus affecting the anti-tumor effect of immune cells. Accumulating studies have shown that ROS could regulate tumor immune checkpoints through several pathways. Due to different types and stages of tumor, it would be clinical beneficial to understand the mechanistic link of ROS on tumor immune checkpoint, and choose appropriate ROS regulators combined with immune checkpoint inhibitors to maximize anti-tumor effects. This article reviews the common metabolic sources and characteristics of ROS, the regulatory effect and mechanism of ROS on tumor immune checkpoints and its therapeutic application.

8.
Acta Pharmaceutica Sinica ; (12): 2352-2363, 2022.
Article in Chinese | WPRIM | ID: wpr-937036

ABSTRACT

Using the concepts and methods of epigenetics and metabolomics, to investigate the overall action molecular mechanism of Chrysanthemi indici C (CIC), the anti-hepatitis B virus (HBV) active extracts from Flos chrysanthemi indici. The inhibitory effects of CIC on proliferation and hepatitis B surface antigen (HBsAg), hepatitis B envelope antigen (HBeAg) and HBV-DNA of HepG2.2.15 cells were detected by CCK-8 and antigen kit. The DNA methyltransferases (DNMTs)/ten-eleven-translocation-2 (TET2) equilibrium was detected by ELISA. Illumina 850K methylation chip, pyrosequencing and qPCR were used to determine the action pathway and target of CIC by GO and KEGG analysis. Cell metabolites were extracted with 80% methanol, and the changes of differential metabolites, differential metabolic pathways and cell microenvironment were detected by LC-MS and other metabolomics methods. The results showed that CIC could inhibit the proliferation, HBsAg, HBeAg and HBV-DNA of HepG2.2.15 cells obviously, down-regulate DNA methyltransferase 1 (DNMT1), DNA methyltransferase 3a (DNMT3a) and DNA methyltransferase 3b (DNMT3b), up-regulate TET2, and restore the balance of DNMTs/TET2. The action targets of CIC were phospholipase C gamma 2 (PLCG2), phosphoinositide-3-kinase regulatory subunit 3 (PIK3R3), 1-acylglycerol-3-phosphate O-acyltransferase 2 (AGPAT2), 5-hydroxytryptamine receptor 2B (HTR2B), nerve growth factor (NGF), mainly involved in lipid metabolism, inflammation mediated regulation of transient receptor potential (TRP), phospholipase D signaling and advanced glycation end product-receptor for AGE (AGE-RAGE) signaling in diabetic complications pathways. CIC could significantly affect fatty acid metabolism and had great influence on phenolic acid, alkaloid and lipid metabolites in cell microenvironment. These results suggest that the action mechanism of CIC may be the synergistic action of multiple pathways and multiple targets, including related inflammatory pathways, immune pathways and lipid metabolism, through regulating epigenetic expression balance and restoring the balance of cell microenvironment.

9.
Chinese Journal of Endocrinology and Metabolism ; (12): 859-864, 2022.
Article in Chinese | WPRIM | ID: wpr-957626

ABSTRACT

Objective:To evaluate the association of HbA 1C level and variability with annual decline in glomerular filtration rate in elderly patients with type 2 diabetes. Methods:A total of 527 elderly type 2 diabetic patients with baseline estimated glomerular filtration rate(eGFR)≥60 mL·min -1·(1.73 m 2) -1 at the diabetes center of a tertiary hospital in Jiangsu province were included and followed up. The mean value and the variability of HbA 1C, including standard deviation(HbA 1C-SD), variation coefficient(HbA 1C-CV), and adjusted standard deviation(Adj-HbA 1C-SD) were calculated. According to the annual decreased rate of eGFR, the patients were divided into △eGFR>5% group and △eGFR≤5% group. Cox proportional risk regression model was used to evaluate the relationship between HbA 1C variability and the risk of decreased glomerular filtration rate. Results:With a mean follow-up time of 19 months, there were 176 patients whose △eGFR>5%. Compared with △eGFR≤5% group, the HbA 1C-mean and HbA 1C variability were significantly higher in △eGFR>5% group( P<0.05). Cox regression analysis showed that HbA 1C-mean, HbA 1C-SD, HbA 1C-CV, and Adj-HbA 1C-SD were significantly correlated with decreased glomerular filtration rate. After adjustment for age, gender, HbA 1C-mean, and other factors, only Adj-HbA 1C-SD was correlated with renal insufficiency [ HR=3.32(1.68-6.57)]. Conclusions:HbA 1C variability is independently associated with annual decline in glomerular filtration rate in elderly patients with type 2 diabetes. The Adj-HbA 1C-SD is the most sensitive indicator in predicting decreased glomerular filtration rate.

10.
Journal of Forensic Medicine ; (6): 653-660, 2021.
Article in English | WPRIM | ID: wpr-984067

ABSTRACT

OBJECTIVES@#To explore the possible mechanism of Yunaconitine poisoning by studying the changes of urine metabolic profile in rats chronically poisoned by Yunaconitine via non-targeted metabolomics.@*METHODS@#A rat model of Yunaconitine poisoning was established, and a metabolomics method based on UPLC-QTOF-MS technology was used to obtain the urine metabolic profile. Principal component analysis (PCA), orthogonal projections to latent structures-discriminant analysis (OPLS-DA), variable importance in projection (VIP) value greater than 1, fold change (FC) value greater than 3 or less than 0.33 and P value less than 0.05 were used to screen potential biomarkers related to the toxicity of Yunaconitine. The metabolic pathway analysis was performed through the MetaboAnalyst website and pathological changes of related tissues were observed.@*RESULTS@#Sixteen potential biomarkers including L-isoleucine were screened, which mainly involved six metabolic pathways including the biosynthesis and degradation of valine, leucine and isoleucine, pentose and glucuronate interconversions, and propanoate metabolism, alanine, aspartate and glutamate metabolism, tyrosine metabolism. Pathological studies showed that rat toxic change in nervous system, liver and cardiac caused by Yunaconitine.@*CONCLUSIONS@#Yunaconitine may cause neurotoxicity, hepatotoxicity and cardiotoxicity by affecting amino acid and glucose metabolism.


Subject(s)
Animals , Rats , Aconitine/analogs & derivatives , Biomarkers/metabolism , Chromatography, High Pressure Liquid , Metabolome , Metabolomics
11.
China Journal of Chinese Materia Medica ; (24): 845-854, 2021.
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 , Humans , Rats , Caco-2 Cells , Hepatic Stellate Cells/metabolism , Liver Cirrhosis/genetics , NF-kappa B/metabolism , Signal Transduction
12.
Chinese Journal of Radiation Oncology ; (6): 1233-1237, 2021.
Article in Chinese | WPRIM | ID: wpr-910543

ABSTRACT

Objective:To assess the role of Glasgow prognostic score (GPS) in the prognostic evaluation of nasopharyngeal carcinoma patients.Methods:Clinical data of 129 nasopharyngeal carcinoma patients who received radical radiotherapy in Affiliated Hospital of Jiangnan University from January 2012 to December 2013 were retrospectively analyzed. Clinicopathological characteristics of the patients were collected, including gender, age, TNM staging, pathological type and treatment regimen, etc. The GPS before and at 3 months after radiotherapy were calculated. The survival curve was drawn by the Kaplan- Meier method. Cox regression model was used for analysis of prognostic factors. The area under the receiver operating characteristic (ROC) curve (AUC) was utilized to evaluate the predictive capability of clinical parameters on prognosis. Results:With a median follow-up of 89.0 months (range: 5.1-104.6 months), the 5-year progression-free survival (PFS) of 129 patients was 79.8% and 84.5% for the 5-year overall survival (OS). At 3 months after radiotherapy, the 5-year PFS were 85.6%, 61.1% and 33.3% in the GPS 0, 1 and 2 groups, and 90.4%, 66.7% and 33.3% for the 5-year OS, respectively (all P<0.01). At 3 months after radiotherapy, the GPS, clinical staging (Ⅰ-Ⅲ vs. Ⅳ A) and concurrent chemotherapy were significantly correlated with PFS and OS (all P<0.01). ROC curve showed that at 3 months after radiotherapy, the AUC values of GPS, clinical staging and two combined in predicting OS were 0.694, 0.815 and 0.860, respectively. Conclusions:At 3 months after radiotherapy, higher GPS is an independent poor prognostic factor for nasopharyngeal carcinoma patients. The combination of GPS and clinical staging yields high accuracy in the prognostic evaluation of nasopharyngeal carcinoma patients.

13.
Chinese Journal of Pharmacology and Toxicology ; (6): 740-741, 2021.
Article in Chinese | WPRIM | ID: wpr-909588

ABSTRACT

OBJECTIVE Our previous studies demonstrated that various ingredients from the traditional Chinese medicine (TCM) for promoting blood circulation and removing blood stasis, as exemplified by cryptotanshinone and salvi?anolic acid B, exerted striking effects on modulating angiogenesis and vascular permeability, which suggests that they may be effective in treating vascular leak-driven diseases (e.g. tumor, cerebral cavernous malformation and diabetic reti?nopathy). However, the lack of reliable and advanced technologies and models sets up difficult hurdles for better under?standing the role of TCM for promoting blood circulation and removing blood stasis. To this end, this study is to outline numerous cutting-edge platforms that can be utilized for exploring the function of TCM for promoting blood circulation and removing blood stasis in vascular leak-driven diseases. METHODS Two-photon laser scanning fluorescence micros?copy was used to observe the interactions between neutrophils and blood vessels in a real-time manner. Dynamic flow system was employed to mimic the in vivo behaviors of neutrophils. RIP1-Tag5 spontaneous pancreatic cancer model was used to study the function of tumor blood vessels. CCM2ECKO (deletion of CCM2 in endothelial cells) mice were employed to establish the cerebral cavernous malformation (CCM) animal model. Micro-computed tomography (micro-CT) was utilized to assess the CCM lesion. Müller cell-knockout mouse model was used to study the progression of dia?betic retinopathy. Vascular permeability in this model was assessed by fluorescein angiography. RESULTS The interac?tions between neutrophils and endothelial cells involve a series of complicated processes, including rolling, adhesion, intraluminal crawling and transmigration, which were all monitored in vivo by two-photon laser scanning fluorescence microscopy in a real-time manner. Dynamic flow system was capable of recapitulating the biological behaviors of neutro?phils in vitro. Tumor vascular function in particular vascular perfusion could be assessed in the RIP1-Tag5 spontaneous pancreatic cancer model. In terms of CCM studies, specific deletion of CCM2 in endothelial cells resulted in the initiation of CCM lesion. The size and number of CCM lesions could be visualized and quantified by micro-CT. Furthermore, the Müller cell-knockout mouse model was able to precisely reflect the clinical symptoms of diabetic retinopathy. Vascular leak could be monitored at different time points using fluorescein angiography. CONCLUSION An array of high technol?ogies and animal models can be used in investigating the occurrence and progression of multiple vascular leak-driven diseases. The pre-clinical and clinical studies of TCM for promoting blood circulation and removing blood stasis provide fundamental support for the application of the above-mentioned platforms, with the purpose of uncovering the scientific basis of TCM for promoting blood circulation and removing blood stasis.

14.
Chinese Journal of Schistosomiasis Control ; (6): 177-187, 2021.
Article in Chinese | WPRIM | ID: wpr-876710

ABSTRACT

Objective To explore the dynamic expression of programmed cell death-1 (PD-1) and its ligand PD-L1 at the maternal-fetal interface of mice post-infection with Toxoplasma gondii at early pregnancy and examine its interaction with interferon-γ (IFN-γ). Methods A total of 20 mice at day 0 of pregnancy were randomly assigned into 4 groups, including the 12-day pregnancy control group (12 dpn group), 12-day pregnancy and infection group (12 dpi group), 18-day pregnancy control group (18 dpn group) and 18-day pregnancy and infection group (18 dpi group), respectively. On the 6th day of the pregnancy, mice in the 12 dpi and 18 dpi groups were injected intraperitoneally with 150 tachyzoites of the T. gondii PRU strain, while mice in the 12 dpn and 18 dpn groups were injected with the same volume of PBS. All mice in the four groups were sacrificed on 12th and 18th day of the pregnancy, and the number of placenta and fetus was counted and the weight of placenta and fetus was measured. Then, the placental and uterine tissues of the pregnant mice in each group were sampled for pathological examinations. The mRNA expression of PD-1, PD-L1, T. gondii surface antigen SAG-1 and IFN-γ genes was quantified using a quantitative real-time PCR (qPCR) assay, and the correlation between PD-1 and IFN-γ expression was examined. In addition, the 12 dpn group, 12 dpi group, 18 dpn group, 18 dpi group, PBS negative control of the 12 pdi group and PBS negative control of the 18 dpi group were assigned, and the PD-1 expression was determined in the uterine and placenta tissues of the pregnant mice. Results Adverse pregnant outcomes were seen in mice in the 12 dpi and 18 dpi groups, including placental dysplasia and fetal maldevelopment, and the placental weights and fetal body weights were significantly lower in mice in the 12 dpi and 18 dpi groups than those in the 12 dpn and 18 dpn groups (t = 5.52, 11.44, 12.63 and 11.67, all P < 0.01). The histopathological examinations showed that the decidua and junctional regions of the placental tissues were loosely connected in the 12 dpi and 18 dpi groups, and a large number of inflammatory cells infiltration and congestion were seen in the placental and uterine tissues. qPCR assay detected significant differences in PD-1, PD-L1, IFN-γ and SAG-1 expression in the placental and uterine tissues among the 12 dpn, 12 dpi, 18 dpn and 18 dpi groups (F = 22.48, 51.23, 9.61, 47.49, 16.08, 21.52, 28.66 and 238.90, all P < 0.05), and the PD-1, PD - L1, IFN - γ and SAG - 1 expression was all significantly higher in the placental and uterine tissues of mice in the 12 dpi group than in the 12 dpn group (all P values < 0.05). The PD-1 and PD-L1 expression was significantly lower in the placental tissues of mice in the 18 dpi group than in the 18 dpn group (all P values < 0.05), and the IFN-γ and SAG-1 expression was significantly higher in the placental and uterine tissues of mice in the 18 dpi group than in the 18 dpn group (all P values < 0.05), while the PD-1 and PD-L1 expression was significantly lower in the placental and uterine tissues of mice in the 18 dpi group than in the 12 dpi group (all P values < 0.05). Immunohistochemical staining showed PD-1 expression in the inflammatory cells of the placental tissues of mice in the 12 dpi group, and no apparent PD-1 expression in the 18 dpi group, while strongly positive PD-1 expression was found in the uterine epithelium of mice in the 12 dpi group, and mildly strong expression was in the 18 dpi group. In addition, the IFN-γ mRNA expression was positively correlated with the PD-1 mRNA expression in placental (rs = 0.99, P < 0.01) and uterine tissues of mice in the 12 dpi group (rs = 0.97, P < 0.01) and in placental (rs = 0.82, P < 0.01) and uterine tissues of mice in the 18 dpi group (rs = 0.81, P < 0.01). Conclusions Following T. gondii infection at early pregnancy, the PD-1 and PD-L1 expression shows a remarkable rise at middle pregnancy and a reduction at late pregnancy in placental and uterine tissues of mice, which appears the same tendency with IFN-γ expression during the same time period, and PD-1 expression positively correlates with IFN-γ expression. The dynamic expression of PD-1 and PD-L1 on the maternal-fetal interface of mice may be mutually mediated by IFN-γ induced by T. gondii infection.

15.
Chinese Journal of Schistosomiasis Control ; (6): 28-34, 2021.
Article in Chinese | WPRIM | ID: wpr-873744

ABSTRACT

Objective To explore the mechanism of the intestinal barrier damage caused by Blastocystis hominis infections in rats. Methods Thirty SD rats were randomly divided into the control group, and the 1-, 3-, 6- and 9-week-infection groups, of 6 rats in each group. Rats in each infection group were orally infected with B. hominis trophozoites at a density of 2 × 108 parasites per rat, and the control group was given an equal volume of phosphate buffered saline solution. The 7-hour urine samples were collected 1, 3, 6 and 9 weeks post-infection for the measurement of the intestinal permeability. Then, rats were sacrificed using the cervical dislocation method, and the cecum specimens were collected for the detection of the intestinal epithelial cell permeability. The expression of tight junction-related Occludin and Claudin - 1 genes and apoptosis-related Bcl - 2 and Bax genes was quantified in cecum epithelial cells using the real-time fluorescent quantitative PCR (qPCR) assay, and cell apoptosis was detected in the rat cecum using the TdT-mediated dUTP nick-end labeling (TUNEL) assay. Results The median urinary lactolose to mannitol ratios were 0.29, 0.72, 0.44, 0.46 and 0.38 in the control group, and the 1-, 3-, 6- and 9-week-infection groups, respectively, and the difference was statistically significant (H = 12.09, P < 0.05). B. hominis invasion and epithelial injury were observed in intestinal epithelial cells of rats infected with B. hominis, and transmission electron microscopy displayed the destruction of tight junctions between intestinal epithelial cells. The relative expression of Occludin, Claudin-1, Bcl-2 and Bax genes was 1.04, 0.62, 0.71, 0.68 and 0.96; 1.03, 0.61, 0.63, 0.76 and 0.86; 1.08, 0.70, 0.75, 0.74 and 1.03; and 1.00, 1.57, 1.33, 1.35 and 1.10 in the control group and the 1-, 3-, 6- and 9-week-infection groups, respectively, and all differences were statistically significant (F = 2.86, 2.85, 3.37 and 4.45, all P values < 0.05). The median number of positive staining cells were 1.00, 13.00, 9.00, 3.50 and 1.00 in rat cecum specimens in the control group, and the 1-, 3-, 6- and 9-week-infection groups, respectively, and the difference was statistically significant (H = 22.95, P < 0.01). Conclusion B. hominis infection may cause an increase in the rat intestinal permeability through triggering the apoptosis of intestinal epithelial cells to destroy the tight junction between intestinal epithelial cells, thereby destroying the intestinal barrier function.

16.
Acta Pharmaceutica Sinica ; (12): 1238-1245, 2021.
Article in Chinese | WPRIM | ID: wpr-887085

ABSTRACT

Wnt/β-catenin signaling pathway plays an important role in the proliferation, growth, invasion, and metastasis of human cancers. Moreover, β-catenin/T-cell factor 4 (TCF4) interaction regulates the transcription of the key oncogenes in Wnt/β-catenin signaling pathway. Therefore, β-catenin/TCF4 interaction would be a promising therapeutic target for the development of highly selective anticancer agents. At present, most ongoing small-molecule inhibitors targeting β-catenin/TCF4 interaction, including PKF222-815, iCRT3/5/14, LF3, and sanguinarine, have been developed in preclinical studies for human cancer therapeutics. In this review, we summarized the research advances of up-to date inhibitors targeting β-catenin/TCF4 interaction, including the molecular structure and cellular functions of β-catenin in canonical Wnt signaling pathway. This review holds a hopeful avenue for the development of novel and highly selective Wnt inhibitors targeting β-catenin/TCF4 interaction for future anticancer strategy.

17.
Chinese Journal of Practical Nursing ; (36): 1230-1234, 2021.
Article in Chinese | WPRIM | ID: wpr-883138

ABSTRACT

Objective:To summarize the nursing experience of 7 cases of "zero blood transfusion" type A acute aortic dissection during the perioperative period.Methods:Preoperative risk assessment, control of heart rate, blood pressure, analgesia and sedation to avoid dissection;fully keep warm during operation and recover blood from operation field;after operation, avoid heart rate and blood pressure fluctuations to reduce oozing, monitor coagulation indicators, observe the amount and characteristics of drainage fluid, ensure the safety of anticoagulation during Renal replacement therapy, and avoid blood waste.Results:The 7 patients all transitioned to the operation smoothly. Intraoperative and postoperative infusion of pre-storage and recovery autologous blood of 200-1 200 ml, no allogeneic blood transfusion. One patient had a lot of drainage after surgery. The drainage volume was 1 450 ml on the day and the first day. He was given autologous blood infusion combined with hemostatic drugs, and the hemoglobin could be maintained above 80 g/L; 2 patients complicated with hypoxemia, were sequential High-flow oxygen; 2 patients with acute kidney injury underwent continuous renal replacement therapy without unplanned dismissal. All 7 patients recovered and were discharged after active treatment.Conclusions:For patients with type A acute aortic dissection surgery, through careful blood protection care, you can reduce dependence on allogeneic blood.

18.
Chinese Journal of Surgery ; (12): 110-113, 2020.
Article in Chinese | WPRIM | ID: wpr-787668

ABSTRACT

To examine the effect of VAE and open surgery on the postoperativelocal recurrence of benign phyllodes tumors of breast and to investigate the clinical efficacy of VAE in the treatment of benign phyllodes tumors. The clinical data of 128 patients with benign phyllodes tumors of breast admitted to the Guangdong Women and Children Hospital from January 2013 to January 2018 were retrospectively analyzed. All patients were female, aged (37.7±9.1) years (range: 16 to 56 years). Eighty patients underwent ultrasound-guided VAE (minimally invasive group) and 48 patients underwent open surgery (open group). The -test, χ(2) test or Fisher exact probability method were used to compare the clinical characteristics of the two groups of patients. Logistic regression was used to analyze the prognostic factors of postoperative local recurrence. The maximum diameter of tumor in the minimally invasive group was smaller than that in the open group ((20.6±7.4) mm . (42.0±2.0) mm, -7.173, 0.000). The follow-up time was (36.4±1.8) months (range: 12 to 71 months). There were 7 cases of local recurrences during the follow-up period. The local recurrence rates in the minimally invasive and open groups were 5.0% (4/80) and 6.3% (3/48). The results of multivariate analysis showed that the maximum tumor diameter of 25 mm was an independent prognosis factor for postoperativelocal recurrence (0.122, 95: 0.016 to 0.901, 0.039). While surgical procedure, age, menopausal status and history of fibroadenomas in the ipsilateral breast is not an independent prognostic factor for postoperative local recurrence. In the minimally invasive surgery group, the local recurrence rates were 2.9% (2/69) and 2/11 in patients with tumor maximum diameters<25 mm and ≥25 mm, respectively. Local recurrence of breast benign phyllodes tumors is closely related to the tumor size. For patients with tumor diameter25 mm, the postoperative local recurrence rate of VAE is low, which can be used in clinical practice. Intraoperative complete resection to achieve a negative surgical margin should be guaranteed to avoid local recurrence.

19.
Acta Pharmaceutica Sinica ; (12): 884-891, 2020.
Article in Chinese | WPRIM | ID: wpr-821691

ABSTRACT

To develop a fluorescence polarization (FP)-based high-throughput screening (HTS) assay to identify novel small-molecule antagonists targeting β-catenin/TCF4 (T-cell factor 4) interaction, recombinant human β-catenin was expressed in Escherichia coli Rosetta (DE3) cells and purified by HisTrapTM column. The bioactivity of purified β-catenin was further analyzed by enzyme-linked immunosorbent assay (ELISA). According to FP principle, the β-catenin/TCF4 binding model was performed, and fluorescence isothiocyanate (FITC) labeled TCF4 peptide (FITC-TCF4) served as the molecular probe of adaptor for binding to β-catenin. The FITC-TCF4 and β-catenin working concentration were optimized, and the binding conditions (complex stability and dimethylsulfoxide (DMSO) tolerance) have been investigated yet for further hits screening. The results showed that recombinant human β-catenin was successfully expressed and purified β-catenin exhibited favorable bioactivity in ELISA binding assay. Subsequently, the FP-based HTS assay was performed using 20 nmol·L-1 FITC-TCF4 and 100 nmol·L-1 β-catenin. Under these optimized conditions, a high Z´factor of 0.88 was achieved in a 384-well format and this FP-based HTS assay was very stable with regard to DMSO. Through screening of a natural-based product library (NBPL) using the established FP-based HTS assay, three hits (sanguinarine, chelerythrine, and compound S720) were identified as potential β-catenin/TCF4 interaction antagonists. Taken together, we have successfully developed a simple, robust and reliable FP-based HTS assay for screening of novel antagonists targeting β-catenin/TCF4 interaction.

20.
West China Journal of Stomatology ; (6): 42-47, 2019.
Article in Chinese | WPRIM | ID: wpr-772702

ABSTRACT

OBJECTIVE@#This study aims to explore the influence of three-wall osseous defects on periodontal ligament stress under normal occlusal forces.@*METHODS@#A finite element model for mandibular total dentition, periodontal ligament and alveolar bone was created based on cone beam computed tomography (CBCT) DICOM images. Mesial or distal proximal three-wall osseous defects at varying depths (namely, 1/3, 2/3 and 3/3 of the root) were simulated by modifying the elastic modulus of elements within the defects area. Occlusal forces with an angle of 45° to the long axis of the tooth were applied to the finite element model. In addition, the equivalent stresses of the periodontal ligament were analysed.@*RESULTS@#In the case of no bone defect, the mean value of the periodontal ligament equivalent stress of 14 teeth was 5.71 MPa. The equivalent stresses of the periodontal ligament at different depths (namely, 1/3, 2/3 and 3/3 of the root) were 6.61, 7.14 and 7.42 MPa, respectively. With increasing depth of the osseous defects, stress on the periodontal ligament increased considerably, and the initial stress increment was greater than that of a later stage. Periodontal ligament stresses with mesial proximal three-wall osseous defects (at depths of 1/3, 2/3 and 3/3 of the root) were 6.62, 7.19 and 7.51 MPa respectively. Periodontal ligament stresses with distal proximal three-wall osseous defects (at depths of 1/3, 2/3 and 3/3 of the root) were 6.60, 7.10 and 7.33 MPa, respectively. For three-wall osseous defects located in the mesial surface and distal surface, a significant difference in periodontal ligament stress was lacking. In the case of the same absorption depth, the size relationship of periodontal ligament stress was in the following order: premolars>molars>incisors>canines.@*CONCLUSIONS@#Shallow three-wall osseous defects will likely cause a notable loss in strength of the periodontal ligament. Therefore, teeth with three-wall osseous defects should become the focus of clinical research. Treatment for these teeth should be administered as early as possible.


Subject(s)
Alveolar Process , Dental Stress Analysis , Finite Element Analysis , Imaging, Three-Dimensional , Incisor , Periodontal Ligament , Stress, Mechanical
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