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1.
Article in Chinese | WPRIM | ID: wpr-940687

ABSTRACT

ObjectiveTo explore the effect of Xiao Xianxiongtang (XXXT) on the transforming growth factor (TGF)-β1-induced invasion, metastasis, and epithelial-mesenchymal transition (EMT) of gastric cancer MGC-803 cells and the underlying mechanism. MethodThe molecular docking between XXXT and nuclear factor of activated T cells (NFAT) was performed by CB-DOCK (http://clab.labshare.cn/cb-dock/). The invasion and metastasis model of MGC-803 cells was established with 10 μg·L-1 TGF-β1. MGC-803 cells were classified into blank group, model group, 0.1 g·L-1 XXXT group, 0.2 g·L-1 XXXT group, and 0.4 g·L-1 XXXT group. For further clarifying the key role of Wnt5a/Ca2+/NFAT signaling pathway in the inhibition of XXXT on gastric cancer, MGC-803 cells were transfected with Wnt5a overexpression plasmid, and then the cells were classified into blank plasmid group, Wnt5a-OE group, blank plasmid + XXXT (0.4 g·L-1) group, and Wnt5a-OE + XXXT (0.4 g·L-1) group. Cell viability was determined by cell counting kit-8 (CCK-8) assay, cell invasion and migration ability by Transwell invasion assay and wound healing assay, expression of EMT-related proteins (E-cadherin, N-cadherin, Vimentin, Snail) and Wnt5a/Ca2+/NFAT signaling pathway-related key proteins [Wnt5a, calcineurin (CaN), NFAT1, and p-NFAT1] by Western blot, and changes in intracellular Ca2+ concentration by immunofluorescence assay. ResultMolecular docking suggested that XXXT acted on Wnt5a/Ca2+/NFAT signaling pathway. XXXT (0.1, 0.2, 0.4 g·L-1) significantly promoted the loss of MGC-803 cell viability (P<0.05,P<0.01). It inhibited cells from invading the transwell lower chamber and slowed down the healing of cell wounds in a dose-dependent manner (P<0.05, P<0.01). Moreover, it promoted the expression of E-cadherin while suppressed the expression of N-cadherin, Vimentin, and Snail (P<0.05, P<0.01). Further experiments showed that XXXT could inhibit the expression of Wnt5a, CaN, NFAT1, and p-NFAT1, and reduce the nuclear expression of NFAT1 and the transcription activity mediated by NFAT1, so as to reduce the cellular Ca2+ concentration (P<0.05, P<0.01). XXXT can reverse the effect of Wnt5a (P<0.05, P<0.01). ConclusionXXXT can attenuate the invasion, metastasis, and EMT of MGC-803 cells via the Wnt5a/Ca2+/NFAT pathway, thereby weakening the tumor-promoting effect of TGF-β1. In summary, XXXT may exert therapeutic effect on gastric cancer by regulating the invasion, metastasis, and EMT of gastric cancer cells.

2.
Article in Chinese | WPRIM | ID: wpr-940532

ABSTRACT

ObjectiveTo explore the guidance value of “treatment of disease in accordance with three conditions” theory in the prevention and treatment of corona virus disease 2019(COVID-19) based on the differences of syndromes and traditional Chinese medicine(TCM) treatments in COVID-19 patients from Xingtai Hospital of Chinese Medicine of Hebei province and Ruili Hospital of Chinese Medicine and Dai Medicine of Yunnan province and discuss its significance in the prevention and treatment of the unexpected acute infectious diseases. MethodDemographics data and clinical characteristics of COVID-19 patients from the two hospitals were collected retrospectively and analyzed by SPSS 18.0. The information on formulas was obtained from the hospital information system (HIS) of the two hospitals and analyzed by the big data intelligent processing and knowledge service system of Guangdong Hospital of Chinese Medicine for frequency statistics and association rules analysis. Heat map-hierarchical clustering analysis was used to explore the correlation between clinical characteristics and formulas. ResultA total of 175 patients with COVID-19 were included in this study. The 70 patients in Xingtai,dominated by young and middle-aged males,had clinical symptoms of fever, abnormal sweating,and fatigue. The main pathogenesis is stagnant cold-dampness in the exterior and impaired yin by depressed heat, with manifest cold, dampness, and deficiency syndromes. The therapeutic methods highlight relieving exterior syndrome and resolving dampness, accompanied by draining depressed heat. The core Chinese medicines used are Poria,Armeniacae Semen Amarum,Gypsum Fibrosum,Citri Reticulatae Pericarpium,and Pogostemonis Herba. By contrast,the 105 patients in Ruili, dominated by young females, had atypical clinical symptoms, and most of them were asymptomatic patients or mild cases. The main pathogenesis is dampness obstructing the lung and the stomach, with obvious dampness and heat syndromes. The therapeutic methods are mainly invigorating the spleen, resolving dampness, and dispersing Qi with light drugs. The core Chinese medicines used are Poria,Atractylodis Macrocephalae Rhizoma,Glycyrrhizae Radix et Rhizoma,Coicis Semen,Platycodonis Radix,Lonicerae Japonicae Flos, and Pogostemonis Herba. ConclusionThe differences in clinical characteristics, TCM syndromes, and medication of COVID-19 patients from the two places may result from different regions,population characteristics, and the time point of the COVID-19 outbreak. The “treatment of disease in accordance with three conditions” theory can help to understand the internal correlation and guide the treatments.

3.
Article in Chinese | WPRIM | ID: wpr-940516

ABSTRACT

ObjectiveTo observe the inhibitory effect of modified Xiao Xianxiongtang on epithelial-mesenchymal transition (EMT) of human gastric cancer MGC803 cells and its relationship with secretory glycoprotein Wnt/β-catenin pathway. MethodThe BALB/c nude mice were implanted with human gastric cancer MGC803 cell suspension in the heterotopic subcutaneous position for inducing tumor. After successful modeling, they were randomly divided into the model group, low-, medium-, and high-dose (16.0,32.0,and 64.0 g·kg-1) groups of modified Xiao Xianxiongtang, and capecitabine (400 mg·kg-1) group, with eight mice in each group, and gavaged with the corresponding drugs, once per day, for 28 consecutive days. Those in the capecitabine group received one-week discontinuation after every two weeks of treatment. The general state and body weight of the nude mice were observed, and the transplanted tumor volume was measured. After being killed, they were weighed and the tumor inhibition rate was calculated. Hematoxylin-eosin (HE) staining was carried out for observing the pathological changes in transplanted tumor tissues. The gene and protein expression levels of Wnt1 and β-catenin were detected by real-time fluorescence quantitative polymerase chain reaction (Real-time PCR) and Western blot, followed by the determination of matrix metalloproteinase-9 (MMP-9), vascular endothelial growth factor (VEGF), N-cadherin, E-cadherin, Vimentin, and Snail protein expression by Western blot. The expression levels of cyclooxygenase 2 (COX2) and prostaglandin E2 (PGE2) were detected by enzyme-linked immunosorbent assay (ELISA). ResultIt was found that the transplanted tumor in each group showed different growth trends with time, with the most obvious growth observed in the model group. Compared with the model group, the low-, medium-, and high-dose modified Xiao Xianxiongtang groups exhibited reduced tumor volume and slowed growth to varying degrees over time. After medication for days 7,14,21,and 28, the tumor volumes in the low- and high-dose modified Xiao Xianxiongtang groups and capecitabine group declined (P<0.05, P<0.01), and that in the medium-dose Xiao Xianxiongtang group was also remarkably reduced after medication for days 14,21,and 28 (P<0.01). Compared with the model group, the high-dose modified Xiao Xianxiongtang group and capecitabine group showed a significant reduction in the relative tumor volume after treatment for days 7,14,21,28 (P<0.01), and the low- and medium-dose modified Xiao Xianxiongtang groups also presented with decreased relative tumor volume after treatment for days 14,21,28 (P<0.05, P<0.01). Compared with the model group, the modified Xiao Xianxiongtang at low, medium, and high doses and capecitabine all increased the tumor inhibition rate to varying degrees (P<0.01), down-regulated the mRNA and protein expression levels of Wnt1 and β-catenin in tumor tissue (P<0.05, P<0.01) and protein expression levels of MMP-9, VEGF, N-cadherin, Vimentin, and Snail (P<0.05, P<0.01), up-regulated E-cadherin protein expression (P<0.05, P<0.01), and reduced COX2 and PGE2 contents (P<0.05, P<0.01). ConclusionModified Xiao Xianxiongtang inhibits the EMT of human gastric cancer MGC803 cell-transplanted tumor, which may be related to Wnt/β-catenin pathway.

4.
Article in Chinese | WPRIM | ID: wpr-878923

ABSTRACT

This study aimed to assess whether chrysin(ChR) can inhibit epithelial-mesenchymal transition(EMT) of type Ⅱ alveolar epithelial cell and produce anti-pulmonary fibrosis effect by regulating the NF-κB/Twist 1 signaling pathway. Sixty rats were randomly divided into the control group, the bleomycin(BLC) group, BLC+ChR(50 mg·kg~(-1)) group and BLC+ChR(100 mg·kg~(-1)) group, with 15 rats in each group. The pulmonary fibrosis model was induced by intratracheal injection of BLC(7 500 U·kg~(-1)). Rats were orally administered with different doses of ChR after BLC injection for 28 days. The cells were divided into control group, TGF-β1 group(5 ng·mL~(-1)), and TGF-β1+ChR(1, 10, 100 μmol·L~(-1)) groups. The type Ⅱ alveolar epithelial cells were treated with TGF-β1 for 24 h, and then treated with TGF-β1 for 48 h in the presence or absence of different doses of ChR(1, 10 and 100 μmol·L~(-1)). The morphological changes and collagen deposition in lung tissues were analyzed by HE staining, Masson staining and immunohistochemistry. The mRNA and protein expression levels of collagen Ⅰ, E-cadherin, zonula occludens-1(ZO-1), vimentin, alpha smooth muscle actin(α-SMA), inhibitor of nuclear factor kappa B alpha(IκBα), nuclear factor-kappa B p65(NF-κB p65), phospho-NF-κB p65(p-p65) and Twist 1 in lung tissues and cells were detected by qPCR and Western blot, respectively. The animal experiment results showed that as compared with the BLC group, after administration of ChR for 28 days, bleomycin-induced pulmonary fibrosis in rats was significantly relieved, collagen Ⅰ expression in lung tissues was significantly reduced(P<0.05 or P<0.01), and EMT of alveolar epithelial cells was obviously inhibited [the expression levels of E-cadherin and ZO-1 were increased and the expression levels of vimentin and α-SMA were decreased(P<0.05 or P<0.01)], concomitantly with significantly reduced IκBα and p65 phosphorylation level in cytoplasm and decreased NF-κB p65 and Twist 1 expression in nucleus(P<0.05 or P<0.01). The cell experiment results showed that different doses of ChR(1, 10 and 100 μmol·L~(-1)) significantly reduced TGF-β1-induced collagen Ⅰ expression(P<0.05 or P<0.01), significantly inhibited EMT of type Ⅱ alveolar epithelial cells[the expression levels of E-cadherin and ZO-1 were increased and the expression levels of vimentin and α-SMA were decreased(P<0.05 or P<0.01)], and inhibited IκBα and p65 phosphorylation in cytoplasm and down-regulated NF-κB p65 and Twist 1 expression in nucleus induced by TGF-β1(P<0.05 or P<0.01). The results suggest that ChR can reverse EMT of type Ⅱ alveolar epithelial cell and alleviate pulmonary fibrosis in rats, and its mechanism may be associated with reducing IκBα phosphorylation and inhibiting NF-κB p65 phosphorylation and nuclear transfer, thus down-regulating Twist 1 expression.


Subject(s)
Alveolar Epithelial Cells/metabolism , Animals , Epithelial-Mesenchymal Transition , Flavonoids , NF-kappa B/metabolism , Rats , Signal Transduction , Transforming Growth Factor beta1/genetics
5.
Article in Chinese | WPRIM | ID: wpr-906538

ABSTRACT

Hydroxytyrosol as one of natural anti-oxidants,extracted from the fruits and leaves of Olea europaea,is a natural polyphenol compound in the form of esters. Recently,considerable studies showed that hydroxytyrosol demonstrated intrinsic biological activity for metabolic syndromes, cardiovascular- and neurodegenerative-related diseases,and it was revealed to play the roles in the anti-activities of cancerous,inflammatory as well as depressing issues. In addition,hydroxytyrosol is an oleophilic and hydrophilic compound with high bioavailability and low cellular cytotoxicity. It could be absorbed by various tissues and could easily passe through blood brain barrier. Therefore,hydroxytyrosol was introduced as one of the key subjects targeted by innovative drug development. However,it has a short half-life in vivo and non-tissue specific,which lead to its limitation in clinical application, so further in-depth studies are still needed. The authors had a literature review of hydroxytyrosol,and summarized the basic properties of its pharmacokinetic,pharmacological effects and molecular mechanisms. This article mainly focused on it’s pharmacological activity and the mechanism involved in treating damages induced by the oxidative stress,in alleviating cardiovascular diseases and in inhibition of neurodegenerative diseases. In this article, its anti-inflammatory,anti-tumor,anti-depressant effects,other biological activities,and pharmacokinetics were also briefly reviewed. The authors put forward some personal thoughts on its future research direction,hoping to provide ideas and inspirations for the vast number of researchers,and provide references for its further development,research and application.

6.
China Occupational Medicine ; (6): 46-50, 2021.
Article in Chinese | WPRIM | ID: wpr-881968

ABSTRACT

OBJECTIVE: To explore the protective effect of tea polyphenols and its mechanism in potassium dichromate(PD)-induced acute renal injury in mice. METHODS: The specific pathogen free weaned Kunming mice were divided into control group, model group and low-, middle-and high-dose tea polyphenols groups, with 12 mice in each group. Mice in the control group were given 0.9% sodium chloride solution, and mice in other four groups were given PD solution with 4.275 mg/kg body weight every morning by intragastric administration. Then, mice in the control group and model group were given 0.9% sodium chloride solution in the afternoon, while mice in the low-, middle-and high-dose tea polyphenols groups were given 0.3 mL tea polyphenols solution with a dose of 200, 400 or 600 mg/kg body weight, respectively by gavage, once a day for two consecutive weeks. The body mass of mice was weighed during the experiment. At the end of the experiment, the mice were sacrificed. The kidneys were removed and weighed. The kidney organ coefficients were calculated. The levels of urea nitrogen and creatinine in serum were determined by two-point method, the activities of catalase(CAT) and glutathione peroxidase(GSH-Px) in serum of mice were detected by colorimetry. The pathological change of kidney in mice was observed. RESULTS: The body weight of mice in the model group decreased(P<0.05), while the kidney mass, renal organ coefficient, serum levels of urea nitrogen and creatinine increased(all P<0.05), and the serum activities of CAT and GSH-Px decreased(all P<0.05) compared with the control group. The body weight of mice in the three tea polyphenols groups increased(all P<0.05), while the kidney mass, renal organ coefficient, urea nitrogen and creatinine levels in serum decreased(all P<0.05), and the activities of CAT and GSH-Px in serum increased with the increasing intervention dose of tea polyphenols(all P<0.05) compared with the model group. The change of acute renal injury was mainly caused by renal tubular injury in the model group. The pathological changes of renal tissue in the three tea polyphenols intervention groups were improved compared to that in the model group, and the improvement showed a dose-effect relationship with the intervention of tea polyphenols. CONCLUSION: Tea polyphenols have a protective effect on PD-induced acute renal injury with a dose-effect relationship. Its mechanism of action is related to the fact that tea polyphenols can reduce or reverse oxidative stress and inflammation in the kidney.

7.
Article in English | WPRIM | ID: wpr-878349

ABSTRACT

Objective@#To evaluate the safety and effectiveness of a vaccine based on latent membrane protein 2 (LMP2) modified dendritic cells (DCs) that boosts specific responses of cytotoxic T lymphocytes (CTLs) to LMP2 before and after intradermal injection in patients with nasopharyngeal carcinoma (NPC).@*Methods@#DCs were derived from peripheral blood monocytes of patients with NPC. We prepared LMP2-DCs infected by recombinant adenovirus vector expressing LMP2 (rAd-LMP2). NPC patients were immunized with 2 × 10 @*Results@#We demonstrated that DCs derived from monocytes displayed typical DC morphologies; the expression of LMP2 in the LMP2-DCs vaccine was confirmed by immunocytochemical assay. Twenty-nine patients with NPC were enrolled in this clinical trial. The LMP2-DCs vaccine was well tolerated in all of the patients. Boosted responses to LMP2 peptide sub-pools were observed in 18 of the 29 patients with NPC. The follow-up data of 29 immunized patients from April, 2010 to April 2015 indicated a five-year survival rate of 94.4% in responders and 45.5% in non-responders.@*Conclusion@#In this pilot study, we demonstrated that the LMP2-DCs vaccine is safe and effective in patients with NPC. Specific CTLs responses to LMP2 play a certain role in controlling and preventing the recurrence and metastasis of NPC, which warrants further clinical testing.


Subject(s)
Adult , Aged , Cancer Vaccines/therapeutic use , China , Dendritic Cells/immunology , Female , Humans , Immunotherapy/methods , Injections, Intradermal , Male , Middle Aged , Nasopharyngeal Carcinoma/therapy , Nasopharyngeal Neoplasms/therapy , T-Lymphocytes, Cytotoxic/immunology , Viral Matrix Proteins/therapeutic use , Young Adult
8.
Article in Chinese | WPRIM | ID: wpr-872745

ABSTRACT

Tumor is one of the diseases that seriously endanger human health, and how to treat tumor effectively is still one of the important problems in the field of medicine. At present, most of the radiotherapies and chemical drugs for cancer have serious side effect despite of an obvious efficacy. With a unique syndrome differentiation treatment system and overall concept, traditional Chinese medicine has become the key research and development object of antitumor drugs due to many advantages, such as multiple channels, multiple levels, multiple links, multiple targets and less toxicity, and could can fully mobilize the immune and epidemic prevention mechanism of the body. A large number of studies have shown that Xiao Xianxiongtang and its effective ingredients have obvious antitumor effect. Many doctors have applied Xiao Xianxiongtang and modified formulas in clinical treatment of tumors, and relevant pharmacological studies have also confirmed the effectiveness of this formula, but with a lack of systematic summary of its effective ingredients and its mechanism of action. Now, with alkaloids, ketones, sterols and phenols in Xiao Xianxiongtang as the starting point, this study mainly focuses on inhibition of tumor cell proliferation, invasion and migration, induction of tumor cell apoptosis and autophagy, inhibition of tumor cell cycle, enhancement of tumor cell sensitivity, inhibition of tumor angiogenesis and regulation of immunosuppressive tumor microenvironment from two ways to sort out composition, function and mechanism of drugs. In this paper, effective components, main targets and mechanism of intervention in the tumor development of Xiao Xianxiongtang were reviewed, in order to provide a new idea for subsequent antitumor research and development of this prescription.

9.
Article in Chinese | WPRIM | ID: wpr-871120

ABSTRACT

Objective:To evaluate the monitoring value of amplitude-integrated electroencephalography (aEEG) in brain injury among neonates with severe hyperbilirubinemia.Methods:This study retrospectively recruited 223 full-term infants with severe hyperbilirubinemia who underwent aEEG in the Department of Neonatology of Guangzhou Women and Children Medical Center from October 2018 to June 2020. Differences in serum bilirubin level and the incidence of acute bilirubin encephalopathy (ABE) between the normal group ( n=180) and abnormal aEEG group ( n=43) were compared. The monitoring value of aEEG in ABE, and its association with brain stem auditory evoked potential (BAEP) and MRI were studied. Two-independent sample t-test, Mann-Whitney U test and Chi-square test were used for comparing the differences between groups. Goodman-Kruskal Gamma was used for correlation analysis. Results:The total serum bilirubin level [(536.2±154.6) vs (422.1±103.0) μmol/L, t=-5.109, P<0.001] and the incidence of ABE [62.8% (27/43) vs 9.4% (17/180), χ2=62.366, P<0.001] in the abnormal aEEG group were significantly higher than those in the normal aEEG group. The sensitivity and specificity of aEEG in the diagnosis of ABE were 61.3% and 91.1%, respectively. With the progression of ABE from warning period to spasmodic stage, more severe voltage suppression (Gamma=0.847, P=0.003), more disordered sleep-wake cycles (Gamma=0.941, P<0.001) and a more frequent epileptic discharge (Gamma=0.976, P<0.001) were observed. Out of the 223 cases, 148 underwent BAEP. The abnormal rate of aEEG in abnormal BAEP group was significantly higher than that in normal BAEP group [32.7% (33/101) vs 6.4% (3/47), χ2=12.040, P=0.001]. The incidence of abnormal voltage in severe abnormal BAEP group was significantly higher than that in mild abnormal BAEP group [20.6% (7/34) vs 2.6% (1/38), χ2=5.858, P=0.016]. The incidence of epileptic discharge in severe abnormal BAEP group was significantly higher than that in mild abnormal BAEP group [32.4% (11/34) vs 2.6% (1/38), χ2=11.413, P=0.001] and moderate abnormal BAEP group [32.4% (11/34) vs 3.5% (1/29), χ2=8.480, P=0.004]. Among the 223 cases, 108 received MRI examination. The incidence of epileptic discharge in the cases with bilirubin brain injury image was significantly higher than those with normal MRI images [28.6% (10/35) vs 2.6% (1/39), χ2=9.864, P=0.002] and those with other abnormal images [28.6% (10/35) vs 2.9% (1/34), χ2=8.451, P=0.004]. Conclusions:aEEG monitoring is helpful in the diagnosis of ABE and can reflect disease severity. Severe hyperbilirubinemia-induced brain injury in neonates mainly manifests as increased and more frequent epileptic discharge on aEEG. There is a correlation between aEEG monitoring with BAEP and MRI findings.

10.
Article in Chinese | WPRIM | ID: wpr-843241

ABSTRACT

Objective: To investigate the value of serum miR-133a in early diagnosis and the assessment of 30-day incidence of cardiovascular adverse events in patients with acute myocardial infarction (AMI). Methods: Ninety patients with acute chest pain within 6 h were included, and 63 cases of AMI, 13 cases of unstable angina pectoris (UAP) and 14 cases of control (chest pain of other causes) were finally diagnosed. The levels of troponin I (cTnI), creatine kinase MB (CK-MB) and myoglobin (Mb) were measured by electrochemical fluorescence. Quantitative real-time PCR (qPCR) was used to detect the expression of miR-133a in the serum of patients immediately after admission and 24 h after percutaneous coronary intervention (PCI). The Gensini score of patients who underwent coronary angiography was recorded. The incidence of cardiovascular adverse events was observed within 30 days. Spearman correlation analysis, multivariate Logistic regression analysis and receiver operator characteristic curve (ROC curve) were used to analyze the corresponding data. Results: The expression of miR-133a in the AMI group was significantly higher than that in the UAP group and the control group (both P<0.05). Spearman correlation analysis showed that the expression of miR-133a was positively correlated with cTnI, CK-MB, MB level and Gensini scores (all P<0.05). Multivariate Logistic regression analysis showed that miR-133a and the history of coronary heart disease were independent risk factors for AMI. ROC curve showed that the area under the curve (AUC) of miR-133a in the diagnosis of AMI was 0.816 (95% CI 0.716-0.917), and the AUC of 30 days cardiovascular adverse event was 0.700 (95% CI 0.535-0.865). Conclusion: The expression of miR-133a in patients with AMI is significantly increased, which is expected to be a biomarker for early diagnosis of AMI. The expression level of miR-133a in serum may be related to the severity of coronary artery disease and short-term prognosis.

11.
Article in Chinese | WPRIM | ID: wpr-827995

ABSTRACT

This project is to study the metabolites of Laportea bulbifera extract in rat feces. After the SD rats were gavaged with the extract(136 g·kg~(-1), according to the crude drug dose), the metabolites in their feces were detected by UHPLC-Q-TOF-MS~E technique, and the obtained mass spectrometry data was combined with UNIFI software for prediction. The prototype components and metabolites in rat feces were identified with reference materials and related literature. A total of 43 metabolites were identified(including 8 prototype components and 35 metabolites). The metabolic pathways mainly include monocaffeoylquinic acid(hydrogenation reduction, ring-opening cracking, sulfation, hydroxylation, glucuronidation), quercetin(O-C2 bond ring-opening cleavage, C2-C3 double bond reduction, rutin carbonylation) and so on. The metabolites and metabolic process of L. bulbifera extract in rat feces were clarified, which provided a basis for the study of the active substances and its mechanism of action.


Subject(s)
Administration, Oral , Animals , Chromatography, High Pressure Liquid , Feces , Plant Extracts , Rats , Rats, Sprague-Dawley , Urticaceae
12.
Article in Chinese | WPRIM | ID: wpr-827814

ABSTRACT

To observe whether the mechanism of small dose capsaicin (Cap) against pulmonary fibrosis in mouse is mediated by agitating transient receptor potential vanilloid 1 (TRPV1). Methods: A total of 60 BALB/c mice were randomly divided into control (CON) group, bleomycin (BLM)group, Cap (0.5, 1,2 mg/kg) groups and Cap (2 mg/kg) plus SB-452533 (2.5 mg/kg) group. C57BL/6 mice were intratracheally injected with 3.5 mg/kg BLM to induce pulmonary fibrosis model. Animals for drugs treatment received daily drug via subcutaneous injection for 21 days. The morphological changes and collagen deposition in lung tissues were analysed by HE staining, Masson staining and immunohistochemistry. The concentration of calcitonin gene-related peptide (CGRP) in plasma was determined by ELISA. The mRNA and (or) proteins levels of α-CGRP, β-CGRP, collagen I, collagen III, E-Cadherin, zonula occludens-1 (ZO-1), vimentin, alpha smooth muscle actin (α-SMA), TRPV1, p-ERK1/2 and eukaryotic initiation factor 3a (eIF3a) were detected by qPCR and (or) Western blot. Compared with the BLM group, small dose Cap significantly reduced bleomycin-induced pulmonary fibrosis in mice and obviously reversed alveolar epithelial cells epithelial-mesenchymal transition (EMT) (the expression of E-cadherin and ZO-1 were increased(P<0.05 or P<0.01)and the expression of α-SMA and Vimentin were decreased (P<0.05 or P<0.01) after drugs treatment for 21 day, concomitantly with the increase the expressions of TRPV1 and CGRP (P<0.05 or P<0.01), and inhibiting ERK1/2 phosphorylation and eIF3a expression (P<0.05 or P<0.01). These effects of small dose Cap were abolished in the presence of TRPV1 receptor antagonist SB-452533. The results suggest that small dose Cap can reverse alveolar epithelial cells EMT and alleviate bleomycin-induced pulmonary fibrosis in mice by inhibiting ERK1/2/eIF3asignaling pathway, which is related to agitating TRPV1 receptor and releasing of CGRP.

13.
China Pharmacy ; (12): 1683-1690, 2020.
Article in Chinese | WPRIM | ID: wpr-823043

ABSTRACT

OBJECTIVE:To explore the metabolic charact eristics of Miao medicine Laportea bulbifera extract in isolated human intestinal flora. METHODS :L. bulbifera was extracted with 70% ethanol reflux extraction. After concentration,extraction with n-butanol and drying ,L. bulbifera extract was obtained. Taking 0.05 g/mL L. bulbifera extract 1 mL mixed with isolated human intestinal flora fluid 10 mL and cultured for 36 h in anaerobic environment (setting up blank control without drugs or human intestinal bacterial solution ),so as to simulate the metabolic process of the extract in human intestine. The metabolites were detected by UPLC-Q-TOF/MS. The determination was performed on Agilent Eclipse Plus C 18 RRHD column with mobile phase consisted of 0.01% formic acid water solution- 0.01% formic acid acetonitrile solution (gradient eluetion )at the flow rate of 0.25 mL/min. The column temperature was set at 40 ℃,and the sample size was 1 µL. ESI detection was adopted and scanned by negative ion mode (ESI-);the capillary voltage was 4.5 kV,the ion source temperature was 120 ℃,the collision energy was 15-32 V,and the scanning range was m/z 50-1 000. The “Strip”module of MassLynx V 4.1 software was used to analyze the differential chromatograms between the reaction solution and the blank control of L. bulbifera extract. Mass spectrum data and UNIFI so ftware were used to predict relative molecular weight and formula ;based on the information of substance control and related literature reports , the structure and biotransformation pathway of L. bulbifera metabolites in isolated human intestinal flora were predicted and analyzed. RESULTS & CONCLUSIONS : A total of 3 prototype : products(rutin,quercetin,kaempferol-3-O-rutinoside)and 22metabolites (mainly the metabolites of quercetin ,mono- caffeoylquinic acid ,isoquercitrin,etc.) were detected after metabolized in isolated human intestinal flora. Itsbiotransformation pathway is phase Ⅰ reaction,which mainly consisted of reduction ,oxidation and hydrolysis.

14.
Article in Chinese | WPRIM | ID: wpr-775119

ABSTRACT

OBJECTIVE@#To construct the recombinant adenoviral vector carrying the rat interleukin-10 (rIL-10) gene, and to investigate whether it is stably expressed in bone marrow mesenchymal stem cells.@*METHODS@#The rIL-10 gene was amplified by PCR from template rIL-10 cDNA, and the recovered 656 bp rIL-10 DNA fragment was cloned into pcDNA3.1 to construct pcDNA3.1-IL-10. Then HEK293 cells were transfected with pcDNA3.1-IL-10 and adenoviral vector for homologous recombination, and sequencing and PCR were used to evaluate whether recombination was successful. HEK293 cells were lysed by repeated freeze-thaw cycles, and bone marrow mesenchymal stem cells were infected with the virus solution containing the rIL-10 gene. Western blot was used to measure the expression of rIL-10 in bone marrow mesenchymal stem cells.@*RESULTS@#Sequencing and PCR verified that the rIL-10 adenoviral vector was successfully constructed, with a virus titer of 4×10 PFU/mL. The expression of IL-10 was detected after bone marrow mesenchymal stem cells were infected by the virus solution containing the rIL-10 gene.@*CONCLUSIONS@#The constructed rIL-10 recombinant adenovirus can mediate the stable expression of rIL-10 gene in bone marrow mesenchymal stem cells, which provides a basis for gene transplantation therapy of inflammatory bowel disease.


Subject(s)
Adenoviridae , Animals , Bone Marrow Cells , Genetic Vectors , HEK293 Cells , Humans , Interleukin-10 , Mesenchymal Stem Cells , Rats , Transfection
15.
Article in Chinese | WPRIM | ID: wpr-802521

ABSTRACT

Objective: To explore the protective effect and the preliminary mechanism of Dihuang Yinzi on cerebral ischemia-reperfusion injury in rats. Method: The middle cerebral artery occlusion (MCAO) model was established. Totally 90 SD rats were randomly divided into 6 groups:sham operation group, model group, nimodipine group (0.01 g·kg-1) and high, medium, low-dose Dihuang Yinzi groups (38.80, 19.40, 9.70 g·kg-1), with 20 rats in each group.The modified neurological severity score (mNSS) was assayed at the 7th, 14th, 28th days after operation, and the volume of cerebral infarction, pathological changes of brain tissue, the BrdU positive cells and mRNA levels of Notch1, Jagged1 and Hes1 in subventricular zone(SVZ)were observed respectively by triphenyl tetrazolium chloride(TTC) stain, htorylin eastin(HE) stain, immunofluorescence technique and reverse transcriphase polymerase chain reaction(Real-time PCR) methods at the 28th day after the operation. Result: The mNSS on the 7th, 14th, 28th days of high, medium-dose Dihuang Yinzi groups and nimodipine group were significantly lower than that of model group(PPth day, the percentage of cerebral infarction volume in brain tissue volume of high, medium-dose Dihuang Yinzi groups and nimodipine group were smaller than that of model group(Pth day, the BrdU positive cells in SVZ of the above 3 groups were significantly higher than model group(PPPth day, the mRNA levels of Notch1, Jagged1 and Hes1 of high, medium-dose Dihuang Yinzi groups and nimodipine group were significantly higher than those of model group(PPPPConclusion: Dihuang Yinzi can improve the nerve function defect of MCAO rat model, and reduce the volume of cerebral infarction and the pathological changes of brain tissue, thus playing a protective role in cerebral ischemia-reperfusion injury rats. Its mechanism may be related to the activation of the Notch signaling pathway, and the up-regulation of expressions of Notch1, Jagged1 and Hes1 mRNA, thus promoting the proliferation of NSCs.

16.
Acta Physiologica Sinica ; (6): 405-414, 2019.
Article in Chinese | WPRIM | ID: wpr-777173

ABSTRACT

The present study was aimed to investigate the expression relationship of Hippo signaling molecules and ovarian germline stem cell (OGSC) markers in the development schedule of OGSCs during ovarian aging in women and mice. The ovaries of 2-month-old mature (normal control) and 12-month-old (physiological ovarian aging) KM mice were sampled, and the ovarian cortex samples of young (postpuberty to 35 years old), middle age (36-50 years old) and menopausal period (51-60 years old) women were obtained with consent. The mice model of pathological ovarian aging was established by intraperitoneal injection of cyclophosphamide/busulfan (CY/BUS). HE staining was used to detect the changes of follicles at different stages, and the localization and expression changes of Hippo signaling molecules and OGSCs related factors (MVH/OCT4) were detected by immunohistochemistry and immunofluorescence staining. Western blot was used to detect the protein expression levels of the major molecules in the Hippo signaling pathway and OGSCs related factors. The results showed that there were not any normal follicles, but a few atresia follicles in the ovaries from physiological and pathological ovarian aging mice. Compared with the normal control mice, both the physiological and pathological ovarian aging mice showed decreased protein expression levels of the main Hippo signaling molecules (pYAP1) and MVH/OCT4; Whereas only the pathological ovarian aging mice showed increased ratio of pYAP1/YAP1. In comparison with the young women, the middle age and menopausal women showed looser structure of ovarian surface epithelium (OSE) and less ovarian cortical cells. The protein expression level of LATS2 in the OSE was the highest in young women, MST1 expression was the lowest in the menopausal period women, and the expression levels of YAP1 and pYAP1 were the highest in middle age women. Compared with the young women, the middle age and menopausal period women exhibited significantly decreased ratio of OSE pYAP1/YAP1, whereas there was no significant difference between them. The expression level of MVH protein in OSE from the young women was significantly higher than those of the middle age and menopausal period women. These results indicate that there is an expression relationship between the main molecules of Hippo signaling pathway and OGSCs related factors, which suggests that Hippo signaling pathway may regulate the expression levels of OGSCs related factors, thus participating in the process of physiological and pathological degeneration of ovarian.


Subject(s)
Adaptor Proteins, Signal Transducing , Metabolism , Adult , Aging , Animals , Epithelium , Female , Humans , Mice , Middle Aged , Octamer Transcription Factor-3 , Metabolism , Oogonial Stem Cells , Metabolism , Ovarian Follicle , Ovary , Phosphoproteins , Metabolism , Protein Serine-Threonine Kinases , Metabolism , Signal Transduction , Tumor Suppressor Proteins , Metabolism
17.
Article in Chinese | WPRIM | ID: wpr-776555

ABSTRACT

OBJECTIVE@#To observe the protective effects of epalrestat (EPS) on interstitial fibrosis in unilateral ureteral obstruction (UUO) rats and its mechanism.@*METHODS@#Rats were randomly divided into four groups: sham group, UUO group, UUO + epalrestat (50 or 100 mg/kg), 8 rats in each group.Rats in UUO and UUO + epalrestat group were obstructed left ureter.In the sham group, rats had their left ureters exposed and manipulated without ligation.Animals for epalrestat treatment received daily drug via gavage for 3 weeks, the rats of sham and UUO groups received equal amount of sodium carboxymethyl cellulose with the same regimen.Renal tissues pathological changes and collagen deposition were observed by HE and Masson's staining.The aldose reductase(AR) expression in renal tissues was measured by immunohistochemisty.The expression levels of collagen I, collagen III, alpha-smooth muscle actin (α-SMA), fibroblast-specific protein1 (FSP-1), fibronectin (FN), epithelial cadherin (E-cadherin), transforming growth factor-β1 (TGF-β1) and AR from kidney tissues were measured by real-time RT-PCR or Western blot.@*RESULTS@#Compared with the sham group, the renal tissues of the UUO group showed significant fibrosis, including renal tubular epithelial cell atrophy and vacuolated degeneration, collagen deposition, fibroblasts and myofibroblasts proliferation and inflammatory cell infiltration, and concomitantly with the expressions of collagen I, collagen III, TGF-β1, AR, α-SMA, FSP-1 and FN were remarkably up-regulated, but E-cadherin was significantly reduced in UUO group.Compared with the UUO group, after 3 weeks epalrestat administration, the level of renal interstitial fibrosis was obviously ameliorated and the expressions of collagen I, collagen III, TGF-β1, AR, α-SMA, FSP-1 and FN were remarkably down-regulated, but E-cadherin was significantly increased in rats of epalrestat groups.@*CONCLUSION@#These results suggest that epalrestat attenuates renal interstitial fibrosis possibly through inhibition of EMT via inhibiting TGF-β1 and AR expression.


Subject(s)
Animals , Enzyme Inhibitors , Pharmacology , Fibrosis , Drug Therapy , Random Allocation , Rats , Rats, Sprague-Dawley , Rhodanine , Pharmacology , Thiazolidines , Pharmacology , Ureteral Obstruction , Drug Therapy
18.
Article in Chinese | WPRIM | ID: wpr-743472

ABSTRACT

Objective To explore the clinical features and risk factors of poor prognosis in neonatal necrotizing enterocolitis(NEC).Methods A retrospective study was carried out in the infants with NEC admitted to 6 cooperative hospitals in Guangdong Province between January 2005 and December 2014.The clinical features and risk factors of poor prognosis in preterm and full-term infants diagnosed NEC,early onset and late onset NEC were analyzed.Results A total of 449 cases who met the criteria were admitted during the study time.The mortality was 23.6% (106/449 cases),of which the preterm group was 24.6% (58/238 cases) while the full-term group was 22.7% (48/211 cases),the early onset group was 22.1% (45/204 cases) while the late onset group was 24.3% (57/235 cases).The median number of NEC onset in preterm group was 11 d after birth while the number of the full-term group was 6 d.Full-term infants who diagnosed NEC were more likely to manifest themselves as abdominal distension (52.1% vs.42.0%,x2 =4.597,P =0.032),vomiting(36.5% vs.17.2%,x2 =21.428,P =0.000) and bloody stool(30.3% vs.21.4%,x2 =4.653,P =0.031);but in the onset of NEC,preterm infants more likely to have feeding intolerance (21.0% vs.12.8%,x2=5.309,P =0.021).The early onset group of full-term NEC was much common in twins or multiplets(9.4% vs.1.1%,x2 =6.226,P =0.013),which rate of surgical therapy was much higher (41.0% vs.27.0%,P =0.036) and the breast-feeding rate before NEC was lower than the late onset group(14.5% vs.32.6%,x2 =9.500,P =0.002),the differences were statistically significant.The gestational age and birth weight were bigger in the early onset group of preterm NEC[(33.8 ±2.5) weeks vs.(32.2 ±2.8) weeks,t =4.261,P =0.000;(2.1 ±0.5) kg vs.(1.7 ± 0.5) kg,t =4.735,P =0.000)],but length of stay was shorter than the late onset group (18.0 d vs.26.5 d,P =0.000).Logistic regression analysis showed that the risk factors of poor prognosis of full-term NEC were shock,peritonitis and sepsis;while risk factors of poor prognosis of preterm NEC were small for gestational age infant,pulmonary hemorrhage,shock,intestinal perforation and sepsis;the risk factors of poor prognosis of the early onset group of full-term NEC was shock;while those of the late onset group were shock and peritonitis;the risk factors of poor prognosis in the early onset group of preterm NEC were shock and sepsis,while those in the late onset group were pulmonary hemorrhage,shock,intestinal perforation and sepsis.Conclusions Compared to the preterm NEC,the onset time of full-term NEC was earlier and the clinical manifestations were more typical.Early identification and management of shock,peritonitis,intestinal perforation,sepsis and pulmonary hemorrhage can reduce the risk of poor prognosis of neonate NEC.

19.
Article in Chinese | WPRIM | ID: wpr-801712

ABSTRACT

Objective: To investigate and compare enzymatic kinetics of scutellarin,apigenin-7-O-glucronide and paeoniflorin from Xinshao fomula in liver microsomes of sham-operated rats and middle cerebral artery occlusion(MCAO) rats with focal cerebral ischemia-reperfusion injury. Method: Xinshao fomula were incubated respectively with liver microsomes of sham-operated rats and MCAO rats,UPLC-MS and substrate elimination method was employed,Michaelis constant(Km),maximum velocity of enzymatic reaction(Vmax) and intrinsic clearance(CLint) of these three components from Xinshao fomula in liver microsomes of sham-operated rats and MCAO rats were calculated,these parameters between different groups were evaluated by statistical analysis. Result: The Km values of scutellarin,apigenin-7-O-glucronide and paeoniflorin in liver microsomes of MCAO rats were (0.798±0.031),(0.213±0.017),(0.499±0.029) μmol·L-1,which were quite different to these in liver microsomes of sham-operated rats.Compared with the sham-operated group,Vmax and CLint values of scutellarin and paeoniflorin in liver microsomes of MCAO rats were significantly reduced(PPVmax of apigenin-7-O-glucronide in liver microsomes of MCAO rat was also significantly reduced(PConclusion: Metabolic rates of these three active components from Xinshao fomula in liver microsomes of MCAO rats with focal cerebral ischemia-reperfusion injury decrease with low elimination rate.

20.
Practical Oncology Journal ; (6): 27-33, 2019.
Article in Chinese | WPRIM | ID: wpr-752808

ABSTRACT

Objective The objective of this study was to investigate the effect of depression on serum levels of C-reactive protein(CRP)and high-sensitivity C-reactive protein(hs-CRP),and prognosis in liver cancer patients. Methods A total of 251 patients with liver cancer undergoing hepatectomy were enrolled. The hospital anxiety and depression scale( HADS-D) and 9-item patients health questionnaire(PHQ9) were assessed for depression before 3 days for surgery. Patients were divided into depression group(n=95)and non-depression group(n=156) according to the scores. Preoperative serum levels of CRP,hs-CRP,ALT and AST were measured and compared between the depression and non-depression groups. Survival analysis Kaplan-Meier method was used to compare the disease-free survival(DFS)and total survival(OS)between the two groups. Results The serum levels of CRP, hs-CRP,ALT and AST in the depression group were significantly higher than those in the non-depression group(P<0. 05). The follow-up of 3. 5-year showed that 164 patients(65 in depression group and 99 in non-depression group)had recurrence or metas-tasis and 47 patients(22 in depression group and 25 in non-depression group) died. The DFS and OS in the depression group were significantly lower than those in the non-depression group(P< 0. 05). Cox multiple regression analysis showed that liver function grading,BCLC staging and depression were independent risk factors for the prognosis of liver cancer. Spearman correlation analysis showed that patients′degree of depression was positively correlated with serum levels of CRP and hs-CRP(P<0. 05),DFS and OS were negatively correlated with serum levels of CRP and hs-CRP(P<0. 05). Conclusion Depression may mediate elevated serum levels of CRP and hs-CRP,maintain inflammatory response in patients,lead to increased liver function damage,elevate levels of ALT and AST,and thus adversely affect the prognosis of patients with liver cancer.

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