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1.
Journal of Experimental Hematology ; (6): 1394-1402, 2021.
Article in Chinese | WPRIM | ID: wpr-922271

ABSTRACT

OBJECTIVE@#To investigate the effect of glycolytic enzyme pyruvate kinase type 2 (PKM2) on the proliferation and apoptosis of human leukemia HL-60 cells.@*METHODS@#si-PKM2 plasmid was transfected into HL-60 cells (set as si-PKM2 group), and blank vector transfected cells were set as control group (si-Ctl group). The expression levels of PKM2 mRNA and protein in si-Ctl group and si-PKM2 group were detected by RT-qPCR and Western blot. CCK-8 cell detection kit was used to detect the proliferation ability of the cells in the two groups. Flow cytometry was used to detect the changes of cell cycle and apoptosis. Western blot and RT-qPCR were used to detect the changes of p-Akt and p-mTOR protein levels in PI3K/Akt/mTOR signaling pathway and the changes of glycolysis-related mRNA levels of the cells in the two groups. The changes in glucose consumption and lactic acid production of the cells were assayed. Over expressed PKM2, HL-60 cells were treated with PI3K inhibitor LY294002 or galactose, the changes in cell proliferation ability, cell cycle and apoptosis, as well as changes in glucose consumption and lactic acid production were detected.@*RESULTS@#Interfered by si-PKM2, mRNA and protein levels of PKM2 in si-PKM2 group significantly decreased, and proliferation ability of the cells was also reduced (P<0.05). After PKM2 knockdown, the cells were significantly blocked at G@*CONCLUSION@#PKM2 knockdown can inhibit the proliferation and induce apoptosis of HL-60 cells, and its molecular mechanism may be related to the PKM2-mediated PI3K/Akt/mTOR-glycolysis, which suggesting that PKM2 may serve as a molecular target for the prevention and treatment of leukemia.


Subject(s)
Apoptosis , Cell Proliferation , Glycolysis , Humans , Phosphatidylinositol 3-Kinases/metabolism , Pyruvate Kinase
2.
Article in Chinese | WPRIM | ID: wpr-921747

ABSTRACT

This study investigated the differential mechanisms of Rehmanniae Radix and Rehmanniae Radix Praeparata in improving diabetes in mice through AMPK-mediated NF-κB/NLRP3 signaling pathway. The diabetic mouse model was established with high-fat diet coupled with streptozotocin(STZ, intraperitoneal injection, 100 mg·kg~(-1), once a day for three consecutive days), after which the mice were randomly divided into model group, low-dose(5 g·kg~(-1)) and high-dose(15 g·kg~(-1)) Rehmanniae Radix groups, low-dose(5 g·kg~(-1)) and high-dose(15 g·kg~(-1)) Rehmanniae Radix Praeparata groups, catalpol group(250 mg·kg~(-1)), 5-hydroxymethylfurfural(5-HMF) group(250 mg·kg~(-1)), metformin group(250 mg·kg~(-1)), with the normal group also set. The organ indexes of heart,liver, spleen, lung, kidney and pancreas were calculated after four weeks of administration. The pathological changes and fibrosis of pancreas, kidney and liver in mice were observed by hematoxylin-eosin(HE) staining and Masson staining. Western blot was used to determine the expression levels of Toll-like receptor-4(TLR4), nuclear factor-κB(NF-κB), Nod-like receptor protein 3(NLRP3),interleukin-1β(IL-1β), adenosine monophosphate-activated protein kinase(AMPK), phosphorylated AMPK(p-AMPK) in the pancreas, kidney and liver of mice. Compared with the model group, the administration groups witnessed significant decrease in the liver,spleen, kidney, pancreas and fat indexes of diabetic mice, and there was no significant difference in heart and lung indexes. The pathological states and fibrosis of pancreatic, kidney and liver tissues were significantly improved after administration. Additionally, the expression levels of TLR4, NF-κB and NLRP3 in pancreas, kidney and liver of diabetic mice were significantly lowered. The expression levels of p-AMPK/AMPK were enhanced significantly in kidney and liver of mice in Rehmanniae Radix group while in pancreas, kidney and liver in Rehmanniae Radix Praeparata group. This suggests that Rehmanniae Radix and Rehmanniae Radix Praeparata differ in the mechanism of regulating energy metabolism of multiple organs and thereby exerting anti-inflammatory effects to alleviate symptoms of diabetic mice.


Subject(s)
AMP-Activated Protein Kinases/genetics , Animals , Diabetes Mellitus, Experimental/drug therapy , Diet, High-Fat/adverse effects , Mice , NF-kappa B/metabolism , NLR Family, Pyrin Domain-Containing 3 Protein , Plant Extracts , Rehmannia , Signal Transduction , Streptozocin
3.
Acta Physiologica Sinica ; (6): 795-804, 2021.
Article in English | WPRIM | ID: wpr-921282

ABSTRACT

Farnesoid X receptor (FXR) has been identified as an inhibitor of platelet function and an inducer of fibrinogen protein complex. However, the regulatory mechanism of FXR in hemostatic system remains incompletely understood. In this study, we aimed to investigate the functions of FXR in regulating antithrombin III (AT III). C57BL/6 mice and FXR knockout (FXR KO) mice were treated with or without GW4064 (30 mg/kg per day). FXR activation significantly prolonged prothrombin time (PT) and activated partial thromboplastin time (APTT), lowered activity of activated factor X (FXa) and concentrations of thrombin-antithrombin complex (TAT) and activated factor II (FIIa), and increased level of AT III, whereas all of these effects were markedly reversed in FXR KO mice. In vivo, hepatic AT III mRNA and protein expression levels were up-regulated in wild-type mice after FXR activation, but down-regulated in FXR KO mice. In vitro study showed that FXR activation induced, while FXR knockdown inhibited, AT III expression in mouse primary hepatocytes. The luciferase assay and ChIP assay revealed that FXR can bind to the promoter region of AT III gene where FXR activation increased AT III transcription. These results suggest FXR activation inhibits coagulation process via inducing hepatic AT III expression in mice. The present study reveals a new role of FXR in hemostatic homeostasis and indicates that FXR might act as a potential therapeutic target for diseases related to hypercoagulation.


Subject(s)
Animals , Antithrombin III , Blood Coagulation , Hepatocytes , Liver , Mice , Mice, Inbred C57BL , Mice, Knockout , Receptors, Cytoplasmic and Nuclear/genetics
4.
Acta Physiologica Sinica ; (6): 681-689, 2021.
Article in Chinese | WPRIM | ID: wpr-887702

ABSTRACT

Prostaglandin E2 (PGE2), a bioactive lipid mediator, is one of the most important locally acting factors involved in a variety of physiological and pathophysiological processes. PGE2 binds with four EP receptors (EP1-4) to activate G protein-coupled receptor signaling responses. Recent functional and molecular studies have revealed that PGE2 plays an essential role in regulation of renal fluid transport via a variety of mechanisms. The water balance mainly depends on the regulation of aquaporin-2 (AQP2) by arginine vasopressin (AVP) in renal collecting duct principal cells. In recent years, increasing evidence suggests that PGE2 plays an important role in renal water reabsorption in the collecting ducts. In this paper, we reviewed the role of PGE2 and its receptors in the regulation of water reabsorption in the kidney, which may provide a new therapeutic strategy for many diseases especially nephrogenic diabetes insipidus.


Subject(s)
Aquaporin 2/metabolism , Biological Transport , Diabetes Insipidus, Nephrogenic , Dinoprostone , Humans , Water/metabolism
5.
Acta Physiologica Sinica ; (6): 657-664, 2021.
Article in Chinese | WPRIM | ID: wpr-887700

ABSTRACT

Arachidonic acid (AA) is an ω-6 polyunsaturated fatty acid, which mainly exists in the cell membrane in the form of phospholipid. Three major enzymatic pathways including the cyclooxygenase (COX), lipoxygenase (LOX) and cytochrome P450 monooxygenase (CYP450) pathways are involved in AA metabolism leading to the generation of a variety of lipid mediators such as prostaglandins, leukotrienes, hydroxyeicosatetraenoic acids (HETEs) and epoxyeicoastrienoic acids (EETs). These bioactive AA metabolites play an important role in the regulation of many physiological processes including the maintenance of liver glucose and lipid homeostasis. As the central metabolic organ, the liver is essential in metabolism of carbohydrates, lipids and proteins, and its dysfunction is associated with the pathogenesis of many metabolic diseases such as type 2 diabetes mellitus, dyslipidemia and nonalcoholic fatty liver disease (NAFLD). This article aims to provide an overview of the enzymatic pathways of AA and discuss the role of AA-derived lipid mediators in the regulation of hepatic glucose and lipid metabolism and their associations with the pathogenesis of major metabolic disorders.


Subject(s)
Arachidonic Acid/metabolism , Diabetes Mellitus, Type 2 , Glucose/metabolism , Homeostasis , Humans , Lipid Metabolism , Liver
7.
Article in Chinese | WPRIM | ID: wpr-873839

ABSTRACT

Objective To provide reliable indicators for effective prevention and control of COVID-19, we examined the biochemical indicators as well as anti-SARS-CoV-2 IgM and IgG antibodies in confirmed and suspected COVID-19 patients. Methods A total of 56 confirmed and suspected COVID-19 cases quarantined during January-March, 2020 in Gansu Provincial People′s Hospital and People′s Hospital of Xigu District, Gansu Province were included.Based on the results of nucleic acid testing and CT scan finding, they were divided into three groups: positive in both nucleic acid testing and CT scan finding; positive in nucleic acid testing but negative in CT scan finding; negative in both nucleic acid testing and CT scan finding.COVID-19 viral nucleic acid was detected and chest CT scan was performed.The following biochemical indicators were examined: total protein, albumin, total bilirubin, alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, γ-glutamyltranspeptidase, creatine kinase and lactate dehydrogenase.SPSS 22.0 statistical software was used to analyze the differences in the biochemical indicators among these three groups, as well as the temporal trend of IgM and IgG antibodies at different points of time. Results There were significant differences in the mean values of alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, and lactate dehydrogenase between these three groups (P < 0.05), whereas no significant difference in the mean value of total protein and albumin (P>0.05).ROC curve indicated that aspartate aminotransferase had the largest maximum area under the curve (AUC, 0.834), whereas alanine aminotransferase had the highest sensitivity (1.0) and total bilirubin had the highest specificity (0.927).Thus, aspartate transaminase provided the best prediction for the diagnosis of COVID-19, with sensitivity of 0.786, specificity of 0.854, and the maximum AUC of 0.834.In 12 of 16 confirmed COVID-19 patients tested IgG positive after 10 days of diagnosis, and 10 of 10 confirmed COVID-19 patients tested IgG positive after 14 days of diagnosis. Conclusion Aspartate aminotransferase may be the most useful indicator in the diagnosis of COVID-19.

8.
Article in Chinese | WPRIM | ID: wpr-872774

ABSTRACT

Objective:A systematical study on the anti-breast cancer mechanism of tryptanthrin in breast cancer-bearing mice was done by Label-free proteomics. Method:UPLC-MS was used to detect the expressed-proteins of tryptanthrin inhibiting breast cancer in mice, chromatographic separation was achieved on the Ionoptics nano UPLC C18 column (0.075 mm×250 mm, 1.6 μm), and gradient elution was performed with 0.1% formic acid aqueous solution-0.1% formic acid acetonitrile solution as mobile phase. Data acquisition was carried out in electrospray ionization (ESI) under the positive ion mode, the scanning range was m/z 100-1 700, MaxQuant 1.6.5.0 was used for database retrieval. Label-free proteomics with high resolution mass spectrometry was used to screen differentially expressed proteins between the model group of 4T1 breast cancer mice and oral administration group of tryptanthrin (100 mg·kg-1). The proteomics of tryptanthrin against breast cancer was carried out. Result:A total of 3 997 proteins were identified in this proteomics research, and 2 911 proteins were quantifiable. A total of 750 differentially expressed proteins were identified between the model group and the tryptanthrin group, 286 proteins were up-regulated and 464 proteins were down-regulated. Gene ontology analysis showed that these differentially expressed proteins were mainly involved in biological processes of proliferation, cell migration, apoptosis, immunity, angiogenesis, inflammatory regulation, etc. Kyoto encyclopedia of genes and genomes pathway analysis further indicated that these proteins were mainly concentrated in T cell receptors, B cell receptors, Toll-like receptors, nuclear transcription factor-κB (NF-κB), Ras proteins, interleukin-17, tumor necrosis factor, phosphatidylinositol 3-kinase/protein kinase B (PI3K-Akt), mitogen-activated protein kinase (MAPK) and other signaling pathways. Conclusion:The differentially expressed proteins closely related to anti-breast cancer effect of tryptanthrin on 4T1 breast cancer mice are effectively screened out, including up-regulating proteins of leukocyte differentiation antigen 14 (CD14), prostaglandin G/H synthase 2 (PTGS2), E3 ubiquitin-protein ligase and down-regulating proteins of CD44, heat shock 70 kDa protein 1A (HSPA1A), macrophage migration inhibitory factor (MIF), NF-κB, ribosomal protein S6 kinase alpha-4 (RPS6KA4) and high mobility group protein B1 (HMGB1). These findings suggest that tryptanthrin can inhibit breast cancer in mice mainly through regulating tumor inflammatory microenvironment.

9.
Article in Chinese | WPRIM | ID: wpr-849659

ABSTRACT

Objective To investigate the safety and effectiveness of bilateral transverse thoracic muscle plane (TTP) block (modified approach) combined with general anesthesia in off-pump coronary artery bypass grafting (OPCABG). Methods The clinical data of 60 patients undergoing OPCABG, selected from March to August 2019 in General Hospital of Northern Theater Command, were retrospectively analyzed and divided into TTP block with general anesthesia group (TTP+general anesthesia group, n=30) and general anesthesia group (n=30) according to anesthesia mode. Patients in TTP+general anesthesia group undergone bilateral TTP block (modified approach, 0.25% ropivacaine 20 ml each side) before anesthesia induction, and both groups were induced by routine anesthesia. The mean arterial pressure (MAP) and heart rate (HR) were recorded and analyzed before and after cutting, splitting and closing the sternum, and the total dosage of sufentanil at the end of operation was recorded. The levels of lactic acid and blood glucose in blood gas analysis of patients at the time they entered the room, the operation ended and at 2, 4, 6, 8, 10, 12, 16, 20 and 24 h after the operation were recorded. The visual analogue scale (VAS) scores in resting and moving state at 12, 24 and 48 h after operation were recorded. The numbers of patients who were first added analgesic drugs (pethidine) on the day, the first day and the second day after operations were recorded, and the occurrence of postoperative adverse reactions was recorded. Results Compared with general anesthesia group, the change rate of MAP and HR in TTP+general anesthesia group decreased slightly at each time point, but the difference was not statistically significant (P>0.05). The differences of lactic acid at 2 and 4 h after operation were statistically significant (P0.05); while the dosage of sufentanil in TTP+general anesthesia group was obviously decreased, and the number of patients who were added analgesics at the postoperative day was markedly reduced, both were with statistical significance (P0.05). The incidence of postoperative chills was obviously lower in TTP+general anesthesia group than in general anesthesia group with a statistical difference (P<0.05). Conclusion Bilateral TTP block (modified approach) combined with general anesthesia can provide good perioperative analgesia for patient undergoing OPCABG, reduce the use of opioids, and inhibit the stress response to a certain extent, thus having better safety and effectiveness.

10.
Article in Chinese | WPRIM | ID: wpr-829039

ABSTRACT

OBJECTIVE@#To investigate the expression level of miR-181b in CD19+ B lymphocytes of patients with chronic lymphocytic leukemia (CLL), to analyze the relationship between its expression and the prognosis of CLL patients, and to predict the potential target gene of miR-181b in CLL by using bioinformatics.@*METHODS@#Eight-four patients with CLL treated in People's Hospital of Xinjiang Uygur Autonomous Region from June 2013 to June 2018 were selected. and 20 healthy people were selected as control group. RNA was extracted from CD19+B lymphocytes of peripheral blood by magnetic bead sorting, the expression level of miR-181b was detected, and it's expression differences in different IPI groups were analyzed. The correlation between the expression level of miR-181b and PFS of CLL patients also was analyzed. miR-181b target genes were predicted by online database and literatures, and gene annotation analysis and relevant signal pathway analysis were performed for candidate target genes.@*RESULTS@#The expression level of miR-181b in CLL patients was significantly lower than that in control group (P<0.01); The expression level of miR-181b in the low-risk group was higher than that in high-risk group and extremely high-risk group (P<0.05), but there was no statistical difference between low-risk group and medium-risk group (P=1.00). The expression level of miR-181b in medium-risk group was higher than that in high-risk group and extremely high-risk group (P<0.05), but there was no difference between high-risk group and extremely high-risk group (P=1.00). ROC curve results showed that the area under the curve (AUC) was 0.792 (P<0.01).When the expression level of miR-181b was at the threshold value of 0.279, it showed a better sensitivity (62.9%) and specificity (91.8%). Survival analysis results suggested that compared with the high expression group, the miR-181b low expression group had poor PFS (log rank: P=0.047). Prediction of miR-181b by using the starBase, targetscan and picTar database and its combination with literature reports indicated that CARD11, ZFP36L1, RUNX1, NR4A3, ATP1B1, PUM1 and PLAG1 related with blood diseases, and up-regulated CARD11 and ZFP36L1 participated in lymphoid tumor formation by promoting cell proliferation and inhibiting cell aging.@*CONCLUSION@#The expression level of miR-181b in CLL group are significantly lower than that in the controls group, and the low expression of miR-181b relates with poor prognosis of CLL patients. Through bioinformatics prediction and combined with literature reports, it is speculated that CARD11 and ZFP36L1 as target genes of miR-181b may be participated in the occurrence and development of CLL. Further experiments are needed to verify this result.


Subject(s)
Apoptosis Regulatory Proteins , Cell Proliferation , Humans , Leukemia, Lymphocytic, Chronic, B-Cell , Genetics , MicroRNAs , Prognosis
11.
Acta Physiologica Sinica ; (6): 311-318, 2019.
Article in Chinese | WPRIM | ID: wpr-777184

ABSTRACT

As a member of the nuclear receptor superfamily, the pregnane X receptor (PXR) is a ligand-activated transcription factor. PXR is highly expressed in liver and intestinal tissues, and also found in other tissues and organs, such as stomach and kidney. After heterodimerization with retinoid X receptor (RXR), PXR recruits numerous co-activating factors, and binds to specific DNA response elements to perform transcriptional regulation of the downstream target genes. As an acknowledged receptor for xenobiotics, PXR was initially considered as a nuclear receptor regulating drug metabolizing enzymes and transporters. However, nowadays, PXR has also been recognized as an important endobiotic receptor. Recent studies have shown that PXR activation can regulate glucose metabolism, lipid metabolism, steroid endocrine homeostasis, detoxification of cholic acid and bilirubin, bone mineral balance, and immune inflammation in vivo. This review focuses on the role of PXR in metabolism of endogenous substances.


Subject(s)
Animals , Gene Expression Regulation , Humans , Pregnane X Receptor , Metabolism , Xenobiotics , Metabolism
12.
Acta Physiologica Sinica ; (6): 361-370, 2019.
Article in Chinese | WPRIM | ID: wpr-777178

ABSTRACT

Prostaglandin E2 (PGE2) is a cyclooxygenase metabolite of arachidonic acid. It acts as a bioactive lipid and plays an important role in regulating many biological processes. PGE2 binds to 4 different G protein-coupled receptors including prostaglandin E2 receptor subtypes EP1, EP2, EP3 and EP4. The EP4 receptor is widely expressed in most of human organs and tissues. Increasing evidence demonstrates that EP4 is essential for cardiovascular homeostasis and participates in the pathogenesis of many cardiovascular diseases. Here we summarize the role of EP4 in the regulation of cardiovascular function and discuss potential mechanisms by which EP4 is involved in the development of cardiovascular disorders with a focus on its effect on inflammation.


Subject(s)
Cardiovascular Diseases , Cyclooxygenase 2 , Dinoprostone , Physiology , Humans , Receptors, Prostaglandin E, EP4 Subtype , Physiology
13.
Acta Physiologica Sinica ; (6): 491-496, 2019.
Article in Chinese | WPRIM | ID: wpr-777163

ABSTRACT

Adipose tissue is the energy storage organ of the body, and excess energy is stored in adipocytes in the form of lipid droplets. The homeostasis of adipose tissue is the basis for the body to maintain normal metabolic activity. Prostaglandin E (PGE) is an important lipid mediator in the body. It is synthesized in almost all tissues and participates in the regulation of many physiological processes such as blood pressure, glucose and lipid metabolism, and inflammation. PGE is abundant in white adipose tissue, where it is involved in the regulation of fat metabolism. PGE plays its biological role through binding to four G protein coupled receptors (prostaglandin E receptors), including EP-1, -2, -3, and -4. The EP4 subtype has been proved to play an important role in adipogenesis and adipose metabolism: it could inhibit adipogenesis while it was activated, whereas its knockout could promote lipolysis. This review summarized the relationship between EP4 and adipose metabolism, hoping to identify new targets of drug development for metabolic disorders.


Subject(s)
Adipocytes , Adipogenesis , Adipose Tissue , Metabolism , Humans , Receptors, Prostaglandin E, EP4 Subtype , Physiology
14.
Chinese Medical Journal ; (24): 2820-2826, 2019.
Article in English | WPRIM | ID: wpr-781738

ABSTRACT

BACKGROUND@#During cup implantation, vertical height of the cup center (V-HCC) should be precisely controlled to achieve sufficient bone-cup coverage (BCC). Our study aimed to investigate the acetabular bone stock and the quantitative relationship between V-HCC and BCC in Crowe types I to III hips.@*METHODS@#From November 2013 to March 2016, pelvic models of 51 patients (61 hips) with hip dysplasia were retrospectively reconstructed using a computer software. Acetabular height and doom thickness were measured on the mid-acetabular coronal cross section. V-HCC was defined as the vertical distance of cup rotational center to the interteardrop line (ITL). In the cup implantation simulation, the cup was placed at the initial preset position, with a V-HCC of 15 mm, and moved proximally by 3-mm increments. At each level, the BCC was automatically calculated by computer. Analysis of variance and Kruskal-Wallis test were used to compare the differences between groups.@*RESULTS@#There were no significant between-group differences in maximum thickness of the acetabular doom; however, peak bone stock values were obtained at heights of 41.63 ± 5.14 mm (Crowe type I), 47.58 ± 4.10 mm (Crowe type II), and 55.78 ± 3.64 mm (Crowe type III) above the ITL. At 15 mm of V-HCC, median BCC was 78% (75-83%) (Crowe type I), 74% (66-71%) (Crowe type II), and 61% (57-68%) (Crowe type III). To achieve 80% of the BCC, the median V-HCC was 16.27 (15.00-16.93) mm, 18.19 (15.01-21.53) mm, and 24.13 (21.02-28.70) mm for Crowe types I, II, and III hips, respectively.@*CONCLUSION@#During acetabular reconstruction, slightly superior placement with V-HCC <25 mm retained sufficient bone coverage in Crowe I to III hips.

15.
Article in English | WPRIM | ID: wpr-773369

ABSTRACT

OBJECTIVE@#The aim of this study was to determine whether low calf circumference (CC) could predict nutritional risk and the cutoff values of CC for predicting nutritional risk in hospitalized patients aged ⪖ 80 years.@*METHODS@#A total of 1,234 consecutive patients aged ⪖ 80 years were enrolled in this study. On admission, demographic data, CC, and laboratory parameters were obtained. Patients with Nutritional Risk Screening 2002 (NRS-2002) total score ⪖ 3 were considered as having nutritional risk.@*RESULTS@#CC values were significantly lower in patients with nutritional risk compared to those in patients without nutritional risk [27.00 (24.50-31.00) vs. 31.00 (29.00-33.50], P < 0.001]. CC was negatively correlated with age and nutritional risk scores. Logistic regression analysis of nutritional risk revealed that body mass index, albumin level, hemoglobin level, cerebral infarction, neoplasms, and CC (OR, 0.897; 95% confidence interval, 0.856-0.941; P < 0.001) were independent impact factors of nutritional risk. Nutritional risk scores increased with a decrease in CC. In men, the best CC cutoff value for predicting nutritional risk according to the NRS-2002 was 29.75 cm. In women, the cutoff value was 28.25 cm.@*CONCLUSION@#CC is a simple, noninvasive, and valid anthropometric measure to predict nutritional risk for hospitalized patients aged ⪖ 80 years.


Subject(s)
Aged, 80 and over , Anthropometry , Methods , China , Female , Hospitalization , Humans , Leg , Male , Nutritional Status , Risk Assessment , Methods
16.
Article in Chinese | WPRIM | ID: wpr-776507

ABSTRACT

OBJECTIVE@#To investigate the effects and molecular mechanisms of 2-12alkyl-6-methoxycyclohexa-2,5-diene-1,4-dione(DMDD) on diffuse large B lymphoma (DLBCL).@*METHODS@#In animal experiments, 4-week-aged BALB/C mice were divided into 5 groups, 20 mice in each group. Mice were inguinal injected with DLBCL cell line OCI-LY19 cells 0.1 ml at the concention of 1 × 10 /ml. Two days later, mice were treated with DMDD at the doses of 0, 1, 5, 25 and 125 mg/kg by intragastric administration respectively, once /2 days. Ten mice of each group were killed on the 18th day of administration, and the tumor tissues were weighed. The survival time of the remaining mice were recorded. In cell experiments, OCI-LY19 cells were added to 96-well culture plates, 100 μl 1×10 cells/ml per well, then 100 μl DMDD was added to the well and the final concentrations were 0, 1, 5, 25 and 125 μmol/L respectively. The cells were treated with DMDD for 0, 24, 48 and 72 h, three wells in each group. The cell proliferation activity was detected by MTS assay. According to the results of cell proliferation experiments, OCI-LY19 cells were treated with DMDD at the concentrations of 0 μmol/L, 5 μmol/L and 25 μmol/L for 24 h. The apoptosis rate was analyzed by flow cytometry, the nuclear type was observed by hoechst staining, the mitochondrial membrane potential was observed by JC-1 staining, cytotoxicity of drugs was evaluated by LDH release experiment, gene expression and transcription were analyzed by qPCR and Western blot.@*RESULTS@#Compared with 0 mg/kg drug group, DMDD at the dose of 1~125 mg/kg could inhibit the growth of tumor tissue in mice and prolong their survival time (P<0.01). Cell experiments showed: in DMDD group, the proliferation activity of OCI-LY19 cells was decreased significantly and the level of apoptosis was increased significantly (P<0.01), nuclear fragmentation, agglutination, apoptotic bodies occurred and mitochondrial membrane potential was decreased, the LDH release rate was increased significantly (P<0.01), the expressions of caspase-3 and bax genes and the phosphorylation level of Ikappa B alpha in cells were up-regulated significantly, the protein expression levels of bcl-2, bcl-xL, jak2 and stat3 were inhibited significantly (P<0.01).@*CONCLUSION@#DMDD can inhibit the expressions of JAK2, STAT3 and p-Ikappa B alpha in JAK2/STAT3 and NF-kappa B signal pathways, down-regulate BCL-2/BAX and activate Caspase-3, finally, activate the endogenous pathway of mitochondrial apoptosis in OCI-LY19 cells and promote the apoptosis of DLBCL cells, inhibit proliferation of OCI-LY19 cells. It has inhibitive effects on DLBCL.


Subject(s)
Animals , Apoptosis , Cell Line, Tumor , Cell Proliferation , Cyclohexenes , Pharmacology , Lymphoma, Large B-Cell, Diffuse , Drug Therapy , Pathology , Mice , Mice, Inbred BALB C , Signal Transduction
17.
Article in English | WPRIM | ID: wpr-327727

ABSTRACT

Objective To evaluate the diagnostic performance of elastography in the diagnosis of thyroid nodules in the context of Hashimoto's thyroiditis(HT). Methods The study evaluated 43 thyroid nodules by conventional ultrasound (CU) and elastography in 38 patients co-existed with HT who were referred for operation. The patients underwent CU and elastography before operation. The sensitivity,specificity,positive and negative predictive values,and accuracy for CU,elastography,and combination of these two techniques were assessed by using histopathological results as the gold standard. Results Among these 43 thyroid nodules,pathology confirmed 29 (67.4%) malignant nodules and 14 (32.6%) benign ones. There were statistically significant differences between malignant and benign groups in features such as solid shape (96.6% vs. 64.0%;OR:15.6,95%CI:1.600-151.262,P=0.004),irregularity (90.0% vs. 42.9%;OR:11.6,95%CI:2.341-57.032,P=0.001),taller than wide shape (72.0% vs. 21.4%;OR:9.6,95% CI:2.117-43.753,P=0.002),microcalcification (69% vs. 28.6%;OR:5.6,95% CI:1.368-22.556,P=0.012) and irregular blood flow (90.0% vs. 28.6%;OR:17.3,95%CI:3.186-94.290,P=0.000). The diagnostic performance of elastography and CU was as follows:sensitivity (86.2 % vs.96.6%),specificity (71.4% vs.42.9%),positive predictive value (86.2% vs.77.8%),negative predictive value (71.4% vs.85.7%),and accuracy (81.4% vs.79.0%). The combination of these two techniques had a sensitivity of 93.1%,a specificity of 71.4%,a positive predictive value of 87.1%,a negative predictive value of 83.3%,and an accuracy of 86.0%. Conclusions Elastography has a higher specificity in the diagnosis of thyroid nodules in HT,while its sensitivity is slightly lower than that of CU. Combination of these two techniques can increase the specificity and accuracy.

18.
Chinese Pharmacological Bulletin ; (12): 797-803, 2018.
Article in Chinese | WPRIM | ID: wpr-705129

ABSTRACT

Aim To observe the protective effects of cordycepin ( Cor) on dopaminergic neurons in 1-meth-yl-4-phenyl-1 , 2 , 3 , 6-tetrahydropyridine ( MPTP )-in-duced mouse model of Parkinson's disease ( PD) and to explore its mechanism. Methods C57BL/6 mice were administered with MPTP to establish the PD mod-el. Mice in Cor groups were pretreated with Cor (2.5,5.0 and 10.0 mg·kg-1 ) by intragastric administra-tion, respectively. The motor functions of the mice were observed in the open-field test, rotarod test and pole test. The content of DA, the numbers of TH-im-munoreactive cells and apoptotic cells were measured respectively by HPLC-ECD, immunohistochemistry staining and TUNEL staining. The expression of apop-tosis related proteins and MAPK signaling pathway-re-lated proteins ( p38 , p-p38 , ERK1/2 , p-ERK1/2 JNK1/2 and p-JNK1/2 ) were determined by Western blot. Results Cor could significantly improve the mo-tor dysfunction in PD mice. The contents of DA, DOPAC and HVA in the striatum remarkably increased after administration of Cor in MPTP-induced mice. Mo-reover, Cor could obviously reduce both the loss of TH-immunoreactive neurons and the numbers of TUNEL-positive cells in substantia nigra pars compacta ( SNpc) of PD mice. The protein expressions of Bax and cleaved caspase-3 were markedly down-regulated,whereas those of Bcl-2 and the ration of Bcl-2/Bax were significantly up-regulated by Cor pre-treatment followed by MPTP treatment. Furthermore, the protein expressions of p-p38 , p-ERK1/2 and p-JNK1/2 signif-icantly decreased in substantia nigra in Cor groups. Conclusions The results suggest that Cor can protect DA neurons against MPTP-induced injury by inhibiting apoptosis, which may be closely relevant to the inhibi-tion of MAPK signaling pathways.

19.
China Journal of Endoscopy ; (12): 53-57, 2018.
Article in Chinese | WPRIM | ID: wpr-702969

ABSTRACT

Objective?To evaluate the effect on removal of ovarian cyst by laparoendoscopic single site surgery and enhanced recovery after surgery (ERAS).?Methods?A prospective, single-institution study was performed for patients who were diagnosed benign ovarian cyst, underwent removal ovarian cyst, and adopted ERAS nursing care from June 2015 to June 2017. 40 patients who adopted laparo-endoscopic single site surgery were experimental group and 40 patients who adopted traditional laparoscopy surgery were control group. We compared the operation time, blood loss volume during operation, the time of getting out-of bed after operation, the postoperative exhausting time, the defecation time after surgery, the incidence of postoperative febrile and other complications, the time of hospital stay, and hospitalization expenses between the two groups. The measurement data was tested by t test, and the counting data was tested by χ2 test, which was statistically significant with P < 0.05.?Results?The results showed that the time of getting out-of bed after operation, the postoperative exhausting time, the defecation time after surgery and the time of hospital stay in experimental group was significantly shorter than the control group;Meanwhile the hospitalization expense was lower than the control group. These results were statistically significant (P < 0.05). While there was not statistically significant in the operation time, blood loss volume during operation, and the incidence of postoperative febrile and other complications between the experimental group and the control group (P > 0.05) .?Conclusion?ERAS combined with laparo-endoscopic single site surgery is helpful to the reduction of hospitalization cost and the clinical promotion and application.

20.
Chinese Journal of Immunology ; (12): 810-814, 2018.
Article in Chinese | WPRIM | ID: wpr-702822

ABSTRACT

Objective:To compare the effect of chloroquine on apoptosis of normal gastric epithelial cells and gastric cancer cell line HGC-27. Methods:Change of these two kinds of cells were observed by inverted microscope after treating with CQ. HGC-27 cells were detected on the effect of apoptosis by DAPI nuclear staining after treating with CQ. The proliferation of cells were measured by CCK-8. Changes of mitochondrial membrane potential were investigated by JC-1 after treating with CQ. The expression of apoptosis protein effector enzyme Caspase-3 and substrate PARP in these two kinds of cells were tested by Western blot after using chloroquine (CQ) and rapamycin ( rapamycin, RAP ) to treat cells 72 h. Results: After treated with 10 μmol/L CQ 72 h, morphological characteristics of GES-1 cells and HGC-27 cells could be visible under the microscope,CQ induced apoptosis of GES-1 cells,on the contrary,it could make the HGC-27 cell get widened,the number of apoptotic cells gradually increased,the cell density decreased,cell atrophy and gradually turned round,cytoplasm reduced,at last,lose normal cell morphology. After two kinds of cells treated with CQ 72 h,as for GES-1 cell nuclei stained light,nuclear size and shape were not changed,however,HGC-27 nuclei showed pyknosis or granular fluorescence dense concentrated form. CCK-8 results showed that comparing with normal gastric epithelial cells GES-1,the pro-liferation of gastric cancer HGC-27 cells activity could be inhibited by CQ. JC-1 results showed that the change of the red fluorescence to green fluorescence in HGC-27 cells treated by CQ. Western blot showed that after being treated with CQ and RAP in normal gastric epithelial cells and HGC-27 cell line 72 h,the expression of apoptosis protein Caspase-3 and PARP in gastric cancer cell HGC-27 decreased significantly,comparing to that in GES-1 cells. Conclusion:Compared to normal gastric epithelial cells,CQ can inhibit human gastric cancer HGC-27 cell viability and induce apoptosis.

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