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1.
Hepatol Int ; 17(4): 870-881, 2023 Aug.
Article in English | MEDLINE | ID: mdl-37237087

ABSTRACT

BACKGROUND: There are limited data on the long-term adverse clinical outcomes of adults with metabolic dysfunction-associated fatty liver disease (MAFLD). METHODS: This is a single-centre prospective study of a well-characterized cohort of MAFLD patients who underwent liver biopsy and followed every 6-12 months for adverse clinical outcomes. RESULTS: The data for 202 patients were analyzed [median age 55.0 (48.0-61.3) years old; male, 47.5%; obese, 88.6%; diabetes mellitus, 71.3%; steatohepatitis, 76.7%; advanced fibrosis, 27.2%]. The median follow-up interval was 7 (4-8) years. The cumulative incidence of liver-related events, cardiovascular events, malignancy and mortality was 0.43, 2.03, 0.60 and 0.60 per 100 person-years of follow-up, respectively. Liver-related events were only seen in patient with advanced fibrosis at 9.1% vs 0% in patient without advanced liver fibrosis (p < 0.001). The cumulative incidence of liver-related events among patients with advanced fibrosis was 1.67 per 100 person-years of follow-up. When further stratified to bridging fibrosis and cirrhosis, the cumulative incidence of liver-related events was 1.47 and 3.85 per 100 person-years of follow-up, respectively. Advanced fibrosis was not significantly associated with cardiovascular events, malignancy or mortality. The cumulative incidence of liver-related events, cardiovascular events, malignancy and mortality were not significantly different between patients with and without steatohepatitis and between obese and non-obese patients. However, liver-related events were only seen among obese patients. CONCLUSION: Overall, the cumulative incidence of liver-related event is low in patients with MAFLD, but it is much higher among those with advanced fibrosis. However, there is a relatively high cumulative incidence of cardiovascular event among patients with MAFLD.


Subject(s)
Cardiovascular Diseases , Non-alcoholic Fatty Liver Disease , Humans , Adult , Male , Middle Aged , Prospective Studies , Non-alcoholic Fatty Liver Disease/pathology , Liver Cirrhosis/complications , Fibrosis , Biopsy , Obesity/complications , Cardiovascular Diseases/etiology , Cardiovascular Diseases/complications
2.
Ann Hepatol ; 28(2): 100888, 2023.
Article in English | MEDLINE | ID: mdl-36586588

ABSTRACT

INTRODUCTION AND OBJECTIVES: The Hepamet fibrosis score was introduced for the diagnosis of advanced liver fibrosis in patients with non-alcoholic fatty liver disease (NAFLD). To date, external validation is limited, and its utility in combination with liver stiffness measurement (LSM) has not been explored. MATERIAL AND METHODS: This is a cross-sectional study on NAFLD patients who had a liver biopsy and LSM on the same day. The diagnostic performance of the Hepamet fibrosis score was evaluated using the area under the receiver operating characteristic curve (AUROC). RESULTS: The data for 196 patients were analyzed (mean age 50 ± 11 years old, 50% men, 56.6% Malay, 27.6% Chinese, 15.8% Indian, 67.9% NASH, 15.8% advanced liver fibrosis). The AUROC of Hepamet fibrosis score for the diagnosis of advanced liver fibrosis was 0.85 (95% CI, 0.80 - 0.91). Using the <0.12 and ≥0.47 cut-offs from the original study, the sensitivity, specificity, positive predictive value, negative predictive value, the proportion of indeterminate results and misclassification rate were 81.8%, 91.8%, 47.4%, 98.2%, 32.1% and 6.1%, respectively. Using LSM <10 kPa and ≥15 kPa for the diagnosis of absence and presence of advanced liver fibrosis, respectively, in patients with Hepamet fibrosis score ≥0.47 (i.e., the two-step approach) reduced indeterminate results and misclassification to 16.1% and 3.6%, respectively. CONCLUSIONS: We found the Hepamet fibrosis score to have good diagnostic accuracy in a population that was largely unrepresented in earlier work and demonstrated its utility in a two-step approach with LSM for the diagnosis of advanced liver fibrosis.


Subject(s)
Elasticity Imaging Techniques , Non-alcoholic Fatty Liver Disease , Male , Humans , Adult , Middle Aged , Female , Non-alcoholic Fatty Liver Disease/diagnostic imaging , Non-alcoholic Fatty Liver Disease/pathology , Liver/diagnostic imaging , Liver/pathology , Cross-Sectional Studies , Elasticity Imaging Techniques/methods , Liver Cirrhosis/diagnostic imaging , Liver Cirrhosis/pathology , Biopsy/methods
3.
Article in Chinese | WPRIM (Western Pacific) | ID: wpr-971094

ABSTRACT

OBJECTIVE@#To investigate the effect of Cyr61 on imatinib (IM) resistance in chronic myeloid leukemia (CML) and its mechanism.@*METHODS@#Cyr61 level in cell culture supernatant was determined by enzyme-linked immunosorbent assay. The expression of Cyr61 and Bcl-xL were measured by real-time PCR and Western blot. Cell apoptosis was analyzed using an Annexin V-APC Kit. Expression of signal pathways related proteins was determined by Western blot.@*RESULTS@#The level of Cyr61 obviously increased in K562G cells (IM resistance to CML cell line K562). Down-regulating the expression of Cyr61 decreased the resistance of K562G cells to IM and promoted IM induced apoptosis. In CML mouse model, down-regulating the expression of Cyr61 could increase the sensitivity of K562G cells to IM. The mechanism studies showed that Cyr61 mediated IM resistance in CML cells was related to the regulation of ERK1/2 pathways and apoptosis related molecule Bcl-xL by Cyr61.@*CONCLUSION@#Cyr61 plays an important role in promoting IM resistance of CML cells. Targeting Cyr61 or its related effectors pathways may be one of the ways to overcome IM resistance of CML cells.


Subject(s)
Animals , Humans , Mice , Apoptosis , Drug Resistance, Neoplasm , Imatinib Mesylate/pharmacology , K562 Cells , Leukemia, Myelogenous, Chronic, BCR-ABL Positive/metabolism , Signal Transduction
4.
Article in Chinese | WPRIM (Western Pacific) | ID: wpr-992744

ABSTRACT

Objective:To investigate the early curative effects of robot-assisted total knee arthroplasty (TKA) in the treatment of valgus knee.Methods:A retrospective study was conducted to analyze the data of 40 patients with valgus knee who had been treated by TKA at Department of Orthopaedics, The 920th Hospital of Joint Logistics Support Force of Chinese People's Liberation Army from January to December 2021. The patients were divided into 2 groups according to whether a robot had been used or not for TKA. In the observation group of 15 cases for which TKA was assisted by a robot, there were 4 males and 11 females with an age of (65.5±6.2) years, and the disease course was 42 (36, 54) months; in the control group of 25 cases for which conventional TKA was performed, there were 8 males and 17 females with an age of (65.8±7.5) years, and the disease course was 42 (36, 60) months. Surgical time, hemoglobin decrease, and knee joint range of motion, American Knee Society Score (KSS), hip-knee-ankle angle (HKA), lateral distal femoral angle (LDFA), and medial proximal tibial angle (MPTA) at 12 months after surgery were compared between the 2 groups.Results:There was no significant difference in the preoperative general data between the 2 groups, indicating comparability ( P>0.05). The surgical time in the observation group was (148.0±21.2) min, significantly longer than that in the control group [(115.2±7.1) min], and the hemoglobin decreased by (11.8±1.1) g/L in the observation group, significantly less than that in the control group [(18.1±1.8) g/L] ( P<0.05). The observation group and the control group were followed up for 13 (13, 14) and 13 (13, 14) months after surgery, respectively, showing no statistically significant difference ( P>0.05). At 12 months after surgery, the KSS knee score, KSS functional score, and knee range of motion in the observation group were (86.1±4.6) points, (86.9±3.1) points, and 115.7°±5.0°, significantly larger than those in the control group [(82.2±3.5) points, (82.8±0.9) points, and 108.2°±5.0°] ( P<0.05). Reexamination of full-length radiographs of both lower limbs in all patients showed good positions of the prostheses and no such adverse events as loosening or sinking at 12 months after surgery. The HKA (178.5°±1.2°) and LDFA (89.1°±0.7°) at 12 months after surgery in the observation group were significantly larger than those in the control group (176.6°±1.5°, 88.2°±8.2°) ( P<0.05); there was no statistically significant difference in MPTA between the 2 groups ( P>0.05). Conclusions:In the treatment of valgus knee, robot-assisted TKA can correct joint deformity, and achieve precise osteotomy and functional alignment of lower limbs, leading to better early curative effects than conventional TKA.

5.
Entropy (Basel) ; 23(7)2021 Jun 24.
Article in English | MEDLINE | ID: mdl-34202445

ABSTRACT

A critical question relevant to the increasing importance of crowd-sourced-based finance is how to optimize collective information processing and decision-making. Here, we investigate an often under-studied aspect of the performance of online traders: beyond focusing on just accuracy, what gives rise to the trade-off between risk and accuracy at the collective level? Answers to this question will lead to designing and deploying more effective crowd-sourced financial platforms and to minimizing issues stemming from risk such as implied volatility. To investigate this trade-off, we conducted a large online Wisdom of the Crowd study where 2037 participants predicted the prices of real financial assets (S&P 500, WTI Oil and Gold prices). Using the data collected, we modeled the belief update process of participants using models inspired by Bayesian models of cognition. We show that subsets of predictions chosen based on their belief update strategies lie on a Pareto frontier between accuracy and risk, mediated by social learning. We also observe that social learning led to superior accuracy during one of our rounds that occurred during the high market uncertainty of the Brexit vote.

6.
Z Orthop Unfall ; 159(1): 54-66, 2021 Feb.
Article in English | MEDLINE | ID: mdl-31746442

ABSTRACT

OBJECTIVE: TGFß1 plays an important role in the metabolism of articular cartilage and bone; however, the pathological mechanism and targets of TGFß1 in cartilage degradation and uncoupling of subchondral bone remodeling remain unclear. Therefore, in this study, we investigated the relationship between TGFß1 and major protein-degrading enzymes, and evaluated the role of high levels of active TGFß1 in the thickening of subchondral bone and calcification of articular cartilage. MATERIALS AND METHODS: The expression of TGFß1 and protein-degrading enzymes in clinical samples of articular cartilage and subchondral bone obtained from the knee joint of patients with osteoarthritis was detected by immunohistochemistry. The expression levels of TGFß1, MMP-3, MMP-13 and IL-1ß in cartilage and subchondral bone tissues were detected by absolute real-time quantitative RT-PCR. The expression of TGFß1, nestin and osterix in subchondral bone was detected by Western blot analysis and immunohistochemistry. The degree of subchondral bone thickening was determined by micro-computed tomography (CT) imaging. RESULTS: Expression of TGFß1 and cartilage-degrading enzymes was higher in the cartilage-disrupted group than that in the intact group. Furthermore, expression of TGFß1, nestin and osterix was significantly higher in the OA group than that in the control group. Micro-CT imaging showed that in the OA group, the subchondral bone plate is thickened and the density is increased. The trabecular bone structure is thick plate-like structure, the thickness of the trabecular bone is increased and the gap is small. CONCLUSIONS: The data suggest that highly active TGFß1 activates the expression of cartilage-degrading enzymes. Abnormally activated TGFß1 may induce formation of the subchondral bone and expansion of the calcified cartilage area, eventually leading to degradation of the cartilage tissue.


Subject(s)
Bones of Lower Extremity/metabolism , Cartilage, Articular , Enzymes/metabolism , Extracellular Matrix Proteins/biosynthesis , Knee Joint/metabolism , Osteoarthritis, Knee , Transforming Growth Factor beta/biosynthesis , Bones of Lower Extremity/diagnostic imaging , Calcinosis/diagnostic imaging , Calcinosis/metabolism , Cartilage, Articular/diagnostic imaging , Cartilage, Articular/metabolism , Extracellular Matrix Proteins/metabolism , Humans , Immunohistochemistry , Knee Joint/diagnostic imaging , Osteoarthritis, Knee/diagnostic imaging , Osteoarthritis, Knee/metabolism , Proteins/metabolism , Transforming Growth Factor beta/metabolism , X-Ray Microtomography
7.
EMBO Mol Med ; 13(1): e13207, 2021 01 11.
Article in English | MEDLINE | ID: mdl-33283973

ABSTRACT

The approval of bedaquiline has placed energy metabolism in the limelight as an attractive target space for tuberculosis antibiotic development. While bedaquiline inhibits the mycobacterial F1 F0 ATP synthase, small molecules targeting other components of the oxidative phosphorylation pathway have been identified. Of particular interest is Telacebec (Q203), a phase 2 drug candidate inhibitor of the cytochrome bcc:aa3 terminal oxidase. A functional redundancy between the cytochrome bcc:aa3 and the cytochrome bd oxidase protects M. tuberculosis from Q203-induced death, highlighting the attractiveness of the bd-type terminal oxidase for drug development. Here, we employed a facile whole-cell screen approach to identify the cytochrome bd inhibitor ND-011992. Although ND-011992 is ineffective on its own, it inhibits respiration and ATP homeostasis in combination with Q203. The drug combination was bactericidal against replicating and antibiotic-tolerant, non-replicating mycobacteria, and increased efficacy relative to that of a single drug in a mouse model. These findings suggest that a cytochrome bd oxidase inhibitor will add value to a drug combination targeting oxidative phosphorylation for tuberculosis treatment.


Subject(s)
Mycobacterium tuberculosis , Tuberculosis , Animals , Anti-Bacterial Agents , Antitubercular Agents/pharmacology , Electron Transport Complex IV/metabolism , Mice , Oxidoreductases , Tuberculosis/drug therapy
8.
Journal of Integrative Medicine ; (12): 251-257, 2021.
Article in English | WPRIM (Western Pacific) | ID: wpr-881017

ABSTRACT

OBJECTIVE@#To investigate the therapeutic effect of moxibustion on sarcomas from mesenchymal tissues, which have a low response rate to chemotherapy and radiotherapy.@*METHODS@#S180 sarcoma cell line was inoculated in C57BL/6 mice to form transplanted tumor. Moxibustion therapy was directly applied at the transplanted tumor sites, at a distance of 3.0 cm, 10 min per session, till skin temperature reached 45 °C, once a day, for 14 consecutive days of intervention. After the mice were killed, serum was collected and used to detect concentrations of interleukin-10 (IL-10), transforming growth factor-β1 (TGF-β1), IL-4 and interferon-γ (IFN-γ) by Luminex liquid suspension chip. The numbers of Treg@*RESULTS@#Weight of S180 transplanted tumor in the control group was (2.03 ± 0.54) g, and that in the moxibustion group was (1.27 ± 0.29) g, which was statistically different (P = 0.023). The mean value of Foxp3@*CONCLUSION@#Moxibustion may have therapeutic effects on sarcomas by reducing the number of Treg cells in the blood and controlling the infiltration of Treg cells in the TME.

9.
FEBS Lett ; 594(17): 2829-2839, 2020 09.
Article in English | MEDLINE | ID: mdl-32557576

ABSTRACT

The ability of Mycobacteria to overcome oxidative stress is of paramount importance for its survival within the host. One of the key enzymes that are involved in protecting the bacterium from reactive oxygen species is the catalase-peroxidase (KatG). However, in strains resistant to the antibiotic isoniazid, KatG is rendered ineffective, which is associated with an increased expression of alkylhydroperoxide reductase subunit C (AhpC). Mycobacterial AhpC possesses a unique helical displacement when compared to its bacterial counterparts. Here, via mutagenesis studies, we demonstrate the importance of this helix for redox modulation of the catalytic activity of AhpC. Along with structural insights from crystallographic data, the impact of critical residues on the structure and flexibility of the helix and on AhpC oligomerization is described.


Subject(s)
Mycobacterium tuberculosis/chemistry , NADP/chemistry , Peroxiredoxins/chemistry , Protein Subunits/chemistry , Amino Acid Sequence , Catalytic Domain , Cloning, Molecular , Crystallography, X-Ray , Escherichia coli/genetics , Escherichia coli/metabolism , Gene Expression , Genetic Vectors/chemistry , Genetic Vectors/metabolism , Kinetics , Models, Molecular , Mycobacterium tuberculosis/enzymology , NADP/metabolism , Oxidation-Reduction , Peroxiredoxins/genetics , Peroxiredoxins/metabolism , Protein Binding , Protein Conformation, alpha-Helical , Protein Conformation, beta-Strand , Protein Interaction Domains and Motifs , Protein Multimerization , Protein Subunits/genetics , Protein Subunits/metabolism , Recombinant Proteins/chemistry , Recombinant Proteins/genetics , Recombinant Proteins/metabolism , Sequence Alignment , Sequence Homology, Amino Acid
10.
ACS Infect Dis ; 6(4): 725-737, 2020 04 10.
Article in English | MEDLINE | ID: mdl-32092260

ABSTRACT

The ability to respire and generate adenosine triphosphate (ATP) is essential for the physiology, persistence, and pathogenicity of Mycobacterium tuberculosis, which causes tuberculosis. By employing a lead repurposing strategy, the malarial cytochrome bc1 inhibitor SCR0911 was tested against mycobacteria. Docking studies were carried out to reveal potential binding and to understand the binding interactions with the target, cytochrome bcc. Whole-cell-based and in vitro assays demonstrated the potency of SCR0911 by inhibiting cell growth and ATP synthesis in both the fast- and slow-growing M. smegmatis and M. bovis bacillus Calmette-Guérin, respectively. The variety of biochemical assays and the use of a cytochrome bcc deficient mutant strain validated the cytochrome bcc oxidase as the direct target of the drug. The data demonstrate the broad-spectrum activity of SCR0911 and open the door for structure-activity relationship studies to improve the potency of new mycobacteria specific SCR0911 analogues.


Subject(s)
Antimalarials/pharmacology , Antitubercular Agents/pharmacology , Drug Repositioning , Electron Transport Complex IV/antagonists & inhibitors , Mycobacterium/drug effects , Adenosine Triphosphate/biosynthesis , Bacterial Proteins/metabolism , Drug Resistance, Multiple, Bacterial , Molecular Docking Simulation
11.
Article in Chinese | WPRIM (Western Pacific) | ID: wpr-869859

ABSTRACT

Objective:To evaluate the effect of astaxanthin on neuropathic pain in rats and the role of spinal heme oxygenase-1 (HO-1).Methods:Seventy-two SPF-grade healthy adult male Sprague-Dawley rats, weighing 200-250 g, in which intrathecal catheters were successfully implanted, were divided into 6 groups ( n=12 each) by a random number table method: blank control group (group C), sham operation group (Sham group), neuropathic pain (NP) group, NP plus dimethyl sulfoxide (DMSO) group (NP + DMSO group), NP plus astaxanthin group (NP + AST group) and NP plus zinc protoporphyrin plus astaxanthin group (NP+ ZnPP+ AST group). NP was induced by chronic constriction injury in anesthetized rats.In Sham group, the sciatic nerve was only isolated without ligation.At 5 days after establishing the model, 0.5% DMSO 10 μl was intrathecally injected in NP+ DMSO group, astaxanthin 1 μg (dissolved in 10 μl DMSO) was intrathecally injected in NP+ AST group, HO-1 inhibitor zinc protoporphyrin 24 μg (dissolved in 10 μl DMSO) was intrathecally injected, and 3 h later astaxanthin 1 μg (dissolved in 10 μl DMSO) was intrathecally injected in NP+ ZnPP+ AST group.Injection was given once a day for 10 consecutive days in the 3 groups mentioned above.The mechanical paw withdrawal threshold (MWT) and thermal paw withdrawal latency (TWL) were measured at 1 day before establishing the model and 3, 7 and 14 days after establishing the model.The rats were sacrificed at 14 days after establishing the model, and the L 4-6 lumbar segments of the spinal cord were removed for determination of the contents of tumor necrosis factor-alpha (TNF-α), interleukin-1beta (IL-1β), superoxide dismutase (SOD) and glutathione peroxidase (GHS-PX)(by enzyme-linked immunosorbent assay) and expression of HO-1 (by Western blot). Results:Compared with group C and group Sham, the MWT was significantly decreased and TWL was shortened at each time point after establishing the model, the contents of TNF-α and IL-1β were increased, and the expression of HO-1 was up-regulated in the other four groups, the SOD and GSH-PX contents were significantly decreased in NP group, NP+ DMSO group and NP+ ZnPP+ AST group, and the SOD and GSH-PX contents were significantly increased in NP+ AST group ( P<0.05). Compared with NP group, the MWT was significantly increased and TWL was prolonged at 7 and 14 days after establishing the model, the contents of TNF-α and IL-1β were decreased, and the expression of HO-1 was up-regulated in NP+ AST group, the expression of HO-1 was down-regulated in NP+ ZnPP+ AST group ( P<0.05), and no significant change was found in the parameters mentioned above in NP+ DMSO group ( P>0.05). Compared with NP+ AST group, the MWT was significantly decreased and TWL was shortened at 7 and 14 days after establishing the model, the contents of SOD and GSH-PX were decreased, the contents of TNF-α and IL-1β were increased, and the expression of HO-1 was down-regulated in NP+ ZnPP+ AST group ( P<0.05). Conclusion:Astaxanthin can reduce NP in rats, and the mechanism is related to up-regulating the expression of HO-1 in the spinal cord and inhibiting oxidative stress and inflammatory responses.

12.
Article in Chinese | WPRIM (Western Pacific) | ID: wpr-751486

ABSTRACT

As a glycopeptide antibiotic,vancomycin is the first choice for treatment of methicilin-resistant staphylococcus aureus (MRSA) infection.Because of the metabolic individual difference,if children were given the dose according to the instruction,few patients can achieve the valley concentration as recommended in the guideline.So it's necessary for optimizing individual vancomycin dosage regimen with the help of therapeutic drug monitoring (TDM) and population pharmacokinetics model-nonlinear mixed effect model (NONMEM),in order to realiz the combination of effect and safety.This article will introduce the population pharmacokinetics model of vancomycin in children and discuss about major parameters influencing vancomycin metabolism,including age,body mass index,renal function,health condition,and drug combination.With rational therapeutic drug monitoring and optimizing parameters of NONMEM,we hope to realize area under concentration-time curve/minimum inhibit concentration (AUC/MIC) ratio ≥400,and to provide the reference for safe and rational pediatric dosage regimen.

13.
Article in English | MEDLINE | ID: mdl-29710824

ABSTRACT

Earth-rock dams make up a large proportion of the dams in China, and their failures can induce great risks. In this paper, the risks associated with earth-rock dam failure are analyzed from two aspects: the probability of a dam failure and the resulting life loss. An event tree analysis method based on fuzzy set theory is proposed to calculate the dam failure probability. The life loss associated with dam failure is summarized and refined to be suitable for Chinese dams from previous studies. The proposed method and model are applied to one reservoir dam in Jiangxi province. Both engineering and non-engineering measures are proposed to reduce the risk. The risk analysis of the dam failure has essential significance for reducing dam failure probability and improving dam risk management level.


Subject(s)
Engineering/standards , Equipment Failure , Fuzzy Logic , Rivers , China , Humans , Hydrodynamics
14.
Article in Chinese | WPRIM (Western Pacific) | ID: wpr-951603

ABSTRACT

Objective: To explore the effect of bortezomib on migration and invasion of cervical carcinoma HeLa cell and specific molecular mechanism. Methods: The effect of bortezomib on the viability of HeLa cell was measured by MTT assay. The effect of bortezomib on cell migration and invasion was measured by Transwell assay and invasion experiment respectively. The activation of Akt/mTOR signaling pathway and expression level of MMP2, MMP9 were assayed by western blot. Results: MTT assay indicated bortezomib (2.5μM, 5μM, 10μM) could inhibit HeLa cell viability, and the inhibitory rate was highest at 48h. Transwell assay and invasion experiment results showed that bortezomib inhibited HeLa cell migration and invasion. Western blotting assays presented bortezomib could suppress the phosphorylation of Akt and mTOR, and down-regulate the expression of MMP2 and MMP9. Conclusions: These results suggested bortezomib could inhibit migration and invasion in cervical carcinoma HeLa cell, which might be related to Akt/mTOR signal pathway.

15.
Article in English | WPRIM (Western Pacific) | ID: wpr-820328

ABSTRACT

OBJECTIVE@#To explore the effect of bortezomib on migration and invasion of cervical carcinoma HeLa cell and specific molecular mechanism.@*METHODS@#The effect of bortezomib on the viability of HeLa cell was measured by MTT assay. The effect of bortezomib on cell migration and invasion was measured by Transwell assay and invasion experiment respectively. The activation of Akt/mTOR signaling pathway and expression level of MMP2, MMP9 were assayed by western blot.@*RESULTS@#MTT assay indicated bortezomib (2.5 μM, 5 μM, 10 μM) could inhibit HeLa cell viability, and the inhibitory rate was highest at 48 h. Transwell assay and invasion experiment results showed that bortezomib inhibited HeLa cell migration and invasion. Western blotting assays presented bortezomib could suppress the phosphorylation of Akt and mTOR, and down-regulate the expression of MMP2 and MMP9.@*CONCLUSIONS@#These results suggested bortezomib could inhibit migration and invasion in cervical carcinoma HeLa cell, which might be related to Akt/mTOR signal pathway.

16.
Article in Chinese | WPRIM (Western Pacific) | ID: wpr-499694

ABSTRACT

Objective: To explore the effect of bortezomib on migration and invasion of cervical carcinoma HeLa cell and specific molecular mechanism. Methods:The effect of bortezomib on the viability of HeLa cell was measured by MTT assay. The effect of bortezomib on cell migration and invasion was measured by Transwell assay and invasion experiment respectively. The activation of Akt/mTOR signaling pathway and expression level of MMP2, MMP9 were assayed by western blot. Results:MTT assay indicated bortezomib (2.5μM, 5μM, 10μM) could inhibit HeLa cell viability, and the inhibitory rate was highest at 48 h. Transwell assay and invasion experiment results showed that bortezomib inhibited HeLa cell migration and invasion. Western blotting assays presented bortezomib could suppress the phosphorylation of Akt and mTOR, and down-regulate the expression of MMP2 and MMP9. Conclusions:These results suggested bortezomib could inhibit migration and invasion in cervical carcinoma HeLa cell, which might be related to Akt/mTOR signal pathway.

17.
Article in Chinese | WPRIM (Western Pacific) | ID: wpr-239162

ABSTRACT

<p><b>OBJECTIVE</b>To investigate the effects of the furin inhibitor α1-PDX on the growth, invasion, and tumorigenicity of cervical cancer cells and explore the mechanisms.</p><p><b>METHODS</b>The changes in the growth, migration and invasion of α1-PDX-transfected HeLa cells were observed using MTT assay, Boyden migration and invasion assay. The protein levels of furin and MT1-MMP were measured using Western blotting and furin activity was detected by enzyme activity assay in the transfected cells. HeLa cells were seeded subcutaneously in nude mice and the tumor volume changes were recorded.</p><p><b>RESULTS</b>Compared with the control cells, α1-PDX-treated cells showed a significant growth inhibition by 18.4% at 24 h (P<0.01) with obviously lowered migration ability and cell invasiveness (P<0.01). Treatment with α1-PDX significantly reduced furin enzyme activity and MTI-MMP protein levels in HeLa cells. In nude mice, α1-PDX-treated HeLa cells exhibited a delayed and lowered tumorigenicity with reduced size of the tumors.</p><p><b>CONCLUSION</b>α1-PDX can inhibit the growth, metastasis and tumorigenicity of HeLa cells, the mechanism of which may involve a decreased furin activity and MTI-MMP expression.</p>


Subject(s)
Animals , Female , Humans , Mice , Furin , HeLa Cells , Mice, Nude , Neoplasm Transplantation , Transfection , Uterine Cervical Neoplasms , Pathology , alpha 1-Antitrypsin , Pharmacology
18.
Chinese Medical Journal ; (24): 3035-3041, 2011.
Article in English | WPRIM (Western Pacific) | ID: wpr-292758

ABSTRACT

<p><b>BACKGROUND</b>The goal of surgery in the treatment of intrinsic cerebral tumors is to resect the maximum tumor volume, and to spare the eloquent areas. However, it is difficult to discover the eloquent areas intraoperatively due to individual anatomo-functional variability both for sensori-motor and language functions. Consequently, the surgery of intrinsic cerebral tumors frequently results in poor extent of resection or permanent postoperative deficits, or both, and remains a difficult problem for neurosurgeons.</p><p><b>METHODS</b>From January 2003 to January 2010, 112 patients with neuroepithelial tumors in/close to the eloquent areas were operated on under awake anesthesia with the intraoperative direct electrical stimulation for functional mapping of the eloquent areas. The extent of the tumors was verified by intraoperative ultrasonography. The maximal resection of the tumors and minimal damage of the eloquent areas were the surgical goal of all patients.</p><p><b>RESULTS</b>Totally 356 cortical sites in 99 patients were detected for motor response by intraoperative direct electrical stimulation, 50 sites in 16 patients for sensory, 72 sites in 48 patients for language. Sixty-six patients (58.9%) achieved total resection, 34 (30.4%) subtotal and 12 (10.7%) partial. Fifty-eight patients (51.8%) had no postoperative deficit, while 37 patients (33.0%) had transitory postoperative paralysis, 26 patients (23.2%) with transitory postoperative language disturbance and 3 patients (2.7%) with permanent neurological deficits. No patient complained of pain recollection following operation.</p><p><b>CONCLUSIONS</b>Awake anesthesia, intraoperative direct electrical stimulation and ultrasonography are three core techniques for the resection of intrinsic cerebral tumors near the eloquent areas. This new concept allows an improvement in the quality of surgery for neuroepithelial tumors in/adjacent to eloquent areas.</p>


Subject(s)
Adolescent , Adult , Aged , Female , Humans , Male , Middle Aged , Anesthesia , Methods , Brain Mapping , Methods , Brain Neoplasms , Diagnostic Imaging , General Surgery , Deep Brain Stimulation , Methods , Neoplasms, Neuroepithelial , Diagnostic Imaging , General Surgery , Ultrasonography
19.
Article in Chinese | WPRIM (Western Pacific) | ID: wpr-332564

ABSTRACT

<p><b>OBJECTIVE</b>To determine the minimum alveolar concentration (EC(50) and EC(95)) of sevoflurane in body movement response to surgical incision during combined anesthesia with dexmedetomidine, sevoflurane and fentanyl.</p><p><b>METHODS</b>Twenty-six ASA class I or II patients (aged 18-60 years) underwent selective surgery for lumbar disc herniation under general anesthesia with the combination of with dexmedetomidine, sevoflurane and fentanyl. All the patients received infusion with 0.5 mg/kg dexmedetomidine for 10 min before anesthesia induction with intravenous injection of 3 µg/kg fentanyl 8% sevoflurane inhalation. Upon loss of consciousness, sevoflurane concentration was reduced to 5% with intravenous injection of 1-2 mg/kg succinylcholine, and intubation was started after muscles relaxation. Anesthesia was maintained by sevoflurane and dexmedetomidine (0.2 µg·kg(-1)·h(-1)). Before the surgery, a steady state end-tidal sevoflurane concentration was maintained for at least 10 min. The first patient of the series was tested with 1.5% sevoflurane, and the concentration was adjusted according to modified Dixons up-and-down method (with a step size of 0.2%). Probit analysis was used for calculating EC(50), EC(95) and the 95% confidence interval (CI).</p><p><b>RESULTS</b>The EC(50) of sevoflurane was 0.94% (95%CI of 0.76%-1.07% ) and EC(95) was 1.23% (95%CI 1.09%-2.05% ).</p><p><b>CONCLUSION</b>The EC(50) and EC(95) of sevoflurane are 0.94% and 1.23%, respectively, for suppressing body movement in response to surgical incision during combined anesthesia with sevoflurane, dexmedetomidine and fentanyl.</p>


Subject(s)
Adolescent , Adult , Female , Humans , Male , Middle Aged , Young Adult , Anesthesia , Methods , Anesthetics , Dexmedetomidine , Fentanyl , Methyl Ethers , Pharmacokinetics , Pulmonary Alveoli , Metabolism , Reference Values
20.
Article in Chinese | WPRIM (Western Pacific) | ID: wpr-416814

ABSTRACT

Objective To investigate the feasibility of NR2B small interference RNA(NR2B siRNA)carried by water-soluble lipopolymer(WSLP)for treatment of neuropathic pain in rats.Methods One hundred healthy male SD rats weighing 180-200 g were randomly divided into 5 groups(n=20 each):normal control group (group C),sham operation group(group S),neuropathic pain group(group NP),group WSLP-NR2B siRNA (group W)and group WSLP-negative NR2B siRNA(group WN).Neuropathic pain was induced by partial ligation of sciatic nenre.WSLP-NR2B siRNA complex was formed by binding WSLP and NR2B siRNA.Normal saline.WSLP-NR2B siRNA complex and WSLP-negative NR2B siRNA 20μl were injected intrathecally after operation in NP,W and WN groups respectively.Mechanical withdrawal threshold(MWT)and thermal withdrawal duration (TWD)were measured before(baseline)and at 3,7,14 and 21 days after operation.Ten animals in each group were sacrificed on the 3rd day after operation and the lumbar segment(L4-6)of the dorsal root ganglia was removed for determination of the expression of NR2B mRNA and protein using RT-PCR and Western blot analysis.Results Sciatic nerve ligation significantly decreased MWT and prolonged TWD and increased NR2B mRNA and protein expression in group NP as compared with group C.WSLP-NR2B siRNA complex significantly reduced sciatic nerve ligation-induced hyperalgesia and decreased NR2B mRNA and protein expression in group W as compared with group NP.Conclusion WSLP not only mediates NR2B siRNA successfully and inhibits the expression of NR2B,but also reduces neuropathic pain in rats.

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