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Objective: To compare the prognosis and perioperative situation of patients with stage Ⅱ endometrial cancer (EC) between radical hysterectomy/modified radical hysterectomy (RH/mRH) and simple hysterectomy (SH). Methods: A total of 47 patients diagnosed EC with stage Ⅱ [International Federation of Gynecology and Obstetrics (FIGO) 2009] by postoperative pathology, from January 2006 to January 2021 in Peking University People's Hospital, were analyzed retrospectively. The patients were (54.4±10.7) years old, and the median follow-up time was 65 months (ranged 9-138 months). They were divided into RH/mRH group (n=14) and SH group (n=33) according to the scope of operation. Then the prognosis of patients between the groups were compared, and the independent prognostic factors of stage Ⅱ EC were explored. Results: (1) The proportions of patients with hypertension in RH/mRH group and SH group were 2/14 and 45% (15/33), the amounts of intraoperative blood loss were (702±392) and (438±298) ml, and the incidence of postoperative complications were 7/14 and 15% (5/33), respectively. There were significant differences (all P<0.05). (2) The median follow-up time of RH/mRH group and SH group were 72 vs 62 months, respectively (P=0.515). According to Kaplan-Meier analysis and log-rank method, the results showed that there were no significant difference in 5-year progression-free survival (PFS) rate (94.3% vs 84.0%; P=0.501), and 5-year overall survival rate (92.3% vs 92.9%; P=0.957) between the two groups. Cox survival analysis indicated that age, pathological type, serum cancer antigen 125 (CA125), and estrogen receptor (ER) status were associated with 5-year PFS rate (all P<0.05). But the scope of hysterectomy (RH/mRH and SH) did not affect the 5-year PFS rate of stage Ⅱ EC patients (P=0.508). And level of serum CA125 and ER status were independent prognostic factors for 5-year PFS rate (all P<0.05). Conclusions: This study could not find any survival benefit from RH/mRH for stage Ⅱ EC, but increases the incidence of postoperative complications. Therefore, the necessity of extending the scope of hysterectomy is questionable.
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Female , Humans , Adult , Middle Aged , Aged , Disease-Free Survival , Retrospective Studies , Neoplasm Staging , Prognosis , Endometrial Neoplasms/pathology , Hysterectomy/methods , Postoperative Complications/epidemiology , Uterine Cervical Neoplasms/pathologyABSTRACT
OBJECTIVE@#In order to solve the technical problems, clinical researchers face the process of medical imaging analysis such as data labeling, feature extraction and algorithm selection, a medical imaging oriented multi-disease research platform based on radiomics and machine learning technology was designed and constructed.@*METHODS@#Five aspects including data acquisition, data management, data analysis, modeling and data management were considered. This platform provides comprehensive functions such as data retrieve and data annotation, image feature extraction and dimension reduction, machine learning model running, results validation, visual analysis and automatic generation of analysis reports, thus an integrated solution for the whole process of radiomics analysis has been generated.@*RESULTS@#Clinical researchers can use this platform for the whole process of radiomics and machine learning analysis for medical images, and quickly produce research results.@*CONCLUSIONS@#This platform greatly shortens the time for medical image analysis research, decreasing the work difficulty of clinical researchers, as well as significantly promoting their working efficiency.
Subject(s)
Machine Learning , Diagnostic Imaging , Algorithms , RadiographyABSTRACT
The immune checkpoint blockade therapy has profoundly revolutionized the field of cancer immunotherapy. However, despite great promise for a variety of cancers, the efficacy of immune checkpoint inhibitors is still low in colorectal cancer (CRC). This is mainly due to the immunosuppressive feature of the tumor microenvironment (TME). Emerging evidence reveals that certain chemotherapeutic drugs induce immunogenic cell death (ICD), demonstrating great potential for remodeling the immunosuppressive TME. In this study, the potential of ginsenoside Rg3 (Rg3) as an ICD inducer against CRC cells was confirmed using in vitro and in vivo experimental approaches. The ICD efficacy of Rg3 could be significantly enhanced by quercetin (QTN) that elicited reactive oxygen species (ROS). To ameliorate in vivo delivery barriers associated with chemotherapeutic drugs, a folate (FA)-targeted polyethylene glycol (PEG)-modified amphiphilic cyclodextrin nanoparticle (NP) was developed for co-encapsulation of Rg3 and QTN. The resultant nanoformulation (CD-PEG-FA.Rg3.QTN) significantly prolonged blood circulation and enhanced tumor targeting in an orthotopic CRC mouse model, resulting in the conversion of immunosuppressive TME. Furthermore, the CD-PEG-FA.Rg3.QTN achieved significantly longer survival of animals in combination with Anti-PD-L1. The study provides a promising strategy for the treatment of CRC.
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Objective To explore the associations of body mass index (BMI), waist circumference (WC), waist height ratio (WHtR) and the prevalence of hypertension in elderly residents over 60 years in Baodi district, Tianjin. Methods Residents over 60 who underwent medical examinations in the Koudong Health Center, Baodi district, Tianjin, were all invited to participate in the study from April to May, 2018. Participants were asked to fill out structured questionnaires and undergo physical examinations. Stratified analysis and logistic regression analysis were applied to examine joint effects and interactions of BMI and WC (or WHtR) on the risk of hypertension. Results A total of 1 417 residents (83.75%) out of 1 692 residents participated in the study. The prevalence of hypertension in the participants was 46.36%. 66.50% of the participants were BMI overweight or obese. Participants with central obesity accounted for 74.66% (measured by the WC) and 75.38% (by the WHtR). Compared to the normal weight measured by the BMI or the WC, BMI overweight (OR=1.65, 95%CI: 1.19-2.30) or obesity (OR=3.41, 95%CI: 2.23-5.20) and WC central obesity (OR: 1.49, 95%CI: 1.00-2.23) were associated with increased risk of hypertension. The joint effects of BMI and WC (OR=2.49, 95%CI: 1.78-3.46), or BMI and WHtR (WHtR overweight: OR=2.05, 95%CI: 1.41-2.99; WHtR obesity: OR=2.37, 95%CI: 1.50-3.76) were greater than the single effect of the latter (WC overweight/obesity: OR=1.39, 95%CI: 0.90-2.15; WHtR overweight: OR=1.02, 95%CI: 0.62-1.66; WHtR obesity: OR=1.44, 95%CI：0.55-3.81). Conclusions Of the three indices, BMI is strongly correlated with the risk of hypertension. BMI overweight or obesity has enhanced the association of WC or WHtR and the risk of hypertension, suggesting that weight control in the normal range, especially measured by the BMI index, may prevent and control hypertension.
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Objective: To observe the clinical efficacy of Chaoyi Qingfei Xiegan Tang on type 2 diabetes mellitus (T2DM), and the regulatory effect on inflammatory markers and intestinal flora. Method: One hundred and twenty-two patients were randomly divided into control group (65 cases) and observation group (67 cases) by random number table. Patients in control group got metformin hydrochloride, 0.25 g/time, 2-3 times/day, and the dose was regulated based on glycemic control. In addition to the therapy in control groups, patients in observation group were also given Qingfei Xiegan Tang, 1 dose/day. A course of treatment was 2 months. Before and after treatment, levels of fasting blood glucose (FPG), 2 h-postprandial plasma glucose (2 h PPG), glycosylated hemoglobin (HbA1c), fasting insulin (FINS), triglyceride (TG), total cholesterol (TC), high-density lipoprotein cholesterol (HLD), low-density lipoprotein (LDL-C), interleukin-6 (IL-6), IL-8, tumor necrosis factor-α(TNF-α) and C-reactive protein (CRP) were detected. And insulin sensitivity index (ISI), HOMA insulin resistance index (HOMA-IR) and intestinal flora were detected. And scores of TCM symptoms were graded. Result: By rank sum test, the clinical efficacy of disease in observation group was better than that in control group (Pα and CRP were lower than those in control group (PPPPConclusion: Qingfei Xiegan Tang can ameliorate 2 h PG, regulate levels of glucose, lipid and intestinal flora, relieve clinical symptoms, and inhibit inflammatory response, with a better clinical efficacy than that of pure western medicine.
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Characterized by eminent mechanical properties, chemical stability and biosafety, polyetheretherketone (PEEK), as a brand-new type of biomedical material, has been applied in the field of stomatology. This review elaborates on basic behaviors and fabrication methods of PEEK and its composite, and their application in fixed dental prostheses (FDP) as frameworks as well as their adhesive properties. Meanwhile, this review also looks into the prospect of the integration of additive manufacturing in fabricating frameworks of PEEK and its composite in FDP.
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Objective@#To explore the effect of Huangqi-Baoxin decoction combined with conventional western medicine on the cardiac function of the patients with diabetic cardiomyopathy (DCM).@*Methods@#A total of 103 DCM patients who met the inclusion criteria were divided into the control group (51 cases) and the research group (52 cases) by random number table method. The control group was treated with conventional therapy, while the study group was treated with Huangqi-Baoxin decoction on the basis of the control group. Both groups were treated for 3 months. TCM syndromes were scored before and after treatment. The serum GSH-Px, SOD and CRP levels were measured by ELISA. Left ventricular ejection fraction (LVEF) and E/A ratio of early diastolic peak velocity to late diastolic peak velocity (E/A) were measured by echocardiography and then evaluate the clinical efficacy.@*Results@#The total effective rate was 92.3% (48/52) in the study group and 76.5% (39/51) in the control group. There was significant difference between the two groups (χ2=4.922, P=0.027). After treatment, the scores of palpitation, shortness of breath, chest tightness and chest pain, fatigue, hypochondriac mass, spontaneous sweating, edema and total scores in the study group were significantly lower than those in the control group (t values were 10.603, 9.997, 10.546, 10.074, 5.211, 3.981, 6.438, 13.502, P<0.01). After treatment, LVEF (46.03% ± 1.70% vs. 42.33% ± 1.63%, t=11.271) and E/A (1.02 ± 0.17 vs. 0.90 ± 0.16, t=3.796) in the study group were significantly higher than those in the control group (P<0.01). After treatment, the serum GSH-Px and SOD levels in the study group were significantly higher than those in the control group (t values were 7.585, 6.816, P<0.01), and CRP level was significantly lower than the control group (t=10.854, P<0.01).@*Conclusions@#The Huangqi-Baoxin decoction combined with routine western medicine therapy can improve the clinical symptoms and cardiac function of DCM patients, reduce oxidative stress injury and inhibit inflammation.
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Objective To explore the effect of Huangqi-Baoxin decoction combined with conventional western medicine on the cardiac function of the patients with diabetic cardiomyopathy (DCM). Methods A total of 103 DCM patients who met the inclusion criteria were divided into the control group (51 cases) and the research group (52 cases) by random number table method. The control group was treated with conventional therapy, while the study group was treated with Huangqi-Baoxin decoction on the basis of the control group. Both groups were treated for 3 months. TCM syndromes were scored before and after treatment. The serum GSH-Px, SOD and CRP levels were measured by ELISA. Left ventricular ejection fraction (LVEF) and E/A ratio of early diastolic peak velocity to late diastolic peak velocity (E/A) were measured by echocardiography and then evaluate the clinical efficacy. Results The total effective rate was 92.3% (48/52) in the study group and 76.5% (39/51) in the control group. There was significant difference between the two groups (χ2=4.922, P=0.027). After treatment, the scores of palpitation, shortness of breath, chest tightness and chest pain, fatigue, hypochondriac mass, spontaneous sweating, edema and total scores in the study group were significantly lower than those in the control group (t values were 10.603, 9.997, 10.546, 10.074, 5.211, 3.981, 6.438, 13.502, P<0.01). After treatment, LVEF (46.03% ± 1.70% vs. 42.33% ± 1.63%, t=11.271) and E/A (1.02 ± 0.17 vs. 0.90 ± 0.16, t=3.796) in the study group were significantly higher than those in the control group (P<0.01). After treatment, the serum GSH-Px and SOD levels in the study group were significantly higher than those in the control group (t values were 7.585, 6.816, P<0.01), and CRP level was significantly lower than the control group (t=10.854, P<0.01). Conclusions The Huangqi-Baoxin decoction combined with routine western medicine therapy can improve the clinical symptoms and cardiac function of DCM patients, reduce oxidative stress injury and inhibit inflammation.
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Objective To make epidemiological investigation on children and teenagers with congenital heart disease (CHD) from October 2015 to November 2016 in three counties in Zhaotong area. Methods The examination was divided into the following two phases: primary screening, secondary screening. Standardized echocardiographic examination was performed for the students with suspected CHD. we combined comprehensive analysis of electrocardiogram, X-ray and cardiac catheterization to make a clear diagnosis for patients. The index of prevalence rate of CHD, the types of the disease, and gender of the patients in 14957 children and teenagers were statistically analyzed. Results Altogether 61 cases of CHD were discovered. The total prevalence of CHD was 4.08‰ (61 of 14957 cases), the prevalence rate in male was 4.55‰, in female was 3.61‰, No difference of the prevalence rate was found between male and female (χ2=0.823, P＞0.05);the difference among different age groups had no statistical significance (χ2=4.692, P＞0.05);The prevalence rate of CHD in Qiaojia was 5.17‰, in Daguan was 6.36‰, and in Zhenxiong was 3.03‰, There was no significant difference in the prevalence rate among different countries (χ2=5.897, P＞0.05). In terms of the types of the disease, atrial septal defect accounted for the first (37.7％ ), followed by ventricular septal defect (26.2％ ) and patent ductus arteriosus (19.7％ ), others types of CHD were rare. Conclusion The prevalence of CHD in investigated area is slightly higher than the average level of the nationwide. The main types of CHD are atrial septal defect, ventricular septal defect and patent ductus arteriosus.
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Objective Scutellarin (SCU), a Chinese traditional medicine, has a protective effect against ischemia-reperfusion (IR) induced myocardial injury, but it is not yet clear whether SCU acts against vascular endothelial IR injury via extracellular signal-regulated kinase 1/2 (ERK1/2).The aim of this study was to explore the effect of SCU on hypoxia-reoxygenation (HR)-induced injury to human cardiac microvascular endothelial cells (HCMECs) and its influence on the ERK1/2 signaling pathway.Methods HCMECs were subjected to normal culture and divided into a normal control, a DMSO, an SCU 1 μmol/L, and an SCU 10 μmol/L group.The model of HR injury was established by exposing the HCMECs to 12-h hypoxia and 12-h reoxygenation after treated with DMSO or SCU at 1 and 10 μmol/L for 2 hours.Then, the survival rate of the HCMECs was detected by MTT and trypan blue staining, the concentration of malondialdehyde (MDA) in the cells measured, and the expressions of the p-ERK1/2, ERK2 and GAPDH proteins determined by Western blot.Results SCU at 1 and 10 μmol/L significantly increased the survival rate of the normally cultured HCMECs ([110.40±2.34] and [122.00±1.25] ％) as compared with that of the normal control (100％) (P<0.05), while HR injury markedly decreased the vitality of the HCMECs ([68.00±4.06] ％) in comparison with that of the blank control (100％) (P<0.05).The survival rate of the HCMECs was remarkably higher in the HR+SCU 1 μmol/L and HR+SCU 10 μmol/L groups than in the HR model group ([90.53±3.67] and [92.04±2.32] ％) (P<0.05), and so was their vitality in the SCU 10 μmol/L group than in the normal control ([96.78±2.01] vs [90.06±1.85] ％, P<0.01), while their survival rate was significantly lower in the HR model than in the blank control ([73.72±4.91] vs [91.83±2.34] ％, P<0.01) and remarkably higher in the SCU 10 μmol/L ([87.59±2.64] ％) than in the HR model group (P<0.05).The MDA concentration in the HCMECs was markedly increased in the HR model and HR+DMSO groups as compared with the blank control (P<0.01), but decreased in the HR+SCU 1 μmol/L and HR+SCU 10 μmol/L groups in comparison with the HR model group (P<0.05).The expression of the p-ERK1/2 protein was significantly down-regulated in the HR model group as compared with the blank control (P<0.01), but up-regulated in the HR+SCU 10 μmol/L group in comparison with the HR model (P<0.01).Conclusion HR injury reduces the vitality of HCMECs, increases the MDA concentration, and down-regulates the expression of the p-ERK1/2 protein in HCMECs, while SCU acts against ischemia-reperfusion injury to HCMECs by increasing ERK phosphorylation.
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Objective To investigate the correlation between morphological abnormalities and abnormal myelodysplastic syn-dromes(MDS)cloning.Methods 82 cases of MDS were collected with complete FISH and morphological abnormalities. The relationship between MDS cell morphology and chromosome abnormality was investigated.Results 45 cases of chromo-somal abnormalities were found,and +8 were the most frequent chromosomal abnormalities.8 cases were +8,-5 and 5q-were 6,20q-were 7,-7 and 7q-were 5,complex karyotypes(>3 abnormalities)were 6.There were statistically significant differences in the proportion of primordial cells,megakaryocyte dysplasia,megakaryocyte abnormalities between karyotype abnormal group and karyotype normal group(P<0.05).There were statistically significant differences in the proportion of abnormal karyotype among high risk group and low risk group,the low risk group and medium risk group(P<0.05).Con-clusion The chromosomal abnormalities of MDS patients would be related to morphological changes.
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@#Objective To explore the characteristics of blink reflex (BR) and brainstem auditory evoked potential (BAEP) in patients with consciousness disorder and the role of BR and BAEP in the evaluation of brain stem function. Methods From January to December, 2015, 31 patients with consciousness disorder were examined with BAEP, BR and Glasgow Coma Scale (GCS), and the outcome was record-ed one month after examination. Results BAEP and BR were positively related with GCS score (r≥0.562, P<0.05) and outcome (χ2=9.644, P<0.01). Conclusion Both BR and BAEP can reflect the brain stem function and respective pathway. Their combination could provide ob-jective basis for prognosis evaluation.
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@#Objective To explore the characteristics of blink reflex (BR) and brainstem auditory evoked potential (BAEP) in patients with consciousness disorder and the role of BR and BAEP in the evaluation of brain stem function. Methods From January to December, 2015, 31 patients with consciousness disorder were examined with BAEP, BR and Glasgow Coma Scale (GCS), and the outcome was record-ed one month after examination. Results BAEP and BR were positively related with GCS score (r≥0.562, P<0.05) and outcome (χ2=9.644, P<0.01). Conclusion Both BR and BAEP can reflect the brain stem function and respective pathway. Their combination could provide ob-jective basis for prognosis evaluation.
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Betulinic acid is a naturally occurring pentacyclic triterpenoid, which has antiretroviral, antimalarial, and anti-inflammatory properties. The purpose of this study is to investigate the HBV DNA replication inhibition in the mouse model with betulinic acid. Hydrodynamic injection method via the tail vein with the Paywl. 3 plasmid was used to establish the animal mode (n = 15), and the mice were randomly divided into the PBS control group (n = 5), Betulinic acid treatment group (n = 5) and lamivudine control group (n = 5). The day after successful modeling , the mice would have taken Betulinic acid (100 mg x kg(-1)), lamivudine (50 mg x kg(-1)), PBS drugs orally, once daily for 7 days, blood samples were acquired from the orbital venous blood at 3, 5, 7 days after the administering, HBsAg and HBeAg in serum concentration were measured by ELISA and the mice were sacrificed after 7 days, HBV DNA southern detections were used with part of mice livers. The results showed that betulinic acid significantly inhibited the expression of HbsAg in the mice model at the fifth day compared with the control group, and there was no significant differences between the effects of lamivudine and the PBS control group; both the betulinic acid and lamivudine groups had no significant inhibition for the HBeAg expression; the HBV DNA expressions of the liver tissue from the betulinic acid and lamivudine groups were inhibited compared with the control group. Taken together, these results reveal betulinic acid can inhibit the HBsAg expression and replication of the liver HBV DNA in the mouse model.
Subject(s)
Animals , Male , Mice , Acute Disease , Antiviral Agents , Pharmacology , DNA Replication , DNA, Viral , Hepatitis B , Blood , Virology , Hepatitis B Surface Antigens , Blood , Hepatitis B virus , Genetics , Allergy and Immunology , Physiology , Plasmids , Genetics , Triterpenes , Pharmacology , Virus ReplicationABSTRACT
Objective To investigate the value of neutrophil to lymphocyte ratio (NLR) in predicting in-stent restenosis (ISR) in patients with coronary heart disease. Methods We collected the data of 618 patients with coronary heart disease hospitalized in the Department of Cardiology in the First Affiliated Hospital of Kunming Medical University from January 2011 to June 2012. All selected patients underwent coronary angiography and stent implantation, and were divided into two groups according to the average size of NLR. The relationship between the neutrophil to lymphocyte ratio and coronary heart disease in-stent restenosis was investigated. Results There were statistically significant differences in the presence of diabetes, high density lipoprotein, low density lipoprotein, the percentage of neutrophils and lymphocytes in patients between two groups (P<0.05) . We found 13 patients (4.2%) and 32 patients (10.4%) with in-stent restenosis in the first group and the second group, respectively, and there was a statistically significant difference between two groups (P<0.01) . Conclusion Neutrophil to lymphocyte ratio is correlated with ISR,and has clinical value in predicting ISR.
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<p><b>OBJECTIVE</b>To investigate the preventive effect of Rhodiola extract on cisplatin (cDDP)-induced testicular toxicity in mouse TM4 Sertoli cell line and its possible mechanism in vitro.</p><p><b>METHODS</b>We treated mouse TM4 Sertoli cells with Rhodiola extract and/or cDDP. Then we detected the proliferation of the TM4 cells by MTT assay, observed their morphological changes, and determined the contents of malondialdehyde (MDA), superoxide dismutase (T-SOD) and glutathione (GSH) in the cells.</p><p><b>RESULTS</b>MTT assay showed that Rhodiola extract at the concentration of 0.0125-2.5 mg/L significantly inhibited the cDDP-induced decrease in the proliferation of the TM4 cells (P < 0.01) and improved their morphological changes. Anti-oxidation test exhibited a dramatically increased level of MDA in the TM4 cells treated with cDDP at 0.0147 g/L as compared with the normal control cells ([3.63 +/- 0.02] vs [2.15 +/- 0.02] nmol/mg prot, P < 0.01) and decreased levels of T-SOD ([6.57 +/- 0.05] vs [10.86 +/- 0.02] U/mg prot, P < 0.01) and GSH ([1.42 +/- 0.06] vs [2.59 +/- 0.05] mg/g prot, P < 0.01). Rhodiola extract at 0.1 mg/L significantly reduced the MDA content ([1.94 +/- 0.00] nmol/mg prot, P < 0.01) and the activity of T-SOD ([8.50 +/- 0.02] U/mg prot, P < 0.01) and GSH ([2.41 +/- 0.04] mg/g prot, P < 0.01) in the TM4 cells treated with cDDP.</p><p><b>CONCLUSION</b>Rhodiola extract can significantly inhibit cDDP-induced damage to TM4 cells in mice, which may be associated with its antioxidant activity.</p>
Subject(s)
Animals , Male , Mice , Antioxidants , Pharmacology , Cell Line , Cisplatin , Glutathione , Metabolism , Malondialdehyde , Metabolism , Oxidative Stress , Plant Extracts , Pharmacology , Rhodiola , Chemistry , Sertoli Cells , Superoxide Dismutase , MetabolismABSTRACT
<p><b>OBJECTIVE</b>To make an animal periodontitis and atherosclerosis compound model, and to study the effects of periodontitis on atherosclerosis.</p><p><b>METHODS</b>36 Japan rabbits were randomly divided into four groups: Including periodontitis model group, periodontitis and atherosclerosis compound model group, atherosclerosis model group and control group. Periodontitis model was initiated by ligating floss around teeth cervical and oral inoculating with Porphyromonas gingivalis (P. gingivalis). Atherosclerosis was established by single iliac artery of balloon-injured rabbit. Histopathological change of injured iliac artery was observed under optical microscope after hematoxylin-eosion stain. Elastica van Gieson-stained sections were used for the morphometric analysis. We measured intimal and medial lesion areas in iliac artery cross-sections as well as the intimal/medial ratio (I/M). We also analyzed P. gingivalis 16S rDNA amplification with nested-polymerase chain reaction (nested-PCR), and detect systemic proinflammatory mediators with enzyme linked immunosorbent assay (ELISA), including C-reactive protein (CRP), interleukin-6 (IL-6) and interleukin-1beta (IL-1beta).</p><p><b>RESULTS</b>The serum levels of CRP, IL-6 and IL-1beta increased obviously among the compound model group than other groups (P<0.01). Histopathological observation revealed the compound model group in I/M was bigger than other groups (P<0.01). P. gingivalis 16S rDNA was detected among the periodontitis model group and the compound model group by nested-PCR.</p><p><b>CONCLUSION</b>Periodontitis may accelerate intimal hyperplasia in balloon-injured iliac arteries by upgrade of systemic inflammation factors and local bacterial infection.</p>
Subject(s)
Animals , Rabbits , Animal Experimentation , Atherosclerosis , C-Reactive Protein , Disease Models, Animal , Enzyme-Linked Immunosorbent Assay , Interleukin-6 , Periodontitis , Porphyromonas gingivalisABSTRACT
Bone marrow-derived mesenchymal stem cells (MSCs) have emerged as attractive candidates for cellular therapies for heart and other organ-system disorders. However, a major dilemma in stem cell therapy for ischemic heart diseases is the low survival of transplanted cells in the ischemic and peri-infarcted region. In this study, MSCs were treated by hypoxia and serum deprivation (H/SD) to mimic the ischemic microenvironment of infarcted hearts where MSCs were transplanted. The effects of proteasome inhibitor MG-132 on H/SD-induced apoptosis and paracrine effects were investigated. Apoptosis of MSCs was detected by Annexin V-FITC flow cytometric analysis. Transcriptional levels of IL-1β, TNF-α and IL-10 were examined by real-time PCR. The nuclear translocation of NF-κBp65 was assessed by immunocytochemical staining. Translational changes of IL-1β and TNF-α were detected by Western blot. The secretion of IL-10 from MSCs was examined by ELISA assay. The results showed that MG-132 could effectively suppress H/SD-induced MSCs apoptosis. Furthermore, the induced IL-1β and TNF-α transcription was also inhibited by MG-132 treatment, which may be due to the inhibition of NF-κBp65 nuclear translocation by MG-132. Importantly, MG-132 effectively enhanced H/SD-induced transcription and secretion of IL-10, which is an important paracrine factor from MSCs. Our findings suggest that pretreatment of MSCs by MG-132 before cell transplantation may be an effective strategy to improve cell survival and enhance paracrine effects of MSCs.
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Animals , Female , Male , Rats , Apoptosis , Bone Marrow Cells , Cell Biology , Cell Hypoxia , Cell Survival , Cells, Cultured , Culture Media, Serum-Free , Cysteine Proteinase Inhibitors , Pharmacology , Interleukin-10 , Bodily Secretions , Leupeptins , Pharmacology , Mesenchymal Stem Cells , Cell Biology , Rats, Sprague-DawleyABSTRACT
<p><b>OBJECTIVE</b>To investigate the effect of ADMA on macrophage migration inhibitory factor (MIF) expression and tumor necrosis factor-α (TNF-α) and IL-8 secretion in THP-1 monocyte-derived macrophages. METHIDS: THP-1 monocytes were induced to differentiate into macrophages by a 24-h incubation with 160 nmol/L PMA. The THP-1 monocyte-derived macrophages were exposed to different concentrations of ADMA for 24 h, and the changes in MIF mRNA and protein expressions were analyzed with RT-PCR and Western blotting, respectively. Enzyme-linked immunosorbent assay was used to detect the levels of TNF-α and IL-8 in the supernatant of THP-1-derived macrophages following ADMA treatments.</p><p><b>RESULTS</b>ADMA obviously up-regulated MIF mRNA and protein expressions in THP-1-derived macrophages in a concentration- dependent manner. Exposure of the cells to 15 µmol/L ADMA for 24 h showed the most potent effect in up-regulating MIF mRNA and protein expressions. ADMA treatment also resulted in a dose-dependent increase of the levels of TNF-α and IL-8 in the culture supernatant of the macrophages, and the peak levels occurred following the treatment with 15 µmol/L ADMA.</p><p><b>CONCLUSION</b>ADMA can up-regulate MIF expression and induce TNF-α and IL-8 secretion in THP-1 monocyte-derived macrophages.</p>
Subject(s)
Humans , Arginine , Pharmacology , Cell Differentiation , Cell Line , Interleukin-8 , Bodily Secretions , Intramolecular Oxidoreductases , Genetics , Metabolism , Macrophage Migration-Inhibitory Factors , Genetics , Metabolism , Macrophages , Cell Biology , Metabolism , Monocytes , Cell Biology , Phenanthrenes , Pharmacology , RNA, Messenger , Genetics , Metabolism , Tumor Necrosis Factor-alpha , Bodily SecretionsABSTRACT
Autotaxin (ATX), a member of nucleotide pyrophosphatase/phosphodiesterase (NPP) family, is also named as phosphodiesterase Iα (PD-Iα) or NPP2. ATX is the unique member among the NPPs that can function as a lysophospholipase D (lysoPLD), converting lysophosphatidylcholine into lysophosphatidic acid (LPA). LPA acts on specific G-protein-coupled receptors to elicit a wide range of cellular response, including cell proliferation, cell migration and cell contraction, etc. As the major LPA-producing phospholipase, many ATX's features and functions are dependent on the production of LPA. ATX and LPA together form the ATX-LPA functional axis. The present review summarizes the current progress in function and biological activities of ATX-LPA axis.