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Objective: To investigate the anti-inflammatory effects of the total flavonoids from Saussurea involucrata on lipopolysaccharides (LPS)-stimulated murine RAW264.7 macrophages and explore its underlying mechanism of action. Methods: Total flavonoids from Saussurea involucrata were extracted using chromatographic column method. Cell viability was determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide assay. The production of nitric oxide was detected by Griess assay and the release of cytokines (IL-10 and TNF-α) and chemokines (MCP-1, MIP-1a, and CCL5/RANTES) was determined by ELISA to evaluate the anti-inflammatory activity of total flavonoids from Saussurea involucrata. Moreover, nuclear translocation of p65, c-Jun, and IRF3 was detected by immunofluorescence microscopy and Western blotting analysis was performed to determine the expression of related proteins. Results: Total flavonoids extracted from Saussurea involucrata were 751.5 mg/g and the content of rutin was 506.5 mg/g. The production of inflammatory mediators including nitric oxide, cytokines, and chemokines was effectively inhibited by total flavonoids from Saussurea involucrata. Meanwhile, total flavonoids also suppressed the nuclear translocation of p65, c-Jun, and IRF3 in LPS-stimulated RAW264.7 cells. The LPS-induced expression of iNOS and COX-2 was remarkably reduced by treatment with total flavonoids from Saussurea involucrata. Moreover, total flavonoids decreased the expression levels of p-IKKa/β, p-TBK1, p-p38, p-ERK, p-JNK, p-p65, p-c-Jun, and p-IRF3 in LPS-exposed RAW264.7 macrophages. Conclusions: Total flavonoids from Saussurea involucrata potentially inhibit the secretion of pro-inflammatory mediators, which may be related to inhibition of p65, c-Jun, and IRF3 signaling pathways in LPS-stimulated RAW264.7 cells.
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Objective: To investigate the anti-inflammatory effects of the total flavonoids from Saussurea involucrata on lipopolysaccharides (LPS)-stimulated murine RAW264.7 macrophages and explore its underlying mechanism of action. Methods: Total flavonoids from Saussurea involucrata were extracted using chromatographic column method. Cell viability was determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide assay. The production of nitric oxide was detected by Griess assay and the release of cytokines (IL-10 and TNF-α) and chemokines (MCP-1, MIP-1a, and CCL5/RANTES) was determined by ELISA to evaluate the anti-inflammatory activity of total flavonoids from Saussurea involucrata. Moreover, nuclear translocation of p65, c-Jun, and IRF3 was detected by immunofluorescence microscopy and Western blotting analysis was performed to determine the expression of related proteins. Results: Total flavonoids extracted from Saussurea involucrata were 751.5 mg/g and the content of rutin was 506.5 mg/g. The production of inflammatory mediators including nitric oxide, cytokines, and chemokines was effectively inhibited by total flavonoids from Saussurea involucrata. Meanwhile, total flavonoids also suppressed the nuclear translocation of p65, c-Jun, and IRF3 in LPS-stimulated RAW264.7 cells. The LPS-induced expression of iNOS and COX-2 was remarkably reduced by treatment with total flavonoids from Saussurea involucrata. Moreover, total flavonoids decreased the expression levels of p-IKKa/β, p-TBK1, p-p38, p-ERK, p-JNK, p-p65, p-c-Jun, and p-IRF3 in LPS-exposed RAW264.7 macrophages. Conclusions: Total flavonoids from Saussurea involucrata potentially inhibit the secretion of pro-inflammatory mediators, which may be related to inhibition of p65, c-Jun, and IRF3 signaling pathways in LPS-stimulated RAW264.7 cells.
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BACKGROUND@#Clinical observational studies revealed that 99Tc-methylene diphosphonate (99Tc-MDP) could reduce joint pain and swollenness in rheumatoid arthritis (RA) patients. This multicenter, randomized, double-blind, double-dummy study aimed to evaluate the effects of 99Tc-MDP plus methotrexate (MTX) vs. MTX alone or 99Tc-MDP alone on disease activity and structural damage in MTX-naïve Chinese patients with moderate to severe RA.@*METHODS@#Eligible patients with moderate to severely active RA were randomized to receive 99Tc-MDP plus MTX (n = 59) vs. MTX (n = 59) alone or 99Tc-MDP (n = 59) alone for 48 weeks from six study sites across four provinces in China. The primary outcomes were the American College of Rheumatology 20% improvement (ACR20) response rates at week 24 and changes in modified total Sharp score at week 48.@*RESULTS@#At week 24, the proportion of participants achieving ACR20 was significantly higher in the MTX + 99Tc-MDP combination group (69.5%) than that in the MTX group (50.8%) or 99Tc-MDP group (47.5%) (P = 0.03 for MTX + 99Tc-MDP vs. MTX, and MTX + 99Tc-MDP vs.99Tc-MDP, respectively). The participants in the MTX + 99Tc-MDP group and the 99Tc-MDP group had significantly less important radiographic progression than the participants in the MTX group over the 48 weeks (MTX + 99Tc-MDP vs. MTX: P = 0.03, 99Tc-MDP vs. MTX: P = 0.03, respectively). There was no significant difference in terms of adverse events (AEs) among the groups. No serious AEs were observed.@*CONCLUSIONS@#This study demonstrated that the combination of 99Tc-MDP with MTX inhibited structural damage and improved disease activity in RA patients compared with MTX and 99Tc-MDP monotherapies, without increasing the rate of AEs. Additional clinical studies of 99Tc-MDP therapy in patients with RA are warranted.@*TRIAL REGISTRATION@#Chictr.org, ChiCTR-IPR-14005684; http://www.chictr.org.cn/showproj.aspx?proj=10088.
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Humans , Antirheumatic Agents/therapeutic use , Arthritis, Rheumatoid/drug therapy , China , Diphosphonates , Double-Blind Method , Drug Therapy, Combination , Methotrexate/therapeutic use , Technetium/therapeutic use , Treatment OutcomeABSTRACT
Objective In 2016,European League Against Rheumatism (EULAR)/American College of Rheumatology (ACR)/Pediatric rheumatology international trials organization (PRINTO) released the classification criteria for macrophage activation syndrome (MAS) in patients with systemic juvenile idiopathic arthritis (sJIA).Due to the similarities of both clinical manifestations and pathogenesis between adult-onset Still dsease (AOSD) and sJIA,we hope to evaluate the 2016 sJIA-AMS classification in AOSD patients.Methods A total of 169 AOSD patients who were hospitalized in Renji Hospital were enrolled in this study.AOSD patients were divided into AOSD with MAS and AOSD without MAS,using the 2016 sJIA-MAS criteria.The data of the two groups were analyzed by Chi-square test,Mann-Whitney U test and binary Logistic analysis,and factors influencing the prognosis of patients were analyzed by Kaplan-Meier and COX regression analysis.Results According to sJIA-MAS criteria,56 AOSD patients with MAS were identified in all the 169 AOSD cases.In AOSD patients,the incidence of splenomegaly and pericarditis/myocarditis was significantly higher in patients with MAS than in AOSD without MAS [42.9％ vs 14.2％,OR(95％CI)=4.50(2.13,9.51),P＜0.01;10.7％ vs 0.9％,OR(95％CI)=13.21 (1.56,113.57),P＜0.01],also the incidence of liver dysfunction was higher in AOSD with MAS [67.8％ vs 11.5％,OR(95％CI)=0.18(7.26,36.33),P＜0.01].Among the AOSD with MAS,62.5％(35/56) of these patients received large-dose glucocorticoid therapy,5.4％ (3/56) received the glucocorticoid pulse therapy,48.2％(27/56) were treated with IVIG,and 26.8％(15/56) were treated with calcium phosphatase inhibitors.The mortality rates of AOSD with MAS was 8.9％(5/56),which was significantly higher than 1.8％(2/113) (OR =5.44,P＜0.05),the mortality rate of the AOSD without MAS.Patients who fulfilled the sJIA-MAS criteria suggested poor prognosis (OR=0.041,P=5.44),and the platelet count ≤ 181× 109/L (OR=12.17,P=0.002),alanine aminotransferase ＞48 U/L (OR=9.43,P=9.040) were also highly suggestive of poor prognosis.Conclusion The 2016 sJIA-MAS classification criteria are particularly valuable for early recognization of MAS in AOSD patients,and convenient to use.AOSD patients fulfilled sJIA-MAS criteria are more severe,and require larger doses of glucocorticoid and more immunosuppression therapy compared to patients without MAS,and the prognosis of these patients is also poor.
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Objective The objective of this study was to explore the effect of astragalin on human ovarian cancer OVCAR-8 cells in 2 D and 3 D culture conditions and its possible mechanism. Methods CCK-8 assay was use to detect the effect of astra-galin on the proliferation of OVCAR-8 cells in 2 D culture conditions. The 3 D cell proliferation activity assay kit was used to detect the effect of astragalin on OVCAR-8 cells in 3 D culture conditions. Cell apoptosis kit was used to detect the cell apoptosis rate after astragaline treatment. In addition,Western blot was used to detect the levels of apoptosis related proteins such as Bcl2(B-cell lym-phoma 2),Bax(Bcl-2-associated X protein),cleaved-caspase-3 and glycolysis related proteins such as Glut-1(Glucose trans-porter-1),Glut3,HK2(Hexokinase 2),PDK-1(Pyruvate dehydrogenase lipoamide kinase-1),PDK3 and HIF-1α(hypoxia-in-ducible factor-1α)in OVCAR-8 cells after astragaline treatments in 2 D and 3 D culture conditions. HK2 activity was detected in OVCAR-8 cells by Elisa. Results Astragaline at doses of 4~100 μmol/L significantly inhibited the proliferation of OVCAR-8 cells in 2 D culture conditions,and showed a dose-and time-dependent manner(P<0. 05). Astragalin significantly inhibited the proliferation of OVCAR-8 cells in 3 D culture conditions(P<0. 05). Astragalin also significantly inhibited the migration ability of OVCAR-8 cells(P<0. 05). In addition,astragaline significantly increased apoptosis rate,decreased the levels of Bcl2,Glut1,Glut3, HK2,PDK1 and PDK3 proteins and increased the levels of Bax and cleaved-caspase-3 proteins in OVCAR-8 cells both in 2 D and 3 D culture conditions(P<0. 05). Astragaline significantly decreased the expression of HIF-1α in OVCAR-8 cells in 3 D cul-ture conditions(P<0. 05). In addition,astragalin decreased HK2 activity in OVCAR-8 cells under 2 D culture conditions in a dose-dependent manner(P<0. 05). Conclusion Astragalin has an inhibitory effect on the proliferation of OVCAR-8 cells both in 2 D and 3 D culture conditions. Its mechanism may be related to inhibiting glycolytic and the mitochondrial apoptotic pathways induced by HIF-1α.
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Objective· To investigate the clinical features of macrophage activation syndrome (MAS) associated with adult-onset Still's disease (AOSD),and provide the basis for clinical diagnosis and treatment of the disease.Methods· The clinical data of 42 patients with AOSD,including 14 patients with AOSD-induced MAS (the MAS group) and 28 AOSD patients paired by age and sex (the non-MAS group),diagnosed in Department of Rheumatology,Renji Hospital,Shanghai Jiao Tong University School of Medicine from October 2013 to June 2016 were collected and then retrospectively analyzed.Results· There was no significant difference in age,sex and duration of AOSD between two groups.The mortality rate of patients in MAS group was significantly higher than that of patients in non-MAS group,as well as the rates of rash,splenomegaly and hemophagocytosis.The levels of ALT and serum ferritin in MAS group were higher than those in non-MAS group,while the level of FDP is lower.Glucocorticoids were used in all 42 patients,and the dosage of glucocorticoids was significantly higher in MAS group than non-MAS group.Only 1 patient with AOSD-induced MAS received MTX,the percentage of patients receiving MTX was significantly lower in MAS group than non-MAS group.Five patients with AOSD-induced MAS received IVIG,the percentage of patients receiving IVIG was significantly higher in MAS group than non-MAS group.Two patients with AOSD-induced MAS received VP-16.Conclusion · The mortality rate of patients in MAS group was significantly higher than that of patients in non-MAS group,as well as the rates of rash,splenomegaly and hemophagocytosis.The levels of ALT and serum ferritin in patients with AOSD-induced MAS were higher than patients without MAS,while the level of FDP was lower.Early diagnosis and active treatment is the key point to improve clinical outcome.
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Objective To setup a platform for genetic diagnosis of Cryopyrin associated periodic syndrome (CAPS) and to use it for clinical diagnosis.Methods The peripheral blood cells of the patient and the controls were collected for DNA extraction.Nine exons of CAPS associated gene NLRP3 were amplified using polymerase chain reaction (PCR) and subjected to sequencing.Blast was used to compare the sequencing results with the reference gene and to locate mutation.The clinical information of the patient was collected and the relevant literature was reviewed.Results We set up a platform for exon sequencing of NLRP3 gene.Using this platform,we identified a nonsynonymous mutation in a female patient (D303N,aspartic acid at locus 303 mutated to asparagine).Considering the clinical manifestations of the patient,chronic infantile neurologic cutaneous and articular syndrome (CINCA) was diagnosed.Conclusion The set up of the platform for NLRP3 genetic analysis will facilitate the clinical awareness and research on CAPS.
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<p><b>OBJECTIVE</b>To identify the underlying mechanisms of the protective effects of Dingxin Recipe (: , DXR), a Chinese compound prescription that has been used clinically in China for more than 20 years, on ischemia/reperfusion (I/R)-induced arrhythmias in rat model.</p><p><b>METHODS</b>A total of 30 rats were randomly divided into three groups: sham group, I/R group, and DXR-pretreated I/R (DXR-I/R) group. Rats in the DXR-DXRI/R group were intragastrically administrated with DXR (12.5 g/kg per day) for consecutive 7 days, while rats I/in the sham and I/R groups were administrated with normal saline. Arrhythmias were introduced by I/R and electrocardiograms (ECG) were recorded. Two-dimensional (2-D) polyacrylamide gel electrophoresis and matrix-matrix assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS) were used to identify assisted differentially expressed proteins. Immunohistochemistry, real-time quantitative polymerase chain reaction (RQ-RQPCR), Western blot, and enzyme-linked immunosorbent assay (ELISA) were performed to analyze proteins PCR), obtained in the above experiments.</p><p><b>RESULTS</b>DXR significantly reduced the incidence and mean duration of ventricular tachycardia and ventricular fibrillation and dramatically decreased the mortality, as well as arrhythmia score, compared with those of the I/R group. Among successfully identified proteins, prohibitin (PHB) and heart fatty acid binding protein (hFABP) were up-regulated in DXR-pretreated I/R rats compared with those of the I/R rats. In addition, compared with the I/R group, the level of glutathione (GSH) was elevated accompanied by reduced expressions of interleukin-6 (IL-6) and neutrophil infiltration in I/R rats with DXR pretreatment.</p><p><b>CONCLUSIONS</b>DXR could alleviate I/R-induced arrhythmias, which might be related to increased expression of PHB. The enhanced expression of PHB prevented against the depletion of GSH and consequently inhibited apoptosis of cardiomyocytes. Furthermore, up-regulation of PHB might ameliorate I/R-induced cell death and leakage of hFABP by suppressing neutrophil infiltration and IL-6 expressions.</p>
Subject(s)
Animals , Male , Rats , Arrhythmias, Cardiac , Drugs, Chinese Herbal , Pharmacology , Therapeutic Uses , Electrophoresis, Gel, Two-Dimensional , Fatty Acid Binding Protein 3 , Fatty Acid-Binding Proteins , Metabolism , Glutathione , Metabolism , Heart Ventricles , Metabolism , Pathology , Immunohistochemistry , Inflammation , Metabolism , Pathology , Interleukin-6 , Metabolism , Myocardial Infarction , Drug Therapy , Pathology , Neutrophil Infiltration , Peptide Mapping , Proteomics , Rats, Wistar , Reperfusion Injury , Repressor Proteins , Metabolism , Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization , Spectrophotometry , Up-RegulationABSTRACT
<p><b>OBJECTIVE</b>To explore the molecular mechanism of realgar-induced apoptosis of cervical cancer cells.</p><p><b>METHODS</b>The cervical cancer cell line Siha was used to determine the cell viability and apoptosis after treatment with realgar using MTT assay and flow cytometry. The activities of caspase-3, -8, and -9 were detected by fluorescence resonance energy transfer technology and colorimetric assay, while the levels of Bcl-2, cytochrome c, and Bax were detected by Western blot method.</p><p><b>RESULTS</b>Induction of apoptosis by realgar was detected in Siha cell line in a dose-dependent manner. The apoptosis was accompanied by a significant increase in cytochrome c release and activation of caspase-3 and caspase-9 but not caspase-8. Further, the realgar-induced apoptosis was inhibited by a broad-spectrum caspase inhibitor, a caspase-3 inhibitor, and a caspase-9 inhibitor but not by a caspase-8 inhibitor. Bcl-2 and Bax protein expressions were not changed by realgar.</p><p><b>CONCLUSION</b>The induction of apoptosis by realgar is mediated through a cytochrome c-dependent pathway, which sequentially activates caspase-9 and caspase-3.</p>
Subject(s)
Female , Humans , Apoptosis , Physiology , Arsenicals , Pharmacology , Caspase 3 , Metabolism , Caspase 8 , Metabolism , Caspase 9 , Metabolism , Caspase Inhibitors , Cell Line, Tumor , Cell Survival , Physiology , Cytochromes c , Metabolism , Dose-Response Relationship, Drug , Enzyme Activation , Enzyme Inhibitors , Pharmacology , Fluorescence Resonance Energy Transfer , Sulfides , Pharmacology , Uterine Cervical Neoplasms , Drug Therapy , Metabolism , PathologyABSTRACT
Sclerosing angiomatoid nodular transformation (SANT) is a rarely encountered benign spleen lesion which has recently been gaining recognition. However,the actual pathogenesis of this disease remains unclear.SANT's remarkably characteristic appearance consists grossly of multiple well-circumscribed vascular/angiomatoid nodules of various sizes in a fibrosclerotic stroma. Immunohistochemical studies display a heterogeneous staining pattern of endothelial phenotypes in the angiomatoid nodules,with some cells resembling splenic sinusoids (CD34 -/CD31 +/CD8 + ),capillaries (CD34 +/CD31 +/CD8 - ) and small veins (CD34 -/CD31+/CD8-).Due to the rarity of this disease,it is often mistaken for splenic hamartoma,inflammatory pseudotumor,littoral cell angima or hemangioendothelioma. So far,SANT exhibits a benign clinical course because splenectomy can be curative.In this review,we outline the clinical and pathologic features of SANT and discuss its probable disease mechanism to provide a holistic overview of the disease at this time.
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To investigate the presence of transforming growth factor-beta 1 [TGF-beta 1] and connective tissue growth factor [CTGF] in women with pelvic organ prolapse [POP]. This study was conducted from May to December 2009. Fifty patients with POP that underwent vaginal hysterectomy in the Department of Gynecology, Renmin Hospital of Wuhan University, Hubei, Wuhan, China were enrolled in this study. They were divided into: Group 1 [n-10]; Group 2 [n=10]; and Group 3 [n=10] according to Pelvic Organ Prolapse Quantitation [POP-Q]. Meanwhile, 20 cases treated by vaginal hysterectomy for other benign gynecological diseases were selected as the control group. Immunohistochemical staining and Western blot were performed to detect the expression of TGF-beta 1 and CTGF. Immunohistochemical staining of TGF- beta 1 and CTGF were mainly expressed in the cytoplasm of fibroblast cells. The expression of TGF- beta 1 and CTGF protein was significantly negatively correlated with POP-Q stage. There were significantly positive correlations between the expression of TGF- beta 1 and CTGF protein. The expression of TGF- beta 1 protein among the 3 POP groups were all significantly lower than that of the control group, while there was no significant differences in the expression of TGF- beta 1 protein among the POP groups, excluding the comparison between Groups 1 and 3. The expression of CTGF protein in the 3 POP groups were all significantly lower than that of the control group, and significant differences were also detected among the 3 POP groups. In this study, we found that the TGF- beta 1 and CTGF protein expression may be associated with POP, especially in POP-Q stages
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Humans , Female , Transforming Growth Factor beta1 , Connective Tissue Growth Factor , Blotting, Western , ImmunohistochemistryABSTRACT
Objective To investigate the effect on the menstrual patterns and sexual quality of life of patients with adenomyosis after treated with Mirena IUD.Methods56 patients with adenomyosis who were treated with Mirena IUD were recruited from August 2009 to December 2009.We used Menstrual blood loss chart method,Dysmenorrhea score method and Brief Index of Sexual Function for Women (BISF-W) to evaluate the menstrual pattern,the volume of uterus and sexual quality after1,3,6,9,12 months.{Results53 patients were followed up,the rate was 94.6%.The condition of 56 patients became better after treated with Mirena for 3,6,9,12 months,dysmenorrhea[Placed before:(3.15±0.91)points;After placing:(1.41±0.51)points,(0.22±0.09)points,(0.07±0.01)points,0 points]and menstrual quantity[Placed before:(12.0±57.5)points;After placing:(71±23.1)points,(29±19.4)points,(18±10.5)points,(10±4.7)points]were both reduced(P＜0.05),the symptoms were not significantly improved after 1 month(P＞0.05).D2 indicators was significantly improved after 3 months of treatment (P＜0.05),sexual function was also improved after 6 months(P＜0.05～0.01).ConclusionsMirena IUD has a good effect on the menstrual pattern and sexual function for patients with adenomyosis.
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<p><b>OBJECTIVE</b>To study the effects of sophoridine on the transplanted solid tumor SW480 and the expression of p53 and vascular endothelial growth factor (VEGF) in the tumor in nude mice.</p><p><b>METHODS</b>The nude mouse model bearing transplanted solid tumor SW480 was established, and the changes in the volume and weight of the tumor were determined after treatment of the mice with sophoridine. Western blotting and immunohistochemistry were employed to examine the expressions of p53 and VEGF proteins, respectively, and fluorescence quantitative PCR used to detect their mRNA expressions in the tumor tissue.</p><p><b>RESULTS</b>The volume and weight of the tumor xenograft in sophoridine group decreased in comparison with those in the control group. Sophoridine treatment resulted in lowered expressions of p53 and VEGF at both the protein and mRNA levels in the tumor explants as compared with the control group, with a tumor inhibition rate of 34.07% in nude mice.</p><p><b>CONCLUSION</b>Sophoridine can inhibit the growth of transplanted solid tumor of human SW480 cell line, the mechanism of which involves the inhibition of p53 and VEGF expression.</p>
Subject(s)
Animals , Humans , Mice , Alkaloids , Pharmacology , Cell Line, Tumor , Colonic Neoplasms , Metabolism , Pathology , Mice, Inbred BALB C , Mice, Nude , Quinolizines , Pharmacology , RNA, Messenger , Genetics , Tumor Suppressor Protein p53 , Metabolism , Vascular Endothelial Growth Factor A , Metabolism , Xenograft Model Antitumor AssaysABSTRACT
Objective To explore the effects of systemic lupus erythematosus (SLE) susceptibility gene IFIT1 on chemokine expression in RAW264.7 macrophages and its possible role in the pathogenesis of SLE. Methods The expression vector of pEGFP-N1/IFIT1 was transfected into RAW264.7 cells by electroporation. 24 h after transfection, cells were stimulated with LPS ( 1 μg/ml). The transcriptional levels of chemokine MIP-1α, RANTES, CCL9, CXCL2 and IP-10 were measured at various time points after stimu-lation using real-time quantitative PCR. The chemokine expression levels in the kidneys of 8 week-old NZB/NZW F1 mice were also determined by real time PCR. Results Compared with cells transfected with null vector, IFIT1 high RAW264.7 cells produced significantly increased levels of MIP-1α, RANTES, CCL9, CXCL2 and IP-10 both at 4 h and 24 h after stimulation (P<0.05). Chemokine expression levels were signi-ficantly elevated in kidneys of 8 week-old NZB/NZW F1 mice compared with those of 8 week-old BALB/c mice controls (P<0.05). Conclusion IFIT1 may participate in target organ damages in SLE via augmentation of chemokine production by macrophage cells.
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Objective To correlate the expression levels of interferon inducible genes (IFIGs) with disease activity and clinical features in systemic lupus erythematosus (SLE) patiems,.Methods Peripheral blood cells obtained from 67 SLE patients and 23 healthy donors (HDs) were subjected to real-time PCR to measure the transcriptional levels of five IFIGs (OAS-1,Mx-1,Ly6e,IFIT1 and IFIT4).Interferon scores were calculated and were compared between various groups of SLE patients as well as between patients and controls;ISRE lucife:rase reporter gene activity was measured in 17 of 67 patients and correlated with interferon score.Results Interferon scores were strongly correlated with ISRIE reporter gene aetivity,which represented for the type Ⅰ interferon activity in serum.The expression.levels of IFIGs and jinterferon scores were significantly elevated in SLE patients compared with HDs (P＜0.0001).Interferon scores were correlated positively with SLEDAI-2K(P=0.0006) and negatively with C3 levels(P=0.0162).Interferon scores were also significantly elevated in SLE patients with a positive anti-Sm or anti-RNP autoantibodies.Clonclusion The interferon score may be regarded as a good indicator for serum type I interferon activity in SLE and serves as a new hiomarker for disease activity in SLE patients.
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Objective To study the effect of lumbrokinase treatment on hemorheology, glucose and lipids of type 2 diabetes mellitus (T2DM). Methods 76 cases with T2DM whose blood glucose was controlled at FPG0.05). Conclusions Lumbrokinase can decrease the levels of the blood rheology and triglyceride in T2DM. It may prevent and cure the complication of diabetes mellitus
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Objective To correlate the chemokine score with disease activity,organ damages and clinical features in systemic lupus erythematosus (SLE) patients.Methods Peripheral blood cells obtained from 60 SLE patients,20 rheumatoid arthritis (RA) patients and 23 healthy donors (HDs) were subjected to real-time PCR to measure the transcriptional levels of seven chemokines (RANTES,MCP-1,CCL19,MIG,IP-10,CXCL11,and IL-8).Chemokine scores were calculated and were compared between various groups of SLE patients as well as between patients and controls.Results Chemokine scores were significantly elevated in SLE patients compared with RA patients and HDs (P=0.0112 and P=0.0019,respectively).Chemokine scores were correlated positively with SLEDAI (P=0.0061) and negatively with C3 levels (P=0.003).Compared to patients without lupus nephritis (LN),chemokine scores were elevated in SLE patients with active LN,especially when their daily prednisone dosage was less than 30 mg (P=0.0418 and P=0.002,respectively).Chemokine scores were also associated with cumulative organ damage (SLICC damage index [SDI]＞0) and positive anti-Sm and anti-RNP autoantibodies.Conclusion The chemokine score may serve as a new biomarker for disease activity and organ damage in SLE patients.
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<p><b>OBJECTIVE</b>To investigate the incidence and clinicopathologic significance of MSI and LOH on 3P in breast carcinoma and its precancerous lesions, intraductal papillary adenoma and ductal carcinoma in situ.</p><p><b>METHODS</b>41 paired sporadic invasive breast carcinomas, 13 archival precancerous lesion specimens of the breast and 14 couples of benign hyperplasia were collected. Twelve microsatellites on chromosomes 2p, 3p, 5q, 6q, 16q, 17q, eleven markers on chromosome 3p were amplified for MSI and LOH, respectively, by polymerase chain reaction ( PCR ) with designed primers and detecting after polyacrylamide gel electrophoresis. In addition, the expression of protein of hMSH2, hMLHI, FHIT, ER, and PR were detected by immunohistochemistry.</p><p><b>RESULTS</b>MSI was observed, at least two microsatellite markers, in 15 out of 41 (36. 6%) of the carcinomas, almost all belonging to poorly or intermediately differentiated carcinoma. Instability was shown in 9 of the 13 cases of precancerous lesions, but only 2 among them had more than 2 MSI sites. There was no MSI in benign hyperplasia. MSI was targeted predominately at D3S1766, D2S2739 in both carcinomas and precancerous lesions. Of the 11 loci examined, D3S1295, D3S1029 and D3S1038 were identified as the locus with most frequent LOH which were all correlated significantly with some clinicopathological parameters such as histological type, lymph node metastasis in breast cancer, while D3S1295 and D3S1029 were the most frequent markers in precancerous lesions. LOH of D3S1295 had significant correlation with negative expression of FHIT. Positive expression of hMLH1 and hMSH2 protein was detected in breast carcinomas in scattered distribution and their positive rate was 45% and 40% , respectively. In precancerous lesions, hMLH1 and hMSH2 protein showed diffuse expression and their positive rate was 61. 54% and 76. 92% , respectively, significantly lower than that in the control tissues.</p><p><b>CONCLUSION</b>Defective expression of MMR genes is closely associated with the development of breast cancer. Genomic instability might play a role in the early stage during multi-step mammary carcinogenesis. MSI indicates poor histological differentiation in breast carcinoma. D3S1766 and D2S2739 might be the sensitive sites to detect MSI in breast carcinoma and precancerous lesions. The smallest common LOH deletion regions seem likely to be situated between 3p14 and 3p25, indicating the existence of breast tumor related genes in those regions and some of them might affect tumor development.</p>
Subject(s)
Adult , Aged , Female , Humans , Middle Aged , Acid Anhydride Hydrolases , Metabolism , Adaptor Proteins, Signal Transducing , Metabolism , Adenoma , Genetics , Metabolism , Pathology , Breast , Metabolism , Pathology , Breast Neoplasms , Genetics , Metabolism , Pathology , Carcinoma, Ductal, Breast , Genetics , Metabolism , Pathology , Chromosome Deletion , Chromosomes, Human, Pair 3 , Genetics , DNA Mismatch Repair , Hyperplasia , Immunohistochemistry , Loss of Heterozygosity , Lymphatic Metastasis , Microsatellite Instability , MutL Protein Homolog 1 , MutL Proteins , Neoplasm Proteins , Metabolism , Neoplasm Staging , Nuclear Proteins , Metabolism , Polymerase Chain Reaction , Precancerous Conditions , Genetics , Metabolism , Pathology , Receptors, Estrogen , Metabolism , Receptors, Progesterone , MetabolismABSTRACT
OBJECTIVE@#To investigate the interacting effects between pregnancy and flares of systemic lupus erythematosus (SLE) and to explore the best occasion for SLE patients' conception and the management during the pregnancy.@*METHODS@#Thirty one cases of pregnancy complicated with SLE were investigated retrospectively, among whom 18 were in remission of SLE at the beginning of conception (Group A), and the other 13 either had high-activity of the disease or were first diagnosed as SLE during the pregnancy (Group B). Various doses of prednisone were administered to control SLE.@*RESULTS@#SLE flares still occurred in 6 cases in Group A, but in all cases in Group B. Compared with Group A, the rates of fetal loss and early delivery were significantly higher in Group B (P < 0.05), while the survival rate and the weight of the new born were notably decreased in Group B (P < 0.05).@*CONCLUSION@#Pregnancy and SLE interacted with each other unfavorably. Selection of remission stage for conception and proper management during the pregnancy could significantly improve the maternal-fetal safety.
Subject(s)
Adult , Female , Humans , Pregnancy , Lupus Erythematosus, Systemic , Therapeutics , Pregnancy Complications , Therapeutics , Pregnancy Outcome , Time FactorsABSTRACT
Objective To observe the treatment of ~(99)Te-MDP on typeⅡcollagen induced arthritis (CIA)in rat,and the effect on the expression of synovial MMP-3 and TIMP-1 mRNA.To explore the mech anisms of the ~(99)Te-MDP in the treatment of rheumatoid arthritis.Methods The rats in which C1A(n=24)were divided into three group:the control group(n=8),~(99)Tc-MDP group(n=8)and Methotrexate group(n=8). Arthritis were evaluated by arthritis index and histopathological index and the expressions of MMP-3 and TIMP-1 mRNA in synovium were detected by RT-PCR.Results①The arthritis indexs of the control group, the methotrexate group,the ~(99)Tc-MDP group were increased with time.②The histopathological scnres of the control group were significantly higher than those of methotrexate group and ~(99)Tc-MDP group(P＜0.01).The histopathological scores of cartilage destruction and bone erosion of ~(99)Tc-MDP group were lower than those of methotrexate group(P＜0.05).③The levels of MMP-3 mRNA of the control group,~(99)Tc-MDP group, methotrexate group were notably higher than those of the control group(P＜0.01).The levels of control group was notably higher than that of the ~(99)Tc-MDP group(P＜0.05).There was not significant difference in all groups on the levels of TIMP-1 mRNA(P＞0.05).Conclusions ~(99)Tc-MDP can notably relieve the arthritis symdrome and retard the catilage damage and bone erosion of CIA in rats,and could significantly decrease the MMP-3 mRNA in the synovium.Which may be one of the therapeutic mechanism.~(99)Tc-MDP is better than methotrexate in retarding catilage and bone erosion and decreasing MMP-3 mRNA in CIA rats in a 3-week therapeutic intervention.