Connective tissue is a dynamic structure that reacts to environmental cues to maintain homeostasis,including mechanical properties.Mechanical load influences extracellular matrix(ECM)—cell interactions and modulates ...Connective tissue is a dynamic structure that reacts to environmental cues to maintain homeostasis,including mechanical properties.Mechanical load influences extracellular matrix(ECM)—cell interactions and modulates cellular behavior.Mechano-regulation processes involve matrix modification and cell activation to preserve tissue function.The ECM remodeling is crucial for force transmission.Cytoskeleton components are involved in force sensing and transmission,affecting cellular adhesion,motility,and gene expression.Proper mechanical loading helps to maintain tissue health,while imbalances may lead to pathological processes.Active and passive movement,including manual mobilization,improves connective tissue elasticity,promotes ECM-cell homeostasis,and reduces fibrosis.In rehabilitation,understanding mechanical-regulation processes is necessary for ameliorating and developing treatments aimed at preserving tissue elasticity and preventing fibrosis.In this commentary,we aim to globally describe the biological processes involved in mechanical force transmission in connective tissue as support for translational studies and clinical applications in the rehabilitation field.展开更多
BACKGROUND Mixed connective tissue disease(MCTD)is a rare autoimmune disorder charac-terized by overlapping features of systemic lupus erythematosus,systemic sc-lerosis,and polymyositis,and presence of anti-U1 ribonuc...BACKGROUND Mixed connective tissue disease(MCTD)is a rare autoimmune disorder charac-terized by overlapping features of systemic lupus erythematosus,systemic sc-lerosis,and polymyositis,and presence of anti-U1 ribonucleoprotein antibodies.Coexistence with tuberculosis(TB),a common infectious disease in endemic areas,poses a significant diagnostic challenge due to overlapping clinical and radio-logical features.CASE SUMMARY We report a 35-year-old Pakistani female presenting with oral ulcers,body rash,worsening dyspnea,and a history of joint pains initially treated as rheumatoid arthritis.She was on antituberculous therapy(ATT)for presumed pulmonary TB.Laboratory findings revealed anemia,leukopenia,raised erythrocyte sedimen-tation rate,positive anti-Sm/RNP,anti-dsDNA,and anti-SSA/Ro antibodies,confirming MCTD with clinical features of systemic lupus erythematosus,Sjogren syndrome,and systemic sclerosis.The patient was also positive for hepatitis C and active TB.Treatment involved corticosteroids alongside continuation of ATT,resulting in significant clinical improvement over 12 days,with resolution of symptoms and improved laboratory parameters.The patient remained stable on follow-up with hydroxychloroquine and prednisolone.CONCLUSION This case highlights the diagnostic complexity when autoimmune diseases coexist with TB,particularly in TB-endemic regions.Early recognition and integrated management of both conditions are crucial to improving outcomes.Clinicians should maintain a broad differential diagnosis and perform compre-hensive immunological workup in patients with overlapping symptoms.展开更多
Background:To investigate adverse event(AE)signals associated with six proton pump inhibitors(PPIs),enhance drug labeling information,and provide guidance for their safe clinical use.Methods:Adverse reaction data for ...Background:To investigate adverse event(AE)signals associated with six proton pump inhibitors(PPIs),enhance drug labeling information,and provide guidance for their safe clinical use.Methods:Adverse reaction data for musculoskeletal and connective tissue disorders related to six PPI formulations—omeprazole,pantoprazole,lansoprazole,esomeprazole,rabeprazole,and dexlansoprazole—from Q12004 to Q42023 were collected from the FDA Adverse Event Reporting System(FAERS).Signal detection was performed using the Reporting Odds Ratio(ROR),Proportional Reporting Ratio(PRR),Bayesian Confidence Propagation Neural Network(BCPNN),and Empirical Bayesian Geometric Mean(EBGM).Data processing and statistical analysis were conducted using R Studio 4.40.Results:A total of 6,635,3,853,1,792,15,731,483,and 534 adverse events were identified for the six PPIs,respectively.The four algorithms(ROR,PRR,BCPNN,and EBGM)generated 17,19,8,27,5,and 2 positive signals.Notably,signals for renal osteodystrophy and osteoporosis were more frequent,with stronger signals for lumbar flexion syndrome and renal osteodystrophy.Conclusion:Patients with chronic kidney disease,a high risk of osteoporosis and fractures,or those using statins should select PPIs with a lower risk of adverse musculoskeletal and connective tissue reactions to minimize these adverse effects and ensure standardized clinical use of PPIs.展开更多
AIM:To investigate the role of connective tissue growth factor(CTGF)and vascular endothelial growth factor(VEGF)in the protein profile of the aqueous humor in patients with proliferative diabetic retinopathy(PDR)follo...AIM:To investigate the role of connective tissue growth factor(CTGF)and vascular endothelial growth factor(VEGF)in the protein profile of the aqueous humor in patients with proliferative diabetic retinopathy(PDR)following intravitreal injection of conbercept.METHODS:This study included 72 PDR patients and 8 cataract patients as controls.PDR patients were divided into 3 groups according to the intervals of 3,5,and 7d between intravitreal conbercept(IVC,0.5 mg/0.05 mL)injection and pars plana vitrectomy(PPV)performed.Aqueous humor samples were collected before and after IVC and PPV for VEGF and CTGF levels detected with enzyme-linked immunosorbent assay(ELISA).The differential proteomics of 10 patients who underwent PPV surgery 5d after IVC and 8 normal controls was studied,Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)analysis were performed on the data,and the protein interaction network of 23 differential proteins was studied.RESULTS:Post-IVC,VEGF levels decreased and CTGF levels increased significantly in aqueous humor,with the CTGF/VEGF ratio rising significantly at all intervals.Liquid chromatography tandem mass spectrometry(LC-MS/MS)identified differentially expressed proteins between preand post-IVC samples.GO and KEGG analyses revealed involvement in immune response,stress response,complement and coagulation cascades,ferroptosis,and PPAR signaling pathways.PPI analysis highlighted key proteins like APOA1,C3,and transferrin(TF).ELISA assay confirmed the differential expression of proteins such as HBA1,SERPINA1,COL1A1,and ACTB,with significant changes in the IVC groups.CONCLUSION:The study demonstrates that IVC effectively reduces VEGF levels while increasing CTGF levels,thereby modifying the CTGF/VEGF ratio,and IVC significantly alters the protein profile in the aqueous humor of patients with PDR.Proteomic analysis reveals that these changes are associated with critical biological pathways and protein interactions involved in immune response,stress response,and cellular metabolism.展开更多
AIM:To examine the disparities in macular retinal vascular density between individuals with connective tissue disease-related interstitial lung disease(CTD-ILD)and healthy controls(HCs)by optical coherence tomography ...AIM:To examine the disparities in macular retinal vascular density between individuals with connective tissue disease-related interstitial lung disease(CTD-ILD)and healthy controls(HCs)by optical coherence tomography angiography(OCTA)and to investigate the changes in microvascular density in abnormal eyes.METHODS:For a retrospective case-control study,a total of 16 patients(32 eyes)diagnosed with CTD-ILD were selected as the ILD group.The 16 healthy volunteers with 32 eyes,matched in terms of age and sex with the patients,were recruited as control group.The macular retina’s superficial retinal layer(SRL)and deep retinal layer(DRL)were examined and scanned using OCTA in each individual eye.The densities of retinal microvascular(MIR),macrovascular(MAR),and total microvascular(TMI)were calculated and compared.Changes in retinal vascular density in the macular region were analyzed using three different segmentation methods:central annuli segmentation method(C1-C6),hemispheric segmentation method[uperior right(SR),superior left(SL),inferior left(IL),and inferior right(IR)],and Early Treatment Diabetic Retinopathy Study(ETDRS)methods[superior(S),inferior(I),left(L),and right(R)].The data were analyzed using Version 9.0 of GraphPad prism and Pearson analysis.RESULTS:The OCTA data demonstrated a statistically significant difference(P<0.05)in macular retinal microvessel density between the two groups.Specifically,in the SRL and DRL analyses,the ILD group exhibited significantly lower surface density of MIR and TMI compared to the HCs group(P<0.05).Furthermore,using the hemispheric segmentation method,the ILD group showed notable reductions in SL,SR,and IL in the superficial retina(P<0.05),as well as marked decreases in SL and IR in the deep retina(P<0.05).Similarly,when employing the ETDRS method,the ILD group displayed substantial drops in superficial retinal S and I(P<0.05),along with notable reductions in deep retinal L,I,and R(P<0.05).In the central annuli segmentation method,the ILD group exhibited a significant decrease in the superficial retinal C2-4 region(P<0.05),whereas the deep retina showed a notable reduction in the C3-5 region(P<0.05).Additionally,there was an observed higher positive likelihood ratio in the superficial SR region and deep MIR.Furthermore,there was a negative correlation between conjunctival vascular density and both deep and superficial retinal TMI(P<0.001).CONCLUSION:Patients with CTD-ILD exhibits a significantly higher conjunctival vascular density compared to the HCs group.Conversely,their fundus retinal microvascular density is significantly lower.Furthermore,CTD-ILD patients display notably lower superficial and deep retinal vascular density in comparison to the HCs group.The inverse correlation between conjunctival vascular density and both superficial and deep retinal TMI suggests that detecting subtle changes in ocular microcirculation could potentially serve as an early diagnostic indicator for connective tissue diseases,thereby enhancing disease management.展开更多
Connective tissue diseases (CTDs) are Autoimmune diseases (AIDs) characterized by the appearance of autoantibodies, which are diagnostic markers. Investigations of these autoantibodies play a major role in the managem...Connective tissue diseases (CTDs) are Autoimmune diseases (AIDs) characterized by the appearance of autoantibodies, which are diagnostic markers. Investigations of these autoantibodies play a major role in the management of several autoimmune diseases. The objective of this study was to describe the profile of anti-ENA antibodies according to the clinical symptoms of mixed CTDs in Conakry teaching Hospital. We performed a cross-sectional study during six months. A total of 20 patients was recruited and we measured antibodies using the ELISA technique. The mean age of our patients was 36.5 years, with a predominance of females. Cutaneous and rheumatological signs were the main clinical manifestations. SLP was the most frequent CTDs;the threshold of ENA antibodies positivity was higher in scleroderma with and SLP. Anti-ENA identification reveals the frequency of anti-SSA (83.33%), anti-U1RNP (66.66%) and anti-histone (50%) antibodies. Antinuclear antibodies (ANA) react with various components of the cell nucleus. Their detection is of major interest in the diagnosis of CTDs. Our results highlight the importance of determining the specificity of these antibodies to guide differential diagnosis.展开更多
Purpose: Studies on imaging findings in mixed connective tissue disease (MCTD) are limited. This study assessed the relationship between CT-derived parameters (pulmonary artery diameter [PAD] and lung parenchymal abno...Purpose: Studies on imaging findings in mixed connective tissue disease (MCTD) are limited. This study assessed the relationship between CT-derived parameters (pulmonary artery diameter [PAD] and lung parenchymal abnormalities [LPA]) and estimated pulmonary artery pressure (PAP) in patients with MCTD. Materials and Methods: This single-center retrospective study enrolled consecutive patients with MCTD who underwent CT and echocardiography within 6 months between December 2004 and November 2021. Chest CT was used to measure PAD (mm) and evaluate LPA (%). LPA was quantitatively assessed for reticular, ground-glass opacities, consolidation, or honeycombing. Peak tricuspid regurgitation velocity (TRV) on echocardiography was considered to reflect PAP. Correlation and partial correlation analyses were performed to assess the relationship between CT-derived parameters and peak TRV. Results: Overall, 116 patients (mean age 50.0 ± 17.0 years [SD]) with a median disease duration of 3.0 years had a median peak TRV of 2.28 m/sec and median PAD of 27.0 mm. Pulmonary hypertension was found in 18 (15.5%) patients. LPA was observed in 52 patients, with a median of 0.0% and a mean of 4.5% ± 8.9 [SD]. Peak TRV was correlated with PAD (r = 0.58, p Conclusion: A moderate positive correlation was observed in patients with MCTD between PAD and estimated PAP, irrespective of the presence of LPA, whereas LPA was not correlated with estimated PAP.展开更多
This study investigated the effect of explicit instruction about DCs in argumentative writings by 15 Chinese learners of English. This study involved in a 4-week experiment. Pre-and post-writing tests were quantitativ...This study investigated the effect of explicit instruction about DCs in argumentative writings by 15 Chinese learners of English. This study involved in a 4-week experiment. Pre-and post-writing tests were quantitatively analyzed to examine whether the explicit instruction about DCs had a significant effect on the students'argumentative writing. The findings revealed that the ex-plicit instruction of the target DCs facilitated the improvement of the participants in their argumentative writing .展开更多
AIM:To establish the frequency and clinical features of connective tissue diseases(CTDs)in a cohort of Chinese patients with primary biliary cirrhosis(PBC).METHODS:Three-hundred and twenty-two Chinese PBC patients wer...AIM:To establish the frequency and clinical features of connective tissue diseases(CTDs)in a cohort of Chinese patients with primary biliary cirrhosis(PBC).METHODS:Three-hundred and twenty-two Chinese PBC patients were screened for the presence of CTD,and the systemic involvement was assessed.The differences in clinical features and laboratory findings between PBC patients with and without CTD were documented.The diversity of incidence of CTDs in PBC of different countries and areas was discussed.For the comparison of normally distributed data,Student’s t test was used,while non-parametric test(Wilcoxon test)for the non-normally distributed data and 2×2χ2or Fisher’s exact tests for the ratio.RESULTS:One-hundred and fifty(46.6%)PBC patients had one or more CTDs.The most common CTD was Sj gren’s syndrome(SS,121 cases,36.2%).There were nine cases of systemic sclerosis(SSc,2.8%),12of systemic lupus erythematosus(SLE,3.7%),nine of rheumatoid arthritis(RA,2.8%),and 10 of polymyositis(PM,3.1%)in this cohort.Compared to patients with PBC only,the PBC+SS patients were more likely to have fever and elevated erythrocyte sedimentation rate(ESR),higher serum immunoglobulin G(IgG)levels and more frequent rheumatoid factor(RF)and interstitial lung disease(ILD)incidences;PBC+SSc patients had higher frequency of ILD;PBC+SLE patients had lower white blood cell(WBC)count,hemoglobin(Hb),platelet count,γ-glutamyl transpeptidase and immunoglobulin M levels,but higher frequency of renal involvement;PBC+RA patients had lower Hb,higher serum IgG,alkaline phosphatase,faster ESR and a higher ratio of RF positivity;PBC+PM patients had higher WBC count and a tendency towards myocardial involvement.CONCLUSION:Besides the common liver manifestation of PBC,systemic involvement and overlaps with other CTDs are not infrequent in Chinese patients.When overlapping with other CTDs,PBC patients manifested some special clinical and laboratory features which may have effect on the prognosis.展开更多
AIM: To examine the expression of connective tissue growth factor (CTGF), also known as CCN2, in gastric carcinoma (GC), and the correlation between the expression of CTGF, clinicopathologic features and clinical outc...AIM: To examine the expression of connective tissue growth factor (CTGF), also known as CCN2, in gastric carcinoma (GC), and the correlation between the expression of CTGF, clinicopathologic features and clinical outcomes of patients with GC. METHODS: One hundred and twenty-two GC patients were included in the present study. All patients were followed up for at least 5 years. Proteins of CTGF were detected using the Powervision two-step immunostaining method. RESULTS: Of the specimens from 122 GC patients analyzed for CTGF expression, 58 (58/122, 47.5%) had a high CTGF expression in cytoplasm of gastric carcinoma cells and 64 (64/122, 52.5%) had a low CTGF expression. Patients with a high CTGF expression showed a higher incidence of lymph node metastasis than those with a low CTGF expression (P = 0.032). Patients with a high CTGF expression had significantly lower 5-year survival rate than those with a low CTGF expression (27.6% vs 46.9%, P = 0.0178), especially those staging Ⅰ+Ⅱ+Ⅲ (35.7% vs 65.2%, P = 0.0027). CONCLUSION: GC patients with an elevated CTGF expression have more lymph node metastases and a shorter survival time. CTGF seems to be an independent prognostic factor for the successful differentiation of high-risk GC patients staging Ⅰ+Ⅱ+Ⅲ. Over-expression of CTGF in human GC cells results in an increased aggressive ability.展开更多
Objective:Large segmental bone defect repair remains a clinical and scientific challenge with increasing interest focusing on combining gene transfection with tissue engineering techniques.The aim of this study is to ...Objective:Large segmental bone defect repair remains a clinical and scientific challenge with increasing interest focusing on combining gene transfection with tissue engineering techniques.The aim of this study is to investigate the effect of connective tissue growth factor(CTGF) on the proliferation and osteogenic differentiation of the bone marrow mesenchymal stem cells(MSCs).Methods:A CTGF-expressing plasmid(pCTGF) was constructed and transfected into MSCs.Then expressions of bone morphogenesis-related genes,proliferation rate,alkaline phosphatase activity,and mineralization were examined to evaluate the osteogenic potential of the CTGF gene-modified MSCs.Results:Overexpression of CTGF was confirmed in pCTGF-MSCs.pCTGF transfection significantly enhanced the proliferation rates of pCTGF-MSCs(P<0.05).CTGF induced a 7.5-fold increase in cell migration over control(P<0.05).pCTGF transfection enhanced the expression of bone matrix proteins,such as bone sialo-protein,osteocalcin,and collagen type I in MSCs.The levels of alkaline phosphatase(ALP) activities of pCTGF-MSCs at the 1st and 2nd weeks were 4.0-and 3.0-fold higher than those of MSCs cultured in OS-medium,significantly higher than those of mock-MSCs and normal control MSCs(P<0.05).Overexpression of CTGF in MSCs enhanced the capability to form mineralized nodules.Conclusion:Overexpression of CTGF could improve the osteogenic differentiation ability of MSCs,and the CTGF gene-modified MSCs are potential as novel cell resources of bone tissue engineering.展开更多
AIM:To determine the expression characteristics of connective tissue growth factor(CTGF/CCN2) in human hepatocellular carcinoma(HCC) in histology and to elucidate the roles of CCN2 on hepatoma cell cycle progression a...AIM:To determine the expression characteristics of connective tissue growth factor(CTGF/CCN2) in human hepatocellular carcinoma(HCC) in histology and to elucidate the roles of CCN2 on hepatoma cell cycle progression and metastasis in vitro.METHODS:Liver samples from 36 patients(who underwent hepatic resection for the first HCC between 2006 and 2011) and 6 normal individuals were examined for transforming growth factor β1(TGF-β1) or CCN2 mRNA by in situ hybridization.Computer image analysis was performed to measure integrated optimal density of CCN2 mRNA-positive cells in carcinoma foci and the surrounding stroma.Fibroblast-specific protein-1(FSP-1) and E-cadherin were examined to evaluate the process of epithelial to mesenchymal transition,α-smooth muscle actin and FSP-1 were detected to identify hepatic stellate cells,and CD34 was measured to evaluate the extent of vascularization in liver tissues by immunohistochemical staining.CCN2 was assessed for its stimulation of HepG2 cell migration and invasion using commercial kits while flow cytometry was used to determine CCN2 effects on HepG2 cell-cycle.RESULTS:In situ hybridization analysis showed that TGF-β1 mRNA was mainly detected in connective tissues and vasculature around carcinoma foci.In comparison to normal controls,CCN2 mRNA was enhanced 1.9-fold in carcinoma foci(12.36 ± 6.08 vs 6.42 ± 2.35) or 9.4-fold in the surrounding stroma(60.27 ± 28.71 vs 6.42 ± 2.35),with concomitant expression of CCN2 and TGF-β1 mRNA in those areas.Epithelial-mesenchymal transition phenotype related with CCN2 was detected in 12/36(33.3%) of HCC liver samples at the edges between carcinoma foci and vasculature.Incubation of HepG2 cells with CCN2(100 ng/mL) resulted in more of the cells transitioning into S phase(23.85 ± 2.35 vs 10.94 ± 0.23),and induced a significant migratory(4.0-fold) and invasive(5.7-fold) effect.TGF-β1-induced cell invasion was abrogated by a neutralizing CCN2 antibody showing that CCN2 is a downstream mediator of TGF-β1-induced hepatoma cell invasion.CONCLUSION:These data support a role for CCN2 in the growth and metastasis of HCC and highlight CCN2 as a potential novel therapeutic target.展开更多
AIM： To determine the effect of hammerhead ribozyme targeting connective tissue growth factor （CCN2） on human hepatic stellate cell （HSC） function.METHODS： CCN2 hammerhead ribozyme cDNA plus two self-cleaving se...AIM： To determine the effect of hammerhead ribozyme targeting connective tissue growth factor （CCN2） on human hepatic stellate cell （HSC） function.METHODS： CCN2 hammerhead ribozyme cDNA plus two self-cleaving sequences were inserted into pTriEx2 to produce pTriCCN2-Rz. Each vector was individually transfected into cultured LX-2 human HSCs, which were then stimulated by addition of transforming growth factor （TGF）-β1 to the culture medium. Semiquantitative RT-PCR was used to determine mRNA levels for CCN2 or collagen I, while protein levels of each molecule in cell /ysates and conditioned medium were measured by ELISA. Cell-cycle progression of the transfected cells was assessed by flow cytometry.RESULTS： In pTriEx2-transfected LX-2 cells, TGF-β1 treatment caused an increase in the mRNA level for CCN2 or collagen I, and an increase in produced and secreted CCN2 or extracellular collagen I protein levels, pTriCCN2-Rz-transfected LX-2 cells showed decreased basal CCN2 or collagen mRNA levels, as well as produced and secreted CCN2 or collagen I protein. Furthermore, the TGF-β1-induced increase in mRNA or protein for CCN2 or collagen I was inhibited partially in pTriCCN2-Rz-transfected LX-2 cells. Inhibition of CCN2 using hammerhead ribozyme cDNA resulted in fewer of the cells transitioning into S phase.CONCLUSION： Endogenous CCN2 is a mediator of basal or TGF-β1-induced collagen I production in human HSCs and regulates entry of the cells into S phase.展开更多
Objective To investigate the prevalence of anti-endothelial cell antibodies (AECAs) in the sera of connective tissue diseases (CTD) patients with pulmonary arterial hypertension (PAH) and its correlation with clinical...Objective To investigate the prevalence of anti-endothelial cell antibodies (AECAs) in the sera of connective tissue diseases (CTD) patients with pulmonary arterial hypertension (PAH) and its correlation with clinical manifestations. Methods AECAs in sera of 39 CTD patients with PAH,22 CTD patients without PAH,and 10 healthy donors as controls were detected with Western blotting. The prevalence of different AECAs in different groups was compared and its correlation with clinical manifestations was also investigated. Results The prevalence of AECAs was 82.1% in CTD patients with PAH,72.7% in CTD patients without PAH,and 20.0% in healthy donors. Anti-22 kD AECA was only detected in CTD patients with PAH (15.4%). Anti-75 kD AECA was more frequently detected in CTD patients with PAH than in those without PAH (51.3% vs. 22.7%,P<0.05). In CTD patients with PAH,anti-75 kD AECA was more frequently detected in those with Raynaud’s phenomenon or with positive anti-RNP antibody. Conclusion AECAs could be frequently detected in CTD patients with or without PAH,while anti-22 kD and anti-75 kD AECA might be specific in CTD patients with PAH.展开更多
Hyperthyroid heart disease(HHD)is one of the most severe complications of overt hyperthyroidism and increases the risk of mortality in affected patients.Early identification of patients at a higher risk of developing ...Hyperthyroid heart disease(HHD)is one of the most severe complications of overt hyperthyroidism and increases the risk of mortality in affected patients.Early identification of patients at a higher risk of developing HHD can improve clinical outcomes through active surveillance and management.Connective tissue growth factor(CTGF),a secreted extracellular protein,plays a significant role in cardiac remodeling and dysfunction.We aimed to investigate the association between plasma CTGF level and the risk of HHD in this study.A total of 142 overt hyperthyroid patients without HHD and 99 patients with HHD were included.The plasma CTGF levels were measured using ELISA kits.Routine clinical medical data and echocardiography parameters were recorded for analysis.The plasma CTGF level was significantly higher in patients with HHD than in those without HHD(P=0.002).The plasma CTGF level was positively correlated with free triiodothyronin,tryrotropin receptor antibody,troponin I and lactate dehydrogenase levels and the left atrium diameters,right atrium diameters,and right ventricular end-diastolic diameters(all P<0.05).Logistic regression analysis showed that quartiles 3 and 4 of plasma CTGF levels were significantly associated with the increased risk of HHD(crude OR:2.529;95%CI:1.188-5.387).However,after adjustment for the potentially confounding variables,quartile 4 alone was significantly associated with the higher risk of HHD relative to quartile I.Hyperthyroid patients with HHD display higher plasma CTGF levels.Furthermore,CTGF is an independent risk factor for HHD.Therefore,the plasma CTGF level may be a potential biomarker for the risk of HHD.展开更多
Diabetic retinopathy（DR） is one of the most important types of diabetic microangiopathy, which is a specific change of fundus lesions and is one of the most serious complications of diabetes. When DR develops to pro...Diabetic retinopathy（DR） is one of the most important types of diabetic microangiopathy, which is a specific change of fundus lesions and is one of the most serious complications of diabetes. When DR develops to proliferative DR, the main factors of decreasing vision, and even blindness, include retinal detachment and vitreous hemorrhage caused by contraction of blood vessels by fiber membrane. Recent studies reported that the formation of fiber vascular membrane is closely related to retinal fibrosis. The connective tissue growth factor（CTGF） is a cytokine that is closely related to DR fibrosis. However, its mechanism is poorly understood. This paper summarizes the recent studies about CTGF on DR fibrosis for a comprehensive understanding of the role and mechanism of CTGF in PDR.展开更多
OBJECTIVE: To investigate the efficacy of the full composition granules of Huanglian(Rhizoma Coptidis)(FGC) on the serum monocyte chemotactic protein-1(MCP-1) and connective tissue growth factor(CTGF) levels and kidne...OBJECTIVE: To investigate the efficacy of the full composition granules of Huanglian(Rhizoma Coptidis)(FGC) on the serum monocyte chemotactic protein-1(MCP-1) and connective tissue growth factor(CTGF) levels and kidney nuclear factor-κB(NF-κB) expression in rats with high-fat diet-induced diabetes.METHODS: Diabetes was induced in rats by feeding a high-fat chow combined with intravenous streptozotocin injection. Forty diabetic SpragueDawley rats were randomly assigned to a normal group(NG), model group(MG), irbesartan group(IG), and low-, middle-, and high-dosage FGC groups(LFGC, MFGC, HFGC), with eight rats per group. The IG rats received 31.25 mg·kg^(-1)·d^(-1) irbesartan tablets, whereas those in the LFGC, MFGC,and HFGC were administered 52, 312.5, and 625 mg·kg^(-1)·d^(-1) FGC, respectively. After 12 weeks,bodyweight(BW), left kidney weight(KW), hemoglobin A1c(HbA1c), serum creatinine(Scre), blood urea nitrogen(BUN), and serum MCP-1 and CTGF levels were determined, pathological changes of the kidney were recorded, and kidney NF-κB p65(A) expression was measured.RESULTS: The 24-h urine albumin and levels of HbA1c, Scre, BUN, and serum MCP-1 and CTGF were significantly increased in in the MG compared with the NG, as was the kidney NF-κB(p65) expression(P < 0.05). Furthermore, clear pathological changes in kidney fibrosis were observed in the MG rats. Following irbesartan and FGC administration,the 24-h urine albumin and the levels of HbA1c,Scre, and serum MCP-1 and CTGF were significantly decreased in FCG groups compared with those in the MG, which is in agreement with the change in the kidney NF-κB(p65) expression, whereas the similarly significant decrease only exist in 24-h urine albumin and the levels of serum CTGF after irbesartan administration. Hematoxylin-eosin(HE)staining results indicated that the fibrosis observed in the MG samples was alleviated through FGC treatment.CONCLUSION: FGC may alleviate potential kidney injury by decreasing the serum MCP-1 and CTGF levels and inhibiting NF-k B expression in diabetic nephropathy in rats with high-fat diet-induced diabetes.展开更多
The pathogenesis of rheumatoid arthritis(RA) remains to be completely elucidated so far; however, it is known that proinflammatory cytokines play a pivotal role in the induction of RA. Tumor necrosis factor(TNF-α), i...The pathogenesis of rheumatoid arthritis(RA) remains to be completely elucidated so far; however, it is known that proinflammatory cytokines play a pivotal role in the induction of RA. Tumor necrosis factor(TNF-α), in particular, is considered to play a central role in bone destruction by mediating the abnormal activation of osteoclasts or the production of proteolytic enzymes through direct or indirect mechanisms. The use of TNF-α blocking agents has a significant impact on RA therapy. Anti-TNF-α blocking agents such as infliximab are very effective for treatment of RA, especially for the prevention of articular destruction. We have previously shown that several proteins exhibited extensive changes in their expression after amelioration of RA with infliximab treatment. Among the proteins, connective tissue growth factor(CTGF) has a significantrole for the development of RA. Herein, we review the function of CTGF in the pathogenesis of RA and discuss the possibility of a novel treatment for RA. We propose that CTGF is a potentially novel effector molecule in the pathogenesis of RA. Blocking the CTGF pathways by biological agents may have great beneficial effect in patients with RA.展开更多
AIM:To investigate the mechanisms involved in a possible modulator role of interleukin(IL) -6 signalling on CYR61-CTGF-NOV(CCN) 2/connective tissue growth factor(CTGF) expression in hepatocytes(PC) and to look for a r...AIM:To investigate the mechanisms involved in a possible modulator role of interleukin(IL) -6 signalling on CYR61-CTGF-NOV(CCN) 2/connective tissue growth factor(CTGF) expression in hepatocytes(PC) and to look for a relation between serum concentrations of these two parameters in patients with acute inflammation. METHODS:Expression of CCN2/CTGF,p-STAT3,p-Smad 3/1 and p-Smad2 was examined in primary freshly isolated rat or cryo-preserved human PC exposed to various stimuli by Western blotting,electrophoretic mobility shift assay(EMSA) ,reporter-gene-assays and reversetranscriptase polymerase chain reaction. RESULTS:IL-6 strongly down-regulated CCN2/CTGF protein and mRNA expression in PC,enhanceable by extracellular presence of the soluble IL-6 receptor gp80,and supported by an inverse relation between IL-6 and CCN2/CTGF concentrations in patients'sera.The inhi-bition of TGFβ1 driven CCN2/CTGF expression by IL-6 did not involve a modulation of Smad2(and Smad1/3) signalling.However,the STAT3 SH2 domain binding peptide,a selective inhibitor of STAT3 DNA binding activity,counteracted the inhibitory effect of IL-6 on CCN2/CTGF expression much more pronounced than pyrrolidine-dithiocarbamate,an inhibitor primarily of STAT3 phosphorylation.An EMSA confirmed STAT3 binding to the proposed proximal STAT binding site in the CCN2/CTGF promoter. CONCLUSION:CCN2/CTGF is identified as a hepatocellular negative acute phase protein which is downregulated by IL-6 via the STAT3 pathway through interaction on the DNA binding level.展开更多
OBJECTIVE:To determine the effect of Houttuynia cordata Aetherolea on connective tissue growth factor and adiponectin in a rat model of diabetes mellitus(DM).METHODS:DM was induced in rats using streptozotocin(STZ) an...OBJECTIVE:To determine the effect of Houttuynia cordata Aetherolea on connective tissue growth factor and adiponectin in a rat model of diabetes mellitus(DM).METHODS:DM was induced in rats using streptozotocin(STZ) and high glucose-lipid animal feed.Animals were then treated with Houttuynia cordata Aetherolea for 8 weeks.Changes in connective tissue growth factor and adiponectin levels in rats were observed.RESULTS:Connective tissue growth factor and adiponectin levels in rats with DM improved after Houttuynia cordata Aetherolea treatment.CONCLUSION:Houttuynia cordata Aetherolea had a positive effect on rats with DM by reducing levels of connective tissue growth factor and increasing adiponectin levels.展开更多
文摘Connective tissue is a dynamic structure that reacts to environmental cues to maintain homeostasis,including mechanical properties.Mechanical load influences extracellular matrix(ECM)—cell interactions and modulates cellular behavior.Mechano-regulation processes involve matrix modification and cell activation to preserve tissue function.The ECM remodeling is crucial for force transmission.Cytoskeleton components are involved in force sensing and transmission,affecting cellular adhesion,motility,and gene expression.Proper mechanical loading helps to maintain tissue health,while imbalances may lead to pathological processes.Active and passive movement,including manual mobilization,improves connective tissue elasticity,promotes ECM-cell homeostasis,and reduces fibrosis.In rehabilitation,understanding mechanical-regulation processes is necessary for ameliorating and developing treatments aimed at preserving tissue elasticity and preventing fibrosis.In this commentary,we aim to globally describe the biological processes involved in mechanical force transmission in connective tissue as support for translational studies and clinical applications in the rehabilitation field.
文摘BACKGROUND Mixed connective tissue disease(MCTD)is a rare autoimmune disorder charac-terized by overlapping features of systemic lupus erythematosus,systemic sc-lerosis,and polymyositis,and presence of anti-U1 ribonucleoprotein antibodies.Coexistence with tuberculosis(TB),a common infectious disease in endemic areas,poses a significant diagnostic challenge due to overlapping clinical and radio-logical features.CASE SUMMARY We report a 35-year-old Pakistani female presenting with oral ulcers,body rash,worsening dyspnea,and a history of joint pains initially treated as rheumatoid arthritis.She was on antituberculous therapy(ATT)for presumed pulmonary TB.Laboratory findings revealed anemia,leukopenia,raised erythrocyte sedimen-tation rate,positive anti-Sm/RNP,anti-dsDNA,and anti-SSA/Ro antibodies,confirming MCTD with clinical features of systemic lupus erythematosus,Sjogren syndrome,and systemic sclerosis.The patient was also positive for hepatitis C and active TB.Treatment involved corticosteroids alongside continuation of ATT,resulting in significant clinical improvement over 12 days,with resolution of symptoms and improved laboratory parameters.The patient remained stable on follow-up with hydroxychloroquine and prednisolone.CONCLUSION This case highlights the diagnostic complexity when autoimmune diseases coexist with TB,particularly in TB-endemic regions.Early recognition and integrated management of both conditions are crucial to improving outcomes.Clinicians should maintain a broad differential diagnosis and perform compre-hensive immunological workup in patients with overlapping symptoms.
文摘Background:To investigate adverse event(AE)signals associated with six proton pump inhibitors(PPIs),enhance drug labeling information,and provide guidance for their safe clinical use.Methods:Adverse reaction data for musculoskeletal and connective tissue disorders related to six PPI formulations—omeprazole,pantoprazole,lansoprazole,esomeprazole,rabeprazole,and dexlansoprazole—from Q12004 to Q42023 were collected from the FDA Adverse Event Reporting System(FAERS).Signal detection was performed using the Reporting Odds Ratio(ROR),Proportional Reporting Ratio(PRR),Bayesian Confidence Propagation Neural Network(BCPNN),and Empirical Bayesian Geometric Mean(EBGM).Data processing and statistical analysis were conducted using R Studio 4.40.Results:A total of 6,635,3,853,1,792,15,731,483,and 534 adverse events were identified for the six PPIs,respectively.The four algorithms(ROR,PRR,BCPNN,and EBGM)generated 17,19,8,27,5,and 2 positive signals.Notably,signals for renal osteodystrophy and osteoporosis were more frequent,with stronger signals for lumbar flexion syndrome and renal osteodystrophy.Conclusion:Patients with chronic kidney disease,a high risk of osteoporosis and fractures,or those using statins should select PPIs with a lower risk of adverse musculoskeletal and connective tissue reactions to minimize these adverse effects and ensure standardized clinical use of PPIs.
文摘AIM:To investigate the role of connective tissue growth factor(CTGF)and vascular endothelial growth factor(VEGF)in the protein profile of the aqueous humor in patients with proliferative diabetic retinopathy(PDR)following intravitreal injection of conbercept.METHODS:This study included 72 PDR patients and 8 cataract patients as controls.PDR patients were divided into 3 groups according to the intervals of 3,5,and 7d between intravitreal conbercept(IVC,0.5 mg/0.05 mL)injection and pars plana vitrectomy(PPV)performed.Aqueous humor samples were collected before and after IVC and PPV for VEGF and CTGF levels detected with enzyme-linked immunosorbent assay(ELISA).The differential proteomics of 10 patients who underwent PPV surgery 5d after IVC and 8 normal controls was studied,Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)analysis were performed on the data,and the protein interaction network of 23 differential proteins was studied.RESULTS:Post-IVC,VEGF levels decreased and CTGF levels increased significantly in aqueous humor,with the CTGF/VEGF ratio rising significantly at all intervals.Liquid chromatography tandem mass spectrometry(LC-MS/MS)identified differentially expressed proteins between preand post-IVC samples.GO and KEGG analyses revealed involvement in immune response,stress response,complement and coagulation cascades,ferroptosis,and PPAR signaling pathways.PPI analysis highlighted key proteins like APOA1,C3,and transferrin(TF).ELISA assay confirmed the differential expression of proteins such as HBA1,SERPINA1,COL1A1,and ACTB,with significant changes in the IVC groups.CONCLUSION:The study demonstrates that IVC effectively reduces VEGF levels while increasing CTGF levels,thereby modifying the CTGF/VEGF ratio,and IVC significantly alters the protein profile in the aqueous humor of patients with PDR.Proteomic analysis reveals that these changes are associated with critical biological pathways and protein interactions involved in immune response,stress response,and cellular metabolism.
基金Supported by National Natural Science Foundation of China(No.82160195)Key R&D Program of Jiangxi Province(No.20223BBH80014)General Science and Technology Program of the Department of Traditional Chinese Medicine,Jiangxi Provincial Health Commission(No.2017A241).
文摘AIM:To examine the disparities in macular retinal vascular density between individuals with connective tissue disease-related interstitial lung disease(CTD-ILD)and healthy controls(HCs)by optical coherence tomography angiography(OCTA)and to investigate the changes in microvascular density in abnormal eyes.METHODS:For a retrospective case-control study,a total of 16 patients(32 eyes)diagnosed with CTD-ILD were selected as the ILD group.The 16 healthy volunteers with 32 eyes,matched in terms of age and sex with the patients,were recruited as control group.The macular retina’s superficial retinal layer(SRL)and deep retinal layer(DRL)were examined and scanned using OCTA in each individual eye.The densities of retinal microvascular(MIR),macrovascular(MAR),and total microvascular(TMI)were calculated and compared.Changes in retinal vascular density in the macular region were analyzed using three different segmentation methods:central annuli segmentation method(C1-C6),hemispheric segmentation method[uperior right(SR),superior left(SL),inferior left(IL),and inferior right(IR)],and Early Treatment Diabetic Retinopathy Study(ETDRS)methods[superior(S),inferior(I),left(L),and right(R)].The data were analyzed using Version 9.0 of GraphPad prism and Pearson analysis.RESULTS:The OCTA data demonstrated a statistically significant difference(P<0.05)in macular retinal microvessel density between the two groups.Specifically,in the SRL and DRL analyses,the ILD group exhibited significantly lower surface density of MIR and TMI compared to the HCs group(P<0.05).Furthermore,using the hemispheric segmentation method,the ILD group showed notable reductions in SL,SR,and IL in the superficial retina(P<0.05),as well as marked decreases in SL and IR in the deep retina(P<0.05).Similarly,when employing the ETDRS method,the ILD group displayed substantial drops in superficial retinal S and I(P<0.05),along with notable reductions in deep retinal L,I,and R(P<0.05).In the central annuli segmentation method,the ILD group exhibited a significant decrease in the superficial retinal C2-4 region(P<0.05),whereas the deep retina showed a notable reduction in the C3-5 region(P<0.05).Additionally,there was an observed higher positive likelihood ratio in the superficial SR region and deep MIR.Furthermore,there was a negative correlation between conjunctival vascular density and both deep and superficial retinal TMI(P<0.001).CONCLUSION:Patients with CTD-ILD exhibits a significantly higher conjunctival vascular density compared to the HCs group.Conversely,their fundus retinal microvascular density is significantly lower.Furthermore,CTD-ILD patients display notably lower superficial and deep retinal vascular density in comparison to the HCs group.The inverse correlation between conjunctival vascular density and both superficial and deep retinal TMI suggests that detecting subtle changes in ocular microcirculation could potentially serve as an early diagnostic indicator for connective tissue diseases,thereby enhancing disease management.
文摘Connective tissue diseases (CTDs) are Autoimmune diseases (AIDs) characterized by the appearance of autoantibodies, which are diagnostic markers. Investigations of these autoantibodies play a major role in the management of several autoimmune diseases. The objective of this study was to describe the profile of anti-ENA antibodies according to the clinical symptoms of mixed CTDs in Conakry teaching Hospital. We performed a cross-sectional study during six months. A total of 20 patients was recruited and we measured antibodies using the ELISA technique. The mean age of our patients was 36.5 years, with a predominance of females. Cutaneous and rheumatological signs were the main clinical manifestations. SLP was the most frequent CTDs;the threshold of ENA antibodies positivity was higher in scleroderma with and SLP. Anti-ENA identification reveals the frequency of anti-SSA (83.33%), anti-U1RNP (66.66%) and anti-histone (50%) antibodies. Antinuclear antibodies (ANA) react with various components of the cell nucleus. Their detection is of major interest in the diagnosis of CTDs. Our results highlight the importance of determining the specificity of these antibodies to guide differential diagnosis.
文摘Purpose: Studies on imaging findings in mixed connective tissue disease (MCTD) are limited. This study assessed the relationship between CT-derived parameters (pulmonary artery diameter [PAD] and lung parenchymal abnormalities [LPA]) and estimated pulmonary artery pressure (PAP) in patients with MCTD. Materials and Methods: This single-center retrospective study enrolled consecutive patients with MCTD who underwent CT and echocardiography within 6 months between December 2004 and November 2021. Chest CT was used to measure PAD (mm) and evaluate LPA (%). LPA was quantitatively assessed for reticular, ground-glass opacities, consolidation, or honeycombing. Peak tricuspid regurgitation velocity (TRV) on echocardiography was considered to reflect PAP. Correlation and partial correlation analyses were performed to assess the relationship between CT-derived parameters and peak TRV. Results: Overall, 116 patients (mean age 50.0 ± 17.0 years [SD]) with a median disease duration of 3.0 years had a median peak TRV of 2.28 m/sec and median PAD of 27.0 mm. Pulmonary hypertension was found in 18 (15.5%) patients. LPA was observed in 52 patients, with a median of 0.0% and a mean of 4.5% ± 8.9 [SD]. Peak TRV was correlated with PAD (r = 0.58, p Conclusion: A moderate positive correlation was observed in patients with MCTD between PAD and estimated PAP, irrespective of the presence of LPA, whereas LPA was not correlated with estimated PAP.
文摘This study investigated the effect of explicit instruction about DCs in argumentative writings by 15 Chinese learners of English. This study involved in a 4-week experiment. Pre-and post-writing tests were quantitatively analyzed to examine whether the explicit instruction about DCs had a significant effect on the students'argumentative writing. The findings revealed that the ex-plicit instruction of the target DCs facilitated the improvement of the participants in their argumentative writing .
基金Supported by Grants from the Research Special Fund for Public Welfare Industry of Health,No.201202004the National Major Scientific and Technological Special Project for"Significant New Drugs Development",No.2012ZX09303006-002the National High Technology Research and Development Program of China,No.2011AA020111
文摘AIM:To establish the frequency and clinical features of connective tissue diseases(CTDs)in a cohort of Chinese patients with primary biliary cirrhosis(PBC).METHODS:Three-hundred and twenty-two Chinese PBC patients were screened for the presence of CTD,and the systemic involvement was assessed.The differences in clinical features and laboratory findings between PBC patients with and without CTD were documented.The diversity of incidence of CTDs in PBC of different countries and areas was discussed.For the comparison of normally distributed data,Student’s t test was used,while non-parametric test(Wilcoxon test)for the non-normally distributed data and 2×2χ2or Fisher’s exact tests for the ratio.RESULTS:One-hundred and fifty(46.6%)PBC patients had one or more CTDs.The most common CTD was Sj gren’s syndrome(SS,121 cases,36.2%).There were nine cases of systemic sclerosis(SSc,2.8%),12of systemic lupus erythematosus(SLE,3.7%),nine of rheumatoid arthritis(RA,2.8%),and 10 of polymyositis(PM,3.1%)in this cohort.Compared to patients with PBC only,the PBC+SS patients were more likely to have fever and elevated erythrocyte sedimentation rate(ESR),higher serum immunoglobulin G(IgG)levels and more frequent rheumatoid factor(RF)and interstitial lung disease(ILD)incidences;PBC+SSc patients had higher frequency of ILD;PBC+SLE patients had lower white blood cell(WBC)count,hemoglobin(Hb),platelet count,γ-glutamyl transpeptidase and immunoglobulin M levels,but higher frequency of renal involvement;PBC+RA patients had lower Hb,higher serum IgG,alkaline phosphatase,faster ESR and a higher ratio of RF positivity;PBC+PM patients had higher WBC count and a tendency towards myocardial involvement.CONCLUSION:Besides the common liver manifestation of PBC,systemic involvement and overlaps with other CTDs are not infrequent in Chinese patients.When overlapping with other CTDs,PBC patients manifested some special clinical and laboratory features which may have effect on the prognosis.
文摘AIM: To examine the expression of connective tissue growth factor (CTGF), also known as CCN2, in gastric carcinoma (GC), and the correlation between the expression of CTGF, clinicopathologic features and clinical outcomes of patients with GC. METHODS: One hundred and twenty-two GC patients were included in the present study. All patients were followed up for at least 5 years. Proteins of CTGF were detected using the Powervision two-step immunostaining method. RESULTS: Of the specimens from 122 GC patients analyzed for CTGF expression, 58 (58/122, 47.5%) had a high CTGF expression in cytoplasm of gastric carcinoma cells and 64 (64/122, 52.5%) had a low CTGF expression. Patients with a high CTGF expression showed a higher incidence of lymph node metastasis than those with a low CTGF expression (P = 0.032). Patients with a high CTGF expression had significantly lower 5-year survival rate than those with a low CTGF expression (27.6% vs 46.9%, P = 0.0178), especially those staging Ⅰ+Ⅱ+Ⅲ (35.7% vs 65.2%, P = 0.0027). CONCLUSION: GC patients with an elevated CTGF expression have more lymph node metastases and a shorter survival time. CTGF seems to be an independent prognostic factor for the successful differentiation of high-risk GC patients staging Ⅰ+Ⅱ+Ⅲ. Over-expression of CTGF in human GC cells results in an increased aggressive ability.
基金supported by the National Basic Research Program (973) of China(No.2005CB623900)
文摘Objective:Large segmental bone defect repair remains a clinical and scientific challenge with increasing interest focusing on combining gene transfection with tissue engineering techniques.The aim of this study is to investigate the effect of connective tissue growth factor(CTGF) on the proliferation and osteogenic differentiation of the bone marrow mesenchymal stem cells(MSCs).Methods:A CTGF-expressing plasmid(pCTGF) was constructed and transfected into MSCs.Then expressions of bone morphogenesis-related genes,proliferation rate,alkaline phosphatase activity,and mineralization were examined to evaluate the osteogenic potential of the CTGF gene-modified MSCs.Results:Overexpression of CTGF was confirmed in pCTGF-MSCs.pCTGF transfection significantly enhanced the proliferation rates of pCTGF-MSCs(P<0.05).CTGF induced a 7.5-fold increase in cell migration over control(P<0.05).pCTGF transfection enhanced the expression of bone matrix proteins,such as bone sialo-protein,osteocalcin,and collagen type I in MSCs.The levels of alkaline phosphatase(ALP) activities of pCTGF-MSCs at the 1st and 2nd weeks were 4.0-and 3.0-fold higher than those of MSCs cultured in OS-medium,significantly higher than those of mock-MSCs and normal control MSCs(P<0.05).Overexpression of CTGF in MSCs enhanced the capability to form mineralized nodules.Conclusion:Overexpression of CTGF could improve the osteogenic differentiation ability of MSCs,and the CTGF gene-modified MSCs are potential as novel cell resources of bone tissue engineering.
基金Supported by National Natural Scientific Foundation,No. 30872236,81070370,to Gao RPNIH 5R01AA016003,to Brigstock DR
文摘AIM:To determine the expression characteristics of connective tissue growth factor(CTGF/CCN2) in human hepatocellular carcinoma(HCC) in histology and to elucidate the roles of CCN2 on hepatoma cell cycle progression and metastasis in vitro.METHODS:Liver samples from 36 patients(who underwent hepatic resection for the first HCC between 2006 and 2011) and 6 normal individuals were examined for transforming growth factor β1(TGF-β1) or CCN2 mRNA by in situ hybridization.Computer image analysis was performed to measure integrated optimal density of CCN2 mRNA-positive cells in carcinoma foci and the surrounding stroma.Fibroblast-specific protein-1(FSP-1) and E-cadherin were examined to evaluate the process of epithelial to mesenchymal transition,α-smooth muscle actin and FSP-1 were detected to identify hepatic stellate cells,and CD34 was measured to evaluate the extent of vascularization in liver tissues by immunohistochemical staining.CCN2 was assessed for its stimulation of HepG2 cell migration and invasion using commercial kits while flow cytometry was used to determine CCN2 effects on HepG2 cell-cycle.RESULTS:In situ hybridization analysis showed that TGF-β1 mRNA was mainly detected in connective tissues and vasculature around carcinoma foci.In comparison to normal controls,CCN2 mRNA was enhanced 1.9-fold in carcinoma foci(12.36 ± 6.08 vs 6.42 ± 2.35) or 9.4-fold in the surrounding stroma(60.27 ± 28.71 vs 6.42 ± 2.35),with concomitant expression of CCN2 and TGF-β1 mRNA in those areas.Epithelial-mesenchymal transition phenotype related with CCN2 was detected in 12/36(33.3%) of HCC liver samples at the edges between carcinoma foci and vasculature.Incubation of HepG2 cells with CCN2(100 ng/mL) resulted in more of the cells transitioning into S phase(23.85 ± 2.35 vs 10.94 ± 0.23),and induced a significant migratory(4.0-fold) and invasive(5.7-fold) effect.TGF-β1-induced cell invasion was abrogated by a neutralizing CCN2 antibody showing that CCN2 is a downstream mediator of TGF-β1-induced hepatoma cell invasion.CONCLUSION:These data support a role for CCN2 in the growth and metastasis of HCC and highlight CCN2 as a potential novel therapeutic target.
基金Supported by National Natural Scientific Foundation No.30872236 to Run-Ping Gao and NIH 5R01AA016003 to David R Brigstock
文摘AIM： To determine the effect of hammerhead ribozyme targeting connective tissue growth factor （CCN2） on human hepatic stellate cell （HSC） function.METHODS： CCN2 hammerhead ribozyme cDNA plus two self-cleaving sequences were inserted into pTriEx2 to produce pTriCCN2-Rz. Each vector was individually transfected into cultured LX-2 human HSCs, which were then stimulated by addition of transforming growth factor （TGF）-β1 to the culture medium. Semiquantitative RT-PCR was used to determine mRNA levels for CCN2 or collagen I, while protein levels of each molecule in cell /ysates and conditioned medium were measured by ELISA. Cell-cycle progression of the transfected cells was assessed by flow cytometry.RESULTS： In pTriEx2-transfected LX-2 cells, TGF-β1 treatment caused an increase in the mRNA level for CCN2 or collagen I, and an increase in produced and secreted CCN2 or extracellular collagen I protein levels, pTriCCN2-Rz-transfected LX-2 cells showed decreased basal CCN2 or collagen mRNA levels, as well as produced and secreted CCN2 or collagen I protein. Furthermore, the TGF-β1-induced increase in mRNA or protein for CCN2 or collagen I was inhibited partially in pTriCCN2-Rz-transfected LX-2 cells. Inhibition of CCN2 using hammerhead ribozyme cDNA resulted in fewer of the cells transitioning into S phase.CONCLUSION： Endogenous CCN2 is a mediator of basal or TGF-β1-induced collagen I production in human HSCs and regulates entry of the cells into S phase.
基金Supported by Chinese National Key Technology R&D Program (2006BAI01A07, 2008BAI59B02)Clinical Grant of Chinese Medicine Association (08010270105)
文摘Objective To investigate the prevalence of anti-endothelial cell antibodies (AECAs) in the sera of connective tissue diseases (CTD) patients with pulmonary arterial hypertension (PAH) and its correlation with clinical manifestations. Methods AECAs in sera of 39 CTD patients with PAH,22 CTD patients without PAH,and 10 healthy donors as controls were detected with Western blotting. The prevalence of different AECAs in different groups was compared and its correlation with clinical manifestations was also investigated. Results The prevalence of AECAs was 82.1% in CTD patients with PAH,72.7% in CTD patients without PAH,and 20.0% in healthy donors. Anti-22 kD AECA was only detected in CTD patients with PAH (15.4%). Anti-75 kD AECA was more frequently detected in CTD patients with PAH than in those without PAH (51.3% vs. 22.7%,P<0.05). In CTD patients with PAH,anti-75 kD AECA was more frequently detected in those with Raynaud’s phenomenon or with positive anti-RNP antibody. Conclusion AECAs could be frequently detected in CTD patients with or without PAH,while anti-22 kD and anti-75 kD AECA might be specific in CTD patients with PAH.
基金supported by Natural Science Foundation of Hubei Province from the Science and Technology Department of Hubei Province,China(No.2013CFB091)。
文摘Hyperthyroid heart disease(HHD)is one of the most severe complications of overt hyperthyroidism and increases the risk of mortality in affected patients.Early identification of patients at a higher risk of developing HHD can improve clinical outcomes through active surveillance and management.Connective tissue growth factor(CTGF),a secreted extracellular protein,plays a significant role in cardiac remodeling and dysfunction.We aimed to investigate the association between plasma CTGF level and the risk of HHD in this study.A total of 142 overt hyperthyroid patients without HHD and 99 patients with HHD were included.The plasma CTGF levels were measured using ELISA kits.Routine clinical medical data and echocardiography parameters were recorded for analysis.The plasma CTGF level was significantly higher in patients with HHD than in those without HHD(P=0.002).The plasma CTGF level was positively correlated with free triiodothyronin,tryrotropin receptor antibody,troponin I and lactate dehydrogenase levels and the left atrium diameters,right atrium diameters,and right ventricular end-diastolic diameters(all P<0.05).Logistic regression analysis showed that quartiles 3 and 4 of plasma CTGF levels were significantly associated with the increased risk of HHD(crude OR:2.529;95%CI:1.188-5.387).However,after adjustment for the potentially confounding variables,quartile 4 alone was significantly associated with the higher risk of HHD relative to quartile I.Hyperthyroid patients with HHD display higher plasma CTGF levels.Furthermore,CTGF is an independent risk factor for HHD.Therefore,the plasma CTGF level may be a potential biomarker for the risk of HHD.
基金Supported by the National Natural Science Foundation(No.81460089 No.81570872)Tianjin Applied Basic and Frontier Technology Research Plan Project(No.15JCYBJC24900)
文摘Diabetic retinopathy（DR） is one of the most important types of diabetic microangiopathy, which is a specific change of fundus lesions and is one of the most serious complications of diabetes. When DR develops to proliferative DR, the main factors of decreasing vision, and even blindness, include retinal detachment and vitreous hemorrhage caused by contraction of blood vessels by fiber membrane. Recent studies reported that the formation of fiber vascular membrane is closely related to retinal fibrosis. The connective tissue growth factor（CTGF） is a cytokine that is closely related to DR fibrosis. However, its mechanism is poorly understood. This paper summarizes the recent studies about CTGF on DR fibrosis for a comprehensive understanding of the role and mechanism of CTGF in PDR.
基金Supported by Beijing Traditional Chinese Medicine Science and Technology Project:Study on the Mechanism of High Dose Huanglian (Rhizoma Coptidis) in Treating Diabetic Nephropathy (No.QN2014-08)。
文摘OBJECTIVE: To investigate the efficacy of the full composition granules of Huanglian(Rhizoma Coptidis)(FGC) on the serum monocyte chemotactic protein-1(MCP-1) and connective tissue growth factor(CTGF) levels and kidney nuclear factor-κB(NF-κB) expression in rats with high-fat diet-induced diabetes.METHODS: Diabetes was induced in rats by feeding a high-fat chow combined with intravenous streptozotocin injection. Forty diabetic SpragueDawley rats were randomly assigned to a normal group(NG), model group(MG), irbesartan group(IG), and low-, middle-, and high-dosage FGC groups(LFGC, MFGC, HFGC), with eight rats per group. The IG rats received 31.25 mg·kg^(-1)·d^(-1) irbesartan tablets, whereas those in the LFGC, MFGC,and HFGC were administered 52, 312.5, and 625 mg·kg^(-1)·d^(-1) FGC, respectively. After 12 weeks,bodyweight(BW), left kidney weight(KW), hemoglobin A1c(HbA1c), serum creatinine(Scre), blood urea nitrogen(BUN), and serum MCP-1 and CTGF levels were determined, pathological changes of the kidney were recorded, and kidney NF-κB p65(A) expression was measured.RESULTS: The 24-h urine albumin and levels of HbA1c, Scre, BUN, and serum MCP-1 and CTGF were significantly increased in in the MG compared with the NG, as was the kidney NF-κB(p65) expression(P < 0.05). Furthermore, clear pathological changes in kidney fibrosis were observed in the MG rats. Following irbesartan and FGC administration,the 24-h urine albumin and the levels of HbA1c,Scre, and serum MCP-1 and CTGF were significantly decreased in FCG groups compared with those in the MG, which is in agreement with the change in the kidney NF-κB(p65) expression, whereas the similarly significant decrease only exist in 24-h urine albumin and the levels of serum CTGF after irbesartan administration. Hematoxylin-eosin(HE)staining results indicated that the fibrosis observed in the MG samples was alleviated through FGC treatment.CONCLUSION: FGC may alleviate potential kidney injury by decreasing the serum MCP-1 and CTGF levels and inhibiting NF-k B expression in diabetic nephropathy in rats with high-fat diet-induced diabetes.
基金Supported by Grant-in-Aid for Scientific Research(C),The Ministry of Education,Culuture,Sports,Science and Technology and The Institute for Environment and Gender-specific Medicine,Juntendo University Graduate School of Medicine
文摘The pathogenesis of rheumatoid arthritis(RA) remains to be completely elucidated so far; however, it is known that proinflammatory cytokines play a pivotal role in the induction of RA. Tumor necrosis factor(TNF-α), in particular, is considered to play a central role in bone destruction by mediating the abnormal activation of osteoclasts or the production of proteolytic enzymes through direct or indirect mechanisms. The use of TNF-α blocking agents has a significant impact on RA therapy. Anti-TNF-α blocking agents such as infliximab are very effective for treatment of RA, especially for the prevention of articular destruction. We have previously shown that several proteins exhibited extensive changes in their expression after amelioration of RA with infliximab treatment. Among the proteins, connective tissue growth factor(CTGF) has a significantrole for the development of RA. Herein, we review the function of CTGF in the pathogenesis of RA and discuss the possibility of a novel treatment for RA. We propose that CTGF is a potentially novel effector molecule in the pathogenesis of RA. Blocking the CTGF pathways by biological agents may have great beneficial effect in patients with RA.
文摘AIM:To investigate the mechanisms involved in a possible modulator role of interleukin(IL) -6 signalling on CYR61-CTGF-NOV(CCN) 2/connective tissue growth factor(CTGF) expression in hepatocytes(PC) and to look for a relation between serum concentrations of these two parameters in patients with acute inflammation. METHODS:Expression of CCN2/CTGF,p-STAT3,p-Smad 3/1 and p-Smad2 was examined in primary freshly isolated rat or cryo-preserved human PC exposed to various stimuli by Western blotting,electrophoretic mobility shift assay(EMSA) ,reporter-gene-assays and reversetranscriptase polymerase chain reaction. RESULTS:IL-6 strongly down-regulated CCN2/CTGF protein and mRNA expression in PC,enhanceable by extracellular presence of the soluble IL-6 receptor gp80,and supported by an inverse relation between IL-6 and CCN2/CTGF concentrations in patients'sera.The inhi-bition of TGFβ1 driven CCN2/CTGF expression by IL-6 did not involve a modulation of Smad2(and Smad1/3) signalling.However,the STAT3 SH2 domain binding peptide,a selective inhibitor of STAT3 DNA binding activity,counteracted the inhibitory effect of IL-6 on CCN2/CTGF expression much more pronounced than pyrrolidine-dithiocarbamate,an inhibitor primarily of STAT3 phosphorylation.An EMSA confirmed STAT3 binding to the proposed proximal STAT binding site in the CCN2/CTGF promoter. CONCLUSION:CCN2/CTGF is identified as a hepatocellular negative acute phase protein which is downregulated by IL-6 via the STAT3 pathway through interaction on the DNA binding level.
基金Supported by the Project of Natural Foundation of Shanghai Science and Technology Committee (No. 10Zr28600)
文摘OBJECTIVE:To determine the effect of Houttuynia cordata Aetherolea on connective tissue growth factor and adiponectin in a rat model of diabetes mellitus(DM).METHODS:DM was induced in rats using streptozotocin(STZ) and high glucose-lipid animal feed.Animals were then treated with Houttuynia cordata Aetherolea for 8 weeks.Changes in connective tissue growth factor and adiponectin levels in rats were observed.RESULTS:Connective tissue growth factor and adiponectin levels in rats with DM improved after Houttuynia cordata Aetherolea treatment.CONCLUSION:Houttuynia cordata Aetherolea had a positive effect on rats with DM by reducing levels of connective tissue growth factor and increasing adiponectin levels.
