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1.
Rev. bras. cir. cardiovasc ; 37(2): 200-206, Apr. 2022. tab, graf
Article in English | LILACS-Express | LILACS | ID: biblio-1376527

ABSTRACT

Abstract Introduction: Drug-eluting stents (DES) coated with rapamycin or paclitaxel as antiproliferative substances significantly reduced the incidence of clinical restenosis and had fewer side effects after percutaneous coronary intervention. However, DES coated with rapamycin or paclitaxel still cause restenosis due to abnormal tissue growth which remained a therapeutic problem, particularly in certain subgroups, possibly due to drug concentrations. This study examined the impact of different concentrations of rapamycin and paclitaxel on cytokine, cell viability and proliferation in human aortic smooth muscle cells (HASMC)-derived foam cells. Methods: The foam cell model was established in vitro by incubating HASMC with 20 µg/mL oxidized low-density lipoprotein (ox-LDL) for 48 hours. Subsequently, foam cells were treated with different concentrations (0.01 µg/mL, 0.1 µg/mL, 0.5 µg/mL, 1 µg/mL, 5 µg/mL and 10 µg/mL) of rapamycin or paclitaxel for 48 hours, to measure cytokine, cell viability and proliferation by ELISA and MTT, respectively. Finally, viability and proliferation were measured by MTT after the foam cells were treated with 1 µg/mL rapamycin or paclitaxel combined with cytokine antibody for 48 hours. Results: After incubation of HASMC with ox-LDL, the ratios of cholesterol ester and total cholesterol increased significantly (55.29%) (P<0.01). Lipid staining with Oil Red O showed many lipid vacuoles and red dye particles in the cells. Meanwhile, cell viability and proliferation significantly increased compared with the control. This indicated that HASMC had been transformed into foam cells (P<0.01) while rapamycin or paclitaxel concentrations ≥0.1 µg/mL can significantly decrease the foam cell proliferation (P<0.05 or P<0.01), and 1 µg/mL of rapamycin or paclitaxel appeared the most effective concentration. As for cytokines, rapamycin or paclitaxel concentrations ≥1 ug/mL could significantly increase the level of inflammatory cytokines IL-6 (P<0.05 or P<0.01), which was enhanced with the increase of drug concentration. However, rapamycin or paclitaxel concentrations ≥1 µg/mL could significantly reduce the levels of anti-inflammatory cytokines IL-35 and transforming growth factor beta (TGF-β) (P<0.05 or P<0.01), which decreased with the increase of drug concentration. In addition, rapamycin or paclitaxel combined with anti-IL-1β, anti-IL-6, anti- TNF-α or anti-IL-35 had no significant effect on foam cell proliferation compared to the drug alone. However, rapamycin or paclitaxel combined with anti-IL-10 or anti-TGF-β can significantly enhance foam cell proliferation (P<0.01). In addition, there was no difference in the effects of the same concentrations of rapamycin and paclitaxel on foam cells. Conclusion: Although rapamycin or paclitaxel can reduce foam cell proliferation, too high or too low concentrations could decrease effectiveness. In particular, a high dose can induce foam cells to increase inflammatory cytokines secretion, reduce anti-inflammatory cytokines secretion, and thus affect the inhibiting proliferation. For rapamycin- and paclitaxel-eluting stents, this conclusion may explain the clinical observation of in-stent restenosis after percutaneous coronary intervention. DES coated with an appropriate concentration of rapamycin or paclitaxel may, at least to some extent, contribute significantly to reducing incidence of late in-stent restenosis.

2.
International Eye Science ; (12): 71-75, 2022.
Article in Chinese | WPRIM | ID: wpr-906733

ABSTRACT

@#Proliferative vitreoretinopathy(PVR)is a common complication of perforation injury and surgery for rhegmatogenous retinal detachment. The pathogenesis of this disease is still unclear. However, studies have shown that retina pigment epithelium(RPE)cells have the ability to secrete cytokines, and many growth factors are overexpressed in vitreous or subretinal fluid in PVR patients. These growth factors and their receptors play an important role in the occurrence and development of PVR. When the blood-retinal barrier is broken, the physiological balance of growth factors disappears, and RPE cells are stimulated by growth factors to undergo epithelial-mesenchymal transformation(EMT), migration and proliferation, this leads to the formation of the preretinal membrane, which pulls on the retina and causes retinal detachment. In recent years, scholars have done a lot of researches on the signaling pathways, EMT process and cell proliferation involved in the formation of PVR with growth factors. This article will summarize the function of growth factors involved in the formation of PVR and the therapeutic effects of antagonistic growth factors in the development of PVR.

3.
International Eye Science ; (12): 67-70, 2022.
Article in Chinese | WPRIM | ID: wpr-906732

ABSTRACT

@#Proliferative vitreoretinopathy(PVR)is a eye disease characterized by the formation of epiretinal membranes(ERM)composed of extracellular matrix(ECM)and various types of cells in the vitreous and/or the surface of the retina through the wound repair and fibrotic process. ERM shrinks to form retinal folds and stretches the retina to cause retinal detachment(RD). Epithelial-mesenchymal transition(EMT)of retinal pigment epithelial(RPE)cells and accumulation of ECM are considered to be the main pathological mechanisms for the formation of ERM. RPE cells undergo a process named EMT induced by transforming growth factor-β(TGF-β), by which differentiated epithelial cells go through epithelial phenotypic loss, the weakness of cell-cell contact and mesenchymal phenotype expression. Fibroblast-like cells differentiated from mesenchymal cells produce ECM and other components, which forms ERM together with glial cells and fibroblasts, <i>etc</i>. Recent studies indicated a lot of cytokines/growth factors, transcriptional factors, and microRNA(miRNA)regulate the development of EMT in RPE cells, in which miRNA is a novel and powerful regulatory gene and plays a critical regulatory role in the EMT process of PVR. This review focuses on the current understandings of the mechanism and the interventional treatments of miRNA in PVR.

4.
Article in Chinese | WPRIM | ID: wpr-934584

ABSTRACT

Objective: To observe the effect of moxibustion on the colonic mucosal barrier of rats with ulcerative colitis (UC) induced by dextran sulfate sodium (DSS). Methods: Forty male Sprague-Dawley rats were randomly divided into a normal group and a modeling group, with 20 rats in each group. Rats in the modeling group were subjected to preparing experimental UC models by drinking 4% DSS for seven consecutive days. Two modeled rats and two normal rats were randomly selected for model identification. After the success of UC model was confirmed, the remaining 18 modeled rats were randomly divided into three groups, a model group, a model + herbal cake-partitioned moxibustion group, and a model + mild moxibustion group, with six rats in each group; the remaining normal rats were randomly divided into three groups, a normal group, a normal + herbal cake-partitioned moxibustion group, and a normal + mild moxibustion group, with six rats in each group. After 7 d of intervention with the herbal cake-partitioned moxibustion or the mild moxibustion, hematoxylin-eosin (HE) staining technique was used to observe the pathological changes of colon tissue under a light microscope; Western blotting and/or immunohistochemical techniques were used to detect the protein expression levels of Occludin, Claudin, junction adhesion molecular 1 (JAM1), mucin 2 (MUC2), and transforming growth factor beta1 (TGF-β1) in rat colon tissue. Results: Compared with the normal group, the colon tissue was severely damaged, the pathological score was significantly increased, and the protein expression levels of Occludin, Claudin, JAM1, MUC2, and TGF-β1 were significantly decreased in the model group (P<0.01); while there were no significant differences in the colonic histopathological score, protein expression levels of Occludin, Claudin, JAM1, MUC2, and TGF-β1 in the normal + herbal cake-partitioned moxibustion group and the normal + mild moxibustion group (P>0.05). Compared with the model group, the model + herbal cake-partitioned moxibustion group and the model + mild moxibustion group showed repaired colon tissue, ulcer healing, significantly reduced pathological score, and significantly increased protein expression levels of JAM1, MUC2, and TGF-β1 (P<0.05); the Occludin protein expression level in the colon tissue of the model + mild moxibustion group was increased (P<0.01). Conclusion: Neither herbal cake-partitioned moxibustion nor mild moxibustion influences the colonic histopathology and intestinal mucosal barrier-related protein expression in the normal rats; both herbal cake-partitioned moxibustion and mild moxibustion can up-regulate the protein expression levels of JAM1, MUC2, and TGF-β1 in the colon tissue of UC rats. Mild moxibustion can up-regulate Occludin protein expression. This may be a mechanism of moxibustion in reducing colonic mucosa inflammation in UC.

5.
Chinese Journal of Geriatrics ; (12): 580-585, 2022.
Article in Chinese | WPRIM | ID: wpr-933126

ABSTRACT

Objective:To investigate the role and mechanisms of fibulin-1 in senescence-related calcification of rat vascular smooth muscle cells induced by high-concentrationphosphate treatment.Methods:From September 2020 to September 2021, rat primary vascular smooth muscle cells were extracted from the thoracic aorta and abdominal aorta of 10 male SD rats aged 6 to 8 weeks.Phosphate(2.5 mmol/L Pi)was used to stimulate the calcification of vascular smooth muscle cells(VSMCs)in a model of stress-induced senescence-related calcification.Cellular senescence was assessed by SA-β-gal staining.Cellular calcification was determined by alizarin red staining and quantification of calcium deposition.Phenotypic transformation indexes and the expression of fibulin-1 during the process of calcification were detected by Western blot.The expression of fibulin-1 in primary rat vascular smooth muscle cells was knocked down by siRNA, the expression of pSmad3 was detected by immunofluorescence, and the effects of fibulin-1 on phenotypic transformation indexes of smooth muscle cells were detected by Western blot.The cells were cultured with recombinant fibulin-1 while transforming growth factor beta(TGF-β)inhibitor A83-01 and pSmad3 inhibitor SIS3 were also added.The senescence and calcification indexes of smooth muscle cells were detected by Western blot.Results:In the stress-induced aging model with phosphate stimulation of calcification in rat VSMCs, the expression of fibulin-1 was up-regulated( t=11.20, P<0.01), the expressions of MHC and SM22α was down-regulated( t=7.97, P<0.01; t=10.27, P<0.01), and the expression of osteoblastic phenotype markers OPN and Bmp2 and senescence marker P53 was up-regulated( t=4.79, P<0.01; t=9.56, P<0.01; t=14.07, P<0.01). Knockdown of fibulin-1 attenuated the degree of senescence and calcium deposition in VSMCs( t=12.90, P<0.05)and decreased the expression of OPN, Bmp2 and P53( t=5.92, P<0.05; t=10.15, P<0.01; t=8.28, P<0.01), at the same time, and TGF-β and pSmad3 expression was inhibited( t=12.90, P<0.01; t=7.46, P<0.01). After the addition of TGF-β/ smad3 pathway inhibitors, the stimulatory effect of recombinant fibulin-1 on phenotypic transformation and senescence protein expression inVSMCs was significantly reduced( t=4.52, P<0.01; t=9.82, P<0.01; t=3.85, P<0.05). Conclusions:Fibulin-1 can promote aging-related calcification of vascular smooth muscle cells through the TGF-β/smad3 signaling pathway.

6.
Clinical Medicine of China ; (12): 268-273, 2022.
Article in Chinese | WPRIM | ID: wpr-932179

ABSTRACT

Objective:To investigate the correlation between serum concentration of vasohibin-1 (VASH-1) and urinary albumin creatinine ratio (UACR) in patients with type 2 diabetes mellitus (T2DM) and diabetic nephropathy.Methods:The clinical data of 196 patients with T2DM from February 2017 to December 2020 were analyzed retrospectively. According to whether diabetic nephropathy (DN) was combined, 33 patients without DN of T2DM were divided into the control group,and 163 patients with DN of T2DM were divided into the case group, and the case group was divided into four groups:normal albuminuria group (groupⅠ, UACR <30 mg/g, 21 cases),microalbuminuria group (groupⅡ, UACR ≥30-≤300 mg/g, 50 cases), clinical albuminuria group (group Ⅲ, UACR>300 mg/g, 43 cases), and clinical albuminuria hypertensive group (groupⅣ, UACR >300 mg/g with hypertension, 49 cases). Serum levels of VASH-1,C-reactive protein(CRP), erythrocyte sedimentation rate (ESR) and transforming growth factor β1 (TGF-β1) with other biochemical indicators were measured. T-test was used for comparison between measurement data groups in accordance with normal distribution, one-way ANOVA was used for comparison between multiple groups, q-test was used for pairwise comparison, and χ2 test was used for comparison between counting data groups. The influencing factors were analyzed by multivariate Logistic regression.Pearson correlation analysis was used to analyze the correlation between vash-1 and UACR. Results:UACR((1 175.9±120.4) mg/g), CRP((9.80±2.01) mg/L), ESR((20.61±2.20) mm/h),TGF-β1((16.75±2.05) μg/L), VASH-1((645.3±183.5) ng/L) in case group were higher than that in the control group((11.5±2.0) mg/g, (4.77±1.34) mg/L, (8.33±1.56) mm/h, (10.63±1.97) μg/L, (416.3±162.1) ng/L), and there were significant differences between the two groups ( t=123.39,13.76,30.54,15.75,6.66; all P<0.001). Multivariate logistic regression analysis showed that VASH-1 ( OR=1.881,95% CI 1.146-3.089), UACR( OR=1.511,95% CI 1.064-2.146), TGF-β1( OR=1.846,95% CI 1.135-3.001)were all risk factors for DN of T2DM ( P values were 0.009, 0.022 and 0.012). Serum VASH-1 ((693.5±201.4), (709.8±214.7) ng/L] in group Ⅲ and group Ⅳ were higher than those in group Ⅰ and group Ⅱ ((585.3±162.1), (632.9±165.5) ng/L). There was significant difference between the two groups ( F=129.46, P<0.001). The CRP ((7.08±1.36), (8.99±3.72), (10.58±3.48), (11.64±3.50) mg/L), ESR ((17.36±1.76), (19.05±4.12), (21.45±5.74), (22.69±9.13) mm/h) and TGF- β1 ((14.75±1.97), (16.50±1.90), (17.06±1.23), (18.39±1.46) μg/L) of groupⅠ, groupⅡ, groupⅢ and groupⅣ increased gradually, and there were significant differences between the four groups ( F values were 73.48, 156.61, 25.83; all P<0.001). Pearson correlation analysis showed that there was a significant positive correlation between VASH-1 and UACR ( r=0.532, P=0.008). Conclusion:The concentration of VASH-1 in serum of patients with T2DM complicated with DN increased with the increase of UACR. VASH-1 may become a new marker for predicting early DN of T2DM.

7.
Article in Chinese | WPRIM | ID: wpr-931702

ABSTRACT

Objective:To investigate the effects of tamoxifen on high glucose-induced epithelial-to-mesenchymal transition of rat peritoneal mesothelial cells and the underlying mechanism.Methods:The peritoneal mesothelial cells of normal male SD rats were selected between January 2015 and June 2016 and then cultured and divided into blank control, high-glucose stimulation and drug intervention groups. High-glucose stimulation group: primary cultured rat peritoneal mesothelial cells (RPMCs) were treated with 60 mmol/L high-concentration glucose to induce epithelial-to-mesenchymal transition. Drug intervention group: (1) RPMCs were treated with 60 mmol/L high-concentration glucose and different concentrations (0.5 μmol/L, 2 μmol/L) of tamoxifen. After 72 hours of stimulation, protein was extracted. (2) RPMCs were treated with 60 mmol/L high-concentration glucose and 2 μmol/L tamoxifen with or without 2 μmol/L ER-α antagonist for 1 hour to extract protein and for 6 hours to extract RNA. (3) RPMCs were treated with high-concentration glucose and 2 μmol/L tamoxifen with or without 1 μmol/L 1 μM proteasome inhibitor for 1 hour to extract protein. Western blot analysis was performed to analyze change in E-cadherin, α-SMA, Smad2, p-Smad2, Smad3, p-Smad3 and Smad4 protein. Real-time fluorescence quantitative PCR was performed to detect the change in mRNA expression of Smad2, Smad3, connective tissue growth factor and plasminogen activator inhibitor 1.Results:Tamoxifen attenuated epithelial-to-mesenchymal transition on RPMCs induced by high-level glucose, showing increased expression of epithelial cell marker E-cadherin and decreased expression of α-SMA in a concentration-dependent manner ( tE-cadherin = 2.31, tα-SMA =-2.53, both P < 0.05).TGF-β1/R-Smad signal pathway was activated by high-concentration glucose. Phosphorylation of Smad2/3 and mRNA expression of CTGF and PAI-1 were increased. Tamoxifen remarkably reduced protein and mRNA level of above mentioned protein and related target genes ( tp-Smad2 = -3.38, tCTGF = -3.81, P < 0.05), which could be blocked by ER-α antagonist. Finally, proteasome inhibitor could weaken the inhibitory effects of tamoxifen on p-Smad2/3 and increase p-Smad2/3 protein level ( tp-Smad2 = 3.94, P < 0.05). Conclusion:Tamoxifen activates ER-α on RPMCs, weakens the activation of TGF-β1/R-Smad signal pathway through decreasing p-Smad2 protein level, and effectively inhibits the progression of high-concentration glucose-induced epithelial-to-mesenchymal transition possibly through degrading p-Smad2 protein through proteasome. The role of tamoxifen in epithelial-to-mesenchymal transition may provide a possible guide for research, prevention and treatment of peritoneal fibrosis.

8.
Article in Chinese | WPRIM | ID: wpr-931623

ABSTRACT

Objective:To investigate the effects of removable periodontal splint combined with minocycline on periodontal indexes and tooth aesthetics in patients with severe periodontal disease.Methods:A total of 102 patients with severe periodontal disease treated in the School and Hospital of Stomatology, China Medical University from November 2018 to April 2020 were included in this study. They were randomly allocated into study and control groups ( n = 51/group). The control group was subject to repair with removable periodontal splint based on routine interventions. The study group was subject to medication with minocycline in addition to the treatments used in the control group. Clinical efficacy, periodontal status (sulcus bleeding index, plaque index, periodontal pocket depth) and gingival crevicular fluid inflammatory factors (transforming growth factor β, monocyte chemoattractant protein-1, interleukin-6, matrix metalloproteinase-8) and bone metabolism indexes [osteocalcin, N-terminal procollagen of type I (PINP), N-terminal propeptide of type I procollagen (PINP), C-terminal telopeptide of type I collagen (CTX) levels], comfort and aesthetics scores, and patient satisfaction were compared between the two groups. Results:Total response rate was significantly higher in the study group than in the control group [94.12% (48/51) vs. 80.39% (41/51), χ2 = 4.32, P < 0.05]. At 1 and 3 months after treatment, sulcus bleeding index (1.32 ± 0.41, 1.11 ± 0.36), plaque index (1.51 ± 0.44, 1.32 ± 0.51), periodontal pocket depth [(3.29 ± 0.70) mm, (2.51 ± 0.63) mm] were significantly lower in the study group than in the control group [1.65 ± 0.39, 1.45 ± 0.38, 1.92 ± 0.42, 1.88 ± 0.49, (5.05 ± 0.79) mm, (3.82 ± 0.86) mm, t = 4.16, 4.63, 4.81, 5.65, 11.90, 8.77, all P < 0.001]. At 1 and 3 months after treatment, the level of transforming growth factor β in the gingival crevicular fluid was significantly higher, and the level of matrix metalloproteinase-8 in the gingival crevicular fluid was significantly lower, in the study group compared with the control group (both P < 0.001). At 1 and 3 months after treatment, the level of osteocalcin in the gingival crevicular fluid was significantly higher, and the level of C-terminal telopeptide of type I collagen in the gingival crevicular fluid was significantly lower, in the study group compared with the control group ( t = -9.97, -10.71, -5.77, -7.40, 7.24, 16.11, all P < 0.001). At 1 and 3 months after treatment, the scores of comfort and aesthetics in the study group were significantly higher than those in the control group ( t = 7.49, 8.26, 7.84, 9.10, all P < 0.001). Patient satisfaction in the study group was significantly higher than that in the control group (94.12% vs. 80.39%, χ2 = 4.32, P < 0.05). Conclusion:Repair with a removable periodontal splint combined with minocycline can increase the therapeutic effects through reducing periodontal inflammation and regulating bone metabolism, thereby improving the periodontal condition, and improving tooth comfort and aesthetics and patient satisfaction in patients with severe periodontal disease.

9.
Article in Chinese | WPRIM | ID: wpr-930994

ABSTRACT

Objective:To study the regulatory effects of transforming growth factor beta-activated kinase 1 (TAK1) on microglia pyroptosis in hypoxic-ischemic brain damage (HIBD).Methods:Primary microglia cells were isolated from fetal mice and randomly assigned into 4 groups: the control group, 5z-7-oxozeaneol (5z-7) group, oxygen-glucose deprivation (OGD) group and OGD+5z-7 group. OGD models of microglia cells were established for the OGD groups and 5z-7 groups received a small molecule TAK1 inhibitor 5z-7. Expression of phosphorylated TAK1(P-TAK1), pyroptosis related proteins including NOD-like receptor pyrin domain containing 3 (NLRP-3), apoptosis-associated speck-like protein containing a CARD (ASC) oligomers, N terminal of Gasdermin D (GSDMD-N) and interleukin 1β (IL-1β) were examined using Western blot at 0 h, 6 h and 24 h after intervention. Lactate dehydrogenase (LDH) test and transmission electron microscope were used for pyroptosis evaluation.Results:(1) Compared with the control group, expressions of all proteins including P-TAK1, NLRP-3, ASC oligomers, GSDMD-N, IL-1β and LDH level showed no significant differences in the OGD group at 0 h ( P>0.05). P-TAK1 levels in OGD group at 6 h and 24 h were lower than the control group and the levels of NLRP-3, ASC oligomers, GSDMD-N, IL-1β and LDH were significantly higher ( P<0.05). Microglia pyroptosis (characterized by disruption of cell membrane, extravasation of cytoplasm and chromatin margin aggregation) was observed under electron microscope. (2) 5z-7 group and OGD+5z-7 group had lower P-TAK1 levels and higher NLRP-3, ASC oligomers, GSDMD-N, IL-1β and LDH levels than the control group and OGD group at 6 h and 24 h. Conclusions:The down-regulation of TAK1 phosphorylation level may promote microglia pyroptosis in HIBD. This regulatory effects is related to the up-regulation of NLRP-3 expression and the oligomerization of ASC.

10.
Journal of Clinical Hepatology ; (12): 2040-2045, 2022.
Article in Chinese | WPRIM | ID: wpr-942657

ABSTRACT

Objective To investigate the effect of Yangxue Rougan pills on a rat model of liver fibrosis induced by multiple factors and the mechanism of action of Yangxue Rougan pills in the treatment of liver fibrosis. Methods A total of 50 male rats were randomly divided into blank control group, multi-factor model group, Fuzheng Huayu capsule group, and high-, middle-, and low-dose Yangxue Rougan pill groups. The rats in the blank control group were given normal water and feed, and those in the other groups were given modified high-fat low-protein diet and 5% alcohol, as well as subcutaneous injection of olive oil solution containing 40% carbon tetrachloride and intraperitoneal injection of pig serum 0.5 mL per rat, twice a week for 12 consecutive weeks. Since week 7, the rats in the high-, middle-, and low-dose Yangxue Rougan pill groups were given Yangxue Rougan pills at a dose of 9.5, 4.75, and 2.38 g/kg, respectively, those in the Fuzheng Huayu capsule group were given Fuzheng Huayu capsules at a dose of 0.75 g/kg, and those in the blank control group and the multi-factor model group were given an equal volume of distilled water by gavage every day for 6 consecutive weeks. The rats were treated at week 12. HE staining and Masson staining were used to observe the degree of liver fibrosis in rats, and PCR and Western blot were used to measure the expression of TGF-β1, Smad3, and Smad7 in the liver. A one-way analysis of variance was used for comparison of continuous data between multiple groups, and the Dunnett's t -test was used for further comparison between two groups. Results Compared with the blank control group, the multi-factor model group had a severely damaged lobular structure and a significantly higher degree of liver fibrosis, with the formation of pseudolobules with different sizes; compared with the multi-factor model group, the Yangxue Rougan pill groups had a significant improvement in the degree of liver fibrosis, with the most significant therapeutic effect in the high- and middle-dose Yangxue Rougan pill groups. Compared with the blank control group, the multi-factor model group had significant increases in the expression of TGF-β1 and Smad3 and a significant reduction in the expression of Smad7 in liver tissue (all P < 0.05); compared with the multi-factor model group, the Yangxue Rougan pill groups had a significant reduction in the expression of TGF-β1 and a significant increase in the expression of Smad7 (all P < 0.05); compared with the multi-factor model group, the high- and middle-dose Yangxue Rougan pill groups had a significant reduction in the expression of Smad3 (both P < 0.05). Conclusion Yangxue Rougan pills can significantly inhibit liver fibrosis in rats by downregulating the expression of TGF-β1 and Smad3 and upregulating the expression of Smad7, and therefore, the TGF-β1/Smad signaling pathway is one of the mechanisms of action of Yangxue Rougan pills in improving liver fibrosis.

11.
Article in Chinese | WPRIM | ID: wpr-930141

ABSTRACT

Objective:To observe the effect of Ginsenoside Re on the proliferation and protein secretion of primary cardiac fibroblasts (CFs) cultured in high glucose by vitro, and the regulation of Wnt/β-catenin signaling pathway.Methods:The myocardial fibroblast proliferation model induced by high glucose in vitro was used. Cell proliferation was detected by MTT method, cell cycle was measured by flow cytometry, concentration of type Ⅰ,Ⅲ collagens and TGF-β 1 protein were tested by ELISA assay. Protein expression of β-catenin, GSK-3β and p-GSK-3β were determined by Western blot. Results:Compared with the model group, the cell proliferation in Ginsenoside Re high, medium, low group were significantly decreased ( P<0.01), the percentage of cells in G 0 + G 1 phase was increased ( P<0.01), and the percentage of cells in S + G 2 + M phase was decreased ( P<0.01), the content of TGF-β 1 was significantly decreased( P<0.01). The content of type Ⅲ collagen [(6.566±1.620)ng/ml,(7.170±0.470)ng/ml vs. (11.241±2.234)ng/ml] in Ginsenoside Re high, medium group were significantly decreased ( P<0.01). The expression of β-catenin (0.281±0.016, 0.301±0.021 vs. 0.409±0.037) was significantly decreased and the expression of p-GSK-3β (0.369±0.049 vs. 0.268±0.048) in Ginsenoside Re high, medium group were significantly increased ( P<0.01). Conclusion:Ginsenoside Re plays an important role in inhibiting CFs proliferation and reducting the synthesis of collagen and TGF-β 1 by regulating abnormal expression of Wnt/β-catenin signaling pathway. It has the potential to delay the myocardial fibrosis of diabetes mellitus.

12.
International Eye Science ; (12): 1133-1136, 2022.
Article in Chinese | WPRIM | ID: wpr-929493

ABSTRACT

Pterygium is an ocular surface disease formed by many factors and associate with a series of changes caused by ultraviolet irradiation and radiation, its pathogenesis is still uncertain. Elevated vascular endothelial growth factor(VEGF), inflammatory infiltrates, angiogenesis, oxidative stress, epithelial-mesenchymal cell transition(EMT), and tumor suppressor gene inactivation are currently recognized causes of pterygium. The mechanism of this factor in pterygium deveopment is still not completely understood. This review aimed to investigate the role of these factors in pterygium formation and provide targeted therapy and effective preventive measures for clinical diagnosis and treatment.

13.
Mem. Inst. Oswaldo Cruz ; 117: e210395, 2022.
Article in English | LILACS-Express | LILACS | ID: biblio-1360602

ABSTRACT

Transforming growth factor beta (TGF-β) is deeply involved on the pathogenesis of Chagas disease. Our group has been investigating the participation of this pleiotropic cytokine in different aspects of Chagas disease over the last 20 years. Important observations have been made, such as: (i) the ability of Trypanosoma cruzi in activating latent TGF-β; (ii) the potential involvement of TGF-β pathway on T. cruzi invasion of host cells; (iii) association of TGF-β with parasite intracellular replication; (iv) cardiac fibrosis development and maintenance; (v) disruption of Connexin-43 plaque structures and (vi) inflammation and immune response. In this perspective article we intend to discuss the advances of the potential use of new therapies targeting TGF-β to treat the cardiac alterations of Chagas disease-affected patients.

14.
International Eye Science ; (12): 931-935, 2022.
Article in Chinese | WPRIM | ID: wpr-924207

ABSTRACT

@#AIM: To explore the effect of SiWuWuZi decoction combined with intravitreal injection of conbercept on patients with wet age-related macular degeneration(ARMD)and its effects on serum vascular endothelial growth factors(VEGF), transforming growth factor-β1(TGF-β1)and inflammatory factors.<p>METHODS: A retrospective study. A total of 60 cases(60 eyes)wet ARMD patients admitted to the ophthalmology department of our hospital from May 2019 to November 2020 were divided into 30 cases(30 eyes)of the control group were treated with intravitreal injection of conbercept, while observation group 30 cases(30 eyes)was added with SiWuWuZi decoction on the basis of treatment for control group. The best corrected visual acuity(BCVA), the neovascular area were not be vanished fundus hemorrhage, exudation, choriocapillario-Bruch's membrane-retinal pigment epithelium complex(CBRC), and retinal neuroepithelial layer(RNL), serum VEGF, TGF-β1, interleukin-6(IL-6)and interleukin-13(IL-13)levels and overall efficacy after 3mo were compared.<p>RESULTS: After 3mo treatment, BCVA, fundus hemorrhage, exudation, CBRC and RNL thickness in 2 groups were improved compared with before treatment(<i>P</i><0.05), and the observation group was better than the control group(<i>P</i><0.05). Compared with before treatment, serum VEGF, TGF-β1, IL-6 and IL-13 in 2 groups after 3mo treatment were decreased(<i>P</i><0.001), and serum VEGF, TGF-β1, IL-6 and IL-13 levels in observation group were significantly lower than those in control group(<i>P</i><0.05). The overall effect of observation group was significantly better than control group(<i>P</i>=0.037). <p>CONCLUSION: SiWuWuZi decoction combined with intravitreal injection of conbercept can gradually vanish fundus neovascularization in patients with wet ARMD, serum levels of VEGF, TGF-β1 and inflammatory factors, improve ocular microcirculation and promote vision recovery in patients with wet ARMD.

15.
Braz. dent. j ; 32(6): 1-7, Nov.-Dec. 2021. graf
Article in English | LILACS-Express | LILACS, BBO | ID: biblio-1355841

ABSTRACT

Abstract This study investigated the cytotoxicity and release of Transforming Growth Factor Beta 1 (TGF-β1) from cultured human apical papilla cells (APCs) after application of four bioactive materials. Culture of APCs was established and used for cytotoxic and quantitative assays. Extracts of Biodentine, Bio-C Repair, MTA Repair and White MTA were prepared and diluted (1, 1:4 and 1:16) and used for MTT assays up to 72 h. Total TGF-β1 was quantified by ELISA. Data were analyzed by ANOVA and Tukey's test (α = 0.05). For Biodentine, at 24 h and 48 h, cell viability was lower than control (p < 0.05). At 72 h, only undiluted extract of Biodentine were cytotoxic (p < 0.05). At 24 h, a cytotoxic effect was found for undiluted and 1:4 dilution of Bio-C Repair (p < 0.05). At 48 h, however, Bio-C Repair at 1:4 and 1:8 dilution showed higher cell viability (p < 0.05). At 24 and 48 h, the cell viability for undiluted MTA Repair were higher than control (p < 0.05). For White MTA, at 24 and 48 h, all dilutions were cytotoxic (p < 0.05). All cements led to reduced release of total TGF-β1 from the APCs (p < 0.05). In conclusion, cell viability varied depending on the material and dilution. Only Bio-C repair and MTA repair led to higher cell viability of APCs. All materials induced a decrease in the release of total TGF-β1 from the APCs.


Resumo Este estudo investigou a citotoxicidade e liberação do Fator de Crescimento Transformador Beta 1 (TGF-β1) em células da papila apical humana (APCs) cultivadas após a aplicação de quatro materiais bioativos. A cultura de APCs foi estabelecida e usada para ensaios citotóxicos e quantitativos. Extratos de Biodentine, Bio-C Repair, MTA Repair e White MTA foram preparados e diluídos (1, 1: 4 e 1:16) e usados para ensaios de MTT por até 72 h. O TGF-β1 total foi quantificado por ELISA. Os dados foram analisados por ANOVA e teste de Tukey (α = 0,05). Para o Biodentine, em 24 h e 48 h, efeito citotóxico foi observado (p <0,05). Em 72 h, apenas o extrato não diluído de Biodentine teve efeito citotóxico (p <0,05). Em 24 h, valores mais baixos de viabilidade celular foram encontrados para o extrato não diluído e diluidi 1:4 de Bio-C Repair (p <0,05). Em 48 h, no entanto, Bio-C Repair na diluição 1:4 e 1:8 mostrou maior viabilidade celular (p <0,05). A viabilidade celular para MTA Repair não diluído em 24 e 48 h foi maior que o controle (p <0,05). Para White MTA, às 24 e 48 h, a viabilidade celular em todas as diluições foram citotóxicas (p <0,05). Todos os cimentos levaram à redução da liberação de TGF-β1 total das APCs (p <0,05). Em conclusão, a viabilidade celular variou dependendo do material e da diluição. Biodentine, Bio-C Repair e MTA Repair levaram a uma maior viabilidade celular de APCs. Todos os materiais induziram uma diminuição na liberação de TGF-β1 total das APCs.

16.
Med. UIS ; 34(1): 119-127, ene.-abr. 2021. tab
Article in Spanish | LILACS-Express | LILACS | ID: biblio-1360592

ABSTRACT

Resumen El síndrome de Camurati-Engelmann, también conocido como displasia diafisaria progresiva, es una enfermedad rara, autosómica dominante y con una prevalencia de uno por cada millón de habitantes. Genera mutaciones del factor de crecimiento transformante beta, que participa en la proliferación ósea. Son frecuentes las manifestaciones osteomusculares y neurológicas, con escasas expresiones de laboratorio. El diagnóstico se basa en la clínica, los hallazgos radiológicos y la confirmación genética; el tratamiento se dirige al control sintomático y el pronóstico es incierto. La presente publicación tiene como objetivo compartir con la comunidad médica el tercer caso de síndrome de Camurati-Engelmann conocido en Colombia. Se trata de una paciente femenina de 33 años con cuadro clínico de distonías intensas y signos y síntomas característicos de este síndrome, cuyo diagnóstico fue confirmado por prueba molecular, encontrando la presencia de la variante patogénica p.Arg156Cys en el gen TGF-β1, con presentación de novo. MÉD.UIS.2021;34(1): 119-27.


Abstract Camurati-Engelmann syndrome, also known as progressive diaphyseal dysplasia, is a rare, autosomal dominant disease with a prevalence of one per million inhabitants. It generates mutations of the transforming growth factor beta, which participates in bone proliferation. Osteomuscular and neurological manifestations are frequent, with few laboratory expressions. The diagnosis is based on the clinic, radiological findings, and genetic confirmation, treatment is aimed at symptom control and prognosis is uncertain. The objective of this publication is to share with the medical community the third case of Camurati-Engelmann syndrome known in Colombia. This is a 33-year- old female patient with a clinical picture of intense dystonia and characteristic signs and symptoms of this syndrome, whose diagnosis was confirmed by molecular testing, finding the presence of the pathogenic variant p.Arg156Cys in the TGF-β1 gene, with de novo presentation. MÉD.UIS.2021;34(1): 119-27.

17.
Acta cir. bras ; 36(6): e360604, 2021. tab, graf
Article in English | LILACS, VETINDEX | ID: biblio-1284910

ABSTRACT

ABSTRACT Purpose Herein we evaluated the effects of platelet concentrate (PC) and platelet-poor plasma (PPP) on bone repair using noncritical defects in the calvaria of rabbits and compared them to the presence of TGF-β1 and osteocalcin on reparative sites. Methods Five noncritical defects of 8.7 mm in diameter were created on the calvaria of 15 animals. Each defect was treated differently, using autograft (ABG), ABG associated with PC (ABG + PC), ABG with PPP (ABG + PPP), isolated PPP, and blood clot (control). The animals were submitted to euthanasia on the second, fourth and sixth week post-surgery. Results The defects that received ABG+PC or PPP demonstrated lower bone formation when compared to specimens that received ABG in the same period. These results coincided to significant higher immunopositivity for TGF-β1 for specimens that received PC, and lower presence of cytokine in the group PPP. However, either higher or lower presence of TGF-β1 were also correlated to lower presence of osteocalcin. Likewise, these results were similar to findings in specimens treated only with PPP when compared to control. Conclusions PC and PPP were not effective when applied in association with ABG. Similarly, isolated use of PPP was not beneficial in optimizing the bone repair.


Subject(s)
Animals , Osteogenesis , Transforming Growth Factor beta1/metabolism , Rabbits , Skull/surgery , Osteocalcin , Autografts
18.
Article in Chinese | WPRIM | ID: wpr-912649

ABSTRACT

Objective:To compare the effects of circular arch device and dressing device on the secretion of collagen, matrix metalloproteinase (MMP-1), transforming growth factor (TGF-β) of fibroblasts in the treated skin, and to explore the changes and mechanisms.Methods:The animals were purchased from the Southern Medical University Laboratory Animal Center. Using the established animal model, 54 mice were randomly divided into three groups: 18 mice each group, including control group, dressing device group and and circular arch device group. At the first, third and fifth day after negative pressure suction treatment, dermal thickness and density of collagen levels were and eosin staining, collagen level in local skin was determined using spectrophotometry, and MMP-1 and TGF-β levels were determined using enzyme linked immunosorbent assay.Results:Dermal thickness level was increased significantly in negative suction treated groups [after 5 days of treatment, control group: (71±8) μm; circular arch device group: (351±9) μm; dressing device group: (267±12) μm, P< 0.05]. Compared with the control group, collagen level in the dermis was significantly higher in circular arch device groups [after 5 days of treatment, control group: (30.9±4.3) mg/g; circular arch device group: (72.7±3.6) mg/g, P< 0.05]. TGF-β level in circular arch device treated group was increasing gradually, and markedly higher than that in the dressing device group and the control group [after 5 days of treatment, control group: (0.24±0.1) ng/ml; circular arch device group: (0.78±0.08) ng/ml; dressing device group: (0.39±0.18) ng/ml, P< 0.05], while MMP-1 level was decreasing. In addition, TGF-β and MMP-1 levels in the dressing device treated group remained stable during the entire experiment. Conclusions:The interface of the circular arch negative pressure suction device can effectively activate the fibroblasts, promote the secretion of TGF-β and collagen, and thicken the skin tissue.

19.
Chinese Journal of Nephrology ; (12): 1001-1007, 2021.
Article in Chinese | WPRIM | ID: wpr-911920

ABSTRACT

Objective:To establish a rat model of neurogenic bladder and analyze the changes in kidney morphology and function and the expression of proteins in AngiotensinⅡ(AngⅡ)/transforming growth factor β1 (TGF-β1)/Smads pathway.Methods:Sprague-Dawley rats were randomly divided into experimental group (spinal nerve amputation, n=36) and control group (sham operation, n=12). At 6, 12, and 24 weeks, the bladder compliance was measured by cystometry, the kidney morphology was detected by B-ultrasound, blood urea nitrogen (BUN) and serum creatinine (Scr) in blood samples were examined, the kidney pathological changes were detected by Masson and HE staining, the distribution of AngⅡ/TGF-β1/Smads pathway proteins was analyzed by immunohistochemisty, and the protein expressions in kidney were detected by Western blotting. Results:Urodynamics showed that the basic bladder pressure in experimental group was higher than that in control group. B-ultrasound showed that compared with the control group, the diameter of the renal pelvis of the rats with nerve dissection gradually increased ( P<0.05), and the hydronephrosis was gradually obvious. Compared with the control group, the BUN and Scr in experimental group gradually increased (both P<0.01). Masson and HE staining showed that compared with the control group, the collagen expression and renal tubulointerstitial scores in experimental group were gradually increased (both P<0.01). Immunohistochemisty showed that compared with the control group, in experimental group the expression of angiotensinⅡ receptor type 1 (AT1), TGF-β receptor 1(TGF-βR1), phosphorylated Smad2 gradually increased (all P<0.01), the pathway inhibitor Smad6 gradually decreased ( P<0.01), and the distribution of each protein in kidney was consistent. Western blotting showed a corresponding expression trend with immunohistochemisty. Conclusions:In neurogenic bladder caused by bilateral spinal nerve amputation, due to bladder dysfunction, increased bladder pressure induces hydronephrosis, destruction of the nephron structure, activation of AngⅡ/TGF-β1/Smads pathway, and renal fibrosis. This method is effective and has clinical similarities, laying a foundation for exploring neurogenic bladder treatment.

20.
Chinese Journal of Nephrology ; (12): 911-917, 2021.
Article in Chinese | WPRIM | ID: wpr-911912

ABSTRACT

Objective:To investigate the role and mechanism of (histone deacetylase 6, HDAC6) in the epithelial-mesenchymal transition (EMT) of renal tubular epithelial cells and the activation of renal interstitial fibroblasts.Methods:Human renal tubular epithelial cells (HK-2) and rat renal interstitial fibroblast (NRK-49F) were cultured in vitro, and divided into 4 groups: control group, Tubastatin A (TA) group (treated with 10 μmol/L HDAC6 inhibitor TA for 36 h), transforming growth factor-β1 (TGF-β1) group (10 ng/ml TGF-β1 for 36 h), and TGF-β1+TA group (treated with 10 ng/ml TGF-β1 and 10 μmol/L TA for 36 h). The expression levels of fibronectin, α-smooth muscle actin (α-SMA), collagen I, E-cadherin, HDAC6, acetyl histone H3, histone H3, acetyl α-tubulin, α-tubulin, TGF-β receptor (TGF-βR) 1, p-Smad3, Smad3, connective tissue growth factor (CTGF), epidermal growth factor receptor (EGFR) and p-EGFR in HK-2 and NRK-49F cell samples were detected by Western blotting, and quantitative analysis was performed according to gray level. Results:(1) In HK-2 cells stimulated by TGF-β1, TA decreased the expression of fibronectin, α-SMA, collagen I, and increased the expression of epithelial cell marker E-cadherin. Meanwhile, TA decreased the expression of HDAC6 and increased the expression levels of acetyl histone H3 and acetyl α-tubulin (all P<0.05). (2) Compared with the TGF-β1 group, the expressions of TGF-βR1, p-Smad3, CTGF and p-EGFR in TGF-β1+TA group were decreased (all P<0.05), while the total protein levels of Smad3 and EGFR were not significantly different (both P>0.05). (3) In NRK-49F cells stimulated by TGF-β1, TA decreased the expressions of fibronectin, α-SMA, collagen I, TGF-βR1 and p-Smad3 (all P<0.05). Conclusions:Blockade of HDAC6 by TA may inhibit the EMT of renal tubular epithelial cells and the activation of renal interstitial fibroblasts via regulating multiple signaling pathways including TGF-β/Smad3, CTGF and EGFR.

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