Shenmai Injection Improves Hypertensive Heart Failure by Inhibiting Myocardial Fibrosis via TGF-β 1/Smad Pathway Regulation / 中国结合医学杂志

OBJECTIVE@#To study effects of Shenmai Injection on hypertensive heart failure and its mechanism for inhibiting myocardial fibrosis.@*METHODS@#Salt-sensitive (Dahl/SS) rats were fed with normal diet (0.3% NaCl) and the high-salt diet (8% NaCl) to observe the changes in blood pressure and heart function, as the control group and the model group. Salt-insensitive rats (SS-13BN) were fed with the high-salt diet (8% NaCl) as the negative control group. After modeling, the model rats were randomly divided into heart failure (HF) group, Shenmai Injection (SMI) group and pirfenidone (PFD) group by a random number table, with 6 rats in each group. They were given sterilized water, SMI and pirfenidone, respectively. Blood pressure, cardiac function, fibrosis and related molecular expression were detected by sphygmomanometer, echocardiogram, enzyme linked immunosorbent assay (ELISA), hematoxylin-eosin staining, Masson staining, immunofluorescence and qPCR analysis.@*RESULTS@#After high-salt feeding, compared with the control and negative control group, in the model group the blood pressure increased significantly, the left ventricular ejection fraction (LVEF) and left ventricular fraction shortening (LVFS) were significantly reduced, and the serum NT-proBNP concentration increased significantly (all P<0.05); furthermore, the arrangement of myocardial cells was disordered, the edema was severe, and the degree of myocardial fibrosis was also significantly increased (P<0.05); the protein and mRNA expressions of collagen type I (Col I) were up-regulated (P<0.05), and the mRNA expressions of transforming growth factor β 1 (TGF- β 1), Smad2 and Smad3 were significantly up-regulated (P<0.05). Compared with HF group, after intervention of Shenmai Injection, LVEF and LVFS increased, myocardial morphology was improved, collagen volume fraction decreased significantly (P<0.05), and the mRNA expressions of Col I, TGF- β 1, Smad2 and Smad3, as well as Col I protein expression, were all significantly down-regulated (all P<0.05).@*CONCLUSION@#Myocardial fibrosis is the main pathological manifestation of hypertensive heart failure, and Shenmai Injection could inhibit myocardial fibrosis and effectively improve heart failure by regulating TGF-β 1/Smad signaling pathway.

Effect of recombinant human fibroblast growth factor 21 on the mineralization of cementoblasts and its related mechanism / 华西口腔医学杂志

OBJECTIVES@#To investigate the effect of recombinant human fibroblast growth factor 21 (rhFGF21) on the proliferation and mineralization of cementoblasts and its mechanism.@*METHODS@#Hematoxylin eosin, immunohistochemical staining, and immunofluorescence were used to detect the expression and distribution of fibroblast growth factor 21 (FGF21) in rat periodontal tissues and cementoblasts (OCCM-30), separately. Cell Counting Kit-8 was used to detect the proliferation of OCCM-30 under treatment with rhFGF21. Alkaline phosphatase staining and Alizarin Red staining were used to detect the mineralization state of OCCM-30 after 3 and 7 days of mineralization induction. The transcription and protein expression of the osteogenic-related genes Runx2 and Osterix were detected by real-time quantitative polymerase chain reaction (PCR) and Western blot analysis. The expression levels of genes of transforming growth factor β (TGFβ)/bone morphogenetic protein (BMP) signaling pathway in OCCM-30 were detected through PCR array analysis.@*RESULTS@#FGF21 was expressed in rat periodontal tissues and OCCM-30. Although rhFGF21 had no significant effect on the proliferation of OCCM-30, treatment with 50 ng/mL rhFGF21 could promote the mineralization of OCCM-30 cells after 7 days of mineralization induction. The transcriptional levels of Runx2 and Osterix increased significantly at 3 days of mineralization induction and decreased at 5 days of mineralization induction. Western blot analysis showed that the protein expression levels of Runx2 and Osterix increased during mineralization induction. rhFGF21 up-regulated Bmpr1b protein expression in cells.@*CONCLUSIONS@#rhFGF21 can promote the mineralization ability of OCCM-30. This effect is related to the activation of the TGFβ/BMP signaling pathway.

Oxidative stress and its correlation with nuclear factor-κB and transforming growth factor-β1 in liver injury induced by different doses of X-rays in mice / 环境与职业医学

Background Radiation-induced liver damage is a major complication for primary liver cancer and other upper abdominal tumors during radiation therapy. The early biological effects of radiation-induced liver damage at different doses of radiation and its mechanisms of action have not yet been elucidated. Objective To establish X-ray-induced radioactive mouse liver damage model and explore the level of oxidative stress and its correlation with nuclear factor-κB (NF-κB) and transforming growth factor-β1 (TGF-β1). Methods A total of 24 male C57BL/6J mice aged 6 weeks were randomly divided into 4 groups (control, 0.8 Gy, 1.6 Gy, and 4 Gy), with 6 mice in each group. X-rays irradiated the whole body of mice singly in each dose group. At 24 h after radiation, histopathological changes in mouse liver were evaluated; peripheral blood cell count, serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels, as well as liver tissue superoxide dismutase (SOD) activity, malondialdehyde (MDA) level, reduced glutathione (GSH) level, and 8-hydroxy-2′-deoxyguanosine (8-OHdG) level were measured; real-time fluorescence quantitative PCR was used to detect liver tissue NF-κB p65 and TGF-β1 mRNA expression levels; the correlations of oxidative stress indicators with NF-κB p65 and TGF-β1 mRNA expression levels were analyzed by Pearson correlation. Results Compared with the control group, at 24 h after different doses of X-ray radiation, early injury-related histopathological changes were observed in liver, and the serum levels of AST and ALT were significantly increased in the 4 Gy group (P<0.05); the numbers of peripheral blood leukocytes and lymphocytes were decreased in the radiation exposure groups (P<0.05), showing a decreasing trend with increasing radiation doses; the levels of liver oxidative stress indicators (MDA, SOD, and GSH) in exposed mice were significantly increased (P<0.05), showing an increasing trend with increasing radiation doses. The liver 8-OHdG were significantly increased in the 1.6 Gy and 4 Gy groups compared with the control and the 0.8 Gy groups, respectively (P<0.05). The NF-κB p65 and TGF-β1 mRNA expression levels in the liver of mice were significantly increased in the 1.6 Gy and 4 Gy groups compared with the control group (P<0.05). The TGF-β1 mRNA expression level also exhibited an increasing trend with increasing radiation doses. The results of correlation analysis showed that the levels of MDA, SOD, GSH, and 8-OHdG in liver tissues were significantly and positively correlated with the expression levels of NF-κB p65 and TGF-β1 mRNA (P<0.05). Conclusion X-rays of various doses can affect the degree of liver injury, peripheral blood cell count, serum levels of AST and ALT, and liver oxidative stress levels in mice. The level of oxidative stress induced by X-ray is positively correlated with NF-κB and TGF-β1 in liver tissues, and it may participate in the process of radiation-induced liver injury.

Effect of vascular endothelial growth factor-A165 on scleral remodeling of guinea pigs with form-deprivation myopia / 国际眼科杂志(Guoji Yanke Zazhi)

AIM: To investigate the effect of the intravitreal injection of vascular endothelial growth factor-A165(VEGF-A165)on the scleral remodeling of guinea pigs with form-deprivation myopia(FDM).METHODS: A total of 120 tricolor guinea pigs, aged three weeks, were randomly divided into 6 groups, with 20 in each group. The blank group did not undergo any intervention. In the FDM group, only the FDM model was established. In the phosphate buffer saline(PBS)group, 2.5 μL of PBS was injected into the vitreous cavity before establishing the FDM model. In the 1ng group, 5ng group, and 10ng group, VEGF-A165 was injected into the vitreous cavity at concentrations of 1, 5 and 10ng, respectively, before the establishment of the FDM model. The FDM model was established by covering the right eyes of guinea pigs with translucent balloons for 14d. The diopter and axial length of the right eyes were measured before and after covering. After 14d, the content of dopamine(DA)in retina was measured by high performance liquid chromatography. Additionally, the mRNA and protein expression levels of matrix metalloproteinase-2(MMP-2), tissue inhibitor of matrix metalloproteinase-2(TIMP-2), transforming growth factor(TGF)-β1, TGF-β2 and α-smooth muscle actin(α-SMA)in sclera were detected by reverse transcription polymerase chain reaction(RT-PCR)and Western blot.RESULTS: Before covering, there were no significant differences in the diopter and axial length of the right eyes of guinea pigs in all groups(P&#x003E;0.05). After 14d of modeling, when compared with the blank group, FDM group showed an increase in the degree of myopia in the right eye, a prolongation of the axial length, a decrease in the content of DA in the retina, and an increase in the expression of MMP-2, TGF-β2 and α-SMA in the sclera. Conversely, the expression of TIMP-2 and TGF-β1 were decreased(P&#x003C;0.01). However, in comparison to the FDM group, the degree of myopia in the 1ng, 5ng, and 10ng groups of guinea pigs decreased, the growth trend of axial length slowed, the content of DA in the retina increased, and the expression of MMP-2, TGF-β2 and α-SMA in the sclera decreased. Furthermore, the expression of TIMP-2 and TGF-β1 in the sclera increased(P&#x003C;0.01). As the concentration of intravitreal injection of VEGF-A165 increased, the degree of myopia in the right eye of guinea pigs gradually increased, and the axial length gradually prolonged. The content of DA in the retina gradually decreased, the expression of MMP-2, TGF-β2, and α-SMA in the sclera gradually increased, while the expression of TIMP-2 and TGF-β1 decreased gradually.CONCLUSION: Intravitreal injection of VEGF-A165 can increase the content of DA in the retina of FDM guinea pigs, affect the expression of MMP-2, TIMP-2, TGF-β1, TGF-β2 and α-SMA in the sclera, and inhibit scleral remodeling of guinea pigs. Notably, the VEGF-A165 at the concentration of 1ng showed the most significant efficacy.

Mechanism of Dahuang Zhechongwan in Treating Myocardial Fibrosis of Rats via TGF-β1/Smads/miR29 Pathway / 中国实验方剂学杂志

ObjectiveTraditional Chinese medicine， namely Dahuang Zhechongwan （DHZCW） was used to treat myocardial fibrosis in model rats， observe its effect on myocardial fibrosis in rats， and explore its action mechanism. MethodThirty-six SPF male Kunming rats were divided into blank group， model group， low-， medium-， high-dose groups of DHZCW （0.056， 0.084， 0.168 g·kg-1）， captopril group （10 mg·kg-1）， with six rats in each group. Except for the blank group， the other groups were intraperitoneally injected isoproterenol solution of 5 mg·kg-1 for 15 consecutive days to replicate the myocardial fibrosis model. At the beginning of modeling， the rats in each group took drugs， and they were sacrificed 28 days after administration. Serum and heart tissue were collected for the corresponding detection. Hematoxylin-eosin （HE） staining and Masson staining were used to observe tissue inflammation， cellular degeneration， necrosis， and fibrosis. The contents of hydroxyproline （HYP）， tumor necrosis factor-α （TNF-α）， interleukin-1β （IL-1β）， interleukin-6 （IL-6）， hyaluronic acid （HA）， laminin （LN）， type-Ⅲ procollagen （PC Ⅲ） in serum of rats and rats were determined by enzyme-related immunosorbent assay （ELISA）. The expression levels of key pathway proteins transforming growth factor-β1 （TGF-β1）， α-smooth muscle actin （α-SMA）， Smad2， Smad3， and Smad7 were detected by Western blot. The expression levels of key pathway genes TGF-β1， α-SMA， Smad2， Smad3， Smad7， miR-29a-5p， miR-29b-2-5p， and miR-29c-5p were detected by Real-time quantitative polymerase chain reaction （Real-time PCR）. ResultCompared with the blank group， the pathological changes of fibrosis in the model group were obvious， the contents of serum HYP， TNF-α， IL-1β， IL-6， HA， LN， and PCⅢ were increased （P<0.01）， the protein expression levels of TGF-β1， α-SMA， Smad2， and Smad3 were increased； the protein expression level of Smad7 was decreased （P<0.01）. The mRNA expression levels of TGF-β1， α-SMA， Smad2， and Smad3 were increased （P<0.05， P<0.01）， while those of Smad7， miR-29a-5p， miR-29b-2-5p， and miR-29c-5p were decreased （P<0.01）. Compared with the model group， after 28 days of administration， serum HYP， TNF-α， IL-1β， IL-6， HA， LN， and PCⅢ in high-， medium-， and low-dose groups of DHZCW and captopril groups were decreased （P<0.01）. Except for the low-dose group， the protein contents of TGF-β1， α-SMA， Smad2， and Smad3 were decreased， while the protein content of Smad7 was increased （P<0.01）. The mRNA expression levels of TGF-β1， Smad2， α-SMA， and Smad3 in high-dose group of DHZCW were decreased （P<0.05，P<0.01）， while those of Smad7， miR-29a-5p， miR-29b-2-5p， and miR-29c-5p were increased （P<0.05）. The mRNA expressions of TGF-β1， Smad2， and Smad3 in the medium-dose group of DHZCW were decreased （P<0.05， P<0.01）， while mRNA expression of Smad7 was increased （P<0.01）. The mRNA levels of TGF-β1 and Smad2 in the low-dose group of DHZCW were decreased （P<0.01）. ConclusionDHZCW can improve myocardial fibrosis in rats， and its action mechanism may be related to the regulation of the TGF-β1/Smads/miR-29 pathway. In addition， there is dose dependence in the range of 0.056-0.168 g·kg-1， and the effect of the high-dose group is more stable.

Huangqi Decoction, a compound Chinese herbal medicine, inhibits the proliferation and activation of hepatic stellate cells by regulating the long noncoding RNA-C18orf26-1/microRNA-663a/transforming growth factor-β axis / 中西医结合学报

OBJECTIVE@#Huangqi Decoction (HQD), a classical traditional Chinese medicine formula, has been used as a valid treatment for alleviating liver fibrosis; however, the underlying molecular mechanism is still unknown. Although our previous studies showed that microRNA-663a (miR-663a) suppresses the proliferation and activation of hepatic stellate cells (HSCs) and the transforming growth factor-β/small mothers against decapentaplegic (TGF-β/Smad) pathway, whether long noncoding RNAs (lncRNAs) are involved in HSC activation via the miR-663a/TGF-β/Smad signaling pathway has not yet reported. The present study aimed to investigate the roles of lncRNA lnc-C18orf26-1 in the activation of HSCs and the mechanism by which HQD inhibits hepatic fibrosis.@*METHODS@#The expression levels of lnc-C18orf26-1, miR-663a and related genes were measured by quantitative reverse transcription-polymerase chain reaction. HSCs were transfected with the miR-663a mimic or inhibitor and lnc-C18orf26-1 small interfering RNAs. The water-soluble tetrazolium salt-1 assay was used to assess the proliferation rate of HSCs. Changes in lncRNA expression were evaluated in miR-663a-overexpressing HSCs by using microarray to identify miR-663a-regulated lncRNAs. RNA hybrid was used to predict the potential miR-663a binding sites on lncRNAs. Luciferase reporter assays further confirmed the interaction between miR-663a and the lncRNA. The expression levels of collagen α-2(I) chain (COL1A2), α-smooth muscle actin (α-SMA) and TGF-β/Smad signaling pathway-related proteins were determined using Western blotting.@*RESULTS@#Lnc-C18orf26-1 was upregulated in TGF-β1-activated HSCs and competitively bound to miR-663a. Knockdown of lnc-C18orf26-1 inhibited HSC proliferation and activation, downregulated TGF-β1-stimulated α-SMA and COL1A2 expression, and inhibited the TGF-β1/Smad signaling pathway. HQD suppressed the proliferation and activation of HSCs. HQD increased miR-663a expression and decreased lnc-C18orf26-1 expression in HSCs. Further studies showed that HQD inhibited the expression of COL1A2, α-SMA, TGF-β1, TGF-β type I receptor (TGF-βRI) and phosphorylated Smad2 (p-Smad2) in HSCs, and these effects were reversed by miR-663a inhibitor treatment.@*CONCLUSION@#Our study identified lnc-C18orf26-1 and miR-663a as promising therapeutic targets for hepatic fibrosis. HQD inhibits HSC proliferation and activation at least partially by regulating the lnc-C18orf26-1/miR-663a/TGF-β1/TGF-βRI/p-Smad2 axis.

Non-coding RNA-mediated TGF-β1/Smads Signaling Pathway and Liver Fibrosis， and Intervention by Active Components of Chinese Medicinal： A Review / 中国实验方剂学杂志

Liver fibrosis is a wound healing response that occurs in the setting of chronic liver injury and is caused by imbalance in the synthesis and degradation of extracellular matrix （ECM）. If left untreated， it can progress to liver cirrhosis and hepatocellular carcinoma. The activation of hepatic stellate cell （HSC） is now well established as a central driver of liver fibrosis. The activated HSC will transform into myofibroblasts that produce ECM protein. Transforming growth factor-β1 （TGF-β1） can induce the activation of hepatic stellate cell （HSC）， and TGF-β1/Smads signaling pathway is one of the important pathways to promote liver fibrosis. Non-coding RNA （ncRNA） does not encode proteins during the transcription but plays an important regulatory role in the post-transcriptional process of genes. Accumulating evidence shows that the occurrence of liver fibrosis is closely related to the abnormal expression of ncRNA which participates in the activation of HSC by regulating TGF-β1 signal transduction and then affects the process of liver fibrosis. MiRNA-mediated TGF-β1/Smads signaling pathway can not only promote liver fibrosis but also play a role in anti-fibrosis. Long non-coding RNA （lncRNA） not only promotes the development of liver fibrosis by binding to target genes but also enhances TGF-β1 signal transduction by acting as competitive endogenous RNA. circular RNA （circRNA） acts as a ''sponge'' to regulate TGF-β1/Smads pathway， thereby inhibiting HSC activation and exerting the anti-liver fibrosis effect. Chinese medicinal plays an essential part in the prevention and treatment of liver fibrosis， and the active components can inhibit TGF-β1/Smads pathway by regulating the expression of miRNA， thus alleviating liver fibrosis. This article reviews the role and mechanism of miRNA-， lncRNA- and circRNA-mediated TGF-β1/Smads signaling pathway in liver fibrosis and summarizes the anti-liver fibrosis effect of active components of Chinese medicinals by regulating miRNA-mediated TGF-β1/Smads signaling pathway， which can serve as a reference for clinical treatment of liver fibrosis and the development of new drugs.

Ethyl Acetate Extract of Qigesan Intervenes in Migration and Invasion of Esophageal Cancer Cells via Inhibiting TGF-β1 Signaling Pathway / 中国实验方剂学杂志

ObjectiveTo explore the mechanism of Qigesan （QGS） in intervening in the migration and invasion of esophageal carcinoma TE-1 cells. MethodMicroarray technology was used to screen differentially expressed genes （DEGs） in the normal group and the QGS group， and the ontological functions and signaling pathways of DEGs were analyzed. The thiazolyl tetrazolium （MTT） assay was used to detect the effect of QGS on the viability of TE-1 cells. In the subsequent experiments for verification， a blank group， a transforming growth factor-β1 （TGF-β1） group， a TGF-β1 + QGS group， and a TGF-β1 + SB431542 group were set up. The cell morphology in each experimental group was observed by microscopy. The migration and invasion abilities of cells were detected by wound healing assay， and the mRNA expression levels of E-Cadherin， vimentin， Smad2， and Smad7 were detected by Real-time quantitative polymerase chain reaction （Real-time PCR）. The protein expression of E-Cadherin， vimentin， p-Smad2/3， Smad2/3， and Smad7 was detected by Western blot. ResultThere were 1 487 DEGs between the QGS group and the blank group， including 1 080 down-regulated ones （accounting for 72.63%） and 407 up-regulated ones. The down-regulated genes were mainly involved in biological processes such as cytoskeletal protein binding， ATP binding， adenylate nucleotide binding， and adenylate ribonucleotide binding， and the involved Kyoto Encyclopedia of Genes and Genomes （KEGG） pathways included TGF-β signaling pathway， cell cycle， extracellular matrix-receptor interaction protein， tumor pathways， and oocyte meiosis. The up-regulated genes were mainly involved in RNA binding， DNA binding， transcriptional regulator activity， transcriptional activator activity， and nucleotide binding， and the KEGG pathways involved mainly included mitogen-activated protein kinase （MAPK） signaling pathway， bladder cancer， renal cell carcinoma， cancer pathways， and p53 signaling pathway. Compared with the blank group， the inhibition rate of cell viability of TE-1 cells increased after QGS （20， 30， 40， 60， 80 mg·L-1） intervention for 12， 24， 36， 48， 60 h （P<0.05）， and the inhibition rate was time- and dose-dependent. Compared with the blank group， the TGF-β1 group showed lengthened cells with fibroblast phenotype. Compared with the TGF-β1 group， the TGF-β1 + QGS group showed shortened cells with normal morphology and epithelial phenotype. The cell morphology in the TGF-β1 + SB431542 group was similar to that of the TGF-β1 + QGS group. Compared with the blank group， the TGF-β1 group showed potentiated ability of cell migration and invasion （P<0.05）. Compared with the TGF-β1 group， the TGF-β1 + QGS group and the TGF-β1 + SB431542 group showed inhibited and weakened migration and invasion abilities of cells （P<0.05）. However， there was no significant difference in migration and invasion abilities between the TGF-β1 + QGS group and the TGF-β1 + SB431542 group. The mRNA expression levels of vimentin and Smad2 in the TGF-β1 group were higher （P<0.05）， and the mRNA expression levels of E-Cadherin and Smad7 were lower （P<0.05） than those in the blank group. Compared with the TGF-β1 group， the TGF-β1 + QGS group and the TGF-β1+ SB431542 group exhibited decreased expression levels of vimentin and Smad2 mRNA （P<0.05）， and elevated expression levels of E-Cadherin and Smad7 mRNA （P<0.05）. Compared with the blank group， the TGF-β1 group showed up-regulated protein expression levels of vimentin， p-Smad2/3， and Smad2/3 （P<0.05）， and reduced protein expression levels of E-Cadherin and Smad7 （P<0.05）. Compared with the TGF-β1 group， the TGF-β1 + QGS group and the TGF-β1 + SB431542 group displayed decreased protein expression levels of vimentin， p-Smad2/3， and Smad2/3 （P<0.05）， and increased protein expression levels of E-Cadherin and Smad7 （P<0.05）. ConclusionThe ethyl acetate extract of QGS inhibits the epithelial-mesenchymal transition （EMT） of TE-1 cells through the TGF-β1 pathway to reduce the migration and invasion of TE-1 cells.

Predictive value of serum thrombospondin-1 and transforming growth factor-β1 levels in preterm infants with bronchopulmonary dysplasia / 中国小儿急救医学

Objective:To study the early predictive values of serum thrombospondin-1(TSP-1)and transforming growth factor-β1(TGF-β1) for bronchopulmonary dysplasia(BPD)in preterm infants.Methods:From September 2020 to April 2022, preterm infants with gestational age<32 weeks and ≥28 weeks as well as birth weight<1 500 g admitted to neonatal intensive care unit within 2 hours after birth were enrolled in the study.The dynamic changes of serum TSP-1 and TGF-β1 levels in preterm infants were observed on 1st, 7th, 14th, and 28th day after birth.Preterm infants were divided into BPD group and non-BPD group according to the diagnostic criteria of BPD.Receiver operating characteristic(ROC) curve and area under curve(AUC)was used to analyze the predictive value of serum TSP-1 and TGF-β1 for preterm infants with BPD.Results:According to the diagnostic criteria of BPD, 38 cases were in the BPD group and 52 cases in the non-BPD group.There was no significant difference in gestational age, birth weight and gender between the two groups( P>0.05). The levels of TSP-1 and TGF-β1 in the serum of BPD group were gradually increased, which were significantly higher than those of non-BPD group on the 1st, 7th, 14th, and 28th day( P<0.001). ROC results showed that AUC of TSP-1, TGF-β1 and their combination for predicting BPD were 0.889(95% CI 0.819~0.959), 0.826(95% CI 0.743~0.910), and 0.923(95% CI 0.870~0.976), respectively.The sensitivity were 86.80%, 86.70%, 89.50%, and the specificity were 86.50%, 73.10%, 80.80%, respectively.Cutoff values of TSP-1 and TGF-β1 for predicting BPD were 44.50 μg/L and 6.13 μg/L, respectively. Conclusion:Combined detection of serum TSP-1 and TGF-β1 on the first day after birth has an early predictive value for BPD in preterm infants.

Effects of EW-7197 on the proliferation and migration of TGF-β1 induced human Tenon fibroblasts and its mechanism / 国际眼科杂志(Guoji Yanke Zazhi)

AIM: To investigate the effect of ALK5 inhibitor EW-7197 on the proliferation and migration of human Tenon fibroblasts(HTFs)induced by transforming growth factor-β1(TGF-β1)and its mechanism.METHODS: The cell proliferation rate was detected by MTS assay, and the optimal concentration and time of EW-7197 were explored. Then HTFs were divided into three groups: normal control group, TGF-β1 induced group and TGF-β1+EW-7197 group. Cell migration was observed by Transwell assay. The protein expression levels of Fibronectin, α-SMA, as well as the phosphorylated Smad2, Smad3(p-Smad2, p-Smad3)were measured by Western blot.RESULTS: MTS assay showed that the proliferation rate of cells treated with 6.0 μmol/L EW-7197 for 24h was the lowest(all P&#x003C;0.01). Transwell assay showed that the migrated number of HTFs in TGF-β1 induced group was 228.0±17.0/field, which was significantly more than that in normal control group(149.0±15.0/field)and TGF-β1+EW-7197 group(46.0±8.0/field; all P&#x003C;0.01). Western blot showed that the protein relative expression levels of Fibronectin, α-SMA and p-Smad2, p-Smad3 of HTFs in TGF-β1 induced group were significantly higher than that in normal control group and TGF-β1+EW-7197 group(all P&#x003C;0.001).CONCLUSION:EW-7197 can suppress the proliferation and migration of TGF-β1-induced HTFs through TGF-β/Smad signaling pathways.

LRG1 inhibits hepatic macrophage activation by enhancing TGF-β1 signaling to alleviate MAFLD in mice / 南方医科大学学报

OBJECTIVE@#To explore the effect of leucine-rich α-2-glycoprotein (LRG1) derived from hepatocytes on activation of hepatic M1 Kupffer cells.@*METHODS@#A metabolic dysfunction-associated fatty liver disease (MAFLD) model was established in BALB/c mice by high-fat diet (HFD) feeding for 16 weeks. Oleic acid was used to induce steatosis in primary cultures of mouse hepatocytes. The mRNA and protein expressions of LRG1 in mouse liver tissues and hepatocytes were detected by real-time PCR and Western blotting. Primary hepatic macrophages were stimulated with the conditioned medium (CM) from steatotic hepatocyte along with LRG1 or transforming growth factor-β1 (TGF-β1), or both for 24 h, and the expression levels of inducible nitric oxide synthase (iNOS) was detected with Western botting, and the mRNA expressions of iNOS, chemokine ligand 1 (CXCL-1) and interleukin-1β (IL-1β) were measured by RT-PCR. The MAFLD mice were injected with LRG1 (n=6), TGF-β1 (n=6), or both (n=6) through the caudal vein, and the live tissues were collected for HE staining and immumohistochemical detection of F4/80 expression; the mRNA expressions of iNOS, CXCL-1 and IL-1β in liver tissues were detected using RT-PCR.@*RESULTS@#The mRNA and protein expression levels of LRG1 were significantly downregulated in the liver tissues of MAFLD mice and steatotic hepatocytes (P < 0.05). Treatment of the hepatic macrophages with CM from steatosis hepatocytes significantly enhanced the mRNA expression levels of iNOS, CXCL-1 and IL-1β, and these changes were significantly inhibited by the combined treatment with TGF-β1 and LRG1 (P < 0.05). In MAFLD mice, injections with either LRG1 or TGF-β1 alone reduced hepatic lipid deposition and intrahepatic macrophage infiltration, and these effects were significantly enhanced by their combined treatment, which also more strongly inhibited the mRNA expression levels of iNOS, CXCL-1 and IL-1β (P < 0.05).@*CONCLUSION@#LRG1 inhibits hepatic macrophage infiltration by enhancing TGF-β1 signaling to alleviate fatty liver inflammation in MAFLD mice.

Suppression of NLRP3 inflammasome by ivermectin ameliorates bleomycin-induced pulmonary fibrosis / 浙江大学学报（英文版）（B辑：生物医学和生物技术）

Ivermectin is a US Food and Drug Administration (FDA)-approved antiparasitic agent with antiviral and anti-inflammatory properties. Although recent studies reported the possible anti-inflammatory activity of ivermectin in respiratory injuries, its potential therapeutic effect on pulmonary fibrosis (PF) has not been investigated. This study aimed to explore the ability of ivermectin (0.6 mg/kg) to alleviate bleomycin-induced biochemical derangements and histological changes in an experimental PF rat model. This can provide the means to validate the clinical utility of ivermectin as a treatment option for idiopathic PF. The results showed that ivermectin mitigated the bleomycin-evoked pulmonary injury, as manifested by the reduced infiltration of inflammatory cells, as well as decreased the inflammation and fibrosis scores. Intriguingly, ivermectin decreased collagen fiber deposition and suppressed transforming growth factor-‍β1 (TGF-‍β1) and fibronectin protein expression, highlighting its anti-fibrotic activity. This study revealed for the first time that ivermectin can suppress the nucleotide-binding oligomerization domain (NOD)‍-like receptor family pyrin domain-containing protein 3 (NLRP3) inflammasome, as manifested by the reduced gene expression of NLRP3 and the apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC), with a subsequent decline in the interleukin‍-‍1β (IL‍-‍1β) level. In addition, ivermectin inhibited the expression of intracellular nuclear factor-‍κB (NF‍-‍κB) and hypoxia‑inducible factor‑1α (HIF‍-‍1α) proteins along with lowering the oxidative stress and apoptotic markers. Altogether, this study revealed that ivermectin could ameliorate pulmonary inflammation and fibrosis induced by bleomycin. These beneficial effects were mediated, at least partly, via the downregulation of TGF-‍β1 and fibronectin, as well as the suppression of NLRP3 inflammasome through modulating the expression of HIF‑1α and NF-‍κB.

Effect of mycophenolate mofetil alleviates carbon tetrachloride-induced liver fibrosis in mice / 中南大学学报(医学版)

OBJECTIVES@#Hepatic fibrosis is a serious pathological consequence of chronic liver disease. Mycophenolate mofetil (MMF) is a commonly used immunosuppressant after organ transplant. However, the relationship between MMF and hepatic fibrosis remains unclear. This study aims to explore the effect of MMF on hepatic fibrosis in mice and the potential mechanism.@*METHODS@#A total of 24 mice (male, 8-week old, C57BL/6) were randomly divided into a control group, a MMF group, a carbon tetrachloride (CCl4) group and a CCl4+MMF group (n=6 in each group). After the mice were sacrificed, the serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels were detected. The liver tissues were taken up for Masson staining and collagen I (COL1) immunohistochemistry. The levels of transforming growth factor-β1 (TGF-β1) and α-smooth muscle actin (α-SMA) were detected by Western blotting. Finally, the levels of mRNA for TGF-β1, α-SMA, and COL1 were detected using real-time PCR.@*RESULTS@#Compared with the CCl4 group, the ALT and AST levels were lower (both P<0.05), the degree of liver fibrosis was alleviated, and the deposition of COL1 in the liver was significantly decreased (P<0.01) in the CCl4+MMF group. Compared with the CCl4 group, the protein expression levels of TGF-β1 and α-SMA were significantly decreased (both P<0.05) and the relative expression levels of TGF-β1, α-SMA and COL1 mRNA in the liver were significantly decreased (all P<0.05) in the CCl4+MMF.@*CONCLUSIONS@#MMF could reduce CCl4-induced hepatic fibrosis, which might be related to the inhibition of TGF-β1. This study is expected to provide a target for the treatment of hepatic fibrosis.

Association between single nucleotide polymorphisms of TGFβ2 gene and Keshan disease in Shaanxi Province / 中华地方病学杂志

Objective:To investigate the relationship between single nucleotide polymorphisms of transforming growth factor-β2 (TGFβ2) gene and Keshan disease (KD) in Han population of Shaanxi Province.Methods:KD region in Huangling County, Yan'an City, Shaanxi Province was selected as the investigation site in this study. Using the method of cluster random sampling, 52 families with KD in 6 administrative villages in Huangling County (Duanjiawan Village, Taoqu Village, Yaoping Village, Jianzhuang Village, Anjiao Village in Yaoping Town, and Houziping Village in Diantou Town) were selected for epidemiological investigation. According to the "Diagnosis of Keshan Disease" (WS/T 210-2011), 285 subjects were identified, including 79 patients with KD (case group) and 206 healthy controls (control group). Genomic DNA was extracted from the peripheral venous blood. The polymorphism of genetic variation of TGFβ2 gene rs6658835 was genotyped by matrix-assisted laser desorption/ionization-time of flight (MALDI-TOF). Chi-square (χ 2) test and t-test were used to analyze the baseline data, and binary logistic regression model was used to analyze the influencing factors of KD, all samples were tested for Hardy-Weinberg equilibrium using goodness-of-fit χ 2 test, differences in genotype and allele frequencies between case and control groups were compared by χ 2 test, and logistic regression analysis was used to compare the genotype frequencies between two groups after adjusting for confounding factors. Results:Epidemiological investigation showed that there were significant differences in age and heart murmur between case group and control group ( t = 7.03, χ 2 = 9.66, P < 0.05). The analysis of binary logistic regression model showed that the influence of age on KD was statistically significant (χ 2 = 20.72, P < 0.001). The gene frequency distribution of TGFβ2 gene rs6658835 in case group and control group conformed to the Hardy-Weinberg equilibrium (χ 2 = 0.02, P = 0.900). Correlation analysis results: the difference of genotype frequency of TGFβ2 gene rs6658835 in case group (GG, GA, AA: 6.3%, 38.0%, 55.7%) and control group (GG, GA, AA: 10.7%, 43.7%, 45.6%) was not statistically significant (χ 2 = 2.78, P = 0.249). After adjustment by age, the difference of genotype frequency and dominant model of TGFβ2 gene rs6658835 in case group and control group was statistically significant (χ 2adj = 5.43, 4.86, P < 0.05), the difference of recessive model of TGFβ2 gene rs6658835 in case group and control group was not statistically significant (χ 2adj = 2.12, P = 0.145). Conclusion:TGFβ2 gene rs6658835 is associated with KD in Han population of Shaanxi Province.

Effect of Yifei Huatan Decoction on Relieving Airway Hyperviscosity in Asthmatic Rats with Spleen Deficiency Syndrome and Its Mechanism / 中国实验方剂学杂志

ObjectiveTo explore the effect of Yifei Huatan decoction on relieving airway hyperviscosity in asthmatic rats with spleen deficiency syndrome and its mechanism. MethodFifty-five SPF level SD rats at 8-9 week of age were used to induce asthma with spleen deficiency syndrome by animal modeling of traditional Chinese medicine combined with asthma of western medicine. After successful modeling， the rats were divided into model group， dexamethasone group， low， medium， and high-dose Yifei Huatan decoction groups by random number table method， and 11 clean SD rats at 8-9 week of age were recorded as a normal group. Rats in the dexamethasone group were given 0.087 5 mg kg-1 dexamethasone acetate by gavage. Rats in the low， medium， and high-dose Yifei Huatan decoction groups were given 0.8， 1.6， 3.2 g kg-1 Yifei Huatan decoction liquid extract by gavage， respectively. Rats in the model group and the normal group were given 10 mL kg-1 distilled water. The medicine were given once per day for 8 w， and the general situation of each group was observed. The levels of interleukin-4 （IL-4）， IL-13， and interferon-γ （IFN-γ） in bronchoalveolar lavage fluid （BALF） were determined by enzyme-linked immunosorbent assay （ELISA）. The pathological changes in lung tissues of rats were observed by hematoxylin-eosin （HE） staining. Alcian blue-periodic acid Schiff （AB-PAS） staining was used to detect the hyperplasia of airway goblet cells and mucus secretion in rats. The mRNA expressions of transforming growth factor-β1 （TGF-β1）， Smad2， Smad3， mucin 5AC （MUC5AC）， and mucin 5B （MUC5B） in the lung tissues of rats were detected by real-time quantitative polymerase chain reaction （Real-time PCR）. The protein expressions of TGF-β1， Smad2， Smad3， MUC5AC， and MUC5B in the lung tissues of rats were detected by Western blot. ResultAs compared with the normal group， rats in the model group showed the symptoms of spleen deficiency syndrome， such as decreased body weight， muscle emaciation， decreased food intake， increased water intake， increased anal temperature， tiredness， and decreased swimming endurance， accompanied by dyspnea symptoms such as wheezing and nodding. As compared with the normal group， IL-4 and IL-13 levels in the BALF of the model group were significantly increased （P<0.01）， while the IFN-γ level was significantly decreased （P<0.01）. In the model group， a large number of inflammatory cells were observed in the mucosa and submucosa of the airway， and the smooth muscle of the trachea was significantly thickened. The hyperplasia， deformation， and exfoliation of various epithelial cells were observed in the mucosa， and the pathological scores of lung tissue increased significantly （P<0.01） in the model group. A large number of goblet cells were observed in the airway with the formation of plenty of mucous thrombus in the model group， and the positive relative staining area of airway， and mRNA and protein expressions of TGF-β1， Smad2， Smad3， MUC5AC， and MUC5B were significantly increased （P<0.01）. As compared with the model group， IL-4 and IL-13 levels in BALF of the dexamethasone group and the Yifei Huatan decoction groups decreased， while the IFN-γ level increased. The inflammatory cell infiltration in airway mucosa and submucosa， the thickening of tracheal smooth muscle， the hyperplasia， deformation， and exfoliation of epithelial cells in mucosa were gradually decreased， and the pathological scores of lung tissues decreased significantly （P<0.01） in the dexamethasone group and the Yifei Huatan decoction groups. Goblet cell proliferation gradually decreased， and the positive relative staining area of airway， and mRNA and protein relative expressions of TGF-β1， Smad2， Smad3， MUC5AC， and MUC5B decreased with statistically significant difference （P<0.05， P<0.01）. There was no significant difference in the above indexes in the dexamethasone group and the Yifei Huatan decoction low-dose group. The above indexes were dose-dependent in the low， medium， and high-dose Yifei Huatan decoction groups. ConclusionYifei Huatan decoction reduces airway hyperviscosity in asthmatic rats with spleen deficiency syndrome， which may be related to the inhibition of TGF-β1， Smad2， Smad3， MUC5AC， and MUC5B expressions， down-regulation of IL-4 and IL-13 levels， and up-regulation of IFN-γ level.

Dihydromyricetin mediates epithelial mesenchymal transformation and regulates the proliferation and apoptosis of esophageal squamous cell carcinoma cells / 中华肿瘤杂志

Objective: To study the effects of dihydromyricetin (DMY) on the proliferation, apoptosis and epithelial mesenchymal transition (EMT) of esophageal squamous cell carcinoma (ESCC) cell KYSE150 and KYSE410. Methods: KYSE150 and KYSE410 cells were treated with different concentrations of DMY (0, 25, 50, 100, 150, 200 μmol/L) for 24 hours. The median inhibition concentration (IC50) values of KYSE150 and KYSE410 were detected by cell counting kit-8 (CCK-8) method. Then 0.5‰ dimethyl sulfoxide (DMSO) was used as control group, dihydromyricetin (DMY), dihydromyricetin and transforming growth factor-β1 (DMY+ TGF-β1), transforming growth factor-β1 (TGF-β1) were used as experimental group. Cell proliferation and apoptosis rates were measured by clonal formation and flow cytometry. Transwell invasion and wound healing assay were used to detect cell invasion and migration. The protein expression levels of Caspase-3, Caspase-9, Bcl-2, Bax, Smad2/3, phosphorylation-Smad2/3 (p-Smad2/3) and Vimentin were detected by western blot. Results: The IC50 values of DMY on KYSE410 and KYSE150 cells were 100.51 and 101.27 μmol/L. The clone formation numbers of KYSE150 and KYSE410 in DMY group [(0.53±0.03) and (0.31±0.03)] were lower than those in DMSO group [(1.00±0.10) and (1.00±0.05), P<0.05]. The apoptosis rates of KYSE150 and KYSE410 cells in DMY group [(1.84±0.22)% and (2.80±0.07)%] were higher than those in DMSO group [(1.00±0.18)% and (1.00±0.07)%, P<0.05]. The invasion numbers of KYSE150 and KYSE410 cells in DMY group [(0.42±0.03) and (0.29±0.05)] were lower than those in DMSO group [(1.00±0.08) and (1.00±0.05), P<0.05]. The migration rates of KYSE150 and KYSE410 cells in DMY group [(0.65±0.14)% and (0.40±0.17)%] were lower than those in DMSO group [(1.00±0.10)% and (1.00±0.08)%, P<0.05]. The clone formation numbers of KYSE150 and KYSE410 in TGF-β1 group [(1.01±0.08) and (0.99±0.25)] were higher than those in DMY+ TGF-β1 group [(0.73±0.10) and (0.58±0.05), P<0.05]. The apoptosis rates of KYSE150 and KYSE410 cells in TGF-β1 group [(0.81±0.14)% and (1.18±0.10)%] were lower than those in DMY+ TGF-β1 group [(1.38±0.22)% and (1.85±0.04)%, P<0.05]. The invasion numbers of KYSE150 and KYSE410 cells in TGF-β1 group [(1.19±0.11) and (1.39±0.11)] were higher than those in DMY+ TGF-β1 group [(0.93±0.09) and (0.93±0.05), P<0.05]. The migration rates of KYSE150 and KYSE410 cells in TGF-β1 group [(1.87±0.19)% and (1.32±0.04)%] were higher than those in DMY+ TGF-β1 group [(0.86±0.16)% and (0.77±0.12)%, P<0.05]. The protein expression levels of Bax, Caspase-3 and Caspase-9 in KYSE150 and KYSE410 cells in DMY group were higher than those in DMSO group, while the protein expression level of Bcl-2 was lower than that in DMSO group (P<0.05). The protein expression levels of p-Smad2/3, Smad2/3 and Vimentin in KYSE150 and KYSE410 cells in DMY group were lower than those in DMSO group (P<0.05). The protein expression levels of Bax, Caspase-3 and Caspase-9 in KYSE150 and KYSE410 cells in TGF-β1 group were lower than those in DMY+ TGF-β1 group, and the protein expression level of Bcl-2 was higher than that in DMY+ TGF-β1 group (P<0.05). The protein expression levels of Bax, Caspase-3 and Caspase-9 in KYSE150 and KYSE410 cells in DMY+ TGF-β1 group were lower than those in DMY group, and the protein expression level of Bcl-2 was higher than that in DMY group (P<0.05). The protein expression levels of p-Smad2/3, Smad2/3 and Vimentin in KYSE150 and KYSE410 cells in TGF-β1 group were higher than those in DMY+ TGF-β1 group (P<0.05). Conclusion: DMY can inhibit the proliferation and EMT of ESCC mediated by TGF-β1 and promote cell apoptosis.

Expression of lncRNA TGFB2-AS1 in the placenta of preeclampsia and its relationship with placental spiral artery recasting / 中华内分泌外科杂志

Objective:To investigate the relationship between the expression level of long non-coding RNA transforming growth factor β2-antisense RNA1 (lncRNA TGFB2-AS1) and placental spiral artery recasting in the placenta of preeclampsia.Methods:A total of 108 pregnant women with severe preeclampsia who were hospitalized in Zaozhuang Maternal and Child Health Hospital and delivered by cesarean section from Oct. 2019 to Jun. 2021 were selected as the research objects, and they were divided into the late-onset preeclampsia group (late-onset severe preeclampsia pregnant women, 56 cases) and early-onset preeclampsia group (early-onset severe preeclampsia pregnant women, 52 cases) ; at the same time, 58 normal pregnant women were selected as the normal pregnancy group. The general data of pregnant women were collected, such as age, systolic blood pressure and diastolic blood pressure. Real-time fluorescent quantitative PCR (qRT-PCR) method was used to detect the expression level of lncRNA TGFB2-AS1 in placental tissues, a scanning electron microscope was used to measure the lumen area and wall thickness of spiral arteries. Pearson correlation analysis method was used to analyze the correlation between the level of lncRNA TGFB2-AS1 in the placenta tissue and the thickness of the spiral artery wall and the area of the lumen of pregnant women with early-onset and late-onset severe preeclampsia.Results:The tube wall thickness [ (119.69±8.31) μm], systolic blood pressure [ (162.86±4.94) mmHg], diastolic blood pressure [ (103.09±2.35) mmHg], and 24-hour urine protein [ (2.17±0.31) g/24 h] in the early preeclampsia group were higher than those in the late preeclampsia group [ (101.04±5.78) μm, (146.95±6.43) mmHg, (92.13±4.74) mmHg, (1.62±0.23) g/24 h] and the normal pregnancy group [ (99.82±5.56) μm, (116.42±9.31) mmHg, (74.25±6.74) mmHg, (0.06±0.02) g/24 h], the placental tissue lncRNA TGFB2-AS1 level (0.62±0.16), lumen area [ (133.74±20.16) μm 2], gestational week of delivery [ (32.15±1.74) weeks], weight of the newborns [ (2.25±0.26) g] were lower than those in the late-onset preeclampsia group [ (0.99±0.21), (185.49±22.75) μm 2, (36.14±1.59) weeks, (3.37±0.32) g] and the normal pregnancy group [ (1.02±0.23), (186.42±23.71) μm 2, (38.19±1.56) weeks, (3.42±0.37) g] ( P<0.05). The systolic blood pressure, diastolic blood pressure, and 24-hour urine protein in the late preeclampsia group were higher than those in the normal pregnancy group, gestational week of delivery was lower than the normal pregnancy group ( P<0.05). Placental tissue lncRNA TGFB2-AS1 of pregnant women with early-onset severe preeclampsia was positively correlated with the lumen area, and negatively correlated with the thickness of the tube wall ( P<0.05). There was no correlation between lncRNA TGFB2-AS1 and the lumen area and wall thickness in the placental tissue of pregnant women with late-onset severe preeclampsia ( P>0.05) . Conclusion:The lncRNA TGFB2-AS1 expression in the placenta tissue of pregnant women with early-onset severe preeclampsia is abnormally low, which may be related to the insufficient recasting of the placental spiral artery.

Research progress of TGF-β in the formation of epiretinal membrane / 国际眼科杂志(Guoji Yanke Zazhi)

Epiretinal membrane(ERM)is a retinal disease characterized by a fibrocell membranes that can develop on the inner surface of the retina. The existing clinical guidelines and literature have reached a consensus on the diagnosis and treatment of ERM, but the explanation of their mechanism is still controversial. Transforming growth factor-β(TGF-β)is a highly pleiotropic cytokine that plays an important role in wound healing, angiogenesis, immune regulation, cancer, inflammation and fibrosis diseases. Studies have increasingly shown that ERM is a kind of pathological changes in fibrosis that caused by the posterior vitreous detachment(PVD)and lead to the retinal inflammatory damage and epithelial to mesenchymal transition(EMT)of retinal pigment epithelial cells. A variety of cytokines regulate TGF-β-mediated EMT process by participating in the non-classical TGF-β-Snail pathway and the classical TGF-β-Smad pathway. At present, some drugs targeting cytokines related to the above pathway have entered the development stage, which is of great significance to provide new ideas for clinical treatment and prevention of ERM. This review reviews the progress of TGF-β related cytokines in ERM formation.

Effects of foraging exercise on behavior and the expression of 5-hydroxytryptamine 1A and transforming growth factor β1 in the frontal lobes of rats modelling post-stroke depression / 中华物理医学与康复杂志

Objective:To explore the effect of foraging exercise (FE) on the behavior of rats with post-stroke depression (PSD) and the expression of 5-Hydroxytryptamine 1A (5-HT1A) receptor and transforming growth factor β1 (TGF-β1) in their frontal lobes.Methods:Thirty-six healthy male Sprague-Dawley rats were randomly divided into an ischemia-reperfusion (I/R) group, a PSD group and a PSD+ FE (FE) group, each of 12. The right middle cerebral artery of each was occluded using the thread occlusion method with 1.5h of ischemia. In the PSD and FE groups, mild stimulation was administered at unpredictable intervals over 3 weeks beginning 1 week after the successful modeling. The rats in the I/R group were raised in a group. Those in the PSD group were raised in individual cages. Those in the FE group were raised in a single cage and foraged freely for a total of 4 weeks. Four and eight weeks after the modeling, the body weights were measured, and the open field, social interaction (SIT) and sugar preference tests were administered to all of the groups. Four weeks later, all of the rats were sacrificed and their brains were sliced and stained. The expression of 5-HT1A receptor and TGF-β1 in the frontal lobe was detected using western blotting.Results:One week after modeling, there was no significant difference in average body weight or the average behavioral scores among the three groups. After four weeks the PSD and FE groups had significantly lower average body weight than the I/R group, fewer counts of rearing and grid crossing, longer SIT latency, less interaction time and lower average sugar preference (all significant differences). After eight weeks the average body weight had increased in each group. SIT latency had shortened and interaction time had increased in the FE group, and the rearing and grid crossing counts and sugar preference had increased in the PSD and FE groups. At that point the FE group had significantly greater average body weight than the PSD group, more counts of rearing and grid crossing, shorter SIT latency, increased interaction time, and greater sugar preference. The ratio of residual brain volume in the right hemisphere of the PSD and FE groups was significantly lower on average than in the I/R group. However, there was no significant difference in the right residual brain volume ratio between the PSD and FE groups. Staining revealed that the pathological changes in the frontal lobes of the FE group had been significantly relieved compared with the PSD group. Eight weeks after the operation the increases in average 5-HT 1A receptor and TGF-β1 levels in the FE group were significantly greater than in the PSD group.Conclusion:Foraging can relieve the depressive symptoms of rats modeling post-stoke depression. The mechanism may be related to alleviating the pathological damage and increasing the expression of 5-HT1AR and TGF-β1 in the frontal lobe. Early chronic stress may increase the volume of cerebral infarction, at least in rats.

The effects of extracorporeal shock wave treatment on the expression of TGF-β1 and IL-1β in the cartilage of an osteaoarthritic knee / 中华物理医学与康复杂志

Objective:To seek any effect of extracorporeal shockwave treatment on the expression of transforming growth factor-β1 (TGF-β1) and interleukin-1β (IL-1β) in the cartilage tissue of rabbits with knee osteoarthritis (OA), and its therapeutic mechanism.Methods:Fifty female New Zealand rabbits were randomly divided into a normal control group, a model group, and three shockwave groups A, B and C, each of 10. Except for the normal control group, an OA model was established in the other groups using Hulth′s method. The shockwave groups were given 2000 shocks in each weekly session over 4 weeks. The energy flow density in group A was 0.05mJ/mm 2; in B it was 0.11mJ/mm 2 and in C 0.22mJ/mm 2. The normal control and model groups were not shocked. All the rabbits were then sacrificed and their right knee cartilage tissue was sampled to observe any pathological changes and assign improved Mankin scores. Immunohistochemistry was used to count the number of TGF-β1 and IL-1β-positive cells in the cartilage. Western blotting and real-time fluorescence quantitative polymerase chain reactions were employed to determine the protein and mRNA expression of IL-1β and TGF-β1. Results:Compared with the normal group, degeneration of articular cartilage was observed in the model group. The average Mankin′s score of the model group was significantly higher than that of the normal control group. The average expression of TGF-β1 and IL-1β protein and mRNA in the model group had increased significantly compared with the normal control group. The average Mankin′s scores of the shock wave groups were all significantly lower than the model group′s average. Group C′s average expression levels of TGF-β1 and IL-1β protein and mRNA were significantly lower than the model group′s averages.Conclusions:Extracorporeal shockwave therapy can reduce the expression of TGF-β1 and IL-1β in the cartilage of an arthritic knee, at least in rabbits. Its therapeutic effect is positively correlated with the density of the energy flow, suggesting that shock waves may reduce the expression of inflammatory factor IL-1β by regulating the expression of TGF-β1. They should be applied in the prevention and treatment of osteoarthritis.