The effects of prestrain and annealing temperature on phase transformation temperatures in Fel4Mn5Si8Cr4Ni shape memory alloy have been studied. The results showed that when the annealing temperature was 673 K, both t...The effects of prestrain and annealing temperature on phase transformation temperatures in Fel4Mn5Si8Cr4Ni shape memory alloy have been studied. The results showed that when the annealing temperature was 673 K, both the At and the Ms temperatures increased appreciably as the prestrain increased, the As temperature increased slightly with increasing prestrain; the resistivity difference at 303 K between the heating and cooling curve also increased with increasing prestrain, which agreed with the recovery strain. The shape memory effect in Fe-Mn-Si-Cr-Ni shape memory alloy is caused by the stress-induced γ→ε martensite transformation and its reverse transformation. When the prestrain was 10%, the Ms temperature decreased remarkably as the annealing temperature increased.展开更多
Objective Despite the fact that the bioavailability of trace metals indicated by their speciation has been an indispensable parameter in the assessment and treatment of the environmental pollution of trace metals, ma...Objective Despite the fact that the bioavailability of trace metals indicated by their speciation has been an indispensable parameter in the assessment and treatment of the environmental pollution of trace metals, many studies have suggested that the bioavailability of trace metals may change according to the conditions of the environment, and the speciation of trace metals can also transform between some fractions. These transformations are related with these factors such as the compositions, microorganism, time, and other physical-chemical conditions of the system. Our work aims to systematically investigate and probe the factors to affect the transformation aside from analysis at certain time-place. The results of these understanding and investigations can be used for reasonably determining the allocation of financial and technical resources in natural and engineered processes, with bringing about inspirations from the evolution of the speciation of the trace metals on environmental impacts.展开更多
BACKGROUND The effects of T-cell immunoglobulin mucin molecule-3(Tim-3),transforming growth factor β(TGF-β),and chemokine-12(CXCL12) expression on the prognosis of patients with diffuse large B-cell lymphoma(DLBCL) ...BACKGROUND The effects of T-cell immunoglobulin mucin molecule-3(Tim-3),transforming growth factor β(TGF-β),and chemokine-12(CXCL12) expression on the prognosis of patients with diffuse large B-cell lymphoma(DLBCL) have not been elucidated.AIM To examine the correlation between Tim-3,TGF-β and CXCL12 expression and DLBCL prognosis.METHODS Lymph node tissues of 97 patients with DLBCL and 93 normal-response hyperplastic lymph node tissues treated from January 2017 to May 2019 were selected as the DLBCL and control groups,respectively.The expression of Tim-3,TGF-β,and CXCL12 was detected immunohistochemically.Patients were followed up for 3 years,and progression-free survival was recorded.Cox mult-ifactorial analysis was performed to analyze the risk factors for poor prognosis.RESULTS The positive expression rates of Tim-3,TGF-β,and CXCL12 were higher in DLBCL tissues than in non-cancerous(control) tissues(P < 0.05).One-year postsurgery,the positive expression rates of Tim-3,TGF-β,and CXCL12 were higher in patients with effective treatment than in those with ineffective treatment(P < 0.05).The 3-year progression-free survival of 97 patients with DLBCL was 67.01%(65/97).Univariate analysis revealed that clinical stage,bone marrow infiltration,International Prognostic Index(IPI) score,Tim-3 positivity,TGF-β positivity,and CXCL12 positivity were associated with poor prognosis(P < 0.05).Multivariate Cox regression analysis demonstrated that clinical stage Ⅲ–Ⅳ,bone marrow infiltration,mediate-to-high-risk IPI scores,Tim-3 positivity,TGF-β positivity,and CXCL12 positivity were independent risk factors affecting prognosis(P < 0.05).CONCLUSION DLBCL tissues exhibit high positive expression of Tim-3,TGF-β,and CXCL12,and a high expression of all three indicates a poor prognosis.展开更多
Dualcolor systems were used to reduce the collinearity of multicomponent spectra, which is described by the angles between spectra vectors. Combined with iterative target transformation factor analysis, single rare ea...Dualcolor systems were used to reduce the collinearity of multicomponent spectra, which is described by the angles between spectra vectors. Combined with iterative target transformation factor analysis, single rare earth element was determined in its mixture. The calculated results show that the average angle between rare earth spectra in one color system(trichloroarsenazorare earths, pH 34) is 45, and that in two color systems(trichloroarsenazorare earths, pH 34, 14) is 215. This technique makes it easy to select the real number of the components in mixtures, and the determination results show dualcolor system method is an effective technique in rare earth mixture analysis.展开更多
OBJECTIVES:To investigate the effect of Bushen Tongluo recipe(BSTLR, 补肾通络方) on rats with diabetic kidney disease(DKD) and to explore the underlying mechanism of action. METHODS:The rat model of DKD was establishe...OBJECTIVES:To investigate the effect of Bushen Tongluo recipe(BSTLR, 补肾通络方) on rats with diabetic kidney disease(DKD) and to explore the underlying mechanism of action. METHODS:The rat model of DKD was established, and rats were treated with different doses of BSTLR. Body weight and the levels of urinary protein, α1-microglobulin, glucose, blood urea nitrogen, creatinine, Cystatin C, superoxide dismutase, malondialdehyde, and catalase were analyzed biochemically or by enzyme-linked immunosorbent assay. The pathological damage to renal tissues was assessed by hematoxylin-eosin staining. Immunohistochemical staining was carried out to detect the expression levels of fibronectin, E-cadherin, α-smooth muscle actin, laminin, vimentin, collagen type Ⅳ in kidney tissues. Western blot analysis was conducted to analyze the expression levels of Nephrin, Desmin, Podocin, transforming growth factor-β1, mothers against decapentaplegic homolog 3(Smad3), Notch1, jagged, hairy and enhancer of split 1(Hes1) in kidney tissues, and the expression levels of maternally expressed gene 3(MEG3) and mi R-145 were measured by quantitative reverse transcription-polymerase chain reaction. Moreover, dual-luciferase reporter assay was employed to verify the binding of mi R-145 to MEG3. RESULTS:BSTLR increased the body weight of DKD rats, effectively ameliorated the renal function and pathological injury in DKD, regulated the balance of renal oxidative stress, inhibited the TGF/Notch signaling pathway, and affected the variations in the lnc RNA MEG3/mi R-145 axis. CONCLUSION:BSTLR improved oxidative stress homeostasis, inhibited the TGF/Notch signaling pathway, and regulated the lnc RNA MEG3/mi R-145 axis, effectively delaying the progression of DKD.展开更多
OBJECTIVE:To explore the role and mechanism of Qufeng Jiejing(祛风解痉,QFJJ)formula in the asthma progression.METHODS:The Bagg Albino/c mice treated with Ovalbumin and AL(OH)3,and airway smooth muscle cells(ASMCs)trea...OBJECTIVE:To explore the role and mechanism of Qufeng Jiejing(祛风解痉,QFJJ)formula in the asthma progression.METHODS:The Bagg Albino/c mice treated with Ovalbumin and AL(OH)3,and airway smooth muscle cells(ASMCs)treated with platelet-derived growth factor(PDGF)-BB to establish a asthma model in vivo and in vitro.The cell morphology was observed with microscope and immunofluorescence staining.The cell viability was assessed with methyl thiazolyl tetrazolium assay.The tumor necrosis factor-αlpha(TNF-α),interleukin-1beta(IL-1β),laminin,fibronectin and collagen IV levels in the ASMCs were detected with corresponding enzyme linked immunosorbent assay kits.Transwell and wound healing assays were conducted to test the cell migration.The TGF-β1,Smad2 and Smad3 levels were measured with Western blot.RESULTS:We found that QFJJ formula treatment dramatically decreased the cell viability,TNF-α,IL-1β,laminin,fibronectin and collagen IV levels in the PDGFBB stimulated ASMCs.Additionally,the protein levels of TGF-β1,Smad2 and Smad3 in the PDGF-BB stimulated ASMCs were prominently depleted after QFJJ formula treatment.Besides,SRI treatment neutralized the role of QFJJ formula in the PDGF-BB stimulated ASMCs.CONCLUSION:QFJJ formula effectively relieved the asthma progression through ameliorate the ASMCs function,which was achieved through suppressing the TGF-β1/Smads signaling pathway.展开更多
AIM:To determine whether paeonol(Pae),a naturally occurring phenolic compound,can serve as an effective pharmacological inhibitor of posterior capsular opacification(PCO).METHODS:A rat model of cataract surgery—induc...AIM:To determine whether paeonol(Pae),a naturally occurring phenolic compound,can serve as an effective pharmacological inhibitor of posterior capsular opacification(PCO).METHODS:A rat model of cataract surgery—induced PCO was established,and Pae was administered via anterior chamber injection to evaluate its preventive effect on capsular opacification and fibrotic remodeling.Histological and immunohistochemical analyses were performed to assess epithelial-mesenchymal transition(EMT)—related changes in lens epithelial cells(LECs).Ex vivo lens capsule cultures were employed to examine the expression of Vimentin and Zonula Occludens-1(ZO-1)by immunofluorescence and immunohistochemistry.In the human LEC line SRA01/04,EMT marker expression at both mRNA and protein levels was analyzed following transforming growth factor beta 2(TGF-β2)stimulation,with Pae treatment.Western blotting and immunofluorescence were used to investigate the effect of Pae on TGF-β/Smad signaling and AMP-activated protein kinase(AMPK)activation.Molecular docking was performed to predict Pae–AMPK binding,and rescue experiments with AMPK inhibition were conducted to validate the mechanistic pathway.RESULTS:Pae significantly reduced capsular opacification and fibrotic remodeling in the rat PCO model compared with controls.In LECs,Pae markedly suppressed TGF-β2–induced EMT,evidenced by decreased expression of mesenchymal markers,such as Vimentin,Fibronectin,Collagen 1A1,α-SMA and preserved epithelial junctional protein ZO-1.Mechanistically,Pae was predicted to directly interact with the catalytic pocket of AMPK,which was experimentally confirmed by enhanced AMPK phosphorylation and nuclear translocation(P<0.05).This activation disrupted canonical TGF-β/Smad signaling,leading to suppression of EMT.Rescue experiments using AMPK inhibition abrogated the anti-EMT effect of Pae,further validating the AMPK-dependent mechanism.CONCLUSION:Pae exerts a potent inhibitory effect on PCO formation by blocking EMT of LECs through direct activation of AMPK and subsequent disruption of TGF-β/Smad signaling.展开更多
The transforming growth factor-β(TGF-β)and bone morphogenetic protein(BMP)signaling pathways are pivotal regulators of cellular processes,playing indispensable roles in embryogenesis,postnatal development,and tissue...The transforming growth factor-β(TGF-β)and bone morphogenetic protein(BMP)signaling pathways are pivotal regulators of cellular processes,playing indispensable roles in embryogenesis,postnatal development,and tissue homeostasis.These pathways are particularly critical within the skeletal system,as they coordinate osteogenesis,chondrogenesis,and bone remodeling through intricate molecular mechanisms.TGF-β/BMP signaling is primarily transduced via canonical Smad-dependent pathways(e.g.,ligands,receptors,and intracellular Smads)and the non-canonical Smad-independent(e.g.,p38 mitogen-activated protein kinase,MAPK)cascade.Both pathways converge on master transcriptional regulators,including Runx2 and Osterix,and their precise coordination is indispensable for skeletal development,maintenance,and repair.The dysregulation of TGF-β/BMP signaling contributes to a spectrum of skeletal dysplasia and bone pathologies.Advances in molecular genetics,particularly gene-targeting strategies and transgenic mouse models,have deepened our understanding of the spatiotemporal control of TGF-β/BMP signaling in bone and cartilage development.Moreover,emerging research underscores extensive crosstalk between TGF-β/BMP and other critical pathways,such as Wnt/β-catenin,mitogen-activated protein kinase(MAPK),parathyroid hormone(PTH)/PTH-related protein(PTHrP),fibroblast growth factors(FGF),Hedgehog,Notch,insulin-like growth factors(IGF)/insulin-like growth factors receptor(IGFR),Mammalian target of rapamycin(mTOR),and autophagy,forming an integrated regulatory network that ensures skeletal integrity.Our review synthesizes the current knowledge on the molecular components,regulatory mechanisms,and functional integration of TGF-β/BMP signaling in skeletal biology,with an emphasis on its roles in development,regeneration,and disease.By elucidating the molecular underpinnings of TGF-β/BMP pathways and their contextual interactions,we aim to highlight translational opportunities and novel therapeutic strategies for treating skeletal disorders.展开更多
Aim: To investigate the stage-specific localization of transforming growth factor (TGF) β1 and β3 during spermatogenesis in adult human testis. Methods: The localization of TGFβ1 and β3 was investigated by immunoh...Aim: To investigate the stage-specific localization of transforming growth factor (TGF) β1 and β3 during spermatogenesis in adult human testis. Methods: The localization of TGFβ1 and β3 was investigated by immunohis tochemical staining method employing specific polyclonal antibodies. Results: Both TGFβ1 and β3 and their recep tors were preponderant in the Leydig celis. TGFβ1 could not be detected in the seminiferous tubules. TGFβ3 and TGFβ-Receptor (R) I were mainly seen in the elongated spermatids, while TGFβ-RⅡ in the pachytene spermatocytes and weak in the spermatogonia, spermatids and Sertoli celis. Only TGFβ-RⅡ was detected in the Sertoli celis. TGFβ3, TGFβ-RⅠ and TGFβ-RⅡ showed a staining pattern dependent upon the stages of the seminiferous epithelium cycle. Conclusion: TGFβ isoforms and their receptors are present in the somatic and germ celis of the adult human testis, suggesting their involvement in the regulation of spermatogenesis.展开更多
AIM： To investigate the effects of transforming growth factor β1 （TGF-β1） on the differentiation of colonic lamina propria fibroblasts （CLPF） into myofibroblasts in vitro.METHODS： Primary CLPF cultures were in...AIM： To investigate the effects of transforming growth factor β1 （TGF-β1） on the differentiation of colonic lamina propria fibroblasts （CLPF） into myofibroblasts in vitro.METHODS： Primary CLPF cultures were incubated with TGF-β1 and analyzed for production of m-smooth muscle actin （α-SMA）, fibronectin （FN） and FN isoforms. Migration assays were performed in a modified 48-well Boyden chamber. Levels of total and phosphorylated focal adhesion kinase （FAK） in CLPF were analyzed after induction of migration.did not change α-SMA levels, while TGF-β1 treatment for 6 d significantly increased α-SIVlA production. Short term incubation （6 h） with TGF-β1 enhanced CLPF migration, while long term treatment （6 d） of CLPF with TGF-β1 reduced migration to 15%-37% compared to untreated cells. FN and FN isoform mRNA expression were increased after short term incubation with TGF-β1 （2 d） in contrast to long term incubation with TGF-β1 for 6 d. After induction of migration, TGF-β1-preincubated CLPF showed higher amounts of FN and its isoforms and lower levels of total and phosphorylated FAK than untreated cells.CONCLUSION： Long term incubation of CLPF with TGF-β1 induced differentiation into myofibroblasts with enhanced α-SMA, reduced migratory potential and FAK phosphorylation, and increased FN production. In contrast, short term contact （6 h） of fibroblasts with TGF-β1 induced a dose-dependent increase of cell migration and FAK phosphorylation without induction of α-SMA production.展开更多
AIM: To investigate the expression of the transforming growth factor beta 1(TGF-beta 1) mRNA in different stages of alcoholic liver disease (ALD) and its clinical value. METHODS: One hundred and seven male alcoholics ...AIM: To investigate the expression of the transforming growth factor beta 1(TGF-beta 1) mRNA in different stages of alcoholic liver disease (ALD) and its clinical value. METHODS: One hundred and seven male alcoholics were grouped by clinical findings into four groups: alcohol abusers without liver impairment (n =22), alcoholic steatosis (n =30); alcoholic hepatitis (n=31); and alcoholic cirrhosis(n=24). Using peripheral blood mononuclear cells (PBMC) as samples the gene expression of TGF-beta 1 was examined quantitatively by reverse transcription polymerase chain reaction (RT-PCR) and dot blot. There are 34 healthy subjects served as control. RESULTS: The expression of TGF-beta 1 from all ALD patients was significantly greater than that in controls (1.320 +/- 1.162 vs 0.808 +/- 0.276, P【0.001). The differences of the expressions were significant between the patients from each groups (alcoholic steatosis, alcoholic hepatitis and alcoholic cirrhosis) and the controls (1.168 +/- 0.852, 1.462 +/- 1.657, 1.329 +/- 0.610 vs 0.808 +/- 0.276, P【0.050). No significant differences of TGF -beta 1 mRNA expression were observed between alcohol abusers without liver impairment and controls. The expressions in patients with alcoholic hepatitis and alcoholic cirrhosis were significantly greater than that in alcohol abusers respectively (1.462 +/- 1.657, 1.329 +/- 0.610 vs 0.841 +/- 0.706, P【0.050). No significant differences of TGF-beta 1 mRNA expression were observed between alcoholic fatty liver men and alcohol abusers. CONCLUSION: TGF-beta 1 expression level can be a risk factor for alcoholic liver disease and might be related to the inflammatory activity and fibrosis of the liver in patients.展开更多
BACKGROUND: Transforming growth factors (TGF)-beta 1, TGF-beta R2 and Smad4 belong to the TGF family, and play important roles in carcinogenesis and the development of carcinoma, especially hepatocellular carcinoma (H...BACKGROUND: Transforming growth factors (TGF)-beta 1, TGF-beta R2 and Smad4 belong to the TGF family, and play important roles in carcinogenesis and the development of carcinoma, especially hepatocellular carcinoma (HCC). TGF-beta 1 is a multipotent polypeptide, which inhibits the growth of epithelial cells including hepatoma cell lines and hepatocytes by inducing apoptosis. TGF-beta R2 forms a heterodimeric complex upon binding to TGF-beta, and then generates the first step in the signal transduction pathway leading to growth inhibition in coordination with the type I receptor. Smad4 protein is an important mediator in the TGF-beta signaling pathway, and negatively regulates the growth of epithelial cells. This study aimed to detect the expression of TGF-beta 1, TGF-beta R2 and Smad4 in HCCs and their adjacent normal tissues, while assessing its relations with the clinicopathological parameters of HCC. METHODS: Forty-seven HCC specimens and their adjacent normal tissues were obtained surgically at the Affiliated Hospital of Medical College, Qingdao University. The expression of TGF-beta 1, TGF-beta R2 and Smad4 was separately detected by immunohistochemistry in all HCC specimens and their adjacent normal tissues, and its relations with the clinicopathological parameters of HCC were assessed. RESULTS: The positive expression of TGF-beta 1 was 72.34% in the HCC specimens, which was higher than that in the adjacent normal tissues (P < 0.001). The positive expression of Smad4 and TGF-beta R2 was 34.04% and 59.57% respectively in the carcinoma specimens. The expression of TGF-beta 1, TGF-beta R2 and Smad4 was significantly higher in groups with a tumor embolus of the portal vein, integrity of the amicula, and Edmondson's III-IV than that in other groups, but it was not related to tumor size (P < 0.05). CONCLUSIONS: TGF-beta 1 may play an important role in the occurrence and development of HCC. Combined detection of TGF-beta 1, TGF-beta R2 and Smad4 may be useful for the determination of the degree of malignancy and the prognosis of HCC.展开更多
Objective To investigate the optimal dosage of pirfenidone for the treatment of pulmonary fibrosis induced by bleomycin in Wistar rats, and the alteration of expressions of transforming growth factor beta-1 （ TGF-β1...Objective To investigate the optimal dosage of pirfenidone for the treatment of pulmonary fibrosis induced by bleomycin in Wistar rats, and the alteration of expressions of transforming growth factor beta-1 （ TGF-β1 ）, tissue inhibitor of metalloproteinase-1 （ TIMP-1 ）, and matrix metalloproteinase-13 （ MMP-13 ） in lung tissue. Methods Male Wistar rats were endotracheally instilled with bleomycin or normal saline. Pirfenidone （25-800 mg · kg^-l · d^-1 ）, dexamethasone （3 mg/kg）, or 1% carboxymethylcellulose sodium were given daily by feed 2 days before instillation of bleomycin. Groups T7 and T14 were fed pirfenidone 50 mg · kg^-1 · d^-1 at 7 days or 14 daYs after bleomycin instillation. Lungs were harvested at 28 days after bleomycin instillation. Patholological changes in luffg tissues were evaluated with HE staining. Lung collagen was stained by sirius red and measured by content of hydroxypro- line. Expression of proteins of TGF-β1 TIMP-1, and MMP-13 were detected by Western blotting. Results At doses of 25, 50, and 100 mg· kg^- 1 · d ^- 1, pirfenidone had significant anti-fibrotic effects for bleomy- cin-induced rat pulmonary fibrosis, and these effects were most significantly attenuated at the dosage of 50 mg · kg^-1 ·d^ -1（ HE： P 〈 0. 01, P 〈 0.01, and P = 0.064; sirius red： P 〈0.05, P 〈 0.01, and P 〈 0.05 ; hydroxyproline： P = 0.595, P 〈 0.01, and P = 0.976）. Pirfenidone at a dosage of 50 mg · kg^- l · d^-1 inhibited protein expression of TGF-131 and TIMP-1 in lung tissue in the early phase （0.79 and 0.75 times of control group）, but had no effect on ex- nr^eelnn nf MMP-13. Conclusion Low dose pirfenidone, especially at dosage of 50 mg · kg^-1 · d^-1, has significant anti-fibrotic effects on bleomycin-induced rat pulmonary fibrosis. Pirfenidone partially inhibits the enhancement of the expression of TGF-131 and TIMP-β1 in lung tissue.展开更多
We review the biology and role of transforming growth factor beta 1(TGF-β1)in peripheral nerve injury and regeneration,as it relates to injuries to large nerve trunks(i.e.,sciatic nerve,brachial plexus),which often l...We review the biology and role of transforming growth factor beta 1(TGF-β1)in peripheral nerve injury and regeneration,as it relates to injuries to large nerve trunks(i.e.,sciatic nerve,brachial plexus),which often leads to suboptimal functional recovery.Experimental studies have suggested that the reason for the lack of functional recovery resides in the lack of sufficient mature axons reaching their targets,which is a result of the loss of the growth-supportive environment provided by the Schwann cells in the distal stump of injured nerves.Using an established chronic nerve injury and delayed repair animal model that accu-rately mimics chronic nerve injuries in humans,we summarize our key findings as well as others to better understand the pathophysiology of poor functional recovery.We demonstrated that 6 month TGF-β1 treat-ment for chronic nerve injury significantly improved Schwann cell capacity to support axonal regeneration.When combined with forskolin,the effect was additive,as evidenced by a near doubling of regenerated axons proximal to the repair site.We showed that in vivo application of TGF-β1 and forskolin directly onto chronically injured nerves reactivated chronically denervated Schwann cells,induced their proliferation,and upregulated the expression of regeneration-associated proteins.The effect of TGF-β1 and forskolin on old nerve injuries is quite impressive and the treatment regiment appears to mediate a growth-supportive milieu in the injured peripheral nerves.In summary,TGF-β1 and forskolin treatment reactivates chronical-ly denervated Schwann cells and could potentially be used to extend and prolong the regenerative responses to promote axonal regeneration.展开更多
BACKGROUND: Pancreatic stellate cells (PSCs) play a major role in promoting pancreatic fibrosis. Transforming growth factor beta 1 (TGF-beta 1) is a critical mediator of this process. This study aimed to determine the...BACKGROUND: Pancreatic stellate cells (PSCs) play a major role in promoting pancreatic fibrosis. Transforming growth factor beta 1 (TGF-beta 1) is a critical mediator of this process. This study aimed to determine the expression of the Smad3 and Smad7 genes in the process of PSC activation, and explore the mechanisms of chronic pancreatitis. METHODS: The expressions of Smad3 and Smad7 in PSCs before and after TGF-beta 1 treatment were detected by reverse transcription-polymerase chain reaction and Western blotting analysis. Smad3 expression was detected in PSCs after treatment with 5 ng/ml of TGF-beta 1 for 24 hours. RESULTS: Smad7 expression was decreased in TGF-beta 1 -activated PSCs (P<0.05) in a dose-dependent manner. When TGF-beta 1 concentration reached 10 ng/ml, the expression of p-Smad3, Smad3, and Smad7 was inhibited (P<0.05). CONCLUSIONS: TGF-beta 1 promotes the expression of Smad3 and inhibits the expression of Smad7 during the activation of PSCs. In contrast, high-dose TGF-beta 1 downregulates the expression of Smad3 in completely activated PSCs.展开更多
OBJECTIVE: To investigate the effect of Danggui Buxue Tang(DBT), a decoction from Traditional Chinese Medicine, on bleomycin-induced pulmonary fibrosis in rats, and to propose the possible underlying mechanism.METHODS...OBJECTIVE: To investigate the effect of Danggui Buxue Tang(DBT), a decoction from Traditional Chinese Medicine, on bleomycin-induced pulmonary fibrosis in rats, and to propose the possible underlying mechanism.METHODS: Forty male Sprague-Dawley rats were randomly divided into sham group, model group,prednisone group and DBT group. Pulmonary fibrosis rat model was established by intratracheal injection with bleomycin. Body weight and lung index were monitored. Histopathologic examination and collagen deposition were determined using Hematoxylin and eosin(HE) and Masson's trichrome staining. Immunohistochemistry staining was applied to observe the expression of alpha-smooth muscle actin(α-SMA). m RNA expression of α-SMA,collagen Ⅰ and collagen Ⅲ were measured by realtime fluorescence quantitative PCR(RT-q PCR). Inflammatory cytokines, including tumor necrosis factor alpha(TNF-α), interleukin-6(IL-6) and IL-1β in serum were detected by Enzyme-linked immunosorbent assay. Alkali hydrolysis method was conducted to investigate the content of hydroxyproline(HYP). Transforming growth factor-β1(TGF-β1),Smad3 and plasminogen activator inhibitor-1(PAI-1) protein level were examined by Western blot assay.RESULTS: DBT significantly reduced the severity of bleomycin-induced pulmonary fibrosis and inflammation as indicated by minimizing the lost of weight, and by lowering the levels of lung index, inflammation score, Ashcroft score, collagen volume fraction(%), HYP, α-SMA, collagen Ⅰ, collagen Ⅲ,TNF-α, IL-6, IL-1β, TGF-β1, Smad3 and PAI-1, consistent with the effect of prednisone.CONCLUSION: Our findings suggest that DBT is able to ameliorate the pulmonary fibrosis, the possible mechanism may involve inhibition of pulmonary inflammation and collagen deposition, possibly via suppressing TGF-β1/Smad3/PAI-1 signaling pathway.展开更多
AIM： To uncover the mutations profile of transforming growth factor beta-induced （TGFBI） gene in Chinese corneal dystrophy patients and further investigate the characteristics of genotype-phenotype correlations. M...AIM： To uncover the mutations profile of transforming growth factor beta-induced （TGFBI） gene in Chinese corneal dystrophy patients and further investigate the characteristics of genotype-phenotype correlations. METHODS： Forty-two subjects （6 unrelated families including 15 patients and 8 unaffected members, and 19 sporadic patients） of Chinese origin were subjected to phenotypic and genotypic characterization. The corneal phenotypes of patients were documented by slit lamp photography. Mutation screening of the coding regions of TGFBI was performed by direct sequencing. RESULTS： We detected four corneal dystrophy types. The most frequent phenotypes were granular corneal dystrophy （GCD） （including 3 families and 8 sporadic patients） and lattice corneal dystrophy （LCD） （including 2 families and 9 sporadic patients）. The next phenotypes were corneal dystrophy of Bowman layer （CDB） （1 family and 1 sporadic patient） and epithelial basement membrane dystrophy （EBMD） （1 sporadic patient）. Six distinct mutations responsible for TGFBI corneal dystrophies were identified in 30 individuals with corneal dystrophies. Those were, p.R124H mutation in 1 family and 2 sporadic patients with GCD, p.R555W mutation in 2 families and 3 sporadic patients with GCD, p.R124C mutation in 2 families and 7 sporadic patients with LCD, p.A620D mutation in 1 sporadic patient with LCD, p.H626R mutation in 1 sporadic patient with LCD, and p.R555Q in 1 family and 1 sporadic patient with CDB. No mutation was detected in the remaining 3 atypical GCD patients and 1 EBMD patient, CONCLUSION： GCD and LCD are the most frequent phenotypes in Chinese population. R555W was the most common mutation for GCD; R124C was the most common mutation for LCD, Our findings extend the mutational spectrum of TFGBI , and this is the extensively delineated TGFBI mutation profile associated with the various corneal dystrophies in the Chinese population.展开更多
There is currently no effective medical treatment for temporomandibular joint osteoarthritis(TMJ-OA) due to a limited understanding of its pathogenesis. This study was undertaken to investigate the key role of transfo...There is currently no effective medical treatment for temporomandibular joint osteoarthritis(TMJ-OA) due to a limited understanding of its pathogenesis. This study was undertaken to investigate the key role of transforming growth factor-β(TGF-β)signalling in the cartilage and subchondral bone of the TMJ using a temporomandibular joint disorder(TMD) rat model, an ageing mouse model and a Camurati–Engelmann disease(CED) mouse model. In the three animal models, the subchondral bone phenotypes in the mandibular condyles were evaluated by μCT, and changes in TMJ condyles were examined by TRAP staining and immunohistochemical analysis of Osterix and p-Smad2/3. Condyle degradation was confirmed by Safranin O staining, the Mankin and OARSI scoring systems and type X collagen(Col X), p-Smad2/3 a and Osterix immunohistochemical analyses. We found apparent histological phenotypes of TMJ-OA in the TMD, ageing and CED animal models, with abnormal activation of TGF-βsignalling in the condylar cartilage and subchondral bone. Moreover, inhibition of TGF-β receptor I attenuated TMJ-OA progression in the TMD models. Therefore, aberrant activation of TGF-β signalling could be a key player in TMJ-OA development.展开更多
In order to investigate the biological function of transforming growth factor-β1（TGF-β1） during fibrosis in denervated skeletal muscle,we recruited sciatic nerve injury model of SD rats in which denervated gastroc...In order to investigate the biological function of transforming growth factor-β1（TGF-β1） during fibrosis in denervated skeletal muscle,we recruited sciatic nerve injury model of SD rats in which denervated gastrocnemius was isolated for analysis.At different time points after operation,denervated muscle was examined by several methods.Masson trichrome staining showed morphological changes of denervated skeletal muscle.Quantitative RT-PCR detected the rapid increase of TGF-β1 expression at mRNA level after nerve injury.It was found that a peak of TGF-β1 mRNA expression appeared one week post-operation.The expression of collagen Ⅰ（COL Ⅰ） mRNA was up-regulated in the nerve injury model as well,and reached highest level two weeks post-injury.Immunoblot revealed similar expression pattern of TGF-β1 and COL Ⅰ in denervated muscles at protein level.In addition,we found that the area of the gastrocnemius muscle fiber was decreased gradually along with increased interstitital fibrosis.Interestingly,this pathological change could be prevented,at least partly,by local injection of TGF-β1 antibodies,which could be contributed to the reduced production of COL Ⅰ by inhibiting function of TGF-β1.Taken together,in this study,we demonstrated that the expression of TGF-β1 was increased significantly in denervated skeletal muscle,which might play a crucial role during muscle fibrosis after nerve transection.展开更多
Summary: Rat transforming growth factor β1 (rTGFβ1) cDNA from rat lymphocytes was cloned by RT-PCR and inserted into pcDNA3 to construct an eukaryotic expression vector, which was named pcDNA3-TGFβ1. The cloned gen...Summary: Rat transforming growth factor β1 (rTGFβ1) cDNA from rat lymphocytes was cloned by RT-PCR and inserted into pcDNA3 to construct an eukaryotic expression vector, which was named pcDNA3-TGFβ1. The cloned gene was confirmed to code rat TGFβ1 by restriction enzyme analysis. pcDNA3-TGFβ1 plasmid was transfected into rat osteoblasts by using liposome-mediated gene transfer technique and the expression of TGFβ1 was detected by using irnmunohistochemical staining assay. It was found that the rat TGFβ1 expression product was obviously detectable in the transfected osteoblasts in 48 h. High expression of TGFβ1 was obtained in the rat osteoblasts in which the constructed TGFβ1 expression vector was transfected.展开更多
文摘The effects of prestrain and annealing temperature on phase transformation temperatures in Fel4Mn5Si8Cr4Ni shape memory alloy have been studied. The results showed that when the annealing temperature was 673 K, both the At and the Ms temperatures increased appreciably as the prestrain increased, the As temperature increased slightly with increasing prestrain; the resistivity difference at 303 K between the heating and cooling curve also increased with increasing prestrain, which agreed with the recovery strain. The shape memory effect in Fe-Mn-Si-Cr-Ni shape memory alloy is caused by the stress-induced γ→ε martensite transformation and its reverse transformation. When the prestrain was 10%, the Ms temperature decreased remarkably as the annealing temperature increased.
基金funded by the National Natural Science Foundation of China(grant No.41572329)
文摘Objective Despite the fact that the bioavailability of trace metals indicated by their speciation has been an indispensable parameter in the assessment and treatment of the environmental pollution of trace metals, many studies have suggested that the bioavailability of trace metals may change according to the conditions of the environment, and the speciation of trace metals can also transform between some fractions. These transformations are related with these factors such as the compositions, microorganism, time, and other physical-chemical conditions of the system. Our work aims to systematically investigate and probe the factors to affect the transformation aside from analysis at certain time-place. The results of these understanding and investigations can be used for reasonably determining the allocation of financial and technical resources in natural and engineered processes, with bringing about inspirations from the evolution of the speciation of the trace metals on environmental impacts.
基金Supported by Ningbo Science and Technology Program,No.2019A6-10312.
文摘BACKGROUND The effects of T-cell immunoglobulin mucin molecule-3(Tim-3),transforming growth factor β(TGF-β),and chemokine-12(CXCL12) expression on the prognosis of patients with diffuse large B-cell lymphoma(DLBCL) have not been elucidated.AIM To examine the correlation between Tim-3,TGF-β and CXCL12 expression and DLBCL prognosis.METHODS Lymph node tissues of 97 patients with DLBCL and 93 normal-response hyperplastic lymph node tissues treated from January 2017 to May 2019 were selected as the DLBCL and control groups,respectively.The expression of Tim-3,TGF-β,and CXCL12 was detected immunohistochemically.Patients were followed up for 3 years,and progression-free survival was recorded.Cox mult-ifactorial analysis was performed to analyze the risk factors for poor prognosis.RESULTS The positive expression rates of Tim-3,TGF-β,and CXCL12 were higher in DLBCL tissues than in non-cancerous(control) tissues(P < 0.05).One-year postsurgery,the positive expression rates of Tim-3,TGF-β,and CXCL12 were higher in patients with effective treatment than in those with ineffective treatment(P < 0.05).The 3-year progression-free survival of 97 patients with DLBCL was 67.01%(65/97).Univariate analysis revealed that clinical stage,bone marrow infiltration,International Prognostic Index(IPI) score,Tim-3 positivity,TGF-β positivity,and CXCL12 positivity were associated with poor prognosis(P < 0.05).Multivariate Cox regression analysis demonstrated that clinical stage Ⅲ–Ⅳ,bone marrow infiltration,mediate-to-high-risk IPI scores,Tim-3 positivity,TGF-β positivity,and CXCL12 positivity were independent risk factors affecting prognosis(P < 0.05).CONCLUSION DLBCL tissues exhibit high positive expression of Tim-3,TGF-β,and CXCL12,and a high expression of all three indicates a poor prognosis.
文摘Dualcolor systems were used to reduce the collinearity of multicomponent spectra, which is described by the angles between spectra vectors. Combined with iterative target transformation factor analysis, single rare earth element was determined in its mixture. The calculated results show that the average angle between rare earth spectra in one color system(trichloroarsenazorare earths, pH 34) is 45, and that in two color systems(trichloroarsenazorare earths, pH 34, 14) is 215. This technique makes it easy to select the real number of the components in mixtures, and the determination results show dualcolor system method is an effective technique in rare earth mixture analysis.
文摘OBJECTIVES:To investigate the effect of Bushen Tongluo recipe(BSTLR, 补肾通络方) on rats with diabetic kidney disease(DKD) and to explore the underlying mechanism of action. METHODS:The rat model of DKD was established, and rats were treated with different doses of BSTLR. Body weight and the levels of urinary protein, α1-microglobulin, glucose, blood urea nitrogen, creatinine, Cystatin C, superoxide dismutase, malondialdehyde, and catalase were analyzed biochemically or by enzyme-linked immunosorbent assay. The pathological damage to renal tissues was assessed by hematoxylin-eosin staining. Immunohistochemical staining was carried out to detect the expression levels of fibronectin, E-cadherin, α-smooth muscle actin, laminin, vimentin, collagen type Ⅳ in kidney tissues. Western blot analysis was conducted to analyze the expression levels of Nephrin, Desmin, Podocin, transforming growth factor-β1, mothers against decapentaplegic homolog 3(Smad3), Notch1, jagged, hairy and enhancer of split 1(Hes1) in kidney tissues, and the expression levels of maternally expressed gene 3(MEG3) and mi R-145 were measured by quantitative reverse transcription-polymerase chain reaction. Moreover, dual-luciferase reporter assay was employed to verify the binding of mi R-145 to MEG3. RESULTS:BSTLR increased the body weight of DKD rats, effectively ameliorated the renal function and pathological injury in DKD, regulated the balance of renal oxidative stress, inhibited the TGF/Notch signaling pathway, and affected the variations in the lnc RNA MEG3/mi R-145 axis. CONCLUSION:BSTLR improved oxidative stress homeostasis, inhibited the TGF/Notch signaling pathway, and regulated the lnc RNA MEG3/mi R-145 axis, effectively delaying the progression of DKD.
基金Supported by Science and Technology Innovation Project of China Academy of Chinese Medical Sciences of Study on the Mechanism of Qufeng Jiejing Formula in Regulating Mitogen-activated Protein Kinase Signaling Pathway to Inhibit Phenotypic Transformation of Airway Smooth Muscle Cells in Asthma(No.CI2021A01108)Cultivation Project of The National Natural Science Foundation of China of Xiyuan Hospital,China Academy of Chinese Medical Sciences of Research on the Role of Traditional Chinese Medicines-Qufeng Jiejing in the Proliferation,Migration and Phenotypic Transformation of Airway Smooth Muscle Cells in Asthma(No.XY20-17)。
文摘OBJECTIVE:To explore the role and mechanism of Qufeng Jiejing(祛风解痉,QFJJ)formula in the asthma progression.METHODS:The Bagg Albino/c mice treated with Ovalbumin and AL(OH)3,and airway smooth muscle cells(ASMCs)treated with platelet-derived growth factor(PDGF)-BB to establish a asthma model in vivo and in vitro.The cell morphology was observed with microscope and immunofluorescence staining.The cell viability was assessed with methyl thiazolyl tetrazolium assay.The tumor necrosis factor-αlpha(TNF-α),interleukin-1beta(IL-1β),laminin,fibronectin and collagen IV levels in the ASMCs were detected with corresponding enzyme linked immunosorbent assay kits.Transwell and wound healing assays were conducted to test the cell migration.The TGF-β1,Smad2 and Smad3 levels were measured with Western blot.RESULTS:We found that QFJJ formula treatment dramatically decreased the cell viability,TNF-α,IL-1β,laminin,fibronectin and collagen IV levels in the PDGFBB stimulated ASMCs.Additionally,the protein levels of TGF-β1,Smad2 and Smad3 in the PDGF-BB stimulated ASMCs were prominently depleted after QFJJ formula treatment.Besides,SRI treatment neutralized the role of QFJJ formula in the PDGF-BB stimulated ASMCs.CONCLUSION:QFJJ formula effectively relieved the asthma progression through ameliorate the ASMCs function,which was achieved through suppressing the TGF-β1/Smads signaling pathway.
基金Supported by the Projects of Medical and Health Technology Development Program in Shandong Province(No.202107021009)Shandong Provincial Traditional Chinese Medicine Science and Technology Project(No.M-2023118).
文摘AIM:To determine whether paeonol(Pae),a naturally occurring phenolic compound,can serve as an effective pharmacological inhibitor of posterior capsular opacification(PCO).METHODS:A rat model of cataract surgery—induced PCO was established,and Pae was administered via anterior chamber injection to evaluate its preventive effect on capsular opacification and fibrotic remodeling.Histological and immunohistochemical analyses were performed to assess epithelial-mesenchymal transition(EMT)—related changes in lens epithelial cells(LECs).Ex vivo lens capsule cultures were employed to examine the expression of Vimentin and Zonula Occludens-1(ZO-1)by immunofluorescence and immunohistochemistry.In the human LEC line SRA01/04,EMT marker expression at both mRNA and protein levels was analyzed following transforming growth factor beta 2(TGF-β2)stimulation,with Pae treatment.Western blotting and immunofluorescence were used to investigate the effect of Pae on TGF-β/Smad signaling and AMP-activated protein kinase(AMPK)activation.Molecular docking was performed to predict Pae–AMPK binding,and rescue experiments with AMPK inhibition were conducted to validate the mechanistic pathway.RESULTS:Pae significantly reduced capsular opacification and fibrotic remodeling in the rat PCO model compared with controls.In LECs,Pae markedly suppressed TGF-β2–induced EMT,evidenced by decreased expression of mesenchymal markers,such as Vimentin,Fibronectin,Collagen 1A1,α-SMA and preserved epithelial junctional protein ZO-1.Mechanistically,Pae was predicted to directly interact with the catalytic pocket of AMPK,which was experimentally confirmed by enhanced AMPK phosphorylation and nuclear translocation(P<0.05).This activation disrupted canonical TGF-β/Smad signaling,leading to suppression of EMT.Rescue experiments using AMPK inhibition abrogated the anti-EMT effect of Pae,further validating the AMPK-dependent mechanism.CONCLUSION:Pae exerts a potent inhibitory effect on PCO formation by blocking EMT of LECs through direct activation of AMPK and subsequent disruption of TGF-β/Smad signaling.
基金supported by grants by National Natural Science Foundation of China(No.82571024,No.81400489)Zhejiang Provincial Natural Science Foundation of China(LZ23H140001,LTGY23H200006,LGC22H200012)+3 种基金Zhejiang Qianjiang Talent Program(21040040-E)the Fundamental Research Funds of Zhejiang Sci-Tech University(2021Q031)Zhejiang Jiaxing Science Technology Foundation(2023AZ31004,2023AY11045,2023AY31012,2020AY10001)Zhejiang Drug&Health Foundation(2022507032,2023KY340)。
文摘The transforming growth factor-β(TGF-β)and bone morphogenetic protein(BMP)signaling pathways are pivotal regulators of cellular processes,playing indispensable roles in embryogenesis,postnatal development,and tissue homeostasis.These pathways are particularly critical within the skeletal system,as they coordinate osteogenesis,chondrogenesis,and bone remodeling through intricate molecular mechanisms.TGF-β/BMP signaling is primarily transduced via canonical Smad-dependent pathways(e.g.,ligands,receptors,and intracellular Smads)and the non-canonical Smad-independent(e.g.,p38 mitogen-activated protein kinase,MAPK)cascade.Both pathways converge on master transcriptional regulators,including Runx2 and Osterix,and their precise coordination is indispensable for skeletal development,maintenance,and repair.The dysregulation of TGF-β/BMP signaling contributes to a spectrum of skeletal dysplasia and bone pathologies.Advances in molecular genetics,particularly gene-targeting strategies and transgenic mouse models,have deepened our understanding of the spatiotemporal control of TGF-β/BMP signaling in bone and cartilage development.Moreover,emerging research underscores extensive crosstalk between TGF-β/BMP and other critical pathways,such as Wnt/β-catenin,mitogen-activated protein kinase(MAPK),parathyroid hormone(PTH)/PTH-related protein(PTHrP),fibroblast growth factors(FGF),Hedgehog,Notch,insulin-like growth factors(IGF)/insulin-like growth factors receptor(IGFR),Mammalian target of rapamycin(mTOR),and autophagy,forming an integrated regulatory network that ensures skeletal integrity.Our review synthesizes the current knowledge on the molecular components,regulatory mechanisms,and functional integration of TGF-β/BMP signaling in skeletal biology,with an emphasis on its roles in development,regeneration,and disease.By elucidating the molecular underpinnings of TGF-β/BMP pathways and their contextual interactions,we aim to highlight translational opportunities and novel therapeutic strategies for treating skeletal disorders.
文摘Aim: To investigate the stage-specific localization of transforming growth factor (TGF) β1 and β3 during spermatogenesis in adult human testis. Methods: The localization of TGFβ1 and β3 was investigated by immunohis tochemical staining method employing specific polyclonal antibodies. Results: Both TGFβ1 and β3 and their recep tors were preponderant in the Leydig celis. TGFβ1 could not be detected in the seminiferous tubules. TGFβ3 and TGFβ-Receptor (R) I were mainly seen in the elongated spermatids, while TGFβ-RⅡ in the pachytene spermatocytes and weak in the spermatogonia, spermatids and Sertoli celis. Only TGFβ-RⅡ was detected in the Sertoli celis. TGFβ3, TGFβ-RⅠ and TGFβ-RⅡ showed a staining pattern dependent upon the stages of the seminiferous epithelium cycle. Conclusion: TGFβ isoforms and their receptors are present in the somatic and germ celis of the adult human testis, suggesting their involvement in the regulation of spermatogenesis.
文摘AIM： To investigate the effects of transforming growth factor β1 （TGF-β1） on the differentiation of colonic lamina propria fibroblasts （CLPF） into myofibroblasts in vitro.METHODS： Primary CLPF cultures were incubated with TGF-β1 and analyzed for production of m-smooth muscle actin （α-SMA）, fibronectin （FN） and FN isoforms. Migration assays were performed in a modified 48-well Boyden chamber. Levels of total and phosphorylated focal adhesion kinase （FAK） in CLPF were analyzed after induction of migration.did not change α-SMA levels, while TGF-β1 treatment for 6 d significantly increased α-SIVlA production. Short term incubation （6 h） with TGF-β1 enhanced CLPF migration, while long term treatment （6 d） of CLPF with TGF-β1 reduced migration to 15%-37% compared to untreated cells. FN and FN isoform mRNA expression were increased after short term incubation with TGF-β1 （2 d） in contrast to long term incubation with TGF-β1 for 6 d. After induction of migration, TGF-β1-preincubated CLPF showed higher amounts of FN and its isoforms and lower levels of total and phosphorylated FAK than untreated cells.CONCLUSION： Long term incubation of CLPF with TGF-β1 induced differentiation into myofibroblasts with enhanced α-SMA, reduced migratory potential and FAK phosphorylation, and increased FN production. In contrast, short term contact （6 h） of fibroblasts with TGF-β1 induced a dose-dependent increase of cell migration and FAK phosphorylation without induction of α-SMA production.
文摘AIM: To investigate the expression of the transforming growth factor beta 1(TGF-beta 1) mRNA in different stages of alcoholic liver disease (ALD) and its clinical value. METHODS: One hundred and seven male alcoholics were grouped by clinical findings into four groups: alcohol abusers without liver impairment (n =22), alcoholic steatosis (n =30); alcoholic hepatitis (n=31); and alcoholic cirrhosis(n=24). Using peripheral blood mononuclear cells (PBMC) as samples the gene expression of TGF-beta 1 was examined quantitatively by reverse transcription polymerase chain reaction (RT-PCR) and dot blot. There are 34 healthy subjects served as control. RESULTS: The expression of TGF-beta 1 from all ALD patients was significantly greater than that in controls (1.320 +/- 1.162 vs 0.808 +/- 0.276, P【0.001). The differences of the expressions were significant between the patients from each groups (alcoholic steatosis, alcoholic hepatitis and alcoholic cirrhosis) and the controls (1.168 +/- 0.852, 1.462 +/- 1.657, 1.329 +/- 0.610 vs 0.808 +/- 0.276, P【0.050). No significant differences of TGF -beta 1 mRNA expression were observed between alcohol abusers without liver impairment and controls. The expressions in patients with alcoholic hepatitis and alcoholic cirrhosis were significantly greater than that in alcohol abusers respectively (1.462 +/- 1.657, 1.329 +/- 0.610 vs 0.841 +/- 0.706, P【0.050). No significant differences of TGF-beta 1 mRNA expression were observed between alcoholic fatty liver men and alcohol abusers. CONCLUSION: TGF-beta 1 expression level can be a risk factor for alcoholic liver disease and might be related to the inflammatory activity and fibrosis of the liver in patients.
文摘BACKGROUND: Transforming growth factors (TGF)-beta 1, TGF-beta R2 and Smad4 belong to the TGF family, and play important roles in carcinogenesis and the development of carcinoma, especially hepatocellular carcinoma (HCC). TGF-beta 1 is a multipotent polypeptide, which inhibits the growth of epithelial cells including hepatoma cell lines and hepatocytes by inducing apoptosis. TGF-beta R2 forms a heterodimeric complex upon binding to TGF-beta, and then generates the first step in the signal transduction pathway leading to growth inhibition in coordination with the type I receptor. Smad4 protein is an important mediator in the TGF-beta signaling pathway, and negatively regulates the growth of epithelial cells. This study aimed to detect the expression of TGF-beta 1, TGF-beta R2 and Smad4 in HCCs and their adjacent normal tissues, while assessing its relations with the clinicopathological parameters of HCC. METHODS: Forty-seven HCC specimens and their adjacent normal tissues were obtained surgically at the Affiliated Hospital of Medical College, Qingdao University. The expression of TGF-beta 1, TGF-beta R2 and Smad4 was separately detected by immunohistochemistry in all HCC specimens and their adjacent normal tissues, and its relations with the clinicopathological parameters of HCC were assessed. RESULTS: The positive expression of TGF-beta 1 was 72.34% in the HCC specimens, which was higher than that in the adjacent normal tissues (P < 0.001). The positive expression of Smad4 and TGF-beta R2 was 34.04% and 59.57% respectively in the carcinoma specimens. The expression of TGF-beta 1, TGF-beta R2 and Smad4 was significantly higher in groups with a tumor embolus of the portal vein, integrity of the amicula, and Edmondson's III-IV than that in other groups, but it was not related to tumor size (P < 0.05). CONCLUSIONS: TGF-beta 1 may play an important role in the occurrence and development of HCC. Combined detection of TGF-beta 1, TGF-beta R2 and Smad4 may be useful for the determination of the degree of malignancy and the prognosis of HCC.
基金Supported by National Ministry of Education Doctor Foundation of China(20020023045)
文摘Objective To investigate the optimal dosage of pirfenidone for the treatment of pulmonary fibrosis induced by bleomycin in Wistar rats, and the alteration of expressions of transforming growth factor beta-1 （ TGF-β1 ）, tissue inhibitor of metalloproteinase-1 （ TIMP-1 ）, and matrix metalloproteinase-13 （ MMP-13 ） in lung tissue. Methods Male Wistar rats were endotracheally instilled with bleomycin or normal saline. Pirfenidone （25-800 mg · kg^-l · d^-1 ）, dexamethasone （3 mg/kg）, or 1% carboxymethylcellulose sodium were given daily by feed 2 days before instillation of bleomycin. Groups T7 and T14 were fed pirfenidone 50 mg · kg^-1 · d^-1 at 7 days or 14 daYs after bleomycin instillation. Lungs were harvested at 28 days after bleomycin instillation. Patholological changes in luffg tissues were evaluated with HE staining. Lung collagen was stained by sirius red and measured by content of hydroxypro- line. Expression of proteins of TGF-β1 TIMP-1, and MMP-13 were detected by Western blotting. Results At doses of 25, 50, and 100 mg· kg^- 1 · d ^- 1, pirfenidone had significant anti-fibrotic effects for bleomy- cin-induced rat pulmonary fibrosis, and these effects were most significantly attenuated at the dosage of 50 mg · kg^-1 ·d^ -1（ HE： P 〈 0. 01, P 〈 0.01, and P = 0.064; sirius red： P 〈0.05, P 〈 0.01, and P 〈 0.05 ; hydroxyproline： P = 0.595, P 〈 0.01, and P = 0.976）. Pirfenidone at a dosage of 50 mg · kg^- l · d^-1 inhibited protein expression of TGF-131 and TIMP-1 in lung tissue in the early phase （0.79 and 0.75 times of control group）, but had no effect on ex- nr^eelnn nf MMP-13. Conclusion Low dose pirfenidone, especially at dosage of 50 mg · kg^-1 · d^-1, has significant anti-fibrotic effects on bleomycin-induced rat pulmonary fibrosis. Pirfenidone partially inhibits the enhancement of the expression of TGF-131 and TIMP-β1 in lung tissue.
文摘We review the biology and role of transforming growth factor beta 1(TGF-β1)in peripheral nerve injury and regeneration,as it relates to injuries to large nerve trunks(i.e.,sciatic nerve,brachial plexus),which often leads to suboptimal functional recovery.Experimental studies have suggested that the reason for the lack of functional recovery resides in the lack of sufficient mature axons reaching their targets,which is a result of the loss of the growth-supportive environment provided by the Schwann cells in the distal stump of injured nerves.Using an established chronic nerve injury and delayed repair animal model that accu-rately mimics chronic nerve injuries in humans,we summarize our key findings as well as others to better understand the pathophysiology of poor functional recovery.We demonstrated that 6 month TGF-β1 treat-ment for chronic nerve injury significantly improved Schwann cell capacity to support axonal regeneration.When combined with forskolin,the effect was additive,as evidenced by a near doubling of regenerated axons proximal to the repair site.We showed that in vivo application of TGF-β1 and forskolin directly onto chronically injured nerves reactivated chronically denervated Schwann cells,induced their proliferation,and upregulated the expression of regeneration-associated proteins.The effect of TGF-β1 and forskolin on old nerve injuries is quite impressive and the treatment regiment appears to mediate a growth-supportive milieu in the injured peripheral nerves.In summary,TGF-β1 and forskolin treatment reactivates chronical-ly denervated Schwann cells and could potentially be used to extend and prolong the regenerative responses to promote axonal regeneration.
基金supported by grants from the Natural Science Foundation of Jiangsu Province,China (No. BK2006241)the Foundation for Talents in Six Fields of Jiangsu Province (No. 07-B-038)
文摘BACKGROUND: Pancreatic stellate cells (PSCs) play a major role in promoting pancreatic fibrosis. Transforming growth factor beta 1 (TGF-beta 1) is a critical mediator of this process. This study aimed to determine the expression of the Smad3 and Smad7 genes in the process of PSC activation, and explore the mechanisms of chronic pancreatitis. METHODS: The expressions of Smad3 and Smad7 in PSCs before and after TGF-beta 1 treatment were detected by reverse transcription-polymerase chain reaction and Western blotting analysis. Smad3 expression was detected in PSCs after treatment with 5 ng/ml of TGF-beta 1 for 24 hours. RESULTS: Smad7 expression was decreased in TGF-beta 1 -activated PSCs (P<0.05) in a dose-dependent manner. When TGF-beta 1 concentration reached 10 ng/ml, the expression of p-Smad3, Smad3, and Smad7 was inhibited (P<0.05). CONCLUSIONS: TGF-beta 1 promotes the expression of Smad3 and inhibits the expression of Smad7 during the activation of PSCs. In contrast, high-dose TGF-beta 1 downregulates the expression of Smad3 in completely activated PSCs.
基金Supported by the Government Funded Clinical Medicine Eexcellent Talent Training and Basic Research Project PlanNatural Science Foundation of Hebei(No.H2019423092)+2 种基金Higher Education Science and Technology Research Project of Hebei(No.ZD2016056)Postgraduate Innovation Ability Development Project of Hebei Education Department(No.CXZZBS2019159)Basic Research Business Expenses of Provincial Universities of Hebei University of Chinese Medicine Project of Excellent Student Research Capacity Improvement(No.YXZ2019001)。
文摘OBJECTIVE: To investigate the effect of Danggui Buxue Tang(DBT), a decoction from Traditional Chinese Medicine, on bleomycin-induced pulmonary fibrosis in rats, and to propose the possible underlying mechanism.METHODS: Forty male Sprague-Dawley rats were randomly divided into sham group, model group,prednisone group and DBT group. Pulmonary fibrosis rat model was established by intratracheal injection with bleomycin. Body weight and lung index were monitored. Histopathologic examination and collagen deposition were determined using Hematoxylin and eosin(HE) and Masson's trichrome staining. Immunohistochemistry staining was applied to observe the expression of alpha-smooth muscle actin(α-SMA). m RNA expression of α-SMA,collagen Ⅰ and collagen Ⅲ were measured by realtime fluorescence quantitative PCR(RT-q PCR). Inflammatory cytokines, including tumor necrosis factor alpha(TNF-α), interleukin-6(IL-6) and IL-1β in serum were detected by Enzyme-linked immunosorbent assay. Alkali hydrolysis method was conducted to investigate the content of hydroxyproline(HYP). Transforming growth factor-β1(TGF-β1),Smad3 and plasminogen activator inhibitor-1(PAI-1) protein level were examined by Western blot assay.RESULTS: DBT significantly reduced the severity of bleomycin-induced pulmonary fibrosis and inflammation as indicated by minimizing the lost of weight, and by lowering the levels of lung index, inflammation score, Ashcroft score, collagen volume fraction(%), HYP, α-SMA, collagen Ⅰ, collagen Ⅲ,TNF-α, IL-6, IL-1β, TGF-β1, Smad3 and PAI-1, consistent with the effect of prednisone.CONCLUSION: Our findings suggest that DBT is able to ameliorate the pulmonary fibrosis, the possible mechanism may involve inhibition of pulmonary inflammation and collagen deposition, possibly via suppressing TGF-β1/Smad3/PAI-1 signaling pathway.
基金Supported by the National Natural Science Foundation of China (No.81370990)the Young and MiddleAged Scientists Research Awards Fund of Shandong Province, China (No. BS2013YY013, No. BS2015YY014)the Science and Technology Foundation of Shinan District, Qingdao, Shandong Province, China (No. 2013-13-014-YY)
文摘AIM： To uncover the mutations profile of transforming growth factor beta-induced （TGFBI） gene in Chinese corneal dystrophy patients and further investigate the characteristics of genotype-phenotype correlations. METHODS： Forty-two subjects （6 unrelated families including 15 patients and 8 unaffected members, and 19 sporadic patients） of Chinese origin were subjected to phenotypic and genotypic characterization. The corneal phenotypes of patients were documented by slit lamp photography. Mutation screening of the coding regions of TGFBI was performed by direct sequencing. RESULTS： We detected four corneal dystrophy types. The most frequent phenotypes were granular corneal dystrophy （GCD） （including 3 families and 8 sporadic patients） and lattice corneal dystrophy （LCD） （including 2 families and 9 sporadic patients）. The next phenotypes were corneal dystrophy of Bowman layer （CDB） （1 family and 1 sporadic patient） and epithelial basement membrane dystrophy （EBMD） （1 sporadic patient）. Six distinct mutations responsible for TGFBI corneal dystrophies were identified in 30 individuals with corneal dystrophies. Those were, p.R124H mutation in 1 family and 2 sporadic patients with GCD, p.R555W mutation in 2 families and 3 sporadic patients with GCD, p.R124C mutation in 2 families and 7 sporadic patients with LCD, p.A620D mutation in 1 sporadic patient with LCD, p.H626R mutation in 1 sporadic patient with LCD, and p.R555Q in 1 family and 1 sporadic patient with CDB. No mutation was detected in the remaining 3 atypical GCD patients and 1 EBMD patient, CONCLUSION： GCD and LCD are the most frequent phenotypes in Chinese population. R555W was the most common mutation for GCD; R124C was the most common mutation for LCD, Our findings extend the mutational spectrum of TFGBI , and this is the extensively delineated TGFBI mutation profile associated with the various corneal dystrophies in the Chinese population.
基金supported by 2016JQ0054 and NSFC grants 81470711 to L.Z.National Key Research and Development Program of China 2016YFC1102700 to X.Z.
文摘There is currently no effective medical treatment for temporomandibular joint osteoarthritis(TMJ-OA) due to a limited understanding of its pathogenesis. This study was undertaken to investigate the key role of transforming growth factor-β(TGF-β)signalling in the cartilage and subchondral bone of the TMJ using a temporomandibular joint disorder(TMD) rat model, an ageing mouse model and a Camurati–Engelmann disease(CED) mouse model. In the three animal models, the subchondral bone phenotypes in the mandibular condyles were evaluated by μCT, and changes in TMJ condyles were examined by TRAP staining and immunohistochemical analysis of Osterix and p-Smad2/3. Condyle degradation was confirmed by Safranin O staining, the Mankin and OARSI scoring systems and type X collagen(Col X), p-Smad2/3 a and Osterix immunohistochemical analyses. We found apparent histological phenotypes of TMJ-OA in the TMD, ageing and CED animal models, with abnormal activation of TGF-βsignalling in the condylar cartilage and subchondral bone. Moreover, inhibition of TGF-β receptor I attenuated TMJ-OA progression in the TMD models. Therefore, aberrant activation of TGF-β signalling could be a key player in TMJ-OA development.
基金supported by a grant from the National Natural Sciences Foundation of China (No. 30872627)
文摘In order to investigate the biological function of transforming growth factor-β1（TGF-β1） during fibrosis in denervated skeletal muscle,we recruited sciatic nerve injury model of SD rats in which denervated gastrocnemius was isolated for analysis.At different time points after operation,denervated muscle was examined by several methods.Masson trichrome staining showed morphological changes of denervated skeletal muscle.Quantitative RT-PCR detected the rapid increase of TGF-β1 expression at mRNA level after nerve injury.It was found that a peak of TGF-β1 mRNA expression appeared one week post-operation.The expression of collagen Ⅰ（COL Ⅰ） mRNA was up-regulated in the nerve injury model as well,and reached highest level two weeks post-injury.Immunoblot revealed similar expression pattern of TGF-β1 and COL Ⅰ in denervated muscles at protein level.In addition,we found that the area of the gastrocnemius muscle fiber was decreased gradually along with increased interstitital fibrosis.Interestingly,this pathological change could be prevented,at least partly,by local injection of TGF-β1 antibodies,which could be contributed to the reduced production of COL Ⅰ by inhibiting function of TGF-β1.Taken together,in this study,we demonstrated that the expression of TGF-β1 was increased significantly in denervated skeletal muscle,which might play a crucial role during muscle fibrosis after nerve transection.
文摘Summary: Rat transforming growth factor β1 (rTGFβ1) cDNA from rat lymphocytes was cloned by RT-PCR and inserted into pcDNA3 to construct an eukaryotic expression vector, which was named pcDNA3-TGFβ1. The cloned gene was confirmed to code rat TGFβ1 by restriction enzyme analysis. pcDNA3-TGFβ1 plasmid was transfected into rat osteoblasts by using liposome-mediated gene transfer technique and the expression of TGFβ1 was detected by using irnmunohistochemical staining assay. It was found that the rat TGFβ1 expression product was obviously detectable in the transfected osteoblasts in 48 h. High expression of TGFβ1 was obtained in the rat osteoblasts in which the constructed TGFβ1 expression vector was transfected.
