Regulation mechanism of macrophage transition in renal fibrosis / 器官移植

Renal fibrosis is a common pathological change from development to end-stage renal diseases in all progressive chronic kidney diseases. Renal fibrosis after kidney transplantation will severely affect the renal graft function. Macrophages are characterized with high heterogeneity and plasticity. During the process of kidney injury, macrophages are recruited, activated and polarized by local microenvironment, and participate in the process of renal tissue injury, repair and fibrosis through multiple mechanisms. Recent studies have shown that macrophages may transit into myofibroblasts and directly participate in the formation of renal fibrosis. This process is known as macrophage-myofibroblast transition. Nevertheless, the regulatory mechanism remains elusive. In this article, the role of macrophages in renal fibrosis, the characteristics of macrophage-myofibroblast transition and the possible regulatory mechanism were reviewed, aiming to provide reference for relevant research of renal fibrosis.

Search for potential target genes in dexamethasone-induced open-angle glaucoma by bioinformatics / 中华实验眼科杂志

Objective:To predict potential target genes in dexamethasone-induced open-angle glaucoma via bioinformatics technology.Methods:The GEO datasets GSE16643, GSE37474, and GSE124114 were used to analyze the differentially expressed genes by GEO2R.Gene Set Enrichment Analysis (GSEA) was performed on the differentially expressed genes between GSE37474 and GSE124114.Intersection of the three datasets were displayed by Venn diagram.The annotation and enrichment analysis of the intersection genes were performed through Gene Ontology (GO)/Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis and then were compared with normal tissue in GTEx Portal database.The corresponding protein interaction network was obtained by STRING.Finally, the candidate genes were searched for their transcription factors in UCSC and JASPAR.Primary human trabecular cells were divided into dexamethasone group and control group, treated with 2 ml 500 nmol/L dexamethasone and the same amount of ethanol, respectively.The expression of BDKRB1 and TAGLN in trabecular cells was detected by Western blot.Results:Differential genes between GSE37474 and GSE124114 datasets enriched in complement and coagulation cascade by GSEA.There were 89 intersecting genes of the three datasets.These genes mainly regulated the formation of extracellular matrix by GO analysis.The gene with the highest enrichment score and collagen-containing extracellular matrix was found to be associated with fibroblasts in GTEx Portal database.ACTA2, MYL9, TAGLN, and LMOD1 were closely related in STRING protein-protein interaction network.Transcription factor SP1 in UCSC and JASPAR according to related genes, BDKRB1, NID1, MFGE8 and TAGLN.The relative expression levels of BDKRB1 and TAGLN proteins were 1.32±0.14 and 0.44±0.09 in dexamethasone group, respectively, which were significantly higher than 1.00±0.00 and 0.20±0.10 in the control group, respectively ( t=-3.61, 2.89; both at P<0.05). Conclusions:Bioinformatics analysis showed that transcription factor SP1 may play a role in human trabecular meshwork cells to myofibroblasts transition after dexamethasone treatment.

Amino acid metabolism of fibroblasts involved in the occurrence and development of pulmonary fibrosis / 药学学报

Pulmonary fibrosis is a common pathological change in many chronic lung diseases, and its pathogenesis and characteristics are mainly caused by repeated lung alveolar injury leading to abnormal activation of fibroblasts and the accumulation of large amounts of extracellular matrix (ECM) deposition. Fibroblasts are not only responsible for constituting the interstitial structure of the lung but are also involved in the post-injury repairment in healthy lung tissue. In contrast, fibroblasts show a typical pro-fibrotic metabolic phenotype after differentiation into myofibroblasts during the development of pulmonary fibrosis. To synthesis large amount of collagen, the myofibroblasts have a strong metabolism characteristic of serine/glycine, glutamine, proline, and arginine. At the same time, the myofibroblast get the ability to resist cell apoptosis. As an important cell type for collagen degradation, fibroblasts reuse the amino acids of collagen to maintain cell metabolism. However, the myofibroblasts cannot degrade the ECM due to the suppression of autophagy activity, thus accelerating the progression of pulmonary fibrosis. This review attempts to summarize how amino acid metabolism of fibroblasts influence the pulmonary fibrosis.

Expression of interleukin-31 in hypertrophic scar from postoperative incision tissue / 中华医学美学美容杂志

Objective:To explore the interleukin-31 protein expression in the hypertrophic scar of incision tissue after surgery and its underlying pathological impact.Methods:From February 2022 to February 2023, three HS patients scar tissue (HS) and their normal skin tissue (Control, NS) were obtained. Two patients were female and one patient was male. The tissues were fixed in 4% formalin and embedded in paraffin. Haematoxylin-eosin (HE) stain and immunohistochemical stain were used to evaluate the epidermal thickness, myofibroblasts of dermis and the expression level of IL-31 between HS and NS.Results:The epidermis thickness was (303.88±46.03) μm in HS group, while (133.02±17.40) μm in NS group ( t=12.60, P<0.001). The expression level of IL-31 protein was measured by IRS score and positive cell density. The IRS score was 9.89±2.03 of the basal layer in HS group and was 4.33±1.66 of the basal layer in NS group. The positive cell density was 786 343.83±159 627.97 of the basal layer in HS group ( P<0.001) and was 555 457.61±128 097.21 of the basal layer in NS group ( P=0.014). In the dermis layer, the IRS score was 7.11±1.05 in HS group and was 4.33±0.71 in NS group, the positive cell density was 156 760.97±26 046.10 in HS group ( P<0.001) and was 49 576.01±52 369.33 in NS group ( P<0.001). In the dermis layer, the count of myofibroblasts was 120.44±15.75 in HS group while was 27.39±14.89 in NS group ( t=23.79, P<0.001). Conclusions:Our study demonstrates that both myofibroblast count and IL-31 protein expression level are notably increased in HS patients. The expression of IL-31 protein is prominent in the cytoplasm of myofibroblasts, basal cells, macrophages and mast cells which could implicate that IL-31 may be a potential therapeutic target to enhance the resolution of HS.

Medicated Serum of Bupleuri Radix Regulates HFL1 Apoptosis and Fibroblast-myofibroblast Transition via Smad3/Rheb Axis / 中国实验方剂学杂志

ObjectiveTransforming growth factor-β1 （TGF-β1） was used to stimulate human fetal lung fibroblast 1 （HFL1） for simulating the pathological process of idiopathic pulmonary fibrosis （IPF） and thereby the effects and mechanism of medicated serum of Bupleuri Radix against IPF were investigated. MethodTGF-β1 （10 μg·L-1） was employed to stimulate HFL1， and cells were treated with medicated serum of Bupleuri Radix （5%， 10%， 15%， 20%） for 24 h. Then cell proliferation rate was determined with cell counting kit-8 （CCK-8）. Subsequently， cells were classified into the control group （20% blank serum）， TGF-β1 group （20% blank serum and 10 μg·L-1 TGF-β1）， TGF-β1 + medicated serum of Bupleuri Radix group （5% blank serum， 15% medicated serum， and 10 μg·L-1 TGF-β1）， and TGF-β1 + SIS3 group （3 μmol·L-1 SIS3， 20% blank serum， 10 μg·L-1 TGF-β1）. Based on in situ end labeling （TUNEL） staining， the apoptosis rate was examined， and mRNA expression of apoptosis-related proteins B-cell lymphoma 2 （Bcl-2）， Bcl-2 associated X protein （Bax） and myofibroblast marker α-smooth muscle actin （α-SMA） was detected by Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR）. The protein expression of α-SMA， Ras homolog enriched in brain （Rheb）， and phosphorylated （p）-Smad3 was determined by immunofluorescence. Expression of Rheb， p-Smad3， and Smad3 was examined by Western blot. ResultThe cell proliferation rate of TGF-β1 group increased compared with that of the control group （P<0.05）. The cell proliferation rate of TGF+15% medicated serum of Bupleuri Radix group and TGF+20% medicated serum of Bupleuri Radix group decreased compared with that of the TGF-β1 group （P<0.01）. Compared with the control group， TGF-β1 group showed decrease in apoptosis rate， increase in mRNA expression of Bcl-2 and α-SMA， reduction in Bax mRNA expression， and rise of α-SMA and Rheb protein expression and p-Smad3 level （P<0.05）. Compared with TGF-β1 group， TGF-β1 + medicated serum of Bupleuri Radix group and TGF-β1 + SIS3 group demonstrated high apoptosis rate， low Bcl-2 and α-SMA mRNA expression， high Bax mRNA expression， and low α-SMA and Rheb protein expression and p-Smad3 level （P<0.05）. ConclusionMedicated serum of Bupleuri Radix can inhibit TGF-β1-induced HFL1 proliferation and fibroblast-myofibroblast transition and promote fibroblast apoptosis by regulating the Smad3/Rheb axis.

Estudo da imunoexpressão de proteínas envolvidas na transição epitélio-mesênquima em tumores de glândula salivar / Study of the immunoexpression of proteins involved in the epithelial-mesenchymal transition in salivary gland tumors

Os tumores de glândula salivar (TGS) apresentam notável complexidade clínica e biológica, razão para a qual muitos estudos investigam os eventos envolvidos na sua progressão. Uma das dinâmicas envolvidas na invasão tumoral de diversos tipos de carcinomas é a transição epitélio-mesênquima (TEM). Neste processo, as células epiteliais sofrem transição para um estado mesenquimal móvel, favorecendo a invasão e metástase. Sendo assim, esta pesquisa analisou a expressão imuno-histoquímica de E-caderina, Twist1, Snail1, α-SMA, metaloproteinases de matriz 9 (MMP-9) e Vimentina (VM) em 90 casos de TGS, correlacionando-os entre si e com parâmetros clinicopatológicos. Foram selecionados 20 casos de Adenoma pleomórfico (AP), 20 casos de Carcinoma mucoepidermoide (CME), 20 casos de Carcinoma adenoide cístico (CAC), 10 casos de Adenocarcinoma polimorfo (ACP), 10 casos de Carcinoma epitelial-mioepitelial (CEME) e 10 casos de Carcinoma ex-adenoma pleomórfico (CexAP). A análise de E-caderina, Twist1, Snail1 foi realizada em parênquima tumoral sendo observado o percentual de células positivas (PP), com escores variando de 0 a 4, e a intensidade de expressão (IE), cujos escores variaram de 0 a 3. A avaliação de MMP-9 foi realizada em parênquima e estroma tumoral, também avaliando-se a PP e a IE, ambos baseados em escores que variaram de 0 a 3. A marcação para α-SMA e VM foi analisada em região de estroma tumoral. Células positivas para α-SMA foram contabilizadas em 10 campos, obtendo-se, então a média. A VM foi avaliada de forma qualitativa, utilizando-se 4 escores de acordo com a IE e se a marcação é difusa ou focal. Os dados obtidos foram analisados no software Statistical Package for Social Science, GraphPad Prism e STATA. O nível de significância de 5% foi adotado para os testes estatísticos. Foi verificada menor imunomarcação de E-caderina nos APs em relação às neoplasias malignas de glândula salivar (NMGS). Observou-se baixa imunoexpressão de Twist1 e Snail1 em APs. Em relação a expressão nuclear do Twist1, constatou-se maior expressão nas neoplasias malignas quando comparadas aos APs. Ainda, Twist1 em núcleo foi correlacionado à expressão citoplasmática de E-caderina nas NMGS. No que concerne aos parâmetros clinicopatológicos, esta proteína se relacionou estatisticamente com maiores chances de óbito. Foi evidenciada baixa imunoexpressão de Snail1 entre as NMGS. No entanto, na análise dos CACs, foi verificada maior expressão nuclear na variante sólida em relação às demais. A expressão de MMP-9 em parênquima demonstrou correlação positiva com Twist1 citoplasmático e Snail1nuclear nas NMGS. A MMP-9 também apresentou correlação positiva na comparação da sua imunoexpressão em região de parênquima e de estroma. A VM se apresentou como um biomarcador a ser considerado na avaliação clínica dos pacientes, já que esta apresentou relação significativa com tamanho do tumor (T3-T4) e maior frequência de óbito. Ademais, a alta expressão desta proteína se apresentou como um fator preditivo independente para piores taxas de sobrevida global (SG). A avaliação dos demais fatores clinicopatológicos apresentou estágios clínicos avançados como indicador de valor prognóstico independente para menores taxas de SG, enquanto que para a sobrevida livre da doença, estes foram a localização em glândula salivar menor e presença de metástase à distância. Os resultados deste estudo sugerem que o processo de TEM pode estar relacionado ao estágio de diferenciação celular em APs e à progressão tumoral nas NMGS. Ressalta-se, também, maior participação de Twist1 e MMP-9 no cenário da TEM em tumores malignos de glândula salivar, além da possibilidade de utilização da VM como indicador de valor prognóstico (AU).

Salivary gland tumors (SGTs) present remarkable clinical and biological complexity; therefore, many studies investigate the events involved in their progression. One of the dynamics involved in the tumor invasion of different types of carcinomas is the epithelial-mesenchymal transition (EMT). In this process, epithelial cells undergo a transition to a mobile mesenchymal state, favoring invasion and metastasis. Therefore, this research analyzed the immunohistochemical expression of E-cadherin, Twist1, Snail1, α-SMA, vimentin (VM) and matrix metalloproteinase 9 (MMP-9) in 90 SGTs cases; correlations among the biomarkers, as well as between the biomarkers and clinicopathological parameters were made. We selected 20 cases of pleomorphic adenoma (PA), 20 cases of mucoepidermoid carcinoma (MEC), 20 cases of adenoid cystic carcinoma (ACC), 10 cases of polymorphous adenocarcinoma (PAC), 10 cases of epithelial-myoepithelial carcinoma (EMC) and 10 cases of carcinoma ex-pleomorphic adenoma (CXPA). E-cadherin, Twist1, and Snail1 were analyzed in tumor parenchyma, observing the percentage of positive cells (PP) using scores ranging from 0 to 4, and the expression intensity (EI), whose scores were ranged from 0 to 3. The evaluation of MMP-9 was performed in tumor parenchyma and stroma, also evaluating PP and IE, both based on scores that ranged from 0 to 3. The labeling for α-SMA and VM was analyzed in stromal cells. Positive cells for α-SMA were counted in 10 fields and the mean was calculated. VM was evaluated qualitatively, using 4 scores according to EI and whether the labeling was diffuse or focal. Obtained data were analyzed using Statistical Package for Social Science, GraphPad Prism, and STATA software. The significance level of 5% was adopted for the statistical tests. Patients were mostly female, with a mean age of 49.8 years; the major salivary glands were the most affected anatomical site, mainly the parotid gland. A lower E-cadherin immunostaining was verified in PAs in comparison to malignant neoplasms of salivary glands (MNSGs). Low immunoexpression of Twist1 and Snail1 was observed in PAs. Regarding the nuclear expression of Twist1, it was found greater expression in malignant neoplasms than in PAs. Furthermore, Twist1 in the nucleus was correlated with cytoplasmic expression of E-cadherin in MNSGs. Regarding clinicopathological parameters, this protein was statistically related to higher chances of death. Low immunoexpression of Snail1 was evidenced among the MNSGs. However, in the analysis of CACs, greater nuclear expression was observed in the solid variant compared to the others. Expression of MMP-9 in parenchyma showed a positive correlation with cytoplasmic Twist1 and Snail1nuclear in MNSGs. MMP-9 also showed a positive correlation when comparing its immunoexpression in the parenchyma and the stroma. VM was presented as a biomarker to be considered in the clinical evaluation of patients since it showed a significant correlation between greater tumor size and a higher frequency of death. Furthermore, the high expression of this protein appeared as an independent predictive factor for worse overall survival (OS) rates. The evaluation of the rest of the clinicopathological factors showed advanced clinical stages as an indicator of independent prognostic value for lower rates of OS. For disease-free survival, these indicators were the location in the minor salivary gland and the presence of distant metastasis. Our results suggest that the EMT may be related to myoepithelial differentiation in PAs and tumor progression in MNSGs. Also, Twist1 and MMP-9 appear to play a greater role in the scenario of EMT in MNSGs; finally, VM might be used as a prognostic value indicator (AU).

Establishment of Serum Free Chemically Defined Culture Medium to Study the Interactions Between Colonic Myofibroblasts and Colorectal Cancer Cells

@#Introduction: A crucial factor in cell culture technology is the use of appropriate culture medium which can promote cell growth and cellular functions. Development of serum free chemically defined medium enables the researchers to conduct the experiment in a more controlled manner. Myofibroblasts of the tumour microenvironment drive the colorectal carcinogenesis. In vitro study of the tumour-myofibroblast interaction using serum free medium may give a better insight into potential treatment for colorectal cancer (CRC) in the future. This study aims to establish serum free chemically defined medium to study the interplay between myofibroblast and CRC cells. Methods: A myofibroblast-specific serum free culture medium named as M-CIL, was developed to study the interactions between myofibroblasts and CRC cell lines in vitro. The influence of substrate (collagen type I) and subculturing of cells under incubation with M-CIL medium were also analysed. The effect of M-CIL medium on CRC cell growth also was studied. Gene expression analysis using quantitative real time polymerase chain reaction on amine oxidase, copper containing 3 (AOC3) was conducted to investigate the effect of individual components of the medium on myofibroblasts. Results: M-CIL medium supports the proliferation of myofibroblasts and produce minimal effect on CRC cells’ growth. Our data also shows the influence of M-CIL components on gene expression in myofibroblasts. Conclusion: M-CIL culture medium, which was designed with known and defined components, proved to be a suitable alternative to complete medium (DMEM + 10% FBS) for co-culture experiments of myofibroblasts and CRC cell lines.

Research advances in pathomechanism and treatment of joint contracture / 中国骨伤

Joint contracture is one of the common musculoskeletal disorders. It has seriously disturbed patients' activities of daily living in various aspects. The pathogenesis of it is eager to explore to distinct degree. Nowadays the thickeness and fibrosis of joint capsular is redarded as the major reason to joint contracture. It is reported that excessive fibroblasts and myofibroblasts activity, collagen hyperplasia, and extracellular matrix (ECM) deposition in these fibrotic condtions lead to the contracture. In addition, upregulators of myofibroblast and collagen synthesis, transforming growth factor-beta 1 (TGF-β1), and connective tissue growth factor (CTGF) were shown to be increased. Altered levels of cytokines were also thought to play a role in this process as elevated levelsof tumor necrosis factor-α(TNF-α), matrix metalloproteinases(MMPs) and abnormal distribution tissue inhibitors of MMPs(TIMPs) were demonstrated in contracted capsules. At present, the methods for clinical treatment of joint contracture mainly include two major categories:stretching therapy, physical factor therapy, exercise therapy, botulinum toxin injection and other non-surgical treatments, arthroscopic lysis, open lysis, and other surgical treatments. Surgical treatment is performed when non-surgical treatment is difficult to achieve further improvement. It has a good effect on mild to moderate joint contracture, but it is difficult to completely restore joint activity for serious joint contracture. Although clinical treatment methods are diverse, the clinical effects are staggered and the effectiveness of their treatment is controversial. Joint contracture is an important challenge faced by orthopedics and rehabilitation physicians, therapists and patients. The review summarized the pathogenesisand treatment of joint contracture and provided a theoretical basis for clinical diagnosis and treatment.

New progress on transforming growth factor β in ocular fibroproliferative diseases / 国际眼科杂志(Guoji Yanke Zazhi)

@#Fibrotic disease can disrupt the normally transparent ocular tissues resulting in irreversible loss of vision. A common feature in fibrotic eye disease is the transdifferentiation of cells into myofibroblasts that can occur through a process known as epithelial-mesenchymal transition. Transforming growth factor β has a central role in fibrogenesis by modulating the fibroblast function, inducing myofibroblast transdifferentiation and promoting extracellular matrix accumulation. It has been implicated in numerous fibrotic eye diseases. This article aims to introduce the new progression on TGFβ and fibrotic ocular diseases and its clinical significance for providing the reference in clinical practices.

Histopathological spectrum of spindle cell tumours of gastro-intestinal tract

Background: Spindle cell lesions of gastro-intestinal tract (GIT) are relatively uncommon tumours compared to epithelial tumours. The anatomic location of spindle cell tumour is important, whether the tumour is located in mucosa, submucosa or muscularis propria.Methods: Authors endeavoured to study the histopathological spectrum of spindle cell lesions for a period of one year from January 2018 to December 2018 in our hospital.Results: This was a prospective study of 1 year starting from January 2018 to December 2018. A total of 30 cases of spindle cell lesions of gastrointestinal tract were seen. Out of 30 cases 23 were gastrointestinal stromal tumours (GIST), 2 cases were schwannomas, 2 cases were of leiomyomas, 1 case was fibromatosis, 1 case was inflammatory fibroid polyp, and one case was inflammatory myofibroblast tumour.Conclusion: GISTs are the commonest spindle cell tumours of GIT. Besides GIST, there are other spindle cell tumours which range from benign to malignant, and need to be differentiated from GIST for proper management

Relationship between the Number of Neutrophils and Myofibroblasts during Diabetic Wound Healing and Wound Age / 法医学杂志

Objective To investigate the sequential changes of the number of neutrophils and myofibroblasts during diabetic wound healing, and discuss its application value in wound age estimation. Methods Diabetic DB mice and mice of the same age in the normal control group were selected, a wound healing model was established, wound samples were taken at different time points, while the number of neutrophils and myofibroblasts during diabetic wound healing were determined by immunohistochemical staining technique. Results The number of infiltrated neutrophils in the wounds of control and diabetic groups reached the peak respectively at 12 h and 5 d after injury. Compared with the control group, the number of neutrophils in the diabetic group decreased significantly from 6 h to 1 d after injury, but increased markedly from 5 d to 14 d. From 5 d to 10 d after injury, the average number of neutrophils at high magnification in wounds of the diabetic group was over 30, while that of neutrophils in wounds of the control group was less than 20. Myofibroblasts appeared in wounds from 3 d to 14 d after injury in the control group and from 5 d to 14 d after injury in the diabetic group. The difference in the number of myofibroblasts in wounds between control group and diabetic group from 3 to 7 d after injury had statistical significance. Conclusion In comparison with normal wound healing, the number of neutrophils and myofibroblasts during diabetic wound healing shows different sequential changes. The results of this study can provide reference for wound age estimation of patients with severe diabetes.

Effects of cyclosporin, nifedipine and phenytoin on gingival myofibroblast transdifferentiation in monkeys

Abstract Objective: Myofibroblasts have been associated with the development of several pathologic fibrotic conditions. This longitudinal study aims to assess the proliferative and antiapoptotic effects of cyclosporin, nifedipine and phenytoin on gingival connective tissue cells of nonhuman primate, as well as to analyze a possible role of myofibroblasts in gingival overgrowth. Materials and Methods: Gingival samples from the right superior canine area were obtained from 12 male monkeys ( Sapajus spp ) to comprise the control group. After one week, the animals were randomly assigned to three groups, which received daily oral doses of cyclosporin, nifedipine or phenytoin for 120 days. Gingival samples were collected from the left superior canine area of two animals of each group at 52 and 120 days. Histological sections were stained with hematoxylin and eosin, and immunoreacted against α-SMA, Ki- 67 and bcl-2. Results: α-SMA immunoreaction was negative in the control and experimental groups. Similarly, no difference between groups concerning immunostaining against Ki-67 and bcl-2 was observed in connective tissue cells. Conclusion: Based on this methodology, it may be concluded that gingival overgrowths induced by cyclosporin, nifedipine and phenytoin are not associated with neither myofibroblast transdifferentiation, proliferation nor apoptosis of gingival connective cells in monkeys.

Research progress of Hedgehog signaling pathway in renal fibrosis / 医学研究生学报

Renal fibrosis is a common pathological manifestation of most chronic kidney disease (CKD) and a major pathological change leading to end-stage renal disease. Recent studies have found that the Hedgehog (Hh) signaling pathway plays an important role in renal fibrosis. This pathway is different from the TGF-β and Wnt pathways that have been studied in the past. Its activation mainly directly targets the central event of renal fibrosis-activation, proliferation and transformation of myofibroblasts. It suggests that this pathway plays an important role in the process of renal fibrosis, and this pathway interacts with other pathways to promote the development of renal fibrosis. Further research into this pathway may provide new ideas for the treatment of renal fibrosis. This article reviews the relationship between Hh signaling pathway and renal fibrosis.

A piglet model of pulmonary vein stenosis / 中国胸心血管外科临床杂志

@#Objective    Pulmonary vein banding was used to establish a piglet model of pulmonary vein stenosis. We investigated the pathomorphological alterations of pulmonary veins in the model and compared it with the vascular tissue of recurrent stenosis after total anomalous pulmonary venous connection (TAPVC). Methods    Ten pigs of 6 weeks old were selected and randomly divided into 2 groups: 5 in a sham operation group and 5 in a pulmonary vein banding group. The operation had two stages, in which thoracotomies through intercostal space were done respectively on both sides. Biocompatible materials were applied around the pulmonary veins in the experimental group. The same method was used in the sham group. But the pulmonary veins were not banded. Six weeks after the operation, the pulmonary veins of the animals were harvested for hematoxylin-eosin staining and immunofluorescence staining to observe the pathological alterations of pulmonary veins. The proliferative tissues of patients with recurrent stenosis after TAPVC repair were collected and observed by hematoxylin-eosin staining and immunofluorescence staining. Results    Both the sham operation group and the pulmonary vein banding group survived. But the pulmonary vein banding group had obvious clinical manifestations of pulmonary venous stenosis. Compared with the sham group, the pulmonary vein banding group showed intimal hyperplasia, decreased expression of endothelial marker and increased expression of mesenchymal markers, and co-expression of endothelial and mesenchymal markers in intimal cells. Human pathology also showed intimal hyperplasia and co-expression of endothelial and mesenchymal markers in intimal cells. Conclusion    The surgical pulmonary vein stenosis in piglets shows intimal hyperplasia and myofibroblasts, which was consistent with clinical pathology.

Expression of myofibroblast in gingival after orthodontic loading / 华西口腔医学杂志

OBJECTIVE@#To examine the expression of myofibroblast in gingival after orthodontic loading.@*METHODS@#Eight patients were selected as experimental group and treated with orthodontic force for 4 months. Ten patients were selected as the control group, were not loaded. The gingival protein expressions of collagen typeⅠ, collagen type Ⅲ, α-smooth muscle actin (α-SMA) were evaluated by immunohistochemistry method.@*RESULTS@#Positive expressions of collagen typeⅠ, collagen type Ⅲ were founded, while no positive staining for α-SMA in the gingival tissue except vascular epithelium before loading. In experimental group, collagen type I and collagen type Ⅲ were increased after orthodontic loading (P<0.05), the expression of α-SMA was detected and statistically significant (P<0.05).@*CONCLUSIONS@#The myofibroblast exists in gingival tissue after orthodontic loading, and it may be concerned with orthodontic teeth relapse.

Curcumin blunt epithelial to mesenchymal transduction of hepatocytes to aggravate liver fibrosis through promoting autophagy in hepatocytes / 中国药理学通报

Aim To clarify the role of autophagy in the regulation mechanism of epithelial-mesenchymal transition(EMT) in hepatocytes and the transition to myofibroblast. Methods BNL CL. 2, a mouse embryonic hepatocyte, and BNL CL. 2 cells knocked-down BECN1 genes were treated with TGF-β1(2 μg . L-1) and curcumin(10, 20, 30 jimol • L - 1 ) . Real-time PCR and Western blot were used to detect Beclin-1, LC3, Vimentin and α-SMA gene and protein expression in BNL cl. 2 cells. The optical microscope was used to observe the changes of cell morphology. And the changes in cell autophagy were detected by GFPLC3 plasmid transfection. Results After the intervention of TGF-β1, the expression of Vimentin and α-SMA, the mesenchymal marker, increased and the autophagy decreased. Curcumin could inhibit Vimentin and a-SMA expression in hepatocytes. Moreover, curcumin could increase the autophagy related genes and protein expression of Beclin-1 and LC3 in hepatocytes. Curcumin could increase the level of autophagy and inhibit the cell transformation to myofibroblast-like cells. After interfering with BECN1, the effect of curcumin inhibiting hepatic EMT was partially blocked. Conclusions Curcumin could inhibit the process of EMT of hepatocytes by increasing the level of autophagy. The occurrence and development of liver fibrosis was consequently inhibited.

A Case of Dermatomyofibroma on Inguinal Area in a Middle Aged Woman / 대한피부과학회지

No abstract available.

Pathomechanisms of pericyte-myofibroblast transition in kidney and interventional effects of Chinese herbal medicine / 中国中药杂志

In the kidney, pericyte is the major source of myofibroblast (MyoF) in renal interstitium. It is reported that pericyte-myofibroblast transition（PMT）is one of the important pathomechanisms of renal interstitial fibrosis（RIF）. Among them, the main reasons for promoting RIF formation include pericyte recruitment, activation and isolation, as well as the lack of pericyte-derived erythropoietin. During the PMT startup process, pericyte activation and its separation from microvessels are controlled by multiple signal transduction pathways, such as transforming growth factor-β（TGF-β）pathway, vascular endothelial growth factor receptor (VEGFR) pathway and platelet derived growth factor receptor (PDGFR) pathway;Blocking of these signaling pathways can not only inhibit PMT, but also suppress renal capillaries reduction and further alleviate RIF. In clinic, many traditional Chinese medicine compound prescriptions, single traditional Chinese herbal medicine (CHM) and their extracts have the clear effects in alleviating RIF, and some of their intervention actions may be related to pericyte and its PMT. Therefore, the studies on PMT and its drug intervention will become the main development direction in the research field of anti-organ fibrosis by CHM.

Effects of botulinum toxin type A on accelerating skin expansion in rats / 中华医学美学美容杂志

Objective To observe the effect of botulinum toxin type A (BTX-A) on the rate of skin expansion and the immediate retract rate of skin flaps in rats,and to explore new methods for drug-assisted skin expansion.Methods 18 Sprague-Dawley rats were randomly divided into two groups.After BTX-A or normal saline was injected intradermally into the back marking area,an expander was implanted.The expanders were inflated periodically by injecting normal saline to reach the designated intraexpander pressure.The inflation volume was recorded and the area of marked region was measured regularly.After 4 weeks of expansion,the expanded tissues were harvested and the immediate retract rates were measured.The hematoxylin-eosin staining was performed to observe the thickness of epidermis,dermis and the fibrous capsule,while Masson staining for detection of fibrous capsule collagen.Immunohistochemical staining with α-smooth muscle actin for myofibroblasts was also performed.Results The mean inflation volume and area of marked region of BTX-A group were significantly greater than those of the control group.There were lower immediate retract rate,thinner fibrous capsule,less collagen content and fewer α-SMA positive myofibroblasts in the fibrous capsule of the BTX-A group with statistically significant differences (P ＜ 0.05).There was no signigicant difference in the thicknesses of epidermis and dermis between the two groups (P＞0.05).Conclusions BTX-A can inhibit the formation of fibrous capsule to promote skin expansion,while reducing the immediate retract rate.It possess a potential for assisting effectively skin expansion.