Expression of MMP-9 in patients with chronic rhinosinusitis and its correlation with epithelial-mesenchymal transition / 天津医药

Objective To investigate the mechanism of matrix metalloproteinase(MMP)-9 involved in epithelial mesenchymal transformation(EMT)in chronic sinusitis(CRS).Methods The expression of MMP-9 from polypoid middle turbinate tissue was detected by immunohistochemical staining qPCR and Western blot assay in 42 patients with CRS and 8 patients underwent septoplasty.Primary human nasal epithelial cells HNEpc were cultured in vitro and divided into the control group,the TGF-β1 group(5 μg/L TGF-β1 intervention)and the TGF-β1+si-MMP-9 group(transfected with si-MMP-9 and 5 μg/L TGF-β1 intervention).The expression of MMP-9 was detected by cell immunofluorescence staining.Expression levels of TGF-β1,MMP-9 and EMT-related proteins E-cadherin,vimentin and α-SMA were detected by Western blot assay.Results(1)The positive expression rate of MMP-9 was significantly higher in the nasal mucosa of CRS with nasal polyps(CRSwNP)group(54.5%,12/22)than that of the CRS without polyps(25.0%,5/20)group and the control group(12.8%,1/8).The relative expression levels of MMP-9 mRNA and protein in nasal mucosa were higher in the CRSwNP group than those in the CRSsNP group and the control group(P＜0.05).(2)Compared with the control group,the expressions levels of TGF-β1,MMP-9,vimentin and α-SMA were increased in the TGF-β1 group,while the expression of E-cadherin was decreased(P＜0.05).Compared with the TGF-β1 group,expression levels of TGF-β1,MMP-9,vimentin and α-SMA were decreased in the TGF-β1+si-MMP-9 group,and the expression of E-cadherin was increased(P＜0.05).Conclusion The expression of MMP-9 is increased in CRS patients,which may be involved in the development of CRS through the regulation of EMT.

miRNA derived from mesenchymal stem cells and its derivatives in treatment of pathological scar / 中国组织工程研究

BACKGROUND:Stem cell therapy has become an emerging method of treating pathological scars.miRNAs are involved in scarring mechanisms,and the targeted action of some stem cell sources of miRNA is mediated by exosomes. OBJECTIVE:To review the biological properties of miRNA derived from mesenchymal stem cells and its derivatives,the mechanism of treatment of scarring through anti-inflammation,suppression of excessive tissue reconstruction and antioxidation. METHODS:The first author used a computer in September 2023 to retrieve the relevant literature published from January 2000 to September 2023,searching for"stem cell,exosome,miRNA,keloid"in English,and"stem cells,exosome,keloid"in Chinese,eventually incorporating 74 papers for analysis. RESULTS AND CONCLUSION:(1)miRNAs with high expression of exosomes derived from mesenchymal stem cells increase the proportion of M2-type macrophages by promoting the polarization of macrophages,target the regulation of transforming growth factor β,transforming growth factor β receptors or related signaling pathways,inhibit the expression of pro-inflammatory factors,promote the expression of anti-inflammatory factors and other mechanisms to inhibit inflammation and thus suppress scar lesions.(2)miRNAs with high expression of exosomes derived from mesenchymal stem cells can reduce the secretion of matrix metalloproteinases,regulate the balance between matrix metalloproteinase inhibitors and matrix metalloproteinases,inhibit the proliferation and migration of fibroblasts and myofibroblasts,directly reduce the production of collagen and other mechanisms,and ultimately lead to the normal degradation of extracellular matrix,thereby inhibiting excessive tissue remodeling and cicatricial lesions.(3)miRNAs with high expression of exosomes from mesenchymal stem cells can improve the resistance of scar fibroblasts to oxidative stress by regulating reactive oxygen species and hypoxia-inducing factors,and then regulate the proliferation and apoptosis of scar fibroblasts to inhibit scar lesions.(4)Exosomes derived from mesenchymal stem cells have good prospects for scar treatment.Studies on this aspect can find mirnas that regulate inflammatory cells,inflammatory factors,signaling pathways,matrix metalloproteinases,fibroblasts,reactive oxygen species,hypoxia-inducing factors and other key factors from the three aspects of inflammation,tissue remodeling and oxidative stress.Then,by inducing mesenchymal stem cells with high expression of the above miRNA,exosomes were extracted,and finally verified and clinical trials were carried out.

The development of nasal polyps involves early middle meatus mucous remodeling via TGF-β1 mediated PAI-1 reduction

Abstract Objective Our study aimed to elucidate the effect of PAI-1 (Plasminogen Activator Inhibitor-1) and t-PA (Tissue-type Plasminogen Activator) in tissue remodeling in nasal polyps patients. Methods Samples were streamed as early Nasal Polyps (eNP, n = 10) and inferior tissue from the same patient, mature Nasal Polyps (mNP, n = 14), and Control group (n = 15), respectively. Immunohistochemistry and immunofluorescence were applied to detect localization. Quantitative Real-Time Polymerase Chain Reaction (qRT-PCR) and Western blot were used to measure different levels among three groups. The mNP tissue was cultured in vitro and treated with TGF-β1 (Transforming Growth Factor-beta 1) activator, TGF-β1 inhibitor (SB431542), and PAI-1 inhibitor (TM5275); then Western blot, qRT-PCR, and ELISA were used to assess changes. Results The immunohistochemistry and immunofluorescence showed that PAI-1 expression decreased in eNP and mNP, mainly in epithelium and glands. The transcriptional expression and protein level of TGF-β1/t-PA/PAI-1/Collagen1 were lower in eNP than IT while mNP group demonstrated lower mRNA expression and protein level of TGF-β1/t-PA/PAI-1/Collagen1 than Control group. In mNP tissue culture in vitro, TGF-β1 activator elevated t-PA, PAI-1, and Collagen1 with higher release of PAI-1 and Collagen1 in supernatant, whereas SB431542 suppressed above reactions; TM5275 lowered transcriptional and protein level of Collagen1 in supernatant. Conclusion Early Nasal polyps' formation in middle meatus mucous is related with fibrillation system PAI-1/t-PA and tissue remodeling; moreover, nasal polyps' development is regulated by TGF-β1-mediated PAI-1 reduction. Level of evidence 3b.

The Role of MicroRNA in Force-Related Periodontal Inflammatory Response and Tissue Remodeling / 医用生物力学

Micro-ribonucleic acid(miRNA) is a kind of non-coding single-stranded RNA, which can regulate the expression of genetic information by inhibiting mRNA translation of the target gene and participate in the occurrence and development of a variety of biological processes in vivo. miRNAs also take part in inflammatory diseases and tissue remodeling induced by mechanical forces. Mechanosensitive cells in periodontal tissue can lead to pathological/physiological changes such as periodontal inflammatory response and periodontal remodeling. miRNAs might have played important roles in the occurrence and development of force-related periodontal inflammatory diseases and tissue remodeling, by inhibiting the translation of specific genes in these cells. This article reviews the roles of miRNAs in force-related inflammatory response and tissue remodeling, especially in periodontal inflammatory response and tissue remodeling.

Role of TGF-β1/Smads signaling pathway in tissue remodeling of cultured nasal polyps in vitro / 上海交通大学学报（医学版）

Objective: To further explore the role of TGF-β1/Smads signaling pathway in the tissue remodeling process of cultured nasal polyps in vitro. Methods: Fifteen cases of chronic rhinosinusitis with nasal polyps (CRSwNP) and 15 cases of chronic rhinosinusitis without nasal polyps (CRSsNP) were screened out, and the control group was 10 patients with deviation of nasal septum. The location and expression of proteins in tissues were analyzed by immunohistochemistry. The expression and distribution of collagen were detected by using the method of Masson trichrome staining. The levels of mRNA and protein expression were detected by quantitative realtime polymerase chain reaction (qRT-PCR) and Western blotting respectively. Nasal polyps were treated ex vivo by TGF-β1 (n=15). The levels of mRNA and protein expression in culture pellets and collagen expression in culture supernatant were analyzed by qRT-PCR, Western blotting and ELISA respectively. Results: The TGF-β1, Smad2, Smad3 mRNA and protein expression levels were significantly decreased in the CRSwNP group compared with the CRSsNP group (all P<0.05). TGF-β1 and pSmad2/3 protein level showed positive correlation in CRS (r=0.991, P<0.01), so was TGF-β1 and Smad2, Smad3 mRNA levels (r=0.581, r=0.658, both P<0.01). TGF-β1 had positive correlation with collagen expression in CRS (r=0.982, P<0.01). Compared with the controls ex vivo, the levels of Smad2, Smad3, pSmad2/3 and collagen were markedly increased after TGF-β1 treatment. Conclusion: TGF-β1/Smads signaling pathway may play an important role in tissue remodeling of CRSwNP, and cause collagen reduction and edematous mucous membrane in nasal polyps.

Expression of hypoxia-inducible factor 1α in the pressure-side periodontium during orthodontic tooth movement in rats / 口腔疾病防治

Objective @#To assess hypoxia-inducible factor 1α (HIF-1α) expression levels in the periodontal tissues of the pressure side during orthodontic tooth movement in rats.@*Methods@#A total of 50 male 6-week-old Sprague Dawley (SD) rats were randomly divided into 10 groups of 5 rats each. The upper left first molar was the experimental tooth and was pulled mesially with an orthodontic force of 10-15 g for 0, 1, 3, 6, or 12 h, or 1, 3, 7, 14, or 21 d. Routine five-micrometer paraffin-embedded tissue sections were processed for HE staining and immunohistochemical staining for HIF-1α. The Image-Pro Plus system was used to quantitatively analyze the stained slices. The expression of HIF-1α in the periodontal tissue of the pressure side changed during the process of orthodontic tooth movement.@*Results@#The expression of HIF-1α increased immediately after loading for 1 h, reached a small peak at 3 h, and then decreased. After 12 h, the expression increased again, reached a peak after 1 d, and then gradually decreased to near the pre-loading level(P < 0.05). @*Conclusion@#There were differences in expression of HIF-1α in different groups in the periodontal tissues of the pressure side during orthodontic tooth movement in rats.

Vγ1+γδT Cells Are Correlated With Increasing Expression of Eosinophil Cationic Protein and Metalloproteinase-7 in Chronic Rhinosinusitis With Nasal Polyps Inducing the Formation of Edema

PURPOSE: We have found that expression of γδT cells is increased in pathological mucosa of chronic rhinosinusitis with nasal polyps (CRSwNP) compared with normal nasal mucosa. This increase is correlated with the infiltration of eosinophils in CRSwNP. Here, we investigated the expression of γδT cells, inflammation and tissue remodeling factors as well as their probable relationships in different types of chronic rhinosinusitis (CRS) in China. METHODS: A total of 76 surgical tissue samples that included 43 CRSwNP samples (15 eosinophilic and 28 non-eosinophilic), 17 CRS samples without nasal polyps (CRSsNP), and 16 controls were obtained. Quantitative reverse transcription-polymerase chain reaction (RT-PCR) was used to measure the mRNA expression levels of Vγ1⁺γδT cells, Vγ4⁺γδT cells, eosinophil cationic protein (ECP), interleukin (IL)-8, transforming growth factor (TGF)-β2, metalloproteinase (MMP)-7, tissue inhibitor of metalloproteinase (TIMP)-4 and hypoxia-inducible factor (HIF)-1α. Enzyme linked immunosorbent assay (ELISA) was used to measure the protein level of ECP and MMP-7 in CRSwNP. The eosinophils were counted and the level of edema was analyzed with HE staining. RESULTS: The mRNA expression levels of the Vγ1 subset, ECP and MMP-7 were significantly increased in CRSwNP with histological characteristics of eosinophilic infiltration and edema. The expression of the Vγ1 gene in CRSwNP correlated positively with the expression of both ECP and MMP-7. No significant decreases in the mRNA expression levels of TGF-β2, TIMP-4 or HIF-1α were observed in the CRSwNP samples. The expression levels of Vγ1 gene, ECP and MMP-7 were significantly increased in eosinophilic CRSwNP compared to non-eosinophilic CRSwNP. CONCLUSIONS: Our results suggest the associations between Vγ1⁺γδT cells, ECP and MMP-7 in CRSwNP, indicating that Vγ1⁺γδT cells can induce the eosinophilic inflammation, which has a further effect on the formation of edema.

Correlation of IL-19 and its receptors with tissue remodeling in chronic rhinosinusitis / 中国病理生理杂志

AIM:To explore the differential expression of interleukin-19 (IL-19) and its receptors (IL-20R1/IL-20R2) in the samples of chronic rhinosinusitis (CRS) with or without nasal polyps (CRSwNP and CRSsNP), and to investigate the correlation of IL-19 and its receptors with tissue remodeling factors, including matrix metalloproteinase (MMP)-2, MMP-9 and tissue inhibitor of metalloproteinase (TIMP)-1 in CRS.METHODS:The polyps from CRSwNP patients (n=30), the sinus mucosa from CRSsNP patients (n=15) and the inferior turbinal mucosa of nasal septum de-viation patients (n=15) were collected.The expression of IL-19 and its receptors (IL-20R1/IL-20R2) in each group was detected by real-time RT-PCR and immunohistochemistry.The expression of tissue remodeling factors MMP-2, MMP-9 and TIMP-1 in different groups was detected by real-time RT-PCR and ELISA.RESULTS:Increased mRNA and protein expression levels of IL-19, IL-20R1, IL-20R2 and MMP-9 were observed in CRSwNP group compared with CRSsNP and control group (P<0.05), while elevated expression level of TIMP-1 was observed in CRSsNP group compared with CRSwNP and control group (P<0.05).The relative expression of MMP-2 among the 3 groups showed no obvious difference.The expression of IL-19 and its receptors showed significantly positive correlations with MMP-9 in CRSwNP (P<0.05).No significant correlation between IL-19 and/or its receptors with TIMP-1 in CRSwNP group was observed.CONCLUSION:The high expression levels of IL-19, IL-20R1 and IL-20R2 and their positive correlations with MMP-9 in CRSwNP indica-te that IL-19 and its receptors may be involved in the tissue remodeling of chronic rhinosinusitis.

Study of histology in accellular dermal matrix after being transplanted in vivo over time / 实用医学杂志

Objective To demonstrate the histology in acellular dermal matrix(ADM)after being transplanted in vivo over time. Methods Forty male SD rats were recruited for the experiment. Subcutaneous implantation of an 1 cm × 1 cm ADM was given in the left sides on the back of the rat for the experimental group, while only dissection and suturing were performed in right side of the back for the control group. All the animals will be sacrificed at appointed time after operation, Five ADM samples were harvested in each time point. The content and proportion of collagen type were examined with HE staining, Picrosirius staining, Masson′s trichrome staining, and Immunohistochemical staining (targets: pan macrophage, M1 macrophage and M2 macrophage). Results All rats survived after operative without any complications. Significant differences of thickness were not observed at the end of 5 months; HE scores suggested that ADM increased in cell infiltration scores in 2 weeks before the plateau , vascularity also showed a similar trend; Collagen trichrome staining showed a substantial increase in density of collagen bundles with time. The comparison of the proportion of collagen among days showed significant differences (P < 0.05). Immunohistochemical staining of M1 and M2 showed that macrophages had distinct polarization profiles in materials. Furthermore, the comparison of M1 vs M2 response associated with different materials showed significant differences in all time points (P < 0.05). Conclusions The chemically cross-linked ADM could keep long time in the body; ADM significantly stimulated proinflammatory of M2 differentiation from M1 in constructive remodeling.

Obesity and adipose tissue remodeling / 中国药理学通报

Obesity is a major risk factor for the generation and development of diabetes, atherosclerosis, hyperlipidemia and cancer. Obesity is accompanied with remodeling of adipose tis-sue, such as changed cell component and function, angiogene-sis, extracellular matrix remodeling and infiltration of inflamma-tory cells. It is important for the prevention of obesity to study adipose tissue remodeling. This review summarizes recent ad-vances in adipose tissue remodeling.

Expression and significance of TSP-1 and BMP-7 in nasal mucosa of chronic rhinosinusitis / 基础医学与临床

Objective To explore the expression of thrombospondin-1 ( TSP-1 ) and bone morphogenetic protein-7 ( BMP-7 ) in mucus membrcane of chronic rhinosinusitis ( CRS ) and its potential significance in pathogenesis . Methods TSP-1 ,BMP-7 and TGF-β1 were detected by ELISA .Results The expression level of TSP-1 and TGF-β1 increased gradually with the advanced stage of CRSsNP ( P<0.05 ) .The expression of BMP-7 decreased gradu-ally with the advanced stage of CRSsNP ( P<0.05 ) .The expression of TSP-1 and TGF-β1 decreased gradually with the advanced stage of CRSwNP ( P<0.05 ) .The expression level of BMP-7 increased gradually with the ad-vanced stage of CRSwNP ( P<0.05 ) .Conclusions The expressions of TSP-1 and BMP-7 were abnormal in nasal mucosa of CRS , which might be involved in the pathogenesis of CRS .

Relação entre biomarcadores inflamatórios, de adesão celular, de estresse oxidativo, de lesão endotelial, remodelamento tecidual e vascular e os diferentes estágios da doença venosa crônica primária (classes clínicas CEAP C0a, C2, C3, C4) / Relationship between biomarkers of inflammation, cell adhesion, oxidative stress, endothelial cell damage, vascular and tissue remodeling and the different stages of primary chronic venous disease (CEAP clinical classes C0a, C2, C3, C4)

A doença venosa crônica (DVC) é uma desordem complexa que compreende sinais e sintomas que variam das telangiectasias às úlceras ativas. A DVC é classificada de acordo com aspectos clínicos, etiológicos, anatômicos e fisiopatológicos (CEAP) em sete classes variando de C0 à C6. A principal causa da DVC é a hipertensão venosa que altera o fluxo venoso e, consequentemente, a força de cisalhamento que induz alterações fenotípicas nas células endoteliais que passam a expressar mediadores pró-inflamatórios e pró-trombóticos, que levam à adesão de leucócitos, ao aumento do estresse oxidativo, da permeabilidade vascular e do dano endotelial e ao remodelamento tecidual e vascular.Em virtude dos inúmeros mecanismos e da diversidade de moléculas envolvidas na patogênese e progressão da DVC, é essencial conhecer a interação entre elas e também saber quais são as moléculas (biomarcadores) que se correlacionam positivamente ou negativamente com a gravidade da doença. Foram avaliados os níveis de Interleucina-6 (IL-6), sL-selectina, sE-selectina, sP-selectina, molécula de adesão intercelular-1solúvel (sICAM-1), molécula de adesão das células vasculares-1 solúvel (sVCAM-1), ativador tecidual do plasminogênio (tPA), atividade do inibidor do ativador do plasminogênio-1 (PAI-1), trombomodulina solúvel (sTM), fator de von Willebrand (vWF), metaloproteinase de matriz (MMP)-2, MMP-3, MMP-9, inibidor tecidual das MMPs -1 (TIMP-1), angiopoietina-1 e -2, sTie-2 e s-Endoglina e fator de crescimento do endotélio vascular (VEGF) no sangue coletado da veia braquial de 173 mulheres com DVC primária divididas em grupos C2, C3, C4 e C4 menopausadas (C4m) e de 18 voluntárias saudáveis (grupo C0a). Foram também analisados os níveis urinários de ent-prostaglandina F2α nesses grupos. Não foram encontradas diferenças estatisticamente significativas com relação às concentrações sanguíneas e urinárias de sE-selectina, sP-selectina, sICAM-1, atividade de PAI-1, MMP-3, razão TIMP-1/MMP-3 ...

Chronic Venous Disease (CVD) is a complex disorder, which encompasses signs and symptoms that vary from telangiectasias to active ulcers. The CVD is classified according Clinical, Etiologic, Anatomical and Pathophysiological (CEAP) aspects into seven classes varying from C0 to C6. The main cause of CVD is venous hypertension, which alters venous flow and consequently, shear stress. Abnormal shear stress induces phenotypic changes in endothelial cells that start to express pro-inflammatory and pro-thrombotic mediators that lead to leukocyte adhesion, oxidative stress, increased vascular permeability and endothelial cell damage and tissue and vascular remodeling. Due to several mechanisms and the diversity of molecules involved in the pathogenesis and progression of CVD, is essential to know the interplay between them and which are the molecules (biomarkers) that correlate positively and negatively with the severity of the disease. We investigated the levels of interleukin-6 (IL-6), sL-selectin, sE-selectin, sP-selectin, soluble intercellular adhesion molecule-1 (sICAM-1), soluble vascular cell adhesion molecule-1 (sVCAM-1), tissue plasminogen activator (tPA), plasminogen activator inhibitor-1 (PAI-1) activity, soluble thrombomodulin (sTM), von Willebrand factor (vWf), matrix metalloproteinase (MMP)-2, MMP-3, MMP-9, tissue inhibitor of metaloproteinases-1 (TIMP-1), angiopoietin-1 and -2, sTie-2, s-Endoglin, vascular endothelial growth factor (VEGF) in the blood taken from the brachial vein of 173 patients with primary CVD divided into C2, C3, C4 and menopaused C4 (C4m) groups and 18 healthy volunteers (C0a group).We also investigated the urinary levels of ent-prostaglandin F2α in these groups. There was no statistically significant difference between groups with respect to blood or urinary levels of sE-selectin, sP-selectin, sICAM-1, PAI-1 activity, MMP-3, TIMP-1/MMP-3 ratio, angiopoietin-2, angiopoietin-1/angiopoietin-2 ratio, s-Endoglin ...

Participación de MT1-MMP en la remodelación del ligamento periodontal durante la movilización dentaria / Role of MT1-MMP in the remodeling of the periodontal ligament during tooth movement

La movilización dentaria involucra una serie de cambios en los tejidos de soporte caracterizados por la activa remodelación de estos. La MT1-MMP o MMP-14 es una potente enzima proteolítica capaz de degradar colágeno tipo I, la principal molécula estructural del ligamento periodontal. La migración dentaria requiere de la degradación controlada del colágeno constituyente del ligamento periodontal. Sin embargo, no existen evidencias de la participación de MT1-MMP en la remodelación del tejido periodontal durante este proceso. En el presente estudio hemos analizado la expresión de MT1 -MMP y del marcador de actividad osteoclástica Fosfatasa Acida Tartrato Resistente (TRAP) en un modelo de migración dentaria en ratas. La migración dentaria fue activada mediante la inserción de una banda separadora entre los incisivos superiores. La expresión y distribución de TRAP y MT1-MMP fue evaluada a través de citoquímica e inmunohistoquímica a los días 1, 3, 5 y 7. La producción de TRAP fue identificada principalmente en osteoclastos ubicados en la zona de compresión del ligamento periodontal. La producción de MT1-MMP fue observada en fibroblastos de la zona de compresión del ligamento periodontal y osteoclastos ubicados en esta misma región. Nuestros resultados permiten proponer que tanto MT1 -MMP como TRAP participan en la remodelación de los tejidos de soporte periodontal durante la migración dentaria.

Tooth movement involves a series of changes of the supporting periodontal tissues characterized by the active connective tissue remodeling. MT1-MMP or MMP-14 belongs to the family of matrix metalloproteinases that are able to degrade type I collagen, the main molecule involved in periodontal attachment. Tooth migration requires the controlled degradation of periodontal ligament collagen fibers. However, evidences linking MT1 -MMP expression with periodontal tissue remodeling are lacking. In the present study, we have evaluated the expression of MT1-MMPand of the osteoclast marker Tartrate Resistant Acid Phosphatase (TRAP) in a model of tooth migration in rats. Tooth migration was induced after the insertion of a rubber band between the upper incisors. The distribution of TRAP and MT1 -MMP was evaluated by means of cytochemistry and immunohistochemistry respectively at days 1, 3, 5 and 7. TRAP production was identified in osteoclasts at the area of compression of the periodontal ligament. MT1-MMP distribution was observed in fibroblastsatthe compressed area of the periodontal ligament and also in osteoclasts of the same region. Our findings allow us to propose that MT1-MMP and TRAP take part of the tissue remodeling events observed during tooth movement.

Dieta hiperlipídica materna e pós-natal promove remodelamento adverso do fígado, pâncreas e tecido adiposo na prole / Maternal and postnatal high-fat diet and promotes adverse remodeling of the liver, pancreas and adipose tissue in offspring

A dieta hiperlipídica (high-fat, HF) materna durante a gestação e/ou lactação aumenta a susceptibilidade da prole para o desenvolvimento de doenças crônicas na fase adulta. Verificar a hipótese que a ingestão materna de dieta HF nos períodos críticos de desenvolvimento (gestação e/ou lactação) predispõe à doença não alcoólica do fígado gorduroso e alterações pancreáticas e no tecido adiposo de camundongos machos adultos. Camundongos C57BL/6 fêmeas receberam durante a gestação e/ou lactação dieta padrão (standard chow, SC) ou HF. Filhotes machos foram divididos em cinco grupos: SC - provenientes de mães SC; G - provenientes de mães HF durante a gestação; L - provenientes de mães HF durante a lactação; GL/HF - provenientes de mães HF durante a gestação/lactação, mantendo a mesma dieta HF no período pós-natal (do desmame aos 3 meses de idade); GL - provenientes de mães HF durante a gestação/lactação trocando a dieta para SC no período pós-natal (do desmame aos 3 meses de idade). Foi analisada ao longo do experimento a massa corporal da prole. No sacrifício (3 meses), o fígado, o pâncreas e a gordura epididimária foram removidos, pesados e processados e o sangue foi coletado para análise bioquímica. Ao nascimento e ao desmame, filhotes GL/HF foram mais pesados (+6% e +44%, p<0,05, respectivamente) que os filhotes SC. Os filhotes G apresentaram resistência à insulina e menor expressão do transportador de glicose no fígado (GLUT-2). A esteatose hepática foi observada nos grupos G, L, GL e principalmente nos filhotes do grupo GL/HF. A expressão hepática da proteína ligante de elementos regulatórios de esteróis (SREBP-1c) estava aumentada nos filhotes G, GL e GL/HF. Os filhotes G, GL e GL/HF apresentaram hipertrofia da ilhota pancreática e dos adipócitos quando comparados com o grupo SC. O consumo de dieta HF durante a gestação mostra-se ser o período mais prejudicial para os filhotes adultos de camundongos. A programação metabólica por dieta HF ...

Maternal high-fat diet (HF) during gestation and/or lactation period increases the susceptibility to development of chronic disease in offspring adult life. This work aimed to verify the hypothesis that maternal intake of high-fat diet in critical periods of pregnancy and/or suckling period predisposes to non alcoholic fatty liver disease, pancreatic and adipose tissue alterations in adulthood mice offspring. C57BL/6 female mice were fed, during gestation and/or lactation phases, with standard chow (SC) of HF diet. Male pups were divided into 5 groups: SC - from SC fed dam; G - from HF fed dam during gestation period; L - from HF fed dam during lactation period; GL - from HF fed dam during gestation and lactation periods and GL/HF - from HF fed dam during gestation and lactation, maintaining HF diet from post-weaning to adulthood. We analyzed body mass in all experiment, and at the euthanasia (3 mo-old), liver, pancreas and adipose tissue were removed, weighted and embedded. Blood was collected to biochemical analyses. At birth and at weaning, GL/HF pups were heavier than SC pups (+6% and +44%, p<0.05, respectively). G offspring showed insulin resistance and lower glucose transporter-2 expression (GLUT-2). Hepatic steatosis was present in G, L, GL and mainly in GL/HF offspring. Sterol regulatory element-binding protein-1c (SREBP-1c) expression was higher in G, GL and GL/HF offspring. It is important to mention that pancreatic islet hyperthophy and adipocyte hypertrophy were affected in G, GL and GL/HF offspring in comparison to SC. HF diet administration during gestation period is worse than lactation period. Furthermore, this type of programming by HF predisposes to adverse remodeling in liver, pancreas and adipose tissue in adult mice offspring

Role of brain tumor stem cells in tumor tissue remodeling / 中华神经医学杂志

Objective To investigate the origin of tumor cells and vascular endothelial cells in intraeranial brain tumor stem cell (BTSC) xenografls and elucidate the role of BTSCs in brain tumor tissue remodeling. Methods BTSC spheres were injected into the right candate nucleus of nude mice, and the mice were sacrificed after the occurrence ofcachexia to obtain the tumor tissue. Routine paraffin embedding, slicing, HE staining and human leucocyte antigen (HLA) staining of the tumor tissues were performed for observation of the tumor tissues under optical microscope. Results HE staining displayed dissemination growth of the tumor cells in the host brain tissue. HLA staining revealed the presence of blood vessels constituted directly by the tumor cells. Conclusion In the intracranial xenografts of BTSCs, the tumor cells are extensively distributed and constitute the blood vessels. The BTSCs play an important role in glioma tissue remodeling by differentiating into vascular endothelial cells in the tumors.

Remodeling of skin nerve fibers during wound healing / 中国矫形外科杂志

[Objective]To observe changes of skin reinnervation during burn wound healing and determine remodeling of nerve fibers.[Method]Wound tissue and scars were harvested.Collagen was determined with modified Masson trichrome staining and nerve fibers were labeled with neuro filament protein by immunofluorescent technique.Three dimension reconstruction of nerve fibers regenerated was observed under laser scanning confocal microscope.[Result]The CVF(collagen volume fraction) increased during the process of wound healing.The regenerated nerve fibers were sparse,short and small,which was significant lower the normal control.The skin reinnervation improved during the wound healing process and came to peak NVF(nerve fiber volume fraction) in proliferative stage.Disintegration and fragmentation were observed frequently in samples from proliferative stage,which seldom occurred during mature stage.[Conclusion]The remodeling of skin nerve fibers comprises a sequential process of increasing number,shape distortion during wound healing and then disintegration,number decrease and normal shape.

La función plaquetaria más allá de la hemostasis: participación en las enfermedades respiratorias / Platelet function beyond haemostasis: Role in respiratory diseases

Actualmente se sabe que las plaquetas, además de almacenar diversos mediadores químicos, también tienen la capacidad de realizar síntesis de varios tipos de proteínas a partir de ARN preformados y de interaccionar con diversos tipos de partículas, con componentes de la matriz extracelular y con varios tipos celulares. Estas características posibilitan que las plaquetas intervengan activamente, no sólo en la hemostasis y trombosis, sino también en la inflamación, remodelación tisular y posiblemente en la defensa innata.

Platelets store different chemical mediators and synthetize various types of proteins from preformed RNA; they also interact with different particles, components of the extracellular matrix and with different kinds of cells. This characteristics enable platelets to have important roles In hemostasis, thrombosis, inflammation, tissue remodeling and possibly in mechanisms of innate defense.

A study on the effects of Electrical stimulation by the miniature Electric device on the tooth movement and tissue remodeling / 대한치과교정학회지

Electric current is a highly probable way as a clinical tool for tooth movement. The purposes of this study were to determine the usefulness of exogenous electric currents in accelerating orthodontic tooth movement and to investigate the effects of electric-orthodontic treatment on the remodeling of the periodontal tissue histologically. The study was performed with six male cats weighing around 3kg. The electric device which is providing the direct electric current of 20microA was inserted to the removable appliance. The right and left maxillary canines were assigned as control and experimental sides respectively. The control canine was provided with orthodontic force (75gm) only and the experimental side was given the same amount of force and electricity. The lingual buttons were bonded to the maxillary canines and both sides of canines were retracted with NiTi coil spring. The electric device was adjusted to provide 20microA direct current to the experimental canines 5 hours a day. The amount of the canine movement was measured with electronic caliper every week. After 4 weeks of tooth movement, the animals were sacrificed and the histologic study was performed. The results of this study were as follows : 1. The application of a direct current to the experimental tooth significantly increased the final amount of orthodontic tooth movement. The amount of tooth movement after 28-day was 37% more in the experimental side. 2. The electrically stimulated tooth showed histologic evidence of significant increases in the amount of bones and matrix deposition in the area of tension. 3. In the compression side, the electric-orthodontic treatment stimulated bone resorption more extensively in the experimental canines. 4. After 28 days of electricity exposure and orthodontic force, the experimental side demonstrated significantly more osteoblasts, osteoclasts, capillaries and osteoid tissues, reflecting an increase in the local tissue's cellular activity. 5. Intermittent electrical stimulation (five hours a day) had effects to enhance orthodontic tooth movement and tissue remodeling. These results suggested that the low-intensity exogenous electric current by the miniature electric device might accelerate orthodontic tooth movement and bone remodeling in vivo and have the possibility to reduce the orthodontic treatment duration.

Experimental study on influence of endostatin on pathological features of C_6 glioma / 中国药理学通报

Aim To investigate the influence of endostatin on pathological morphology of C_6 glioma and its molecular pharmacologic mechanism.Methods The C_6 cells,the C_6 clone stably transfected with endostatin cDNA(endo-C_6),which the endostatin with biological activities can be secreted from,and the C_6 clone stably transfected with empty vector pBudCE4.1 cDNA(pBud-C_6) were injected subcutaneous in nude mice to establish different tumoral model respectively.The morphologies of these tumoral tissues were observed and compared to each other under light and electron microscope.The expression of VEGF in tumor tissue was determined by ELISA.Results The expression of VEGF in endo-C_6 glioma(endo-C_6G) tissues was lower than that in C_6 glioma(C_6G) and pBud-C_6 glioma(pBud-C_6G).Moreover,endo-C_6G tissue was characteristic of a mimetic envelope,no intratumor bleeding and cystis degeneration,apoptosis of tumor cells,and edema in and around tumor.Rarefied vessels were found in tumor,and no vessel like structure formed by tumor cells was observed.The large irregular necrosis focus was showed in tumor,but mild vascular reaction around necrosis focus and peritumor,rare surrounding invasion.The basal lamina was discontinued.The basemembrane(BM) was loose.Few vesicular vacuolar organelle(VVO) structures were observed in plasma of endothelial cells.In C_6G and pBud-C_6G,tumor lesions demonstrated significant vascular reaction,intratumor bleeding,necrosis,edema in and around tumor,and surrounding infiltration.Vessel like structure formed by tumor cells was also observed.When examined with electron microscope,plenty of VVO structures were observed in plasma of endothelial cells,the worse the edema,the more the VVO were,which coincided with the expression of VEGF.Mostly,loose basal lamina surrounded by small amounts of collagen fibers was multilayer and integrated and continuous.No correlation between gene transfection and fenestra formation or cleft of capillary endothelial cell was observed,no apoptosis of endothelial cells were found.Conclusion In glioma,the apoptosis of endothelial cells tissue was not induced directly by endostatin,but the angiogenesis and vascular reaction can be inhibit by endostatin by down-regulation of the expression of VEGF in C_6 glioma cells.

Granule tissue remodeling under neoepithelium in pig's full thickness dermal wounds / 中华创伤杂志

Objective To observe the granule tissue remodeling under neoepithelium in minitype pigs' full thickness dermal wounds and discuss the relation between the remodeling and possible ulcers or scars. Methods After the establishment of eight full-thickness dermal wound models with the diameter of 4 cm on the back of six minitype pigs, the specimens were collected from wound edge and wound center immediately, 3, 6, 9, 12, 15, 20, 25, 30 and 45 days, respectively after injury for HE staining, immunohistochemical staining and Van Gieson staining and then observed under light microscope to count the cell number, fibroblasts and vascular endothelial cells as well as evaluate the quantity and arrangement of collagens. Results The mean wound healing time was (29.3?1.8) days. After 9-25 days, the granule tissues in the wound center contained more cells, fibroblasts, collagen and vascular endothelial cells than those under neoepithelium of wound edge (P 0.01). Meanwhile, the collagen quantity and arrangement style of granule tissues under neoepithelium during wounds healing (12-30 days) assembled those under neoepithelium 15 days after wound healing. Conclusion Granule tissue remodeling exists during the healing of full thickness dermal wound.