ObjectiveTo investigate the expressions of type Ⅰ and type Ⅲ collagen protein in hepatic alveolar echinococcosis tissues, and to explore its relationship with the biological behavior in progress of hepatic alveolar echinococcosis (HAE).
MethodsTwenty samples of normal liver tissues and liver tissues at the edge of the lesion with HAE in our hospital from Jan. 2012 to Dec. 2014 were collected, and HE and Masson staining were performed. The pathological changes and the degree of fibrosis of liver tissues around HAE lesion were observed under light microscope. The expressions of type Ⅰ and type Ⅲ collagen protein in liver tissues were detected by immunohistochemical staining.
ResultsThe degree of liver fibrosis of liver tissues at the edge of the lesion with HAE was grade Ⅱ, and the degree of fibrosis of normal liver tissues was grade 0, the difference between the two was statistically significant (P < 0.05). The color index of type Ⅰand type Ⅲ collagen protein in the liver tissues at the edge of the lesion with HAE was 7.45±1.85 and 8.00±1.62, respectively, which were higher than those of normal liver tissues (3.10±1.02 and 3.50±0.89), the difference were statistically significant (t=-9.21, P=0.001;t=-10.88, P=0.001).
ConclusionsThere is liver fibrosis around the lesion in the patients with HAE. HAE may promote the expressions of type Ⅰ and type Ⅲ collagen and then induce the occurrence of liver fibrosis.
Objective To assess value and limitations of non-invasive methods in assessing liver fibrosis．Methods By summarized current situation and advancement of serum fibrotic markers, ultrasound, CT and MRI in assessing liver fibrosis, we investigated their value and limitations. Results In addition to diagnosis, non-invasive methods of assessing liver fibrosis assess severity of liver fibrosis. For liver fibrosis, however, non-invasive methods can not monitor effectively reaction to therapy and progression. Conclusion Non-invasive methods play important roles in diagnosis and assessing severity of liver fibrosis, and reduce the need of liver biopsy.
ObjectiveTo investigate the effect of diammonium glycyrrhizinate (DG) plus bone marrow mesenchymal stem cells (MSCs) transplantation in the treatment of acute exacerbation of pulmonary fibrosis induced by bleomycin (BLM) in rats.MethodsMSCs were isolated from male Wistar rats and cultured in vitro. Twenty-four female Wistar rats were randomly divided into 4 groups. The NC group was intratracheally injected with normal saline; the BLM group, the MSC group and the DGMSC group were intratracheally injected with BLM for 7 days; then the MSC group was injected with 0.5 mL of MSCs solution (2.5×106 cells) into the tail vein; the DGMSC group was intraperitoneally injected with DG for 21 days in a dose of 150 mg·kg–1·d–1 on the base of the MSCs injection. The rats were sacrificed on the 28th day and the lung tissue was extracted. Pathological examination was performed to determine the degree of alveolitis and pulmonary fibrosis. Immunofluorescence was used to detect the number and distribution of alveolar type Ⅱ epithelial cells. Alkali hydrolysis method was used to determine the content of hydroxyproline (HYP) in lung tissue; thiobarbituric acid method was used to measure the content of malondialdehyde (MDA) in lung tissue; colorimetric method was used to determine the superoxide dismutase activity (SOD) and total antioxidant capacity (T-AOC); enzyme linked immunosorbent assay was used to detect the expression levels of tumor necrosis factor-α (TNF-α ) and transforming growth factor-β1 (TGF-β1) in lung tissue homogenates.ResultsThe DG combined with MSCs injection can reduce the degree of alveolitis and pulmonary fibrosis in BLM model rats. The content of HYP and TGF-β1 in lung tissue homogenate of the DGMSC group were significantly lower than those in the MSC group (P<0.05). Meanwhile, DG combined with MSCs injection significantly increased the antioxidant capacity of the BLM model rats. MDA content decreased, SOD activity and T-AOC ability improved significantly in the DGMSC group compared with the MSC group (P<0.05). The alveolar type Ⅱ epithelial cells were significantly increased and the cell morphology was maintained in the DGMSC group compared with the MSC group.ConclusionsDG has a synergistic effect with MSCs in treatment of acute exacerbation of pulmonary fibrosis. The mechanism may be related to reducing inflammatory factors during pulmonary fibrosis, attenuating oxidative stress and promoting MSCs migration into lung tissue and transformation to alveolar type Ⅱ epithelial cells.
Objective To review the current status of magnetic resonance imaging (MRI) techniques in the evaluation of hepatic fibrosis. Methods The application and recent advances of various kinds of MRI techniques in evaluating hepatic fibrosis were summarized by literature review. Results The state-of-the-art of MRI evaluating of hepatic fibrosis included common contrast-enhanced MRI, double contrast-enhanced MRI, and various functional MRI techniques. Common contrast-enhanced MRI could detect morphological changes of the liver, but little value in phasing. Double contrast-enhanced MRI markedly increased the contrast to noise ratio. Except diagnosis liver fibrosis, functional MRI also could phase it by its serverity. Conclusion MRI techniques, especially those functional MRI techniques, are advancing very fast and have very great potentiality in both the diagnosis and severity assessment of hepatic fibrosis.
Objective To explore the effects of 4-phenylbutyric acid (4-PBA) on idiopathic pulmonary fibrosis (IPF) using a murine model of bleomycin (BLM)-induced pulmonary fibrosis. Methods Pulmonary fibrosis was induced in C57BL/6 mice by intratracheal injection of BLM. A total of 120 mice were randomly allocated into three groups: BLM group, BLM+4-PBA group, and control group. Pathology of lung tissue was analyzed to evaluate the degree of pulmonary fibrosis, and the survival of the mice was noted. The expression levels of the endoplasmic reticulum stress markers, activating transcription factor 6 (ATF6) and C/EBP homologous protein (CHOP), were analyzed in lung tissues from mice. Results BLM induced significant collagen deposition in the lungs of the mice, which was alleviated by 4-PBA. 4-PBA also dramatically improved the pulmonary function and increased the survival rate in the BLM+4-PBA group compared with that in the BLM group. Both the mRNA and protein expression levels of ATF6 and CHOP were significantly reduced in mouse lung tissue after 2 weeks of 4-PBA treatment. Conclusions 4-PBA treatment could alleviate BLM-induced pulmonary fibrosis in mice via the attenuation of endoplasmic reticulum stress.
ObjectiveTo investigate the role of PI3K/Akt/HIF-1αsignaling pathway in bleomycin-induced pulmonary fibrosis in mice.
MethodsFifty-six C57BL/6 mice were randomly divided into a control group and a bleomycin (BLM) group.The pulmonary fibrosis model was induced by single intratracheal instillation of BLM(2.5 mg/kg) in the BLM group.Similarly, 0.9% saline was instilled directly into the trachea in the control group.Then all mice were sacrificed on 21st day.The lungs were collected for morphometric analysis with HE and Masson staining.The degree of pulmonary fibrosis was evaluated with Ashcroft score and content of hydroxyproline.The activity of PI3K/Akt/HIF-1αsignaling pathway and pro-surfactant protein C (Pro-SPC) were measured by Western blot.The level of collagen3 mRNA was assessed with quantitative real time PCR analysis.Collagen3 protein and numbers of apoptosis cells were observed with immuno-histochemistry.
ResultsIt was exhibited that the thickening alveolar septa, accumulation of inflammatory cells, and fibrous obliteration in the BLM group but not in the control group.There was a significant difference in Ashcroft score and hydryoproline content in the BLM group.Meanwhile, the activity of PI3K/Akt/HIF-1αsignaling pathway was up-regulated and the protein of Pro-SPC was decreased in the BLM group.It was revealed that the numbers of apoptosis cells, expressions of Collagen3 protein and mRNA were increased in the BLM group.
ConclusionAberrant activity of PI3K/Akt/HIF-1αsignaling pathway may aggravate the pulmonary fibrogenesis.
Liver fibrosis in chronic liver disease refers to the body’s repair response to sustained repeated necrosis or inflammation of liver cells, which results in fibrosis accompanied by relative or absolute lack of fiber degradation and deposition of extracellular matrix in the liver. Early and timely diagnosis and treatment of hepatic fibrosis are of great importance to patients with liver disease. A rational and complete diagnostic model of liver fibrosis should involve clinical pathology and histology, imaging, and serum biochemical markers. Liver biopsy has been regarded as the "gold standard" for the diagnosis of liver fibrosis and as a reference standard for other non-invasive diagnostic tests of liver fibrosis. Since it is invasive, liver biopsy is difficult to implement in clinical practice and a second liver biopsy is even more difficult. As for the non-invasive diagnosis of liver fibrosis, clinical symptoms and signs are not specific. The sensitivity and specificity of individual serum biochemical markers are still very weak, and imaging studies also lack specificity. The mathematical model “FibroTest” of serum biochemical markers has better diagnostic accuracy, but the calculation is complicated, making it difficult to achieve widespread use. There is insufficient evidence to suggest that the "gold standard" of liver biopsy can be replaced. Therefore, further research is needed to investigate how best to balance the benefits and harms of different tests, to identify the best combination, to simplify any calculation steps, to reduce costs, to avoid liver biopsy, and to find new, more specific and sensitive markers.
Objective To investigate the effects of bursopentin ( BP5) on expression of extracellular matrix in human lung fibroblasts ( HLFs) and its mechanism.Methods HLFs were cultured in vitro and divided into five groups. The cells in the control group were cultured in DMEMwithout TGF-β1 or BP5. The cells in TGB-β1 treatment group were cultured in DMEMcontaining 5 μg/L TGF-β1 . While in three TGF-β1 + BP5 treatment groups, the cells were cultured in DMEM containing 5 μg/L TGF-β1 and simultaneously intervened with BP5 at three different concentrations ( 2. 5 μg/mL, 5 μg/mL, and 10 μg/mL respectively) . The expression of α-SMA was detected using a fluorescent-labeling strategy. The expressions of Collagen-Ⅰ, p-Smad2/3, p-Smad3, and Smad7 proteins were measured by Western blot. Results The cells in the TGF-β1 treatment group showed positive expression of α-SMA, implying TGF-β1 had induced fibroblasts to differentiate into myofibroblasts. In the TGF-β1 treatment group, the expressions of collagen-Ⅰ( 1. 402 ±0. 158 vs. 0. 605 ±0. 367) , p-Smad2/3 ( 1. 457 ±0. 111 vs. 0. 815 ±0. 039) , and p-Smad3 ( 1. 320 ±0. 147 vs. 0. 623 ±0. 128) increased with statistical significance ( P lt; 0. 01) . Meanwhile the expression of Smad7 reduced ( 0. 614 ±0. 107 vs. 0. 865 ±0. 063, P lt;0. 05) . But in the TGF-β1 + BP5 treatment groups, over-expressions of collagen-Ⅰ, α-SMA, p-Smad2 and p-Smad3 induced by TGF-β1 were obviously inhibited by BP5, especially at the BP5 concentration of 10 μg/mL ( collagen-Ⅰ: 0. 718 ±0. 049 vs. 1. 402 ±0. 158; p-Smad2 /3: 0. 696 ±0. 031 vs. 1. 457 ±0. 111; p-Smad3: 0. 766 ±0. 006 vs. 1. 320 ±0. 147; all P lt; 0. 01) . Otherwise, the up-regulation of Smad7 ( 1. 237 ±0. 173 vs. 0. 614 ±0. 107) was found.Conclusions Bursopentin can reduce the expressions of collagen-Ⅰ and α-SMA protein of fibroblast stimulated by TGF-β1 , maybe through inhibiting TGF-β1 /Smads transduction pathway. It is suggested that bursopentin may have intervention effect on pulmonary fibrosis.
After pirfenidone and nintedanib showed efficacy, drug treatment for idiopathic pulmonary fibrosis began to focused on anti-fibrosis. Current research on idiopathic pulmonary fibrosis mainly focus on the pathogenesis and therapeutic targets, and more targeted drugs are gradually entering clinical trials. This article summarizes the results of recent studies on the treatment of idiopathic pulmonary fibrosis with pirfenidone and nintedanib alone or in combination by searching the literature, and reviews the mechanism and test results of the new target anti-fibrosis drugs based on molecular biology that are currently undergoing clinical research in various phases, and aims to provide a basis for how to choose drugs to treat idiopathic pulmonary fibrosis.
Idiopathic pulmonary fibrosis (IPF) is a progressive scar-forming disease with a high mortality rate that has received widespread attention. Epithelial mesenchymal transition (EMT) is an important part of the pulmonary fibrosis process, and changes in the biomechanical properties of lung tissue have an important impact on it. In this paper, we summarize the changes in the biomechanical microenvironment of lung tissue in IPF-EMT in recent years, and provide a systematic review on the effects of alterations in the mechanical microenvironment in pulmonary fibrosis on the process of EMT, the effects of mechanical factors on the behavior of alveolar epithelial cells in EMT and the biomechanical signaling in EMT, in order to provide new references for the research on the prevention and treatment of IPF.
