In the central nervous system, the formation of fibrotic scar after injury inhibits axon regeneration and promotes repair. However, the mechanism underlying fibrotic scar formation and regulation remains poorly unders...In the central nervous system, the formation of fibrotic scar after injury inhibits axon regeneration and promotes repair. However, the mechanism underlying fibrotic scar formation and regulation remains poorly understood. M2 macrophages regulate fibrotic scar formation after injury to the heart, lung, kidney, and central nervous system. However, it remains to be clarified whether and how M2 macrophages regulate fibrotic scar formation after cerebral ischemia injury. In this study, we found that, in a rat model of cerebral ischemia induced by middle cerebral artery occlusion/reperfusion, fibrosis and macrophage infiltration were apparent in the ischemic core in the early stage of injury(within 14 days of injury). The number of infiltrated macrophages was positively correlated with fibronectin expression. Depletion of circulating monocyte-derived macrophages attenuated fibrotic scar formation. Interleukin 4(IL4) expression was strongly enhanced in the ischemic cerebral tissues, and IL4-induced M2 macrophage polarization promoted fibrotic scar formation in the ischemic core. In addition, macrophage-conditioned medium directly promoted fibroblast proliferation and the production of extracellular matrix proteins in vitro. Further pharmacological and genetic analyses showed that sonic hedgehog secreted by M2 macrophages promoted fibrogenesis in vitro and in vivo, and that this process was mediated by secretion of the key fibrosis-associated regulatory proteins transforming growth factor beta 1 and matrix metalloproteinase 9. Furthermore, IL4-afforded functional restoration on angiogenesis, cell apoptosis, and infarct volume in the ischemic core of cerebral ischemia rats were markedly impaired by treatment with an sonic hedgehog signaling inhibitor, paralleling the extent of fibrosis. Taken together, our findings show that IL4/sonic hedgehog/transforming growth factor beta 1 signaling targeting macrophages regulates the formation of fibrotic scar and is a potential therapeutic target for ischemic stroke.展开更多
The rapid formation of a glial/fibrotic scar is one of the main factors hampering axon growth after spinal cord injury. The bidirectional Eph B2/ephrin-B2 signaling of the fibroblast-astrocyte contact-dependent intera...The rapid formation of a glial/fibrotic scar is one of the main factors hampering axon growth after spinal cord injury. The bidirectional Eph B2/ephrin-B2 signaling of the fibroblast-astrocyte contact-dependent interaction is a trigger for glial/fibrotic scar formation. In the present study, a new in vitro model was produced by coculture of fibroblasts and astrocytes wounded by scratching to mimic glial/fibrotic scar-like structures using an improved slide system. After treatment with RNAi to downregulate Eph B2, changes in glial/fibrotic scar formation and the growth of VSC4.1 motoneuron axons were examined. Following RNAi treatment, fibroblasts and astrocytes dispersed without forming a glial/fibrotic scar-like structure. Furthermore, the expression levels of neurocan, NG2 and collagen I in the coculture were reduced, and the growth of VSC4.1 motoneuron axons was enhanced. These findings suggest that suppression of Eph B2 expression by RNAi attenuates the formation of a glial/fibrotic scar and promotes axon growth. This study was approved by the Laboratory Animal Ethics Committee of Jiangsu Province, China(approval No. 2019-0506-002) on May 6, 2019.展开更多
AIM: To investigate tumor necrosis factor-α (TNF-α), syndecan 1 and basic fibroblast growth factor (bFGF) balance in Crohn's disease (CD) strictures. METHODS: Our study was performed on 24 surgical specimens of ...AIM: To investigate tumor necrosis factor-α (TNF-α), syndecan 1 and basic fibroblast growth factor (bFGF) balance in Crohn's disease (CD) strictures. METHODS: Our study was performed on 24 surgical specimens of CD fibrotic stenosis. Ten histological normal surgical samples were retrieved for both the large and small bowel from patients with benign conditions and healthy tissue represented control collection. Sex and age in controls did not differ from CD group. Three endoscopic biopsy specimens taken after informed consent in subjects with normal colon were also used as negative controls. TNF-α, syndecan 1 and bFGF were detected by both reverse transcriptase reverse transcriptase polymerase chain reaction after mRNA extraction (results expressed as fold-change) and immunohistochemistry.RESULTS: TNF-α did not show any significant difference between CD and control specimens (1.54 ± 1.19; P > 0.05). Very high levels of bFGF were observed in CD (11.76 ± 4.65; P < 0.001) unlike syndecan 1 which showed a moderate increase (5.53 ± 2.18; P < 0.005). analysis of variance (ANOVA) plus Student-NeumannKeuls showed: bFGF > syndecan 1 > TNF-α = control. Immunoreactivity for bFGF was observed in epithelial, stromal, endothelial cells and even in the muscular layer, whilst in normal tissue it was almost unexpressed. Syndecan 1 and TNF-α staining was confined to mucosal epithelial and stromal cells, while in controls syndecan 1 was found in its normal site, i.e. , basolateral area of the crypts and TNF-α very poorly expressed. CONCLUSION: Fibrotic stenosis of CD may be the final result of an irreversible transformation of different cells into fibrogenic phenotype no longer inhibited by posttranscriptional regulation.展开更多
AIM: To compare the outcome of an Ex-Press implant and subscleral trabeculectomy(SST) in the management of glaucoma after previous trabeculectomy on a fibrotic bleb.METHODS: This randomized prospective study included ...AIM: To compare the outcome of an Ex-Press implant and subscleral trabeculectomy(SST) in the management of glaucoma after previous trabeculectomy on a fibrotic bleb.METHODS: This randomized prospective study included 28 eyes from 28 patients(age range: 42-55 y) with primary open angle glaucoma(POAG) presented with elevated intraocular pressure(IOP) with fibrotic bleb despite previous SST for more than 4 mo. The eyes enrolled in the study were divided into two groups: group I(subjected to Ex-Press implant surgery) and group II [subjected to SST with mitomycin C(MMC)]. The follow-up continued one year after surgery to evaluate IOP, visual acuity(VA), visual field(VF), and postoperative complications. RESULTS: A significant decrease in IOP was found in both groups with a higher reduction in Ex-Press implant surgery with the mean IOP of 14.50 mm Hg(P=0.001), while the SST group recorded the mean IOP of 16.50 mm Hg(P=0.001) after one year. However, the difference between the two groups in terms of the decrease in IOP was insignificant. Fewer postoperative complications were recorded in the Ex-Press implant surgery and more cases requiring further anti-glaucomatous medications were seen in the SST group. Both groups showed stability in terms of VA and VF.CONCLUSION: Ex-Press implant surgery and SST with MMC are two surgical alternatives for controlling IOP in late failure that occurs more than 4 mo after previous SST with a fibrotic bleb. However, Ex-Press shunt is a safer surgery with fewer complications.展开更多
BACKGROUND Fibrotic hypersensitivity pneumonitis(FHP)is an allergic and diffuse pneumonia caused by repeated inhalation of antigenic substances,and sometimes developed in people working in specific environments.While ...BACKGROUND Fibrotic hypersensitivity pneumonitis(FHP)is an allergic and diffuse pneumonia caused by repeated inhalation of antigenic substances,and sometimes developed in people working in specific environments.While novel antigens and exposures continued to be described,physicians should maintain a high suspicion of potential exposures.A detailed assessment of the patient's occupational exposures as well as living environment is necessary and complete allergen avoidance is the first and most important step in the management of FHP once the allergens are determined.CASE SUMMARY A 35-year-old female was admitted to the hospital with a cough and breathing difficulties for more than one year.She was a nonsmoker and a manufacturer of halogen dishes,which are characteristic Chinese foods,for 15 years without any protection.High resolution computed tomography of the chest demonstrated an interstitial pneumonia pattern.Pulmonary function examination showed restricted ventilation dysfunction and a significant reduction in dispersion ability.Cell differentiation in bronchoalveolar lavage fluid demonstrated lymphocytosis(70.4%)with an increased lymphocyte CD4/CD8 ratio(0.94).Transbronchial lung biopsy combined with lung puncture pathology showed diffuse uniform alveolar interval thickening,chronic inflammatory cell infiltration,a proliferation of tissue in the bronchial wall fiber and alveolar epithelial follicle degeneration,resulting in fibrosis.CONCLUSION Exposure to spices used for the production of halogen dishes may cause FHP.展开更多
Background: Complete hypopharyngo-oesophageal occlusion is a rare complication of head and neck radiotherapy and a range of other conditions. Absolute dysphagia is accompanied by aspiration and dependence on gastrosto...Background: Complete hypopharyngo-oesophageal occlusion is a rare complication of head and neck radiotherapy and a range of other conditions. Absolute dysphagia is accompanied by aspiration and dependence on gastrostomy feeding. The condition presents a substantial management challenge. Surgical approaches to re-establish pharyngo-oesophageal continuity are varied, highly invasive and are associated with unpredictable outcomes. Minimally invasive techniques employing endoscopic and radiological techniques are emerging. This report describes a multidisciplinary approach which translates two interventional radiology techniques used in the management of central venous occlusions and biliary strictures to the management of three cases of complete hypopharyngo-oesophageal occlusion. Methods: Three cases with different underlying aetiologies had treatment initiated between 2009 and 2011. Antegrade pharyngoscopic access to the occlusions was accompanied by retrograde endoscopic access via a small gastrostomy. Luminal continuity was re-established by the interventional radiology technique of “sharp recanalisation” followed by passage of a wide bore nasogastric tube which was maintained in situ for 4-6 months, a duration of treatment analogous to that applied in the radiological management of fibrotic biliary strictures. After treatment a radiological contrast swallows examination was performed to gauge the calibre of the re-established lumen, assess functionality and to rule out aspiration. Results: Pharyngo-oesophageal continuity was re-established in all three cases on the first attempt. No complications occurred as a result of the procedures. In two cases, the excellent swallowing function was re-established, although one of these required prolonged post-treatment adjuvant interventions. In one case no swallowing function resulted, despite apparently successful re-establishment of luminal continuity. Conclusions: Complete fibrotic occlusion of the hypopharyngo-oesophageal lumen is rare and presents a substantial management challenge. A minimally invasive treatment combining antegrade radiological and retrograde endoscopic approaches resulted in successful re-establishment of luminal continuity in three cases of complete fibrotic occlusion of the hypopharyngo-oesophageal lumen. However variable responses to treatment suggest that both the underlying aetiology and the chronicity of the occlusion may influence the likelihood of a successful functional outcome. Until definitive management guidelines are established, we suggest that such cases are managed only by motivated multidisciplinary teams keen to develop their expertise in this area.展开更多
Liver fibrosis is a pathological condition characterized by replacement of normal liver tissue with scar tissue,and also the leading cause of liver-related death worldwide.During the treatment of liver fibrosis,in add...Liver fibrosis is a pathological condition characterized by replacement of normal liver tissue with scar tissue,and also the leading cause of liver-related death worldwide.During the treatment of liver fibrosis,in addition to antiviral therapy or removal of inducers,there remains a lack of specific and effective treatment strategies.For thousands of years,Chinese herbal medicines(CHMs)have been widely used to treat liver fibrosis in clinical setting.CHMs are effective for liver fibrosis,though its mechanisms of action are unclear.In recent years,many studies have attempted to determine the possible mechanisms of action of CHMs in treating liver fibrosis.There have been substantial improvements in the experimental investigation of CHMs which have greatly promoted the understanding of anti-liver fibrosis mechanisms.In this review,the role of CHMs in the treatment of liver fibrosis is described,based on studies over the past decade,which has addressed the various mechanisms and signaling pathways that mediate therapeutic efficacy.Among them,inhibition of stellate cell activation is identified as the most common mechanism.This article provides insights into the research direction of CHMs,in order to expand its clinical application range and improve its effectiveness.展开更多
Background and Aims:Occlusive portal vein thrombosis(PVT)often causes portal hypertension-related complications in cirrhotic patients.Transjugular intrahepatic portosystemic shunt(TIPS)is an effective treatment for th...Background and Aims:Occlusive portal vein thrombosis(PVT)often causes portal hypertension-related complications in cirrhotic patients.Transjugular intrahepatic portosystemic shunt(TIPS)is an effective treatment for this difficult problem.However,the factors influencing TIPS success and overall survival in patients with occlusive PVT are unknown.This study investigated the factors influencing TIPS success and overall survival in cirrhotic patients with occlusive PVT.Methods:Cirrhotic patients with occlusive PVT were selected from a prospective database of consecutive patients treated with TIPS in Xijing Hospital between January 2015 and May 2021.Baseline characteristics,TIPS success rate,complications,and survival were collected,and the factors associated with the TIPS success rate and transplant-free survival were analyzed.Results:A total of 155 cirrhotic patients with occlusive PVT were enrolled.TIPS succeeded in 126(81.29%)cases.The 1-year survival rate was 74%.Compared with those without,patients with portal fibrotic cord had a lower TIPS success rate(39.02%vs.96.49%,p<0.001),shorter median overall survival(300 vs.1,730 days,p<0.001)and more operation-related complications(12.20%vs.1.75%,p<0.01).Logistic regression analysis found that portal fibrotic cord(odds ratio 0.024)was a risk factor for TIPS failure.Univariate and multivariate analysis showed that portal fibrotic cord was an independent predictor of death(hazard ratio 2.111;95%CI:1.094-4.071,p=0.026).Conclusions:Portal fibrotic cord increased the TIPS failure rate and is a risk factor for poor prognosis in cirrhotic patients.展开更多
The fibrotic response plays an important role in the performance and longevity of implantable devices. Thus, development of effective anti-inflammatory and anti-fibrosis biomaterial implants has become an urgent task....The fibrotic response plays an important role in the performance and longevity of implantable devices. Thus, development of effective anti-inflammatory and anti-fibrosis biomaterial implants has become an urgent task. In this work, we developed a novel supramolecular polymer hydrogel through the copolymerization of N-acryloyl glycinamide(NAGA) and carboxybetaine acrylamide(CBAA) in the absence of any chemical crosslinker, which the mechanical properties being tunable through changing the monomer concentration and the monomer ratio over a broad scope. The hydrogel possessed the superior mechanical performances: high tensile strength(～1.13 MPa), large stretchability(～1200%), and excellent compressive strength(～9 MPa) at high monomer concentration and NAGA/CBAA ratio. Introduction of CBAA could promote the self-healability, thermoplasticity of suparmolecular polymer hydrogels at lower temperatures, meanwhile dramatically improving anti-fouling property.Histological analysis and in vitro cytotoxicity assays testified the excellent biocompatibility of the hydrogel. This high strength supramolecular polymer hydrogel with integrated multiple functions holds promising potentials as a scaffold biomaterial for treating degenerated soft supporting tissues.展开更多
Annexin A1,a well-known endogenous anti-inflammatory mediator,plays a critical role in a variety of pathological processes.Fibrosis is described by a failure of tissue regeneration and contributes to the development o...Annexin A1,a well-known endogenous anti-inflammatory mediator,plays a critical role in a variety of pathological processes.Fibrosis is described by a failure of tissue regeneration and contributes to the development of many diseases.Accumulating evidence supports that Annexin A1 participates in the progression of tissue fibrosis.However,the fundamental mechanisms by which Annexin A1 regulates fibrosis remain elusive,and even the functions of Annexin A1 in fibrotic diseases are still paradoxical.This review focuses on the roles of Annexin A1 in the development of fibrosis of lung,liver,heart,and other tissues,with emphasis on the therapy potential of Annexin A1 in fibrosis,and presents future research interests and directions in fibrotic diseases.展开更多
Monocytes,including monocyte-derived macrophages and resident microglia,mediate many phases of optic nerve injury pathogenesis.Resident microglia respond first,followed by infiltrating macrophages which regulate neuro...Monocytes,including monocyte-derived macrophages and resident microglia,mediate many phases of optic nerve injury pathogenesis.Resident microglia respond first,followed by infiltrating macrophages which regulate neuronal inflammation,cell proliferation and differentiation,scar formation and tissue remodeling following optic nerve injury.However,microglia and macrophages have distinct functions which can be either beneficial or detrimental to the optic nerve depending on the spatial context and temporal sequence of their activity.These divergent effects are attributed to pro-and anti-inflammatory cytokines expressed by monocytes,crosstalk between monocyte and glial cells and even microglia-macrophage communication.In this review,we describe the dynamics and functions of microglia and macrophages in neuronal inflammation and regeneration following optic nerve injury,and their possible role as therapeutic targets for axonal regeneration.展开更多
AIM: To determine the association between the neutrophil to lymphocyte(N/L) ratio and the degree of liver fibrosis in patients with chronic hepatitis B(CHB) infection. METHODS: Between December 2011 and February 2013,...AIM: To determine the association between the neutrophil to lymphocyte(N/L) ratio and the degree of liver fibrosis in patients with chronic hepatitis B(CHB) infection. METHODS: Between December 2011 and February 2013, 129 consecutive CHB patients who were admitted to the study hospitals for histological evaluation of chronic hepatitis B-related liver fibrosis were included in this retrospective study. The patients were divided into two groups based on the fibrosis score: individuals with a fibrosis score of F0 or F1 were included in the "no/minimal liver fibrosis" group, whereas patients with a fibrosis score of F2, F3, or F4 were included in the "advanced liver fibrosis" group. The Statistical Package for Social Sciences 18.0 for Windows was used to analyze the data. A P value of < 0.05 was accepted as statistically significant.RESULTS: Three experienced and blinded pathologists evaluated the fibrotic status and inflammatory activity of 129 liver biopsy samples from the CHB patients. Following histopathological examination, the "no/minimal fibrosis" group included 79 individuals, while the "advanced fibrosis" group included 50 individuals. Mean(N/L) ratio levels were notably lower in patients with advanced fibrosis when compared with patients with no/minimal fibrosis. The mean value of the aspartate aminotransferase-platelet ratio index was markedly higher in cases with advanced fibrosis compared to those with no/minimal fibrosis.CONCLUSION: Reduced levels of the peripheral blood N/L ratio were found to give high sensitivity, specificity and predictive values in CHB patients with significant fibrosis. The prominent finding of our research suggests that the N/L ratio can be used as a novel noninvasive marker of fibrosis in patients with CHB.展开更多
Fibrosis is a necessary process in the progression of chronic disease to cirrhosis or even cancer,which is a serious disease threatening human health.Recent studies have shown that the early treatment of fibrosis is t...Fibrosis is a necessary process in the progression of chronic disease to cirrhosis or even cancer,which is a serious disease threatening human health.Recent studies have shown that the early treatment of fibrosis is turning point and particularly important.Therefore,how to reverse fibrosis has become the focus and research hotspot in recent years.So far,the considerable progress has been made in the development of effective anti-fibrosis drugs and targeted drug delivery.Moreover,the existing research results will lay the foundation for more breakthrough delivery systems to achieve better anti-fibrosis effects.Herein,this review summaries anti-fibrosis delivery systems focused on three major organ fibrotic diseases such as liver,pulmonary,and renal fibrosis accompanied by the elaboration of relevant pathological mechanisms,which will provide inspiration and guidance for the design of fibrosis drugs and therapeutic systems in the future.展开更多
BACKGROUND:Transplantation of olfactory ensheathing cells (OECs) into the injured spinal cord has been shown to promote axonal regeneration and functional recovery.However,the mechanisms underlying the effects of OEC ...BACKGROUND:Transplantation of olfactory ensheathing cells (OECs) into the injured spinal cord has been shown to promote axonal regeneration and functional recovery.However,the mechanisms underlying the effects of OEC transplantation remain controversial.OBJECTIVE:To observe fibrotic scar formation and axonal regeneration in the damaged spinal cord following OEC transplantation,and to determine whether OEC transplantation promotes neural regeneration by attenuating fibrotic scar formation.DESIGN,TIME AND SETTING:A randomized,controlled animal experiment was performed at the Department of Developmental Morphology,Tokyo Metropolitan Institute for Neuroscience,Fuchu,Japan and at the Department of Human Anatomy,College of Basic Medical Sciences,China Medical University,China between April 2007 and May 2009.MATERIALS:OECs were obtained from olfactory nerves and olfactory bulbs of male,4-week-old,Sprague Dawley rats.Rabbit anti-serotonin polyclonal antibody,rabbit anti-calcitonin gene-related peptide polyclonal antibody,rabbit anti-glial fibrillary acidic protein polyclonal antibody,rabbit anti-type IV collagen polyclonal antibody,and mouse anti-rat endothelial cell antigen-1 monoclonal antibody were used.METHODS:Male,Sprague Dawley rats aged 8 weeks were randomly divided into three groups:sham-surgery (n=3),surgery (n=9),and OEC transplantation (n=11).Spinal cord transection at the T9-10 level was performed and the rats were transplanted with a 2-μL (1 × 105 cells) cell suspension.MAIN OUTCOME MEASURES:Formation of glial and fibrotic scars was examined using immunohistochemistry for glial fibrillary acidic protein and type IV collagen.Serotonin-positive and calcitonin gene-related peptide-positive axons were visualized by immunohistochemistry,respectively.Double immunofluorescence for type IV collagen and rat endothelial cell antigen-1 was also performed to determine co-localization of type IV collagen deposition and blood vessels.RESULTS:At 1 week after spinal cord injury,numerous glial cells were observed around the lesion site.Formation of fibrotic scar was determined by a large amount of type IV collagen deposition in the lesion center,and descending serotonin-or ascending calcitonin gene-related peptide-containing axons stopped at the fibrotic scar that was formed in the lesion site.At 1 week after transplantation,the formation of fibrotic scar was significantly inhibited.In addition,the fibrotic structure was partly formed and centralized in the blood vessel,and serotonergic and calcitonin gene-related peptide-containing axons were regenerated across the lesion site.CONCLUSION:OEC transplantation into the injured spinal cord attenuated fibrotic scar formation and promoted axon regeneration.展开更多
Progressive fibrosis of a tissue or organ in response to a damaging insult may result in loss of organ function if the acute response is excessive, or a chronic fibrotic response is initiated due to the persistence of...Progressive fibrosis of a tissue or organ in response to a damaging insult may result in loss of organ function if the acute response is excessive, or a chronic fibrotic response is initiated due to the persistence of the insult. In the author’s laboratory over the past several years, a number of preclinical models of fibrosis or fibrogenic responses have been characterized for the effectiveness of various treatment approaches to either prevent or impede fibrosis development and progression to identify commonalities and translatable research directions that could provide insights into human diseases. These have mainly included either chemically induced pulmonary fibrosis models or overt physical injury models in rats, pigs and rabbits. Some preliminary studies in human populations have also been undertaken. The interventions evaluated have included fibrinolytic agents and drugs targeting specific cell populations. The results indicate that some approaches lend themselves to modifying fibrotic reactions in some models and not others, while others may have a more generalized impact on fibrogenic responses due to interference with abnormal cell functions in the injury environment.展开更多
基金supported by the National Natural Science Foundation of China,Nos.82171456 (to QY),81971229 (to QY)the Natural Science Foundation of Chongqing,No.cstc2021jcyj-msxmX0263 (to QY)the Postgraduate Research and Innovation Project of Chongqing,Nos.CYB20151 (to QY),CYS19182 (to YC)。
文摘In the central nervous system, the formation of fibrotic scar after injury inhibits axon regeneration and promotes repair. However, the mechanism underlying fibrotic scar formation and regulation remains poorly understood. M2 macrophages regulate fibrotic scar formation after injury to the heart, lung, kidney, and central nervous system. However, it remains to be clarified whether and how M2 macrophages regulate fibrotic scar formation after cerebral ischemia injury. In this study, we found that, in a rat model of cerebral ischemia induced by middle cerebral artery occlusion/reperfusion, fibrosis and macrophage infiltration were apparent in the ischemic core in the early stage of injury(within 14 days of injury). The number of infiltrated macrophages was positively correlated with fibronectin expression. Depletion of circulating monocyte-derived macrophages attenuated fibrotic scar formation. Interleukin 4(IL4) expression was strongly enhanced in the ischemic cerebral tissues, and IL4-induced M2 macrophage polarization promoted fibrotic scar formation in the ischemic core. In addition, macrophage-conditioned medium directly promoted fibroblast proliferation and the production of extracellular matrix proteins in vitro. Further pharmacological and genetic analyses showed that sonic hedgehog secreted by M2 macrophages promoted fibrogenesis in vitro and in vivo, and that this process was mediated by secretion of the key fibrosis-associated regulatory proteins transforming growth factor beta 1 and matrix metalloproteinase 9. Furthermore, IL4-afforded functional restoration on angiogenesis, cell apoptosis, and infarct volume in the ischemic core of cerebral ischemia rats were markedly impaired by treatment with an sonic hedgehog signaling inhibitor, paralleling the extent of fibrosis. Taken together, our findings show that IL4/sonic hedgehog/transforming growth factor beta 1 signaling targeting macrophages regulates the formation of fibrotic scar and is a potential therapeutic target for ischemic stroke.
基金supported by the Priority Academic Program Development of Jiangsu Higher Education Institutes of China(PAPD)the Science and Technology Plan Project of Nantong of China,No.JC2020026(to JW)the National Science Research of Jiangsu Higher Education Institutions of China,No.19KJB310012(to RYY)。
文摘The rapid formation of a glial/fibrotic scar is one of the main factors hampering axon growth after spinal cord injury. The bidirectional Eph B2/ephrin-B2 signaling of the fibroblast-astrocyte contact-dependent interaction is a trigger for glial/fibrotic scar formation. In the present study, a new in vitro model was produced by coculture of fibroblasts and astrocytes wounded by scratching to mimic glial/fibrotic scar-like structures using an improved slide system. After treatment with RNAi to downregulate Eph B2, changes in glial/fibrotic scar formation and the growth of VSC4.1 motoneuron axons were examined. Following RNAi treatment, fibroblasts and astrocytes dispersed without forming a glial/fibrotic scar-like structure. Furthermore, the expression levels of neurocan, NG2 and collagen I in the coculture were reduced, and the growth of VSC4.1 motoneuron axons was enhanced. These findings suggest that suppression of Eph B2 expression by RNAi attenuates the formation of a glial/fibrotic scar and promotes axon growth. This study was approved by the Laboratory Animal Ethics Committee of Jiangsu Province, China(approval No. 2019-0506-002) on May 6, 2019.
文摘AIM: To investigate tumor necrosis factor-α (TNF-α), syndecan 1 and basic fibroblast growth factor (bFGF) balance in Crohn's disease (CD) strictures. METHODS: Our study was performed on 24 surgical specimens of CD fibrotic stenosis. Ten histological normal surgical samples were retrieved for both the large and small bowel from patients with benign conditions and healthy tissue represented control collection. Sex and age in controls did not differ from CD group. Three endoscopic biopsy specimens taken after informed consent in subjects with normal colon were also used as negative controls. TNF-α, syndecan 1 and bFGF were detected by both reverse transcriptase reverse transcriptase polymerase chain reaction after mRNA extraction (results expressed as fold-change) and immunohistochemistry.RESULTS: TNF-α did not show any significant difference between CD and control specimens (1.54 ± 1.19; P > 0.05). Very high levels of bFGF were observed in CD (11.76 ± 4.65; P < 0.001) unlike syndecan 1 which showed a moderate increase (5.53 ± 2.18; P < 0.005). analysis of variance (ANOVA) plus Student-NeumannKeuls showed: bFGF > syndecan 1 > TNF-α = control. Immunoreactivity for bFGF was observed in epithelial, stromal, endothelial cells and even in the muscular layer, whilst in normal tissue it was almost unexpressed. Syndecan 1 and TNF-α staining was confined to mucosal epithelial and stromal cells, while in controls syndecan 1 was found in its normal site, i.e. , basolateral area of the crypts and TNF-α very poorly expressed. CONCLUSION: Fibrotic stenosis of CD may be the final result of an irreversible transformation of different cells into fibrogenic phenotype no longer inhibited by posttranscriptional regulation.
文摘AIM: To compare the outcome of an Ex-Press implant and subscleral trabeculectomy(SST) in the management of glaucoma after previous trabeculectomy on a fibrotic bleb.METHODS: This randomized prospective study included 28 eyes from 28 patients(age range: 42-55 y) with primary open angle glaucoma(POAG) presented with elevated intraocular pressure(IOP) with fibrotic bleb despite previous SST for more than 4 mo. The eyes enrolled in the study were divided into two groups: group I(subjected to Ex-Press implant surgery) and group II [subjected to SST with mitomycin C(MMC)]. The follow-up continued one year after surgery to evaluate IOP, visual acuity(VA), visual field(VF), and postoperative complications. RESULTS: A significant decrease in IOP was found in both groups with a higher reduction in Ex-Press implant surgery with the mean IOP of 14.50 mm Hg(P=0.001), while the SST group recorded the mean IOP of 16.50 mm Hg(P=0.001) after one year. However, the difference between the two groups in terms of the decrease in IOP was insignificant. Fewer postoperative complications were recorded in the Ex-Press implant surgery and more cases requiring further anti-glaucomatous medications were seen in the SST group. Both groups showed stability in terms of VA and VF.CONCLUSION: Ex-Press implant surgery and SST with MMC are two surgical alternatives for controlling IOP in late failure that occurs more than 4 mo after previous SST with a fibrotic bleb. However, Ex-Press shunt is a safer surgery with fewer complications.
文摘BACKGROUND Fibrotic hypersensitivity pneumonitis(FHP)is an allergic and diffuse pneumonia caused by repeated inhalation of antigenic substances,and sometimes developed in people working in specific environments.While novel antigens and exposures continued to be described,physicians should maintain a high suspicion of potential exposures.A detailed assessment of the patient's occupational exposures as well as living environment is necessary and complete allergen avoidance is the first and most important step in the management of FHP once the allergens are determined.CASE SUMMARY A 35-year-old female was admitted to the hospital with a cough and breathing difficulties for more than one year.She was a nonsmoker and a manufacturer of halogen dishes,which are characteristic Chinese foods,for 15 years without any protection.High resolution computed tomography of the chest demonstrated an interstitial pneumonia pattern.Pulmonary function examination showed restricted ventilation dysfunction and a significant reduction in dispersion ability.Cell differentiation in bronchoalveolar lavage fluid demonstrated lymphocytosis(70.4%)with an increased lymphocyte CD4/CD8 ratio(0.94).Transbronchial lung biopsy combined with lung puncture pathology showed diffuse uniform alveolar interval thickening,chronic inflammatory cell infiltration,a proliferation of tissue in the bronchial wall fiber and alveolar epithelial follicle degeneration,resulting in fibrosis.CONCLUSION Exposure to spices used for the production of halogen dishes may cause FHP.
文摘Background: Complete hypopharyngo-oesophageal occlusion is a rare complication of head and neck radiotherapy and a range of other conditions. Absolute dysphagia is accompanied by aspiration and dependence on gastrostomy feeding. The condition presents a substantial management challenge. Surgical approaches to re-establish pharyngo-oesophageal continuity are varied, highly invasive and are associated with unpredictable outcomes. Minimally invasive techniques employing endoscopic and radiological techniques are emerging. This report describes a multidisciplinary approach which translates two interventional radiology techniques used in the management of central venous occlusions and biliary strictures to the management of three cases of complete hypopharyngo-oesophageal occlusion. Methods: Three cases with different underlying aetiologies had treatment initiated between 2009 and 2011. Antegrade pharyngoscopic access to the occlusions was accompanied by retrograde endoscopic access via a small gastrostomy. Luminal continuity was re-established by the interventional radiology technique of “sharp recanalisation” followed by passage of a wide bore nasogastric tube which was maintained in situ for 4-6 months, a duration of treatment analogous to that applied in the radiological management of fibrotic biliary strictures. After treatment a radiological contrast swallows examination was performed to gauge the calibre of the re-established lumen, assess functionality and to rule out aspiration. Results: Pharyngo-oesophageal continuity was re-established in all three cases on the first attempt. No complications occurred as a result of the procedures. In two cases, the excellent swallowing function was re-established, although one of these required prolonged post-treatment adjuvant interventions. In one case no swallowing function resulted, despite apparently successful re-establishment of luminal continuity. Conclusions: Complete fibrotic occlusion of the hypopharyngo-oesophageal lumen is rare and presents a substantial management challenge. A minimally invasive treatment combining antegrade radiological and retrograde endoscopic approaches resulted in successful re-establishment of luminal continuity in three cases of complete fibrotic occlusion of the hypopharyngo-oesophageal lumen. However variable responses to treatment suggest that both the underlying aetiology and the chronicity of the occlusion may influence the likelihood of a successful functional outcome. Until definitive management guidelines are established, we suggest that such cases are managed only by motivated multidisciplinary teams keen to develop their expertise in this area.
基金Liaoning Provincial Local Professional Technology Innovation Platform Construction Project(2016007013)Liaoning Provincial Natural Science Foundation(2014021007)+2 种基金Outstanding Scientiffc Fund of Shengjing Hospital(2011-02)345 Talent Project of Shengjing Hospital(2020-01)The Mechanism of Immune Tolerance Mediated by Myeloid-Derived Suppressor Cells inhibiting T Cell Immune Responses via PD-L1 in Chronic Hepatits B(2022-12).
文摘Liver fibrosis is a pathological condition characterized by replacement of normal liver tissue with scar tissue,and also the leading cause of liver-related death worldwide.During the treatment of liver fibrosis,in addition to antiviral therapy or removal of inducers,there remains a lack of specific and effective treatment strategies.For thousands of years,Chinese herbal medicines(CHMs)have been widely used to treat liver fibrosis in clinical setting.CHMs are effective for liver fibrosis,though its mechanisms of action are unclear.In recent years,many studies have attempted to determine the possible mechanisms of action of CHMs in treating liver fibrosis.There have been substantial improvements in the experimental investigation of CHMs which have greatly promoted the understanding of anti-liver fibrosis mechanisms.In this review,the role of CHMs in the treatment of liver fibrosis is described,based on studies over the past decade,which has addressed the various mechanisms and signaling pathways that mediate therapeutic efficacy.Among them,inhibition of stellate cell activation is identified as the most common mechanism.This article provides insights into the research direction of CHMs,in order to expand its clinical application range and improve its effectiveness.
文摘Background and Aims:Occlusive portal vein thrombosis(PVT)often causes portal hypertension-related complications in cirrhotic patients.Transjugular intrahepatic portosystemic shunt(TIPS)is an effective treatment for this difficult problem.However,the factors influencing TIPS success and overall survival in patients with occlusive PVT are unknown.This study investigated the factors influencing TIPS success and overall survival in cirrhotic patients with occlusive PVT.Methods:Cirrhotic patients with occlusive PVT were selected from a prospective database of consecutive patients treated with TIPS in Xijing Hospital between January 2015 and May 2021.Baseline characteristics,TIPS success rate,complications,and survival were collected,and the factors associated with the TIPS success rate and transplant-free survival were analyzed.Results:A total of 155 cirrhotic patients with occlusive PVT were enrolled.TIPS succeeded in 126(81.29%)cases.The 1-year survival rate was 74%.Compared with those without,patients with portal fibrotic cord had a lower TIPS success rate(39.02%vs.96.49%,p<0.001),shorter median overall survival(300 vs.1,730 days,p<0.001)and more operation-related complications(12.20%vs.1.75%,p<0.01).Logistic regression analysis found that portal fibrotic cord(odds ratio 0.024)was a risk factor for TIPS failure.Univariate and multivariate analysis showed that portal fibrotic cord was an independent predictor of death(hazard ratio 2.111;95%CI:1.094-4.071,p=0.026).Conclusions:Portal fibrotic cord increased the TIPS failure rate and is a risk factor for poor prognosis in cirrhotic patients.
基金supported by the National Natural Science Foundation of China(Grant Nos.51325305,51733006)
文摘The fibrotic response plays an important role in the performance and longevity of implantable devices. Thus, development of effective anti-inflammatory and anti-fibrosis biomaterial implants has become an urgent task. In this work, we developed a novel supramolecular polymer hydrogel through the copolymerization of N-acryloyl glycinamide(NAGA) and carboxybetaine acrylamide(CBAA) in the absence of any chemical crosslinker, which the mechanical properties being tunable through changing the monomer concentration and the monomer ratio over a broad scope. The hydrogel possessed the superior mechanical performances: high tensile strength(～1.13 MPa), large stretchability(～1200%), and excellent compressive strength(～9 MPa) at high monomer concentration and NAGA/CBAA ratio. Introduction of CBAA could promote the self-healability, thermoplasticity of suparmolecular polymer hydrogels at lower temperatures, meanwhile dramatically improving anti-fouling property.Histological analysis and in vitro cytotoxicity assays testified the excellent biocompatibility of the hydrogel. This high strength supramolecular polymer hydrogel with integrated multiple functions holds promising potentials as a scaffold biomaterial for treating degenerated soft supporting tissues.
基金This work was supported by the National Natural Science Foundation of China(No.81770176)the Special Support Plan for Zhejiang Province High-level Talents(No.2019R52011)+1 种基金the Zhejiang Provincial Natural Science Foundation of China(No.LD22H310004)the Scientific Research Foundation of Zhejiang Sci-Tech University(No.21042100-Y).
文摘Annexin A1,a well-known endogenous anti-inflammatory mediator,plays a critical role in a variety of pathological processes.Fibrosis is described by a failure of tissue regeneration and contributes to the development of many diseases.Accumulating evidence supports that Annexin A1 participates in the progression of tissue fibrosis.However,the fundamental mechanisms by which Annexin A1 regulates fibrosis remain elusive,and even the functions of Annexin A1 in fibrotic diseases are still paradoxical.This review focuses on the roles of Annexin A1 in the development of fibrosis of lung,liver,heart,and other tissues,with emphasis on the therapy potential of Annexin A1 in fibrosis,and presents future research interests and directions in fibrotic diseases.
基金supported by NIH Center Core Grant P30EY014801a Research to Prevent Blindness Unrestrictea Grant+3 种基金partially supported by the Walter G.Ross Foundationpartly supported by the Gutierrez Family Research Fundthe Camiener Family Glaucoma Research Fundthe National Natural Science Foundation of China(No.82201170 to XL)。
文摘Monocytes,including monocyte-derived macrophages and resident microglia,mediate many phases of optic nerve injury pathogenesis.Resident microglia respond first,followed by infiltrating macrophages which regulate neuronal inflammation,cell proliferation and differentiation,scar formation and tissue remodeling following optic nerve injury.However,microglia and macrophages have distinct functions which can be either beneficial or detrimental to the optic nerve depending on the spatial context and temporal sequence of their activity.These divergent effects are attributed to pro-and anti-inflammatory cytokines expressed by monocytes,crosstalk between monocyte and glial cells and even microglia-macrophage communication.In this review,we describe the dynamics and functions of microglia and macrophages in neuronal inflammation and regeneration following optic nerve injury,and their possible role as therapeutic targets for axonal regeneration.
文摘AIM: To determine the association between the neutrophil to lymphocyte(N/L) ratio and the degree of liver fibrosis in patients with chronic hepatitis B(CHB) infection. METHODS: Between December 2011 and February 2013, 129 consecutive CHB patients who were admitted to the study hospitals for histological evaluation of chronic hepatitis B-related liver fibrosis were included in this retrospective study. The patients were divided into two groups based on the fibrosis score: individuals with a fibrosis score of F0 or F1 were included in the "no/minimal liver fibrosis" group, whereas patients with a fibrosis score of F2, F3, or F4 were included in the "advanced liver fibrosis" group. The Statistical Package for Social Sciences 18.0 for Windows was used to analyze the data. A P value of < 0.05 was accepted as statistically significant.RESULTS: Three experienced and blinded pathologists evaluated the fibrotic status and inflammatory activity of 129 liver biopsy samples from the CHB patients. Following histopathological examination, the "no/minimal fibrosis" group included 79 individuals, while the "advanced fibrosis" group included 50 individuals. Mean(N/L) ratio levels were notably lower in patients with advanced fibrosis when compared with patients with no/minimal fibrosis. The mean value of the aspartate aminotransferase-platelet ratio index was markedly higher in cases with advanced fibrosis compared to those with no/minimal fibrosis.CONCLUSION: Reduced levels of the peripheral blood N/L ratio were found to give high sensitivity, specificity and predictive values in CHB patients with significant fibrosis. The prominent finding of our research suggests that the N/L ratio can be used as a novel noninvasive marker of fibrosis in patients with CHB.
基金financially supported by the National Science and Technology Major Project(2017YFA0205400)the National Natural Science Foundation of China(81773667,81573369)+2 种基金NSFC Projects of International Cooperation and Exchanges(81811540416)the“111”Project from the Ministry of Education of Chinathe State Administration of Foreign Experts Affairs of China(D17010).
文摘Fibrosis is a necessary process in the progression of chronic disease to cirrhosis or even cancer,which is a serious disease threatening human health.Recent studies have shown that the early treatment of fibrosis is turning point and particularly important.Therefore,how to reverse fibrosis has become the focus and research hotspot in recent years.So far,the considerable progress has been made in the development of effective anti-fibrosis drugs and targeted drug delivery.Moreover,the existing research results will lay the foundation for more breakthrough delivery systems to achieve better anti-fibrosis effects.Herein,this review summaries anti-fibrosis delivery systems focused on three major organ fibrotic diseases such as liver,pulmonary,and renal fibrosis accompanied by the elaboration of relevant pathological mechanisms,which will provide inspiration and guidance for the design of fibrosis drugs and therapeutic systems in the future.
基金the National Natural Science Foundation of China,No.NSFC-30872669a Grant from Japan-China Medical Associationthe Scientific Research Foundation of Technology Department of Liaoning Province in China,No.20082113
文摘BACKGROUND:Transplantation of olfactory ensheathing cells (OECs) into the injured spinal cord has been shown to promote axonal regeneration and functional recovery.However,the mechanisms underlying the effects of OEC transplantation remain controversial.OBJECTIVE:To observe fibrotic scar formation and axonal regeneration in the damaged spinal cord following OEC transplantation,and to determine whether OEC transplantation promotes neural regeneration by attenuating fibrotic scar formation.DESIGN,TIME AND SETTING:A randomized,controlled animal experiment was performed at the Department of Developmental Morphology,Tokyo Metropolitan Institute for Neuroscience,Fuchu,Japan and at the Department of Human Anatomy,College of Basic Medical Sciences,China Medical University,China between April 2007 and May 2009.MATERIALS:OECs were obtained from olfactory nerves and olfactory bulbs of male,4-week-old,Sprague Dawley rats.Rabbit anti-serotonin polyclonal antibody,rabbit anti-calcitonin gene-related peptide polyclonal antibody,rabbit anti-glial fibrillary acidic protein polyclonal antibody,rabbit anti-type IV collagen polyclonal antibody,and mouse anti-rat endothelial cell antigen-1 monoclonal antibody were used.METHODS:Male,Sprague Dawley rats aged 8 weeks were randomly divided into three groups:sham-surgery (n=3),surgery (n=9),and OEC transplantation (n=11).Spinal cord transection at the T9-10 level was performed and the rats were transplanted with a 2-μL (1 × 105 cells) cell suspension.MAIN OUTCOME MEASURES:Formation of glial and fibrotic scars was examined using immunohistochemistry for glial fibrillary acidic protein and type IV collagen.Serotonin-positive and calcitonin gene-related peptide-positive axons were visualized by immunohistochemistry,respectively.Double immunofluorescence for type IV collagen and rat endothelial cell antigen-1 was also performed to determine co-localization of type IV collagen deposition and blood vessels.RESULTS:At 1 week after spinal cord injury,numerous glial cells were observed around the lesion site.Formation of fibrotic scar was determined by a large amount of type IV collagen deposition in the lesion center,and descending serotonin-or ascending calcitonin gene-related peptide-containing axons stopped at the fibrotic scar that was formed in the lesion site.At 1 week after transplantation,the formation of fibrotic scar was significantly inhibited.In addition,the fibrotic structure was partly formed and centralized in the blood vessel,and serotonergic and calcitonin gene-related peptide-containing axons were regenerated across the lesion site.CONCLUSION:OEC transplantation into the injured spinal cord attenuated fibrotic scar formation and promoted axon regeneration.
文摘Progressive fibrosis of a tissue or organ in response to a damaging insult may result in loss of organ function if the acute response is excessive, or a chronic fibrotic response is initiated due to the persistence of the insult. In the author’s laboratory over the past several years, a number of preclinical models of fibrosis or fibrogenic responses have been characterized for the effectiveness of various treatment approaches to either prevent or impede fibrosis development and progression to identify commonalities and translatable research directions that could provide insights into human diseases. These have mainly included either chemically induced pulmonary fibrosis models or overt physical injury models in rats, pigs and rabbits. Some preliminary studies in human populations have also been undertaken. The interventions evaluated have included fibrinolytic agents and drugs targeting specific cell populations. The results indicate that some approaches lend themselves to modifying fibrotic reactions in some models and not others, while others may have a more generalized impact on fibrogenic responses due to interference with abnormal cell functions in the injury environment.
