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Frontiers in Immunology 2022NETosis is a form of neutrophil cell death during which extracellular fibrillary structures composed of cytosolic and granule proteins assembled on scaffolds of...
NETosis is a form of neutrophil cell death during which extracellular fibrillary structures composed of cytosolic and granule proteins assembled on scaffolds of decondensed chromatin, called neutrophil extracellular traps (NETs), are released. NETs normally contribute to host immune defense. Accumulating evidence implicates aberrant NET production and/or reduced NET clearance, along with alterations of molecules involved in NETosis pathway, in humans and animals with lupus. The extruded nuclear antigens released by NET are a source of autoantigens, which can contribute to the breakdown of self-tolerance in lupus. Excessive NET can also promote the production of pro-inflammatory cytokine interferon-α, elicit direct cytotoxic effect on various renal cells, and cause capillary necrosis and podocyte loss. Additionally, NET can induce endothelial-to-mesenchymal transdifferentiation, which can promote activated myofibroblasts leading to extracellular matrix production. Thus, aberrant NETosis can play diverse roles, including autoantibody production, inflammation, and tissue damage, at different stages of lupus pathogenesis. Evidence suggests that treatments currently used in lupus may reduce NETosis, suggesting a potential utility of targeting NETosis to treat lupus. In fact, several approaches are being experimented to therapeutically target pathways of NETosis. Future studies should precisely delineate distinct roles of NETosis at different stages of lupus pathogenesis in humans, which would offer a rational basis for NETosis-targeting treatments in the clinic.
Topics: Animals; Autoantigens; Cell Death; Extracellular Traps; Inflammation; Neutrophils
PubMed: 35686129
DOI: 10.3389/fimmu.2022.895216 -
Diagnostics (Basel, Switzerland) Jan 2023Dermatofibromas (DFs) are benign fibrohistiocytic lesions that usually do not express CD34 protein. This study aimed to analyze the literature concerning the... (Review)
Review
BACKGROUND
Dermatofibromas (DFs) are benign fibrohistiocytic lesions that usually do not express CD34 protein. This study aimed to analyze the literature concerning the immunohistological and ultrastructural features of DFs. It also related these features to the histogenesis of these lesions.
METHODS
This study included a PubMed literature search for studies addressing the clinicopathological, ultrastructural, and immunohistochemical features of DFs. It also presented some current cases of CD34-negative DFs and a subset of these lesions with aberrant expression of this protein.
RESULTS
Analysis of the PubMed literature revealed that DFs with an aberrant expression of CD34 are rare tumors that commonly affect the extremities of adult females. Separating these tumors from dermatofibrosarcoma protuberans (DFSP, CD34-positive tumors) requires using a large panel of immunostains. Ultrastructurally, DFs are composed of diverse cell types, including cells with histiocytic, myofibroblastic, and fibroblastic features. An analysis of the DFs described by this study revealed that cases with an aberrant expression of CD34 protein had slightly high mean age and male sex predominance when compared to CD34-negative cases. The former commonly affected the extremities. There was no evidence of local recurrence or distant metastasis on follow-up.
CONCLUSIONS
DFs have the potential to express CD34 protein, defining a rare aberrant phenotype, which was not associated with any differences in the outcome as compared to CD34-negative DFs.
PubMed: 36672995
DOI: 10.3390/diagnostics13020185 -
Cureus Jan 2024Dupuytren's disease (DD) is a fibroproliferative disorder that manifests as an abnormal growth of myofibroblasts, causing nodule formation and contractures and affecting... (Review)
Review
Comparing Complications and Patient Satisfaction Following Injectable Collagenase Versus Limited Fasciectomy for Dupuytren's Disease: A Systematic Review and Meta-Analysis.
Dupuytren's disease (DD) is a fibroproliferative disorder that manifests as an abnormal growth of myofibroblasts, causing nodule formation and contractures and affecting digit function. If left untreated, these contractures can lead to a loss of mobility and potentially impact hand function. This systematic review critically compares and evaluates the existing literature on the complications and patient satisfaction following injectable collagenase (CCH) versus limited fasciectomy (LF) for DD. We performed a comprehensive search of the PubMed, Medical Literature Analysis and Retrieval System Online (MEDLINE), The Cochrane Library, and Excerpta Medica database (EMBASE) databases from 2006 to August 2023. This research targeted all clinical studies involving adults who underwent injectable collagenase and/or limited fasciectomy in the management of DD. Out of the 437 identified studies, only 53 were considered eligible for our analysis, and merely 14 met our inclusion criteria. These selected studies encompassed a total of 967 patients with 1,344 treated joints, with an average follow-up duration of 19.22 (ranging from one to 84.06) months. Within this cohort, 498 joints from 385 patients underwent LF, while 846 joints from 491 patients received CCH injections. Notably, among the 491 patients treated with CCH, 1,060 complications were reported, averaging 2.15 complications per patient, with the most common being contusion/bruising/hematoma/ecchymosis (22.54%), and edema/swelling (18.96%). In contrast, among the 385 patients treated with LF, only 97 complications were reported, translating to 0.25 complications per patient, with the most frequent being paraesthesia or numbness (23.7%), scar sequelae like skin laceration, tear, fissure, or hypertrophic scar (23.7%), and neuropraxia or nerve injury (22.6%). Our meta-analysis indicates that paraesthesia or numbness is more frequently observed in LF than CCH injections, although without statistical significance, with a risk ratio (RR) of 0.39 (95% confidence interval (CI) 0.13-1.18, p-value 0.1). However, scar sequelae (hypertrophic scar, skin laceration, tear, or fissure) show a contrasting pattern, being more commonly associated with CCH injections than LF, with an RR of 1.98 (95% CI 0.26-14.85, p-value 0.51), which, upon eliminating the source of heterogeneity, becomes statistically significant, with an RR of 4.98 (95% CI 1.40-17.72, p-value 0.01). Our data revealed a higher frequency of complications with CCH compared to LF, although more severe adverse effects were observed in the LF group, such as neuropraxia or nerve injury. Scar sequelae were more common with CCH injections. Despite both treatments showing increased patient satisfaction at the final follow-up, CCH injection resulted in earlier improvements in satisfaction.
PubMed: 38420076
DOI: 10.7759/cureus.53147 -
Journal of the American Heart... Dec 2020Background Human mesenchymal cells are culprit factors in vascular (patho)physiology and are hallmarked by phenotypic and functional heterogeneity. At present, they are... (Meta-Analysis)
Meta-Analysis
Background Human mesenchymal cells are culprit factors in vascular (patho)physiology and are hallmarked by phenotypic and functional heterogeneity. At present, they are subdivided by classic umbrella terms, such as "fibroblasts," "myofibroblasts," "smooth muscle cells," "fibrocytes," "mesangial cells," and "pericytes." However, a discriminative marker-based subclassification has to date not been established. Methods and Results As a first effort toward a classification scheme, a systematic literature search was performed to identify the most commonly used phenotypical and functional protein markers for characterizing and classifying vascular mesenchymal cell subpopulation(s). We next applied immunohistochemistry and immunofluorescence to inventory the expression pattern of identified markers on human aorta specimens representing early, intermediate, and end stages of human atherosclerotic disease. Included markers comprise markers for mesenchymal lineage (vimentin, FSP-1 [fibroblast-specific protein-1]/S100A4, cluster of differentiation (CD) 90/thymocyte differentiation antigen 1, and FAP [fibroblast activation protein]), contractile/non-contractile phenotype (α-smooth muscle actin, smooth muscle myosin heavy chain, and nonmuscle myosin heavy chain), and auxiliary contractile markers (h1-Calponin, h-Caldesmon, Desmin, SM22α [smooth muscle protein 22α], non-muscle myosin heavy chain, smooth muscle myosin heavy chain, Smoothelin-B, α-Tropomyosin, and Telokin) or adhesion proteins (Paxillin and Vinculin). Vimentin classified as the most inclusive lineage marker. Subset markers did not separate along classic lines of smooth muscle cell, myofibroblast, or fibroblast, but showed clear temporal and spatial diversity. Strong indications were found for presence of stem cells/Endothelial-to-Mesenchymal cell Transition and fibrocytes in specific aspects of the human atherosclerotic process. Conclusions This systematic evaluation shows a highly diverse and dynamic landscape for the human vascular mesenchymal cell population that is not captured by the classic nomenclature. Our observations stress the need for a consensus multiparameter subclass designation along the lines of the cluster of differentiation classification for leucocytes.
Topics: Atherosclerosis; Humans; Mesenchymal Stem Cells; Muscle, Smooth, Vascular
PubMed: 33190596
DOI: 10.1161/JAHA.120.017094 -
Frontiers in Immunology 2021Peritoneal fibrosis is characterized by abnormal production of extracellular matrix proteins leading to progressive thickening of the submesothelial compact zone of the...
Peritoneal fibrosis is characterized by abnormal production of extracellular matrix proteins leading to progressive thickening of the submesothelial compact zone of the peritoneal membrane. This process may be caused by a number of insults including pathological conditions linked to clinical practice, such as peritoneal dialysis, abdominal surgery, hemoperitoneum, and infectious peritonitis. All these events may cause acute/chronic inflammation and injury to the peritoneal membrane, which undergoes progressive fibrosis, angiogenesis, and vasculopathy. Among the cellular processes implicated in these peritoneal alterations is the generation of myofibroblasts from mesothelial cells and other cellular sources that are central in the induction of fibrosis and in the subsequent functional deterioration of the peritoneal membrane. Myofibroblast generation and activity is actually integrated in a complex network of extracellular signals generated by the various cellular types, including leukocytes, stably residing or recirculating along the peritoneal membrane. Here, the main extracellular factors and the cellular players are described with emphasis on the cross-talk between immune system and cells of the peritoneal stroma. The understanding of cellular and molecular mechanisms underlying fibrosis of the peritoneal membrane has both a basic and a translational relevance, since it may be useful for setup of therapies aimed at counteracting the deterioration as well as restoring the homeostasis of the peritoneal membrane.
Topics: Animals; Biomarkers; Cell Communication; Cytokines; Disease Susceptibility; Epithelial Cells; Humans; Immunity, Innate; Inflammation Mediators; Leukocytes; Peritoneal Dialysis; Peritoneal Fibrosis; Peritoneum; Peritonitis; Stromal Cells; T-Lymphocyte Subsets
PubMed: 33854496
DOI: 10.3389/fimmu.2021.607204 -
Frontiers in Cardiovascular Medicine 2022Mitral valve prolapse (MVP) due to myxomatous degeneration is one of the most important chronic degenerative cardiovascular diseases in people and dogs. It is a common...
Mitral valve prolapse (MVP) due to myxomatous degeneration is one of the most important chronic degenerative cardiovascular diseases in people and dogs. It is a common cause of heart failure leading to significant morbidity and mortality in both species. Human MVP is usually classified into primary or non-syndromic, including Barlow's Disease (BD), fibro-elastic deficiency (FED) and Filamin-A mutation, and secondary or syndromic forms (typically familial), such as Marfan syndrome (MFS), Ehlers-Danlos syndrome, and Loeys-Dietz syndrome. Despite different etiologies the diseased valves share pathological features consistent with myxomatous degeneration. To reflect this common pathology the condition is often called myxomatous mitral valve degeneration (disease) (MMVD) and this term is universally used to describe the analogous condition in the dog. MMVD in both species is characterized by leaflet thickening and deformity, disorganized extracellular matrix, increased transformation of the quiescent valve interstitial cell (qVICs) to an activated state (aVICs), also known as activated myofibroblasts. Significant alterations in these cellular activities contribute to the initiation and progression of MMVD due to the increased expression of transforming growth factor-β (TGF-β) superfamily cytokines and the dysregulation of the TGF-β signaling pathways. Further understanding the molecular mechanisms of MMVD is needed to identify pharmacological manipulation strategies of the signaling pathway that might regulate VIC differentiation and so control the disease onset and development. This review briefly summarizes current understanding of the histopathology, cellular activities, molecular mechanisms and pathogenesis of MMVD in dogs and humans, and in more detail reviews the evidence for the role of TGF-β.
PubMed: 35656405
DOI: 10.3389/fcvm.2022.872288 -
Indian Journal of Urology : IJU :... 2024Inflammatory myofibroblastic tumors (IMTs) are intermediate-grade lesions that frequently recur and rarely metastasize. There are currently no guidelines on the... (Review)
Review
INTRODUCTION
Inflammatory myofibroblastic tumors (IMTs) are intermediate-grade lesions that frequently recur and rarely metastasize. There are currently no guidelines on the management of bladder IMTs. This systematic review aims to describe the clinical presentation and compare the management options for bladder IMTs.
METHODS
A PubMed/Medline search was conducted, according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, using the following Mesh terms: ("inflammatory myofibroblastic") AND ("tumor") OR ("tumor") AND ("bladder") AND ("case report"). A total of 75 case reports were included in the analysis.
RESULTS
The mean age of the patients was 36 years. 65% of the cases initially presented with hematuria. 68% of the tumors stained positive for anaplastic lymphoma kinase, and 20% invaded the muscularis. Patients underwent either transurethral resection of the bladder tumor (TURBT) only (34%), TURBT followed by complementary partial cystectomy (16%), or TURBT followed by radical cystectomy (4%). 36% and 9% of the cases underwent partial and radical cystectomy after the initial diagnosis, respectively. Cystectomies were performed using an open (74%), laparoscopic (14%), robotic-assisted (10%), or unknown (2%) approach. At a mean follow-up of 14 months, the recurrence and metastasis rates were about 9% and 4%, respectively. In addition, we present the case of a 49-year-old woman with a bladder IMT who underwent TURBT followed by laparoscopic partial cystectomy. The patient remains tumor free postoperatively (follow-up period of 12 months).
CONCLUSION
A complete surgical excision of the bladder IMT is crucial for the optimal management of these cases. Proper differentiation of this tumor from sarcoma or leiomyosarcoma leads to the best outcomes.
PubMed: 38725889
DOI: 10.4103/iju.iju_50_24 -
Journal of Pediatric Genetics Jun 2023Recessive dystrophic epidermolysis bullosa (RDEB) is a severe subtype of epidermolysis bullosa caused by changes in collagen VII with a high risk of early development of... (Review)
Review
Recessive dystrophic epidermolysis bullosa (RDEB) is a severe subtype of epidermolysis bullosa caused by changes in collagen VII with a high risk of early development of cutaneous squamous cell carcinoma (cSCC). This review aimed to discuss the relationship between the recurrent healing process, the appearance of fibrosis, and malignant epithelial transformation in RDEB. We searched PubMed, the Regional Portal of the Virtual Health Library, and Embase for articles on the relationship between blistering, recurrent scarring, and fibrosis in the context of cSCC and RDEB. That alterations of collagen VII result in blister formation, scar deficiency associated with inflammation, and increased expression of transforming growth factor β. These events promote the differentiation of myofibroblasts and the expression of profibrotic proteins, leading to structural changes and the establishment of a microenvironment favorable to carcinogenesis. Patients with RDEB and areas of recurrent scarring and fibrosis may be more prone to the development of cSCC.
PubMed: 37090823
DOI: 10.1055/s-0043-1763257 -
Medicine Sep 2017Human epididymis protein 4 (HE4), a matrix metalloprotease 2 (MMP2), and a matrix metalloprotease 9 (MMP9) inhibitor, promotes renal fibrosis by inhibiting the... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Human epididymis protein 4 (HE4), a matrix metalloprotease 2 (MMP2), and a matrix metalloprotease 9 (MMP9) inhibitor, promotes renal fibrosis by inhibiting the degradation of type I collagen. However, the predictive value of HE4 for renal fibrosis remains controversial, even though it has been identified as one of the most upregulated genes in cultured fibrosis-associated myofibroblasts. This systematic review and meta-analysis was conducted to investigate the potential association between circulating HE4 and renal fibrosis.
METHODS
Original and review articles published until January 2017 that analyzed the performance of serum HE4 in renal fibrosis were systematically searched for in PubMed (1966-2017.1), Cochrane Library, Web of Science, EMBASE (1980-2017.1), China National Knowledge Infrastructure, Wanfang Database, and VIP (Weipu Database). The meta-analysis was performed using RevMan 5.3 version. Pertinent studies were reviewed and the standardized mean difference (SMD) with 95% confidence interval was extracted. A total of 5 studies reporting 460 participants were included in the final analysis. Subgroup and sensitivity analyses were performed to explore the potential sources of between-study heterogeneity.
RESULTS
The results demonstrated that elevated serum HE4 favored the diagnosis of renal fibrosis across all trials (SMD = 1.41; 95% confidence interval, 0.82-2.01; P < .001). The bubble graph indicated statistically robust result. The pooled SMD was similar after removing any single study for sensitivity analysis.
CONCLUSION
The present study suggests a positive association between circulating HE4 and renal fibrosis. Further studies are needed to investigate the effects of interventions on HE4, and the value of HE4 as a biomarker.
Topics: Biomarkers; Female; Fibrosis; Humans; Kidney Diseases; Male; Proteins; Reproducibility of Results; WAP Four-Disulfide Core Domain Protein 2
PubMed: 28885334
DOI: 10.1097/MD.0000000000007824 -
European Review For Medical and... Dec 2018Intestinal fibrosis is a process characterized by an excessive deposition of Extracellular Matrix (ECM) proteins by activated myofibroblasts and represents a consequence...
OBJECTIVE
Intestinal fibrosis is a process characterized by an excessive deposition of Extracellular Matrix (ECM) proteins by activated myofibroblasts and represents a consequence of a chronic inflammation that usually occurs during Inflammatory Bowel Disease (IBD). The relationship between inflammation and fibrosis in IBD remains still unclear and nevertheless the recent pharmacological progresses, currently the only resolutive therapeutic strategy is surgery, especially when complications (stricture, stenosis and obstruction of intestinal tracts) appear. As many different cellular types and molecular mechanisms are implicated in the pathogenesis of IBD, the identification of molecules able to counteract this process could be crucial.
MATERIALS AND METHODS
This is a literature review of several articles published on PubMed databases.
RESULTS
A number of researches suggest that Proliferator-Activated Receptor-gamma (PPAR-γ) has both anti-inflammatory and anti-fibrotic effects in many organs. PPAR-γ has been demonstrated to be able to downregulate pro-inflammatory cytokines production such as Interleukin (IL)-4,-5,-6 but also to interfere with profibrotic molecules as Platelet-Derived Growth Factor (PDGF), IL-1 and Transforming Growth Factor Beta (TGF-β), the main promoter of fibrosis. In preliminary clinical trials and in experimental models of intestinal fibrosis, natural and chemical PPAR-γ ligands have ameliorated the fibrotic process.
CONCLUSIONS
Since PPAR-γ could play a crucial role in the development of the disease, the research of new molecules, capable of ameliorating both inflammation and fibrosis lesions, as PPAR-γ agonists, could represent a valid and effective therapeutic approach for the prevention and treatment of IBD and intestinal fibrosis.
Topics: Fibrosis; Humans; Inflammation; Inflammatory Bowel Diseases; NF-kappa B; PPAR gamma
PubMed: 30575926
DOI: 10.26355/eurrev_201812_16652