The role of the stromal extracellular matrix in the development of pterygium pathology: an update

22 p.Pterygium is a benign fibrovascular lesion of the bulbar conjunctiva with frequent involvement of the corneal limbus. Its pathogenesis has been mainly attributed to sun exposure to ultraviolet-B radiation. Obtained evidence has shown that it is a complex and multifactorial process which involves multiple mechanisms such as oxidative stress, dysregulation of cell cycle checkpoints, induction of inflammatory mediators and growth factors, angiogenic stimulation, extracellular matrix (ECM) disorders, and, most likely, viruses and hereditary changes. In this review, we aim to collect all authors? experiences and our own, with respect to the study of fibroelastic ECM of pterygium. Collagen and elastin are intrinsic indicators of physiological and pathological states. Here, we focus on an in-depth analysis of collagen (types I and III), as well as the main constituents of elastic fibers (tropoelastin (TE), fibrillins (FBNs), and fibulins (FBLNs)) and the enzymes (lysyl oxidases (LOXs)) that carry out their assembly or crosslinking. All the studies established that changes in the fibroelastic ECM occur in pterygium, based on the following facts: An increase in the synthesis and deposition of an immature form of collagen type III, which showed the process of tissue remodeling. An increase in protein levels in most of the constituents necessary for the development of elastic fibers, except FBLN4, whose biological roles are critical in the binding of the enzyme LOX, as well as FBN1 for the development of stable elastin. There was gene overexpression of TE, FBN1, FBLN5, and LOXL1, while the expression of LOX and FBLN2 and -4 remained stable. In conclusion, collagen and elastin, as well as several constituents involved in elastic fiber assembly are overexpressed in human pterygium, thus, supporting the hypothesis that there is dysregulation in the synthesis and crosslinking of the fibroelastic component, constituting an important pathogenetic mechanism for the development of the disease.CIBER-BB

Postimplant intraperitoneal behavior of collagen-based meshes followed by laparoscopy

17 p.Background When repairing an abdominal wall defect, sometimes a prosthetic mesh needs to be placed directly on the parietal peritoneum. Although the standard mesh for this purpose is the laminar implant expanded polytetrafluoroethylene (PTFE), it is gradually being replaced by the laminar collagen-based meshes. This study was designed to assess the intraperitoneal behavior of three of these biomeshes, mainly in terms of their susceptibility to adhesion formation. Methods Two 3-cm x 3-cm fragments of prosthetic material were placed on the parietal peritoneum in male New Zealand White rabbits in the following combinations: PTFE and CollaMend®, PTFE and Permacol®, or PTFE and Surgisis®. The meshes were fixed at the four corners with individual 4/0 polypropylene sutures. Adhesion formation was quantified by sequential laparoscopy and image analysis performed at 3, 7, 14, and 90 days postimplant. All animals were killed at 90 days and the mesh specimens were subjected to microscopy and immunohistochemistry. Results Intensely vascularized adhesions to all the implants were observed, although Surgisis showed the lowest percentage of adhesions at each follow-up time. Adhesions had stabilized by 7-14 days. The PTFE meshes were enveloped by a layer of macrophages and connective tissue, bounded by a monolayer of mesothelial cells. Permacol and CollaMend showed similar histological behavior, including cell ingrowth through their fenestrations with no signs of degradation detected at 90 days. In contrast, the Surgisis mesh at 90 days was practically replaced with neoformed tissue. Conclusions No difference in susceptibility to adhesion formation was noted in the crosslinked collagen meshes compared to PTFE meshes. The noncrosslinked collagen mesh Surgisis showed the best behavior in that it induced fewer adhesions. Ninety days after implant, a more intense macrophage response was observed in CollaMend and Permacol than in PTFE or Surgisis.Fundación Mutua Madrileñ

A novel controlled drug-delivery system for growth hormone applied to healing skin wounds in diabetic rats

Controlled release systems for drugs, hormones and growth factors can be particularly useful in tissue repair processes. These systems act as a biodegradable support containing the substance to be delivered, allowing their gradual release. In the past years, the local application of growth factors has acquired special relevance as a therapeutic option for use in subjects who show de cient tissue scarring, the hormone dose being the limiting factor for its success. In this study, the in vitro biocompatibility of a copolymer formed by vinylpyrrolidone and 2-hydroxyethyl methacrylate, used as an administration vehicle for hGH, was evaluated. The system was then tested in vivo in terms of its capacity for healing incisional wounds in healthy and diabetic rats. For the in vitro studies, polymer and hormone degradation rates were determined, and polymer biocompatibility was evaluated in broblast cultures. In the in vivo experiments, an incision was made in the back of the animals, and polymers discs with/ without hGH, were introduced in the aperture. Morphological, immunohistochemical and morphometric evaluations were performed on wound tissue specimens 3¿10 days after surgery. In vitro, the polymer was found to be biodegradable and showed no toxic effects on broblasts, the hormone being slowly released to the culture medium. In untreated diabetic rats, a delayed skin scarring and cell response were observed, compared to that noted in healthy animals. Skin closure, keratinisationand brosis occurred earlier in the presence of the polymer-hGH system. The use of this co-polymer as an administrationvehicle for hGH improves the wound scarring process in the pathological setting of diabetes

Tropoelastin and fibulin overexpression in the subepitelial connective tissue of human pterigium

Purpose To evaluate possible changes in the collagen and elastic components of the subepithelial connective tissue of human pterygium. Design Immunohistochemical study. Methods Immunohistochemical staining using antitropoelastin, anti-fibulin-2, and anti-fibulin-3 antibodies was performed in 10 normal conjunctival and 20 pterygium specimens. Masson trichome staining also was performed to study subepithelial connective tissue. Sirius red staining was used to identify collagen type I and III components. Tropoelastin, fibulin-2, and fibulin-3 messenger ribonucleic acid (mRNA) expressions were analyzed in 9 conjunctival and 12 pterygium specimens by quantitative real-time polymerase chain reaction assay. Results The subepithelial connective tissue and vessels were more predominant in pterygium compared with the normal conjunctival tissue. Amorphous subepithelial zones were observed in the areas of the pterygium tissue, but not in normal conjunctiva. Increased tropoelastin staining was seen in the pterygium tissue with areas of degenerative changes or immature formation of elastic fibers, as well an increase in tropoelastin mRNA, in contrast with fibulin-2 and fibulin-3 messenger levels. Fibulin-2 and fibulin-3 expression was colocalized in the subepithelial connective tissue and was distributed along blood and lymphatic vessels. Collagen type III, an immature form of collagen, was increased in the pathologic samples in association with a tissue remodeling process. Conclusions Elastin metabolism is dysregulated in the pathogenesis of human pterygium with tropoelastin, fibulin-2, and fibulin-3 overexpression in the subepithelial connective tissue.Hospital Universitario Príncipe de Asturias (Alcalá de Henares, España)Instituto de Salud Carlos III (Madrid, España)

Understanding HAT1: A Comprehensive Review of Noncanonical Roles and Connection with Disease

Histone acetylation plays a vital role in organizing chromatin, regulating gene expression and controlling the cell cycle. The first histone acetyltransferase to be identified was histone acetyltransferase 1 (HAT1), but it remains one of the least understood acetyltransferases. HAT1 catalyzes the acetylation of newly synthesized H4 and, to a lesser extent, H2A in the cytoplasm. However, 20 min after assembly, histones lose acetylation marks. Moreover, new noncanonical functions have been described for HAT1, revealing its complexity and complicating the understanding of its functions. Recently discovered roles include facilitating the translocation of the H3H4 dimer into the nucleus, increasing the stability of the DNA replication fork, replication-coupled chromatin assembly, coordination of histone production, DNA damage repair, telomeric silencing, epigenetic regulation of nuclear lamina-associated heterochromatin, regulation of the NF-kappa B response, succinyl transferase activity and mitochondrial protein acetylation. In addition, the functions and expression levels of HAT1 have been linked to many diseases, such as many types of cancer, viral infections (hepatitis B virus, human immunodeficiency virus and viperin synthesis) and inflammatory diseases (chronic obstructive pulmonary disease, atherosclerosis and ischemic stroke). The collective data reveal that HAT1 is a promising therapeutic target, and novel therapeutic approaches, such as RNA interference and the use of aptamers, bisubstrate inhibitors and small-molecule inhibitors, are being evaluated at the preclinical level

Estudio de la expresión de EGFL7 (Epidermal growth factor-like domain-containing protein 7) en la pared venosa de pacientes con enfermedad venosa crónica

La enfermedad venosa crónica (EVC) se trata de una amplia variedad de anomalías del sistema venoso de gran prevalencia en nuestra sociedad. Frecuentemente, se manifiesta en las extremidades inferiores en forma de vena varicosa (VV), cursando como una situación de hipertensión venosa ambulatoria que se agrava conforme progresa la enfermedad. Cada vez más estudios evidencian la importancia de los cambios moleculares y de la matriz extracelular en la fisiopatogenia de la EVC. EGFL-7 (Epidermal growth factor-like domain-containing protein 7) es un componente de gran importancia en el desarrollo y patología del sistema vascular, aunque su papel en la EVC todavía no ha sido esclarecido. Así, el objetivo del presente trabajo es analizar la expresión génica y proteica de EGFL7 en la pared venosa de pacientes con EVC (n=35) y sanos (n=27), mediante la realización de RT-qPCR e immunohistoquímica, respectivamente. Nuestros resultados muestran como existe una disminución en la expresión de EGFL-7 en pacientes con EVC en comparación con las venas de individuos sanos. En su conjunto, nuestro trabajo apoya el papel de EGFL7 en la pérdida de la homeostasis vascular asociada a la EVC. Futuros estudios son necesarios para profundizar en las implicaciones de estos cambios en el tejido venoso patológico, así como el desarrollo de posibles estrategias dirigidas a esta diana.Chronic venous disease (CVD) is a wide variety of anomalies of the venous system that are highly prevalent in our society. Frequently, it manifests in the lower extremities in the form of varicose veins(VV), presenting as a situation of ambulatory venous hypertension that worsens as the disease progresses. More and more studies show the importance of molecular changes and of the extracellular matrix in the pathophysiology of CVD. EGFL-7 (Epidermal growth factor-like domain-containing protein 7) is a component of great importance in the development and pathology of the vascular system, although its role in CVD has not yet been clarified. Thus, the objective of this study is to analyze the gene and proteinexpression of EGFL7 in the venous wall of patients with CVD (n=35) and healthy patients (n=27), by performing RT-qPCR and immunohistochemistry, respectively. Our results show how there is a decrease in the expression of EGFL-7 in patients with CVD compared to the veins of healthy individuals. As a whole, our work supports the role of EGFL7 in the loss of vascular homeostasis associated with CVD. Future studies are necessary to delve into the implications of these changes in the pathological venous tissue, as well as the development of possible strategies aimed at this target

Histobiología de la grasa parda. Acción de la hidrocortisona sobre el tejido adiposo pardo. Efectos cualitativos y cuantitativos

Tesis Universidad Complutense.ProQuestFac. de MedicinaTRUEpu

Placentas from Women with Late-Onset Preeclampsia Exhibit Increased Expression of the NLRP3 Inflammasome Machinery

2023 Descuento MDPIPre-eclampsia is a harmful and potentially lethal medical condition during pregnancy clinically diagnosed by hypertension and commonly accompanied by proteinuria and multiorgan affections. According to the time of diagnosis, it is differentiated between early-onset (EO-PE) and late-onset preeclampsia (LO-PE). Despite being less dangerous and presenting distinct pathophysiological signatures, LO-PE has a greater prevalence than EO-PE, both having significant consequences on the placenta. Previous works have evidenced that exacerbated inflammation in this organ might play a potential pathogenic role in the development of pre-eclampsia, and there is some preliminary evidence that the hyperactivation of inflammasomes can be related to the altered immunoinflammatory responses observed in the placentas of these patients. However, the precise role of inflammasomes in the placentas of women with LO-PE remains to be fully understood. In this work, we have studied the gene and protein expression of the main components related to the canonical and non-canonical pathways of the inflammasome NLRP3 (NLRP3, ASC, caspase 1, caspase 5, caspase 8, interleukin 1β, and interleukin 18) in the placental tissue of women with LO-PE. Our results show a marked increase in all these components in the placentas of women who have undergone LO-PE, suggesting that NLRP3 inflammasome plays a potentially pathophysiological role in the development of this entity. Future works should aim to evaluate possible translational approaches to this dysregulation in these patients.Instituto de Salud Carlos IIIEuropean CommissionComunidad de MadridDepto. de MedicinaFac. de MedicinaTRUEpubDescuento UC

Dendrimers and dendritic materials: From laboratory to medical practice in infectious diseases

Infectious diseases are one of the main global public health risks, predominantly caused by viruses, bacteria, fungi, and parasites. The control of infections is founded on three main pillars: prevention, treatment, and diagnosis. However, the appearance of microbial resistance has challenged traditional strategies and demands new approaches. Dendrimers are a type of polymeric nanoparticles whose nanometric size, multivalency, biocompatibility, and structural perfection offer boundlesspossibilities in multiple biomedical applications. This review provides the reader a general overview about the uses of dendrimers and dendritic materials in the treatment, prevention, and diagnosis of highly prevalent infectious diseases, and their advantages compared to traditional approaches. Examples of dendrimers as antimicrobial agents per se, as nanocarriers of antimicrobial drugs, as well as their uses in gene transfection, in vaccines or as contrast agents in imaging assays are presented.Despite the need to address some challenges in order to be used in the clinic, dendritic materials appear as an innovative tool with a brilliant future ahead in the clinical management of infectiousdiseases and many other health issues