Tissue Barriers最新文献

Most injuries in the hand and fingers, especially on the digital pulps, are suited for healing by secondary intention. Nevertheless, delay in epithelization seems to unfavorably restrict this technique. The purpose of this controlled randomized clinical trial is to analyze by means of photo planimetry the progression of the healing process by secondary intention in acute wounds of the hand using the standardized extract of Calendula officinalis L. (SEC). The cohort of eligible participants included two groups of 20 patients with skin loss in the hand and fingers treated by secondary intention. Control group (CG) used mineral oil and intervention group (IG) received SEC. Wound pictures were captured at each outpatient assessment until epithelization was achieved and measured with ImageJ. Intervention group (IG) and control group (CG) with 19 wounds each, primarily formed by men in their 40's with wounds in their index and ring fingers on the left side, showed homogeneous variables and similar initial wound areas. Epithelization time was shorter and healing speed was faster in IG (IG = 8.6 ± 4.7 days and 9.5 ± 5.8%day versus CG = 13.2 ± 7.4 days and 6.2 ± 2.9%day, ƿ < 0.05), leading to the conclusion that healing by secondary intention in acute wounds of the hand and fingers with SEC led to a faster epithelization.

Background: Sodium arsenite is a dangerous bio-accumulative poison affecting a large number of people as well as animals throughout the world. It is used clinically in the treatment of certain medical conditions, but due to its harmful damage to different tissues and mainly the cardiotoxicity, its medical application is limited.

Aim: This study was conducted to investigate the protective effects of spirulina on cardiotoxicity induced by sodium arsenite biochemically and histologically.

Methods: 30 young adult male albino rats were randomly equally divided into three groups 10 animals each. Group I (control), Group II Arsenic intoxicated (10 mg/kg/day/ 4 weeks), Group III spirulina protected animals (concomitant sodium arsenite 10 mg/kg/day/ 4 weeks and spirulina 200 mg/kg/day/ 4 weeks).

Results: It was evident from the study that arsenic exposure exerted a significant increase in cardiac enzyme levels, serum creatine kinase MB (CKMB) and troponin. Concomitant treatment with spirulina is considerably recovered their serum levels. Histological alterations associated with arsenite treated animals are significantly decreased after using spirulina.

Conclusions: The results of the present study showed that use of spirulina could alleviate the toxic effects on the heart following exposure to arsenic toxicity.

Stem cells (SC) and amniotic membrane (AM) are recognized for their beneficial impacts on the healing of cutaneous wounds. Thus, this study evaluated the capacity of tissue repair in a skin lesion rat model. Forty Wistar rats were randomized into four groups: group I - control, with full-thickness lesions on the back, without SC or AM; group II-injected SC; group III - covered by AM; group IV-injected SC and covered by AM. Lesion closure was assessed using contraction rate (Cr). Histochemical and immunohistochemical analyses were performed, and collagen, elastic fibers, fibroblast differentiation factor (TGF-β), collagen remodeling (MMP-8), and the number of myofibroblasts and blood vessels (α-SMA) were evaluated. On the 7^th postoperative day, Cr 1^st-7^th day levels were higher in groups III and IV. However, on the 28^th day, Cr 1^st-28^th day were higher in the control group. Picrosirius staining showed that type I collagen was predominant in all groups; however, the SC + AM group obtained a higher average when compared to the control group. Elastic fiber analysis showed a predominance in groups that received treatment. Groups II and IV showed the lowest expression levels of TGF-β and MMP-8, and α-SMA was significantly lower in group IV. The application of SC and AM accelerated the initial healing phase, probably owing to their anti-inflammatory effect that favored early formation of collagen and elastic fibers.

Airway and intestinal epithelial permeability barriers are crucial in epithelial homeostasis. High mobility group box 1 (HMGB1), increased by various stimuli, is involved in the induction of airway inflammation, as well as the pathogenesis of inflammatory bowel disease. HMGB1 enhances epithelial hyperpermeability. Two-and-a-half dimensional (2.5D) culture assays are experimentally convenient and induce cells to form a more physiological tissue architecture than 2D culture assays for molecular transfer mechanism analysis. In 2.5D culture, treatment with HMGB1 induced permeability of FITC-dextran into the lumen formed by human lung, nasal and intestinal epithelial cells. The tricellular tight junction molecule angulin-1/LSR is responsible for the epithelial permeability barrier at tricellular contacts and contributes to various human airway and intestinal inflammatory diseases. In this review, we indicate the mechanisms including angulin-1/LSR and multiple signaling in dysfunction of the epithelial permeability barrier induced by HMGB1 in 2.5D culture of human airway and intestinal epithelial cells.

ZO-2 is a peripheral tight junction (TJ) protein whose silencing in renal epithelia induces cell hypertrophy. Here, we found that in ZO-2 KD MDCK cells, in compensatory renal hypertrophy triggered in rats by a unilateral nephrectomy and in liver steatosis of obese Zucker (OZ) rats, ZO-2 silencing is accompanied by the diminished activity of LATS, a kinase of the Hippo pathway, and the nuclear concentration of YAP, the final effector of this signaling route. ZO-2 appears to function as a scaffold for the Hippo pathway as it associates to LATS1. ZO-2 silencing in hypertrophic tissue is due to a diminished abundance of ZO-2 mRNA, and the Sp1 transcription factor is critical for ZO-2 transcription in renal cells. Treatment of OZ rats with metformin, an activator of AMPK that blocks JNK activity, augments ZO-2 and claudin-1 expression in the liver, reduces the paracellular permeability of hepatocytes, and serum bile acid content. Our results suggest that ZO-2 silencing is a common feature of hypertrophy, and that ZO-2 is a positive regulator of the Hippo pathway that regulates cell size. Moreover, our observations highlight the importance of AMPK, JNK, and ZO-2 as therapeutic targets for blood-bile barrier dysfunction.

Fistula treatment represents a major unmet medical need in the therapy of Crohn's disease (CD). Current medical therapies, such as anti-TNF antibody treatments, are often insufficient and do not achieve permanent fistula closure. Previously published data point toward a critical role for metalloproteinase-9 (MMP-9)/gelatinase B in fistula pathogenesis. The aim of this project was to investigate in detail MMP-9 expression in different fistula types and to confirm that MMP-9 is a potential target for fistula therapy in CD patients.Immunohistochemistry for total and active MMP-9, Cytokeratin 8 (CK-8) and co-staining of active MMP-9/CK-8 was performed in specimen derived from perianal fistulas, entero-enteric fistulas and fistulas from patients not responding to anti-TNF therapy. In addition, fistulas from the xenograft mouse model (anti-TNF treated or untreated) were analyzed.Total and active MMP-9 protein was detectable in cells lining the tracts of perianal and entero-enteric fistulas. Of note, total and active MMP-9 was also expressed in fistulas of CD patients non-responding to anti-TNF treatment. Interestingly, we detected considerable co-staining of active MMP-9 and CK-8 in particular in cells lining the fistula tract and in transitional cells around the fistulas. Furthermore, total and active MMP-9 are detectable in both anti-TNF treated and untreated xenograft fistulas.Taken together, our data suggest that MMP-9 is involved in fistula pathogenesis in CD patients, in fistulas of different origins and particularly in patients non-responding to anti-TNF therapy. Our xenograft fistula model is suitable for in vivo studies investigating a possible therapeutic role for MMP-9 targeting as fistula therapy.

The intestinal barrier function relies on the presence of a single layer of epithelial cells. Barrier dysfunction is associated with the inflammatory bowel diseases (IBD). Understanding the mechanisms involved in intestinal wound healing in order to sustain the barrier function has a great therapeutic potential. Activation of protease-activated receptor-2 (PAR2) induces COX-2 expression in intestinal epithelial cells via EGFR transactivation. COX-2 is well known for its protective effects in the gastrointestinal tract. Therefore, we hypothesized that PAR-2 activation induces a wound healing response in intestinal epithelial cells through COX-2-derived lipid mediators and EGFR transactivation. Immunofluorescence and calcium assay were used to characterize CMT-93 mouse colonic epithelial cell line for PAR2 expression and its activity, respectively. Treatment with PAR2 activating peptide 2-furoyl-LIGRLO-NH₂ (2fLI), but not by its inactive reverse-sequence peptide (2fO) enhanced wound closure in scratch wounded monolayers. The EGFR tyrosine kinase inhibitor (PD153035), broad-spectrum matrix metalloproteinase inhibitor (GM6001) and Src tyrosine kinase inhibitor (PP2) inhibited PAR2-induced wound healing. However, PAR2 activation did not induce COX-2 expression in CMT-93 cells and inhibition of COX-2 by COX-2 selective inhibitor (NS-398) did not alter PAR2-induced wound healing. In conclusion, PAR2 activation drives wound healing in CMT-93 cells via EGFR transactivation. Matrix metalloproteinases and Src tyrosine kinase activity may involve in EGFR transactivation and PAR2-induced wound healing is independent of COX-2 activity. These findings provide a mechanism whereby PAR2 can participate in the resolution of intestinal wounds in gastrointestinal inflammatory diseases.

Due to a lower survival rate in patients with advanced clinical stages of oral cancer, discovering a biomarker that could diagnose and predict disease progression is vital. Cell-cell junctional proteins play a crucial role in the maintenance of tissue architecture but are often deregulated in different cancer. The present study investigates the expression of cell-cell junctional proteins viz: e-cadherin (E-cad) and zonula occludens-1 (ZO-1) in oral precancerous (OED) and cancerous (OSCC) patients to monitor if they can serve as practicable molecular markers. The ultrastructural junctional complex was studied by transmission electron microscopy, and the expression of proteins was performed by immunohistochemistry. The relationship between the expression of protein and clinicopathological features of the patients was checked by Pearson's correlation test. Furthermore, the survival curve of the follow-up data was estimated by the Kaplan-Meier method. We observed a disrupted junctional complex and a significantly decreased immunoexpression of E-cad and ZO-1 in OED and OSCC when compared to the adjacent non-cancerous tissues. The expression of ZO-1 was associated with TNM stages, whereas E-cad was associated with histological grades as well as TNM stages. A positive correlation was observed between the expression of ZO-1 and E-cad proteins in OED and OSCC. Further, follow-up studies revealed that high ZO-1 and E-cad expressing patients survived longer than their low expressed counterparts. The present study shows disruption of junctional complex and alteration of junctional proteins expression that could draw the attention of health professionals to explore junctional proteins as a possible therapeutic target in oral cancer.

In spite of clinical advancements and improved diagnostic techniques, breast cancers are the leading cause of cancer-associated deaths in women worldwide. Although 70% of early breast cancers can be cured, there are no efficient therapies against metastatic breast cancers. Several factors including connexins and gap junctions play roles in breast tumorigenesis. Connexins are critical for cellular processes as a linkage between connexin mutations and hereditary disorders demonstrated their importance for tissue homeostasis. Further, alterations in their expression, localization and channel activities were observed in many cancers including breast cancer. Both channel-dependent and independent functions of connexins were reported in initiation and progression of cancers. Unlike initial reports suggesting tumor suppressor functions, connexins and gap junctions have stage, context and isoform dependent effects in breast cancers similar to other cancers. In this review, we tried to describe the current understanding of connexins in tumorigenesis specifically in breast cancers.

Claudins are major components of tight junctions that maintain cell polarity and intercellular adhesion. The dynamics of claudins in cancer cells have attracted attention as a therapeutic target. During carcinogenesis, claudin expression is generally downregulated; however, overexpression of claudin-18.2 has been observed in several types of cancers. Upregulated and mislocalized claudin-18.2 expression in cancer cells has been suggested as a therapeutic target. Research on claudin-18.2 has revealed its involvement in carcinogenesis. Clinical trials using zolbetuximab, a monoclonal antibody targeting claudin-18.2, for patients with advanced cancer yielded positive results with few high-grade adverse events; thus, it is expected to be a novel and effective therapeutic. Here, we review current insights into the role that claudin-18.2 plays in basic cancer research and clinical applications. A better understanding of these roles will facilitate the development of new treatment strategies for cancer patients with poor prognoses.