Integrin proteins have received a significant increase in attention in recent scientific endeavors. The current trend uses the pre-established knowledge that the arginyl-glycyl-aspartic acid (RGD) structural motif present in the A20FMDV2 peptide is highly selective for the integrin class αvβ6 which is overexpressed in many cancer types. This review will provide an extensive overview of the existing literature research to date to the best of our knowledge, highlighting significant improvements and drawbacks of structure-activity relationships (SAR) work undertaken, aiding future research to identify established SAR for a rational design of future A20FMDV2 mimetic inhibitors. Herein, the review aims to collate the existing structural chemical modifications present on A20FMDV2 in the literature to highlight key structural analogues that display more potent biological activity.

The delivery of Helicobacter pylori CagA into host cells was long believed to occur through the integrin cell surface receptors. However, the role of CEACAM receptors has recently been highlighted, instead. Here, we have categorized the existing experimental evidence according to whether deletion, upregulation, downregulation, or inhibition of the target ligands (T4SS or HopQ) or receptors (integrins or CEACAMs), result in alterations in CagA phosphorylation, cell elongation, or IL-8 production. According to our analysis, the statistics favor the essence of most of the T4SS constituents and the involvement of HopQ adhesin in all three functions. Concerning the integrin family, the collected data is controversial, but yielding towards it being dispensable or involved in CagA translocation. Yet, regarding cell elongation, more events are showing β1 integrin being involved, than αvβ4 being inhibitory. Concerning IL-8 secretion, again there are more events showing α5, β1 and β6 integrins to be involved, than those showing inhibitory roles for β1, β4 and β6 integrins. Finally, CEACAM 1, 3, and 5 are identified as mostly essential or involved in CagA phosphorylation, whereasCEACAM 4, 7, and 8 are found dispensable and CEACAM6 is under debate. Conversely, CEACAM1, 5 and 6 appear mostly dispensable for cell elongation. Noteworthy is the choice of cell type, bacterial strain, multiplicity and duration of infection, as well as the sensitivity of the detection methods, all of which can affect the variably obtained results.

BACKGROUND: Oral cancers have limited diagnostic tools to aid clinical management. Current evidence indicates that alterations in hemidesmosomes, the adhesion complexes primarily involved in epithelial attachment to the basement membrane, are correlated to cancer phenotype for multiple cancers. This systematic review aimed to assess the experimental evidence for hemidesmosomal alterations, specifically in relation to oral potentially malignant disorders and oral squamous cell carcinomas.
METHODS: We conducted a systemic review to summarise the available literature on hemidesmosomal components and their role in oral pre-cancer and cancer. Relevant studies were retrieved from a comprehensive search of Scopus, Ovid MEDLINE, Ovid Embase and Web of Science.
RESULTS: 26 articles met the inclusion criteria, of which 19 were in vitro studies, 4 in vivo studies, 1 in vitro and in vivo study, and 2 in vitro and cohort studies. Among them, 15 studies discussed individual alpha-6 and/or beta-4 subunits, 12 studies discussed the alpha-6 beta-4 heterodimers, 6 studies discussed the entire hemidesmosome complex, 5 studies discussed bullous pemphigoid-180, 3 studies discussed plectin, 3 studies discussed bullous pemphigoid antigen-1 and 1 study discussed tetraspanin.
CONCLUSIONS: Heterogeneity in cell type, experimental models, and methods were observed. Alterations in hemidesmosomal components were shown to contribute to oral pre-cancer and cancer. We conclude that there is sufficient evidence for hemidesmosomes and their components to be potential biomarkers for evaluating oral carcinogenesis.

Despite advances in treating patients with melanoma, there are still many treatment challenges to overcome. Studies with snake venom-derived proteins/peptides describe their binding potential, and inhibition of some proliferative mechanisms in melanoma. The combined use of these compounds with current therapies could be the strategic gap that will help us discover more effective treatments for melanoma. The present study aimed to carry out a systematic review identifying snake venom proteins and peptides described in the literature with antitumor, antimetastatic, or antiangiogenic effects on melanoma and determine the mechanisms of action that lead to these anti-tumor effects. Snake venoms contain proteins and peptides which are antiaggregant, antimetastatic, and antiangiogenic. The in vivo results are encouraging, considering the reduction of metastases and tumor size after treatment. In addition to these results, it was reported that these venom compounds could act in combination with chemotherapeutics (Acurhagin-C; Macrovipecetin), sensitizing and preparing tumor cells for treatment. There is a consensus that snake venom is a promising strategy for the improvement of antimelanoma therapies, but it has been little explored in the current context, combined with inhibitors, immunotherapy or tumor microenvironment, for example. We suggest Lebein as a candidate for combination therapy with BRAF inhibitors.

Seed cells, biomaterials and growth factors are three important aspects in tissue engineering. Biomaterials mimic extra cellular matrix in vivo, providing a sound environment for cells to grow and attach, so as to maintain cell viability and function. The physicochemical properties and modification molecules of material surface mediate cell behaviors like cell adhesion, proliferation, migration and differentiation, which in turn affect cellular function and tissue regeneration efficacy. Furthermore, the modification molecules of material surface are the direct contact point for cell adhesion and growth. Therefore, the interactions between cells and surface modification molecules are the key to tissue engineering. This review summarizes the effects of surface modification molecules on cell phenotypes and functions.

The ongoing COVID-19 pandemic has raised concerns about the risk of SARS-CoV-2 infection in patients with Crohn\'s disease (CD) and patients with ulcerative colitis (UC) taking immunosuppressants or biologics. We conducted a systematic review and meta-analysis to assess the risk of respiratory infections in patients with inflammatory bowel disease (IBD) treated with vedolizumab. We searched PubMed, EMBASE and Scopus to identify randomized controlled trials (RCT) comparing vedolizumab to placebo in patients with IBD. Outcomes were the rate of respiratory tract infections (RTI), upper respiratory tract infections (URTI) and lower respiratory tract infections (LRTI) among patients receiving vedolizumab as compared with placebo. Pooled rates were reported as Odds Ratios (OR) with 95% Confidence Interval (CI). Eight RCT involving 3,287 patients (1873 CD and 1415 UC) were analyzed; 2,493 patients received vedolizumab and 794 received placebo. The rates of RTI and URTI were statistically higher in vedolizumab-treated patients compared to placebo [OR = 1.63; 95% CI (1.07-2.49); OR = 1.64 95% CI (1.07-2.53) respectively]. UC patients, but not CD patients, receiving vedolizumab had a higher risk to develop RTI and URTI [OR = 1.98; 95% CI (1.41-2.77); OR = 2.02; 95% CI (1.42-2.87)] compared to placebo-treated patients. The number of LRTI was small in both treatment groups. Data confirm the good safety profile of vedolizumab even though RTI were more frequent in patients receiving vedolizumab and the risk of URTIs was significantly higher in patients with UC.

Cell-cell adhesion molecules have critically important roles in the early events of reproduction including gamete transport, sperm-oocyte interaction, embryonic development, and implantation. Major adhesion molecules involved in reproduction include cadherins, integrins, and disintegrin and metalloprotease domain-containing (ADAM) proteins. ADAMs on the surface of sperm adhere to integrins on the oocyte in the initial stages of sperm-oocyte interaction and fusion. Cadherins act in early embryos to organize the inner cell mass and trophectoderm. The trophoblast and uterine endometrial epithelium variously express cadherins, integrins, trophinin, and selectin, which achieve apposition and attachment between the elongating conceptus and uterine epithelium before implantation. An overview of the major cell-cell adhesion molecules is presented and this is followed by examples of how adhesion molecules help shape early reproductive events. The argument is made that a deeper understanding of adhesion molecules and reproduction will inform new strategies that improve embryo survival and increase the efficiency of natural mating and assisted breeding in cattle.

Sustained biomaterial thromboresistance has long been a goal and challenge in blood-contacting device design. Endothelialization is one of the most successful strategies to achieve long-term thromboresistance of blood-contacting devices, with the endothelial cell layer providing dynamic hemostatic regulation. It is well established that endothelial cell behavior is influenced by interactions with the underlying extracellular matrix (ECM). Numerous researchers have sought to exploit these interactions to generate improved blood-contacting devices by investigating the expression of hemostatic regulators in endothelial cells on various ECM coatings. The ability to select substrates that promote endothelial cell-mediated thromboresistance is crucial to advancing material design strategies to improve cardiovascular device outcomes. This review provides an overview of endothelial cell regulation of hemostasis, the major components found within the cardiovascular basal lamina, and the interactions of endothelial cells with prominent ECM components of the basement membrane. A summary of ECM-mimetic strategies used in cardiovascular devices is provided with a focus on the effects of key adhesion modalities on endothelial cell regulators of hemostasis.

Despite widespread clinical use of anesthetics, the exact mechanisms of anesthetic action are unclear. In terms of physiological action, a broad mechanism of general anesthesia including perturbations of neurotransmission has been suggested. However, the mechanism of anesthetic action at the molecular level is less clear. Specifically, how anesthetics affect neurons and glial cells and which proteins they interact with remains to be explored. Several recent studies have investigated the molecular interactions between proteins and anesthetics. In this review, we summarize the molecular mechanisms of anesthetic action in the intracellular signaling pathways of neuronal and glial cells.

Epithelial ovarian cancer is a fatal disease, with a cure rate of only 30%. Several recent studies have targeted integrins for cancer treatment. Preclinical studies have shown the effectiveness of several integrin inhibitors for blocking cancer progression, especially by blocking angiogenesis. Because the initial critical step in ovarian cancer metastasis is the attachment of cancer cells to the peritoneum or omentum and because clinical trials have provided positive results for anti-angiogenic therapy, therapies targeting integrins may be the most feasible approach for treating cancer. This review summarizes the current understanding of integrin biology in ovarian cancer metastasis and various therapeutic approaches involving integrin inhibitors. However, no integrin inhibitor has shown favorable results thus far. However, conjugates of cytotoxic agents with the triplet sequence arginine-glycine-aspartate (RGD) peptides targeting α5β1-, αvβ3-, and αvβ6-integrins may be promising integrin-targeting therapies for further clinical investigation.