The CCN family of matricellular proteins are recognized bona fide targets for therapeutically targeting so-called chronic inflammatory diseases, including fibrosis and cancers. The majority of the work supporting this contention has been derived from examining CCN2, formerly, and unhelpfully, termed “connective tissue growth factor.” Both CCN2, and its related protein, CCN1, formerly termed “cysteine-rich

During the last stages of wound healing, myofibroblasts differentiate mainly from fibroblasts. Myofibroblasts from normal skin wounds (Wmyo) can communicate with its surrounding using secreted factors. They also have the capacity to produce microvesicles (MVs), a type of extracellular vesicles, as mediators of intercellular communication. MVs cargo are potentially capable of regulating the behavior

Cancer cells are able to release high amounts of extracellular vesicles, thereby conditioning the normal cells in the surrounding tissue and/or in distant target organs. In the context of bone cancers, previous studies suggested that osteosarcoma cancer cells produce transforming extracellular vesicles able to induce a tumour-like phenotype in normal recipient cells. Indeed, phosphoinositide-specific

Appropriate tools for monitoring sarcoma progression are still limited. The aim of the present study was to investigate the value of miR-34a-5p (miR34a) as a circulating biomarker to follow disease progression and measure the therapeutic response. Stable forced re-expression of miR34a in Ewing sarcoma (EWS) cells significantly limited tumor growth in mice. Absolute quantification of miR34a in the plasma

Circular RNAs(CircRNAs), a new class of non-coding RNAs, possess significant capabilities of gene regulation and are disrupted in various diseases, including diabetes mellitus (DM). However, the underlying mechanism of CircRNAs in DM and diabetic complications remains illusive. A recent study published by Liu et al. (Proc Natl Acad Sci USA 116:7455-7464, 2019) shown that a novel diabetic retinopathy

Lung adenocarcinoma (LA) is a subtype of lung cancer that accounts for about 40% of all lung cancers. Analysis of molecular mechanisms controlling this cancer can help scientists to detect, control and treat LA. Here, a microarray dataset (GSE118370) containing six normal lung (NL) and six LA samples was screened using GEO2R to find differentially expressed genes (DEGs). Then, DAVID, KEGG and ChEA

One of the first targets proposed as an anti-fibrotic therapy was CCN2. Proof of its involvement in fibrosis was initially difficult, due to the lack of appropriate reagents and general understanding of the molecular mechanisms responsible for persistent fibrosis. As these issues have been progressively resolved over the last twenty-five years, it has become clear that CCN2 is a bone fide target for

COVID-19 is a respiratory disease. A recent report in Lancet examined, retrospectively, 137 patients with COVD-19. Patients that died had elevated IL-6 levels and acute respiratory distress syndrome. These data have obvious implications for how to control mortality in COVID-19.

Tobacco smoke's harmful effects are well-known; the harmful effects of tobacco smoke have been well-investigated. Nicotine in tobacco smoke contributes to the pathogenesis of various conditions, such as lung cancer, coronary artery disease and asthma. A decade ago, a seemingly safer alternative to tobacco cigarettes was introduced- the E-cigarette. However, studies have found that E-cigarette smoke

Skeletal muscle fibro-adipogenic progenitors (FAPs) are tissue-resident connective tissue cells and the main cellular source of pathological fibro-fatty scar associated with muscle disorders. Although our knowledge about skeletal muscle mesenchymal progenitor cells has exploded in the past decade, we still lack information about their origin, fate, gene regulation, function, and stemness. A recent

Autophagy occurs at basal levels for cellular homeostasis under normal conditions and is increased in response to nutrient starvation or stress to ensure cell survival. However, excessive autophagy can be deleterious to cardiomyocytes. CCN1/Cyr61, a matricellular protein, is expressed in the stressed heart to induce cardiomyopathy. The role of autophagy in CCN1-associated cardiotoxicity was not clear

Tumour-associated fibroblasts (TAFs) mediate the differentiation of adjacent stromal cells. Berberine (BBR), a monomer of traditional Chinese herbs, exhibits a potent therapeutic effect against cancer. However, the effects of BBR on the differentiation of normal colonic epithelial cells induced by TAFs have not been determined. In the present study, we selected the TAF-like myofibroblast cell line

Chronic myeloid leukemia (CML) is a malignant blood disease with a particular chromosomal aberration that is known as a common form of leukemia. The chromene family exhibits strong anti-cancer effects. Therefore, the effects of six members of the dihydropyrano [2,3-g] chromene family on cell toxicity and apoptosis induction in K562 cancer cells were investigated and compared with those of normal peripheral

Previous studies have demonstrated that the C-terminal of E1A binding proteins (CtBPs) influences tumorigenesis by participating in cell signal transduction in various human malignancies. However, the detailed expression patterns of CtBP isoforms in human osteosarcoma (OS) and the molecular mechanisms of CtBP involvement in tumor cell phenotypes requires further investigation. In the present study

Protein post-translational modifications (PTMs) have emerged to be combinatorial, essential mechanisms used by eukaryotic cells to regulate local chromatin structure, diversify and extend their protein functions and dynamically coordinate complex intracellular signalling processes. Most common types of PTMs include enzymatic addition of small chemical groups resulting in phosphorylation, glycosylation

Pulmonary fibrosis is a severely disabling disease often leading to death. CCN2 (Cellular Communication Network factor 2, also known as CTGF) is a known mediator of fibrosis and clinical trials studying anti-CCN2 efficacy in pulmonary fibrosis are currently underway. Fork head box D1 (FoxD1) transcription factor is transiently expressed in several mesenchymal cell types, including those of fetal lungs

The extracellular matrix microenvironment of adipose tissue is of critical importance for the differentiation, remodeling and function of adipocytes. Fibrillin-1 is one of the main components of microfibrils and a key player in this process. Furin processing of profibrillin-1 results in mature fibrillin-1 and releases the C-terminal propeptide as a circulating hunger hormone, asprosin. Mutations in

This review focuses on current advances in researches of gasdermin family. The distinctive expression patterns and biological roles of members in this family were discussed. Most of them exhibit pore-forming activity on cell membranes and are executors for programmed cell death with cytokines release, and play roles in cancers and inflammation-driven diseases. Therefore, they can be used as potential

CUDC-907 is a novel dual-acting inhibitor of phosphoinositide 3-kinase (PI3K) and histone deacetylase (HDAC). In this study, we aimed to explore the anticancer effects of CUDC-907 on human breast cancer cells. Our results showed that CUDC-907 effectively inhibited breast cancer cell proliferation. Flow cytometry analysis revealed that CUDC-907 induced cell cycle arrest and apoptosis in breast cancer

Basal Cell Carcinoma (BCC) represents the most common form of all cancers. BCC is characteristically surrounded by a fibromyxoid stroma. Previous studies have suggested a shift towards a Th2 response, an increase in T regulatory lymphocytes and the presence of cancer-associated fibroblasts in the BCC tumor microenvironment. In this study, we aimed to further characterize the BCC tumor microenvironment

IRE1α endonuclease is a key regulator of endoplasmic reticulum (ER) stress that controls cell survival/apoptosis in cancers. Inhibition of IRE1α endonuclease leads to decreased splice XBP1 which decreases cell proliferation and increases cell death in cancer cells. Therefore, this study investigated the effects and mechanism of STF-083010 (an IRE1α inhibitor) on the cell growth/apoptosis of ovarian

Erlotinib is an oral tyrosine kinase inhibitor of epidermal growth factor receptor (EGFR) pathway. Although our previous study has proved the efficacy of Erlotinib in head and neck squamous cell carcinoma (HNSCC), it has also demonstrated poor clinical response rates and disappointing results in clinical trials for HNSCC to date. In this study, we discovered elevated cell proliferation and invasion

Na+/H+ exchanger NHE1, a major determinant of intracellular pH (pHi) in mammalian central neurons, promotes neurite outgrowth under both basal and netrin-1-stimulated conditions. The small GTP binding proteins and their effectors have a dominant role in netrin-1-stimulated neurite outgrowth. Since NHE1 has been shown previously to work downstream of the Rho GTPases-mediated polarized membrane protrusion

Hypoxia refers to the decrease in oxygen tension in the tissues, and the central effector of the hypoxic response is the transcription factor Hypoxia-Inducible Factor α (HIF1-α). Transient hypoxia in acute events, such as exercising or regeneration after damage, play an important role in skeletal muscle physiology and homeostasis. However, sustained activation of hypoxic signaling is a feature of skeletal

Retinoblastoma (RB) is one of the most common ophthalmic tumors, and most of the patients have been identified as advanced at the time of diagnosis, which is directly related to high mortality. Recent studies showed that long noncoding RNA (lncRNA) and miRNAs play key roles in the development、progression、or treatment of cancer, such as RB. However, the role of lncRNA -TP73-AS1 in RB remains unclear

Previously, we reported that an extracellular matrix protein, osteopontin (OPN), is involved in various autoimmune diseases using a neutralizing polyclonal antibody against OPN generated in rabbits. However, the antibody cannot be used for long-term mouse models of chronic inflammatory disease because of the induction of antibodies against anti-OPN rabbit IgG. In this study, we generated a new antibody

LDL receptor-related proteins 6 (LRP6) is a type I transmembrane receptor (C-terminus in cytosol), which appears to be essential in numerous biological processes, since it is an essential co-receptor of Wnt ligands for canonical β-catenin dependent signal transduction. It was shown that tissue plasminogen activator (tPA), physically interacting with LRP6, induces protein phosphorylation, which may

It is widely believed that extracellular vesicles (EVs) mediate intercellular communications by functioning as messengers. EVs contain various biomolecules, including nucleic acids and proteins, as cargo in the internal space. Thus, it has been postulated that this cargo can be transferred from donor cells to recipient cells, leading to phenotypic changes in the recipient cells. However, there is a

Paracrine signaling between tumor and surrounding stromal cells is critical for the maintenance of tumor microenvironment during ovarian cancer progression. Small extracellular vesicles (sEVs; exosomes in particular) are nano-sized vesicles secreted actively by many cells including tumor cells and are found to have fundamental roles in intercellular communication through shuttling functional RNAs.

Pulmonary fibrosis is a severely disabling disease often leading to death. CCN2 (Cellular Communication Network factor 2, also known as CTGF) is a known mediator of fibrosis and clinical trials studying anti-CCN2 efficacy in pulmonary fibrosis are currently underway. Fork head box D1 (FoxD1) transcription factor is transiently expressed in several mesenchymal cell types, including those of fetal lungs

Pembrolizumab monotherapy has been demonstrated as a first-line therapy for non-small-cell lung cancer (NSCLC) patients with a programmed death ligand 1 (PD-L1) tumor proportion score (TPS) of ≥50%; however, the clinical efficacy is limited by the unreasonable threshold of the TPS. A recent study published by Mok et al. (Lancet 393:1819-1830, 2019) showed that pembrolizumab monotherapy could also be

Abstract Epithelial tissues provide tissue barriers and specialize in organs and glands. When epithelial homeostasis is physiologically or pathologically stimulated, epithelial cells produce mesenchymal cells through the epithelial-mesenchymal transition, forming new tissues, promoting the cure of diseases or leading to illness. A variety of cytokines are involved in the regulation of epithelial cell

Esophageal squamous cell carcinoma (ESCC) is one of the most common malignant tumors with poor prognosis. Aryl hydrocarbon receptor (AHR) is a ligand-dependent transcription factor and emerging evidence shows it is associated with tumor initiation and promotion. However, the relationship between AHR and ESCC is not clear and it is meaningful to explore whether AHR could be a therapeutic target. In

Interleukin-18 (IL-18) is a member of the IL-1 family of cytokines and was initially described as an IFN-γ-inducing factor derived from anti-CD3-stimulated T-helper (Th)1 cells. IL-18 plays a significant role in the activation of hematopoietic cell types mediating both Th1 and Th2 responses and is the primary inducer of interferon-γ in these cells. The biological activity of IL-18 is mediated through

Diabetic retinopathy (DR) is a major cause of acquired blindness among working adults. The retinal pigment epithelium (RPE), constitutes an outer blood-retinal barrier, is vastly affected in diabetic humans and animals. Lower levels of lutein in the serum and retina of diabetic population, and beneficial effects of carotenoids supplementation in diabetic retinopathy patients created an interest to

BACKGROUND Wnt1-inducible signaling pathway protein 1, or cellular communication network factor 4 (CCN4), a member of CCN family of secreted, extracellular matrix associated signaling proteins, recently was validated as a novel adipose tissue derived cytokine. OBJECTIVE To assess the relationships between circulating CCN4, adipose tissue distribution and function, and chronic low-grade inflammation

The original version of this article unfortunately contained a mistake. In the Abstract section, a production query number (Q2) was inadvertently inserted within the new official gene names of the CCN proteins.

This commentary highlights the unique failures of environmental regulatory standards and related remedial actions to significantly reduce human cancer risks and the failure of cancer therapeutics to significantly impact cancer incidence and survival statistics despite vast resources allocated to both areas over the past half century. These dramatic institutional, scientific, medical, and regulatory

The extracellular matrix (ECM) is a deformable dynamic structure that dictates the behavior, function and integrity of blood vessels. The composition, density, chemistry and architecture of major globular and fibrillar proteins of the matrisome regulate the mechanical properties of the vasculature (i.e., stiffness/compliance). ECM proteins are linked via integrins to a protein adhesome directly connected

Shisha smoking has been epidemiologically linked to oral cancer. However, few studies have investigated the pathobiology of shisha-induced cellular transformation. We studied the effects of chronic shisha exposure (8 months) in an in vitro model using immortalized, non-neoplastic oral keratinocytes (OKF6/TERT1). Quantitative proteomic and phosphoproteomic analyses were performed on OKF6/TERT1 cells

Protease activated receptors (PARs) transactivate both epidermal growth factor receptors (EGFR) and transforming growth factor (TGF)-β receptors (TGFBR1) in vascular smooth muscle leading to the increased expression of genes (CHST11 and CHSY1) which are rate limiting for the enzymes that mediate hyperelongation of glycosaminoglycan (GAG) chains on the lipid-binding proteoglycan, biglycan. This is an

People with diabetes mellitus have shorter telomeres compared with non-diabetic subjects. The aim of this study was to investigate an in-vitro model of telomere shortening under diabetes metabolic conditions. The mechanisms of the accelerated telomere length attrition and the potential telomere protective action of fenofibrate with related cellular mechanisms were also examined. Human dermal fibroblasts

Exosomes were first described as waste carriers implicated in reticulocyte maturation but has during the past decade been associated with many other cellular functions. The biogenesis of exosomes has been extensively studied and several protein machineries have been identified to dictate their production and release. The newly discovered branches of the autophagy system implicate secretion of waste

Colorectal cancer (CRC) is one of the most common leading causes of cancer-related deaths in the world. Recent studies showed that microRNAs (miRNAs) play important roles in the development of diseases, such as CRC. However, the role of miR-873-5p in CRC remains unclear. In this study, we found that miR-873-5p expression was down-regulated in CRC tissues and cell lines, and the down-regulation of miR-873-5p

mTOR, the target of rapamycin, has been promoted as a potential target for cancers, transplantations and even lung fibrosis. However, paradoxically, targeting mTOR has been reported to result in profibrotic side effects. Some recent publications highlight why this might be.

Ionizing radiation (IR) is a standard-of-care treatment for glioma patients; however, the clinical efficacy is limited due to therapeutic resistance. A recent study published by Ma et al. (Cancer Cell 35:504-518, 2019) reported that the phosphorylation of phosphatase and tensin homolog (PTEN) at tyrosine 240 (pY240-PTEN) promotes the radioresistance of human glioma cells. After treatment with IR, the

This commentary briefly summarizes the extraordinary resurgence of hormesis within the biological, biomedical, toxicological and risk assessment domains over the past two decades. It places this resurgence within the context of challenging the scientific validity of the threshold and linear dose responses. It argues that conducting research on mechanisms that actuate and regulate the stimulatory response

The risk of renal cell carcinoma development is correlated with obesity and type II diabetes. Since insulin and insulin-like growth factors play a key role during development of both metabolic diseases, these molecules may be important in RCC pathophysiology We investigated the effect of insulin and IGFs on RCC cells using in vitro model with 786-O, 769-P, Caki-1, Caki-2, ACHN cancer cell lines. Cancer

Limited effectiveness of Raf and MEK inhibitors has impelled the interest to use the inhibitors of Extra-cellular Receptor Kinase (ERK) pathway in combination with Gemcitabine (GEM) in pancreatic cancer. However, off-target abundance of ERK receptors, challenging physico-chemical properties, and dose-limiting toxicity of the inhibitor has presented critical challenges towards fabricating this combination

Angiogenesis is a critical, fine-tuned, multi-staged biological process. Tip-stalk cell selection and shuffling are the building blocks of sprouting angiogenesis. Accumulated evidences show that tip-stalk cell selection and shuffling are regulated by a variety of physical, chemical and biological factors, especially the interaction among multiple genes, their products and environments. The classic

While the dose-response relationship of radiation-induced bystander effect (RIBE) is controversial at low and high linear energy transfer (LET), mechanisms and effectors of cell-to-cell communication stay unclear and highly dependent of cell type. In the present study, we investigated the capacity of chondrocytes in responding to bystander factors released by chondrosarcoma cells irradiated at different

The main goal of this study was to evaluate the inhibition of Pseudomonas aeruginosa virulence factors and Quorum Sensing during exposure to carvacrol. P. aeruginosa (ATCC 10154) was exposed to carvacrol determining changes in biofilm development, motility, acyl-homoserine lactones (AHL) synthesis and relative expression of lasI/lasR. Docking analysis was used to determinate interactions between carvacrol

Melanoma is the most aggressive, therapy-resistant skin cancer. The mammalian target of rapamycin (mTOR), the serine/threonine kinase which integrates both intracellular and extracellular signals, plays a crucial role in coordinating the balance between the growth and death of cells. The object of this study is a comparison of the influence of mTOR inhibitor everolimus in the concentration range between

In our previous study, the expression profile of tight junction (TJ) protein claudins (CLDNs) in human osteosarcoma (OS) cells was examined, and the data found the CLDN10 was high expressed in OS cells versus fetal osteoblast cells. Hence, we aim to determine the impacts and the molecular mechanisms of CLDN10 in the metastatic phenotype of OS. The exact expression profiles of CLDN10 and phosphorylated

TGF-β1 is a main inducer of epithelial to mesenchymal transition (EMT). However, many breast cancer cells are not sensitive to the EMT induction by TGF-β1 alone. So far, the mechanisms underlying the induction of TGF-β1-insensitive breast cancer cells remains unclear. Here we report that TNF-α can induce EMT and invasiveness of breast cancer cells which are insensitive to TGF-β1. Intriguingly, TGF-β1