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Coronaviruses (CoVs), enveloped positive-sense RNA viruses, are a group of viruses that cause infections in the human respiratory tract, which can be characterized clinically from mild to fatal. The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the virus responsible. The global spread of COVID-19 can be described as the worst pandemic in humanity in the last century. To date, COVID-19 has infected more than 3,000,000 people worldwide and killed more than 200,000 people. All age groups can be infected from the virus, but more serious symptoms that can possibly result in death are observed in older people and those with underlying medical conditions such as cardiovascular and pulmonary disease. Novel data report more severe symptoms and even a negative prognosis for the obese patients. A growing body of evidence connects obesity with COVID-19 and a number of mechanisms from immune system activity attenuation to chronic inflammation are implicated. Lipid peroxidation creates reactive lipid aldehydes which in a patient with metabolic disorder and COVID-19 will affect its prognosis. Finally, pregnancy-associated obesity needs to be studied further in connection to COVID-19 as this infection could pose high risk both to pregnant women and the fetus.

The present study focused on the elucidation of the putative anticancer potential of quercetin. The anticancer activity of quercetin at 10, 20, 40, 80 and 120 µM was assessed in vitro by MMT assay in 9 tumor cell lines (colon carcinoma CT-26 cells, prostate adenocarcinoma LNCaP cells, human prostate PC3 cells, pheocromocytoma PC12 cells, estrogen receptor-positive breast cancer MCF-7 cells, acute lymphoblastic leukemia MOLT-4 T-cells, human myeloma U266B1 cells, human lymphoid Raji cells and ovarian cancer CHO cells). Quercetin was found to induce the apoptosis of all the tested cancer cell lines at the utilized concentrations. Moreover, quercetin significantly induced the apoptosis of the CT-26, LNCaP, MOLT-4 and Raji cell lines, as compared to control group (P<0.001), as demonstrated by Annexin V/PI staining. In in vivo experiments, mice bearing MCF-7 and CT-26 tumors exhibited a significant reduction in tumor volume in the quercetin-treated group as compared to the control group (P<0.001). Taken together, quercetin, a naturally occurring compound, exhibits anticancer properties both in vivo and in vitro.

Hyaluronan (HA) is a naturally occurring non-sulfated glycosaminoglycan (GAG) localized to the cell surface and the tissue extracellular matrix (ECM). It is composed of disaccharides containing glucuronic acid and N-acetylglucosamine, is synthesized by the HA synthase (HAS) enzymes and is degraded by hyaluronidase (HYAL) or reactive oxygen and nitrogen species (ROS/RNS) actions. HA is deposited as a high molecular weight (HMW) polymer and degraded to low molecular weight (LMW) fragments and oligosaccharides. HA affects biological functions by interacting with HA-binding proteins (hyaladherins). HMW HA is anti-inflammatory, immunosuppressive, and antiangiogenic, whereas LMW HA has pro-inflammatory, pro-angiogenetic, and oncogenic effects. ROS/RNS naturally degrade HMW HA, albeit at enhanced levels during tissue injury and inflammatory processes. Thus, the degradation of endothelial glycocalyx HA by increased ROS challenges vascular integrity and can initiate several disease progressions. Conversely, HA exerts a vital role in wound healing through ROS-mediated HA modifications, which affect the innate immune system. The normal turnover of HA protects against matrix rigidification. Insufficient turnover leads to increased tissue rigidity, leading to tissue dysfunction. Both endogenous and exogenous HMW HA have a scavenging capacity against ROS. The interactions of ROS/RNS with HA are more complex than presently perceived and present an important research topic.

Glycosaminoglycans (GAGs) and proteoglycans (PGs) are essential components of the extracellular matrix (ECM) with pivotal roles in cellular mechanosensing pathways. GAGs, such as heparan sulfate (HS) and chondroitin sulfate (CS), interact with various cell surface receptors, including integrins and receptor tyrosine kinases, to modulate cellular responses to mechanical stimuli. PGs, comprising a core protein with covalently attached GAG chains, serve as dynamic regulators of tissue mechanics and cell behavior, thereby playing a crucial role in maintaining tissue homeostasis. Dysregulation of GAG/PG-mediated mechanosensing pathways is implicated in numerous pathological conditions, including cancer and inflammation. Understanding the intricate mechanisms by which GAGs and PGs modulate cellular responses to mechanical forces holds promise for developing novel therapeutic strategies targeting mechanotransduction pathways in disease. This comprehensive overview underscores the importance of GAGs and PGs as key mediators of mechanosensing in maintaining tissue homeostasis and their potential as therapeutic targets for mitigating mechano-driven pathologies, focusing on cancer and inflammation.

Disparity during the resolution of inflammation is closely related with the initiation and progression of the tumorigenesis. The transformed cells, through continuously evolving interactions, participate in various exchanges with the surrounding microenvironment consisting of extracellular matrix (ECM) components, cytokines embedded in the ECM, as well as the stromal cells. Proteoglycans (PGs), complex molecules consisting of a protein core into which one or more glycosaminoglycan (GAG) chains are covalently tethered, are important regulators of the cell/matrix interface and, consecutively, biological functions. The discrete expression of PGs and their interacting partners has been distinguished as specific for disease development in diverse cancer types. In this mini-review, we will critically discuss the roles of PGs in the complex processes of cancer-associated modulation of the immune response and analyze their mechanisms of action. A deeper understanding of mechanisms which are capable of regulating the immune response could be harnessed to treat malignant disease.

Extracellular matrix (ECM) is an extraordinarily complex and unique meshwork composed of structural proteins and glycosaminoglycans. The ECM provides essential physical scaffolding for the cellular constituents, as well as contributes to crucial biochemical signaling. Importantly, ECM is an indispensable part of all biological barriers and substantially modulates the interchange of the nanotechnology products through these barriers. The interactions of the ECM with nanoparticles (NPs) depend on the morphological characteristics of intercellular matrix and on the physical characteristics of the NPs and may be either deleterious or beneficial. Importantly, an altered expression of ECM molecules ultimately affects all biological processes including inflammation. This review critically discusses the specific behavior of NPs that are within the ECM domain, and passing through the biological barriers. Furthermore, regenerative and toxicological aspects of nanomaterials are debated in terms of the immune cells-NPs interactions.

Uterine stromal-derived tumors encompass a spectrum of rare neoplasms, ranging from benign endometrial stromal nodules to aggressive high-grade endometrial stromal sarcomas and undifferentiated uterine sarcomas. The classification of these tumors has advanced through molecular and immunohistochemical profiling, but the role of the extracellular matrix (ECM) in their biology is only beginning to be understood. The ECM provides both structural support and dynamic signaling cues, regulating tumor cell proliferation, invasion, angiogenesis, and immune evasion. Altered expression of collagens, proteoglycans, glycosaminoglycans, and matricellular proteins reshapes stromal architecture and contributes to disease progression. Moreover, ECM remodeling enzymes such as matrix metalloproteinases, together with cross-linking factors, create a stiff and pro-tumorigenic microenvironment that facilitates invasion and therapeutic resistance. Furthermore, these matrix alterations intersect with angiogenesis, mechanotransduction pathways, and immune modulation. Studies to date describe the role of ECM molecules in the function of the physiological uterine tissue and data for the uterine stroma-derived tumors is scarce. This review summarizes the existing knowledge in classification, prognosis and diagnosis, and summarizes the ECM-driven mechanisms in tumors described so far, aiming to identify new and prognostic biomarkers and novel therapeutic targets in uterine sarcomas.

Through their interaction with proteins, GAGs can affect the cell-extracellular matrix (ECM) and cell–cell interactions, finely modulating ligand-receptor binding and thus chemokine and cytokine activities as well as growth factor sequestration. [...]GAGs regulate several biological processes under homeostasis; they also participate in disease progression. Recently, significant advances have been made in the analytic, sequencing, and structural characterization of GAG oligosaccharides as well as in GAG profiling in tissues and cells (GAGomics). [...]studies focused on the structure/sequence-function relationships of GAGs have resulted in critical novel insights. [...]characterized quaternary structures of the complexes improve our understanding as to if and how GAGs participate in long-range, multivalent binding with potential synergy when several chains are involved in interactions. [...]the authors confirm the critical role of ECM components such as GAGs in disease progression.

The consecutive steps of tumor growth, local invasion, intravasation, extravasation, invasion of anatomically distant sites, and immunosuppression are obligatorily perpetrated through specific interactions of the tumor cells with their microenvironment [...]

Nanoparticles are increasingly utilized as drug delivery agents. Previously, we have developed a drug delivery system based on amphiphilic derivatives of poly-N-vinylpyrrolidone (PVP-OD4000) with excellent biocompatibility. In the current study, we assessed the pharmacokinetics, anti-inflammatory profile, and ulcerogenic potential of indomethacin (IMC)-loaded PVP-OD4000 nanoparticles compared to the free drug. Wistar male rats were utilized for a pharmacokinetics study and an anti-inflammatory study. Loaded IMC exhibited a slower elimination rate (p < 0.05) and a higher blood plasma concentration at 8 and 24 h after intraperitoneal injection compared with free IMC. In addition, decreased uptake of loaded IMC in the liver and kidney compared to free IMC (p < 0.05) was detected. Furthermore, PVP-OD4000 nanoparticles loaded with IMC showed an enhanced anti-inflammatory effect compared to free IMC (p < 0.05) in carrageenan-induced and complete Freund’s adjuvant-induced–(CFA) sub-chronic and chronic paw edema treatment (p < 0.01; p < 0.01). Notably, upon oral administration of loaded IMC, animals had a significantly lower ulcer score and Paul’s Index (3.9) compared to the free drug (p < 0.05). The obtained results suggest that IMC loaded to PVP nanoparticles exhibit superior anti-inflammatory activity in vivo and a safe gastrointestinal profile and pose a therapeutic alternative for the currently available NSAIDs’ administration.