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Coriolus versicolor (CV) is a common species from the Polyporaceae family that has been used in traditional Chinese herbal medicine for over 2000 years. Among well-described and most active compounds identified in CV are polysaccharopeptides, such as polysaccharide peptide (PSP) and Polysaccharide-K (PSK, krestin), which, in some countries, are already used as an adjuvant agent in cancer therapy. In this paper, research advances in the field of anti-cancer and anti-viral action of CV are analyzed. The results of data obtained in in vitro and in vivo studies using animal models as well as in clinical research trials have been discussed. The present update provides a brief overview regarding the immunomodulatory effects of CV. A particular focus has been given to the mechanisms of direct effects of CV on cancer cells and angiogenesis. A potential use of CV compounds in anti-viral treatment, including therapy against COVID-19 disease, has also been analyzed based on the most recent literature. Additionally, the significance of fever in viral infection and cancer has been debated, providing evidence that CV affects this phenomenon. [ABSTRACT FROM AUTHOR]

The human body's natural protective barrier, the skin, is exposed daily to minor or major mechanical trauma, which can compromise its integrity. Therefore, the search for new dressing materials that can offer new functionalisation is fully justified. In this work, the development of two new types of dressings based on poly(3-hydroxyoctanoate) (P(3HO)) is presented. One of the groups was supplemented with conjugates of an anti-inflammatory substance (diclofenac) that was covalently linked to oligomers of hydroxycarboxylic acids (Oli-dicP(3HO)). The novel dressings were prepared using the solvent casting/particulate leaching technique. To our knowledge, this is the first paper in which P(3HO)-based dressings were used in mice wound treatment. The results of our research confirm that dressings based on P(3HO) are safe, do not induce an inflammatory response, reduce the expression of pro-inflammatory cytokines, provide adequate wound moisture, support angiogenesis, and, thanks to their hydrophobic characteristics, provide an ideal protective barrier. Newly designed dressings containing Oli-dicP(3HO) can promote tissue regeneration by partially reducing the inflammation at the injury site. To conclude, the presented materials might be potential candidates as excellent dressings for wound treatment. [ABSTRACT FROM AUTHOR]

Previous omics research in patients with complex congenital heart disease and single-ventricle circulation (irrespective of the stage of palliative repair) revealed alterations in cardiac and systemic metabolism, inter alia abnormalities in energy metabolism, and inflammation, oxidative stress or endothelial dysfunction. We employed an affinity-proteomics approach focused on cell surface markers, cytokines, and chemokines in the serum of 20 adult Fontan patients with a good functioning systemic left ventricle, and we 20 matched controls to reveal any specific processes on a cellular level. Analysis of 349 proteins revealed 4 altered protein levels related to chronic inflammation, with elevated levels of syndecan-1 and glycophorin-A, as well as decreased levels of leukemia inhibitory factor and nerve growth factor-ß in Fontan patients compared to controls. All in all, this means that Fontan circulation carries specific physiological and metabolic instabilities, including chronic inflammation, oxidative stress imbalance, and consequently, possible damage to cell structure and alterations in translational pathways. A combination of proteomics-based biomarkers and the traditional biomarkers (uric acid, γGT, and cholesterol) performed best in classification (patient vs. control). A metabolism- and signaling-based approach may be helpful for a better understanding of Fontan (patho-)physiology. Syndecan-1, glycophorin-A, leukemia inhibitory factor, and nerve growth factor-ß, especially in combination with uric acid, γGT, and cholesterol, might be interesting candidate parameters to complement traditional diagnostic imaging tools and the determination of traditional biomarkers, yielding a better understanding of the development of comorbidities in Fontan patients, and they may play a future role in the identification of targets to mitigate inflammation and comorbidities in Fontan patients. [ABSTRACT FROM AUTHOR]

The chemotactic cytokine fractalkine (FKN, chemokine CX3CL1) has unique properties resulting from the combination of chemoattractants and adhesion molecules. The soluble form (sFKN) has chemotactic properties and strongly attracts T cells and monocytes. The membrane-bound form (mFKN) facilitates diapedesis and is responsible for cell-to-cell adhesion, especially by promoting the strong adhesion of leukocytes (monocytes) to activated endothelial cells with the subsequent formation of an extracellular matrix and angiogenesis. FKN signaling occurs via CX3CR1, which is the only known member of the CX3C chemokine receptor subfamily. Signaling within the FKN-CX3CR1 axis plays an important role in many processes related to inflammation and the immune response, which often occur simultaneously and overlap. FKN is strongly upregulated by hypoxia and/or inflammation-induced inflammatory cytokine release, and it may act locally as a key angiogenic factor in the highly hypoxic tumor microenvironment. The importance of the FKN/CX3CR1 signaling pathway in tumorigenesis and cancer metastasis results from its influence on cell adhesion, apoptosis, and cell migration. This review presents the role of the FKN signaling pathway in the context of angiogenesis in inflammation and cancer. The mechanisms determining the pro- or anti-tumor effects are presented, which are the cause of the seemingly contradictory results that create confusion regarding the therapeutic goals. [ABSTRACT FROM AUTHOR]

Increasing evidence has been published over recent years on the implication of endocrine-disrupting chemicals (EDCs), including parabens and benzophenones in the pathogenesis and pathophysiology of endometriosis. However, to the best of our knowledge, no study has been published on the ways in which exposure to EDCs might affect cell-signaling pathways related to endometriosis. We aimed to describe the endometriotic tissue expression profile of a panel of 23 genes related to crucial cell-signaling pathways for the development and progression of endometriosis (cell adhesion, invasion/migration, inflammation, angiogenesis, and cell proliferation/hormone stimulation) and explore its relationship with the exposure of patients to parabens (PBs) and benzophenones (BPs). This cross-sectional study included a subsample of 33 women with endometriosis from the EndEA study, measuring their endometriotic tissue expressions of 23 genes, while urinary concentrations of methyl-, ethyl-, propyl-, butyl-paraben, benzophenone-1, benzophenone-3, and 4-hydroxybenzophenone were determined in 22 women. Spearman's correlations test and linear and logistic regression analyses were performed. The expression of 52.2% of studied genes was observed in >75% of endometriotic tissue samples and the expression of 17.4% (n = 4) of them in 50–75%. Exposure to certain PB and BP congeners was positively associated with the expression of key genes for the development and proliferation of endometriosis. Genes related to the development and progression of endometriosis were expressed in most endometriotic tissue samples studied, suggesting that exposure of women to PBs and BPs may be associated with the altered expression profile of genes related to cellular pathways involved in the development of endometriosis. [ABSTRACT FROM AUTHOR]

Although diagnosis and treatment of vestibular schwannomas (VSs) improved in recent years, no factors have yet been identified as being capable of predicting tumor growth. Molecular rearrangements occur in neoplasms before any macroscopic morphological changes become visible, and the former are the underlying cause of disease behavior. Tumor microenvironment (TME) encompasses cellular and non-cellular elements interacting together, resulting in a complex and dynamic key of tumorigenesis, drug response, and treatment outcome. The aim of this systematic, narrative review was to assess the level of knowledge on TME implicated in the biology, behavior, and prognosis of sporadic VSs. A search (updated to November 2022) was run in Scopus, PubMed, and Web of Science electronic databases according to the PRISMA guidelines, retrieving 624 titles. After full-text evaluation and application of inclusion/exclusion criteria, 37 articles were included. VS microenvironment is determined by the interplay of a dynamic ecosystem of stromal and immune cells which produce and remodel extracellular matrix, vascular networks, and promote tumor growth. However, evidence is still conflicting. Further studies will enhance our understanding of VS biology by investigating TME-related biomarkers able to predict tumor growth and recognize immunological and molecular factors that could be potential therapeutic targets for medical treatment. [ABSTRACT FROM AUTHOR]

Colorectal (CRC) and gastric cancers (GC) are the most common digestive tract cancers with a high incidence rate worldwide. The current treatment including surgery, chemotherapy or radiotherapy has several limitations such as drug toxicity, cancer recurrence or drug resistance and thus it is a great challenge to discover an effective and safe therapy for CRC and GC. In the last decade, numerous phytochemicals and their synthetic analogs have attracted attention due to their anticancer effect and low organ toxicity. Chalcones, plant-derived polyphenols, received marked attention due to their biological activities as well as for relatively easy structural manipulation and synthesis of new chalcone derivatives. In this study, we discuss the mechanisms by which chalcones in both in vitro and in vivo conditions suppress cancer cell proliferation or cancer formation. [ABSTRACT FROM AUTHOR]

The ATP-binding cassette superfamily member ABCB5 identifies a subset of skin-resident mesenchymal stem cells (MSCs) that exhibit potent immunomodulatory and wound healing-promoting capacities along with superior homing ability. The ABCB5+ MSCs can be easily accessed from discarded skin samples, expanded, and delivered as a highly homogenous medicinal product with standardized potency. A range of preclinical studies has suggested therapeutic efficacy of ABCB5+ MSCs in a variety of currently uncurable skin and non-skin inflammatory diseases, which has been substantiated thus far by distinct clinical trials in chronic skin wounds or recessive dystrophic epidermolysis bullosa. Therefore, skin-derived ABCB5+ MSCs have the potential to provide a breakthrough at the forefront of MSC-based therapies striving to fulfill current unmet medical needs. The most recent milestones in this regard are the approval of a phase III pivotal trial of ABCB5+ MSCs for treatment of recessive dystrophic and junctional epidermolysis bullosa by the US Food and Drug Administration, and national market access of ABCB5+ MSCs (AMESANAR®) for therapy-refractory chronic venous ulcers under the national hospital exemption pathway in Germany. [ABSTRACT FROM AUTHOR]

Sjögren's syndrome (SS) is a systemic autoimmune rheumatic disorder characterized by the lymphocytic infiltration of exocrine glands and the production of autoantibodies to self-antigens. The involvement of the exocrine glands drives the pathognomonic manifestations of dry eyes (keratoconjunctivitis sicca) and dry mouth (xerostomia) that define sicca syndrome. To date, the molecular mechanisms mediating pathological salivary gland dysfunction in SS remain to be elucidated, despite extensive studies investigating the underlying cause of this disease, hampering the development of novel therapeutic strategies. Many researchers have identified a multifactorial pathogenesis of SS, including environmental, genetic, neuroendocrine, and immune factors. In this review, we explore the latest developments in understanding the molecular mechanisms involved in the pathogenesis of SS, which have attracted increasing interest in recent years. [ABSTRACT FROM AUTHOR]

Coriolus versicolor (CV) is a common species from the Polyporaceae family that has been used in traditional Chinese herbal medicine for over 2000 years. Among well-described and most active compounds identified in CV are polysaccharopeptides, such as polysaccharide peptide (PSP) and Polysaccharide-K (PSK, krestin), which, in some countries, are already used as an adjuvant agent in cancer therapy. In this paper, research advances in the field of anti-cancer and anti-viral action of CV are analyzed. The results of data obtained in in vitro and in vivo studies using animal models as well as in clinical research trials have been discussed. The present update provides a brief overview regarding the immunomodulatory effects of CV. A particular focus has been given to the mechanisms of direct effects of CV on cancer cells and angiogenesis. A potential use of CV compounds in anti-viral treatment, including therapy against COVID-19 disease, has also been analyzed based on the most recent literature. Additionally, the significance of fever in viral infection and cancer has been debated, providing evidence that CV affects this phenomenon.

The vascular endothelial growth factor (VEGF) family, the crucial regulator of angiogenesis, lymphangiogenesis, lipid metabolism and inflammation, is involved in the development of atherosclerosis and further CVDs (cardiovascular diseases). This review discusses the general regulation and functions of VEGFs, their role in lipid metabolism and atherosclerosis development and progression. These functions present the great potential of applying the VEGF family as a target in the treatment of atherosclerosis and related CVDs. In addition, we discuss several modern anti-atherosclerosis VEGFs-targeted experimental procedures, drugs and natural compounds, which could significantly improve the efficiency of atherosclerosis and related CVDs' treatment. [ABSTRACT FROM AUTHOR]

Moyamoya arteriopathy (MA) is a rare cerebrovascular disorder characterized by ischemic/hemorrhagic strokes. The pathophysiology is unknown. A deregulation of vasculogenic/angiogenic/inflammatory pathways has been hypothesized as a possible pathophysiological mechanism. Since lipids are implicated in modulating neo-vascularization/angiogenesis and inflammation, their deregulation is potentially involved in MA. Our aim is to evaluate angiogenic/vasculogenic/inflammatory proteins and lipid profile in plasma of MA patients and control subjects (healthy donors HD or subjects with atherosclerotic cerebrovascular disease ACVD). Angiogenic and inflammatory protein levels were measured by ELISA and a complete lipidomic analysis was performed on plasma by mass spectrometry. ELISA showed a significant decrease for MMP-9 released in plasma of MA. The untargeted lipidomic analysis showed a cumulative depletion of lipid asset in plasma of MA as compared to HD. Specifically, a decrease in membrane complex glycosphingolipids peripherally circulating in MA plasma with respect to HD was observed, likely suggestive of cerebral cellular recruitment. The quantitative targeted approach demonstrated an increase in free sphingoid bases, likely associated with a deregulated angiogenesis. Our findings indicate that lipid signature could play a central role in MA and that a detailed biomarker profile may contribute to untangle the complex, and still obscure, pathogenesis of MA. [ABSTRACT FROM AUTHOR]

Gestational Diabetes Mellitus (GDM) is a transitory metabolic condition caused by dysregulation triggered by intolerance to carbohydrates, dysfunction of beta-pancreatic and endothelial cells, and insulin resistance during pregnancy. However, this disease includes not only changes related to metabolic distress but also placental immunoendocrine adaptations, resulting in harmful effects to the mother and fetus. In this review, we focus on the placenta as an immuno-endocrine organ that can recognize and respond to the hyperglycemic environment. It synthesizes diverse chemicals that play a role in inflammation, innate defense, endocrine response, oxidative stress, and angiogenesis, all associated with different perinatal outcomes. [ABSTRACT FROM AUTHOR]

Cylindromatosis (CYLD) is a deubiquitinase (DUB) enzyme that was initially characterized as a tumor suppressor of adnexal skin tumors in patients with CYLD syndrome. Later, it was also shown that the expression of functionally inactive mutated forms of CYLD promoted tumor development and progression of non-melanoma skin cancer (NMSC). However, the ability of wild-type CYLD to inhibit skin tumorigenesis in vivo in immunocompetent mice has not been proved. Herein, we generated transgenic mice that express the wild type form of CYLD under the control of the keratin 5 (K5) promoter (K5-CYLDwt mice) and analyzed the skin properties of these transgenic mice by WB and immunohistochemistry, studied the survival and proliferating characteristics of primary keratinocytes, and performed chemical skin carcinogenesis experiments. As a result, we found a reduced activation of the nuclear factor kappa B (NF-κB) pathway in the skin of K5-CYLDwt mice in response to tumor necrosis factor-α (TNF-α); accordingly, when subjected to insults, K5-CYLDwt keratinocytes are prone to apoptosis and are protected from excessive hyperproliferation. Skin carcinogenesis assays showed inhibition of tumor development in K5-CYLDwt mice. As a mechanism of this tumor suppressor activity, we found that a moderate increase in CYLD expression levels reduced NF-κB activation, which favored the differentiation of tumor epidermal cells and inhibited its proliferation; moreover, it decreased tumor angiogenesis and inflammation. Altogether, our results suggest that increased levels of CYLD may be useful for anti-skin cancer therapy. [ABSTRACT FROM AUTHOR]