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The extracellular matrix (ECM) scaffold, which surrounds and supports the cells in tissues, consists of fibrillar proteins, proteoglycans, glycosaminoglycans, signaling molecules, and enzymes involved in its remodeling. The stages of cancer progression, e.g., local invasion, intravasation, extravasation, distant invasion and immunosuppression, are obligatorily perpetrated through interactions of these tumor cells with the ECM. Cancer-related ECM changes can be exploited for the evaluation of disease progression, anticancer therapy development, and monitoring of therapy response. Thus, in breast cancer, hyaluronan-mediated wound repair mechanisms are hijacked to promote tumor development. Altered mechanical properties of the pancreatic cancer ECM are immunosuppressive and prevent the penetration of cytotoxic chemotherapy agents. The expression of the proteoglycan syndecan-4 is modulated by anticancer drugs, suggesting its potential druggabilty capacity. Another proteoglycan, lumican, is proposed as a cancer prognosis marker, chemoresistance regulator, and cancer therapy target. Due to their remodeling properties, the MMPs are vital mediators and important therapeutic targets. Treatment of breast cancer cells with sulfated hyaluronan has been shown to attenuate tumor cell growth, migration, and invasion. Extracellular vesicles (EVs), comprising exosomes, microvesicles, and apoptotic bodies, are released by all cells into the ECM and body fluids and can be utilized as diagnostic markers in malignant pleural mesothelioma. These exciting developments encourage tumor biology scientists for further creative research.

Research & information: general --- elastin --- ribosomal protein SA --- tongue carcinoma --- MMP-2 --- EGCG --- pancreatic ductal adenocarcinoma --- syndecans --- proteoglycans --- tumor progression --- angiogenesis --- syndecan-4 --- heparan sulfate --- cancer --- prognosis --- biomarker --- signal transduction --- proteoglycan --- metastasis --- extracellular matrix --- fibrosis --- immune cell modulation --- neutrophils --- neutrophil extracellular trap --- macrophages --- BCC --- MMP --- TIMP --- invasion --- lumican --- cancer cell growth --- motility --- hyaluronan --- RHAMM --- CD44 --- wound repair --- breast cancer --- malignant pleural mesothelioma --- pleural effusion --- extracellular vesicles --- biomarkers --- sulfated hyaluronan --- estrogen receptors --- epithelial-to-mesenchymal transition --- matrix metalloproteinases --- n/a

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The extracellular matrix (ECM) scaffold, which surrounds and supports the cells in tissues, consists of fibrillar proteins, proteoglycans, glycosaminoglycans, signaling molecules, and enzymes involved in its remodeling. The stages of cancer progression, e.g., local invasion, intravasation, extravasation, distant invasion and immunosuppression, are obligatorily perpetrated through interactions of these tumor cells with the ECM. Cancer-related ECM changes can be exploited for the evaluation of disease progression, anticancer therapy development, and monitoring of therapy response. Thus, in breast cancer, hyaluronan-mediated wound repair mechanisms are hijacked to promote tumor development. Altered mechanical properties of the pancreatic cancer ECM are immunosuppressive and prevent the penetration of cytotoxic chemotherapy agents. The expression of the proteoglycan syndecan-4 is modulated by anticancer drugs, suggesting its potential druggabilty capacity. Another proteoglycan, lumican, is proposed as a cancer prognosis marker, chemoresistance regulator, and cancer therapy target. Due to their remodeling properties, the MMPs are vital mediators and important therapeutic targets. Treatment of breast cancer cells with sulfated hyaluronan has been shown to attenuate tumor cell growth, migration, and invasion. Extracellular vesicles (EVs), comprising exosomes, microvesicles, and apoptotic bodies, are released by all cells into the ECM and body fluids and can be utilized as diagnostic markers in malignant pleural mesothelioma. These exciting developments encourage tumor biology scientists for further creative research.

elastin --- ribosomal protein SA --- tongue carcinoma --- MMP-2 --- EGCG --- pancreatic ductal adenocarcinoma --- syndecans --- proteoglycans --- tumor progression --- angiogenesis --- syndecan-4 --- heparan sulfate --- cancer --- prognosis --- biomarker --- signal transduction --- proteoglycan --- metastasis --- extracellular matrix --- fibrosis --- immune cell modulation --- neutrophils --- neutrophil extracellular trap --- macrophages --- BCC --- MMP --- TIMP --- invasion --- lumican --- cancer cell growth --- motility --- hyaluronan --- RHAMM --- CD44 --- wound repair --- breast cancer --- malignant pleural mesothelioma --- pleural effusion --- extracellular vesicles --- biomarkers --- sulfated hyaluronan --- estrogen receptors --- epithelial-to-mesenchymal transition --- matrix metalloproteinases --- n/a

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Immunohistochemistry (IHC) is an ancillary method, widely used in pathologists’ practice, that allows identifying diagnostic and prognostic/predictive of therapeutic response protein markers on tissue samples by the use of specific monoclonal antibodies and chromogenic substances that guarantee the visualization of an antibody–antigene binding complex under a light microscope [1]. Coon et al., in 1941 [2], first introduced the use of fluorochrome-conjugated antibodies in clinical practice. Since then, IHC has gone from being a useful tool for identifying the differentiation line of otherwise undifferentiated cells to a technique capable of providing not only diagnostic but also prognostic and predictive indications of responses to specific therapeutic options [1,3]. The abovementioned peculiarities have made IHC one of the most used ancillary methods in the histopathological approach to human neoplastic and non-neoplastic diseases [3-5]. This Special Issue contains 11 accepted papers that provide readers with a comprehensive update on current and future applications of IHC in medical practice.

Medicine --- training exercise --- NGAL --- VDR --- kidney --- heart --- immunohistochemistry --- ABCB5 --- uveal melanoma --- prognosis --- metastasis --- pericardium --- cytokeratin --- c-kit --- PDGFR --- initial lymphatics --- macroH2A --- prognostic factor --- SLC22A12 --- URAT1 --- hypouricemia --- uric acid transporters --- excretion fraction of uric acid --- Hsp27 --- Hsp60 --- Hsp70 --- Hsp90 --- molecular chaperone --- chaperonopathies --- thyroid --- follicular adenoma --- follicular carcinoma --- differential diagnosis --- carcinogenesis --- matrix metalloproteinases --- temporomandibular joint disorder --- temporomandibular joint --- DEN --- liver --- inflammation --- ultra-structural changes --- oxidative stress --- EGCG --- Vitamin D --- prostate cancer --- urinary tract malformations --- megacystis --- enteric nervous system --- outcome and prognosis --- WT1 --- human embryonal/fetal tissues --- neoplastic tissue --- n/a

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Many macro and micro species, from terrestrial and aquatic environments, produce structurally unique compounds and, in many countries, still are the primary sources of medicines. In fact, secondary metabolites are an important source of chemotherapeutic agents but are also lead compounds for synthetic modification and the optimization of biological activity. Therefore, the exploitation of secondary metabolites, or their inspired synthetic compounds, offers excellent opportunities for the pharmaceutical industry. This Medicines Special Issue focuses on the great potential of secondary metabolites for therapeutic application. The Special Issue contains 16 articles reporting relevant experimental results, and an overview of bioactive secondary metabolites, their biological effects, and new methodologies that improve and accelerate the process of obtained lead compounds with regard to new drug development. We would like to thank all 83 authors, from all over the world, for their valuable contributions to this Special Issue.

antitumor --- triterpenoids --- seaweeds --- diterpenes --- Boswellia --- antioxidant activity --- antiplasmodial --- Maytenus chiapensis --- phenolic derivatives --- secondary metabolites --- medicinal applications --- Malus x domestica --- pectin --- cytotoxic activity --- xanthine oxidase --- phytochemistry --- antioxidant --- Scabiosa --- sugars --- sargaquinoic acid --- pentacyclic triterpenoids --- analysis --- antimicrobial and anticancer activity --- iridoids --- Tuscany --- GC-MS --- (-)-rabdosiin --- kratom --- plant defense --- cembranoids --- tingenone --- deoxypodophyllotoxin --- anticancer --- pristimerin --- inflammation --- boswellic acids --- plants --- anti-inflammatory --- legalization --- Mitragyna speciosa --- Ocimum sanctum --- cordycepin --- cytotoxic --- medicine --- Artemisia species --- antimicrobial activity --- lignans --- Artemisia vachanica --- Cordyceps militaris --- frankincense --- ancient varieties --- sargahydroquinoic acid --- Tajikistan --- antiSMASH --- ABTS --- polyphenols --- therapeutics --- infectious diseases --- antibacterial --- nutraceutics --- total phenolics --- LC-MS/MS --- innate immunity --- HPLC-PAD --- sarganaphthoquinoic acid --- biosynthetic gene clusters --- DPPH --- EGCG --- cneorubenoids --- PPAR-? --- bowel diseases --- amentoflavone --- molecular docking --- sargachromenoic acid --- cannabinoids --- flavonoids --- essential oils --- TCM --- HPLC-PDA --- ascorbic acid --- antioxidants --- Lamiaceae --- nanoemulsion --- malaria --- therapeutic uses --- quinonemethide triterpenoids --- artemisinin --- natural products --- biological activities --- FRAP --- toxicology --- defensins --- Celastraceae --- cannabis --- vector control --- Juniperus --- analytical determination

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Phytotherapy is probably the oldest form of medicine; however, it represents a new therapeutic tool for healthcare workers. Indeed plants are an infinite source of novel molecules, with countless possible combinations. This collection of articles (a Special Issue from Molecules) brings together the most up-to-date studies on the use of plant-derived compounds, ranging from their anti-inflammatory, antioxidant, and anticancer effects to the revision of the prominent literature.

Medicine --- natural products --- phenylpropanoids --- phenolic acids --- plants --- depression --- behavioral disorders --- forced swim test --- tail suspension test --- anti-cancer activities --- multifloroside --- 10-oxyderivatives of oleoside secoiridoids --- structure-activity relationship --- flow cytometry --- epigallocatechin-3-gallate --- EGCG --- catechin --- green tea --- cancer preventive --- pharmacological activities --- Amelanchier alnifolia Nutt. --- carriers --- powders --- bioactive compounds --- functional food --- Ageratina havanensis --- flavonoids --- UPLC-ESI-MS/MS --- P-glycoprotein --- antioxidant potential --- nootkatone --- anti-inflammatory --- acute inflammation --- granuloma --- Pharbitis nil --- colorectal cancer --- KRAS --- muscle function --- juglone --- NLRP3 inflammasome --- caspase-1 --- IL-1β --- IL-18 --- plant secondary metabolites --- natural compounds --- biological activity --- phytochemistry --- pharmacological activity --- plant side effects --- Talisia esculenta --- Brosimum gaudichaudii --- Genipa americana --- Bromelia antiacantha --- RA-3 --- nephrotoxicity --- triterpene --- antioxidant --- hyperuricemia --- Hibiscus acetosella --- phenolic compound --- antibacterial --- UPLC --- Tabebuia impetiginosa --- Taheebo --- traditional uses --- immunopharmacology --- immunological disorders --- hesperidin --- new-clean process extraction --- nanocrystals --- anti-ageing --- zingerone --- lipopolysaccharide --- inflammation --- anti-oxidant --- cytokine storm --- procalcitonin --- histopathology --- doxorubicin --- Mahonia aquifolium --- matrix metalloproteinases --- cytotoxicity --- human lung adenocarcinoma --- n/a