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Matrix metalloproteinases (MMPs) are members of an enzyme family and are critical for maintaining tissue allostasis. MMPs can catalyze normal turnover of the extracellular matrix (ECM) together with other metalloproteinases such as ADAM (a disintegrin and metalloproteinase) and ADAMTS (a disintegrin and metalloproteinase with thrombospondin motif) families. MMP activity is also regulated by a group of endogenous proteins called tissue inhibitor of metalloproteinases (TIMPs). All these proteins have a pivotal role involving ECM remodelling in normal physiological processes such as wound healing, embryogenesis, angiogenesis, bone remodelling, immunity, and the female reproductive cycle. An imbalance in the expression or activity of MMPs can also have important consequences in diseases such as cancer, cardiovascular disease, peripheral vascular disease, chronic leg ulcers, and multiple sclerosis. In recent years, MMPs have been found to play an important role in the field of precision medicine, as they may serve as biomarkers that may predict an individual’s disease predisposition, state, or progression. MMPs are also thought to be a sensible target for molecular therapy. The aim of this Special Issue is to explore the most recent findings in this field that may have an impact in healthcare systems.

hypersensitivity pneumonitis --- metalloproteinases --- genetic association --- autoantibodies --- MMP1 --- MMP2 --- SNPs --- MMPs --- TIMPs --- CKD --- peripheral vascular disease --- biomarkers --- proteinuria --- eGFR --- PAD. --- NGAL --- statins --- arterial aneurysms --- patients --- collagenases --- Crohn’s disease --- dental caries --- mouth --- periodontitis --- matrix metalloproteinase-9 --- dialysis --- on-line hemodiafiltration --- high-flux dialysis --- renal replacement therapy --- kidney transplantation --- Mac-1 --- CD147 --- leukocytes --- platelets --- adhesion --- integrin αMβ2 --- matrix metalloproteinases --- TIMP --- synthetic inhibitors --- RECK --- matrix metalloproteinase --- MAPKs --- ischemia/reperfusion --- eNOS --- iNOS --- inflammatory bowel disease --- inflammation --- NO --- MMP-9 --- cGMP --- Caco-2 --- matrix metalloproteinase-7 --- fibrosis --- acute kidney injury --- chronic kidney disease --- apoptosis --- health --- disease

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In the two last decades, proteases have constituted one of the primary and important targets in drug discovery. The U.S. FDA has approved more than 12 protease therapies in the last 10 years, and a number of next-generation or completely new proteases are under clinical development. Protease inhibition strategies are one of the fastest expanding areas in the field of of drugs that show considerable promise. This Special Issue will focus on the recent advances in the discovery and development of protease inhibitors, covering the synthesis of protease inhibitors, the design of new chemical entities acting as inhibitors of special/particular types of proteases, and their mode of actions (Frolova et al. 2020; Slapak et al. 2020; Künnapuu et al. 2021). In addition, the new applications of these interesting compounds/biomolecules and their limitations have been discussed and described (Wang et al. 2020; Bartošová-Sojková et al. 2021).

MMP --- MMP2 --- MMP9 --- MMP7 --- MMP14 --- matrix metalloproteases --- PDAC --- pancreatic cancer --- Bowman–Birk inhibitor --- ranacyclin --- trypsin inhibitor --- structure–activity relationship --- synergistic effect --- Gentamicin --- matrix metalloproteinase --- extracellular matrix --- nuclei --- cancer --- apoptosis --- immune response --- cysteine protease inhibitor --- stefin --- signal peptide --- parasite --- phylogenetic analysis --- diversification --- protein structure --- vascular endothelial growth factors (VEGFs) --- VEGF-A --- PlGF --- VEGF-B --- VEGF-C --- VEGF-D --- angiogenesis --- lymphangiogenesis --- CCBE1 --- proteases --- ADAMTS3 --- plasmin --- cathepsin D --- KLK3 --- prostate-specific antigen (PSA) --- thrombin --- wound healing --- metastasis --- proteolytic activation --- vascular biology --- lymphedema

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The chemistry of nickel in biological systems has been intensely investigated since the discovery of the essential role played by this transition metal in the enzyme urease, ca. 1975. Since then, several nickel-dependent enzymes have been discovered and characterized at the molecular level using structural, spectroscopic, and kinetic methods, and insight into reaction mechanisms has been elaborated using synthetic and computational models. The dual role of nickel as both an essential nutrient and as a toxin has prompted efforts to understand the molecular mechanisms of nickel toxicology and to uncover the means by which cells select nickel from among a pool of different and more readily available metal ions and thus regulate the intracellular chemistry of nickel. This latter effort highlights the importance of proteins involved in the extra- and intra-cellular sensing of nickel, the roles of nickel-selective proteins for import and export, and nickel-responsive transcription factors, all of which are important for regulating nickel homeostasis. In this Special Issue, the contributing authors have covered recent advances in many of these aspects of nickel biochemistry, including toxicology, bacterial pathogenesis, carcinogenesis, computational and synthetic models, nickel trafficking proteins, and enzymology.

InrS --- nickel-dependent transcriptional regulators --- molecular modelling --- nickel --- hydrogenase --- urease --- Ni-enzymes --- pathogens --- ncRNA --- miRNA --- lncRNA --- lung carcinogenesis --- histidine-rich protein --- carbon monoxide dehydrogenase --- nickel chaperone --- nickel-induced oligomerization --- urease maturation --- metallochaperone --- G-protein --- conformational change --- bioavailability --- carcinogenicity --- genotoxicity --- allergy --- reproductive --- asthma --- nanoparticles --- ecotoxicity --- environment --- biological nickel sites --- nickel-thiolates --- dinuclear nickel metallopeptides --- thiolate oxidative damage --- nickel enzymes --- reaction mechanism --- quantum chemical calculations --- glyoxalase --- streptomyces --- mycothiol --- metalloenzyme --- AD11 --- nickel-dependent enzyme --- methionine salvage pathway --- methionine --- S-adenosylmethionine (SAM) --- methylthioadenosine (MTA) --- enolase phosphatase 1 (ENOPH1) --- polyamine --- matrix metalloproteinase MT1 (MT1-MMP) --- metalloregulator --- chaperone --- [NiFe]-hydrogenase --- n/a

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The aim of this Special Issue is to collect reports regarding all the recent strategies, directed at the improvement of antineoplastic activity of drugs in cancer progression, engaging all the expertise needed for the development of new anticancer drugs: medicinal chemistry, pharmacology, molecular biology, and computational and drug delivery studies.

Research & information: general --- Biology, life sciences --- EGR-1 --- flavonoid --- (E)-5-((4-oxo-4H-chromen-3-yl)methyleneamino)-1-phenyl-1H-pyrazole-4-carbonitrile --- MDA-MB-231 --- MMP9 --- TNFα --- pancreatic ductal adenocarcinoma --- cyclodextrin inclusion complex --- phase solubility studies --- preformulation studies --- biphenylnicotinamide derivatives --- dual inhibitor --- EGFR --- VEGFR2 --- ligand-based pharmacophore --- molecular docking --- molecular dynamics --- leukemias --- doxorubicin --- inflammation --- drug delivery --- tumor targeting --- elastin-like polypeptide --- cell penetrating peptide --- matrix metalloproteinase --- doxorubicin resistance --- photosensitizer delivery system --- PAMAM dendrimer --- photodynamic therapy --- cytotoxicity --- phototoxicity --- colorectal adenocarcinoma --- dicarboximides --- chemical synthesis --- apoptosis --- kinases --- anticancer --- gene profiling --- SAR --- biomarkers --- colorectal cancer --- early detection examination --- liquid biopsy --- personalized medicine --- tumor treatment --- exosomes --- ctDNA --- CTC --- cytotoxic activity --- pyrazole derivatives --- MTT assay --- ADMET analysis --- single-crystal diffraction --- FTIR spectroscopy --- NMR spectroscopy thermogravimetric analysis --- acute myelogenous leukemia --- platelets --- microparticles --- γδ T cells --- immunotherapy --- tumor resistance --- combination therapy --- tumor microenvironment --- immune checkpoint inhibitor --- neuroblastoma --- molecular iodine --- cyclophosphamide --- xenografts --- metronomic therapy --- tamoxifen --- CYP2D6 --- MCF-7 --- Ishikawa cells --- SERM --- TNBC --- uterotrophic --- α-mangostin --- poly(amidoamine) dendrimer --- targeted drug delivery --- biotin targeting --- glioblastoma multiforme --- squamous cell carcinoma --- antiparasitic therapy --- diclofenac --- indomethacin --- oleanolic acid derivative conjugates --- NF-κB --- Nrf2 --- MAPKs --- PSN-1 cells --- reactive oxygen species --- glioblastoma --- brain tumor --- extracellular vesicles --- pancreatic cancer --- paclitaxel --- clathrin --- endocytosis --- sulforaphane --- nicotine --- metalloproteinase-9 --- gastric cancer --- cell invasion --- Arylquin 1 --- colon cancer --- tumor progression --- azelastine --- oxidative stress --- autophagy --- mitotic catastrophe --- chronic myeloid leukemia --- imatinib --- tyrosine kinase --- ketoconazole --- P-glycoprotein --- drug efflux transporter --- non-small-cell lung cancer --- cisplatin resistance --- aldehyde dehydrogenase --- isothiocyanates --- disulfiram --- epithelial to mesenchymal transition --- aminopeptidase N --- acetamidophenones --- Schiff bases --- semicarbazones --- thiosemicarbazones --- inhibition of proliferation

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Asthma is a common complex and heterogeneous respiratory disease with an increasing prevalence in developed countries. Asthma is a disease consisting of different phenotypes that are driven by different mechanistic pathways (endotypes). The recognition of these phenotypes and endotypes is central to asthma management entailing prognostic and therapeutic implications. It is acknowledged that despite optimal treatment, many patients are poorly controlled, highlighting the need for phenotype-guided treatments. In this context, the emergence of novel therapies (monoclonal antibody therapy, bronchial thermoplasty) is paving the way for personalized asthma therapy. A better understanding of disease pathogenesis may enable the identification of biomarkers, mediators, novel therapeutic targets, and treatable traits. Further molecular phenotyping or endotyping of asthma will be necessary to tailor new therapeutic strategies. The present Special Issue on Asthma aims to provide the current knowledge on phenotypes and endotypes in appreciating and managing the heterogeneous condition that is asthma.

asthma --- lactic acidosis --- hyperchloremic acidosis --- hypocapnia --- hypercapnia --- wheezing --- bronchial biopsies --- symptom persistence --- clinical remission --- eosinophil --- adhesion --- viability --- proliferation --- airway smooth muscle cell --- pulmonary fibroblast --- phenotype --- acute severe asthma exacerbation --- near fatal asthma --- severe asthma --- inflammation --- interleukin-5 (IL-5) --- anti-IL-5 --- interleukin-4 --- airway remodeling --- matrix metalloproteinases-9 --- tissue inhibitor of metalloproteinase-1 --- alveolar macrophages --- lung function --- bronchodilation --- resistance --- obstruction --- reproducible --- spirometry --- obstructive sleep apnea --- bronchial asthma --- alternative overlap syndrome --- exacerbation --- reactive oxygen species --- PBMC --- mitochondrial function --- innate immunity --- immune regulation --- NLRP3 --- IL-1β --- allergic airway inflammation --- microbiome --- pathogenesis --- immune responses --- PreDicta --- preschool --- FeNO --- asthma-specific quality of life --- chronic rhinitis --- disease-specific quality of life --- health-related quality of Life (HRQLQ) --- children --- longitudinal study