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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).

Research & information: general --- 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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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).

Research & information: general --- 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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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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The importance of natural products, and especially plant secondary metabolites, for the treatment of diseases and drug development has already been obvious in medicine for several thousand years. Thus, this Special Issue of MDPI Biomedicines collects eight top articles from the field as regular full papers in addition to five reviews. All of the published papers are a vibrant source of information on the therapeutic potential of plant secondary metabolites in the treatment of diseases and drug development.

Cannabis sativa (Cannabis) --- cannabinoids --- tetrahydrocannabinol (THC) --- cannabidiol (CBD) --- cannabinoid receptors (CB1 and CB2) --- Papaver somniferum (opium poppy) --- secondary metabolites --- ursolic acid --- NSCLC --- tumorsphere --- EGFR --- STAT3 --- MMP2 --- PD-L1 --- MAFLD --- tanshinone IIA --- phytochemical --- lipogenesis --- lipid accumulation --- LXRα --- malaria --- quinine --- chloroquine --- artemisinin --- onchocerciasis --- ivermectin --- moxidectin --- cancer --- vincristine --- vinblastine --- anabolic --- diabetes --- Duchenne muscular dystrophy --- β-ecdysone --- ecdysteroid --- ecdysterone --- Mas1 --- osteoporosis --- sarcopenia --- COVID-19 --- cardiometabolic diseases --- respiratory diseases --- natural product --- SARS-CoV-2 --- lung cancer --- United States Food and Drug Administration-approved drug --- natural remedy --- triterpenoid --- molecular ribbon --- Huisgen 1,3-dipolar cycloaddition --- amide bond --- multifunctional PEG3 derivative --- antimicrobial activity --- anti-HIV activity --- cytotoxicity --- supramolecular self-assembly --- phytocannabinoids --- cannabichromene --- thermos-TRPs --- TRPA1 --- α,α-dimethylheptyl effect --- betulinic acid --- BODIPY --- bevirimat --- cell-cycle --- fluorescent microscopy --- maturation inhibitor --- capsaicinoids --- endocannabinoidome --- microbiota --- overweight --- obesity --- food intake --- lipidomics --- metabolism --- alkaloids --- membrane fusion --- viral fusion inhibitor --- antiviral therapy --- curcumin --- cancer cells --- bioavailability --- curcumin derivatives --- curcumin analogues --- curcumin delivery systems --- natural product synthesis --- lignans --- inflammation --- NF-κB inhibition --- n/a

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The importance of natural products, and especially plant secondary metabolites, for the treatment of diseases and drug development has already been obvious in medicine for several thousand years. Thus, this Special Issue of MDPI Biomedicines collects eight top articles from the field as regular full papers in addition to five reviews. All of the published papers are a vibrant source of information on the therapeutic potential of plant secondary metabolites in the treatment of diseases and drug development.

Technology: general issues --- Chemical engineering --- Cannabis sativa (Cannabis) --- cannabinoids --- tetrahydrocannabinol (THC) --- cannabidiol (CBD) --- cannabinoid receptors (CB1 and CB2) --- Papaver somniferum (opium poppy) --- secondary metabolites --- ursolic acid --- NSCLC --- tumorsphere --- EGFR --- STAT3 --- MMP2 --- PD-L1 --- MAFLD --- tanshinone IIA --- phytochemical --- lipogenesis --- lipid accumulation --- LXRα --- malaria --- quinine --- chloroquine --- artemisinin --- onchocerciasis --- ivermectin --- moxidectin --- cancer --- vincristine --- vinblastine --- anabolic --- diabetes --- Duchenne muscular dystrophy --- β-ecdysone --- ecdysteroid --- ecdysterone --- Mas1 --- osteoporosis --- sarcopenia --- COVID-19 --- cardiometabolic diseases --- respiratory diseases --- natural product --- SARS-CoV-2 --- lung cancer --- United States Food and Drug Administration-approved drug --- natural remedy --- triterpenoid --- molecular ribbon --- Huisgen 1,3-dipolar cycloaddition --- amide bond --- multifunctional PEG3 derivative --- antimicrobial activity --- anti-HIV activity --- cytotoxicity --- supramolecular self-assembly --- phytocannabinoids --- cannabichromene --- thermos-TRPs --- TRPA1 --- α,α-dimethylheptyl effect --- betulinic acid --- BODIPY --- bevirimat --- cell-cycle --- fluorescent microscopy --- maturation inhibitor --- capsaicinoids --- endocannabinoidome --- microbiota --- overweight --- obesity --- food intake --- lipidomics --- metabolism --- alkaloids --- membrane fusion --- viral fusion inhibitor --- antiviral therapy --- curcumin --- cancer cells --- bioavailability --- curcumin derivatives --- curcumin analogues --- curcumin delivery systems --- natural product synthesis --- lignans --- inflammation --- NF-κB inhibition --- n/a