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Zinc-dependent matrix metalloproteinases (MMPs) belong to metzincins that comprise not only 23 human MMPs but also other metalloproteinases, such as 21 human ADAMs (a disintegrin and metalloproteinase domain) and 19 secreted ADAMTSs (a disintegrin and metalloproteinase thrombospondin domain). The many setbacks from the clinical trials of broad-spectrum MMP inhibitors for cancer indications in the late 1990s emphasized the extreme complexity of the participation of these proteolytic enzymes in biology. This editorial mini-review summarizes the Special Issue, which includes four review articles and 10 original articles that highlight the versatile roles of MMPs, ADAMs, and ADAMTSs, in normal physiology as well as in neoplastic and destructive processes in tissue. In addition, we briefly discuss the unambiguous involvement of MMPs in wound healing.

Research & information: general --- Biology, life sciences --- hemagglutinin-B --- transwell co-cultures --- matrix metalloproteinases --- TNF-α --- matrix metalloproteinase --- peritoneal mesothelial cell --- gastric cancer --- metastatic dissemination --- MT4-MMP --- cancer --- diseases --- aggrecan --- aggrecanase --- ADAMTS --- cartilage --- arthritis --- MMP-2 --- MMP-9 --- inhibitor --- allodynia --- caspase-3 --- neuropathic --- pain --- dorsal root ganglion --- spinal nerve ligation --- tuberculosis --- tuberculous meningitis --- HIV-TB-associated IRIS --- extracellular matrix breakdown --- adult --- pediatric --- lung --- central nervous system --- matrix-metalloproteinase --- monocytes --- inflammation --- phagocytosis --- apoptosis --- blood sampling --- anticoagulants --- high-molecular-weight heparin --- IL-16 --- sICAM-1 --- IL-8 --- T cells --- a disintegrin and metalloproteinase --- EMMPRIN --- CD147 --- ectodomain shedding --- MMPs --- PTMs --- glycosylation --- phosphorylation --- glycosaminoglycans --- interleukin --- IL-6 --- IL-11 --- trans-signaling --- metalloproteases --- ADAM --- MMP --- meprin --- matrix metalloproteinases (MMPs) --- protease --- signaling --- invasion --- chemokine --- cytokine --- proteomics --- interferon --- Agkistrodon venom --- metalloproteinase --- fibrinogen --- antithrombotic --- metabolomics --- extracellular matrix --- cytokines --- proteinases --- interstitial collagens --- wound healing --- hemagglutinin-B --- transwell co-cultures --- matrix metalloproteinases --- TNF-α --- matrix metalloproteinase --- peritoneal mesothelial cell --- gastric cancer --- metastatic dissemination --- MT4-MMP --- cancer --- diseases --- aggrecan --- aggrecanase --- ADAMTS --- cartilage --- arthritis --- MMP-2 --- MMP-9 --- inhibitor --- allodynia --- caspase-3 --- neuropathic --- pain --- dorsal root ganglion --- spinal nerve ligation --- tuberculosis --- tuberculous meningitis --- HIV-TB-associated IRIS --- extracellular matrix breakdown --- adult --- pediatric --- lung --- central nervous system --- matrix-metalloproteinase --- monocytes --- inflammation --- phagocytosis --- apoptosis --- blood sampling --- anticoagulants --- high-molecular-weight heparin --- IL-16 --- sICAM-1 --- IL-8 --- T cells --- a disintegrin and metalloproteinase --- EMMPRIN --- CD147 --- ectodomain shedding --- MMPs --- PTMs --- glycosylation --- phosphorylation --- glycosaminoglycans --- interleukin --- IL-6 --- IL-11 --- trans-signaling --- metalloproteases --- ADAM --- MMP --- meprin --- matrix metalloproteinases (MMPs) --- protease --- signaling --- invasion --- chemokine --- cytokine --- proteomics --- interferon --- Agkistrodon venom --- metalloproteinase --- fibrinogen --- antithrombotic --- metabolomics --- extracellular matrix --- cytokines --- proteinases --- interstitial collagens --- wound healing

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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 --- 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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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.

Medicine --- 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 --- 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

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Nutritional deficiencies, and different nutritional and dietary lifestyles, whether poor or absent of essential nutrients, aside from excess intake, can lead to inflammatory complications and loss of function. Bioactive compounds are non-nutritional components derived from plants, foods, and beverages with a multitude of biological effects. The improvement of analytical techniques has allowed scientific community to state that the regular consumption of bioactive phytochemicals is related to the prevention of numerous pathologies, through mechanisms that involve oxidative stress reduction, gene expression modulation, and even enzymatic activation inhibition.

Medicine --- quercetin --- nervous system --- molecular signals --- pharmacological potential --- cognitive impairment. --- micronuclei --- radioprotectors --- radiation effects --- melanoma --- PNT2 --- B16F10 cells --- Ulmus parvifolia --- wound healing --- matrix metalloproteinase --- transforming growth factor --- skin rejuvenation --- kaempferol --- naringin --- orientin --- rutin --- vitexin --- chlorogenic acid --- citric acid --- malic acid --- quinic acid --- rosmarinic acid --- curcumin --- nanocurcumin --- neurological disorders --- nanocarriers --- liposomes --- cancer --- diet --- flavonoids --- food supplements --- hormesis --- phytoestrogens --- sulforaphane --- resveratrol --- cardiovascular disease --- nanomedicine --- liposome --- nanoformulation --- RNA-dependent RNA polymerase --- remdesivir --- chloroquine --- SARS-CoV-2 --- COVID-19 --- spike glycoproteins --- Acorus calamus --- ethnomedicinal --- phytochemistry --- toxicity --- pharmacological action --- clinical trial --- neuroprotective --- neurological --- metabolic application --- kurarinone --- coronavirus --- HCoV-OC43 --- autophagy --- infection --- MRC-5 cell --- LC3 --- p62/SQSTM1 protein --- quercetin --- nervous system --- molecular signals --- pharmacological potential --- cognitive impairment. --- micronuclei --- radioprotectors --- radiation effects --- melanoma --- PNT2 --- B16F10 cells --- Ulmus parvifolia --- wound healing --- matrix metalloproteinase --- transforming growth factor --- skin rejuvenation --- kaempferol --- naringin --- orientin --- rutin --- vitexin --- chlorogenic acid --- citric acid --- malic acid --- quinic acid --- rosmarinic acid --- curcumin --- nanocurcumin --- neurological disorders --- nanocarriers --- liposomes --- cancer --- diet --- flavonoids --- food supplements --- hormesis --- phytoestrogens --- sulforaphane --- resveratrol --- cardiovascular disease --- nanomedicine --- liposome --- nanoformulation --- RNA-dependent RNA polymerase --- remdesivir --- chloroquine --- SARS-CoV-2 --- COVID-19 --- spike glycoproteins --- Acorus calamus --- ethnomedicinal --- phytochemistry --- toxicity --- pharmacological action --- clinical trial --- neuroprotective --- neurological --- metabolic application --- kurarinone --- coronavirus --- HCoV-OC43 --- autophagy --- infection --- MRC-5 cell --- LC3 --- p62/SQSTM1 protein

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Rheumatoid Arthritis (RA) is a chronic inflammatory disease leading to joint inflammation and destruction. Treatment of RA includes the use of conventional (cs), biologic (b) disease-modifying anti-rheumatic drugs (DMARDs), and oral or intraarticular (IA) glucocorticoids (GCs). All different classes of drugs have shown to halt disease progression in clinical studies. In real life, a physician has more options than just adding or switching to a new ts/bDMARD if any kind of DMARDs has failed. They can modify or optimize the therapy with concomitant csDMARDs, and oral or IA-GC can be added to the treatment regimen. The EULAR states that therapeutic adjustment including the "optimization of csDMARDs dose or route of administration or intra-articular injections of GCs" is recommended. Thus, a new therapeutic agent can be embedded in a whole strategy with parallel optimization of the csDMARD and GC treatment. The idea of treating to target (T2T) for the treatment of RA patients has been around since the late 1990s. Many clinical studies (Ticora, BsSt, Camera) have demonstrated the superiority of a T2T approach. When I talk to physicians, I understand that most of them only rarely inject joints with GC. Therefore, I would like to create an issue on the T2T approach in reality including primary data, reviews, and real-life data demonstrating the general opinion and execution of T2T in treating RA.

Medicine --- rheumatoid arthritis --- sleep --- sleep disorders --- pain --- osteoporosis --- fracture --- fracture risk assessment tool --- treat-to-target --- certolizumab pegol --- csDMARDs --- glucocorticoids --- intra-articular injections --- DAS 28 --- ACR response --- HAQ-DI --- TNFα --- golimumab --- efficacy --- tolerability --- immunogenicity --- methotrexate --- posology --- titration --- oral route --- subcutaneous route --- bioavailability --- effectiveness --- periodontitis --- periodontal disease --- anti-citrullinated protein autoantibodies --- rheumatoid factor --- smoking --- medication --- Porphyromonas gingivalis --- Rheumatoid arthritis --- matrix metalloproteinase 3 --- infliximab --- pharmacogenomics --- anti-TNF --- personalized medicine --- baricitinib --- disease-modifying antirheumatic drugs --- pain perception --- outcomes research --- patient perspective --- Rheumatoid Arthritis --- therapy --- DMARD --- MTX --- Tumor Necrosis Factor-Alpha Inhibitors --- ankylosing spondylitis --- biosimilar --- switching --- synovial fibroblasts --- cytokine --- osteoclast --- herbal medicine --- methylation --- next-generation sequencing --- recovery of function --- fatigue --- productivity --- tofacitinib --- oral --- Th1.17 --- IL-17A --- IFN-γ, CD73 --- adenosine --- psoriatic arthritis --- regulation --- pseudoerosions --- hand --- foot --- ultrasonography --- radiography --- computed tomography --- magnetic resonance imaging --- rheumatoid arthritis --- sleep --- sleep disorders --- pain --- osteoporosis --- fracture --- fracture risk assessment tool --- treat-to-target --- certolizumab pegol --- csDMARDs --- glucocorticoids --- intra-articular injections --- DAS 28 --- ACR response --- HAQ-DI --- TNFα --- golimumab --- efficacy --- tolerability --- immunogenicity --- methotrexate --- posology --- titration --- oral route --- subcutaneous route --- bioavailability --- effectiveness --- periodontitis --- periodontal disease --- anti-citrullinated protein autoantibodies --- rheumatoid factor --- smoking --- medication --- Porphyromonas gingivalis --- Rheumatoid arthritis --- matrix metalloproteinase 3 --- infliximab --- pharmacogenomics --- anti-TNF --- personalized medicine --- baricitinib --- disease-modifying antirheumatic drugs --- pain perception --- outcomes research --- patient perspective --- Rheumatoid Arthritis --- therapy --- DMARD --- MTX --- Tumor Necrosis Factor-Alpha Inhibitors --- ankylosing spondylitis --- biosimilar --- switching --- synovial fibroblasts --- cytokine --- osteoclast --- herbal medicine --- methylation --- next-generation sequencing --- recovery of function --- fatigue --- productivity --- tofacitinib --- oral --- Th1.17 --- IL-17A --- IFN-γ, CD73 --- adenosine --- psoriatic arthritis --- regulation --- pseudoerosions --- hand --- foot --- ultrasonography --- radiography --- computed tomography --- magnetic resonance imaging