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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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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.
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).
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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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.
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 --- 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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Tea, made from the leaves of the Camellia senenisis plant, is the second most consumed beverage worldwide after water. Accumulating evidence from cellular, animal, epidemiological and clinical studies have linked tea consumption to various health benefits, such as chemoprevention of cancers, chronic inflammation, heart and liver diseases, diabetes, neurodegenerative diseases, etc. Although such health benefits have not been consistently observed in some intervention trials, positive results from clinical trials have provided direct evidence supporting the cancer-protective effect of green tea. In addition, numerous mechanisms of action have been suggested to contribute to tea’s disease-preventive effects. Furthermore, effects of the processing and storage of tea, as well as additives on tea’s properties have been investigated.
polyphenols --- n/a --- cell cycle arrest and apoptosis --- neuroblastoma --- salivary ?-amylase activity --- cancer apoptosis --- yaupon holly --- bioaccessibility --- fracture --- p53 --- tea --- Liubao tea --- BE(2)-C --- matrix metalloproteinase-1 (MMP-1) --- catechin --- renal stone --- oxalate --- protein expression --- 67LR --- Alzheimer’s disease --- EGCG --- nutraceutical --- diseases --- anti-oxidant --- heme oxygenase-1 --- polyphenol --- anxiety --- matcha --- ERCC1/XPF --- neuro-sphere --- tea consumption --- theanine --- Rosmarinic acid --- yerba mate --- hypercalciuria --- gene expression --- microbiota --- cohort study --- histone deacetylase 2 (HDAC2) --- guayusa --- nuclear factor erythroid 2-related factor 2 (Nrf2) --- DNA repair --- mRNA expression --- caffeine --- chemoprevention --- cisplatin --- 6-OH-11-O-hydroxyphenanthrene --- adrenal hypertrophy --- hepatic damage --- anti-photoaging --- cell death --- green tea --- kudingcha --- suberoylanilide hydroxamic acid (SAHA) --- epigallocatechin gallate (EGCG) --- stress-reduction --- calcium oxalate monohydrate --- Camellia sinensis --- chemoresistance --- tea polyphenols --- green tea polyphenols --- green tea catechins --- N-MYC --- cancer --- epigallocatechin-gallate (EGCG) --- Parkinson’s disease --- Alzheimer's disease --- Parkinson's disease
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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
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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.
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 --- n/a
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In recent years, researchers have shown a special interest in natural products as alternative methods for the prevention, treatment, and/or management of various skin illnesses and disorders, primarily due to their natural availability, efficacity, reduced cost, and minimal toxicity. In a similar vein, synthetic bioactives, as well as small molecules, have been studied in vitro, in vivo, and in clinical studies as potential drugs or supplements. This Special Issue of Nutrients comprises an array of literature reviews, original communications, and studies on the roles of natural products, synthetic bioactives, and small molecules in a variety of skin disorders and diseases, such as aging, atopic dermatitis, cutaneous T-cell lymphomas, melanoma, allergies, hyperpigmentation, inflammation, and more, which were investigated through in vitro and ex vivo approaches, preclinical trials, cell-based assays, and animal models. The mechanisms of action of certain compounds are proposed, while others are currently under investigation. The authors of the papers also explore technologies designed to improve the bioavailability and delivery of certain compounds. In lieu of ongoing research on a variety of skin disorders, the wealth of information published in this Special Issue can act as a springboard for the development of new preventive and therapeutic modalities for the management of skin diseases.
Research & information: general --- Biology, life sciences --- keratinocytes --- rutin --- ascorbic acid --- UV radiation --- proteomics --- 3D cell culture --- borage oil --- triacylglycerol metabolism --- acyl-ceramide --- corneocyte lipid envelope --- epidermis --- anti-melanogenesis --- B16/F10 melanoma cell --- hydroxyoctadecadienoic acid --- Sorghum bicolor --- 3-isobutyl-1-methylxanthine --- mycosis fungoides --- atopic dermatitis --- cutaneous lymphomas --- cornified envelope proteins --- FLG --- microalgae --- Planktochlorella nurekis --- skin cells --- proliferation --- senescence --- holothuroids --- glycosaminoglycans --- inflammation --- ear-inflammation --- whey --- Lactobacillus helveticus --- melanin --- α-melanocyte-stimulating hormone --- tyrosinase --- tyrosinase-related protein 1 --- dopachrome tautomerase --- microphthalmia-associated transcription factor --- cosmetics --- black cumin --- Nigella sativa --- Thymocid® --- skin aging --- glycation --- collagen --- collagenase --- elastase --- melanogenesis --- cosmeceutical --- konjac glucomannan --- ultraviolet B --- human epidermal primary melanocytes --- human embryonic fibroblasts --- anti-inflammatory activity --- antioxidant activity --- Cornus officinalis --- molecular docking --- human high-affinity IgE receptors --- α-MSH --- UVB irradiation --- lotus seedpod extract --- epigallocatechin --- propolis --- skin --- matrix metalloproteinase-1 --- UV --- phosphoinositide 3-kinase --- skin care --- skin health --- bioactive substances --- phytonutrients --- antioxidants --- nutraceuticals --- Perilla frutescens --- cell proliferation --- ultraviolet radiation --- DNA repair --- Lactobacillus plantarum CJLP55 --- acne vulgaris --- sebum --- hydration --- urine bacterial extracellular vesicles --- fungal infections --- nanohydrogel --- polysaccharide --- essential oils --- eggshell membrane --- keratinocyte differentiation --- TRPV --- skin thickness --- Lithospermum erythrorhizon --- NC/Nga --- Th1 --- Th2 --- Th17 --- Th22 --- immune balance --- skin barrier function --- n/a
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