1 5454 98 REPURPOSING BELINOSTAT FOR ALLEVIATION OF ATOPIC DERMATITIS. ATOPIC DERMATITIS (AD) IS A HIGHLY PREVALENT CHRONIC INFLAMMATORY SKIN DISEASE THAT IS CHARACTERIZED BY INTENSE PRURITUS, SERIOUSLY AFFECTING PATIENTS' QUALITY OF LIFE. ITS PATHOPHYSIOLOGY, WHICH INVOLVES BOTH THE ADAPTIVE AND INNATE IMMUNE RESPONSES AS WELL AS SKIN BARRIER DEFECTS, IS STILL POORLY UNDERSTOOD. WE RECENTLY IDENTIFIED A MICRORNA, MIR-335, AS A KEY DRIVER OF KERATINOCYTE DIFFERENTIATION AND CORNIFICATION, WHICH IS ESSENTIAL FOR THE ESTABLISHMENT OF A HEALTHY SKIN BARRIER. HOWEVER, EXPRESSION OF MIR-335 IS LOST IN AD, LEADING TO BARRIER DEFECT. WE FURTHER DEMONSTRATED HOW BELINOSTAT, A HISTONE DEACETYLASE INHIBITOR, CAN EFFECTIVELY RESTORE MIR-335 AND RESOLVE THE BARRIER DEFECT IN A DRY SKIN MODEL. HERE, IN THIS COMMENTARY, WE HIGHLIGHT THE ROLE OF BELINOSTAT IN THE TREATMENT OF AD AND DISCUSS THE NEED FOR MORE RESEARCH INTO CROSSTALK BETWEEN EPIGENETIC AND NON-CODING RNA-BASED REGULATION, AS WELL AS POSSIBLE THERAPEUTIC STRATEGIES TARGETING THE EPIGENOME. 2021 2 3333 26 HISTONE DEACETYLASE INHIBITORS AND DIABETIC KIDNEY DISEASE. DESPITE RECENT CLINICAL TRIAL ADVANCES AND IMPROVEMENTS IN CLINICAL CARE, KIDNEY DISEASE DUE TO DIABETES REMAINS THE MOST COMMON CAUSE OF CHRONIC KIDNEY FAILURE WORLDWIDE. IN THE SEARCH FOR NEW TREATMENTS, RECENT ATTENTIONS HAVE TURNED TO DRUG REPURPOSING OPPORTUNITIES, INCLUDING STUDY OF THE HISTONE DEACETYLASE (HDAC) INHIBITOR CLASS OF AGENTS. HDACS ARE A GROUP OF ENZYMES THAT REMOVE FUNCTIONAL ACETYL GROUPS FROM HISTONE AND NON-HISTONE PROTEINS AND THEY CAN AFFECT CELLULAR FUNCTION THROUGH BOTH EPIGENETIC AND NON-EPIGENETIC MEANS. OVER THE PAST DECADE, SEVERAL HDAC INHIBITORS HAVE BEEN ADOPTED INTO CLINICAL PRACTICE, PRIMARILY FOR THE TREATMENT OF HEMATOLOGICAL MALIGNANCY, WHEREAS OTHER EXISTING THERAPIES (FOR INSTANCE VALPROATE) HAVE BEEN FOUND TO HAVE HDAC INHIBITORY EFFECTS. HERE WE REVIEW THE CURRENT HDAC INHIBITORS IN THE CLINIC AND UNDER DEVELOPMENT; THE LITERATURE EVIDENCE SUPPORTING THE RENOPROTECTIVE EFFECTS OF HDAC INHIBITORS IN EXPERIMENTAL DIABETIC KIDNEY DISEASE; AND THE ADVERSE EFFECT PROFILES THAT MAY PREVENT EXISTING THERAPIES FROM ENTERING THE CLINIC FOR THIS INDICATION. WHEREAS RECENT RESEARCH EFFORTS HAVE SHED LIGHT ON THE FUNDAMENTAL ACTIONS OF HDACS IN THE DIABETIC KIDNEY, WHETHER THESE EFFORTS WILL TRANSLATE INTO NOVEL THERAPIES FOR PATIENTS WILL REQUIRE MORE SPECIFIC AND BETTER-TOLERATED THERAPIES. 2018 3 4827 24 OFF-TARGET DRUG EFFECTS RESULTING IN ALTERED GENE EXPRESSION EVENTS WITH EPIGENETIC AND "QUASI-EPIGENETIC" ORIGINS. THIS REVIEW SYNTHESIZES EXAMPLES OF PHARMACOLOGICAL AGENTS WHO HAVE OFF-TARGET EFFECTS OF AN EPIGENETIC NATURE. WE EXPAND UPON THE PARADIGM OF EPIGENETICS TO INCLUDE "QUASI-EPIGENETIC" MECHANISMS. QUASI-EPIGENETICS INCLUDES MECHANISMS OF DRUGS ACTING UPSTREAM OF EPIGENETIC MACHINERY OR MAY THEMSELVES IMPACT TRANSCRIPTION FACTOR REGULATION ON A MORE GLOBAL SCALE. WE EXPLORE THESE AVENUES WITH FOUR EXAMPLES OF CONVENTIONAL PHARMACEUTICALS AND THEIR UNINTENDED, BUT NOT NECESSARILY ADVERSE, BIOLOGICAL EFFECTS. THE QUASI-EPIGENETIC DRUGS IDENTIFIED IN THIS REVIEW INCLUDE THE USE OF BETA-LACTAM ANTIBIOTICS TO ALTER GLUTAMATE RECEPTOR ACTIVITY AND THE ACTION OF CYCLOSPORINE ON MULTIPLE TRANSCRIPTION FACTORS. IN ADDITION, WE REPORT ON MORE CANONICAL EPIGENOME CHANGES ASSOCIATED WITH PHARMACOLOGICAL AGENTS SUCH AS LITHIUM IMPACTING AUTOPHAGY OF ABERRANT PROTEINS, AND OPIOID DRUGS WHOSE CHRONIC USE INCREASES THE EXPRESSION OF GENES ASSOCIATED WITH ADDICTIVE PHENOTYPES. BY EXPANDING OUR APPRECIATION OF TRANSCRIPTOMIC REGULATION AND THE EFFECTS THESE DRUGS HAVE ON THE EPIGENOME, IT IS POSSIBLE TO ENHANCE THERAPEUTIC APPLICATIONS BY EXPLOITING OFF-TARGET EFFECTS AND EVEN REPURPOSING ESTABLISHED PHARMACEUTICALS. THAT IS, EXPLORATION OF "PHARMACOEPIGENETIC" MECHANISMS CAN EXPAND THE BREADTH OF THE USEFUL ACTIVITY OF A DRUG BEYOND THE TRADITIONAL DRUG TARGETS SUCH AS RECEPTORS AND ENZYMES. 2016 4 1678 25 DRUG REPURPOSING AT THE INTERFACE OF MELANOMA IMMUNOTHERAPY AND AUTOIMMUNE DISEASE. CANCER CELLS HAVE A REMARKABLE ABILITY TO EVADE RECOGNITION AND DESTRUCTION BY THE IMMUNE SYSTEM. AT THE SAME TIME, CANCER HAS BEEN ASSOCIATED WITH CHRONIC INFLAMMATION, WHILE CERTAIN AUTOIMMUNE DISEASES PREDISPOSE TO THE DEVELOPMENT OF NEOPLASIA. ALTHOUGH CANCER IMMUNOTHERAPY HAS REVOLUTIONIZED ANTITUMOR TREATMENT, IMMUNE-RELATED TOXICITIES AND ADVERSE EVENTS DETRACT FROM THE CLINICAL UTILITY OF EVEN THE MOST ADVANCED DRUGS, ESPECIALLY IN PATIENTS WITH BOTH, METASTATIC CANCER AND PRE-EXISTING AUTOIMMUNE DISEASES. HERE, THE COMBINATION OF MULTI-OMICS, DATA-DRIVEN COMPUTATIONAL APPROACHES WITH THE APPLICATION OF NETWORK CONCEPTS ENABLES IN-DEPTH ANALYSES OF THE DYNAMIC LINKS BETWEEN CANCER, AUTOIMMUNE DISEASES, AND DRUGS. IN THIS REVIEW, WE FOCUS ON MOLECULAR AND EPIGENETIC METASTASIS-RELATED PROCESSES WITHIN CANCER CELLS AND THE IMMUNE MICROENVIRONMENT. WITH MELANOMA AS A MODEL, WE UNCOVER VULNERABILITIES FOR DRUG DEVELOPMENT TO CONTROL CANCER PROGRESSION AND IMMUNE RESPONSES. THEREBY, DRUG REPURPOSING ALLOWS TAKING ADVANTAGE OF EXISTING SAFETY PROFILES AND ESTABLISHED PHARMACOKINETIC PROPERTIES OF APPROVED AGENTS. THESE PROCEDURES PROMISE FASTER ACCESS AND OPTIMAL MANAGEMENT FOR CANCER TREATMENT. TOGETHER, THESE APPROACHES PROVIDE NEW DISEASE-BASED AND DATA-DRIVEN OPPORTUNITIES FOR THE PREDICTION AND APPLICATION OF TARGETED AND CLINICALLY USED DRUGS AT THE INTERFACE OF IMMUNE-MEDIATED DISEASES AND CANCER TOWARDS NEXT-GENERATION IMMUNOTHERAPIES. 2022 5 79 32 A NEW PROSPECT FOR THE TREATMENT OF NEPHROTIC SYNDROME BASED ON NETWORK PHARMACOLOGY ANALYSIS. NETWORK PHARMACOLOGY IS AN EMERGING FIELD WHICH IS CURRENTLY CAPTURING INTEREST IN DRUG DISCOVERY AND DEVELOPMENT. CHRONIC KIDNEY CONDITIONS HAVE BECOME A THREAT GLOBALLY DUE TO ITS ASSOCIATED LIFELONG THERAPIES. NEPHROTIC SYNDROME (NS) IS A COMMON GLOMERULAR DISEASE THAT IS SEEN IN PAEDIATRIC AND ADULT POPULATION WITH CHARACTERISTIC MANIFESTATION OF PROTEINURIA, OEDEMA, HYPOALBUMINEMIA, AND HYPERLIPIDEMIA. IT INVOLVES PODOCYTE DAMAGE WITH TUBULOINTERSTITIAL FIBROSIS AND GLOMERULOSCLEROSIS. TILL DATE THERE HAS BEEN NO SPECIFIC TREATMENT AVAILABLE FOR THIS CONDITION THAT PROVIDES COMPLETE REMISSION. REPURPOSING OF DRUGS CAN THUS BE A POTENTIAL STRATEGY FOR THE TREATMENT OF NS. RECENTLY, EPIGENETIC MECHANISMS WERE IDENTIFIED THAT PROMOTE PROGRESSION OF MANY RENAL DISEASES. THEREFORE, IN THE PRESENT STUDY, WE INVESTIGATED TWO EPIGENETIC DRUGS VALPROIC ACID (VPA) AND ALL-TRANS RETINOIC ACID (ATRA). EPIGENETIC DRUGS ACT BY BINGING ABOUT CHANGES IN GENE EXPRESSION WITHOUT ALTERING THE DNA SEQUENCE. THE CHANGES INCLUDE DNA METHYLATION OR HISTONE MODIFICATIONS. THE TARGETS FOR THE TWO DRUGS ATRA AND VPA WERE COLLATED FROM CHEMBL AND BINDING DB. ALL THE GENES ASSOCIATED WITH NS WERE COLLECTED FROM DISGENET AND KEGG DATABASE. INTERACTING PROTEINS FOR THE TARGET GENES WERE ACQUIRED FROM STRING DATABASE. THE GENES WERE THEN SUBJECTED TO GENE ONTOLOGY AND PATHWAY ENRICHMENT ANALYSIS USING A FUNCTIONAL ENRICHMENT SOFTWARE TOOL. A DRUG-TARGET AND DRUG-POTENTIAL TARGET-PROTEIN INTERACTION NETWORK WAS CONSTRUCTED USING THE CYTOSCAPE SOFTWARE. OUR RESULTS REVEALED THAT THE TWO DRUGS VPA AND ATRA HAD 65 COMMON TARGETS THAT CONTRIBUTED TO KIDNEY DISEASES. OUT OF WHICH, 25 TARGETS WERE SPECIFICALLY NS ASSOCIATED. FURTHER, OUR WORK EXHIBITED THAT ATRA AND VPA WERE SYNERGISTICALLY INVOLVED IN PATHWAYS OF INFLAMMATION, RENAL FIBROSIS, GLOMERULOSCLEROSIS AND POSSIBLY MITOCHONDRIAL BIOGENESIS AND ENDOPLASMIC RETICULUM STRESS. WE THUS PROPOSE A SYNERGISTIC POTENTIAL OF THE TWO DRUGS FOR TREATING CHRONIC KIDNEY DISEASES, SPECIFICALLY NS. THE OUTCOMES WILL UNDOUBTEDLY INVIGORATE FURTHER PRECLINICAL AND CLINICAL EXPLORATIVE STUDIES. WE IDENTIFY NETWORK PHARMACOLOGY AS AN INITIAL INHERENT APPROACH IN IDENTIFYING DRUG CANDIDATES FOR REPURPOSING AND SYNERGISM. 2022 6 5857 25 SUBSTRATE-SPECIFIC BINDING OF 8-OXOGUANINE DNA GLYCOSYLASE 1 (OGG1) REPROGRAMS MUCOSAL ADAPTATIONS TO CHRONIC AIRWAY INJURY. RECENT ADVANCES HAVE UNCOVERED THE NON-RANDOM DISTRIBUTION OF 7, 8-DIHYDRO-8-OXOGUANINE (8-OXOGUA) INDUCED BY REACTIVE OXYGEN SPECIES, WHICH IS BELIEVED TO HAVE EPIGENETIC EFFECTS. ITS COGNATE REPAIR PROTEIN, 8-OXOGUANINE DNA GLYCOSYLASE 1 (OGG1), READS OXIDATIVE SUBSTRATES AND PARTICIPATES IN TRANSCRIPTIONAL INITIATION. WHEN REDOX SIGNALING IS ACTIVATED IN SMALL AIRWAY EPITHELIAL CELLS, THE DNA REPAIR FUNCTION OF OGG1 IS REPURPOSED TO TRANSMIT ACUTE INFLAMMATORY SIGNALS ACCOMPANIED BY CELL STATE TRANSITIONS AND MODIFICATION OF THE EXTRACELLULAR MATRIX. EPITHELIAL-MESENCHYMAL AND EPITHELIAL-IMMUNE INTERACTIONS ACT COOPERATIVELY TO ESTABLISH A LOCAL NICHE THAT INSTRUCTS THE MUCOSAL IMMUNE LANDSCAPE. IF THE TRANSITIONAL CELL STATE GOVERNED BY OGG1 REMAINS RESPONSIVE TO INFLAMMATORY MEDIATORS INSTEAD OF DIFFERENTIATION, THE COLLATERAL DAMAGE PROVIDES POSITIVE FEEDBACK TO INFLAMMATION, ASCRIBING INFLAMMATORY REMODELING TO ONE OF THE DRIVERS IN CHRONIC PATHOLOGIES. IN THIS REVIEW, WE DISCUSS THE SUBSTRATE-SPECIFIC READ THROUGH OGG1 HAS EVOLVED IN REGULATING THE INNATE IMMUNE RESPONSE, CONTROLLING ADAPTATIONS OF THE AIRWAY TO ENVIRONMENTAL AND INFLAMMATORY INJURY, WITH A FOCUS ON THE READER FUNCTION OF OGG1 IN INITIATION AND PROGRESSION OF EPITHELIAL TO MESENCHYMAL TRANSITIONS IN CHRONIC PULMONARY DISEASE. 2023 7 6566 33 TRANSLATIONAL PERSPECTIVES TO TREAT EPIDERMOLYSIS BULLOSA-WHERE DO WE STAND? EPIDERMOLYSIS BULLOSA (EB) IS THE PROTOTYPICAL EXAMPLE OF GENETIC SKIN FRAGILITY DISORDERS. GENOTYPIC HETEROGENEITY, MODIFIER GENES, EPIGENETIC, BIOCHEMICAL AND ENVIRONMENTAL FACTORS ALTER AND DETERMINE PATHOGENIC TRAITS AND, ULTIMATELY, THE WIDE AND STRIKING PHENOTYPIC VARIABILITY IN EB. BESIDES THE PRIMARY STRUCTURAL-FUNCTIONAL DEFECT, CHRONIC TISSUE DAMAGE WITH INDUCTION AND DYSREGULATION OF INFLAMMATORY PATHWAYS IS A COMMON PATHOGENIC MECHANISM IN EB. IN LOCALIZED VARIANTS, THE INFLAMMATORY ABERRATIONS MAY MAINLY AFFECT THE MICROMILIEU OF LESIONAL SKIN, WHILE A SYSTEMIC INFLAMMATORY RESPONSE WAS SHOWN TO CONTRIBUTE TO THE SYSTEMIC MORBIDITY IN SEVERE EB SUBTYPES WITH EXTENSIVE CUTANEOUS INVOLVEMENT. OUR CONTINUED UNDERSTANDING OF THE PATHOPHYSIOLOGY OF EB, AS WELL AS ADVANCES IN MOLECULAR TECHNOLOGIES, HAS PAVED THE WAY FOR TRANSLATIONAL THERAPEUTIC APPROACHES. THE SPECTRUM COMPRISES OF CORRECTIVE AND SYMPTOM-RELIEVING THERAPIES THAT INCLUDE INNOVATIVE THERAPEUTIC OPTIONS GARNERED FROM THE BENCH, REPURPOSED DRUGS APPROVED FOR OTHER DISEASES, AS WELL AS STRATEGIES FOR GENE-, PROTEIN- AND CELL-BASED THERAPIES. IMMUNOLOGICAL TRAITS FURTHER DEFINE NEW TARGETS OF THERAPY, AIMED AT IMPROVING SKIN BARRIER RESTORATION, MICROBIAL SURVEILLANCE AND INFECTION CONTROL, WOUND HEALING AND ANTI-NEOPLASTIC EFFECTS. CLINICAL AVAILABILITY AND FEASIBILITY OF THESE APPROACHES FOR ALL EB PATIENTS AND SUBTYPES ARE CURRENTLY LIMITED, REFLECTING ISSUES OF EFFICACY, SPECIFICITY, TOLERABILITY AND SAFETY. A MULTISTEP TARGETING APPROACH AND HIGHLY INDIVIDUALIZED, RISK-STRATIFIED COMBINATORY TREATMENT PLANS WILL THUS BE ESSENTIAL FOR SUSTAINED EFFICACY AND IMPROVED OVERALL QUALITY OF LIFE IN EB. 2020 8 5053 28 PHARMACOLOGY OF PULMONARY ARTERIAL HYPERTENSION: AN OVERVIEW OF CURRENT AND EMERGING THERAPIES. PULMONARY ARTERIAL HYPERTENSION IS A RARE AND DEVASTATING DISEASE CHARACTERIZED BY AN ABNORMAL CHRONIC INCREASE IN PULMONARY ARTERIAL PRESSURE ABOVE 20 MMHG AT REST, WITH A POOR PROGNOSIS IF NOT TREATED. CURRENTLY, THERE IS NOT A SINGLE FULLY EFFECTIVE THERAPY, EVEN THOUGH A DOZEN OF DRUGS HAVE BEEN DEVELOPED IN THE LAST DECADES. PULMONARY ARTERIAL HYPERTENSION IS A MULTIFACTORIAL DISEASE, MEANING THAT SEVERAL MOLECULAR MECHANISMS ARE IMPLICATED IN ITS PATHOLOGY. THE MAIN MOLECULAR PATHWAYS REGULATING THE PULMONARY VASOMOTOR TONE-ENDOTHELIN, NITRIC OXIDE, AND PROSTACYCLIN-ARE THE MOST BIOLOGICALLY AND THERAPEUTICALLY EXPLORED TO DATE. HOWEVER, DRUGS TARGETING THESE PATHWAYS HAVE ALREADY FOUND THEIR LIMITATIONS. IN THE LAST YEARS, TRANSLATIONAL RESEARCH AND CLINICAL TRIALS HAVE MADE A STRONG EFFORT IN SUGGESTING AND TESTING NOVEL THERAPEUTIC STRATEGIES FOR THIS DISEASE. THESE APPROACHES INVOLVE TARGETING THE MAIN MOLECULAR PATHWAYS WITH NOVEL DRUGS, DRUG REPURPOSING FOR NOVEL TARGETS, AND ALSO USING COMBINATORIAL THERAPIES. IN THIS REVIEW, WE SUMMARIZE CURRENT STRATEGIES AND DRUGS TARGETING THE ENDOTHELIN, NITRIC OXIDE, AND PROSTACYCLIN PATHWAYS, AS WELL AS, THE EMERGING NEW DRUGS PROPOSED TO COPE WITH VASCULAR REMODELLING, METABOLIC SWITCH, PERIVASCULAR INFLAMMATION, EPIGENETIC MODIFICATIONS, ESTROGEN DEREGULATION, SEROTONIN, AND OTHER NEUROHUMORAL MECHANISMS CHARACTERISTIC OF THIS DISEASE. NOWADAYS, PULMONARY ARTERIAL HYPERTENSION REMAINS AN INCURABLE DISEASE; HOWEVER, THE INCOMING NEW KNOWLEDGE MAKES US BELIEVE THAT NEW PROMISING THERAPIES ARE COMING TO THE CLINICAL ARENA SOON. 2020 9 6621 27 UNDERSTANDING FIBROSIS IN SYSTEMIC SCLEROSIS: SHIFTING PARADIGMS, EMERGING OPPORTUNITIES. FIBROSIS IN MULTIPLE ORGANS IS A PROMINENT PATHOLOGICAL FINDING AND DISTINGUISHING HALLMARK OF SYSTEMIC SCLEROSIS (SSC). FINDINGS DURING THE PAST 5 YEARS HAVE CONTRIBUTED TO A MORE COMPLETE UNDERSTANDING OF THE COMPLEX CELLULAR AND MOLECULAR UNDERPINNING OF FIBROSIS IN SSC. FIBROBLASTS, THE PRINCIPAL EFFECTOR CELLS, ARE ACTIVATED IN THE PROFIBROTIC CELLULAR MILIEU BY CYTOKINES AND GROWTH FACTORS, DEVELOPMENTAL PATHWAYS, ENDOTHELIN 1 AND THROMBIN. INNATE IMMUNE SIGNALING VIA TOLL-LIKE RECEPTORS, MATRIX-GENERATED BIOMECHANICAL STRESS SIGNALING VIA INTEGRINS, HYPOXIA AND OXIDATIVE STRESS SEEM TO BE IMPLICATED IN PERPETUATING THE PROCESS. BEYOND CHRONIC FIBROBLAST ACTIVATION, FIBROSIS REPRESENTS A FAILURE TO TERMINATE TISSUE REPAIR, COUPLED WITH AN EXPANDED POPULATION OF MESENCHYMAL CELLS ORIGINATING FROM BONE MARROW AND TRANSDIFFERENTIATION OF EPITHELIAL CELLS, ENDOTHELIAL CELLS AND PERICYTES. IN ADDITION, STUDIES HAVE IDENTIFIED INTRINSIC ALTERATIONS IN SSC FIBROBLASTS RESULTING FROM EPIGENETIC CHANGES, AS WELL AS ALTERED MICRORNA EXPRESSION THAT MIGHT UNDERLIE THE CELL-AUTONOMOUS, PERSISTENT ACTIVATION PHENOTYPE OF THESE CELLS. PRECISE CHARACTERIZATION OF THE DEREGULATED EXTRACELLULAR AND INTRACELLULAR SIGNALING PATHWAYS, MEDIATORS AND CELLULAR DIFFERENTIATION PROGRAMS THAT CONTRIBUTE TO FIBROSIS IN SSC WILL FACILITATE THE DEVELOPMENT OF SELECTIVE, TARGETED THERAPEUTIC STRATEGIES. EFFECTIVE ANTIFIBROTIC THERAPY WILL ULTIMATELY INVOLVE NOVEL COMPOUNDS AND REPURPOSING OF DRUGS THAT ARE ALREADY APPROVED FOR OTHER INDICATIONS. 2011 10 3335 24 HISTONE DEACETYLASE INHIBITORS FOR CARDIOVASCULAR CONDITIONS AND HEALTHY LONGEVITY. HISTONE DEACETYLASE INHIBITORS (HDACI) REGULATE GENE EXPRESSION VIA EPIGENETIC MECHANISMS. ACCUMULATING EVIDENCE SUGGESTS THAT HDACI EXERT ANTIPROLIFERATIVE, ANTIOXIDANT, ANTINEOPLASTIC, AND PROAPOPTOTIC EFFECTS THROUGH EPIGENETIC MECHANISMS. FURTHERMORE, HDACI ALSO EXERT ANTITHROMBOTIC AND ANTIFIBROTIC EFFECTS THROUGH REGULATION OF THROMBOTIC AND FIBROTIC TRANSDUCTION MECHANISMS. ONE OF THE OLDEST HDACI IS VALPROIC ACID, WHICH WAS FIRST SYNTHESISED IN 1882. AFTER THE DISCOVERY OF ITS ANTICONVULSANT PROPERTIES FOR THE TREATMENT OF EPILEPSY, THE USE OF VALPROIC ACID WAS EXTENDED TO OTHER CONDITIONS, SUCH AS BIPOLAR DISORDER AND MIGRAINE. GIVEN THE ACCUMULATING EVIDENCE SUPPORTING THE ROLE OF HDACI IN THE TREATMENT OF MULTIPLE MEDICAL CONDITIONS BEYOND EPILEPSY, THE INTEREST IN NOVEL POTENTIAL INDICATIONS FOR HDACI HAS BEEN RENEWED. CONSIDERING THE PLEOTROPIC EPIGENETIC EFFECTS OF HDACI, FUTURE STUDIES COULD ASSESS THEIR EFFICACY AND SAFETY FOR CARDIOVASCULAR DISEASE PREVENTION AND TREATMENT; TREATMENT OF VENOUS THROMBOSIS, ALZHEIMER'S DISEASE, AUTOIMMUNE AND PROINFLAMMATORY CONDITIONS, CHRONIC THROMBOEMBOLIC PULMONARY HYPERTENSION, AND PULMONARY ARTERIAL HYPERTENSION; AND AS A COADJUVANT THERAPY FOR CANCER. ADEQUATELY DESIGNED AND POWERED CLINICAL TRIALS ARE REQUIRED TO ASSESS THE EFFICACY AND SAFETY OF HDACI BEFORE THEIR CLINICAL REPURPOSING. 2021 11 429 25 ANTI-INFLAMMATORY TOPICAL MEDICATION - NEW DEVELOPMENTS IN THE TREATMENT OF ATOPIC DERMATITIS. ATOPIC DERMATITIS IS A CHRONIC INFLAMMATORY DISEASE THAT ARISES FROM POLYGENIC DISPOSITION, A DYSFUNCTION OF THE PHYSICOCHEMICAL EPITHELIAL BARRIER, A CUTANEOUS DYSBIOSIS, AND A FAULTY NEUROSENSORY ACTIVITY AND SHOWS A HIGHLY INDIVIDUAL ACUITY DUE TO EPIGENETIC FACTORS. AN ESSENTIAL COMPONENT OF THERAPEUTIC MANAGEMENT IS THE APPLICATION OF ANTI-INFLAMMATORY TOPICAL MEDICATION. CURRENTLY, TOPICAL GLUCOCORTICOIDS AND TOPICAL CALCINEURIN INHIBITORS ARE ROUTINELY USED IN REACTIVE AND PROACTIVE THERAPY. IN RECENT YEARS, THE DEVELOPMENT OF MOLECULAR MEDICINE HAS IDENTIFIED SEVERAL NEW THERAPEUTIC TARGETS THAT HAVE ENABLED THE DEVELOPMENT OF INNOVATIVE THERAPEUTIC APPROACHES. IN ADDITION TO PHOSPHODIESTERASE-4 INHIBITORS AND ARYL HYDROCARBON RECEPTOR MODULATORS, IT IS MAINLY JANUS KINASE INHIBITORS WITH DIFFERENT SELECTIVITY THAT ARE EMERGING AS NEW EFFECTIVE AND SAFE OPTIONS FOR TOPICAL THERAPY. THE CURRENT DATA SUGGESTS THAT IN THE COMING MONTHS AND YEARS REPRESENTATIVES OF THE ABOVE-MENTIONED SUBSTANCE CLASSES WILL BE APPROVED FOR TOPICAL USE. 2021 12 4777 21 NUTRACEUTICALS AND NETWORK PHARMACOLOGY APPROACH FOR ACUTE KIDNEY INJURY: A REVIEW FROM THE DRUG DISCOVERY ASPECT. ACUTE KIDNEY INJURY (AKI) HAS BECOME A GLOBAL HEALTH ISSUE, WITH APPROXIMATELY 12 MILLION REPORTS YEARLY, RESULTING IN A PERSISTENT INCREASE IN MORBIDITY AND MORTALITY RATES. AKI PATHOPHYSIOLOGY IS MULTIFACTORIAL INVOLVING OXIDATIVE STRESS, MITOCHONDRIAL DYSFUNCTION, EPIGENETIC MODIFICATIONS, INFLAMMATION, AND EVENTUALLY, CELL DEATH. HENCE, THERAPIES ABLE TO TARGET MULTIPLE PATHOMECHANISMS CAN AID IN AKI MANAGEMENT. TO CHANGE THE DRUG DISCOVERY FRAMEWORK FROM "ONE DRUG, ONE TARGET" TO "MULTICOMPONENT, MULTITARGET," NETWORK PHARMACOLOGY IS EVOLVING AS A NEXT-GENERATION RESEARCH APPROACH. RESEARCHERS HAVE USED THE NETWORK PHARMACOLOGY APPROACH TO PREDICT THE ROLE OF NUTRACEUTICALS AGAINST DIFFERENT AILMENTS INCLUDING AKI. NUTRACEUTICALS (HERBAL PRODUCTS, ISOLATED NUTRIENTS, AND DIETARY SUPPLEMENTS) BELONG TO THE PIONEERING CATEGORY OF NATURAL PRODUCTS AND HAVE SHOWN PROTECTIVE ACTION AGAINST AKI. NUTRACEUTICALS HAVE RECENTLY DRAWN ATTENTION BECAUSE OF THEIR ABILITY TO PROVIDE PHYSIOLOGICAL BENEFITS WITH LESS TOXIC EFFECTS. THIS REVIEW EMPHASIZES THE NUTRACEUTICALS THAT EXHIBITED RENOPROTECTION AGAINST AKI AND CAN BE USED EITHER AS MONOTHERAPY OR ADJUVANT WITH CONVENTIONAL THERAPIES TO BOOST THEIR EFFECTIVENESS AND LESSEN THE ADVERSE EFFECTS. ADDITIONALLY, THE STUDY SHEDS LIGHT ON THE APPLICATION OF NETWORK PHARMACOLOGY AS A COST-EFFECTIVE AND TIME-SAVING APPROACH FOR THE THERAPEUTIC TARGET PREDICTION OF NUTRACEUTICALS AGAINST AKI. 2023 13 5950 23 TARGETING THE PROGRESSION OF CHRONIC KIDNEY DISEASE. CHRONIC KIDNEY DISEASE (CKD) IS A DEVASTATING CONDITION THAT IS REACHING EPIDEMIC LEVELS OWING TO THE INCREASING PREVALENCE OF DIABETES MELLITUS, HYPERTENSION AND OBESITY, AS WELL AS AGEING OF THE POPULATION. REGARDLESS OF THE UNDERLYING AETIOLOGY, CKD IS SLOWLY PROGRESSIVE AND LEADS TO IRREVERSIBLE NEPHRON LOSS, END-STAGE RENAL DISEASE AND/OR PREMATURE DEATH. FACTORS THAT CONTRIBUTE TO CKD PROGRESSION INCLUDE PARENCHYMAL CELL LOSS, CHRONIC INFLAMMATION, FIBROSIS AND REDUCED REGENERATIVE CAPACITY OF THE KIDNEY. CURRENT THERAPIES HAVE LIMITED EFFECTIVENESS AND ONLY DELAY DISEASE PROGRESSION, UNDERSCORING THE NEED TO DEVELOP NOVEL THERAPEUTIC APPROACHES TO EITHER STOP OR REVERSE PROGRESSION. PRECLINICAL STUDIES HAVE IDENTIFIED SEVERAL APPROACHES THAT REDUCE FIBROSIS IN EXPERIMENTAL MODELS, INCLUDING TARGETING CYTOKINES, TRANSCRIPTION FACTORS, DEVELOPMENTAL AND SIGNALLING PATHWAYS AND EPIGENETIC MODULATORS, PARTICULARLY MICRORNAS. SOME OF THESE NEPHROPROTECTIVE STRATEGIES ARE NOW BEING TESTED IN CLINICAL TRIALS. LESSONS LEARNED FROM THE FAILURE OF CLINICAL STUDIES OF TRANSFORMING GROWTH FACTOR BETA1 (TGFBETA1) BLOCKADE UNDERSCORE THE NEED FOR ALTERNATIVE APPROACHES TO CKD THERAPY, AS STRATEGIES THAT TARGET A SINGLE PATHOGENIC PROCESS MAY RESULT IN UNEXPECTED NEGATIVE EFFECTS ON SIMULTANEOUSLY OCCURRING PROCESSES. ADDITIONAL PROMISING AVENUES INCLUDE PREVENTING TUBULAR CELL INJURY AND ANTI-FIBROTIC THERAPIES THAT TARGET ACTIVATED MYOFIBROBLASTS, THE MAIN COLLAGEN-PRODUCING CELLS. 2020 14 3345 29 HISTONE DEACETYLASES AS EPIGENETIC TARGETS FOR TREATING PARKINSON'S DISEASE. PARKINSON'S DISEASE (PD) IS A CHRONIC PROGRESSIVE NEURODEGENERATIVE DISEASE THAT IS INCREASINGLY BECOMING A GLOBAL THREAT TO THE HEALTH AND LIFE OF THE ELDERLY WORLDWIDE. ALTHOUGH THERE ARE SOME DRUGS CLINICALLY AVAILABLE FOR TREATING PD, THESE TREATMENTS CAN ONLY ALLEVIATE THE SYMPTOMS OF PD PATIENTS BUT CANNOT COMPLETELY CURE THE DISEASE. THEREFORE, EXPLORING OTHER POTENTIAL MECHANISMS TO DEVELOP MORE EFFECTIVE TREATMENTS THAT CAN MODIFY THE COURSE OF PD IS STILL HIGHLY DESIRABLE. OVER THE LAST TWO DECADES, HISTONE DEACETYLASES, AS AN IMPORTANT GROUP OF EPIGENETIC TARGETS, HAVE ATTRACTED MUCH ATTENTION IN DRUG DISCOVERY. THIS REVIEW FOCUSED ON THE CURRENT KNOWLEDGE ABOUT HISTONE DEACETYLASES INVOLVED IN PD PATHOPHYSIOLOGY AND THEIR INHIBITORS USED IN PD STUDIES. FURTHER PERSPECTIVES RELATED TO SMALL MOLECULES THAT CAN INHIBIT OR DEGRADE HISTONE DEACETYLASES TO TREAT PD WERE ALSO DISCUSSED. 2022 15 3197 29 HDAC INHIBITORS: TARGETS FOR TUMOR THERAPY, IMMUNE MODULATION AND LUNG DISEASES. HISTONE DEACETYLASES (HDACS) ARE ENZYMES THAT PLAY A KEY ROLE IN THE EPIGENETIC REGULATION OF GENE EXPRESSION BY REMODELING CHROMATIN. INHIBITION OF HDACS IS A PROSPECTIVE THERAPEUTIC APPROACH FOR REVERSING EPIGENETIC ALTERATION IN SEVERAL DISEASES. IN PRECLINICAL RESEARCH, NUMEROUS TYPES OF HDAC INHIBITORS WERE DISCOVERED TO EXHIBIT POWERFUL AND SELECTIVE ANTICANCER PROPERTIES. HOWEVER, SUCH RESEARCH HAS REVEALED THAT THE EFFECTS OF HDAC INHIBITORS MAY BE FAR BROADER AND MORE INTRICATE THAN PREVIOUSLY THOUGHT. THIS REVIEW WILL PROVIDE INSIGHT INTO THE HDAC INHIBITORS AND THEIR MECHANISM OF ACTION WITH SPECIAL EMPHASIS ON THE SIGNIFICANCE OF HDAC INHIBITORS IN THE TREATMENT OF CHRONIC OBSTRUCTIVE PULMONARY DISEASE AND LUNG CANCER. NANOCARRIER-MEDIATED HDAC INHIBITOR DELIVERY AND NEW APPROACHES FOR TARGETING HDACS ARE ALSO DISCUSSED. 2022 16 1680 25 DRUG TARGET IDENTIFICATION AND DRUG REPURPOSING IN PSORIASIS THROUGH SYSTEMS BIOLOGY APPROACH, DNN-BASED DTI MODEL AND GENOME-WIDE MICROARRAY DATA. PSORIASIS IS A CHRONIC SKIN DISEASE THAT AFFECTS MILLIONS OF PEOPLE WORLDWIDE. IN 2014, PSORIASIS WAS RECOGNIZED BY THE WORLD HEALTH ORGANIZATION (WHO) AS A SERIOUS NON-COMMUNICABLE DISEASE. IN THIS STUDY, A SYSTEMS BIOLOGY APPROACH WAS USED TO INVESTIGATE THE UNDERLYING PATHOGENIC MECHANISM OF PSORIASIS AND IDENTIFY THE POTENTIAL DRUG TARGETS FOR THERAPEUTIC TREATMENT. THE STUDY INVOLVED THE CONSTRUCTION OF A CANDIDATE GENOME-WIDE GENETIC AND EPIGENETIC NETWORK (GWGEN) THROUGH BIG DATA MINING, FOLLOWED BY THE IDENTIFICATION OF REAL GWGENS OF PSORIATIC AND NON-PSORIATIC USING SYSTEM IDENTIFICATION AND SYSTEM ORDER DETECTION METHODS. CORE GWGENS WERE EXTRACTED FROM REAL GWGENS USING THE PRINCIPAL NETWORK PROJECTION (PNP) METHOD, AND THE CORRESPONDING CORE SIGNALING PATHWAYS WERE ANNOTATED USING THE KYOTO ENCYCLOPEDIA OF GENES AND GENOMES (KEGG) PATHWAYS. COMPARING CORE SIGNALING PATHWAYS OF PSORIASIS AND NON-PSORIASIS AND THEIR DOWNSTREAM CELLULAR DYSFUNCTIONS, STAT3, CEBPB, NF-KAPPAB, AND FOXO1 ARE IDENTIFIED AS SIGNIFICANT BIOMARKERS OF PATHOGENIC MECHANISM AND CONSIDERED AS DRUG TARGETS FOR THE THERAPEUTIC TREATMENT OF PSORIASIS. THEN, A DEEP NEURAL NETWORK (DNN)-BASED DRUG-TARGET INTERACTION (DTI) MODEL WAS TRAINED BY THE DTI DATASET TO PREDICT CANDIDATE MOLECULAR DRUGS. BY CONSIDERING ADEQUATE REGULATORY ABILITY, TOXICITY, AND SENSITIVITY AS DRUG DESIGN SPECIFICATIONS, NARINGIN, BUTEIN, AND BETULINIC ACID WERE SELECTED FROM THE CANDIDATE MOLECULAR DRUGS AND COMBINED INTO POTENTIAL MULTI-MOLECULE DRUGS FOR THE TREATMENT OF PSORIASIS. 2023 17 6687 21 VALIDATION OF THE EPIGENETIC READER BROMODOMAIN-CONTAINING PROTEIN 4 (BRD4) AS A THERAPEUTIC TARGET FOR TREATMENT OF AIRWAY REMODELING. STRUCTURAL REMODELING IS CENTRAL TO THE INITIATION AND PROGRESSION OF MANY CHRONIC LUNG DISEASES, REPRESENTING AN IMPORTANT UNMET NEED. WE EXAMINE THE EVIDENCE SUPPORTING BROMODOMAIN-CONTAINING PROTEIN 4 (BRD4) AS A VALIDATED BIOLOGICAL TARGET FOR TREATMENT OF AIRWAY REMODELING. IN EPITHELIAL CELLS AND FIBROBLASTS, BRD4 SERVES AS A SCAFFOLD FOR CHROMATIN REMODELING COMPLEXES IN ACTIVE SUPER-ENHANCERS. IN RESPONSE TO INFLAMMATORY STIMULI, BRD4 IS REPOSITIONED TO INNATE AND MESENCHYMAL GENES ACTIVATING THEIR PRODUCTION. PROOF-OF-CONCEPT STUDIES SHOW PROMISING BENEFIT OF SELECTIVE BRD4 INHIBITORS IN DISRUPTING EPITHELIAL MESENCHYMAL TRANSITION AND MYOFIBROBLAST TRANSITION IN DIVERSE MODELS OF LUNG INJURY. RECENT IDENTIFICATION OF BIOMARKERS OF BRD4 PROVIDES A BASIS FOR FURTHER DRUG DEVELOPMENT FOR APPLICATION IN VIRAL-INDUCED AIRWAY INFLAMMATION, COPD AND INTERSTITIAL LUNG DISEASES. 2020 18 5925 25 TARGETING EPIGENETIC DNA AND HISTONE MODIFICATIONS TO TREAT KIDNEY DISEASE. EPIGENETICS REFERS TO HERITABLE CHANGES IN GENE EXPRESSION PATTERNS NOT CAUSED BY AN ALTERED NUCLEOTIDE SEQUENCE, AND INCLUDES NON-CODING RNAS AND COVALENT MODIFICATIONS OF DNA AND HISTONES. THIS REVIEW FOCUSES ON FUNCTIONAL EVIDENCE FOR THE INVOLVEMENT OF DNA AND HISTONE EPIGENETIC MODIFICATIONS IN THE PATHOGENESIS OF KIDNEY DISEASE AND THE POTENTIAL THERAPEUTIC IMPLICATIONS. THERE IS EVIDENCE OF ACTIVATION OF EPIGENETIC REGULATORY MECHANISMS IN ACUTE KIDNEY INJURY (AKI), CHRONIC KIDNEY DISEASE (CKD) AND THE AKI-TO-CKD TRANSITION OF DIVERSE AETIOLOGIES, INCLUDING ISCHAEMIA-REPERFUSION INJURY, NEPHROTOXICITY, URETERAL OBSTRUCTION, DIABETES, GLOMERULONEPHRITIS AND POLYCYSTIC KIDNEY DISEASE. A BENEFICIAL IN VIVO EFFECT OVER PRECLINICAL KIDNEY INJURY HAS BEEN REPORTED FOR DRUGS THAT DECREASE DNA METHYLATION BY EITHER INHIBITING DNA METHYLATION (E.G. 5-AZACYTIDINE AND DECITABINE) OR ACTIVATING DNA DEMETHYLATION (E.G. HYDRALAZINE), DECREASE HISTONE METHYLATION BY INHIBITING HISTONE METHYLTRANSFERASES, INCREASE HISTONE ACETYLATION BY INHIBITING HISTONE DEACETYLASES (HDACS, E.G. VALPROIC ACID, VORINOSTAT, ENTINOSTAT), INCREASE HISTONE CROTONYLATION (CROTONATE) OR INTERFERE WITH HISTONE MODIFICATION READERS [E.G. INHIBITS OF BROMODOMAIN AND EXTRA-TERMINAL PROTEINS (BET)]. MOST PRECLINICAL STUDIES ADDRESSED CKD OR THE AKI-TO-CKD TRANSITION. CROTONATE ADMINISTRATION PROTECTED FROM NEPHROTOXIC AKI, BUT EVIDENCE IS CONFLICTING ON DNA METHYLATION INHIBITORS FOR PRECLINICAL AKI. SEVERAL DRUGS TARGETING EPIGENETIC REGULATORS ARE IN CLINICAL DEVELOPMENT OR USE, MOST OF THEM FOR MALIGNANCY. THE BET INHIBITOR APABETALONE IS IN PHASE 3 TRIALS FOR ATHEROSCLEROSIS, KIDNEY FUNCTION BEING A SECONDARY ENDPOINT, BUT NEPHROTOXICITY WAS REPORTED FOR DNA AND HDAC INHIBITORS. WHILE RESEARCH INTO EPIGENETIC MODULATORS MAY PROVIDE NOVEL THERAPIES FOR KIDNEY DISEASE, CAUTION SHOULD BE EXERCISED BASED ON THE CLINICAL NEPHROTOXICITY OF SOME DRUGS. 2018 19 2141 33 EPIGENETIC INTERVENTIONS FOR EPILEPTOGENESIS: A NEW FRONTIER FOR CURING EPILEPSY. THIS ARTICLE HIGHLIGHTS THE EMERGING THERAPEUTIC POTENTIAL OF SPECIFIC EPIGENETIC MODULATORS AS PROMISING ANTIEPILEPTOGENIC OR DISEASE-MODIFYING AGENTS FOR CURING EPILEPSY. CURRENTLY, THERE IS AN UNMET NEED FOR ANTIEPILEPTOGENIC AGENTS THAT TRULY PREVENT THE DEVELOPMENT OF EPILEPSY IN PEOPLE AT RISK. THERE IS STRONG EVIDENCE THAT EPIGENETIC SIGNALING, WHICH EXERTS HIGH FIDELITY REGULATION OF GENE EXPRESSION, PLAYS A CRUCIAL ROLE IN THE PATHOPHYSIOLOGY OF EPILEPTOGENESIS AND CHRONIC EPILEPSY. THESE MODIFICATIONS ARE NOT HARD-WIRED INTO THE GENOME AND ARE CONSTANTLY REPROGRAMMED BY ENVIRONMENTAL INFLUENCES. THE POTENTIAL EPIGENETIC MECHANISMS, INCLUDING HISTONE MODIFICATIONS, DNA METHYLATION, MICRORNA-BASED TRANSCRIPTIONAL CONTROL, AND BROMODOMAIN READING ACTIVITY, CAN DRASTICALLY ALTER THE NEURONAL GENE EXPRESSION PROFILE BY EXERTING THEIR SUMMATIVE EFFECTS IN A COORDINATED FASHION. SUCH AN EPIGENETIC INTERVENTION APPEARS MORE RATIONAL STRATEGY FOR PREVENTING EPILEPSY BECAUSE IT TARGETS THE PRIMARY PATHWAY THAT INITIALLY TRIGGERS THE NUMEROUS DOWNSTREAM CELLULAR AND MOLECULAR EVENTS MEDIATING EPILEPTOGENESIS. AMONG CURRENTLY APPROVED EPIGENETIC DRUGS, THE MAJORITY ARE ANTICANCER DRUGS WITH WELL-ESTABLISHED PROFILES IN CLINICAL TRIALS AND PRACTICE. EVIDENCE FROM PRECLINICAL STUDIES SUPPORTS THE PREMISE THAT THESE DRUGS MAY BE APPLIED TO A WIDE RANGE OF BRAIN DISORDERS. TARGETING HISTONE DEACETYLATION BY INHIBITING HISTONE DEACETYLASE ENZYMES APPEARS TO BE ONE PROMISING EPIGENETIC THERAPY SINCE CERTAIN INHIBITORS HAVE BEEN SHOWN TO PREVENT EPILEPTOGENESIS IN ANIMAL MODELS. HOWEVER, DEVELOPING NEURONAL SPECIFIC EPIGENETIC MODULATORS REQUIRES RATIONAL, PATHOPHYSIOLOGY-BASED OPTIMIZATION TO EFFICIENTLY INTERCEPT THE UPSTREAM PATHWAYS IN EPILEPTOGENESIS. OVERALL, EPIGENETIC AGENTS HAVE BEEN WELL POSITIONED AS NEW FRONTIER TOOLS TOWARDS THE NATIONAL GOAL OF CURING EPILEPSY. 2017 20 5769 25 SPECIFIC EPIGENETIC REGULATORS SERVE AS POTENTIAL THERAPEUTIC TARGETS IN IDIOPATHIC PULMONARY FIBROSIS. IDIOPATHIC PULMONARY FIBROSIS (IPF), A DISORDER OBSERVED MOSTLY IN OLDER HUMAN BEINGS, IS CHARACTERISED BY CHRONIC AND PROGRESSIVE LUNG SCARRING LEADING TO AN IRREVERSIBLE DECLINE IN LUNG FUNCTION. THIS HEALTH CONDITION HAS A DISMAL PROGNOSIS AND THE CURRENTLY AVAILABLE DRUGS ONLY DELAY BUT FAIL TO REVERSE THE PROGRESSION OF LUNG DAMAGE. CONSEQUENTLY, IT BECOMES IMPERATIVE TO DISCOVER IMPROVED THERAPEUTIC COMPOUNDS AND THEIR CELLULAR TARGETS TO CURE IPF. IN THIS REGARD, A NUMBER OF RECENT STUDIES HAVE TARGETED THE EPIGENETIC REGULATION BY HISTONE DEACETYLASES (HDACS) TO DEVELOP AND CATEGORISE ANTIFIBROTIC DRUGS FOR LUNGS. THEREFORE, THIS REVIEW FOCUSES ON HOW ABERRANT EXPRESSION OR ACTIVITY OF CLASSES I, II AND III HDACS ALTER TGF-BETA SIGNALLING TO PROMOTE EVENTS SUCH AS EPITHELIAL-MESENCHYMAL TRANSITION, DIFFERENTIATION OF ACTIVATED FIBROBLASTS INTO MYOFIBROBLASTS, AND EXCESS DEPOSITION OF THE EXTRACELLULAR MATRIX TO PROPEL LUNG FIBROSIS. FURTHER, THIS STUDY DESCRIBES HOW CERTAIN CHEMICAL COMPOUNDS OR DIETARY CHANGES MODULATE DYSREGULATED HDACS TO ATTENUATE FIVE FAULTY TGF-BETA-DEPENDENT PROFIBROTIC PROCESSES, BOTH IN ANIMAL MODELS AND CELL LINES REPLICATING IPF, THEREBY IDENTIFYING PROMISING MEANS TO TREAT THIS LUNG DISORDER. 2022