1 5352 162 RE-ESTABLISHING THE COMPREHENSION OF PHYTOMEDICINE AND NANOMEDICINE IN INFLAMMATION-MEDIATED CANCER SIGNALING. RECENT MOUNTING EVIDENCE HAS REVEALED EXTENSIVE GENETIC HETEROGENEITY WITHIN TUMORS THAT DRIVE PHENOTYPIC VARIATION AFFECTING KEY CANCER PATHWAYS, MAKING CANCER TREATMENT EXTREMELY CHALLENGING. DIVERSE CANCER TYPES DISPLAY RESISTANCE TO TREATMENT AND SHOW PATTERNS OF RELAPSE FOLLOWING THERAPY. THEREFORE, EFFORTS ARE REQUIRED TO ADDRESS TUMOR HETEROGENEITY BY DEVELOPING A BROAD-SPECTRUM THERAPEUTIC APPROACH THAT COMBINES TARGETED THERAPIES. INFLAMMATION HAS BEEN PROGRESSIVELY DOCUMENTED AS A VITAL FACTOR IN TUMOR ADVANCEMENT AND HAS CONSEQUENCES IN EPIGENETIC VARIATIONS THAT SUPPORT TUMOR INSTIGATION, ENCOURAGING ALL THE TUMORIGENESIS PHASES. INCREASED DNA DAMAGE, DISRUPTED DNA REPAIR MECHANISMS, CELLULAR PROLIFERATION, APOPTOSIS, ANGIOGENESIS, AND ITS INCURSION ARE A FEW PRO-CANCEROUS OUTCOMES OF CHRONIC INFLAMMATION. A CLEAR UNDERSTANDING OF THE CELLULAR AND MOLECULAR SIGNALING MECHANISMS OF TUMOR-ENDORSING INFLAMMATION IS NECESSARY FOR FURTHER EXPANSION OF ANTI-CANCER THERAPEUTICS TARGETING THE CROSSTALK BETWEEN TUMOR DEVELOPMENT AND INFLAMMATORY PROCESSES. MULTIPLE INFLAMMATORY SIGNALING PATHWAYS, SUCH AS THE NF-KAPPAB SIGNALING PATHWAY, JAK-STAT SIGNALING PATHWAY, MAPK SIGNALING, PI3K/AKT/MTOR SIGNALING, WNT SIGNALING CASCADE, AND TGF-BETA/SMAD SIGNALING, HAVE BEEN FOUND TO REGULATE INFLAMMATION, WHICH CAN BE MODULATED USING VARIOUS FACTORS SUCH AS SMALL MOLECULE INHIBITORS, PHYTOCHEMICALS, RECOMBINANT CYTOKINES, AND NANOPARTICLES (NPS) IN CONJUGATION TO PHYTOCHEMICALS TO TREAT CANCER. RESEARCHERS HAVE IDENTIFIED MULTIPLE TARGETS TO SPECIFICALLY ALTER INFLAMMATION IN CANCER THERAPY TO RESTRICT MALIGNANT PROGRESSION AND IMPROVE THE EFFICACY OF CANCER THERAPY. SIRNA-AND SHRNA-LOADED NPS HAVE BEEN OBSERVED TO DOWNREGULATE STAT3 SIGNALING PATHWAYS AND HAVE BEEN EMPLOYED IN STUDIES TO TARGET TUMOR MALIGNANCIES. THIS REVIEW HIGHLIGHTS THE PATHWAYS INVOLVED IN THE INTERACTION BETWEEN TUMOR ADVANCEMENT AND INFLAMMATORY PROGRESSION, ALONG WITH THE NOVEL APPROACHES OF NANOTECHNOLOGY-BASED DRUG DELIVERY SYSTEMS CURRENTLY USED TO TARGET INFLAMMATORY SIGNALING PATHWAYS TO COMBAT CANCER. 2022 2 1259 35 CURRENT VIEWS IN CHRONIC OBSTRUCTIVE PULMONARY DISEASE PATHOGENESIS AND MANAGEMENT. CHRONIC OBSTRUCTIVE PULMONARY DISEASE (COPD) IS A PROGRESSIVE LUNG DYSFUNCTION CAUSED MAINLY BY INHALING TOXIC PARTICLES AND CIGARETTE SMOKING (CS). THE CONTINUOUS EXPOSURE TO RUINOUS MOLECULES CAN LEAD TO ABNORMAL INFLAMMATORY RESPONSES, PERMANENT DAMAGES TO THE RESPIRATORY SYSTEM, AND IRREVERSIBLE PATHOLOGICAL CHANGES. OTHER FACTORS, SUCH AS GENETICS AND AGING, INFLUENCE THE DEVELOPMENT OF COPD. IN THE LAST DECADE, ACCUMULATING EVIDENCE SUGGESTED THAT MITOCHONDRIAL ALTERATION, INCLUDING MITOCHONDRIAL DNA DAMAGE, INCREASED MITOCHONDRIAL REACTIVE OXYGEN SPECIES (ROS), ABNORMAL AUTOPHAGY, AND APOPTOSIS, HAVE BEEN IMPLICATED IN THE PATHOGENESIS OF COPD. THE ALTERATION CAN ALSO EXTEND TO EPIGENETICS, NAMELY DNA METHYLATION, HISTONE MODIFICATION, AND NON-CODING RNA. THIS REVIEW WILL DISCUSS THE RECENT PROGRESSIONS IN COPD PATHOLOGY, PATHOPHYSIOLOGY, AND MOLECULAR PATHWAYS. MORE FOCUS WILL BE SHED ON MITOCHONDRIAL AND EPIGENETIC VARIATIONS RELATED TO COPD DEVELOPMENT AND THE ROLE OF NANOMEDICINE AS A POTENTIAL TOOL FOR THE PREVENTION AND TREATMENT OF THIS DISEASE. 2021 3 4589 28 NANOPARTICLES IN THE DIAGNOSIS AND TREATMENT OF VASCULAR AGING AND RELATED DISEASES. AGING-INDUCED ALTERNATIONS OF VASCULATURE STRUCTURES, PHENOTYPES, AND FUNCTIONS ARE KEY IN THE OCCURRENCE AND DEVELOPMENT OF VASCULAR AGING-RELATED DISEASES. MULTIPLE MOLECULAR AND CELLULAR EVENTS, SUCH AS OXIDATIVE STRESS, MITOCHONDRIAL DYSFUNCTION, VASCULAR INFLAMMATION, CELLULAR SENESCENCE, AND EPIGENETIC ALTERATIONS ARE HIGHLY ASSOCIATED WITH VASCULAR AGING PHYSIOPATHOLOGY. ADVANCES IN NANOPARTICLES AND NANOTECHNOLOGY, WHICH CAN REALIZE SENSITIVE DIAGNOSTIC MODALITIES, EFFICIENT MEDICAL TREATMENT, AND BETTER PROGNOSIS AS WELL AS LESS ADVERSE EFFECTS ON NON-TARGET TISSUES, PROVIDE AN AMAZING WINDOW IN THE FIELD OF VASCULAR AGING AND RELATED DISEASES. THROUGHOUT THIS REVIEW, WE PRESENTED CURRENT KNOWLEDGE ON CLASSIFICATION OF NANOPARTICLES AND THE RELATIONSHIP BETWEEN VASCULAR AGING AND RELATED DISEASES. IMPORTANTLY, WE COMPREHENSIVELY SUMMARIZED THE POTENTIAL OF NANOPARTICLES-BASED DIAGNOSTIC AND THERAPEUTIC TECHNIQUES IN VASCULAR AGING AND RELATED DISEASES, INCLUDING CARDIOVASCULAR DISEASES, CEREBROVASCULAR DISEASES, AS WELL AS CHRONIC KIDNEY DISEASES, AND DISCUSSED THE ADVANTAGES AND LIMITATIONS OF THEIR CLINICAL APPLICATIONS. 2022 4 4666 44 NEW INSIGHTS AND OPTIONS INTO THE MECHANISMS AND EFFECTS OF COMBINED TARGETED THERAPY AND IMMUNOTHERAPY IN PROSTATE CANCER. CHRONIC INFLAMMATION IS BELIEVED TO DRIVE PROSTATE CARCINOGENESIS BY PRODUCING REACTIVE OXYGEN SPECIES OR REACTIVE NITROGEN SPECIES TO INDUCE DNA DAMAGE. THIS EFFECT MIGHT SUBSEQUENTLY CAUSE EPIGENETIC AND GENOMIC ALTERATIONS, LEADING TO MALIGNANT TRANSFORMATION. ALTHOUGH ESTABLISHED THERAPEUTIC ADVANCES HAVE EXTENDED OVERALL SURVIVAL, TUMORS IN PATIENTS WITH ADVANCED PROSTATE CANCER ARE PRONE TO METASTASIS, TRANSFORMATION INTO METASTATIC CASTRATION-RESISTANT PROSTATE CANCER, AND THERAPEUTIC RESISTANCE. THE TUMOR MICROENVIRONMENT (TME) OF PROSTATE CANCER IS INVOLVED IN CARCINOGENESIS, INVASION AND DRUG RESISTANCE. A PLETHORA OF PRECLINICAL STUDIES HAVE FOCUSED ON IMMUNE-BASED THERAPIES. UNDERSTANDING THE INTRICATE TME SYSTEM IN PROSTATE CANCER MAY HOLD MUCH PROMISE FOR DEVELOPING NOVEL THERAPIES, DESIGNING COMBINATIONAL THERAPEUTIC STRATEGIES, AND FURTHER OVERCOMING RESISTANCE TO ESTABLISHED TREATMENTS TO IMPROVE THE LIVES OF PROSTATE CANCER PATIENTS. IN THIS REVIEW, WE DISCUSS NONIMMUNE COMPONENTS AND VARIOUS IMMUNE CELLS WITHIN THE TME AND THEIR PUTATIVE ROLES DURING PROSTATE CANCER INITIATION, PROGRESSION, AND METASTASIS. WE ALSO OUTLINE THE UPDATED FUNDAMENTAL RESEARCH FOCUSING ON THERAPEUTIC ADVANCES OF TARGETED THERAPY AS WELL AS COMBINATIONAL OPTIONS FOR PROSTATE CANCER. 2023 5 4954 23 PATHOGENESIS OF CHRONIC OBSTRUCTIVE PULMONARY DISEASE. THE PATHOGENESIS OF CHRONIC OBSTRUCTIVE PULMONARY DISEASE (COPD) ENCOMPASSES A NUMBER OF INJURIOUS PROCESSES, INCLUDING AN ABNORMAL INFLAMMATORY RESPONSE IN THE LUNGS TO INHALED PARTICLES AND GASES. OTHER PROCESSES, SUCH AS FAILURE TO RESOLVE INFLAMMATION, ABNORMAL CELL REPAIR, APOPTOSIS, ABNORMAL CELLULAR MAINTENANCE PROGRAMS, EXTRACELLULAR MATRIX DESTRUCTION (PROTEASE/ANTIPROTEASE IMBALANCE), AND OXIDATIVE STRESS (OXIDANT/ANTIOXIDANT IMBALANCE) ALSO HAVE A ROLE. THE INFLAMMATORY RESPONSES TO THE INHALATION OF ACTIVE AND PASSIVE TOBACCO SMOKE AND URBAN AND RURAL AIR POLLUTION ARE MODIFIED BY GENETIC AND EPIGENETIC FACTORS. THE SUBSEQUENT CHRONIC INFLAMMATORY RESPONSES LEAD TO MUCUS HYPERSECRETION, AIRWAY REMODELING, AND ALVEOLAR DESTRUCTION. THIS ARTICLE PROVIDES AN UPDATE ON THE CELLULAR AND MOLECULAR MECHANISMS OF THESE PROCESSES IN THE PATHOGENESIS OF COPD. 2007 6 5140 29 POTENTIAL REGULATORS OF THE SENESCENCE-ASSOCIATED SECRETORY PHENOTYPE DURING SENESCENCE AND AGING. SENESCENT CELLS EXPRESS AND SECRETE A VARIETY OF EXTRACELLULAR MODULATORS THAT INCLUDE CYTOKINES, CHEMOKINES, PROTEASES, GROWTH FACTORS, AND SOME ENZYMES ASSOCIATED WITH EXTRACELLULAR MATRIX REMODELING, DEFINED AS THE SENESCENCE-ASSOCIATED SECRETORY PHENOTYPE (SASP). SASP REINFORCES SENESCENT CELL CYCLE ARREST, STIMULATES AND RECRUITS IMMUNE CELLS FOR IMMUNE-MEDIATED CLEARANCE OF POTENTIALLY TUMORIGENIC CELLS, LIMITS OR INDUCES FIBROSIS, AND PROMOTES WOUND HEALING AND TISSUE REGENERATION. ON THE OTHER HAND, SASP MEDIATES CHRONIC INFLAMMATION LEADING TO THE DESTRUCTION OF TISSUE STRUCTURE AND FUNCTION AND STIMULATING THE GROWTH AND SURVIVAL OF TUMOR CELLS. SASP IS HIGHLY HETEROGENEOUS AND THE ROLE OF SASP DEPENDS ON THE CONTEXT. THE REGULATION OF SASP OCCURS AT MULTIPLE LEVELS INCLUDING CHROMATIN REMODELING, TRANSCRIPTION, MRNA TRANSLATION, INTRACELLULAR TRAFFICKING, AND SECRETION. SEVERAL SASP MODULATORS HAVE ALREADY BEEN IDENTIFIED SETTING THE STAGE FOR FUTURE RESEARCH ON THEIR CLINICAL APPLICATIONS. IN THIS REVIEW, WE SUMMARIZE IN DETAIL THE POTENTIAL SIGNALING PATHWAYS THAT TRIGGER AND REGULATE SASP PRODUCTION DURING AGING AND SENESCENCE. 2022 7 4380 37 MITOCHONDRIAL DYSFUNCTION AND OXIDATIVE STRESS IN RHEUMATOID ARTHRITIS. CONTROL OF EXCESSIVE MITOCHONDRIAL OXIDATIVE STRESS COULD PROVIDE NEW TARGETS FOR BOTH PREVENTIVE AND THERAPEUTIC INTERVENTIONS IN THE TREATMENT OF CHRONIC INFLAMMATION OR ANY PATHOLOGY THAT DEVELOPS UNDER AN INFLAMMATORY SCENARIO, SUCH AS RHEUMATOID ARTHRITIS (RA). INCREASING EVIDENCE HAS DEMONSTRATED THE ROLE OF MITOCHONDRIAL ALTERATIONS IN AUTOIMMUNE DISEASES MAINLY DUE TO THE INTERPLAY BETWEEN METABOLISM AND INNATE IMMUNITY, BUT ALSO IN THE MODULATION OF INFLAMMATORY RESPONSE OF RESIDENT CELLS, SUCH AS SYNOVIOCYTES. THUS, MITOCHONDRIAL DYSFUNCTION DERIVED FROM SEVERAL DANGER SIGNALS COULD ACTIVATE TRICARBOXYLIC ACID (TCA) DISRUPTION, THEREBY FAVORING A VICIOUS CYCLE OF OXIDATIVE/MITOCHONDRIAL STRESS. MITOCHONDRIAL DYSFUNCTION CAN ACT THROUGH MODULATING INNATE IMMUNITY VIA REDOX-SENSITIVE INFLAMMATORY PATHWAYS OR DIRECT ACTIVATION OF THE INFLAMMASOME. BESIDES, MITOCHONDRIA ALSO HAVE A CENTRAL ROLE IN REGULATING CELL DEATH, WHICH IS DEEPLY ALTERED IN RA. ADDITIONALLY, MULTIPLE EVIDENCE SUGGESTS THAT PATHOLOGICAL PROCESSES IN RA CAN BE SHAPED BY EPIGENETIC MECHANISMS AND THAT IN TURN, MITOCHONDRIA ARE INVOLVED IN EPIGENETIC REGULATION. FINALLY, WE WILL DISCUSS ABOUT THE INVOLVEMENT OF SOME DIETARY COMPONENTS IN THE ONSET AND PROGRESSION OF RA. 2022 8 5507 23 RHEUMATOID ARTHRITIS PROGRESSION MEDIATED BY ACTIVATED SYNOVIAL FIBROBLASTS. RHEUMATOID ARTHRITIS (RA) IS A CHRONIC INFLAMMATORY DISEASE CHARACTERIZED BY SYNOVIAL HYPERPLASIA AND PROGRESSIVE JOINT DESTRUCTION. RHEUMATOID ARTHRITIS SYNOVIAL FIBROBLASTS (RASFS) ARE LEADING CELLS IN JOINT EROSION AND CONTRIBUTE ACTIVELY TO INFLAMMATION. RASFS SHOW AN ACTIVATED PHENOTYPE THAT IS INDEPENDENT OF THE INFLAMMATORY ENVIRONMENT AND REQUIRES THE COMBINATION OF SEVERAL FACTORS. ALTHOUGH NEW ASPECTS REGARDING RASF ACTIVATION VIA MATRIX DEGRADATION PRODUCTS, EPIGENETIC MODIFICATIONS, INFLAMMATORY FACTORS, TOLL-LIKE RECEPTOR (TLR) ACTIVATION AND OTHERS HAVE RECENTLY BEEN UNCOVERED, THE PRIMARY PATHOPHYSIOLOGICAL PROCESSES IN EARLY ARTHRITIS LEADING TO PERMANENT ACTIVATION ARE MOSTLY UNKNOWN. HERE, WE REVIEW NEW FINDINGS REGARDING RASF ACTIVATION AND THEIR ALTERED BEHAVIOR THAT CONTRIBUTE TO MATRIX DESTRUCTION AND INFLAMMATION AS WELL AS THEIR POTENTIAL TO SPREAD RA. 2010 9 5322 31 PULMONARY DISEASES AND AGEING. CHRONIC OBSTRUCTIVE PULMONARY DISEASE (COPD) AND IDIOPATHIC PULMONARY FIBROSIS ARE REGARDED AS A DISEASES OF ACCELERATED LUNG AGEING AND SHOW ALL OF THE HALLMARKS OF AGEING, INCLUDING TELOMERE SHORTENING, CELLULAR SENESCENCE, ACTIVATION OF PI3 KINASE-MTOR SIGNALING, IMPAIRED AUTOPHAGY, MITOCHONDRIAL DYSFUNCTION, STEM CELL EXHAUSTION, EPIGENETIC CHANGES, ABNORMAL MICRORNA PROFILES, IMMUNOSENESCENCE AND A LOW GRADE CHRONIC INFLAMMATION DUE TO SENESCENCE-ASSOCIATED SECRETORY PHENOTYPE (SASP). MANY OF THESE AGEING MECHANISMS ARE DRIVEN BY EXOGENOUS AND ENDOGENOUS OXIDATIVE STRESS. THERE IS ALSO A REDUCTION IN ANTI-AGEING MOLECULES, SUCH AS SIRTUINS AND KLOTHO, WHICH FURTHER ACCELERATE THE AGEING PROCESS. UNDERSTANDING THESE MOLECULAR MECHANISMS HAS IDENTIFIED SEVERAL NOVEL THERAPEUTIC TARGETS AND SEVERAL DRUGS AND DIETARY INTERVENTIONS ARE NOW IN DEVELOPMENT TO TREAT CHRONIC LUNG DISEASE. 2019 10 5916 28 TARGETING AGING PATHWAYS IN CHRONIC OBSTRUCTIVE PULMONARY DISEASE. CHRONIC OBSTRUCTIVE PULMONARY DISEASE (COPD) HAS BECOME A GLOBAL EPIDEMIC AND IS THE THIRD LEADING CAUSE OF DEATH WORLDWIDE. COPD IS CHARACTERIZED BY CHRONIC AIRWAY INFLAMMATION, LOSS OF ALVEOLAR-CAPILLARY UNITS, AND PROGRESSIVE DECLINE IN LUNG FUNCTION. MAJOR RISK FACTORS FOR COPD ARE CIGARETTE SMOKING AND AGING. COPD-ASSOCIATED PATHOMECHANISMS INCLUDE MULTIPLE AGING PATHWAYS SUCH AS TELOMERE ATTRITION, EPIGENETIC ALTERATIONS, ALTERED NUTRIENT SENSING, MITOCHONDRIAL DYSFUNCTION, CELL SENESCENCE, STEM CELL EXHAUSTION AND CHRONIC INFLAMMATION. IN THIS REVIEW, WE WILL HIGHLIGHT THE CURRENT LITERATURE THAT FOCUSES ON THE ROLE OF AGE AND AGING-ASSOCIATED SIGNALING PATHWAYS AS WELL AS THEIR IMPACT ON CURRENT TREATMENT STRATEGIES IN THE PATHOGENESIS OF COPD. FURTHERMORE, WE WILL DISCUSS ESTABLISHED AND EXPERIMENTAL COPD TREATMENTS INCLUDING SENOLYTIC AND ANTI-AGING THERAPIES AND THEIR POTENTIAL USE AS NOVEL TREATMENT STRATEGIES IN COPD. 2020 11 4756 52 NOVEL THERAPEUTIC TARGET(S) FOR PSORIATIC DISEASE. PSORIASIS AND PSORIATIC ARTHRITIS, TOGETHER KNOWN AS PSORIATIC DISEASE, IS HIGHLY PREVALENT CHRONIC RELAPSING INFLAMMATORY DISEASE AFFECTING SKIN, JOINTS OR BOTH AND IS ASSOCIATED WITH SEVERAL COMORBIDITIES SUCH AS CARDIOVASCULAR, METABOLIC, PSYCHIATRIC, RENAL DISEASE ETC. THE ETIOPATHOGENESIS OF PSORIASIS IS COMPLEX AND MAINLY DRIVEN BY ABERRANT IMMUNE RESPONSE OWING TO THE GENETIC SUSCEPTIBILITY AND VARIOUS ENVIRONMENTAL FACTORS SUCH AS TRAUMA, INFECTIONS AND DRUGS. RECENT ADVANCES IN UNDERSTANDING MOLECULAR AND CELLULAR PATHWAYS HAVE IDENTIFIED TUMOR NECROSIS FACTOR-ALPHA (TNF-ALPHA), INTERLEUKIN-17 (IL-17), IL-23, IL-22 AS MAJOR CONTRIBUTORS IN PSORIASIS PATHOGENESIS. ADVANCES IN THE KNOWLEDGE OF PATHOPHYSIOLOGY, THE INTERACTION OF AUTOINFLAMMATION AND CLINICAL PHENOTYPES HAVE LED TO THE DEVELOPMENT OF HIGHLY EFFECTIVE TARGETED THERAPEUTIC AGENTS WHICH INCLUDE TNF-ALPHA, IL-17, IL-23, IL-1 ALPHA/BETA OR IL-36 INHIBITORS OR RECEPTOR BLOCKERS, SMALL MOLECULE DRUGS LIKE PHOSPHODIESTERASE-4 INHIBITORS (APREMILAST), JANUS KINASE (JAK) INHIBITORS, RETINOIC ACID RECEPTOR-RELATED ORPHAN RECEPTOR GAMMAT (RORGAMMAT) INHIBITORS. THESE NOVEL DRUGS HAVE PROMISED THE POTENTIAL OF IMPROVED DISEASE CONTROL. IN RECENT YEARS, THE TRANSITION FROM BIOLOGICS TO BIOSIMILARS ESPECIALLY WITH TNF-ALPHA INHIBITORS HAD SIGNIFICANT IMPACT ON DECREASING HEALTH CARE COST AND INCREASING THERAPEUTIC OPTIONS TO THE PATIENTS. HOWEVER, SELECTION OF RIGHT TREATMENT FOR AN INDIVIDUAL PATIENT STILL REMAINS CHALLENGING. MOREOVER, INTERPLAY BETWEEN DIFFERENT EPIGENETIC MECHANISMS SUCH AS THE DNA METHYLATION, CHROMATIN MODIFICATIONS AND NONCODING RNA REGULATION HAS RECENTLY BEEN STARTED TO BE DECIPHERED. ENZYMES INHIBITORS INVOLVED IN EPIGENETIC PATHWAYS SUCH AS DNA METHYLTRANSFERASES AND HISTONE DEACETYLASES DEMONSTRATED TO RESTORE NORMAL EPIGENETIC PATTERNS IN CLINICAL SETTINGS AND HAVE PROVIDED THE POTENTIAL AS NOVEL THERAPEUTIC TARGETS FOR PSORIASIS. IN THIS REVIEW, WE WILL DISCUSS NOVEL BIOLOGIC AGENTS AND NEWER THERAPEUTIC APPROACHES IN TREATMENT OF PSORIATIC DISEASE. 2022 12 1244 31 CURRENT CONCEPTS ON OXIDATIVE/CARBONYL STRESS, INFLAMMATION AND EPIGENETICS IN PATHOGENESIS OF CHRONIC OBSTRUCTIVE PULMONARY DISEASE. CHRONIC OBSTRUCTIVE PULMONARY DISEASE (COPD) IS A GLOBAL HEALTH PROBLEM. THE CURRENT THERAPIES FOR COPD ARE POORLY EFFECTIVE AND THE MAINSTAYS OF PHARMACOTHERAPY ARE BRONCHODILATORS. A BETTER UNDERSTANDING OF THE PATHOBIOLOGY OF COPD IS CRITICAL FOR THE DEVELOPMENT OF NOVEL THERAPIES. IN THE PRESENT REVIEW, WE HAVE DISCUSSED THE ROLES OF OXIDATIVE/ALDEHYDE STRESS, INFLAMMATION/IMMUNITY, AND CHROMATIN REMODELING IN THE PATHOGENESIS OF COPD. AN IMBALANCE OF OXIDANTS/ANTIOXIDANTS CAUSED BY CIGARETTE SMOKE AND OTHER POLLUTANTS/BIOMASS FUELS PLAYS AN IMPORTANT ROLE IN THE PATHOGENESIS OF COPD BY REGULATING REDOX-SENSITIVE TRANSCRIPTION FACTORS (E.G., NF-KAPPAB), AUTOPHAGY AND UNFOLDED PROTEIN RESPONSE LEADING TO CHRONIC LUNG INFLAMMATORY RESPONSE. CIGARETTE SMOKE ALSO ACTIVATES CANONICAL/ALTERNATIVE NF-KAPPAB PATHWAYS AND THEIR UPSTREAM KINASES LEADING TO SUSTAINED INFLAMMATORY RESPONSE IN LUNGS. RECENTLY, EPIGENETIC REGULATION HAS BEEN SHOWN TO BE CRITICAL FOR THE DEVELOPMENT OF COPD BECAUSE THE EXPRESSION/ACTIVITY OF ENZYMES THAT REGULATE THESE EPIGENETIC MODIFICATIONS HAVE BEEN REPORTED TO BE ABNORMAL IN AIRWAYS OF COPD PATIENTS. HENCE, THE SIGNIFICANT ADVANCES MADE IN UNDERSTANDING THE PATHOPHYSIOLOGY OF COPD AS DESCRIBED HEREIN WILL IDENTIFY NOVEL THERAPEUTIC TARGETS FOR INTERVENTION IN COPD. 2011 13 3688 45 INFLAMMATION: GEARING THE JOURNEY TO CANCER. CHRONIC INFLAMMATION PLAYS A MULTIFACETED ROLE IN CARCINOGENESIS. MOUNTING EVIDENCE FROM PRECLINICAL AND CLINICAL STUDIES SUGGESTS THAT PERSISTENT INFLAMMATION FUNCTIONS AS A DRIVING FORCE IN THE JOURNEY TO CANCER. THE POSSIBLE MECHANISMS BY WHICH INFLAMMATION CAN CONTRIBUTE TO CARCINOGENESIS INCLUDE INDUCTION OF GENOMIC INSTABILITY, ALTERATIONS IN EPIGENETIC EVENTS AND SUBSEQUENT INAPPROPRIATE GENE EXPRESSION, ENHANCED PROLIFERATION OF INITIATED CELLS, RESISTANCE TO APOPTOSIS, AGGRESSIVE TUMOR NEOVASCULARIZATION, INVASION THROUGH TUMOR-ASSOCIATED BASEMENT MEMBRANE AND METASTASIS, ETC. INFLAMMATION-INDUCED REACTIVE OXYGEN AND NITROGEN SPECIES CAUSE DAMAGE TO IMPORTANT CELLULAR COMPONENTS (E.G., DNA, PROTEINS AND LIPIDS), WHICH CAN DIRECTLY OR INDIRECTLY CONTRIBUTE TO MALIGNANT CELL TRANSFORMATION. OVEREXPRESSION, ELEVATED SECRETION, OR ABNORMAL ACTIVATION OF PROINFLAMMATORY MEDIATORS, SUCH AS CYTOKINES, CHEMOKINES, CYCLOOXYGENASE-2, PROSTAGLANDINS, INDUCIBLE NITRIC OXIDE SYNTHASE, AND NITRIC OXIDE, AND A DISTINCT NETWORK OF INTRACELLULAR SIGNALING MOLECULES INCLUDING UPSTREAM KINASES AND TRANSCRIPTION FACTORS FACILITATE TUMOR PROMOTION AND PROGRESSION. WHILE INFLAMMATION PROMOTES DEVELOPMENT OF CANCER, COMPONENTS OF THE TUMOR MICROENVIRONMENT, SUCH AS TUMOR CELLS, STROMAL CELLS IN SURROUNDING TISSUE AND INFILTRATED INFLAMMATORY/IMMUNE CELLS GENERATE AN INTRATUMORAL INFLAMMATORY STATE BY ABERRANT EXPRESSION OR ACTIVATION OF SOME PROINFLAMMATORY MOLECULES. MANY OF PROINFLAMMATORY MEDIATORS, ESPECIALLY CYTOKINES, CHEMOKINES AND PROSTAGLANDINS, TURN ON THE ANGIOGENIC SWITCHES MAINLY CONTROLLED BY VASCULAR ENDOTHELIAL GROWTH FACTOR, THEREBY INDUCING INFLAMMATORY ANGIOGENESIS AND TUMOR CELL-STROMA COMMUNICATION. THIS WILL END UP WITH TUMOR ANGIOGENESIS, METASTASIS AND INVASION. MOREOVER, CELLULAR MICRORNAS ARE EMERGING AS A POTENTIAL LINK BETWEEN INFLAMMATION AND CANCER. THE PRESENT ARTICLE HIGHLIGHTS THE ROLE OF VARIOUS PROINFLAMMATORY MEDIATORS IN CARCINOGENESIS AND THEIR PROMISE AS POTENTIAL TARGETS FOR CHEMOPREVENTION OF INFLAMMATION-ASSOCIATED CARCINOGENESIS. 2008 14 4953 39 PATHOGENESIS OF CHRONIC OBSTRUCTIVE PULMONARY DISEASE (COPD) INDUCED BY CIGARETTE SMOKE. CHRONIC OBSTRUCTIVE PULMONARY DISEASE (COPD) IS A COMMON RESPIRATORY DISEASE THAT IS CHARACTERIZED BY FUNCTIONAL AND STRUCTURAL ALTERATIONS PRIMARILY CAUSED BY LONG-TERM INHALATION OF HARMFUL PARTICLES. CIGARETTE SMOKE (CS) INDUCES AIRWAY INFLAMMATION IN COPD, WHICH IS KNOWN TO PERSIST EVEN AFTER SMOKING CESSATION. THIS REVIEW DISCUSSES THE BASIC PATHOGENESIS OF COPD, WITH PARTICULAR FOCUS ON AN ENDOGENOUS PROTECTIVE MECHANISM AGAINST OXIDATIVE STRESS VIA NRF2, ALTERED IMMUNE RESPONSE OF THE AIRWAY INFLAMMATORY CELLS, EXAGGERATED CELLULAR SENESCENCE OF THE LUNG STRUCTURAL CELLS, AND CELL DEATH WITH EXPANDED INFLAMMATION. RECENTLY, CS-INDUCED MITOCHONDRIA AUTOPHAGY IS REPORTED TO INITIATE PROGRAMMED NECROSIS (NECROPTOSIS). NECROPTOSIS IS A NEW CONCEPT OF CELL DEATH WHICH IS DRIVEN BY A DEFINED MOLECULAR PATHWAY ALONG WITH EXAGGERATED INFLAMMATION. THIS NEW CELL DEATH MECHANISM IS OF IMPORTANCE DUE TO ITS ABILITY TO PRODUCE MORE INFLAMMATORY SUBSTANCES DURING THE PROCESS OF EPITHELIAL DEATH, CONTRIBUTING TO PERSISTENT AIRWAY INFLAMMATION THAT CANNOT BE EXPLAINED BY APOPTOSIS-DERIVED CELL DEATH. AUTOPHAGY IS AN AUTO-CELL COMPONENT DEGRADATION SYSTEM EXECUTED BY LYSOSOMES THAT CONTROLS PROTEIN AND ORGANELLE DEGRADATION FOR SUCCESSFUL HOMEOSTASIS. AS WELL AS IN THE PROCESS OF NECROPTOSIS, AUTOPHAGY IS ALSO OBSERVED DURING CELLULAR SENESCENCE. AGING OF THE LUNGS RESULTS IN THE ACQUISITION OF SENESCENCE-ASSOCIATED SECRETORY PHENOTYPES (SASP) THAT ARE KNOWN TO SECRETE INFLAMMATORY CYTOKINES, CHEMOKINES, GROWTH FACTORS, AND MATRIX METALLOPROTEINASES RESULTING IN CHRONIC LOW-GRADE INFLAMMATION. IN FUTURE RESEARCH, WE INTEND TO HIGHLIGHT THE GENETIC AND EPIGENETIC APPROACHES THAT CAN FACILITATE THE UNDERSTANDING OF DISEASE SUSCEPTIBILITY. THE GOAL OF PRECISION MEDICINE IS TO ESTABLISH MORE ACCURATE DIAGNOSIS AND TREATMENT METHODS BASED ON THE PATIENT-SPECIFIC PATHOGENIC CHARACTERISTICS. THIS REVIEW PROVIDES INSIGHTS INTO CS-INDUCED COPD PATHOGENESIS, WHICH CONTRIBUTES TO A VERY COMPLEX DISEASE. INVESTIGATING THE MECHANISM OF DEVELOPING COPD, ALONG WITH THE AVAILABILITY OF THE PARTICULAR INHIBITORS, WILL LEAD TO NEW THERAPEUTIC APPROACHES IN COPD TREATMENT. 2019 15 1275 33 DAMAGE-ASSOCIATED MOLECULAR PATTERNS IN INFLAMMATORY BOWEL DISEASE: FROM BIOMARKERS TO THERAPEUTIC TARGETS. THE CHRONIC INFLAMMATORY PROCESS UNDERLYING INFLAMMATORY BOWEL DISEASE (IBD), COMPRISING CROHN'S DISEASE AND ULCERATIVE COLITIS, DERIVES FROM THE INTERPLAY OF SEVERAL COMPONENTS IN A GENETICALLY SUSCEPTIBLE HOST. THESE COMPONENTS INCLUDE ENVIRONMENTAL ELEMENTS AND GUT MICROBIOTA A DYSBIOSIS. FOR DECADES, IMMUNE ABNORMALITIES HAVE BEEN INVESTIGATED AS CRITICALLY IMPORTANT IN IBD PATHOGENESIS, AND ATTEMPTS TO DEVELOP EFFECTIVE THERAPIES HAVE PREDOMINANTLY TARGETED THE IMMUNE SYSTEM. NEVERTHELESS, IMMUNE EVENTS REPRESENT ONLY ONE OF THE CONSTITUENTS CONTRIBUTING TO IBD PATHOGENESIS WITHIN THE CONTEXT OF THE COMPLEX CELLULAR AND MOLECULAR NETWORK UNDERLYING CHRONIC INTESTINAL INFLAMMATION. THESE FACTORS NEED TO BE APPRECIATED WITHIN THE MILIEU OF NON-IMMUNE COMPONENTS. DAMAGE-ASSOCIATED MOLECULAR PATTERNS (DAMPS), WHICH ARE ESSENTIALLY ENDOGENOUS STRESS PROTEINS EXPRESSED OR RELEASED AS A RESULT OF CELL OR TISSUE DAMAGE, HAVE BEEN SHOWN TO ACT AS DIRECT PRO-INFLAMMATORY MEDIATORS. EXCESSIVE OR PERSISTENT SIGNALLING MEDIATED BY SUCH MOLECULES CAN UNDERLIE SEVERAL CHRONIC INFLAMMATORY DISORDERS, INCLUDING IBD. THE RELEASE OF ENDOGENOUS DAMPS AMPLIFIES THE INFLAMMATORY RESPONSE DRIVEN BY IMMUNE AND NON-IMMUNE CELLS AND PROMOTES EPIGENETIC REPROGRAMMING IN IBD. THE EFFECTS DETERMINE PATHOLOGIC CHANGES, WHICH MAY SUSTAIN CHRONIC INTESTINAL INFLAMMATION AND ALSO UNDERLIE SPECIFIC DISEASE PHENOTYPES. IN ADDITION TO HIGHLIGHTING THE POTENTIAL USE OF DAMPS SUCH AS CALPROTECTIN AS BIOMARKERS, RESEARCH ON DAMPS MAY REVEAL NOVEL MECHANISTIC ASSOCIATIONS IN IBD PATHOGENESIS AND IS EXPECTED TO UNCOVER PUTATIVE THERAPEUTIC TARGETS. 2018 16 4661 21 NEW ASPECTS OF THE EPIGENETIC REGULATION OF EMT RELATED TO PULMONARY FIBROSIS. PULMONARY FIBROSIS IS A CHRONIC AND PROGRESSIVE FIBROTIC DISEASE THAT RESULTS IN IMPAIRED GAS EXCHANGE, VENTILATION, AND EVENTUAL DEATH. THE PRO-FIBROTIC ENVIRONMENT IS INSTIGATED BY VARIOUS FACTORS, LEADING TO THE TRANSFORMATION OF EPITHELIAL CELLS INTO MYOFIBROBLASTS AND/OR FIBROBLASTS THAT TRIGGER FIBROSIS. EPITHELIAL MESENCHYMAL TRANSITION (EMT) IS A BIOLOGICAL PROCESS THAT PLAYS A CRITICAL ROLE IN THE PATHOGENESIS OF PULMONARY FIBROSIS. EPIGENETIC REGULATION OF TISSUE-STROMAL CROSSTALK INVOLVING DNA METHYLATION, HISTONE MODIFICATIONS, NON-CODING RNA, AND CHROMATIN REMODELING PLAYS A KEY ROLE IN THE CONTROL OF EMT. THE REVIEW INVESTIGATES THE EPIGENETIC REGULATION OF EMT AND ITS SIGNIFICANCE IN PULMONARY FIBROSIS. 2023 17 5309 31 PSORIASIS PATHOGENESIS AND TREATMENT. RESEARCH ON PSORIASIS PATHOGENESIS HAS LARGELY INCREASED KNOWLEDGE ON SKIN BIOLOGY IN GENERAL. IN THE PAST 15 YEARS, BREAKTHROUGHS IN THE UNDERSTANDING OF THE PATHOGENESIS OF PSORIASIS HAVE BEEN TRANSLATED INTO TARGETED AND HIGHLY EFFECTIVE THERAPIES PROVIDING FUNDAMENTAL INSIGHTS INTO THE PATHOGENESIS OF CHRONIC INFLAMMATORY DISEASES WITH A DOMINANT IL-23/TH17 AXIS. THIS REVIEW DISCUSSES THE MECHANISMS INVOLVED IN THE INITIATION AND DEVELOPMENT OF THE DISEASE, AS WELL AS THE THERAPEUTIC OPTIONS THAT HAVE ARISEN FROM THE DISSECTION OF THE INFLAMMATORY PSORIATIC PATHWAYS. OUR DISCUSSION BEGINS BY ADDRESSING THE INFLAMMATORY PATHWAYS AND KEY CELL TYPES INITIATING AND PERPETUATING PSORIATIC INFLAMMATION. NEXT, WE DESCRIBE THE ROLE OF GENETICS, ASSOCIATED EPIGENETIC MECHANISMS, AND THE INTERACTION OF THE SKIN FLORA IN THE PATHOPHYSIOLOGY OF PSORIASIS. FINALLY, WE INCLUDE A COMPREHENSIVE REVIEW OF WELL-ESTABLISHED WIDELY AVAILABLE THERAPIES AND NOVEL TARGETED DRUGS. 2019 18 6053 26 THE CRUCIAL ROLE OF NLRP3 INFLAMMASOME IN VIRAL INFECTION-ASSOCIATED FIBROSING INTERSTITIAL LUNG DISEASES. IDIOPATHIC PULMONARY FIBROSIS (IPF), ONE OF THE MOST COMMON FIBROSING INTERSTITIAL LUNG DISEASES (ILD), IS A CHRONIC-AGE-RELATED RESPIRATORY DISEASE THAT RISES FROM REPEATED MICRO-INJURY OF THE ALVEOLAR EPITHELIUM. ENVIRONMENTAL INFLUENCES, INTRINSIC FACTORS, GENETIC AND EPIGENETIC RISK FACTORS THAT LEAD TO CHRONIC INFLAMMATION MIGHT BE IMPLICATED IN THE DEVELOPMENT OF IPF. THE EXACT TRIGGERS THAT INITIATE THE FIBROTIC RESPONSE IN IPF REMAIN ENIGMATIC, BUT THERE IS NOW INCREASING EVIDENCE SUPPORTING THE ROLE OF CHRONIC EXPOSURE OF VIRAL INFECTION. DURING VIRAL INFECTION, ACTIVATION OF THE NLRP3 INFLAMMASOME BY INTEGRATING MULTIPLE CELLULAR AND MOLECULAR SIGNALING IMPLICATES ROBUST INFLAMMATION, FIBROBLAST PROLIFERATION, ACTIVATION OF MYOFIBROBLAST, MATRIX DEPOSITION, AND ABERRANT EPITHELIAL-MESENCHYMAL FUNCTION. OVERALL, THE CROSSTALK OF THE NLRP3 INFLAMMASOME AND VIRUSES CAN ACTIVATE IMMUNE RESPONSES AND INFLAMMASOME-ASSOCIATED MOLECULES IN THE DEVELOPMENT, PROGRESSION, AND EXACERBATION OF IPF. 2021 19 6799 26 [EPIGENETIC AND CURRENT TREATMENT APPROACHES IN CHRONIC OBSTRUCTIVE PULMONARY DISEASE]. EPIGENETICS MECHANISMS SUCH AS DNA METHYLATION, HISTONE ACETYLATION AND NON-CODING RNAS MAY PLAY ARE A ROLE IN THE PATHOGENESIS OF CHRONIC OBSTRUCTIVE PULMONARY DISEASE (COPD). RESEARCHS WITH REGARD EPIGENETIC IN COPD CAN SHED LIGHT ON PATHOGENES AND MAY BE RELEVANT IN THE DEVELOPMENT OF NOVEL TARGETED THERAPIES. THE AIM OF THIS ARTICLE IS TO REVIEW EPIGENETIC MECHANISMS NEW TREATMENTS APPROACHES IN COPD. 2016 20 2221 28 EPIGENETIC MODIFICATIONS IN RHEUMATOID ARTHRITIS, A REVIEW. RHEUMATOID ARTHRITIS IS AN AUTOIMMUNE DISEASE CHARACTERIZED BY CHRONIC JOINT INFLAMMATION AND PROGRESSIVE DESTRUCTION OF CARTILAGE AND BONE WHICH LEADS TO ULTIMATELY LOSS OF FUNCTION AND PAIN. ACTIVATED SYNOVIAL FIBROBLASTS ARE KEY EFFECTOR CELLS IN THE PATHOGENESIS OF RHEUMATOID ARTHRITIS. IN THE RECENT YEARS, EPIGENETIC CHANGES INCLUDING DNA METHYLATION, HISTONE ACETYLATION AND OTHER HISTONE MODIFICATIONS WERE IDENTIFIED THAT ARE ASSOCIATED WITH AN INTRINSIC ACTIVATION AND THE AGGRESSIVE PHENOTYPE OF THESE CELLS. SO FAR, NO THERAPIES TARGETING RHEUMATOID ARTHRITIS SYNOVIAL FIBROBLASTS EXIST. THIS REVIEW COMPRISES RECENT RESEARCH EFFORTS THAT PROPOSE EPIGENETIC MECHANISMS BEHIND THE ACTIVATION OF RHEUMATOID ARTHRITIS SYNOVIAL FIBROBLASTS AND OTHER CELL TYPES. 2013