Search Results (11,832)

Mitochondria and peroxisomes are critical for hepatic energy metabolism, lipid homeostasis, and reactive oxygen species (ROS) detoxification. In chronic hepatitis C virus (HCV) infection, continuous injury leads to cirrhosis; however, the spatial arrangement and reversibility of organelle dysfunction remain poorly understood. This study aimed to examine the zonal distribution of mitochondrial and peroxisomal injury in liver biopsies and elucidate the role of circulating cell-free mitochondrial DNA (ccfDNA) in patients with chronic HCV and cirrhosis following antiviral therapy. We employed advanced microscopy imaging and transcriptomic analysis of liver biopsies and quantified ccf-mtDNA as a noninvasive marker of mitochondrial injury in the peripheral blood of these patients. Transcriptomic data revealed alterations in mitochondrial and peroxisomal pathway alterations in HCV-infected patients. The imaging data displayed distinct zone-specific patterns of organelle damage. Following viral removal, significant improvement in mitochondrial and peroxisomal protein expression were noted, indicating partial recovery of organelle integrity following viral clearance; whether this reflects true subcellular regeneration or an early stage of a longer recovery process remains to be determined. Additionally, we showed that ccf-mtDNA quantitatively reflects intrahepatic mitochondrial dysfunction, indicating its potential as a diagnostic biomarker in therapeutic approaches. These findings indicate that organelle injury in chronic HCV is spatially patterned, disease severity-dependent, and partially reversible following antiviral therapy. Full article

Background/Objectives: Type 2 diabetes mellitus (T2DM) is a metabolic disease characterized by insulin resistance and chronic low-grade inflammation. Tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), the systemic immune-inflammation index (SII), and the systemic inflammation response index (SIRI) are important markers used to evaluate inflammatory status in T2DM. This study aimed to compare inflammatory and metabolic parameters between patients receiving metformin monotherapy and those receiving metformin plus sodium-glucose cotransporter-2 (SGLT-2) inhibitor combination therapy in patients with newly diagnosed T2DM. Methods: This prospective observational study included 64 treatment-naïve patients with newly diagnosed T2DM. Patients were divided into two groups according to treatment strategy: metformin monotherapy (n = 32) and metformin plus SGLT-2 inhibitor combination therapy (n = 32). TNF-α, IL-6, SII, systemic inflammation response index (SIRI), neutrophil to lymphocyte ratio (NLR), C-reactive protein (CRP), metabolic parameters, and insulin resistance-related indices were evaluated at baseline and after six months. Baseline-adjusted multiple linear regression analyses were performed to assess between-group differences at six months, adjusting for the corresponding baseline biomarker value, baseline HbA1c, age, and sex. Results: After six months of follow-up, significant reductions in TNF-α, IL-6, glycated hemoglobin (HbA1c), and fasting plasma glucose levels were observed in both groups (p < 0.001). In baseline-adjusted analyses, the treatment-group association was not statistically significant for TNF-α (B = −26.80, β = −0.15, p = 0.213), CRP (B = 0.06, β = 0.00, p = 0.977), SII (B = −36.94, β = −0.11, p = 0.441), or NLR (B = −0.20, β = −0.18, p = 0.207). In contrast, the treatment group was associated with a lower six-month IL-6 level (B = −37.87, β = −0.31, p = 0.038; 95% CI, −73.52 to −2.23) after adjustment for baseline IL-6, baseline HbA1c, age, and sex. Serum uric acid levels were lower in the metformin plus SGLT-2 inhibitor group than in the metformin monotherapy group at six months in the unadjusted comparison (p = 0.016). However, the adjusted treatment-group association between treatment group and six-month serum uric acid levels was not statistically significant (B = −0.51, β = −0.20, p = 0.065). Conclusions: In patients with newly diagnosed T2DM, both treatment groups showed significant reductions in TNF-α and IL-6 levels over six months. After adjustment for baseline biomarker levels, baseline HbA1c, age, and sex, no significant incremental association with treatment group was detected for TNF-α, CRP, SII, or NLR, whereas a significant adjusted association was observed for IL-6. Given the observational design and physician-directed treatment allocation, the observed IL-6 association should not be interpreted as evidence of a causal anti-inflammatory effect of SGLT-2 inhibitor therapy. Full article

Background/Objectives: Partially covered duodenal stents rapidly relieve malignant gastric outlet obstruction, but tumor overgrowth restenosis limits durability. We compared six preprocedural inflammatory, nutritional, and immune indices for predicting this outcome in patients with gastric cancer. Methods: We retrospectively analyzed 68 consecutive patients from a prospectively maintained cohort. The primary endpoint was endoscopically or radiologically confirmed tumor overgrowth restenosis. Discrimination was assessed using receiver operating characteristic curves (pairwise DeLong tests with Bonferroni correction) and time-dependent areas under the curve (AUCs) accounting for death as a competing risk. Multivariable cause-specific Cox models were restricted to preprocedural covariates; post-stenting chemotherapy or radiotherapy was examined in time-dependent sensitivity analyses. Results: Technical and clinical success rates were 100% and 94.1%. Seventeen patients (25.0%) developed restenosis at a median of 66 days. The C-reactive protein–albumin–lymphocyte (CALLY) index showed the highest AUC (0.859), followed by the C-reactive protein-to-albumin ratio (CAR; 0.822) and neutrophil-to-lymphocyte ratio (0.774); these three indices did not differ significantly. At an exploratory, internally derived cutoff of ≤0.110, CALLY had 76.5% sensitivity and 84.3% specificity and remained associated with restenosis after adjustment for stenosis site and stent length (adjusted hazard ratio, 12.30; 95% confidence interval, 3.89–38.83; C-index, 0.836), with consistent results in continuous, time-dependent, and tumor-covariate-adjusted analyses. The 180-day cumulative incidence was 52.4% with low CALLY versus 4.3% with high CALLY. Conclusions: C-reactive protein-based indices showed the highest numerical discrimination, although pairwise differences among CALLY, CAR, and NLR were not statistically significant. CALLY is a promising exploratory biomarker for restenosis risk stratification, but its cutoff should not guide clinical decisions until externally validated. Full article

Healthy nutrition is pivotal for the prevention of atherosclerotic cardiovascular disease (ASCVD). In addition to traditional risk factors, other components, like low-grade chronic inflammation, play a pathogenetic role in ASCVD. Research efforts aim to identify low-grade chronic inflammation in patients with established ASCVD and in subjects with low ASCVD risk, and to validate effective nutritional strategies. Here, current nutritional approaches to counteract low-grade chronic inflammation related to ASCVD and possibly mitigated ASCVD risk are discussed, along with related molecular pathways and clinical biomarkers. Low-grade chronic inflammation results from a pro-inflammatory response promoted by large multiprotein complexes (inflammasomes). Within the ASCVD context, the nucleotide-binding oligomerization domain (NOD)-like receptor family pyrin domain-containing protein 3 (NLRP3) inflammasome is the most characterized protein complex, whose activation leads to increased release of downstream effectors (interleukin (IL)-1β, IL-18, IL-6). In the current clinical practice, high-sensitivity C-reactive protein (hsCRP) is used as a circulating biomarker for systemic inflammation, although it is not univocally associated with ASCVD. Some nutritional strategies have been shown effective to mitigate low-grade chronic inflammation and to reduce hsCRP, reducing in some cases ASCVD risk. The Mediterranean Diet and related trials showed that their beneficial effects on cardiovascular disorders could also be related to the anti-inflammatory properties of specific active compounds. Contradictory results have also been obtained, due to lack of standardization and to the specific nature of nutritional studies, which often rely on adherence and compliance of participants. Given the relevance of low-grade chronic inflammation for ASCVD risk, future work will need to increase awareness, identify and validate novel biomarkers, and implement novel effective nutrition strategies. Full article

Background/Objectives: Metabolic syndrome (MetS) is a major global public health concern associated with an increased risk of cardiovascular disease and type 2 diabetes mellitus. Iron metabolism has been implicated, but the storage (ferritin) and functional (soluble transferrin receptor, sTfR) axes are rarely assessed within a single model. We aimed to determine whether both axes are independently associated with glycaemia and MetS and to evaluate their diagnostic value. Materials and Methods: A cross-sectional study was conducted in 297 adults (72.8% women) from Turkestan, Kazakhstan. Hierarchical regression models with sequential adjustment were applied for age, sex, body mass index (BMI), high-sensitivity C-reactive protein (hs-CRP), dietary inflammatory index (DII), HFE H63D genotype, and gamma-glutamyl transferase (GGT). Path analysis and receiver operating characteristic (ROC) analysis were also performed. Results: Ferritin and sTfR were independently associated with fasting glucose (β = 0.27 and 0.73, respectively) and metabolic syndrome (OR = 1.52 and 4.53, respectively). When analyzed separately, neither biomarker reached statistical significance for MetS (ferritin: OR = 1.20, p = 0.140; sTfR: OR = 1.93, p = 0.072). Ferritin demonstrated no discriminatory ability in men (AUC = 0.500, 95% CI 0.370–0.630) and modest discrimination in women (AUC = 0.652, 95% CI 0.571–0.732). GGT accounted for approximately 28% of the ferritin–glucose association in a path-analytic model. Ferritin, GGT, and HbA1c levels increased progressively even among individuals with 0–2 MetS components. Conclusions: Both the storage and functional axes of iron metabolism provide independent information on glycaemic status, but their associations become apparent only when assessed simultaneously. Ferritin alone is not suitable as a diagnostic marker for metabolic syndrome. Full article

Cirsium japonicum Fisch. ex DC. has long been used in traditional East Asian medicine and has attracted increasing attention because of its diverse pharmacological activities, including antioxidant, anti-inflammatory, antifibrotic, metabolic regulatory, and anticancer effects. Although numerous studies have investigated its phytochemical composition and biological activities, current evidence has largely been organized according to individual compounds or disease categories, providing limited insight into the shared molecular mechanisms underlying its pleiotropic actions. In this review, we critically re-evaluate the molecular pharmacology of C. japonicum using an evidence-oriented framework that distinguishes experimentally supported mechanisms from pharmacological associations and emerging hypotheses. Rather than accepting changes in signaling proteins or downstream biomarkers as sufficient evidence of mechanism, we assess the strength of evidence based on reproducibility, pathway-specific interventions, genetic or pharmacological validation, and direct target engagement. Current evidence indicates that nuclear factor erythroid 2-related factor 2 (Nrf2)-mediated antioxidant responses and nuclear factor kappa B (NF-κB)-associated inflammatory responses represent the most consistently observed pathway associations, although direct molecular targets and causal pathway dependency remain insufficiently established. Evidence for AMPK/PI3K-Akt-associated metabolic regulation and TGF-β/Smad-associated antifibrotic responses is comparatively more limited. In contrast, modulation of apoptosis and autophagy is currently supported primarily by indirect or context-dependent observations. We further discuss how multiple phytochemicals converge on interconnected signaling networks regulating oxidative stress, inflammation, metabolism, tissue remodeling, and cell fate, thereby providing a systems-level explanation for the broad therapeutic potential of C. japonicum. Finally, we highlight the need for standardized phytochemical characterization, rigorous target validation, multi-omics integration, and artificial intelligence-assisted systems biology to establish causal molecular mechanisms and accelerate the translational development of evidence-based phytopharmaceuticals. Full article

Background: Acute kidney injury (AKI) is associated with poor outcomes in patients with cirrhosis. However, most studies evaluate AKI as a single clinical entity, whereas predictors of mortality and renal recovery, specifically in non-hepatorenal syndrome AKI (non-HRS-AKI), remain poorly defined. Methods: We performed a retrospective cohort study including consecutive patients with liver cirrhosis admitted with non-HRS-AKI to a multidisciplinary emergency hospital between 1 January 2024 and 31 December 2025. Only variables available at hospital admission were included in the multivariable analyses. Independent predictors of in-hospital mortality and factors associated with incomplete renal recovery in survivors at hospital discharge were identified using multivariable logistic regression. Results: A total of 139 patients were included. Overall, 57 patients (41.0%) died during hospitalization. Among the 82 survivors, complete renal recovery occurred in 35 cases (42.7%), whereas 47 patients (57.3%) had incomplete renal recovery at discharge. Independent predictors of in-hospital mortality were a higher MELD-Na score (adjusted OR 1.16 per 1-point increase, 95% CI 1.07–1.26; p < 0.001), an advanced AKI stage (KDIGO stage 3 vs. stage 1, adjusted OR 6.71, 95% CI 1.73–26.04; p = 0.006), the absence of pre-existing chronic kidney disease (adjusted OR 0.233, 95% CI 0.085–0.644; p = 0.005), and higher admission C-reactive protein (adjusted OR 1.12 per 10 mg/L increase, 95% CI 1.01–1.23; p = 0.029). Factors independently associated with incomplete renal recovery among hospital survivors at hospital discharge were pre-existing heart failure (adjusted OR 3.07, 95% CI 1.10–8.62; p = 0.033) and higher admission C-reactive protein (adjusted OR 1.17 per 10 mg/L increase, 95% CI 1.00–1.34; p = 0.047). Conclusions: In patients with cirrhosis-associated non-HRS-AKI, in-hospital mortality was primarily associated with the severity of liver disease and AKI, whereas incomplete renal recovery at hospital discharge was independently associated with pre-existing heart failure. Admission C-reactive protein was independently associated with both outcomes, supporting the role of systemic inflammation in determining short-term prognosis and suggesting that C-reactive protein may serve as a simple, readily available biomarker for early risk stratification. Full article

Endometrial cancer (EC) is the most common gynecological malignancy in high-income countries. Extracellular vesicles (EVs) are key mediators of intercellular communication and metabolic reprogramming, but their molecular cargo in EC remains poorly characterized. EVs were isolated from four EC cell lines representing Type I and Type II subtypes (AN3CA, ISHIKAWA, HEC1A, and KLE). Untargeted metabolomics was performed by HILIC-LC-MS/MS, proteomics by data-independent acquisition (DIA) mass spectrometry, and multi-omics integration using MetaboAnalyst and OmicsNet. Metabolomic profiling identified 1463 annotated features and revealed significant differences among EC cell lines (PERMANOVA, p = 0.002). Twenty-eight differentially abundant metabolites, including lactic acid, succinic acid, and uric acid, were identified. Proteomic analysis quantified 8513 proteins with subtype-specific expression patterns. Integrated analysis revealed seven significantly enriched pathways, including glycolysis/gluconeogenesis, central carbon metabolism in cancer, and the pentose phosphate pathway. Increased LDHA abundance in metastatic AN3CA-derived EVs was confirmed by Western blot (p = 0.047). EC-derived EVs display subtype- and metastatic-status-specific metabolo-proteomic signatures, with glycolysis, TCA cycle remodeling, and central carbon metabolism as convergent pathway signatures of molecular reprogramming. These findings establish a multi-omics framework for characterizing EV cargo in EC and identify candidate enzyme–metabolite nodes for future biomarker validation in patient-derived specimens. Full article

The gut microbiome is positioned at the center of a hub that contributes to both the physiology and pathology of multiple distant organs. It does this by releasing beneficial signaling molecules that are synthesized by various microbial species. Beneficial metabolites that cross from the gut lumen into the circulation include the short-chain fatty acids (SCFAs), a range of tryptophan metabolites (TRPMs), the major polyamines, and certain secondary bile acids. The SCFAs act on G-protein-coupled receptors (GPRs) and on histone deacetylases (HDACs) and, in so doing, suppress inflammation. Tryptophan metabolites act mainly through the nuclear receptor AhR, enhancing gut barrier and blood–brain barrier integrity. The polyamines stabilize nucleic acids and regulate cell proliferation. The secondary bile acids have varied effects on the liver, brain, and lung. In addition, the microbiome contributes to deleterious cometabolites, such as trimethylamine N-oxide, p-cresyl sulfate, and indoxyl sulfate. We predict that clinical laboratories in the future will assay patient samples for an amalgamation of beneficial and detrimental microbiota metabolites as biomarkers of both health and disease risk. Full article

Background/Objectives: Evaluating noninvasive, accessible ocular and blood-based biomarkers could aid in early risk stratification and disease detection during the preclinical phase of Alzheimer’s disease. This study investigates associations between plasma biomarkers of neurodegeneration and retinal structural and microvasculature parameters in cognitively normal adults with familial or genetic risk factors for Alzheimer’s disease. Methods: Forty-one participants underwent plasma sampling for glial fibrillary acidic protein (GFAP), neurofilament light chain (NfL), amyloid-beta42 (β42), amyloid-β42/40 ratio, and phosphorylated-tau217 (p-tau217), and also underwent optical coherence tomography (OCT) and OCT angiography (OCTA) imaging. Apolipoprotein E genotyping and family history of Alzheimer’s disease were recorded. Generalized estimating equations adjusting for age, sex, race, treated hypertension, Alzheimer’s disease family history, and APOE ε4 carrier status assessed associations between plasma biomarker concentrations and OCT and OCTA measurements. Results: Higher plasma GFAP and NfL concentrations were significantly associated with reduced superficial capillary plexus perfusion density and vessel density on macular OCTA. In additional analyses restricted to participants with plasma biomarker and retinal imaging assessments obtained within 9 months, associations with GFAP remained significant, whereas NfL associations no longer remained significant after correction for multiple comparisons. Conclusions: Retinal OCTA and OCT metrics may reflect general neurovascular aging in cognitively normal individuals with familial or genetic risk factors for Alzheimer’s disease. Full article

Background: Traumatic brain injury (TBI) damages brain tissues and affects the ocular system. Ocular manifestations such as orbital fractures, ocular surface disease, photosensitivity, impaired pupillary response, and retinal damage often co-occur with TBI. Despite established diagnostic criteria, a gap remains, particularly in detection, monitoring, and recovery prediction. Since ocular manifestations co-occur with TBI, they may offer non-invasive means to address this gap. Accordingly, this review evaluates whether TBI-associated ocular manifestations can serve as biomarkers for TBI detection, monitoring, and recovery. Methods: A literature search was conducted across three databases for studies that address ocular manifestations of TBI listed above. Results: Orbital fractures occur in 69%, matching TBI severity. Occult fractures may indicate unseen mild TBI on advanced neuroimaging. Dry eye disease prevalence is inconsistent (15 and 37%). Tear film proteomics show altered inflammatory and repair proteins, though this area remains understudied. Vitreous total tau and neurofilament light chain correlate with brain levels in chronic traumatic encephalopathy. Photosensitivity affects approximately 50% of acute TBI and declines to 14% after three months. NPi-200 pupillometer shows high specificity in triaging acute injury but with low sensitivity. PLR-3000 pupillometer and smartphone applications require further validation. Retinal imaging shows biphasic thickening then progressive thinning, modulated by sex, severity and duration. Conclusions: No single ocular biomarker fulfills all roles. Instead, different markers map into distinct stages of the clinical course. Future research should prioritize molecular markers in the tear film, combined with changes in corneal nerves across different TBI severities. Full article

Diet and lifestyle are modifiable determinants of oxidative balance through their influence on exposure to antioxidant and pro-oxidant factors. The oxidative balance score (OBS) is a composite index that reflects the balance between these exposures, with higher scores indicating a predominance of antioxidant factors. In this exploratory pilot study, we examined three OBSs (nutrient-, food-, and lifestyle-based), as well as their combined versions (nutrient–lifestyle and food–lifestyle), across clinical subgroups and evaluated their associations with biomarkers of oxidative stress, inflammation, lipid metabolism, and liver-related biomarkers. A total of 44 older adults were enrolled and stratified into three subgroups (16 healthy, 14 hypercholesterolemia, and 14 post–myocardial infarction). Each participant completed a questionnaire, a 3-day food record, and underwent blood sampling. OBSs were calculated based on 15 nutrients, nine food groups, and two lifestyle components. Correlations and multiple linear regression analyses were performed to examine associations between OBSs and the following biomarkers: plasma total antioxidant capacity (TEAC and FRAP), C-reactive protein (CRP), HDL cholesterol, alanine aminotransferase (ALT), and aspartate aminotransferase (AST). The nutrient–lifestyle OBS (OBSN-L) was significantly associated with lower ALT and AST (adjusted ALT β = −1.06; p = 0.048; AST β = −0.54; p = 0.034). A similar association was observed for the nutrient OBS (OBSN) (adjusted AST β = −0.64; p = 0.022). No significant associations were observed for TEAC, FRAP, or CRP. Neither the OBSF nor the OBSF-L was associated with any circulating biomarkers. Higher nutrient-based OBSs, with or without lifestyle integration, were independently associated with lower liver transaminase levels in older adults with varying levels of cardiovascular risk. OBSs may help to capture dietary and lifestyle patterns associated with liver-related biomarkers. These exploratory findings warrant confirmation in larger, prospective studies. Full article

Oxidative imbalance can accompany physiologically demanding and environmental transitions in sheep, but its magnitude varies with tissue, production stage, diet, health status, and the biomarkers used. Nuclear factor erythroid 2-related factor 2 (Nrf2; encoded by NFE2L2) coordinates inducible cytoprotective responses through Kelch-like ECH-associated protein 1 (Keap1), antioxidant response elements (AREs), and Keap1-independent regulatory routes. This structured narrative review evaluates whether dietary antioxidants engage Nrf2-related responses in sheep and whether such responses translate into health, productivity, or product-quality benefits. Evidence was classified by model and endpoint. Tier 1 comprised ovine dietary interventions with tissue-level Nrf2-pathway measurements; Tier 2 comprised ovine dietary studies with redox or phenotypic outcomes but no pathway assay; Tiers 3 and 4 comprised other-ruminant and non-ruminant or in vitro mechanistic evidence, respectively. Only rutin in transition-period ewes and a water extract of Artemisia annua in lambs met Tier 1 criteria. Both altered Nrf2-related gene expression, but neither used pathway perturbation, DNA-binding assays, or definitive target-engagement methods; the results therefore indicate association rather than causality. Evidence for tannins, essential oils, vitamins, selenium, carotenoid-rich feeds, and other phytochemicals in sheep is broader for oxidative status and product stability than for Nrf2 activation. Growth, fertility, milk yield, and survival outcomes are heterogeneous and strongly context-dependent. Dietary antioxidants may act through direct radical interception, microbial metabolites, metal chelation, membrane protection, mitochondrial effects, receptor signaling, inflammation control, and, in some settings, Nrf2-related adaptation. Future studies should combine dose–response designs, exposure measurements, multiple redox markers, tissue-specific pathway assays, and causal validation. Accordingly, Nrf2 is a plausible mechanistic framework for sheep nutrition, but current evidence does not support broad causal or productivity claims. Full article

Background/Objectives: Ubiquitin C-terminal hydrolase L1 (UCHL1) exhibits context-dependent roles in various cancers, but its clinical significance and biological functions specifically in colorectal cancer (CRC) remain incompletely understood. Methods: We systematically evaluated UCHL1 expression, clinicopathological associations, prognostic value, and immunological role in CRC using multiple public databases (TCGA, GTEx, UALCAN, GEPIA2, GSCA, and ENCORI) combined with immunohistochemical validation on a tissue microarray containing 80 paired CRC and adjacent normal tissues. Functional enrichment was assessed using ssGSEA, and immune cell infiltration was analyzed using the immunedeconv R package. The immunotherapy response was evaluated using the TIDE algorithm. Results: UCHL1 mRNA and protein levels were significantly downregulated in CRC tissues compared with normal tissues. Paradoxically, high UCHL1 expression was significantly associated with advanced T stage, N stage, TNM stage, and poor overall and disease-free survival. ssGSEA revealed positive associations with multiple aspects of oncogenic pathways, including tumor inflammation signature, tumor proliferation signature, epithelial–mesenchymal transition markers, extracellular matrix-related genes, angiogenesis, apoptosis, and G2M checkpoint regulation. Notably, UCHL1 expression was positively correlated with computationally estimated infiltration of macrophages, CD4⁺ T cells, and CD8⁺ T cells, and with elevated expression of immune checkpoint genes, as well as higher TIDE scores. These correlative findings suggest a potential association with immunotherapy-related pathways that warrants further investigation. Conclusions: UCHL1 is downregulated in CRC, but its elevated expression is associated with aggressive disease and poor prognosis. It is implicated in multiple oncogenic pathways and may contribute to an immunosuppressive tumor microenvironment, suggesting its potential as a candidate prognostic biomarker that warrants further functional investigation. Full article

Background: Myocardial infarction (MI) remains a leading cause of morbidity and mortality despite major advances in reperfusion and secondary prevention. Inflammation contributes throughout the MI continuum, from atherosclerotic plaque development and destabilization to myocardial injury, adverse ventricular remodeling, and recurrent cardiovascular events. Objective: This narrative review summarizes current evidence on inflammation across the MI continuum, focusing on inflammatory biomarkers, cardiovascular imaging, residual inflammatory risk, and emerging anti-inflammatory therapies. Methods: We reviewed current evidence on the pathophysiological and clinical relevance of inflammation in MI, with particular emphasis on circulating biomarkers, multimodality imaging, and inflammation-targeted therapeutic strategies. Results: High-sensitivity C-reactive protein remains the best-established biomarker of residual inflammatory risk, while interleukin-6, myeloperoxidase, suPAR, and GlycA provide complementary information. Advanced imaging, including coronary computed tomography-derived perivascular fat attenuation index, cardiac magnetic resonance, and positron emission tomography, may further characterize vascular and myocardial inflammation. Clinical trials support inflammation as a potentially modifiable component of cardiovascular risk; however, therapeutic benefit has been inconsistent across inflammatory targets, agents, and clinical settings. Canakinumab and low-dose colchicine have demonstrated cardiovascular benefit in selected secondary-prevention populations, although recent neutral trials highlight heterogeneity across clinical settings. Similarly, IL-6-targeted strategies have yielded mixed results, with the neutral ZEUS trial underscoring that biomarker reduction does not necessarily translate into cardiovascular benefit, while NLRP3-targeted approaches remain investigational. Conclusions: Integrating inflammatory biomarkers, multimodality imaging, and targeted therapies may improve risk stratification and support personalized secondary prevention. Further evidence is needed to define optimal patient selection and determine whether biomarker- or imaging-guided anti-inflammatory strategies improve clinical outcomes. Full article