Search Results (377)

Background/Objectives: Psoriasis is a systemic immune-mediated inflammatory disease associated with endothelial dysfunction and cardiovascular risk. This study evaluated relationships among clinical severity, cytokine activity, systemic vascular resistance, and skin microvascular reactivity in chronic plaque psoriasis before and after therapy. Methods: In this prospective longitudinal study, 34 patients with chronic plaque psoriasis and 19 matched controls were assessed. Patients were examined at baseline and after 12 months of clinically indicated systemic therapy. Psoriasis Area and Severity Index (PASI), serum IL-17A, IL-22, TNF-α, IL-12(p40), IL-10, VEGF-A, total peripheral resistance, and laser Doppler flowmetry post-occlusive reactive hyperemia indices were analysed. Results: PASI decreased markedly after therapy, from 20.6 ± 7.7 to 4.1 ± 5.3, with excellent discrimination between pre- and post-treatment states. IL-17A, IL-22, and IL-12(p40) decreased significantly, while TNF-α remained associated with disease severity. Total peripheral resistance and delayed psoriatic-skin hyperemia persisted and correlated with inflammatory/angiogenic markers, particularly IL-12(p40) and VEGF-A. Conclusions: Long-term therapy improves clinical and cytokine profiles in psoriasis, but vascular dysfunction may persist despite cutaneous improvement. Integrated cytokine–vascular assessment may complement PASI for evaluating systemic inflammatory burden and cardiovascular risk. Full article

Background: Perioperative cardiovascular complications remain a major concern in patients undergoing noncardiac surgery. Coronary computed tomography (CT)-based imaging, including coronary artery calcium (CAC) scoring, coronary CT angiography (CCTA), and CT-derived fractional flow reserve (CT-FFR), enables noninvasive assessment of coronary plaque burden, anatomic stenosis, and functional ischemia. However, the comparative prognostic value of these CT-based imaging markers for predicting perioperative major adverse cardiac events (MACE) has not been systematically evaluated. Methods: We performed a systematic review and meta-analysis of studies evaluating CT-based coronary imaging before noncardiac surgery. PubMed, Embase, and Cochrane CENTRAL were searched from inception through December 2025. Studies were included if they assessed CAC, CCTA, or CT-FFR and reported perioperative MACE. Risk of bias was independently assessed by two reviewers using the Quality In Prognosis Studies (QUIPS) tool. Pooled effect estimates were calculated using a random-effects model. The CT-FFR analysis was pre-specified as exploratory given the limited number of eligible studies. Results: A total of 13 studies including 10,100 patients undergoing noncardiac surgery were included in the systematic review, and 9 studies were eligible for quantitative meta-analysis. Obstructive coronary artery disease detected by CCTA was strongly associated with perioperative MACE (pooled odds ratio [OR] 7.18, 95% confidence interval [CI] 3.89–13.25). CAC burden was also significantly associated with perioperative cardiac risk (pooled OR 2.48, 95% CI 1.76–3.50). One study evaluating CT-FFR demonstrated a strong association between CT-FFR-defined ischemia and perioperative events (OR 10.77, 95% CI 4.64–25.02). These findings suggest that different CT-based imaging markers provide complementary prognostic information, with anatomic and functional assessment offering higher point estimates than plaque burden scoring. Conclusions: CT-based coronary imaging markers are significantly associated with perioperative MACE in patients undergoing noncardiac surgery. CAC burden and obstructive CAD detected on CCTA demonstrated consistent prognostic associations with perioperative cardiovascular events across multiple studies. CT-FFR showed a strong exploratory signal in a single eligible study, suggesting a potential additional role for functional ischemia assessment, although further validation in larger prospective cohorts is required. CT-based coronary imaging may therefore provide valuable complementary information for perioperative cardiovascular risk stratification. Full article

Background/Objectives: UNet-based models dominate medical image segmentation. Transformers have been added as an internal variant to these UNet-based architectures to improve feature learning. However, they have limitations in generalization and computational efficiency. Motivated by this idea, we have designed a two-stage novel hybrid segmentation framework, where tuners are added in cascade to the base architectures. Methods: Three sets of base UNets were designed, namely: B1: UNet1p, B2: UNet2p, and B3:UNet3p, and four sets of transformer-based tuners were designed, namely: T1:Transformer-augmented UNet, T2: Attention-guided UNet, T3: Swin Transformer-based UNet, and T4: Pyramid-based network, leading to 12 fused systems that combine three base UNets and four Tuners, namely: F1: B1 + T1, F2: B1 + T2, F3: B1 + T3, F4: B1 + T4; F5: B2 + T1, F6: B2 + T2, F7: B2 + T3, F8: B2 + T4, F9: B3 + T1, F10: B3 + T2, F11: B3 + T3, F12: B3 + T4. Results: The two-hybrid segmentation models are more effective and reliable than the single-stage UNet architecture. B3 + T4 achieved a Dice of 94.14% and Jaccard of 88.7%, surpassing prior baselines by 4.2% and 6.8%. It reduced cIMTE to 0.014 mm, a 36% improvement and the lowest reported to date, with cLIE and cMAE errors lowered by 40%. Conclusions: All 12 hybrid automated transformer-based models are highly accurate and reliable for wall segmentation in carotid ultrasound; they are a powerful paradigm for cardiovascular risk. Full article

Background: Accurate segmentation of calcified plaques in coronary computed tomography angiography (CCTA) images is critical for reliable assessment of coronary atherosclerotic burden and for supporting interpretation of luminal stenosis, yet it remains a challenging task due to annotation inconsistencies, blooming artifacts and low contrast at lesion boundaries. These limitations may affect both automated model performance and the clinical trustworthiness of AI systems. This study explores the impact of annotation refinement on segmentation performance and model explainability, as well as the influence of representation learning on explanation quality. Methods: We trained a deep convolutional neural network to segment calcified plaques in coronary arteries using a dataset of expert-labeled CT slices. Initial training on radiologist-provided annotations yielded suboptimal results. To address this, annotations were manually revised and validated by radiologists. In addition to a standard ImageNet-pretrained model, we evaluated a self-supervised representation learning approach using DINOv2. Grad-CAM was used to generate visual explanations for model predictions before and after annotation refinement. Results: Models trained with refined annotations achieved notably improved segmentation accuracy, with clearer delineation of calcified regions. Grad-CAM localization analysis demonstrated improved concentration of model attention within plaque and vessel regions. Furthermore, models incorporating DINOv2 representations produced more spatially coherent attention maps, with improved anatomical localization consistent with coronary vessel regions and reduced off-target activations, as qualitatively confirmed by expert radiologists. Conclusions: Our findings emphasize the importance of high-quality, validated annotations in developing accurate and interpretable AI models for medical imaging. In addition, the results suggest that representation learning influences the reliability and clinical relevance of explainability outputs. The combination of manual annotation refinement, expert validation, and improved feature representations provides a practical workflow for human-in-the-loop AI development in cardiovascular imaging. This study demonstrates that annotation quality is a critical and often underestimated determinant of XAI reliability, and suggests that explainability methods can serve as feedback tools for iterative, clinician-guided dataset curation in cardiovascular imaging. Full article

Matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPs) regulate extracellular matrix remodeling and contribute to the pathogenesis of coronary artery disease (CAD). This study examined the associations between MMP-2, MMP-9, and TIMP-3 and coronary atherosclerotic burden and cardiac function among smokers and non-smokers across the CAD spectrum. A total of 180 male participants were enrolled and divided into six groups (n = 30 per group): acute coronary syndrome (ACS) smokers, ACS non-smokers, chronic coronary syndrome (CCS) smokers, CCS non-smokers, control smokers, and control non-smokers. Serum MMP-2, MMP-9, and TIMP-3 levels were measured using ELISA. Coronary artery plaque severity was assessed using the Gensini score, while cardiac function was evaluated by echocardiography. MMP-9 and TIMP-3 levels were significantly higher in CCS patients than in controls, regardless of smoking status. MMP-9 showed significant positive correlations with the Gensini score in smokers (r = 0.556, p < 0.001) and non-smokers (r = 0.596, p < 0.001) and remained independently associated with coronary plaque severity in both groups. TIMP-3 was independently associated with the Gensini score only in non-smokers (B = 0.667, p = 0.031). Higher MMP-9 levels were independently associated with reduced left ventricular ejection fraction and adverse diastolic parameters. Overall, MMP-9 was independently associated with coronary atherosclerotic burden and cardiac dysfunction, supporting its potential as a biomarker of CAD severity. ACS, rather than smoking status, appeared to have a greater influence on cardiac dysfunction. Full article

Cold-inducible RNA-binding protein (CIRP/CIRBP) is recognized as an extracellular damage-associated molecular pattern. However, its relationship to endothelial redox-inflammatory injury in atherosclerosis remains poorly characterized. Here, we explored the associations among CIRP, endothelial dysfunction, and TLR4-/SIRT6-related changes. In high-fat diet (HFD)-fed ApoE^−/− mice, circulating CIRP was elevated and positively correlated with atherosclerotic plaque burden. This increase coincided with systemic redox imbalance, impaired NO/eNOS activity, and vascular inflammation. In HUVECs, CIRP exposure reduced cell viability and impaired NO/eNOS function. These effects were accompanied by increased ROS accumulation and MDA content, together with reduced GSH-Px activity. CIRP also increased inflammatory cytokine production, NF-κB p65 phosphorylation, and THP-1 adhesion. At the molecular level, CIRP reduced SIRT6 expression. Overexpression of SIRT6 attenuated CIRP-induced endothelial injury, oxidative stress, and NO/eNOS dysfunction. CIRP also increased TLR4 expression. Accordingly, pharmacological TLR4 inhibition with TAK-242 attenuated CIRP-associated endothelial injury and partially restored SIRT6 expression and protein stability. Conversely, SIRT6 silencing weakened the protective effects of TAK-242. In addition, CIRP exposure was accompanied by increased overall eNOS acetylation. This increase was attenuated by TAK-242 and further enhanced by SIRT6 silencing. Exploratory cross-context transcriptomic analysis identified overlapping inflammatory and oxidative stress-related signatures. Representative antioxidant-related changes were further examined in CIRP-treated HUVECs through assessment of GPX4 and CAT mRNA expression and CAT activity. Finally, in a preliminary clinical cohort, serum CIRP levels were higher in patients with coronary heart disease and were positively associated with Gensini score, including selected exploratory multivariable models. Overall, these findings provide preliminary evidence that CIRP is associated with redox-inflammatory endothelial injury. The results are also consistent with the possible involvement of TLR4-/SIRT6-related signaling. These observations should be interpreted cautiously because of the relatively high CIRP concentration used in vitro, the cross-context transcriptomic comparison, and the small clinical cohort. Full article

Background and Objectives: Despite the presence of atherosclerosis risk factors and symptoms associated with occlusive atherosclerotic cardiovascular disease (ASCVD), up to 30% of individuals do not present significant atherosclerotic lesions at the point of diagnostic evaluation. Those in whom ASCVD was ruled out once might be believed to be at low risk of future major cerebral and cardiac events (MACCEs). Despite this, they might still have some residual risk for MACCEs. Therefore, in the present study we aimed to evaluate risk factors for atherosclerosis progression to the stage of occlusive arterial disease in patients with cardiovascular risk factors but initially free from significant ASCVD. Materials and Methods: Between March 2012 and February 2014, a total of 686 consecutive patients presenting with clinical suspicion of significant coronary artery disease were evaluated. The actual status of atherosclerosis burden was verified in four major arterial territories (coronary, carotid, renal, lower limb arteries) with the use of angiography, computed tomography and ultrasonography. For the present study purpose, 188 (27.4%) patients were enrolled, in whom significant ASCVD (in any of the examined territories) was ruled out. In all patients, the incidence and severity of atherosclerotic risk factors, carotid intima–media complex thickness (CIMT) and carotid plaque presence were evaluated during first hospital admission. A ten-year follow-up period for a composite endpoint of MACCEs was included. Univariate and multivariate Cox proportional hazard analyses with the Simon–Makuch method for new-onset type 2 diabetes mellitus (T2DM) were performed for MACCEs. Results: MACCEs occurred in 30 (16%) of 188 patients, including 5 cardiovascular deaths, 19 non-fatal myocardial infarctions, and 6 non-fatal ischemic strokes, in a median of 48 (Q1; Q3: 25; 86) months. Univariate Cox proportional hazard analysis revealed that individuals who presented with baseline LDL cholesterol > 3.2 mmol/L, CIMT > 1 mm, carotid plaque, or experienced new-onset T2DM were predisposed to MACCE with hazard ratios (HRs) of 3.21 (p = 0.003), 3.82 (p = 0.001), 5.41 (p < 0.001), and 36.89 (p < 0.001), respectively. In multivariate Cox analysis, its associations with MACCEs were retained (HRs between 2.19 and 21.47), respectively. Conclusions: Our findings support the need for continued risk factor optimization despite the initial exclusion of obstructive ASCVD. In this study, we identified new-onset T2DM, initial LDL cholesterol, and the presence of subclinical atherosclerosis as risk factors for MACCEs. Full article

Bacteriophages are being revisited as programmable platforms for therapy, diagnostics, and biocontrol. Their value, however, depends on the setting. Therapeutic phages must do more than lyse bacteria in vitro: they need to reach infection sites, persist long enough to act, reduce bacterial burden, and limit resistance under clinically relevant conditions. Diagnostic platforms are judged by another standard, including sensitivity, specificity, matrix tolerance, and stable signal readout. Food, agricultural, and environmental applications instead rely on formulation stability, host specificity, scalable delivery, and ecological safety. This review summarizes the biological and engineering principles that support phage-based platforms, and then evaluates therapeutic, diagnostic, and nonclinical uses through an application-specific evidence framework. For therapy, we focus on evidence hierarchy, active phage exposure, immune clearance, persistence, infection spread, and host-resistance-bypass phenotypes. Recent studies on high-persistence and hyper-aggressive phages suggest that dissemination, plaque expansion, and resistance-bypass behavior should be considered during early candidate selection. Phage cocktails, antibiotic combinations, and engineered phages remain useful, but they should be treated as adaptive strategies rather than universal solutions. Overall, phage technologies require validation frameworks that link biological function with manufacturing quality, regulatory feasibility, and meaningful clinical or environmental endpoints. Full article

Background/Objectives: Cardiovascular risk (CVR) prediction using SCORE2 may incompletely capture the burden of subclinical atherosclerosis in patients with chronic inflammatory conditions. Identifying simple, accessible markers to refine risk stratification remains an unmet need. This study aimed to evaluate whether serum urate improves detection of subclinical atherosclerosis beyond SCORE2 in a psoriatic arthritis cohort. Methods: We conducted a cross-sectional study including 250 patients with psoriatic arthritis fulfilling CASPAR criteria. Vascular assessment comprised carotid and femoral ultrasound and abdominal radiography. Atherosclerotic plaque was defined according to Mannheim criteria. The main outcomes were global plaque (≥1 vascular territory) and extended plaque (≥2 territories). Multivariable logistic regression adjusted for SCORE2 categories assessed independent associations. Incremental value was evaluated using decision curve analysis (DCA), category-free net reclassification improvement (cfNRI), and integrated discrimination improvement (IDI). Results: Hyperuricemia prevalence was 21.6%. Patients with hyperuricemia showed a higher prevalence of global plaque (88.9% vs. 62.8%, p < 0.001). After adjustment for SCORE2, serum urate was independently associated with global plaque (OR 4.23, 95% CI 1.26–14.2). Notably, 64.3% of patients classified as low–moderate risk already exhibited plaque. In the 50–69-year subgroup, adding serum urate improved reclassification (cfNRI +0.60; IDI +0.031) and was associated with higher net clinical benefit across decision thresholds. The combined model (SCORE2+HU+cIMT) achieved the highest curves, although with limited incremental gain over HU alone. Conclusions: SCORE2 categories showed substantial discordance with imaging-defined subclinical atherosclerotic burden in this population. Serum urate, an inexpensive and widely available marker, may help refine cardiovascular risk stratification and identify patients who could benefit from further vascular assessment. Full article

Background/Objectives: Alzheimer’s Disease (AD) and vascular dementia contribute up to ~75% of dementia cases, as determined via autopsy. AD arises in part due to the buildup of aberrant proteins (amyloid beta (Aβ) and Tau); vascular dementia is caused by reduced cerebral blood flow. Each dementia mechanisms damages brain. Bobola et al. found that their low-intensity focused ultrasound (FUS) protocol applied to the brains of the 5XFAD mouse model of AD reduced Aβ by 50% through activation of microglia. Eguchi et al. found that their own FUS protocol applied to the brains of the same mouse model reduced Aβ by 15% and increased cerebral blood flow by 50% through an increase in endothelial nitric oxide synthase (eNOS). Here, we sought to test a combined version of those two FUS protocols, expecting both a decrease in Aβ burden and an increase in eNOS. Methods: Using a diagnostic ultrasound probe, we applied our combined FUS protocol primarily to the left hippocampus of anesthetized 5XFAD mice, for an hour a day, for three days for younger mice and for five days for older mice. On day three or five, respectively, we harvested their brains and performed histological analysis to assess Aβ burden, microglial activation and their co-localization with Aβ, as well as the burden of eNOS within neuronal nuclei (here called intra-neuronal eNOS) and outside of neurons. Results: Relative to untreated mice, the treated younger mice had more activated microglia co-localized with Aβ and reduced Aβ burden for large plaques, as well as no change in each measure of eNOS. In contrast, the treated older AD mice had no change in activated microglia co-localized with Aβ, and no change in Aβ burden. However, relative to untreated older AD mice, FUS decreased total and extra-neuronal eNOS and increased intra-neuronal eNOS. Conclusions: The ability of our FUS protocol to reduce Aβ burden and alter the eNOS distribution depends critically upon the age of the AD mice (more Aβ plaques for a comparable number of microglia for older mice relative to younger mice) and duration of the treatment. The observed decrease in extra-neuronal eNOS distribution in older AD mice caused by FUS raises the concern that our protocol may increase ischemia, while the increase in intra-neuronal eNOS may counteract that effect via protection of synaptic function. These findings also identify two candidate therapeutic windows for our FUS treatment protocol, each requiring more research before translation to humans. One window is early intervention to maximize Aβ plaque removal via activation of microglia. The second is later intervention to protect synaptic function if it is possible to mitigate the potential ischemic risk caused by the differential effects of FUS on eNOS. Full article

Background: Early childhood caries (ECC) is a biofilm-mediated and sugar-driven disease associated with local and systemic inflammatory responses. This study evaluated serum Interleukin-6 (IL-6) and IL-10 concentrations, hematologic inflammatory indices, and oral inflammatory parameters in children with ECC compared with caries-free sibling controls. Methods: This sibling-controlled case–control study included 155 children aged 2.5–6 years, comprising 120 children with active ECC and 35 caries-free siblings. Serum IL-6 and IL-10 concentrations were measured using enzyme-linked immunosorbent assay (ELISA). Complete blood count parameters and derived inflammatory indices, including neutrophil-to-lymphocyte ratio (NLR), lymphocyte-to-monocyte ratio (LMR), systemic immune-inflammation index (SII), systemic inflammation response index (SIRI), aggregate index of systemic inflammation (AISI), cumulative inflammatory index (IIC), and mean corpuscular volume-to-lymphocyte ratio (MCVL), were calculated. Plaque Index (PI) and Gingival Index (GI) were recorded in children with ECC. Group comparisons, correlation analyses, ROC analysis, and multivariable logistic regression were performed. Results: Children with ECC exhibited significantly higher serum IL-6 and IL-10 concentrations than sibling controls. MCVL values were significantly lower in the ECC group, whereas several inflammatory indices indicated an increased systemic inflammatory burden. Stratification by PI tertiles showed progressively higher values for WBC, NEU, NLR, SII, SIRI, AISI, and IIC as plaque accumulation increased (all p < 0.05). PI was strongly correlated with GI (r = 0.811, p < 0.001) and moderately correlated with NLR (r = 0.536), SII (r = 0.536), SIRI (r = 0.654), AISI (r = 0.648), and IIC (r = 0.546) (all p < 0.01). Serum IL-6 and IL-10 were strongly correlated (r = 0.804, p < 0.001) but not with PI or GI. ROC analysis demonstrated moderate discriminatory performance for IL-6 (AUC = 0.701) and IL-10 (AUC = 0.696). Age- and sex-adjusted multivariable logistic regression demonstrated that elevated IL-6 concentrations (adjusted OR = 1.36; 95% CI, 1.10–1.68; p = 0.005) remained independently associated with ECC, whereas increasing MCVL values (adjusted OR = 0.92; 95% CI, 0.86–0.98; p = 0.010) were associated with reduced odds of ECC. Conclusions: ECC is associated with systemic cytokine alterations and increased hematologic inflammatory burden. While IL-6 and IL-10 distinguish children with ECC from sibling controls, plaque accumulation severity is better reflected by composite hematologic inflammatory indices than by isolated cytokine concentrations. IL-6 and MCVL may be promising adjunctive biomarkers for ECC. Full article

Physical activity wields a positive influence on atherosclerosis-related risk factors; however, the effects of high-intensity training on cardiovascular (CV) health are not unequivocal. The prevalence of coronary artery disease (CAD) in middle-aged sportsmen varies from 13.7% to 71%. Despite increased longevity and lower overall CV risk, CAD remains a serious problem in athletes, being responsible for the majority of sudden cardiac death (SCD) cases in sportsmen over 30 years. Endurance athletes engaging in high-intensity training are burdened with increased coronary artery calcification (CAC) of multifactorial pathophysiology, embracing i.a. wall shear stress, excessive reactive oxygen species, inflammatory mediators and increased levels of parathyroid hormone. Thanks to improved coronary vasodilatory capacity and coronary collateralization, sportsmen are rarely affected by hemodynamically significant coronary artery stenosis, and the atherosclerotic plaques are mostly of benign, calcified morphology. The basic screening should embrace medical history, CV risk assessment and rest electrocardiogram (ECG). Stress ECG tests, computed tomography (CT) with or without contrast, and functional imaging tests are additional diagnostic options. Because CAD in athletes remains a subject of research, the article aims at bringing closer the up-to-date findings on this matter, with a summary of diagnostic tools and clinical implications. Full article

Cardiac computed tomography (CT) has evolved into a pivotal tool in precision cardiology, enabling comprehensive, non-invasive evaluation of coronary anatomy, plaque composition, vascular function, and inflammation. From calcium scoring to advanced physiological imaging, CT now integrates multiple layers of cardiovascular information within a unified diagnostic framework. Coronary artery calcium (CAC) quantification provides a robust, reproducible measure of atherosclerotic burden and refines risk estimation beyond traditional algorithms, particularly in asymptomatic individuals with an intermediate likelihood. Building upon this anatomical foundation, coronary CT angiography (CCTA) extends evaluation to the anatomical and morphological characterization of coronary artery disease (CAD), identifying both obstructive and non-obstructive plaques with high prognostic accuracy. The addition of CT-derived fractional flow reserve (FFR-CT) and stress perfusion CT (CTP) bridges anatomy and physiology, improving identification of flow-limiting stenoses and guiding revascularization decisions while reducing unnecessary invasive procedures. Beyond luminal assessment, CT-derived biomarkers such as the perivascular fat attenuation index (pFAI) have introduced a new dimension of vascular inflammation imaging, revealing residual risk even in patients without significant stenosis and suggesting novel pathways for individualized therapeutic targeting. Driven by advances in artificial intelligence and photon-counting detector technology, cardiac CT is transitioning from a purely diagnostic modality to an integrative platform for cardiovascular phenotyping. Taken as a whole, this integration of structural, functional, and biological data provides a genuinely holistic view of coronary health. In practical terms, it shifts clinical decision-making from population-based risk models toward precision-guided patient-specific strategies. Full article

Background/Goals: Traumatic brain injury (TBI) is increasingly recognised as an important risk factor for delayed neurodegeneration and has been implicated in the modulation of Alzheimer’s disease (AD)-related amyloid pathology. However, experimental evidence remains equivocal, suggesting that the effects of TBI on amyloidogenesis are context-dependent and influenced by factors including disease stage, injury severity, and the pre-existing neurodegenerative background. This study aimed to comprehensively assess the effects of TBI on cognitive function, synuclein-family gene expression, neuroinflammatory gene expression and amyloid plaque morphology in APPswe/PS1dE9/Blg mice. Methods: Wild-type and APP/PS1 mice were assigned to four experimental groups: WT, WT-TBI, APP/PS1 and APP/PS1-TBI. TBI was induced at 6 months of age using a controlled cortical impact device (precision impactor). Behavioural assessments were conducted at two post-injury time points to evaluate locomotor activity, object recognition memory, short-term spatial memory and spatial learning. Cortex and hippocampus samples were analysed by qRT-PCR to evaluate synuclein-family gene expression and neuroinflammation-related markers. Amyloid plaque pathology was evaluated in Congo red-stained brain sections using QuPath-based image analysis. Results: TBI did not induce a consistent increase in amyloid plaque burden in APP/PS1 mice. Instead, TBI was associated with changes in plaque-size distribution, particularly at the later post-injury time point. Behavioural assessments revealed early trauma-associated cognitive impairmen; whereas, impairments observed at later stages appeared to be driven predominantly by progression of the APP/PS1 phenotype. Gene expression analysis revealed region- and genotype-dependent alterations in synuclein-family transcripts and inflammatory markers with the most pronounced changes observed in the cortex. Conclusions: These findings indicate that TBI does not uniformly accelerate β-amyloid deposition in APP/PS1 mice with established amyloid pathology. Rather, TBI appears to modify the temporal progression and morphological characteristics of amyloid pathology while interacting with genotype-dependent transcriptional responses involving synuclein-family genes and neuroinflammatory pathways. These results highlight the complex interplay between traumatic injury and pre-existing neurodegenerative processes and warrant further studies at the protein-level and over extended follow-up periods to elucidate the underlying mechanisms. Full article

Alzheimer’s disease (AD) is a progressive neurodegenerative disorder traditionally characterized by the extracellular accumulation of amyloid-beta (Abeta) plaques and the formation of intracellular neurofibrillary tau tangles; however, the prevailing scientific paradigm has shifted toward an integrative model of pathogenesis that recognizes neuroinflammation as a critical, self-perpetuating driver of cognitive attrition. This multifaceted interplay is mediated by the brain–body axis, wherein chronic systemic inflammation—stemming from metabolic dysfunction, cardiovascular disease, or environmental stressors such as fine particulate matter PM_2.5—compromises the structural integrity of the blood–brain barrier. Such environmental insults serve as priming agents for the innate immune system, shifting peripheral immune populations toward a pro-inflammatory phenotype that is further exacerbated by the stabilization of hypoxia-inducible factors (HIFs) through oxidative stress-induced pseudohypoxia, even under normoxic conditions. The subsequent activation of microglia and astrocytes transitions the cerebral microenvironment from a homeostatic, neurosupportive state into a neurotoxic milieu that actively promotes synaptic loss and neuronal death. Consequently, contemporary research has pivoted from broad-spectrum anti-inflammatory interventions toward targeted immune modulation, emphasizing that a comprehensive understanding of how systemic dysfunction perpetuates neuroinflammatory cascades is essential for developing efficacious therapies capable of attenuating AD progression and mitigating its global health burden. Full article