Search Results (1,880)

The long-term inhalation of free silica dust causes silicosis—a prevalent occupational hazard—yet its systemic effect on male reproductive toxicity remains underexplored. Tetrandrine (Tet) is the only plant-derived anti-silicosis drug approved in China. This study investigates silica (SiO₂) -induced male reproductive damage and evaluates Tet’s protective effects. Sixty male C57BL/6 mice (6–8 weeks) were divided into control, SiO₂ exposure, and SiO₂ + Tet groups. SiO₂ was administered via intranasal infusion and Tet via gavage. Mice were sacrificed at day 7 (male reproductive injury model corresponding to the pulmonary inflammation stage) and day 42 (male reproductive injury model corresponding to the pulmonary fibrosis stage). Analyses included sperm morphology, testicular transcriptome sequencing, RT-qPCR, and immunofluorescence. At day 7, SiO₂ exposure upregulated testicular inflammatory markers, which were partially mitigated by Tet. At day 42, SiO₂ increased sperm deformity and testicular fibrosis markers (fibronectin and vimentin); Tet intervention reduced these abnormalities. Transcriptome analysis revealed distinct gene expression patterns at day 7 versus day 42, indicating time-dependent injury mechanisms. Tetrandrine alleviates silica-induced reproductive damage in male mice, suggesting potential therapeutic applications for occupational silica exposure and expanding the understanding of silica toxicity beyond the respiratory system. Full article

Liver cancer, also known as hepatocellular carcinoma (HCC), remains a major global health concern, with high mortality driven by late-stage diagnosis, limited treatment efficacy, and frequent therapeutic resistance. Matrix metalloproteinases (MMPs), a large family of zinc-dependent endopeptidases, are central to the biological processes that drive liver tumor initiation and progression. By degrading and reorganizing extracellular matrix components, MMPs facilitate tumor expansion, tissue invasion, and metastatic dissemination. In addition, these enzymes regulate the availability of growth factors, cytokines, and chemokines, thereby influencing angiogenesis, inflammation, immune cell recruitment, and the development of an immunosuppressive tumor microenvironment. Aberrant expression or activity of multiple MMP family members is consistently associated with aggressive clinicopathologic features, including vascular invasion, increased metastatic potential, and reduced patient survival, highlighting their promise as prognostic markers and actionable therapeutic targets. Past attempts to modulate MMP activity were hindered by broad inhibition profiles and dose-limiting toxicities, underscoring the need for improved specificity and delivery strategies. Recent advances in molecular design, biologics engineering, and nanotechnology have revitalized interest in MMP targeting by enabling more selective, context-dependent modulation of proteolytic activity. Preclinical studies demonstrate that carefully tuned MMP inhibition can limit tumor invasion, enhance anti-angiogenic responses, and potentially improve the efficacy of existing systemic therapies, including immuno-oncology agents. This review synthesizes current knowledge on the multifaceted roles of MMPs in HCC pathobiology and evaluates emerging therapeutic strategies that may finally unlock the clinical potential of targeting these proteases. Full article

Aim: There is an urgent need for systematic and well-designed studies to clarify the role of systemic inflammatory parameters, especially the neutrophil–lymphocyte-ratio (NLR), in the pathophysiology and clinical management of unregulated substance addiction. This review aims to synthesize current evidence on the relationship between unregulated substance addiction and systemic inflammatory parameters, focusing specifically on the NLR as a potential biomarker. Methods: To ensure a transparent approach in the collection of evidence, this review was carried out following the recommendations of the PRISMA 2020 guidelines and registered in PROSPERO (CRD420251151136). We searched the PubMed and Scopus databases in July2025 using combinations of MeSH terms and keywords related to unregulated substance use and inflammatory biomarkers. The strategy included terms such as “cocaine,” “cannabis,” “opioids,” “heroin,” “fentanyl,” “methadone,” “buprenorphine” “nitazene”, “MDMA”, and “methamphetamine,” combined with “neutrophil-to-lymphocyte ratio.” Filters were applied to limit results to human studies published between 2015 and 2025 in English. The methodological quality of the studies included was assessed using the STROBE 22-item checklist. Results: Fifteen studies were included in this review. Methamphetamine and opioid users showed higher NLR and MLR values. For cocaine abuse, although the evidence is limited to a single population-based study, a significant increase in NLR was reported. Controversial results were observed for cannabis use. Conclusions: Systemic inflammation markers are related to unregulated substance abuse disorders; however, the sparse available evidence encourages the need for well-designed large, prospective clinical trials. Full article

Background and Objectives: The Gustave Roussy Immune (GRIm) score, reflecting systemic inflammation and nutritional status, has emerged as a simple and reproducible prognostic biomarker in various malignancies. However, its prognostic interaction with tumor microenvironmental factors remains unclear in gastric cancer. The primary aim of this study was to evaluate the prognostic value of the GRIm score in patients with resectable gastric adenocarcinoma, while the secondary aim was to determine whether integrating the GRIm score with tumor microenvironment–related pathological markers could improve prognostic stratification. Materials and Methods: This retrospective study analyzed 188 patients with resectable gastric adenocarcinoma treated at the Trakya University Faculty of Medicine between 2007 and 2018. GRIm scores were calculated from preoperative lactate dehydrogenase (LDH), albumin, and neutrophil-to-lymphocyte ratio (NLR) values. Pathologic parameters, including programmed death-ligand 1 (PD-L1) expression (combined positive score [CPS] ≥ 1 vs. <1), tumor–stroma ratio (TSR; stromal component ≥ 50% vs. <50%), and tumor-infiltrating lymphocyte (TIL) density (CD8+ ≥ 10% vs. <10%), were evaluated on surgical specimens. Survival outcomes were assessed using Kaplan–Meier and multivariate Cox analyses. Results: The study population had a mean age of 61.8 years and was predominantly male (72.3%). Patients with low GRIm scores had significantly longer disease-free survival (DFS; 24 vs. 12 months; p = 0.004) and overall survival (OS; 32 vs. 19 months; p = 0.006). In multivariate analysis, the GRIm score remained an independent predictor for both disease-free survival (p = 0.035) and overall survival (p = 0.044). Among combined models, the GRIm–TSR classification provided the most pronounced stratification (median DFS = 35 vs. 12 months; OS = 45 vs. 19 months; p = 0.014 and 0.001, respectively), retaining independent prognostic significance (hazard ratio [HR] = 1.23; p = 0.005). Integrating GRIm with PD-L1 and TIL density also improved prognostic discrimination. Conclusions: The GRIm score is a robust and cost-effective biomarker that independently predicts disease-free survival and overall survival in resectable gastric adenocarcinoma. Its combination with microenvironmental markers—PD-L1, TIL, and TSR—captures complementary biological dimensions of tumor aggressiveness, offering an integrative and clinically feasible framework for individualized risk assessment and postoperative management. Prospective multicenter validation is warranted. Full article

Plants from the Zingiberaceae family, particularly Zingiber officinale, Curcuma longa, and Alpinia galanga, are rich sources of bioactive compounds with documented antidiabetic and anti-inflammatory properties. This review summarizes current evidence on their phytochemical profiles and pathways relevant to metabolic regulation. Key compounds, including gingerols, shogaols, curcuminoids, and phenylpropanoids, support glucose homeostasis by enhancing insulin sensitivity, promoting Glucose Transporter Type 4 (GLUT4)-mediated glucose uptake, improving β-cell function, and modulating metabolic signaling pathways such as PI3K/Akt, AMPK, PPARγ, and NF-κB. Their potent antioxidant and anti-inflammatory activities further reduce oxidative stress and chronic low-grade inflammation, both central to the progression of type 2 diabetes and its complications. Evidence from selected clinical and experimental studies suggests that dietary supplementation with whole-rhizome preparations or standardized extracts (including formulation-enhanced products) may improve fasting blood glucose (FBG), glycated hemoglobin (HbA1c), lipid metabolism, and oxidative stress markers. Recent advances in delivery systems, including nanoemulsions, liposomes, and curcumin–piperine complexes, substantially enhance the bioavailability of poorly soluble phytochemicals, strengthening their therapeutic potential. Overall, Zingiberaceae plants emerge as promising natural supplements in nutritional and pharmacological strategies targeting diabetes. Further clinical research is required to refine dosage, confirm long-term efficacy, and support their integration into evidence-based metabolic interventions. Full article

Low social status leads to chronic social stress that predicts risk for physical and mental illness, especially when it starts early in life. To examine the longitudinal effects of low social status on the immune system, this study assessed the effects of low social status on developmental secretory patterns of pro- and anti-inflammatory markers under baseline conditions, as well as in response to an immune challenge (lipopolysaccharide (LPS)-induced activation of pro- and anti-inflammatory cytokines) in a translational rhesus monkey model of lifelong social subordination stress. Baseline blood samples were collected in 27 socially housed female rhesus monkeys (13 dominants, DOM, and 14 subordinates, SUB) during infancy (6 months), the juvenile pre-pubertal period (16 months), and adulthood (9–10 years) to examine the longitudinal effects of social status on inflammatory markers in unstimulated versus LPS-stimulated conditions mimicking exposure to bacterial infection. Basal levels of the stress hormone cortisol in blood were measured to examine associations between inflammation and activity of the hypothalamic–pituitary–adrenal (HPA) axis throughout the life span. Basal peripheral levels of inflammatory markers (e.g., IL-6) increased across development in both SUB and DOM animals with no significant differences. Basal cortisol levels were significantly higher in infancy as compared to adulthood, but no significant effects of social rank were detected. However, in adulthood, SUB animals showed a cytokine-specific immune response to ex vivo LPS stimulation with significantly higher secretions of IL-1β, IL-2, and IL-10 compared to DOM animals, whereas IL-8 response to LPS was lower in SUB animals than in DOMs. This cytokine-specific response to an immune challenge that mimics bacterial infection could reflect dysregulated immune cells that may have short-term adaptation, but at the cost of longer-term risks for low-grade chronic inflammation and accelerated immune aging for socially subordinate female macaques. Full article

Chronic, low-grade inflammation is a characteristic of metabolic diseases like type 2 diabetes. Despite recommendations to select low- or non-fat dairy foods over full-fat dairy foods for metabolic health, recent research suggests potential anti-inflammatory benefits of dairy fat consumption. We aimed to compare the systemic inflammatory tone (i.e., circulating inflammatory biomarker concentrations and ex vivo peripheral blood mononuclear cell inflammatory responses) of individuals with prediabetes after consuming diets with full-fat (3.25%) or non-fat yogurt. We hypothesized that short-term consumption of three daily full-fat yogurt servings beneficially affects inflammatory tone. Thirteen participants aged 45–75 years completed an eight-week randomized, double-masked, controlled crossover study. The two, three-week experimental diets comprised three daily servings of full-fat or non-fat yogurt and were each preceded by a one-week run-in diet. Following each diet, circulating inflammatory biomarkers and cytokine concentrations in the supernatants of peripheral blood mononuclear cells under control or lipopolysaccharide-stimulated conditions were measured. Compared with non-fat yogurt intake, circulating immature granulocyte concentrations were lower following full-fat yogurt intake, but there were no other differences in leukocyte concentrations. Circulating concentrations of cytokines or other inflammatory markers did not differ by diet. Cell supernatant interleukin-1β concentrations were lower following the full-fat yogurt diet under unstimulated conditions but were not different between diets under stimulated conditions. There were no differences by diet in supernatant concentrations of other cytokines under unstimulated or stimulated conditions. Together, minimal differences in inflammatory tone were observed following the short-term consumption of three daily servings of full-fat or non-fat yogurt in individuals with prediabetes. Full article

Background: Systemic inflammation plays a central role in the pathogenesis and progression of type 2 diabetes mellitus (T2DM). Hematologic inflammatory indices-such as the Systemic Immune-Inflammation Index (SII), Neutrophil-to-Lymphocyte Ratio (NLR), Platelet-to-Lymphocyte Ratio (PLR), and Monocyte-to-Lymphocyte Ratio (MLR)-have emerged as accessible markers of chronic inflammation, yet longitudinal comparisons across oral antidiabetic therapies remain limited. This study uniquely integrates longitudinal correlation and network analyses in a large real-world T2DM cohort, allowing assessment of the temporal stability and class-specific inflammatory patterns across four oral antidiabetic therapies. Methods: This retrospective, longitudinal study analyzed 13,425 patients with T2DM treated with Biguanidines, Dipeptidyl Peptidase-4 (DPP-4) inhibitors, Sodium–Glucose Cotransporter-2 (SGLT-2) inhibitors or Thiazolidinediones (TZDs) between 2020 and 2024. Data were retrieved from the Probel^® Hospital Information System and included baseline, early (30–180 days), and late (180–360 days) follow-up laboratory results. Systemic inflammatory indices were computed from hematologic parameters, and correlations among inflammatory and biochemical markers were assessed using Spearman’s coefficients. Results: At baseline, all hematologic indices were strongly intercorrelated (SII–NLR r = 0.83, p < 0.001; SII–PLR r = 0.73, p < 0.001), with moderate associations to C-reactive protein (CRP; r ≈ 0.3–0.4) and weak or no correlations with Ferritin (r ≈ −0.1). These relationships remained stable throughout follow-up, confirming reproducibility of systemic inflammatory coupling. Longitudinally, SII and NLR showed modest early increases followed by significant declines at one year (p < 0.05), while PLR and MLR remained stable. Class-specific differences were observed: SGLT-2 inhibitors and TZDs demonstrated stronger and more integrated anti-inflammatory networks, whereas Biguanidines and DPP-4 inhibitors exhibited moderate coherence. Principal Component Analysis (PCA) explained 62.4% of total variance and revealed distinct clustering for TZD and SGLT-2 groups, reflecting class-specific inflammatory modulation. Conclusions: Systemic inflammatory indices (SII, NLR, PLR) provide reproducible and accessible measures of low-grade inflammation in T2DM. Despite overall inflammation reduction with treatment, drug-specific patterns emerged-SGLT-2 inhibitors and TZDs showed greater anti-inflammatory coherence, while Biguanidines and DPP-4 inhibitors maintained moderate effects. Full article

Curcumin, a natural polyphenol derived from turmeric, functions as a potent exogenous antioxidant and exhibits a range of benefits in the prevention and management of metabolic diseases. Despite its extremely low systemic bioavailability, curcumin demonstrates significant bioactivity in vivo, a phenomenon likely attributable to its accumulation in the intestines and subsequent modulation of systemic oxidative stress and inflammation. This article systematically reviews the comprehensive regulatory effects of curcumin on systemic metabolic networks—including glucose metabolism, amino acid metabolism, lipid metabolism, and mitochondrial metabolism—and explores their molecular basis, particularly how curcumin facilitates systemic metabolic improvements by alleviating oxidative stress and interacting with inflammation. Preclinical studies indicate that curcumin accumulates in the intestines, where it remodels the microbiota through prebiotic effects, enhances barrier integrity, and reduces endotoxin influx—all of which are critical drivers of systemic oxidative stress and inflammation. Consequently, curcumin improves insulin resistance, hyperglycemia, and dyslipidemia across multiple organs (liver, muscle, adipose) by activating antioxidant defense systems (e.g., Nrf2), enhancing mitochondrial respiratory function (via PGC-1α/AMPK), and suppressing pro-inflammatory pathways (e.g., NF-κB). Clinical trials have corroborated these effects, demonstrating that curcumin supplementation significantly enhances glycemic control, lipid profiles, adipokine levels, and markers of oxidative stress and inflammation in patients with obesity, type 2 diabetes, and non-alcoholic fatty liver disease. Therefore, curcumin emerges as a promising multi-target therapeutic agent against metabolic diseases through its systemic antioxidant and anti-inflammatory networks. Future research should prioritize addressing its bioavailability limitations and validating its efficacy through large-scale trials to translate this natural antioxidant into a precision medicine strategy for metabolic disorders. Full article

Hepatocellular carcinoma (HCC) is the main type of liver cancer and one of the malignancies with the highest mortality rates worldwide. HCC is associated with diverse etiological factors including alcohol use, viral infections, fatty liver disease, and liver cirrhosis (a major risk factor for HCC). Unfortunately, many patients are diagnosed at advanced stages of the disease and receive palliative treatment only. Therefore, early markers of HCC and novel therapeutic approaches are urgently needed. The endocannabinoid system is involved in various physiological processes such as motor coordination, emotional control, learning and memory, neuronal development, antinociception, and immunological processes. Interestingly, endocannabinoids modulate signaling pathways involved in cell survival, proliferation, apoptosis, autophagy, and immune response. Consistently, several cannabinoids have demonstrated potential antitumor properties in experimental models. The participation of metabotropic and ionotropic cannabinoid receptors in the biological effects of cannabinoids has been extensively described. In addition, cannabinoids interact with other targets, including several ion channels. Notably, several ion channels targeted by cannabinoids are involved in inflammation, proliferation, and apoptosis in liver diseases, including HCC. In this literature review, we describe and discuss both the endocannabinoid system and exogenous phytocannabinoids, such as cannabidiol and Δ⁹-tetrahydrocannabinol, along with their canonical receptors, as well as the cannabidiol-targeted ion channels and their role in liver cancer and its preceding liver diseases. The cannabidiol-ion channel association is an extraordinary opportunity in liver cancer prevention and therapy, with potential implications for several environments that are for the benefit of cancer patients, including sociocultural, public health, and economic systems. Full article

Background/Objectives: Post-COVID-19 pulmonary fibrosis (PCPF) and idiopathic pulmonary fibrosis (IPF) exhibit significant clinical and pathophysiological overlap, suggesting convergent molecular pathways driving fibrosis. This prospective longitudinal study investigates the sustained dysregulation of matrix metalloproteinases (MMP)-2 and MMP-9 and its relationship with evolving systemic inflammation and endothelial dysfunction in convalescent COVID-19 patients, with comparative analysis to IPF. Methods: We conducted a prospective observational study of 86 patients at 6 and 12 months post-SARS-CoV-2 infection, stratified by high-resolution CT evidence of PCPF (FB+ group, n = 32) or absence of fibrosis (FB− group, n = 54). Gene expression of MMP-2 and MMP-9 in peripheral blood leukocytes and circulating levels of MMP-2, MMP-9, pro-inflammatory cytokines (TNF-α, IL-6), and endothelial dysfunction markers (Endothelin-1 [ET-1], adhesion molecules) were quantified via qRT-PCR and ELISA. A pre-pandemic healthy control group (HD, n = 20) and an IPF patient group (n = 10) served as comparators. Results: A significant, sustained elevation of MMP-2 and MMP-9 was observed in all post-COVID-19 patients versus HDs, most pronounced in the FB+ group and qualitatively similar to IPF. A critical divergence emerged: FB− patients showed resolution of systemic inflammation (reduced TNF-α, IL-6), whereas FB+ patients exhibited persistent cytokine elevation. Critically, a delayed, severe endothelial dysfunction, characterized by a profound surge in ET-1 and elevated adhesion molecules, manifested exclusively in the FB+ cohort at 12 months. Positive correlations linked plasma MMP-2/9 levels with ET-1 (r_s = 0.65, p = 0.004; r_s = 0.49, p = 0.009) and ET-1 with sICAM-1 (r_s = 0.68, p = 0.01). Conclusions: The development of PCPF is associated with a distinct pathogenic triad: sustained MMP dysregulation, failure to resolve inflammation, and severe late-phase endothelial dysfunction. The correlative links between these components suggest a self-reinforcing loop. This systemic signature mirrors patterns in IPF, underscoring shared final pathways in fibrotic lung disease and identifying the MMP–inflammation–endothelial axis as a promising target for biomarker development and therapeutic intervention. Full article

Background and Objectives: Metabolic syndrome (MetS) is a complex condition marked by insulin resistance, central obesity, dyslipidemia, and chronic inflammation. Emerging evidence highlights the roles of hypoxia and mitochondrial stress in its pathophysiology. Hypoxia-inducible factor-1 alpha (HIF1α) and the mitophagy-associated proteins BNIP3 and BNIP3L are key components of hypoxia-responsive mitochondrial stress signaling. This study aimed to evaluate the circulating levels of HIF1α, BNIP3, and BNIP3L in MetS and to explore their associations with metabolic and inflammatory parameters. Materials and Methods: Serum concentrations of HIF1α, BNIP3, and BNIP3L were measured by ELISA in 40 patients with MetS and 40 age and sex-matched controls. Biochemical, hematological, and anthropometric parameters were assessed, and receiver operating characteristic (ROC) analyses were performed to evaluate diagnostic performance. Results: Serum levels of HIF1α, BNIP3, and BNIP3L levels were significantly higher in MetS patients compared with controls (p = 0.001). ROC analysis demonstrated strong diagnostic potential, particularly for BNIP3 (AUC = 0.928), followed by HIF1α (AUC = 0.885) and BNIP3L (AUC = 0.770). These markers showed significant associations with metabolic indicators such as BMI, fasting glucose, triglycerides, and inflammatory markers. Conclusions: The coordinated upregulation of circulating HIF1α, BNIP3, and BNIP3L in MetS is associated with metabolic dysregulation and systemic inflammation, reflecting alterations in hypoxia-responsive mitophagy-associated signaling rather than direct functional impairment of mitophagy. These findings support the potential relevance of these markers as indicators of metabolic stress in MetS. Further tissue-based and mechanistic studies are warranted to clarify their role in disease pathophysiology. Full article

Background: Depression and Metabolic Dysfunction-Associated Steatotic Fatty Liver Disease (MASLD) are common chronic diseases, respectively. However, the causal and molecular links between them remain unclear. In order to explore whether depression contributes to an increased risk of MASLD and whether inflammation mediates this effect, we integrated multi-level evidence from the epidemiology of the National Health and Nutrition Examination Survey (NHANES), the genetics of GWAS, the transcriptomes of GEO, and single-cell RNA sequencing datasets. Methods: A multi-level integrative analysis strategy was used to validate this pathway. First, a cross-sectional epidemiological analysis based on NHANES data was used to reveal the association between depression and MASLD, and to explore the mediating role of inflammation and liver injury markers. Secondly, a two-sample Mendelian randomization analysis was used to infer the causal direction of depression and MASLD, and to verify the mediating effect of systemic inflammation and liver injury indicators at the genetic level. Then, the transcriptome co-expression network analysis and machine learning were used to screen the common hub genes connecting the two diseases. Finally, single-cell transcriptome data were used to characterize the dynamic expression of potential key genes during disease progression at cellular resolution. Results: Depression significantly increased the risk of MASLD, especially in women (OR = 1.39, 95%CI [1.17–1.65]). Parallel mediation analysis showed that high-sensitivity C-reactive protein (hs-CRP) (p < 0.001), γ-glutamyltransferase (GGT) (p < 0.001), and alkaline phosphatase (ALP) (p < 0.001) mediated this relationship. Mendelian randomization analysis confirmed the unidirectional causal effect of depression on MASLD, and there was no reverse association (β = 0.483, SE = 0.146, p = 0.001). Weighted gene co-expression network analysis and machine learning identified CD40LG as a potential molecular bridge between depression-associated immune modules and MASLD. In addition, single-cell data analysis revealed a stage-specific trend of CD40LG expression in CD4⁺ T cells during MASLD progression, while its receptor CD40 was also activated in B cells. In the female sample, CD40LG maintained an upward trend. However, the stability of this result is limited by the limited sample size. Conclusions: This study provides converging multi-omics evidence that depression plays a causal role in MASLD through inflammation-mediated immune signaling. The CD40LG-CD40 axis has emerged as an immune mechanism that transposes depression into the pathogenesis of MASLD, providing a potential target for the intervention of gender-specific metabolic liver disease. Full article

Background: Metabolic syndrome (MetS) comprises interrelated metabolic abnormalities that collectively confer increased risk of cardiovascular disease and hepatic morbidity. The MAF-5 score is a non-invasive prognostic marker of liver fibrosis and mortality, while Cystatin C (CysC) is a sensitive indicator of renal function that also reflects inflammation, atherosclerosis, and metabolic dysfunction. Although both MetS and CysC have been widely studied, their potential interplay via MAF-5 remains unclear. We aimed to investigate the relationship between MAF-5 scores and CysC levels in MetS patients for the first time. Materials and Methods: Adults (≥18 years) with MetS were included in this study. MAF-5 scores (based on waist circumference, BMI, diabetes status, AST, and platelet count) and CysC levels were recorded. The MAF-5–CysC relationship was assessed via Pearson correlation. Participants were grouped into MAF-5 quartiles, and continuous variables were compared using ANOVA with Bonferroni-corrected pairwise tests. Results: We included 347 MetS patients (54.8% female, median age 54 years). The median MAF-5 score was 1.25, and MAF-5 correlated positively with CysC (r = 0.357, p < 0.001). CysC levels differed significantly across MAF-5 quartiles (Q1 = 0.96, Q2 = 0.99, Q3 = 1.06, Q4 = 1.09; p < 0.001), with Q4 showing higher values than Q1 and Q2. Conclusions: A significant correlation was found between MAF-5 scores and CysC in patients with MetS. CysC levels differed significantly across MAF-5 quartiles, suggesting a potential link between systemic inflammation, liver fibrosis, and CysC. These results highlight shared inflammatory and fibrotic pathways, underlying metabolic dysfunction. Clinically, combined assessment of MAF-5 and CysC may improve risk stratification, identifying patients at higher risk for hepatic fibrosis and adverse outcomes. Full article

Background and Objectives: Neutrophil extracellular traps (NETs) have been linked to hypercoagulability, immunothrombosis, and organ injury in COVID-19. Digital morphology of peripheral blood smears enables the identification of NET-compatible appearances (NET-like) in circulation, and associations between NET-like derived indices and clinical outcomes have been reported. However, evidence at hospital admission that relates smear NET-like burden to systemic inflammation and clinical severity remains limited. We therefore aimed to compare the burden of NET-like structures on admission smears according to disease severity and systemic inflammatory markers. Materials and Methods: We included 50 consecutively enrolled adults hospitalized for COVID-19; samples were obtained within 24 h of admission. Severity was defined by the World Health Organization Clinical Progression Scale and grouped as moderate or severe. C-reactive protein (CRP), ferritin, and complete blood counts were measured; the neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) were calculated. Digital morphology assessed 200 leukocytes per patient; the presence of morphological abnormalities, including NET-like events per patient, was recorded. We additionally quantified NET-like events per 100 white blood cells (NET-like/100 WBC) and the neutrophil extracellular trap–segmented neutrophil ratio (NNSR). Results: At admission, CRP, ferritin, NLR, and PLR of patients were above method-specific reference intervals. NET-like events were identified in 66% of patients. NET-like/100 WBC correlated positively with NLR (r = 0.312; p < 0.05). Patients with severe COVID-19 had higher NET-like/100 WBC than those with moderate disease (5.8 ± 7.34 vs. 14.14 ± 15.12; p = 0.0294). Conclusions: Digital morphological identification of NET-like structures on peripheral blood smears is frequent at admission and is associated with systemic inflammatory burden and with greater COVID-19 severity. These findings support the potential complementary value of reporting NET-like events for initial risk stratification in the clinical laboratory. Full article