Search Results (69)

Background/Objectives: Metabolic dysfunction-associated steatotic liver disease (MASLD) represents a major global health challenge characterized by complex adipose–liver interactions mediated by adipokines and hepatokines. Despite rapid field evolution, a comprehensive understanding of research trends and translational advances remains fragmented. This study systematically maps the scientific landscape through bibliometric analysis, identifying emerging domains and future clinical translation directions. Methods: A comprehensive bibliometric analysis of 1002 publications from 2004 to 2025 was performed using thematic mapping, temporal trend evaluation, and network analysis. Analysis included geographical and institutional distributions, thematic cluster identification, and research paradigm evolution assessment, focusing specifically on adipokine–hepatokine signaling mechanisms and clinical implications. Results: The United States and China are at the forefront of research output, whereas European institutions significantly contribute to mechanistic discoveries. The thematic map analysis reveals the motor/basic themes residing at the heart of the field, such as insulin resistance, fatty liver, metabolic syndrome, steatosis, fetuin-A, and other related factors that drive innovation. Basic clusters include metabolic foundations (obesity, adipose tissue, FGF21) and adipokine-centered subjects (adiponectin, leptin, NASH). New themes focus on inflammation, oxidative stress, gut microbiota, lipid metabolism, and hepatic stellate cells. Niche areas show targeted fronts such as exercise therapies, pediatric/novel adipokines (chemerin, vaspin, omentin-1), and advanced molecular processes that focus on AMPK and endoplasmic-reticulum stress. Temporal analysis shows a shift from single liver studies to whole models that include the gut microbiota, mitochondrial dysfunction, and interactions between other metabolic systems. The network analysis identifies nine major clusters: cardiovascular–metabolic links, adipokine–inflammatory pathways, hepatokine control, and new therapeutic domains such as microbiome interventions and cellular stress responses. Conclusions: In summary, this study delineates current trends and emerging areas within the field and elucidates connections between mechanistic research and clinical translation to provide guidance for future research and development in this rapidly evolving area. Full article

Vitamin D deficiency is highly prevalent in individuals with overweight/obesity and this can be largely attributed to the entrapment of VitD in adipose tissue due to impaired lipolytic stimulation. Considering the well-described role of exercise in stimulating lipolysis, the present study investigated the efficacy of multicomponent-type high-intensity interval training (m-HIIT) in increasing 25-hydroxyvitamin D [25(OH)D] levels in males with overweight/obesity. Twenty middle-aged males (43.5 ± 5 years, BMI: 30.7 ± 3.3 kg/m²) participated in three weekly supervised m-HIIT sessions over a 12-week period and underwent assessments at baseline, 6, and 12 weeks. Primary outcomes were total body fat mass, android fat, hepatorenal index, and serum 25(OH)D. Participants’ daily physical activity and dietary intake habits remained unaltered throughout the 12-week training period. The m-HIIT intervention reduced fat mass (by 3% at 12 weeks), android fat (by 3.7% at 6 weeks and 4.4% at 12 weeks), and hepatorenal index (by 8% at 12 weeks). Serum 25(OH)D levels increased by ~14% (+3.21 ng/mL, p = 0.002) and ~31% (+7.24 ng/mL, p < 0.001) at 6 and 12 weeks, respectively. The elevation of 25(OH)D levels at 12 weeks was inversely related to fat mass loss (R = 0.53, p = 0.016). Plasma SGPT, SGOT, ALP, γ-GT, fetuin-A, and calcium levels remained unaltered after the 12-week training period. In conclusion, m-HIIT may be useful as a non-pharmacological intervention to increase circulating VitD levels in adults with overweight/obesity. Full article

Background and Objectives: Fetuin-A is mostly synthesized in the liver. It is a hepatokine, which is an extracellular inhibitor of growth factors. There is a scarcity of data on the clinical utility of serum fetuin-A (SFA) in alcohol-associated cirrhosis (AC). We first investigated the association between SFA levels and disease phenotypes in alcoholic liver disease (ALD) patients, including alcohol-associated steatotic liver (ASL) and alcohol-associated hepatitis (AH), along with AC patients. Materials and Methods: There were 26 healthy controls and 64 ALD patients in this case–control study. The severity of the disease in the AC patients was evaluated using the Child–Pugh classification (CPC-A, -B, and -C), and the FH and AC patients’ Maddrey’s differential function scores and the Model of End-Stage Liver Disease Sodium (MELD-Na) scores were computed. We measured SFA levels using a human fetuin-A enzyme-linked immunosorbent assay (ELISA) kit. Results: The SFA concentrations were lower in the AC group and higher in the ASL group [670.72 (412.36) mg/L vs. 1484.61 (858.16) mg/L, respectively; p < 0.001]. When compared to patients with ASL, the SFA levels in AC patients were noticeably lower. However, similar SFA levels were observed for the AH group and the healthy controls, as well as for the ASL group and the healthy controls. Within the AC group, the CPC-A subgroup had the highest median SFA values, while the CPC-C subgroup had the lowest median SFA value. Furthermore, the median SFA levels demonstrated significant and inverse correlations with the CPC scores and the MELD-Na scores (rho = −0.671, p < 0.001; rho = −0.742, p < 0.001, respectively). A negative correlation was observed between the SFA levels and the MELD-Na scores in the AH group (ρ = −0.621, p = 0.013). Conclusions: In ALD patients, decreased SFA levels, which exhibit disease severity, might be an auxiliary biomarker for the follow-up of AC patients. Full article

Childhood obesity and overweight are linked to subclinical inflammatory conditions. The present manuscript aimed to undertake a scoping review exploring the relationship between childhood obesity and salivary biomarkers to answer the following question: “Are salivary biomarkers trustful factors/indicators for childhood obesity?” The main search terms used were: “obesity and salivary biomarkers and children” (Pubmed, Scielo, Scopus, Embase databases: 1999–2025). Assessed articles were carefully classified according to a predetermined criterion (Newcastle–Ottawa Scale), and the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) were considered. Papers involving children >13 years, duplicates/triplicates, literature reviews, and non-related to the question addressed were excluded. More than 30 salivary biomarkers were assessed in the thirteen studies appraised. Three studies were rated as having a high level of evidence, two as moderate, and eight as having a low level. Fourteen biomarkers were found to be significantly increased in childhood obesity/overweight (p < 0.05): leptin, insulin, α-amylase, tumor necrosis factor α, interleukin 6, vascular endothelial growth factor-A, C-reactive protein, monocyte chemotactic protein-1, resistin, phosphate, nitric oxide, interleukin 1β, uric acid and fetuin-A; and three were found to be significantly decreased (p < 0.05): adiponectin, secretory immunoglobulin A, and interleukin-12p70. In conclusion, the present review supported the idea that saliva might be a promising diagnostic tool in early life and that it is a significant source of obesity biomarkers in children. Full article

Background and Aims: Hepatokines have a regulatory function in adipose tissue inflammation, metabolic dysfunction-associated steatotic liver disease (MASLD), cardiovascular diseases, and atherosclerosis. Our aim was to evaluate the profile of proinflammatory cytokines and hepatokines in patients with MASLD and carotid atherosclerosis (CA). Methods: A prospective and basic research study was conducted on patients with MASLD. Clinical data were collected from a detailed medical history. Liver stiffness was measured using transient elastography, and carotid Doppler ultrasound was performed. Levels of basic biochemical parameters, systemic inflammation markers (TNF-α, IL-6, IL-10, IL-18), and hepatokines (FGF21, ANGPTL4, fetuin-A) were determined. The results were analyzed with SPSS v22.0 software. Results: Sixty-seven patients with MASLD were included, 72.1% were women, and the mean patient age was 53.9 + 11.3 years. Atherosclerosis was found in 11 patients (16.2%), and carotid intima–media thickness (CIMT) was altered in the right carotid of 13 patients (19.1%), in the left carotid of 19 (27.9%), and bilaterally in 7 (10.3%). Greater age (p = 0.001) and high blood pressure (p = 0.028) were correlated with atherosclerosis. There were no differences in systemic inflammation markers, and the hepatokines FGF21 and fetuin-A tended to increase in the presence of CIMT and CA alterations, regardless of fibrosis. Conclusions: In our population, patients with MASLD had a 16.6% prevalence of CA, and the risk increased with age and a history of high blood pressure. FGF21 tended to increase in patients with MASLD + atherosclerosis, and fetuin-A was correlated with CIMT alterations, suggesting that the combination of these markers could guide us to suspect early endothelial alterations in patients with MASLD. Full article

Rheumatoid arthritis (RA) is a chronic autoimmune disease that not only causes joint inflammation but also significantly increases the risk of cardiovascular disease (CVD), leading to a higher morbidity and mortality. RA patients face an accelerated progression of atherosclerosis, attributed to both traditional cardiovascular risk factors and systemic inflammation. This review focuses on emerging biomarkers for cardiovascular risk assessment in RA, aiming to enhance early detection and treatment strategies. Specifically, we examine the roles of interleukin-32 (IL-32), Dickkopf-1 (DKK-1), galectin-3 (Gal-3), catestatin (CST), and fetuin-A (Fet-A) as potential markers for CVD in this patient population. IL-32, a proinflammatory cytokine, is elevated in RA patients and plays a significant role in inflammation and endothelial dysfunction, both of which contribute to atherosclerosis. DKK-1, a Wnt signaling pathway inhibitor, has been associated with both synovial inflammation and the development of atherosclerotic plaques. Elevated DKK-1 levels have been linked to an increased CV mortality and could serve as a marker for CVD progression in RA. Gal-3 is involved in immune modulation and fibrosis, with elevated levels in RA patients correlating with disease activity and cardiovascular outcomes. Catestatin, a peptide derived from chromogranin A, has protective anti-inflammatory and antioxidative properties, though its role in RA-related CVD remains under investigation. Finally, Fet-A, a glycoprotein involved in vascular calcification, shows potential as a biomarker for CV events in RA, though data on its role remain conflicting. These biomarkers provide deeper insights into the pathophysiology of RA and its cardiovascular comorbidities. Although some biomarkers show promise in improving CV risk stratification, further large-scale studies are required to validate their clinical utility. Currently, these biomarkers are in the research phase and are not yet implemented in standard care. Identifying and incorporating these biomarkers into routine clinical practice could lead to the better management of cardiovascular risk in RA patients, thus improving outcomes in this high-risk population. This review highlights the importance of continued research to establish reliable biomarkers that can aid in both diagnosis and the development of targeted therapies for cardiovascular complications in RA. Full article

Background: Fetuin-A prevents the precipitation of hydroxyapatite in supersaturated solutions of calcium and phosphate; however, its relationship with nephrolithiasis has yet to be clarified. The aim of this study was to investigate the protective and predictive roles of serum and urine fetuin-A levels in nephrolithiasis and their relationships with the composite dietary antioxidant index (CDAI). Methods: This study involved 75 adult patients with kidney stone disease and 71 healthy adults without kidney stone disease in the control group. Participants had specific anthropometric measurements taken, and three-day food records were kept. The CDAI was calculated by summing six standard antioxidants, including vitamins A, C, and E, manganese, selenium, and zinc, representing participants’ antioxidant profile. In addition to some analyzed serum and urine parameters of the participants, fetuin-A levels were measured using the enzyme-linked immunosorbent assay (ELISA) method. Results: In patients with kidney stones, both serum and urine fetuin-A levels (676.3 ± 160.14 ng/mL; 166.6 ± 128.13 ng/mL, respectively) were lower than in the control group (1455.6 ± 420.52 ng/mL; 2267.5 ± 1536.78 ng/mL, respectively) (p < 0.00001). In contrast, the CDAI was higher in patients with kidney stones compared to those without kidney stones (p < 0.001). Besides, several dietary parameters had significant positive correlations with serum and/or urinary fetuin-A. Conclusions: The present study suggests that serum and urinary fetuin-A levels may serve as protective factors against kidney stones and could potentially be used as predictive markers for the development of nephrolithiasis. Furthermore, our results suggest that the CDAI above a certain level may increase the risk of stone formation and that some dietary parameters may affect the levels of this biomarker in serum and urine. Full article

Background/Objectives: Post-translationally modified peptide fragments of fetuin-A (FetA) were identified as a potential biomarker of diabetic kidney disease (DKD). An independent association between urinary FetA-derived peptide levels (uPTM3-FetA) and DKD progression in patients with type 2 diabetes (T2D) was evidenced. This study aimed to explore uPTM3-FetA excretion and its associations with insulin resistance, inflammatory and metabolic biomarkers in patients with type 1 diabetes (T1D), and the normal albuminuria and estimated glomerular filtration rate (eGFR) > 60 mL/min/1.73 m². Methods: uPTM3-FetA levels in aliquots of 24 h urine specimens, routine laboratory renal, metabolic and inflammatory tests, adipokines (leptin, adiponectin, resistin), and insulin resistance, assessed as the estimated glucose disposal rate (eGDR), were measured in a cohort of 169 adult T1D patients. To evaluate the changes in early renal dysfunction, the cohort was divided according to the median eGFR. Above- and below-median-eGFR groups were considered as having normal and declining kidney function, respectively. Results: The median (IQR) uPTM3-FetA level was 11.7 (8.43–16.65 µg/24 h), with no significant difference between males and females, as well as normal and declining kidney function patients. However, a sex-specific analysis revealed a significantly higher uPTM3-FetA excretion in male T1D patients with lower eGFRs, when compared to those with higher eGFRs, whereas no such difference was observed in female patients. BMI, hs-CRP, resistin and HDL-cholesterol were identified as independent predictors of uPTM3-FetA excretion. Conclusions: Our results implicate the potential role of uPTM3-FetA in the detection of an early renal dysfunction in male patients with T1DM and pinpoint the importance of a sex-specific approach in diabetes diagnostics and research. Full article

Background: Despite existing evidence of the high predictive value of natriuretic peptides (NPs) in patients with heart failure (HF), patients treated with guideline-directed therapy who have low or near-normal NP levels are unlikely to be correctly stratified for risk of clinical outcomes. The aim of this study is to detect plausible predictors for poor one-year clinical outcomes in patients with HFpEF and low NT-proBNP treated with in accordance with conventional guidelines. Methods: A total of 337 patients with HF with preserved ejection fraction (HFpEF) who had low levels of N-terminal natriuretic pro-peptide (NT-proBNP) at discharge due to optimal guideline-based therapy were enrolled in the study. The course of the observation was 3 years. Echocardiography and the assessment of conventional hematological and biochemical parameters, including NT-proBNP, tumor necrosis factor-alpha, high-sensitivity C-reactive protein (hs-CRP), adropin, irisin, visfatin, and fetuin-A, were performed at baseline and at the end of the study. Results: Three-year cumulative clinical endpoints (cardiovascular death, myocardial infarction or unstable angina or acute coronary syndrome, worsening HF, sudden cardiac death, or cardiac-related surgery or all-cause death) were detected in 104 patients, whereas 233 did not meet the endpoint. After adjusting for an age ≥ 64 years and a presence of atrial fibrillation, diabetes mellitus, chronic kidney disease (CKD) stages 1–3 and dilated cardiomyopathy, the multivariable Cox regression analysis showed that an irisin level of ≤7.2 ng/mL was an independent predictor of cumulative clinical endpoint. Moreover, patients with levels of irisin > 7.2 ng/mL had a better Kaplan–Meier survival rate than those with a lower serum irisin level (≤7.2 ng/mL). Conclusions: Multivariable analysis showed that an age ≥ 64 years; the presence of atrial fibrillation, diabetes mellitus, CKD stages 1–3 and dilated cardiomyopathy; an LAVI ≥ 39 mL/m²; and serum levels of hs-CRP ≥ 6.10 mg/L, irisin ≤ 7.2 ng/mL, and visfatin ≤ 1.1 ng/mL were predictors of poor clinical outcomes in HFpEF with low levels of NT-proBNP. A serum level of irisin ≤ 7.2 ng/mL could emerge as valuable biomarker for predicting long-term prognosis among HFpEF patients with low or near-normal levels of NT-proBNP. Full article

Vascular calcification (VC) is a biological phenomenon characterized by an accumulation of calcium and phosphate deposits within the walls of blood vessels causing the loss of elasticity of the arterial walls. VC plays a crucial role in the incidence and progression of chronic kidney disease (CKD), leading to a significant increase in cardiovascular mortality in these patients. Different conditions such as age, sex, dyslipidemia, diabetes, and hypertension are the main risk factors in patients affected by chronic kidney disease. However, VC may occur earlier and faster in these patients if it is associated with new or non-traditional risk factors such as oxidative stress, anemia, and inflammation. In chronic kidney disease, several pathophysiological processes contribute to vascular calcifications, including osteochondrogenic differentiation of vascular cells, hyperphosphatemia and hypercalcemia, and the loss of specific vascular calcification inhibitors including pyrophosphate, fetuin-A, osteoprotegerin, and matrix GLA protein. In this review we discuss the main traditional and non-traditional risk factors that can promote VC in patients with kidney disease. In addition, we provide an overview of the main pathogenetic mechanisms responsible for VC that may be crucial to identify new prevention strategies and possible new therapeutic approaches to reduce cardiovascular risk in patients with kidney disease. Full article

Fetuin-A, also known as alpha-2-Heremans-Schmid-glycoprotein (Ahsg), is a multifunctional molecule with diverse roles in biological processes such as mineralization, tumor growth, and inflammation. This review explores the involvement of Ahsg in various cancers, including liver, breast, prostate, colorectal, brain, osteosarcoma, and lung cancers. In many cancer types, Ahsg promotes tumor growth, invasion, and metastasis through various mechanisms, including cellular adhesion, spreading, chemotaxis, and modulation of cell-growth signaling pathways. Additionally, Ahsg has been implicated in the regulation of inflammatory cytokine production, making it a potential marker of inflammation in cancer. The complex interplay between Ahsg and cancer progression highlights its potential as a diagnostic biomarker and therapeutic target in various cancers. However, further research is needed to fully elucidate the mechanisms of action of Ahsg in cancer and to explore its clinical implications in cancer diagnosis, prognosis, and treatment. Full article

Cognitive impairment and dementia are common in patients with chronic kidney disease, including those undergoing hemodialysis. Since magnesium and phosphate play important roles in brain function and aging, alterations in these and other factors related to bone mineral disorder (MBD) may contribute to low cognitive performance in patients on hemodialysis. This cross-sectional study examined the associations between cognitive function and MBD-related factors among 1207 patients on maintenance hemodialysis. Cognitive function was assessed by the Modified Mini-Mental State examination (3MS). The exposure variables of interest were serum magnesium, phosphate, calcium, calcium–phosphate product, intact parathyroid hormone, fetuin-A, T50 calciprotein crystallization test, use of phosphate binders, use of cinacalcet, and use of vitamin D receptor activators. Multivariable-adjusted linear regression models were used to examine the associations between 3MS and each of the exposure variables independent of 13 potential non-mineral confounders. We found that lower 3MS was associated with lower serum magnesium, lower phosphate, lower calcium–phosphate product, and nonuse of phosphate binders. These results suggest that magnesium and phosphate play potentially protective roles against cognitive impairment in this population. Full article

The introduction of the term “Metabolic Steatotic Liver Disease” (MASLD) underscores the critical role of metabolic dysfunction in the development and progression of chronic liver disease and emphasizes the need for strategies that address both liver disease and its metabolic comorbidities. In recent years, a liver-focused perspective has revealed that altered endocrine function of the fatty liver is a key contributor to the metabolic dysregulation observed in MASLD. Due to its secretory capacity, the liver’s increased production of proteins known as “hepatokines” has been linked to the development of insulin resistance, explaining why MASLD often precedes dysfunction in other organs and ultimately contributes to systemic metabolic disease. Among these hepatokines, fibroblast growth factor 21 (FGF21) and fetuin-A play central roles in regulating the metabolic abnormalities associated with MASLD, explaining why their dysregulated secretion in response to metabolic stress has been implicated in the metabolic abnormalities of MASLD. This review postulates why their modulation by GLP1-Ras may mediate the beneficial metabolic effects of these drugs, which have increased attention to their emerging role as pharmacotherapy for MASLD. By discussing the crosstalk between GLP1-Ras-FGF21-fetuin-A, this review hypothesizes that the possible modulation of fetuin-A by the novel GLP1-FGF21 dual agonist pharmacotherapy may contribute to the management of metabolic and liver diseases. Although research is needed to go into the details of this crosstalk, this topic may help researchers explore the mechanisms by which this type of pharmacotherapy may manage the metabolic dysfunction of MASLD. Full article

Rheumatoid arthritis (RA) is a chronic autoimmune disease associated with increased cardiovascular disease (CVD) risk and mortality. This work aimed to evaluate the serum levels of the novel CV biomarkers fetuin-A (fet-A), Dickkopf-1 (DKK-1), galectin-3 (Gal-3), interleukin-32 (IL-32), and catestatin (CST) in RA patients and their associations with RA parameters and CVD markers. A cohort of 199 RA patients was assessed for traditional CVD risk factors, RA disease activity, and biomarker levels. Carotid ultrasound was used to measure carotid intima-media thickness (cIMT) and carotid plaque presence (cPP). Multivariate analyses examined correlations between biomarkers and RA parameters, serological markers, and CVD markers. Adjusted models showed that elevated CST expression levels were associated with rheumatoid factor (RF) and anti-citrullinated protein antibody (ACPA) positivity (OR = 2.45, p = 0.0001 and OR = 1.48, p = 0.04, respectively) in the overall cohort and for RF in men and women, respectively. In addition, fet-A concentration was inversely associated with the erythrocyte sedimentation rate (ESR) in the overall cohort (β = −0.15, p = 0.038) and in women (β = −0.25, p = 0.004). Fet-A levels were also negatively correlated with disease activity (DAS28-ESR) scores (β = −0.29, p = 0.01) and fibrinogen concentration (β = −0.22, p = 0.01) in women. No adjusted associations were observed for Gal-3, DKK-1 or IL32 concentration. The study revealed no significant associations between the biomarkers and cIMT or cPP. The measurement of CST and fet-A levels could enhance RA patient management and prognosis. However, the utility of biomarkers for evaluating CV risk via traditional surrogate markers is limited, highlighting the need for continued investigations into their roles in RA. Full article

Background/Objectives: People living with HIV (PLWH) treated with combined antiretroviral therapy (cART) show a greater predisposition to metabolic and inflammatory disturbances compared to the general population. This study aimed to assess the effect of five years of cART use on the level of selected parameters related to carbohydrate and lipid metabolism and inflammation in PLWH compared to the uninfected. Methods: The levels of sirtuins (-1, -3, -6); irisin (IRS); myostatin (MSTN); peptide YY (PYY); glucagon-like peptide-1 (GLP-1); dipeptidyl peptidase IV (DPP-4); fetuin-A (FETU-A); pentraxin 3 (PTX3); chemokine stromal cell-derived factor 1 (SDF-1); regulated on activation, normal T cell expressed and presumably secreted (RANTES); and interleukins (-4, -7, -15) in the plasma of PLWH and a control group were evaluated by immunoassay methods. The results obtained after five years of antiretroviral therapy were compared with the levels obtained before and one year after cART. Results: Analysis of the parameters after five years of cART showed significantly higher levels in PLWH compared to the control group for SIRT-6, IRS, and IL-4 and significantly lower levels for RANTES and IL-7. There were significantly higher levels of SIRT-6, PYY, GLP-1, and PTX3 obtained after five years of cART compared to the results before therapy and after one year of cART. Conclusions: The results indicated changes occur in the expression of selected parameters during cART use in PLWH. Further research on the clinical usefulness of selected parameters and obtaining new information on the development of HIV-related comorbidities needs to be conducted. Full article