The Usefulness of Vitamin K-Dependent Proteins in the Diagnosis of Colorectal Carcinoma.

Colorectal cancer (CRC) is one of the most common neoplasms in developed countries, with increasing incidence and mortality, even in young people. A variety of serum markers have been associated with CRC (CEA, CA 19-9), but neither should be used as a screening tool for the diagnosis or evolution staging of CRC. The sensitivity and specificity of these markers are not as good as is required, so new ones need to be found. Matrix Gla protein and PIVKA II are involved in carcinogenesis, but few studies have evaluated their usefulness in predicting the presence and severity of CRC. Two hundred patients were divided into three groups: 80 patients were included in the control group; 80 with CRC and without hepatic metastasis were included in Group 1; 40 patients with CRC and hepatic metastasis were included in Group 2. Vitamin K-dependent proteins (VKDPs) levels in plasma were determined. Patients with CRC without methastasis (Group 1) and CRC patients with methastasis (Group 2) presented significantly higher values of CEA, CA 19-9, PIVKA II (310.05 ± 38.22 vs. 430.13 ± 122.13 vs. 20.23 ± 10.90), and ucMGP (14,300.00 ± 2387.02 vs. 13,410.52 ± 2243.16 vs. 1780.31 ± 864.70) compared to control group (Group 0). Interestingly, Group 1 presented the greatest PIVKA II values. Out of all the markers, significant differences between the histological subgroups were found only for ucMGP, but only in non-metastatic CRC. Studying the discrimination capacity between the patients with CRC vs. those without, no significant differences were found between the classical tumor markers and the VKDP AUROC curves (PIVKA II and ucMGP AUROCs = 1). For the metastatic stage, the sensitivity and specificity of the VKDPs were lower in comparison with those of CA 19-9 and CEA, respectively (PIVKA II AUROC = 0.789, ucMGP AUROC = 0.608). The serum levels of these VKDPs are significantly altered in patients with colorectal carcinoma; it is possible to find additional value of these in the early stages of the disease.

Diagnostic Performance of Extrahepatic Protein Induced by Vitamin K Absence in the Hepatocellular Carcinoma: A Systematic Review and Meta-Analysis.

BACKGROUND AND OBJECTIVES: the early diagnosis of hepatocellular carcinoma (HCC) benefits from the use of alpha-fetoprotein (AFP) together with imaging diagnosis using abdominal ultrasonography, CT, and MRI, leading to improved early detection of HCC. A lot of progress has been made in the field, but some cases are missed or late diagnosed in advanced stages of the disease. Therefore, new tools (serum markers, imagistic technics) are continually being reconsidered. Serum alpha-fetoprotein (AFP), protein induced by vitamin K absence or antagonist II (PIVKA II) diagnostic accuracy for HCC (global and early disease) has been investigated (in a separate or cumulative way). The purpose of the present study was to determine the performance of PIVKA II compared to AFP. MATERIALS AND METHODS: systematic research was conducted in PubMed, Web of Science, Embase, Medline and the Cochrane Central Register of Controlled Trials, taking into consideration articles published between 2018 and 2022. RESULTS: a total number of 37 studies (5037 patients with HCC vs. 8199 patients-control group) have been included in the meta-analysis. PIVKA II presented a better diagnostic accuracy in HCC diagnostic vs. alpha-fetoprotein (global PIVKA II AUROC 0.851 vs. AFP AUROC 0.808, respectively, 0.790 vs. 0.740 in early HCC cases). The conclusion from a clinical point of view, concomitant use of PIVKA II and AFP can bring useful information, added to that brought by ultrasound examination.

Chronic Inflammation-A Link between Nonalcoholic Fatty Liver Disease (NAFLD) and Dysfunctional Adipose Tissue.

Nonalcoholic fatty liver disease (NAFLD) is a new challenge in modern medicine, due to its high prevalence in the world. The pathogenesis of NAFLD is a complex dysmetabolic process, following the "multiple-hit" hypothesis that involves hepatocytes excessive accumulation of triglycerides, insulin resistance (IR), increased oxidative stress, chronic low-grade inflammatory response and lipotoxicity. In this review, we provide an overview of the interrelation of these processes, the link between systemic and local inflammation and the role of dysfunctional adipose tissue (AT) in the NAFLD development. Multiple extrahepatic triggers of the pathophysiological mechanisms of NAFLD are described: nutritional deficiency or malnutrition, unhealthy food intake, the dysfunction of the liver-gut axis, the involvement of the mesenteric adipose tissue, the role of adipokines such as adiponectin, of food intake hormone, the leptin and leptin resistance (LR) and adipose tissue's hormone, the resistin. In addition, a wide range of intrahepatic players are involved: oxidative stress, fatty acid oxidation, endoplasmic reticulum stress, mitochondrial dysfunction, resident macrophages (Kupffer cells), neutrophils, dendritic cells (DCs), B and T lymphocytes contributing to the potential evolution of NAFLD to nonalcoholic steatohepatitis (NASH). This interdependent approach to complex dysmetabolic imbalance in NAFLD, integrating relevant studies, could contribute to a better clarification of pathogenesis and consequently the development of new personalized treatments, targeting de novo lipogenesis, chronic inflammation and fibrosis. Further studies are needed to focus not only on treatment, but also on prevention strategy in NAFLD.

Cytokines, paraoxonase-1, periostin and non-invasive liver fibrosis scores in patients with non-alcoholic fatty liver disease and persistently elevated aminotransferases: A pilot study.

Non-alcoholic fatty liver disease (NAFLD) is the most common liver disease worldwide. The aim of this study was to evaluate the possible association between paraoxonase-1 (PON1), periostin (POSTN), tumor necrosis factor (TNF)-α, interleukin (IL)-6, IL-10 serum concentration with non-invasive liver fibrosis scores, in a cohort of patients with NAFLD. We studied a cohort of 52 patients diagnosed with NAFLD. The NAFLD fibrosis score (NFS), Fibrosis-4 Index (FIB-4), AST to platelet ratio index (APRI) and BARD scores were calculated for each patient. We determined the PON1, POSTN, TNF-α, IL-6, and IL-10 serum values using ELISA kits. There was no correlation between PON1 or POSTN serum levels and non-invasive liver fibrosis. The TNF-α serum values were independently associated with the liver fibrosis scores (P=0.02 for NFS and P=0.002 for FIB-4). Age and metabolic syndrome were also independently linked to the fibrosis scores. In conclusion, serum levels of TNF-α, age and metabolic syndrome were associated with the non-invasive liver fibrosis scores.

Cardiovascular Risk Factors and Physical Activity for the Prevention of Cardiovascular Diseases in the Elderly.

Cardiovascular diseases create an important burden on the public health systems, especially in the elderly, mostly because this group of patients frequently suffer from multiple comorbidities. Accumulating cardiovascular risk factors during their lifetime has a detrimental effect on an older adult's health status. The modifiable and non-modifiable cardiovascular risk factors are very diverse, and are frequently in a close relationship with the metabolic comorbidities of the elderly, mainly obesity and Diabetes Mellitus. In this review, we aim to present the most important cardiovascular risk factors which link aging and cardiovascular diseases, starting from the pathophysiological links between these factors and the aging process. Next, we will further review the main interconnections between obesity and Diabetes Mellitus and cardiovascular diseases of the elderly. Lastly, we consider the most important aspects related to prevention through lifestyle changes and physical activity on the occurrence of cardiovascular diseases in the elderly.

The Effects of Flavonoids in Cardiovascular Diseases.

Flavonoids are metabolites of plants and fungus. Flavonoid research has been paid special attention to in recent times after the observation of their beneficial effects on the cardiovascular system. These favorable effects are exerted by flavonoids mainly due to their antioxidant properties, which result from the ability to decrease the oxidation of low-density lipoproteins, thus improving the lipid profiles. The other positive effect exerted on the cardiovascular system is the ability of flavonoids to produce vasodilation and regulate the apoptotic processes in the endothelium. Researchers suggested that these effects, including their anti-inflammatory function, are consequences of flavonoids' potent antioxidant properties, but recent studies have shown multiple signaling pathways linked to them, thus suggesting that there are more mechanisms involved in the beneficial effect of the flavonoids on the human body. This review aims to present the latest data on the classification of these substances, their main mechanisms of action in the human body, and the beneficial effects on the physiological and pathological status of the cardiovascular system.

Paraoxonase-1 Serum Concentration and PON1 Gene Polymorphisms: Relationship with Non-Alcoholic Fatty Liver Disease.

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is an important cause of chronic liver diseases around the world. Paraoxonase-1 (PON1) is an enzyme produced by the liver with an important antioxidant role. The aim of this study was to evaluate PON1 serum concentration and PON1 gene polymorphisms in patients with NAFLD. MATERIALS AND METHODS: We studied a group of 81 patients with NAFLD with persistently elevated aminotransferases and a control group of 81 patients without liver diseases. We collected clinical information and performed routine blood tests. We also measured the serum concentration of PON1 and evaluated the PON1 gene polymorphisms L55M, Q192R, and C-108T. RESULTS: There was a significant difference (p < 0.001) in serum PON1 concentrations among the two groups. The heterozygous and the mutated homozygous variants (LM + MM) of the L55M polymorphism were more frequent in the NAFLD group (p < 0.001). These genotypes were found in a multivariate binary logistic regression to be independently linked to NAFLD (Odds ratio = 3.4; p = 0.04). In a multivariate linear regression model, the presence of NAFLD was associated with low PON1 concentration (p < 0.001). CONCLUSIONS: PON1 serum concentrations were diminished in patients with NAFLD, and the presence of NAFLD was linked with low PON1 concentration. The LM + MM genotypes of the PON1 L55M polymorphism were an independent predictor for NAFLD with persistently elevated aminotransferases.

Cytokines Genotype-Phenotype Correlation in Nonalcoholic Steatohepatitis.

NASH consists in lipid accumulation in hepatocytes that trigger oxidative stress, secretion of proinflammatory cytokines leading to steatohepatitis (NASH). The study aimed to investigate the levels of proinflammatory (TNF-α and IL-6) along with anti-inflammatory cytokine IL-10 in patients with NASH and to correlate the cytokines' level with their polymorphism. Sixty-six patients with NASH and 30 healthy volunteers were included in the study. The plasmatic level of IL-6, IL-10, and TNF-α were determined by ELISA. IL-10 -1082 G/A, IL-6 -174 G/C, and TNF-α -308 G/A polymorphisms were determined using the PCR-RFLP technique. IL-6, TNF-α, and CRP levels were significantly higher in patients with NASH. There was a positive correlation between proinflammatory cytokines and a negative correlation between IL-10 and proinflammatory markers. The G allele and GG genotype of IL-6 -174 G/C polymorphism were more frequently noticed in NASH patients. Regarding IL-10 -1082 G/A polymorphism, the AA genotype was correlated with NASH and with a low plasmatic level of IL-10. The A allele in position 308 of the TNF-α gene was associated with high level of cytokine. In conclusion, there was an imbalance between pro- and anti-inflammatory cytokines in NASH patients. IL-10 -1082 G/A and TNF-α -308 G/A genotypes were correlated with the plasmatic levels of cytokines.