Bioactive Potential of Algae and Algae-Derived Compounds: Focus on Anti-Inflammatory, Antimicrobial, and Antioxidant Effects.

Algae, both micro- and macroalgae, are recognized for their rich repository of bioactive compounds with potential therapeutic applications. These marine organisms produce a variety of secondary metabolites that exhibit significant anti-inflammatory, antioxidant, and antimicrobial properties, offering promising avenues for the development of new drugs and nutraceuticals. Algae-derived compounds, including polyphenols, carotenoids, lipids, and polysaccharides, have demonstrated efficacy in modulating key inflammatory pathways, reducing oxidative stress, and inhibiting microbial growth. At the molecular level, these compounds influence macrophage activity, suppress the production of pro-inflammatory cytokines, and regulate apoptotic processes. Studies have shown that algae extracts can inhibit inflammatory signaling pathways such as NF-κB and MAPK, reduce oxidative damage by activating Nrf2, and offer an alternative to traditional antibiotics by combatting bacterial infections. Furthermore, algae's therapeutic potential extends to addressing diseases such as cardiovascular disorders, neurodegenerative conditions, and cancer, with ongoing research exploring their efficacy in preclinical animal models. The pig model, due to its physiological similarities to humans, is highlighted as particularly suitable for validating the bioactivities of algal compounds in vivo. This review underscores the need for further investigation into the specific mechanisms of action and clinical applications of algae-derived biomolecules.

Cyanidin-3-O-glucoside as a Nutrigenomic Factor in Type 2 Diabetes and Its Prominent Impact on Health.

Type 2 diabetes (T2D) accounts for a global health problem. It is a complex disease as a result of the combination of environmental as well as genetic factors. Morbidity is still increasing across the world. One of the possibilities for the prevention and mitigation of the negative consequences of type 2 diabetes is a nutritional diet rich in bioactive compounds such as polyphenols. This review is focused on cyanidin-3-O-glucosidase (C3G), which belongs to the anthocyanins subclass, and its anti-diabetic properties. There are numerous pieces of evidence that C3G exerts positive effects on diabetic parameters, including in vitro and in vivo studies. It is involved in alleviating inflammation, reducing blood glucose, controlling postprandial hyperglycemia, and gene expression related to the development of T2D. C3G is one of the beneficial polyphenolic compounds that may help to overcome the public health problems associated with T2D.

Effect of Dried Apple Pomace (DAP) as a Feed Additive on Antioxidant System in the Rumen Fluid.

The study aimed to evaluate the effect of dried apple pomace (DAP) as a feed additive on the enzymatic activity and non-enzymatic compounds belonging to the antioxidant system in cattle rumen fluid. The experiment included 4 Polish Holstein−Friesian cannulated dairy cows and lasted 52 days. The control group was fed with the standard diet, while in the experimental group, 6% of the feedstuff was replaced by dried apple pomace. After the feeding period, ruminal fluid was collected. The spectrophotometric technique for the activity of lysosomal enzymes, the content of vitamin C, polyphenols, and the potential to scavenge the free DPPH radical was used. The enzyme immunoassay tests (ELISA) were used to establish the activity of antioxidants enzymes and MDA. Among the rumen aminopeptidases, a significant reduction (p < 0.01) from 164.00 to 142.00 was observed for leucyl-aminopeptidase. The activity of glycosidases was decreased for HEX (from 231.00 to 194.00) and ß-Glu (from 1294.00 to 1136.00), while a significant statistically increase was noticed for BGRD (from 31.10 to 42.40), α-Glu (from 245.00 to 327.00), and MAN (from 29.70 to 36.70). Furthermore, the activity of catalase and GSH (p < 0.01) was inhibited. In turn, the level of vitamin C (from 22.90 to 24.10) and MDA (from 0.36 to 0.45) was statistically higher (p < 0.01). The most positive correlations were observed between AlaAP and LeuAP (r = 0.897) in the aminopeptidases group and between ß-Gal and MAN (r = 0.880) in the glycosidases group. Furthermore, one of the most significant correlations were perceived between SOD and AlaAP (r = 0.505) and AcP (r = 0.450). The most negative correlation was noticed between α-Gal and DPPH (r = −0.533) based on these observations. Apple pomace as a feed additive has an influence on lysosomal degradation processes and modifies oxidation−reduction potential in the rumen fluid. Polyphenols and other low-weight antioxidant compounds are sufficient to maintain redox balance in the rumen.

NFKB1 -94ins/delATTG polymorphism is a novel prognostic marker in first line-treated multiple myeloma.

Nuclear factor kappa B (NFKB) plays an important role in multiple myeloma (MM), and bortezomib affects this pathway. We retrospectively analysed the effect of the NFKB1 -94ins/delATTG polymorphism on the survival of 295 MM patients treated at a single centre. The median progression-free survival (PFS) was 790 (659-921) d in patients with NFKB1 homozygous insertion genotype (I/I, n = 99) and 624 (515-733) d in deletion-carriers (I/D&D/D, n = 196, P = 0·013). In multivariate analysis, I/I carriers showed a favourable PFS compared to I/D&D/D with a hazard ratio of 0·622 (0·457-0·847), P = 0·003, in addition to international staging system (ISS) score, fluorescence in situ hybridization (FISH) risk score, age and bortezomib treatment. I/I patients benefited more from bortezomib treatment [PFS 902 (703-1101) and 580 (343-817), P = 0·008] than I/D&D/D patients [PFS 659 (487-831) and 488 (323-653), P = 0·531]; in addition the beneficial effect of low ISS score was not observed in the I/D&D/D group [PFS 639 (454-824) and 650 (458-842), P = 0·226], while it was clear in I/I patients [PFS 1140 (803-1477) and 580 (408-752), P < 0·001]. We conclude that homozygous carriers of the insertion allele of the NFKB1 -94ins/delATTG polymorphism have a better prognosis and probably benefit more from bortezomib treatment than MM patients carrying the deletion allele.

Distinct clinical characteristics of myeloproliferative neoplasms with calreticulin mutations.

Somatic insertions/deletions in the calreticulin gene have recently been discovered to be causative alterations in myeloproliferative neoplasms. A combination of qualitative and quantitative allele-specific polymerase chain reaction, fragment-sizing, high resolution melting and Sanger-sequencing was applied for the detection of three driver mutations (in Janus kinase 2, calreticulin and myeloproliferative leukemia virus oncogene genes) in 289 cases of essential thrombocythemia and 99 cases of primary myelofibrosis. In essential thrombocythemia, 154 (53%) Janus kinase 2 V617F, 96 (33%) calreticulin, 9 (3%) myeloproliferative leukemia virus oncogene gene mutation-positive and 30 triple-negative (11%) cases were identified, while in primary myelofibrosis 56 (57%) Janus kinase 2 V617F, 25 (25%) calreticulin, 7 (7%) myeloproliferative leukemia virus oncogene gene mutation-positive and 11 (11%) triple-negative cases were identified. Patients positive for the calreticulin mutation were younger and had higher platelet counts compared to Janus kinase 2 mutation-positive counterparts. Calreticulin mutation-positive patients with essential thrombocythemia showed a lower risk of developing venous thrombosis, but no difference in overall survival. Calreticulin mutation-positive patients with primary myelofibrosis had a better overall survival compared to that of the Janus kinase 2 mutation-positive (P=0.04) or triple-negative cases (P=0.01). Type 2 calreticulin mutation occurred more frequently in essential thrombocythemia than in primary myelofibrosis (P=0.049). In essential thrombocythemia, the calreticulin mutational load was higher than the Janus kinase 2 mutational load (P<0.001), and increased gradually in advanced stages. Calreticulin mutational load influenced blood counts even at the time point of diagnosis in essential thrombocythemia. We confirm that calreticulin mutation is associated with distinct clinical characteristics and explored relationships between mutation type, load and clinical outcome.

Nutraceutical Properties of Syringic Acid in Civilization Diseases-Review.

Civilization diseases account for a worldwide health issue. They result from daily behavioral, environmental, and genetic factors. One of the most significant opportunities to prevent and alleviate the occurrence of these diseases is a diet rich in antioxidants like polyphenols. This review paper is concentrated on syringic acid (SA), one of the representative compounds of phenolic acids subgroups. There are many in vitro and in vivo studies on SA that assess its pivotal effects on oxidative stress and inflammation parameters. It is effective on metabolic risk factors as well, including hyperglycemia, high blood pressure, and hyperlipidemia. SA is one of the prominent polyphenolic compounds that may help address health issues related to civilization diseases.

The prognostic impact of germline 46/1 haplotype of Janus kinase 2 in cytogenetically normal acute myeloid leukemia.

BACKGROUND: Prognostic risk stratification according to acquired or inherited genetic alterations has received increasing attention in acute myeloid leukemia in recent years. A germline Janus kinase 2 haplotype designated as the 46/1 haplotype has been reported to be associated with an inherited predisposition to myeloproliferative neoplasms, and also to acute myeloid leukemia with normal karyotype. The aim of this study was to assess the prognostic impact of the 46/1 haplotype on disease characteristics and treatment outcome in acute myeloid leukemia. DESIGN AND METHODS: Janus kinase 2 rs12343867 single nucleotide polymorphism tagging the 46/1 haplotype was genotyped by LightCycler technology applying melting curve analysis with the hybridization probe detection format in 176 patients with acute myeloid leukemia under 60 years diagnosed consecutively and treated with curative intent. RESULTS: The morphological subtype of acute myeloid leukemia with maturation was less frequent among 46/1 carriers than among non-carriers (5.6% versus 17.2%, P = 0.018, cytogenetically normal subgroup: 4.3% versus 20.6%, P = 0.031), while the morphological distribution shifted towards the myelomonocytoid form in 46/1 haplotype carriers (28.1% versus 14.9%, P = 0.044, cytogenetically normal subgroup: 34.0% versus 11.8%, P = 0.035). In cytogenetically normal cases of acute myeloid leukemia, the 46/1 carriers had a considerably lower remission rate (78.7% versus 94.1%, P = 0.064) and more deaths in remission or in aplasia caused by infections (46.8% versus 23.5%, P = 0.038), resulting in the 46/1 carriers having shorter disease-free survival and overall survival compared to the 46/1 non-carriers. In multivariate analysis, the 46/1 haplotype was an independent adverse prognostic factor for disease-free survival (P = 0.024) and overall survival (P = 0.024) in patients with a normal karyotype. Janus kinase 2 46/1 haplotype had no impact on prognosis in the subgroup with abnormal karyotype. CONCLUSIONS: Janus kinase 2 46/1 haplotype influences morphological distribution, increasing the predisposition towards an acute myelomonocytoid form. It may be a novel, independent unfavorable risk factor in acute myeloid leukemia with a normal karyotype.

Screening the expression of ABCB6 in erythrocytes reveals an unexpectedly high frequency of Lan mutations in healthy individuals.

Lan is a high-incidence blood group antigen expressed in more than 99.9% of the population. Identification of the human ABC transporter ABCB6 as the molecular basis of Lan has opened the way for studies assessing the relation of ABCB6 function and expression to health and disease. To date, 34 ABCB6 sequence variants have been described in association with reduced ABCB6 expression based on the genotyping of stored blood showing weak or no reactivity with anti-Lan antibodies. In the present study we examined the red blood cell (RBC) surface expression of ABCB6 by quantitative flow cytometry in a cohort of 47 healthy individuals. Sequencing of the entire coding region of the ABCB6 gene in low RBC ABCB6 expressors identified a new allele (IVS9+1G>A, affecting a putative splice site at the boundary of exon 9) and two nonsynonymous SNPs listed in the SNP database (R192Q (rs150221689) and G588 S (rs145526996)). The R192Q mutation showed co-segregation with reduced RBC ABCB6 expression in a family, and we found the G588 S mutation in a compound heterozygous individual with undetectable ABCB6 expression, suggesting that both mutations result in weak or no expression of ABCB6 on RBCs. Analysis of the intracellular expression pattern in HeLa cells by confocal microscopy indicated that these mutations do not compromise overall expression or the endolysosomal localization of ABCB6. Genotyping of two large cohorts, containing 235 and 1039 unrelated volunteers, confirmed the high allele frequency of Lan-mutations. Our results suggest that genetic variants linked to lower or absent cell surface expression of ABCB6/Langereis may be more common than previously thought.

Medium-sized FLT3 internal tandem duplications confer worse prognosis than short and long duplications in a non-elderly acute myeloid leukemia cohort.

Internal tandem duplications (ITDs) of the fms-like tyrosine kinase 3 (FLT3) gene occur in about 25% of patients with adult acute myeloid leukemia (AML). The aim of our study was to investigate the frequency of FLT3-ITD mutations followed by a detailed analysis of the mutational load and size of ITD insertions in a cohort consisting of 324 patients younger than 60 years old and treated with curative intention. FLT3-ITD alone did not influence overall survival (OS) or disease-free survival (DFS). We observed worse OS and DFS for patients with high mutational load indicative for loss of the FLT3 wild type allele (p = 0.010, p = 0.038, respectively). In multivariate analyses, patients with FLT3-ITD(48-60bp) showed worse OS and DFS compared to other groups (FLT3-ITD(neg), FLT3-ITD (< 48b), FLT3-ITD (> 60bp); p = 0.014, p = 0.019, respectively). Our novel observation suggested that not only high FLT3-ITD load, but also medium-sized ITD insertions (48-60 bp) represented an adverse prognostic subgroup of patients with AML.

Type and location of isocitrate dehydrogenase mutations influence clinical characteristics and disease outcome of acute myeloid leukemia.

Mutations of isocitrate dehydrogenase 1 and 2 (IDH1/2) are genetic alterations in acute myeloid leukemia (AML). The aim of our study was to investigate the frequency and prognostic effect of IDH1/2 mutations together followed by an individual analysis of each substitution in a Hungarian cohort consisting of 376 patients with AML. IDH1(mut) and IDH2(mut) were mutually exclusive, detected in 8.5% and 7.5% of cases, respectively. IDH1/2(mut) was associated with: older age (p = 0.001), higher average platelet count (p = 0.001), intermediate karyotype (p < 0.0001), NPM1(mut) (p = 0.022) and lower mRNA expression level of ABCG2 gene (p = 0.006). Overall survival (OS), remission and relapse rates were not different in IDH1(mut) or IDH2(mut) vs. IDH(neg). IDH1(mut) and IDH2(mut) were associated differently with NPM1(mut); co-occurrence was observed in 14.3% of IDH1 R132C vs. 70% of R132H carriers (p = 0.02) and in 47.4% of IDH2 R140Q vs. 0% of R172K carriers (p = 0.02). IDH1 R132H negatively influenced OS compared to IDH(neg) (p = 0.02) or R132C (p = 0.019). Particular amino acid changes affecting the same IDH1 codon influence the clinical characteristics and treatment outcome in AML.

Expression levels of the ABCG2 multidrug transporter in human erythrocytes correspond to pharmacologically relevant genetic variations.

We have developed a rapid, simple and reliable, antibody-based flow cytometry assay for the quantitative determination of membrane proteins in human erythrocytes. Our method reveals significant differences between the expression levels of the wild-type ABCG2 protein and the heterozygous Q141K polymorphic variant. Moreover, we find that nonsense mutations on one allele result in a 50% reduction in the erythrocyte expression of this protein. Since ABCG2 polymorphisms are known to modify essential pharmacokinetic parameters, uric acid metabolism and cancer drug resistance, a direct determination of the erythrocyte membrane ABCG2 protein expression may provide valuable information for assessing these conditions or for devising drug treatments. Our findings suggest that erythrocyte membrane protein levels may reflect genotype-dependent tissue expression patterns. Extension of this methodology to other disease-related or pharmacologically important membrane proteins may yield new protein biomarkers for personalized diagnostics.

NKX2-3 and IRGM variants are associated with disease susceptibility to IBD in Eastern European patients.

AIM: To investigate variants of immunity-related GTPase family M (IRGM) and NKX2-3 genes and genotype-phenotype in Eastern European patients with inflammatory bowel disease (IBD). METHODS: We analyzed 1707 Hungarian and Czech subjects with Crohn's disease (CD) (n = 810, age: 37.1 ± 12.6 years, duration: 10.7 ± 8.4 years) and ulcerative colitis (UC) (n = 428, age: 43.7 ± 15.0 years, duration: 12.6 ± 9.9 years), as well as 469 healthy controls. IRGM rs13361189, NKX2-3 rs10883365 and ECM1 rs13294 polymorphisms were tested by LightCycler allele discrimination. Detailed clinical phenotypes were determined by reviewing the medical charts. RESULTS: NKX2-3 rs10883365 variant allele was associated with increased risk for CD (P = 0.009, OR = 1.24, 95% CI = 1.06-1.48) and UC (P = 0.001, OR = 1.36, 95% CI = 1.13-1.63), whereas variant IRGM allele increased risk for CD (P = 0.029, OR = 1.36, 95% CI = 1.03-1.79). In contrast, ECM1 rs13294 was not associated with either CD or UC. In CD, the variant IRGM allele was associated with a colon-only location (P = 0.02, OR = 1.62, 95% CI = 1.07-2.44), whereas in UC, the ECM1 variant was associated with cutaneous manifestations (P = 0.002, OR = 3.36, 95% CI = 1.48-7.63). Variant alleles did not predict resistance to steroids or azathioprine, efficacy of infliximab, or need for surgery. CONCLUSION: NKX2-3 and IRGM are susceptibility loci for IBD in Eastern European patients. Further studies are needed to confirm the reported phenotype-genotype associations.