Marine-Derived Peptides with Anti-Hypertensive Properties: Prospects for Pharmaceuticals, Supplements, and Functional Food.

Hypertension, a major health concern linked to heart disease and premature mortality, has prompted a search for alternative treatments due to side effects of existing medications. Sustainable harvesting of low-trophic marine organisms not only enhances food security but also provides a variety of bioactive molecules, including peptides. Despite comprising only a fraction of active natural compounds, peptides are ideal for drug development due to their size, stability, and resistance to degradation. Our review evaluates the anti-hypertensive properties of peptides and proteins derived from selected marine invertebrate phyla, examining the various methodologies used and their application in pharmaceuticals, supplements, and functional food. A considerable body of research exists on the anti-hypertensive effects of certain marine invertebrates, yet many species remain unexamined. The array of assessments methods, particularly for ACE inhibition, complicates the comparison of results. The dominance of in vitro and animal in vivo studies indicates a need for more clinical research in order to transition peptides into pharmaceuticals. Our findings lay the groundwork for further exploration of these promising marine invertebrates, emphasizing the need to balance scientific discovery and marine conservation for sustainable resource use.

Self-reported medication information needs among medication users in a general population aged 40 years and above - the Tromsø study.

PURPOSE: To determine the prevalence and associated factors of self-reported medication information needs among medication users in a general population aged 40 years and above - The Tromsø Study. METHODS: Cross-sectional study of medication users (n = 10,231) among participants in the Tromsø Study, a descriptive analysis of questionnaire data and multivariable logistic regression (n = 9,194). RESULTS: Sixteen percent of medication users expressed a need for more information about own medications. Overall, medication users agreed to a higher degree to have received information from the GP compared to the pharmacy. Concerned medication users and those disagreeing to have received information about side effects had the highest odds for needing more information (OR 5.07, 95% CI 4.43-5.81) and (OR 2.21, 95% CI 1.83-2.68), respectively. Medication users who used heart medications (e.g., nitroglycerin, antiarrhythmics, anticoagulants) (OR 1.71, 95% CI 1.46-2.01), medication for hypothyroidism (OR 1.36, 95% CI 1.13-1.64) or had moderately health anxiety had expressed need for medication information. Whereas medication users with lower education, those that never used internet to search for health advice, and medication users who disagreed to have received information about reason-for-use were associated with lower odds (OR 0.75, 95% CI 0.62-0.91), (OR 0.85, 95% CI 0.74-0.98) and (OR 0.68, 95% CI 0.53-0.88), respectively. CONCLUSION: This study demonstrated that there is need for more information about own medications in a general population aged 40 years and above and shed light on several characteristics of medication users with expressed information need which is important when tailoring the right information to the right person.

Cold-pressed minke whale oil reduces circulating LDL/VLDL-cholesterol, lipid oxidation and atherogenesis in apolipoprotein E-deficient mice fed a Western-type diet for 13 weeks.

BACKGROUND: Long-chain n3-polyunsaturated fatty acids (LC n3-PUFA) are well known for their anti-inflammatory activity and their impact on cardiovascular disease. Cold-pressed whale oil (CWO) has half the amount of LC n3-PUFA compared to cod liver oil (CLO). Still, there has been observed more pronounced beneficial effects on cardiovascular disease markers from intake of CWO compared to intake of CLO in human intervention studies. Extracts from CWO deprived of fatty acids have also been shown to display antioxidative and anti-inflammatory effects in vitro. The aim of this study was to investigate whether intake of a high-fat Western-type diet (WD) supplemented with CWO would prevent the development of atherosclerotic lesions in apolipoprotein E-deficient (ApoE-/-) mice. METHODS: Seventy female ApoE-/- mice were fed a WD containing 1% CWO, CLO or corn oil (CO). Atherosclerotic lesion formation, body and tissue weights, hepatic gene expression together with serum levels of LDL/VLDL-cholesterol, ox-LDL, total antioxidant status and various serum cardiovascular disease/proinflammatory markers were evaluated. Statistical analyses were performed using SPSS, and Shapiro-Wilk's test was performed to determine the distribution of the variables. Statistical difference was assessed using One-Way ANOVA with Tukeys' post hoc test or Kruskal-Wallis test. The hepatic relative gene expression was analysed with REST 2009 (V2.0.13). RESULTS: Mice fed CWO had less atherosclerotic lesions in the aortic arch compared to mice fed CO. Levels of LDL/VLDL-cholesterol and ox-LDL-cholesterol were also markedly reduced whereas total antioxidant levels were enhanced in mice fed CWO compared to CO-fed mice. In addition, CWO-fed mice gained less weight and several hepatic genes involved in the cholesterol metabolism were up-regulated compared to CO-fed mice. CONCLUSION: In the present study mice fed a WD supplemented with 1% CWO had reduced formation of atherosclerotic lesions in the aortic arch, reduced serum LDL/VLDL-cholesterol and ox-LDL-cholesterol, increased serum total antioxidant status and reduced body weight compared to mice fed a WD supplemented with 1% CO.

Antioxidant and Anti-Inflammatory Activities in Extracts from Minke Whale (Balaenoptera acutorostrata) Blubber.

Intake of long-chain omega-3 polyunsaturated fatty acids (LC-n3-PUFA) is commonly recognized to reduce cardiovascular disease (CVD). In previous studies, cold-pressed whale oil (CWO) and cod liver oil (CLO) were given as a dietary supplement to healthy volunteers. Even though CWO contains less than half the amount of LC-n3-PUFA of CLO, CWO supplement resulted in beneficial effects on anti-inflammatory and CVD risk markers compared to CLO. In the present study, we prepared virtually lipid-free extracts from CWO and CLO and evaluated the antioxidative capacity (AOC) and anti-inflammatory effects. Oxygen radical absorbance capacity (ORAC) and ferric reducing antioxidant power (FRAP) assays were used to test the AOC, and the results indicated high levels of antioxidants present in all extracts. The anti-inflammatory effects of the extracts were tested with lipopolysaccharide- (LPS-) treated THP-1 cells, measuring its ability to reduce cytokine and chemokine secretion. Several CWO extracts displayed anti-inflammatory activity, and a butyl alcohol extract of CWO most effectively reduced TNF-α (50%, p < 0.05) and MCP-1 (85%, p < 0.001) secretion. This extract maintained a stable effect of reducing MCP-1 secretion (60%, p < 0.05) even after long-term storage. In conclusion, CWO has antioxidant and anti-inflammatory activities that may act in addition to its well-known LC-n3-PUFA effects.

Differentially Expressed MicroRNAs in Meningiomas Grades I and II Suggest Shared Biomarkers with Malignant Tumors.

Meningiomas represent the most common primary tumors of the central nervous system, but few microRNA (miRNA) profiling studies have been reported so far. Deep sequencing of small RNA libraries generated from two human meningioma biopsies WHO grades I (benign) and II (atypical) were compared to excess dura controls. Nineteen differentially expressed miRNAs were validated by RT-qPCR using tumor RNA from 15 patients and 5 meninges controls. Tumor suppressor miR-218 and miR-34a were upregulated relative to normal controls, however, miR-143, miR-193b, miR-451 and oncogenic miR-21 were all downregulated. From 10 selected putative mRNA targets tested by RT-qPCR only four were differentially expressed relative to normal controls. PTEN and E-cadherin (CDH1) were upregulated, but RUNX1T1 was downregulated. Proliferation biomarker p63 was upregulated with nuclear localization, but not detected in most normal arachnoid tissues. Immunoreactivity of E-cadherin was detected in the outermost layer of normal arachnoids, but was expressed throughout the tumors. Nuclear Cyclin D1 expression was positive in all studied meningiomas, while its expression in arachnoid was limited to a few trabecular cells. Meningiomas of grades I and II appear to share biomarkers with malignant tumors, but with some additional tumor suppressor biomarkers expression. Validation in more patients is of importance.

Dietary intake of cod and scallop reduces atherosclerotic burden in female apolipoprotein E-deficient mice fed a Western-type high fat diet for 13 weeks.

BACKGROUND: It is now increasingly recognized that the beneficial effects of seafood consumption is not limited to lipids and fatty acid, but that the protein part, i.e., peptides and amino acids, together with vitamins and even unknown bioactive constituents also are important for disease prevention. This study was designed to evaluate the putative anti-atherogenic effects of different protein sources (a lean seafood and a nonseafood) in apolipoprotein E-deficient (apoE(-/-)) mice. METHODS: Twenty-four 5-week-old female apoE(-/-) mice were fed Western type diets containing chicken or a combination of cod and scallops as dietary protein sources for 13 weeks. Atherosclerotic plaque burden, weight, serum levels of leptin, glucose and LDL cholesterol as well as gene expressions from liver and heart were evaluated. Statistical analyses were performed using SPSS. Differences between the variables were evaluated using independent t-test or Mann-Whitney U test for normally and non-normally distributed variables, respectively. Normality was defined by the Shapiro-Wilk test. RESULTS: The mice fed cod-scallop had a 24 % (p < 0.05) reduced total aorta atherosclerotic plaque burden compared to the chicken fed group, whereas the reduction in plaque in the less lesion prone thoracic and abdominal parts of the descending aorta were 46 % (p < 0.05) and 56 % (p < 0.05), respectively. In addition, mice fed cod-scallop gained less weight, and had lower serum levels of leptin, glucose and LDL cholesterol, compared to those fed chicken. Analysis of expression of the genes from liver and heart showed that hepatic endogenous antioxidant paraoxonase 2 (Pon2 gene) and the vascular cell adhesion molecule VCAM-1 (Vcam1 gene) were down regulated in mice fed cod-scallop compared to mice fed chicken. CONCLUSION: The present study revealed a metabolic beneficial effect of lean seafood compared to chicken, as atherosclerotic plaque burden, serum glucose, leptin and LDL cholesterol levels were reduced in mice fed cod-scallop.

Agnoprotein of polyomavirus BK interacts with proliferating cell nuclear antigen and inhibits DNA replication.

BACKGROUND: The human polyomavirus BK expresses a 66 amino-acid peptide referred to as agnoprotein. Though mutants lacking agnoprotein are severely reduced in producing infectious virions, the exact function of this peptide remains incompletely understood. To elucidate the function of agnoprotein, we searched for novel cellular interaction partners. METHODS: Yeast-two hybrid assay was performed with agnoprotein as bait against human kidney and thymus libraries. The interaction between agnoprotein and putative partners was further examined by GST pull down, co-immunoprecipitation, and fluorescence resonance energy transfer studies. Biochemical and biological studies were performed to examine the functional implication of the interaction of agnoprotein with cellular target proteins. RESULTS: Proliferating cell nuclear antigen (PCNA), which acts as a processivity factor for DNA polymerase δ, was identified as an interaction partner. The interaction between agnoprotein and PCNA is direct and occurs also in human cells. Agnoprotein exerts an inhibitory effect on PCNA-dependent DNA synthesis in vitro and reduces cell proliferation when ectopically expressed. Overexpression of PCNA restores agnoprotein-mediated inhibition of cell proliferation. CONCLUSION: Our data suggest that PCNA is a genuine interaction partner of agnoprotein and the inhibitory effect on PCNA-dependent DNA synthesis by the agnoprotein may play a role in switching off (viral) DNA replication late in the viral replication cycle when assembly of replicated genomes and synthesized viral capsid proteins occurs.

BKV agnoprotein interacts with α-soluble N-ethylmaleimide-sensitive fusion attachment protein, and negatively influences transport of VSVG-EGFP.

BACKGROUND: The human polyomavirus BK (BKV) infects humans worldwide and establishes a persistent infection in the kidney. The BK virus genome encodes three regulatory proteins, large and small tumor-antigen and the agnoprotein, as well as the capsid proteins VP1 to VP3. Agnoprotein is conserved among BKV, JC virus (JCV) and SV40, and agnoprotein-deficient mutants reveal reduced viral propagation. Studies with JCV and SV40 indicate that their agnoproteins may be involved in transcription, replication and/or nuclear and cellular release of the virus. However, the exact function(s) of agnoprotein of BK virus remains elusive. PRINCIPAL FINDINGS: As a strategy of exploring the functions of BKV agnoprotein, we decided to look for cellular interaction partners for the viral protein. Several partners were identified by yeast two-hybrid assay, among them α-SNAP which is involved in disassembly of vesicles during secretion. BKV agnoprotein and α-SNAP were found to partially co-localize in cells, and a complex consisting of agnoprotein and α-SNAP could be co-immunoprecipitated from cells ectopically expressing the proteins as well as from BKV-transfected cells. The N-terminal part of the agnoprotein was sufficient for the interaction with α-SNAP. Finally, we could show that BKV agnoprotein negatively interferes with secretion of VSVG-EGFP reporter suggesting that agnoprotein may modulate exocytosis. CONCLUSIONS: We have identified the first cellular interaction partner for BKV agnoprotein. The most N-terminal part of BKV agnoprotein is involved in the interaction with α-SNAP. Presence of BKV agnoprotein negatively interferes with secretion of VSVG-EGFP reporter.