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Molecules (Basel, Switzerland) Apr 2024Ilama leaves are an important source of secondary metabolites with promising anticancer properties. Cancer is a disease that affects a great number of people worldwide....
Ilama leaves are an important source of secondary metabolites with promising anticancer properties. Cancer is a disease that affects a great number of people worldwide. This work aimed to investigate the in vivo, in vitro and in silico anticancer properties of three acyclic terpenoids (geranylgeraniol, phytol and farnesyl acetate) isolated from petroleum ether extract of ilama leaves. Their cytotoxic activity against U-937 cells was assessed using flow cytometry to determine the type of cell death and production of reactive oxygen species (ROS). Also, a morphological analysis of the lymph nodes and a molecular docking study using three proteins related with cancer as targets, namely, Bcl-2, Mcl-1 and VEGFR-2, were performed. The flow cytometry and histomorphological analysis revealed that geranylgeraniol, phytol and farnesyl acetate induced the death of U-937 cells by late apoptosis and necrosis. Geranylgeraniol and phytol induced a significant increase in ROS production. The molecular docking studies showed that geranylgeraniol had more affinity for Bcl-2 and VEGFR-2. In the case of farnesyl acetate, it showed the best affinity for Mcl-1. This study provides information that supports the anticancer potential of geranylgeraniol, phytol and farnesyl acetate as compounds for the treatment of cancer, particularly with the potential to treat non-Hodgkin's lymphoma.
Topics: Humans; Plant Leaves; Molecular Docking Simulation; Plants, Medicinal; Plant Extracts; Reactive Oxygen Species; Antineoplastic Agents, Phytogenic; Mexico; Apoptosis; Cell Line, Tumor; Animals; Vascular Endothelial Growth Factor Receptor-2; Computer Simulation; Proto-Oncogene Proteins c-bcl-2; U937 Cells
PubMed: 38731446
DOI: 10.3390/molecules29091956 -
Medicine May 2024Warfarin, a widely utilized anticoagulant, is paramount for preventing thromboembolic events in patients with mechanical heart valve replacements. However, its narrow...
Warfarin, a widely utilized anticoagulant, is paramount for preventing thromboembolic events in patients with mechanical heart valve replacements. However, its narrow therapeutic index can lead to over-anticoagulation and overdose, resulting in serious health risks. This study examines the efficacy of human prothrombin complex concentrate (PCC) in managing warfarin overdose, in comparison with traditional treatments. A retrospective analysis was conducted on 162 adults who presented with warfarin overdose (INR > 5.0) at a tertiary care hospital between 2016 and 2020. Participants were divided into 2 groups-those treated with PCC (n = 57) and those treated with conventional methods (n = 105), including vitamin K and fresh frozen plasma. The primary outcome was the rate of reaching the target (International Normalized Ratio) INR within 24 hours. Secondary outcomes included transfusion requirements, thromboembolic events, adverse reactions, 30-day mortality, and length of hospital stay. PCC demonstrated significant efficacy, with 89.5% of patients achieving the target INR within 24 hours, compared to 64.8% in the control group (P < .05). The PCC group also had reduced transfusion requirements and a shorter average hospital stay. There was no significant difference in thromboembolic events or adverse reactions between the 2 groups, and the reduced 30-day mortality in the PCC group was not statistically significant. Human prothrombin complex concentrate is associated with rapid reaching the target INR, decreased transfusion needs, and shortened hospitalization, making it a promising option for warfarin overdose management. While the results are encouraging, larger, multicenter, randomized controlled trials are necessary to further validate these findings and optimize PCC administration protocols.
Topics: Humans; Warfarin; Blood Coagulation Factors; Female; Male; Retrospective Studies; Anticoagulants; International Normalized Ratio; Middle Aged; Drug Overdose; Aged; Heart Valve Prosthesis Implantation; Thromboembolism; Adult; Treatment Outcome; Blood Transfusion; Length of Stay; Vitamin K
PubMed: 38728459
DOI: 10.1097/MD.0000000000038022 -
International Journal of Systematic and... May 2024Two Gram-stain-negative, rod-shaped bacteria, designated as strains KJ10-1 and KJ40-1, were isolated from marine brown algae. Both strains were catalase-positive,...
Two Gram-stain-negative, rod-shaped bacteria, designated as strains KJ10-1 and KJ40-1, were isolated from marine brown algae. Both strains were catalase-positive, oxidase-positive, and facultative aerobic. Strain KJ10-1 exhibited optimal growth at 25 °C, pH 7.0, and 3 % NaCl, whereas strain KJ40-1 showed optimal growth at 25 °C, pH 7.0, and 2 % NaCl. The respiratory quinones of strain KJ10-1 were ubiquinone-8, ubiquinone-7, menaquinone-7, and methylated menaquinone-7, while the respiratory quinone of strain KJ40-1 was only ubiquinone-8. As major fatty acids, strain KJ10-1 contained C, C ω8, iso-C, and summed feature 3 (C 7 and/or C 6) and strain KJ40-1 contained C and summed features 3 and 8 (C 7 and/or C 6). The major polar lipids in strain KJ10-1 were phosphatidylethanolamine, phosphatidylglycerol, and an unidentified aminolipid, whereas those in strain KJ40-1 were phosphatidylethanolamine, phosphatidylglycerol, and diphosphatidylglycerol. The DNA G+C contents of strains KJ10-1 and KJ40-1 were 42.1 and 40.8 mol%, respectively. Based on 16S rRNA gene sequences, strains KJ10-1 and KJ40-1 exhibited the closest relatedness to MMS16-UL250 (98.6 %) and S-1 (95.4 %), respectively. Phylogenetic analyses, based on both 16S rRNA and 92 housekeeping genes, showed that the strains formed distinct phylogenic lineages within the genera and . Digital DNA-DNA hybridization and orthologous average nucleotide identity values between strain KJ10-1 and other species, as well as between strain KJ40-1 and other species, were below the thresholds commonly accepted for prokaryotic species delineation. Based on the phenotypic, chemotaxonomic, and phylogenetic data, strains KJ10-1 and KJ40-1 represent novel species of the genera and , respectively, for which the names sp. nov. and sp. nov. are proposed, respectively. The type strains of and are KJ10-1 (=KACC 22589=JCM 35409) and KJ40-1 (=KACC 22588=JCM 35410), respectively.
Topics: RNA, Ribosomal, 16S; Base Composition; Phylogeny; Fatty Acids; DNA, Bacterial; Bacterial Typing Techniques; Sequence Analysis, DNA; Vibrio; Ubiquinone; Shewanella; Phaeophyceae; Vitamin K 2; Phospholipids; Nucleic Acid Hybridization; Seawater
PubMed: 38728177
DOI: 10.1099/ijsem.0.006378 -
Journal of the American Heart... May 2024A rapid shift has occurred from vitamin K antagonists toward direct oral anticoagulants, which have a lower risk of intracerebral hemorrhage (ICH). However, effects on...
BACKGROUND
A rapid shift has occurred from vitamin K antagonists toward direct oral anticoagulants, which have a lower risk of intracerebral hemorrhage (ICH). However, effects on clinical outcomes after ICH are understudied. We aimed to describe the prevalence of antithrombotic drugs and to study the prognosis among prestroke functionally independent Swedish patients with ICH.
METHODS AND RESULTS
We identified all patients diagnosed with nontraumatic ICH in 2017 to 2021 from the Swedish Stroke Register (n=13 155) and assessed death and functional outcome at 3 months after ICH in prestroke functionally independent patients (n=10 014). Functional outcome was estimated among 3-month survivors on the basis of self-reported activities of daily living scores. Risks of outcomes were estimated using Poisson regression. In 13 155 patients, 14.5% used direct oral anticoagulant, 10.1% vitamin K antagonists, and 21.6% antiplatelets at ICH onset. Among 10 014 pre-stroke activities of daily living-independent patients, oral anticoagulants and antiplatelets were associated with increased mortality risk (adjusted risk ratio, 1.27 [95% CI, 1.13-1.43]; <0.001; and adjusted risk ratio, 1.23 [95% CI, 1.13-1.34]; <0.001 respectively). Mortality risk did not statistically differ between antiplatelets and oral anticoagulants nor between direct oral anticoagulant and vitamin K antagonists. Among 5126 patients with nonmissing functional outcome (69.1% of survivors), antiplatelets (adjusted risk ratio, 1.06 [95% CI, 0.99-1.13]; =0.100) and oral anticoagulants (adjusted risk ratio, 1.01 [95% CI, 0.92-1.12]; =0.768) were not statistically significantly associated with functional dependence.
CONCLUSIONS
There was no statistically significant difference in mortality risk between direct oral anticoagulant and vitamin K antagonists in prestroke functionally independent patients (unadjusted for oral anticoagulant class indication). Furthermore, mortality risk in antiplatelet and oral anticoagulant users might differ less than previously suggested.
Topics: Humans; Male; Female; Sweden; Aged; Registries; Retrospective Studies; Cerebral Hemorrhage; Fibrinolytic Agents; Aged, 80 and over; Anticoagulants; Middle Aged; Platelet Aggregation Inhibitors; Treatment Outcome; Stroke; Vitamin K; Administration, Oral; Activities of Daily Living; Risk Factors; Risk Assessment
PubMed: 38726922
DOI: 10.1161/JAHA.123.034716 -
International Journal of Systematic and... May 2024A yellow pigmented, Gram-stain-positive, motile, facultatively anaerobic and irregular rod-shaped bacteria (strain M0-14) was isolated from a till sample collected from...
A yellow pigmented, Gram-stain-positive, motile, facultatively anaerobic and irregular rod-shaped bacteria (strain M0-14) was isolated from a till sample collected from the foreland of a high Arctic glacier near the settlement of Ny-Ålesund in the Svalbard Archipelago, Norway. Phylogenetic analysis based on 16S rRNA gene sequence comparisons revealed that M0-14 formed a lineage within the family , suborder . M0-14 represented a novel member of the genus and had highest 16S rRNA gene sequence similarity to LRZ-2 (97.3 %). Growth occurred at 4-25 °C (optimum 4-18 °C), at pH 6.0-9.0 (optimum pH 7.0), and in the presence of 0-5 % (w/v) NaCl. The predominant menaquinone was MK-9(H) and the major fatty acids were anteiso-C, C and summed feature 3 (comprising Cω7 and/or Cω6). The major polar lipids were phosphatidylglycerol, phosphatidylinositol mannosides, phosphatidylinositol, one undefined phospholipid and five undefined phosphoglycolipids. The cell-wall diamino acid was l-ornithine whereas rhamnose and mannose were the cell-wall sugars. Polyphosphate particles were found inside the cells of M0-14. Polyphosphate kinase and polyphosphate-dependent glucokinase genes were detected during genomic sequencing of M0-14. In addition, the complete gene cluster and synthesis genes, which are important for the uptake and transport of phosphorus in cells, were annotated in the genomic data. According to the genomic data, M0-14 has a metabolic pathway related to phosphorus accumulation. The DNA G+C content of the genomic DNA was 70.8 %. On the basis of its phylogenetic relationship, phenotypic properties and chemotaxonomic distinctiveness, strain M0-14 represents a novel species of the genus , for which the name sp. nov. is proposed. The type strain is M0-14 (= CCTCC AB 2012967 = NRRL B-59105).
Topics: RNA, Ribosomal, 16S; Phylogeny; Arctic Regions; Fatty Acids; Base Composition; Vitamin K 2; DNA, Bacterial; Bacterial Typing Techniques; Sequence Analysis, DNA; Ice Cover; Phospholipids; Svalbard
PubMed: 38722773
DOI: 10.1099/ijsem.0.006368 -
International Journal of Systematic and... May 2024A Gram-stain-negative, facultative aerobic, catalase- and oxidase-positive, non-motile, non-flagellated, and coccus-shaped bacterium, strain J2-16, isolated from a...
A Gram-stain-negative, facultative aerobic, catalase- and oxidase-positive, non-motile, non-flagellated, and coccus-shaped bacterium, strain J2-16, isolated from a marine green alga, was characterized taxonomically. Strain J2-16 grew at 20-40 °C (optimum, 30 °C), pH 6.0-10.0 (optimum, pH 7.0), and 1.0-4.0 % (w/v) NaCl (optimum, 3.0 %). Menaquinone-7 was identified as the sole respiratory quinone, and major fatty acids (>5 %) were C 9, iso-C, C, anteiso-C, C, C, and C 8. The polar lipids of strain J2-16 consisted of phosphatidylglycerol, phosphatidylethanolamine, two unidentified phospholipids, and three unidentified lipids. The genome size of strain J2-16 was 5384 kb with a G+C content of 52.0 mol%. Phylogenetic analyses based on 16S rRNA gene and 120 protein marker sequences revealed that strain J2-16 formed a distinct phyletic lineage within the genus , closely related to WN38 and DSM 45221 with 16S rRNA gene sequence similarities of 95.7 and 94.4 %, respectively. Average nucleotide identity and digital DNA-DNA hybridization values between strain J2-16 and species were lower than 71.2 and 20.0 %, respectively. The phenotypic, chemotaxonomic, and molecular features support that strain J2-16 represents a novel species of the genus , for which the name sp. nov. is proposed. The type strain is J2-16 (=KACC 22590=JCM 35407).
Topics: RNA, Ribosomal, 16S; Base Composition; Phylogeny; Fatty Acids; Vitamin K 2; DNA, Bacterial; Bacterial Typing Techniques; Sequence Analysis, DNA; Phospholipids; Chlorophyta; Nucleic Acid Hybridization; Seawater
PubMed: 38717925
DOI: 10.1099/ijsem.0.006367 -
Food Chemistry Sep 2024Vitamin K is a multi-function vitamin that has emerging roles in bone, brain and vascular health. Vitamin K composition data remain limited globally and Australia has...
Vitamin K is a multi-function vitamin that has emerging roles in bone, brain and vascular health. Vitamin K composition data remain limited globally and Australia has lacked nationally representative data for vitamin K1 (phylloquinone) in horticultural commodities. Primary samples (n = 927) of 90 Australian-grown fruit, vegetable and nut commodities were purchased in three Australian cities. We measured vitamin K1/phylloquinone in duplicate in 95 composite samples using liquid chromatography with electrospray ionisation-tandem mass spectrometry. The greatest mean concentrations of vitamin K1/phylloquinone were found in kale (565 μg/100 g), baby spinach (255 μg/100 g) and Brussels sprouts (195 μg/100 g). The data contribute to the global collection of vitamin K food composition data. They add to the evidence that vitamin K1/phylloquinone concentrations vary markedly between geographic regions, supporting development of region-specific datasets for national food composition databases that do not yet contain data for vitamin K. Such data are needed globally.
Topics: Australia; Fruit; Vegetables; Vitamin K; Tandem Mass Spectrometry; Nuts; Vitamin K 1
PubMed: 38705117
DOI: 10.1016/j.foodchem.2024.139382 -
Nutrients Apr 2024The Mediterranean diet (MD) is associated with improved longevity and the prevention and management of chronic inflammatory diseases (CIDs). Vitamin K, which is present...
The Mediterranean diet (MD) is associated with improved longevity and the prevention and management of chronic inflammatory diseases (CIDs). Vitamin K, which is present in MD core components such as leafy green vegetables, is also known as a protective factor for CIDs. Estimates of vitamin K intake in Mediterranean settings are still scarce, and the association between MD and vitamin K intake is yet to be established. This study analyzed vitamin K intake and MD adherence in the Algarve region, in Portugal. We conducted a cross-sectional study in a nonrandom sample of adults using an online questionnaire which included a validated food-frequency questionnaire and a screener for MD adherence. A total of 238 participants were recruited (68% women and 32% men). Adherence to the MD was low (11%). Only 10% of the participants had vitamin K intake below the adequate intake. Adherence to the MD was positively correlated with vitamin K intake (r = 0.463; < 0.001) and age (r = 0.223; < 0.001). Our findings underscore the importance of promoting adherence to the MD for optimal vitamin K intake, and future research should focus on developing effective interventions to promote this dietary pattern, particularly among younger individuals and men.
Topics: Humans; Diet, Mediterranean; Female; Male; Cross-Sectional Studies; Vitamin K; Middle Aged; Adult; Portugal; Aged; Diet Surveys; Surveys and Questionnaires; Feeding Behavior
PubMed: 38674788
DOI: 10.3390/nu16081098 -
Thrombosis Research Jun 2024D-dimer testing may help deciding the duration of anticoagulation in subjects at high risk of venous thromboembolism (VTE) recurrence. Two management studies on this... (Comparative Study)
Comparative Study
BACKGROUND
D-dimer testing may help deciding the duration of anticoagulation in subjects at high risk of venous thromboembolism (VTE) recurrence. Two management studies on this issue have been published (DULCIS in 2014 and APIDULCIS in 2022). They had similar designs but had important different results. Aim of this article is to compare their results.
METHODS
Both studies were finalized to extend anticoagulation [with vitamin K anticoagulants (VKAs) in DULCIS or apixaban 2.5 mg BID (kindly provided by BMS-Pfizer Collaboration) in APIDULCIS] only in patients with positive D-dimer results.
RESULTS
More D-dimer assays resulted positive in APIDULCIS than in DULCIS (61.1 % vs 47.7 %, respectively; p < 0.0001). While only 4 (0.5 %) refused low dose apixaban in APIDULCIS, the 22.6 % of patients with positive D-dimer refused to resume VKAs in DULCIS; their rates of recurrence were 187 and 8.8 per 100 person-years, respectively (incidence rate ratio [IRR]: 21.2). The incidence of bleeding was low in those receiving apixaban vs those who resumed VKAs (0.4 vs 2.3 per 100 person-years, respectively; IRR 0.17;). While the recurrence rate was low and similar in the studies in subjects who resumed anticoagulation, it was significantly higher in APIDULCIS than in DULCIS in those who stopped anticoagulation for negative D-dimer (5.6 vs 3.0 per 100 person-years, respectively; IRR 1.9).
CONCLUSION
The low dose Apixaban for extended VTE treatment is effective and safe, and well accepted by patients. Why subjects who stopped anticoagulation for negative D-dimer had a higher recurrence rate in APIDULCIS than in DULCIS remains to be explained.
Topics: Humans; Fibrin Fibrinogen Degradation Products; Venous Thromboembolism; Recurrence; Female; Male; Anticoagulants; Middle Aged; Aged; Pyrazoles; Pyridones; Risk Factors; Vitamin K
PubMed: 38669963
DOI: 10.1016/j.thromres.2024.04.018 -
Cells Apr 2024This review explores the likely clinical impact of Pregnane X Receptor (PXR) activation by vitamin K on human health. PXR, initially recognized as a master regulator of... (Review)
Review
This review explores the likely clinical impact of Pregnane X Receptor (PXR) activation by vitamin K on human health. PXR, initially recognized as a master regulator of xenobiotic metabolism in liver, emerges as a key regulator influencing intestinal homeostasis, inflammation, oxidative stress, and autophagy. The activation of PXR by vitamin K highlights its role as a potent endogenous and local agonist with diverse clinical implications. Recent research suggests that the vitamin K-mediated activation of PXR highlights this vitamin's potential in addressing pathophysiological conditions by promoting hepatic detoxification, fortifying gut barrier integrity, and controlling pro-inflammatory and apoptotic pathways. PXR activation by vitamin K provides an intricate association with cancer cell survival, particularly in colorectal and liver cancers, to provide new insights into potential novel therapeutic strategies. Understanding the clinical implications of PXR activation by vitamin K bridges molecular mechanisms with health outcomes, further offering personalized therapeutic approaches for complex diseases.
Topics: Humans; Clinical Relevance; Health; Pregnane X Receptor; Signal Transduction; Vitamin K
PubMed: 38667296
DOI: 10.3390/cells13080681