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The New Phytologist May 2024Understanding the genetic basis of how plants defend against pathogens is important to monitor and maintain resilient tree populations. Swiss needle cast (SNC) and...
Understanding the genetic basis of how plants defend against pathogens is important to monitor and maintain resilient tree populations. Swiss needle cast (SNC) and Rhabdocline needle cast (RNC) epidemics are responsible for major damage of forest ecosystems in North America. Here we investigate the genetic architecture of tolerance and resistance to needle cast diseases in Douglas-fir (Pseudotsuga menziesii) caused by two fungal pathogens: SNC caused by Nothophaeocryptopus gaeumannii, and RNC caused by Rhabdocline pseudotsugae. We performed case-control genome-wide association analyses and found disease resistance and tolerance in Douglas-fir to be polygenic and under strong selection. We show that stomatal regulation as well as ethylene and jasmonic acid pathways are important for resisting SNC infection, and secondary metabolite pathways play a role in tolerating SNC once the plant is infected. We identify a major transcriptional regulator of plant defense, ERF1, as the top candidate for RNC resistance. Our findings shed light on the highly polygenic architectures underlying fungal disease resistance and tolerance and have important implications for forestry and conservation as the climate changes.
PubMed: 38803110
DOI: 10.1111/nph.19797 -
Revista Medica de Chile Jun 2023Human intoxication by long-acting anticoagulant rodenticides, known as superwarfarins, causes coagulopathy that is difficult to manage. We present the case of a...
Human intoxication by long-acting anticoagulant rodenticides, known as superwarfarins, causes coagulopathy that is difficult to manage. We present the case of a 42-year-old man who ingested a toxic dose of rodenticide in a suicide attempt, evolving with epistaxis, INR of 11.6, and needing hospitalization. For seven days, serial controls of coagulation tests were carried out, with optimization of different doses of Vitamin K supplementation. The case highlights this type of anticoagulant's potency and prolonged half-life (approximately six weeks), which requires regular clinical control and satisfactory treatment adherence.
Topics: Humans; Male; Adult; Rodenticides; Suicide, Attempted; Anticoagulants; 4-Hydroxycoumarins; Vitamin K
PubMed: 38801389
DOI: 10.4067/s0034-98872023000600797 -
Therapeutic Advances in Cardiovascular... 2024Atrial fibrillation (AF) accounts for 40% of all cardiac arrhythmias and is associated with a high risk of stroke and systemic thromboembolic complications. Dabigatran,... (Review)
Review
Atrial fibrillation (AF) accounts for 40% of all cardiac arrhythmias and is associated with a high risk of stroke and systemic thromboembolic complications. Dabigatran, rivaroxaban, apixaban, and edoxaban are direct oral anticoagulants (DOACs) that have been proven to prevent stroke in patients with non-valvular AF. This review summarizes the pharmacokinetics, pharmacodynamics, and drug interactions of DOACs, as well as new data from pharmacogenetic studies of these drugs. This review is aimed at analyzing the scientific literature on the gene polymorphisms involved in the metabolism of DOACs. We searched PubMed, Cochrane, Google Scholar, and CyberLeninka (Russian version) databases with keywords: 'dabigatran', 'apixaban', 'rivaroxaban', 'edoxaban', 'gene polymorphism', 'pharmacogenetics', '', '', '', '', and ''. The articles referred for this review include (1) full-text articles; (2) study design with meta-analysis, an observational study in patients taking DOAC; and (3) data on the single-nucleotide polymorphisms and kinetic parameters of DOACs (plasma concentration), or a particular clinical outcome, published in English and Russian languages during the last 10 years. The ages of the patients ranged from 18 to 75 years. Out of 114 reviewed works, 24 were found eligible. As per the available pharmacogenomic data, polymorphisms affecting DOACs are different. This may aid in developing individual approaches to optimize DOAC pharmacotherapy to reduce the risk of hemorrhagic complications. However, large-scale population studies are required to determine the dosage of the new oral anticoagulants based on genotyping. Information on the genetic effects is limited owing to the lack of large-scale studies. Uncovering the mechanisms of the genetic basis of sensitivity to DOACs helps in developing personalized therapy based on patient-specific genetic variants and improves the efficacy and safety of DOACs in the general population.
Topics: Humans; Atrial Fibrillation; Administration, Oral; Hemorrhage; Pharmacogenomic Variants; Risk Factors; Anticoagulants; Treatment Outcome; Stroke; Risk Assessment; Phenotype; Polymorphism, Single Nucleotide; Vitamin K; Drug Interactions
PubMed: 38801157
DOI: 10.1177/17539447241249886 -
Narra J Apr 2024Fatigue, a condition of lack of energy and motivation resulting in the feeling of extreme tiredness or exhaustion, is usually prevented and treated with ergogenic aids,...
Fatigue, a condition of lack of energy and motivation resulting in the feeling of extreme tiredness or exhaustion, is usually prevented and treated with ergogenic aids, such as in the form of nutritional supplements. Papaya ( may be a potential candidate for ergogenic aids, considering its healthy secondary metabolite properties and number of metabolite compounds that could be affected by the location where the plant growing. The aim of this study was to identify the phytochemicals of papaya leaves from three different locations: geothermal, coastal, and urban areas in Aceh province, Indonesia. Concentrations of papaya leaf with the highest number of secondary metabolite compounds were tested in rats to measure blood lactate acid concentrations after strenuous exercise. The number of chemical compounds identified from the three locations was 24 compounds; 23 compounds and 17 compounds, respectively. The highest concentration of chemical compounds that have antifatigue activity contained in all papaya leaf samples were neophytadiene, linolenic acid, gamma tocopherol, hexadecanoic acid, vitamin E, carpaine, octadecatrienoic acid, nor lean-12-ene, squalene, and phytol. Furthermore, most of the compounds' highest concentrations were found in papaya leaves from the coastal area and, therefore, tested on the animal model. Treatment was provided in 12 male rats with different doses of papaya powder supplements for 15 days. The results showed that lactic acid levels of rats received a dose of 400 mg/kg of papaya leaf extract reduced the lactic acid concentration (=0.014) compared with the control group. This study highlights that papaya leaves from the coastal area have the most potential activities as ergogenic herbal aid and were able to reduce lactic acid levels in rats after strenuous exercise.
Topics: Animals; Carica; Indonesia; Rats; Plant Leaves; Plant Extracts; Male; Fatigue; Phytochemicals; Lactic Acid
PubMed: 38798837
DOI: 10.52225/narra.v4i1.321 -
Cells May 2024The TAM receptor ligand Gas6 is known for regulating inflammatory and immune pathways in various organs including the brain. Gas6 becomes fully functional through the...
The TAM receptor ligand Gas6 is known for regulating inflammatory and immune pathways in various organs including the brain. Gas6 becomes fully functional through the post-translational modification of multiple glutamic acid residues into γ-carboxyglutamic in a vitamin K-dependent manner. However, the significance of this mechanism in the brain is not known. We report here the endogenous expression of multiple components of the vitamin K cycle within the mouse brain at various ages as well as in distinct brain glial cells. The brain expression of all genes was increased in the postnatal ages, mirroring their profiles in the liver. In microglia, the proinflammatory agent lipopolysaccharide caused the downregulation of all key vitamin K cycle genes. A secreted Gas6 protein was detected in the medium of both mouse cerebellar slices and brain glial cell cultures. Furthermore, the endogenous Gas6 γ-carboxylation level was abolished through incubation with the vitamin K antagonist warfarin and could be restored through co-incubation with vitamin K1. Finally, the γ-carboxylation level of the Gas6 protein within the brains of warfarin-treated rats was found to be significantly reduced ex vivo compared to the control brains. In conclusion, we demonstrated for the first time the existence of a functional vitamin K cycle within rodent brains, which regulates the functional modification of endogenous brain Gas6. These results indicate that vitamin K is an important nutrient for the brain. Furthermore, the measurement of vitamin K-dependent Gas6 functionality could be an indicator of homeostatic or disease mechanisms in the brain, such as in neurological disorders where Gas6/TAM signalling is impaired.
Topics: Animals; Intercellular Signaling Peptides and Proteins; Vitamin K; Brain; Mice; Mice, Inbred C57BL; Rats; Male; Warfarin; Microglia; Lipopolysaccharides; Neuroglia
PubMed: 38786095
DOI: 10.3390/cells13100873 -
The New Phytologist May 2024Investigating plant responses to climate change is key to develop suitable adaptation strategies. However, whether changes in land management can alleviate increasing...
Investigating plant responses to climate change is key to develop suitable adaptation strategies. However, whether changes in land management can alleviate increasing drought threats to crops in the future is still unclear. We conducted a management × drought experiment with winter wheat (Triticum aestivum L.) to study plant water and vegetative traits in response to drought and management (conventional vs organic farming, with intensive vs conservation tillage). Water traits (root water uptake pattern, stem metaxylem area, leaf water potential, stomatal conductance) and vegetative traits (plant height, leaf area, leaf Chl content) were considered simultaneously to characterise the variability of multiple traits in a trait space, using principal component analysis. Management could not alleviate the drought impacts on plant water traits as it mainly affected vegetative traits, with yields ultimately being affected by both management and drought. Trait spaces were clearly separated between organic and conventional management as well as between drought and control conditions. Moreover, changes in trait space triggered by management and drought were independent from each other. Neither organic management nor conservation tillage eased drought impacts on winter wheat. Thus, our study raised concerns about the effectiveness of these management options as adaptation strategies to climate change.
PubMed: 38785184
DOI: 10.1111/nph.19851 -
Scientific Reports May 2024This study explored the chemical composition, antioxidant activity, and total phenol content of aerial parts from 25 accessions of three Achillea species (Achillea...
This study explored the chemical composition, antioxidant activity, and total phenol content of aerial parts from 25 accessions of three Achillea species (Achillea wilhelmsii C. Koch, Achillea vermicularis Trin., and Achillea tenuifolia Lam.). The plants were collected from various natural habitats across Iran, encompassing regions such as Central, Western, Southern, Northern, Western, and Northwestern parts of the country. Subsequently, they were grown together under field conditions. The study revealed significant variation in essential oil yields among accessions of A. wilhelmsii, ranging from 0.01 to 0.107%, A. vermicularis with a range of 0.075 to 1.5%, and A. tenuifolia showing a variation of 0.1 to 2%. The study utilized Gas Chromatography-Mass Spectrometry (GC-MS) analysis, revealing 75, 49, and 75 compounds in the essential oils of A. wilhelmsii, A. tenuifolia, and A. vermicularis, respectively. Major components included camphor, 1,8-cineole, anethole, α-pinene, and phytol in A. wilhelmsii, 1,8-cineole, camphor, levo-carvone, and δ-terpinene in A. vermicularis, and β-cubebene, elixene, β-sesquiphellandrene, 1,8-cineole, camphor, and δ-terpinene in A. tenuifolia. The essential oil compositions of A. wilhelmsii and A. vermicularis were predominantly characterized by oxygenated monoterpenes, whereas that of A. tenuifolia was characterized by sesquiterpenes. Cluster analysis grouped accessions into three clusters, with A. tenuifolia forming a distinct group. Principal Component Analysis (PCA) triplot (62.21% of total variance) confirmed these results and provided insights into compound contributions. Furthermore, total phenolic content and antioxidant activity of the accessions of three species were assessed over 2 years. A. tenuifolia exhibited the highest levels in both categories, with statistically significant linear regression between antioxidant activity and total phenol content for A. tenuifolia and A. wilhelmsii. These findings emphasize significant phytochemical diversity within Achillea species, positioning them as promising natural sources of antioxidants. Further exploration and selection of specific accessions within each species are crucial for unlocking their medicinal potential and supporting cultivation and conservation efforts.
Topics: Achillea; Antioxidants; Oils, Volatile; Phytochemicals; Gas Chromatography-Mass Spectrometry; Multivariate Analysis; Phenols; Iran
PubMed: 38783072
DOI: 10.1038/s41598-024-62834-1 -
Heliyon May 2024Globally, the demand for natural remedies such as honey to manage ailments has increased. Yet, the health benefits and chemical composition of African honeys are not...
Globally, the demand for natural remedies such as honey to manage ailments has increased. Yet, the health benefits and chemical composition of African honeys are not well understood. Therefore, this study aimed to characterise the bio-functional properties and the phytochemical composition of 18 honeys from Kenya, Uganda, and Cameroon in comparison to the popular and commercially available Manuka 5+ honey from New Zealand. The 2,2-diphenyl-1-picrylhydrazyl radical scavenging assay (DPPH-RSA) was used to determine the antioxidant property, whilst the agar well diffusion and broth dilution (Minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC)) assays were used to determine antimicrobial property. Further, colorimetric methods were used for phytochemical analysis. Our results showed that honeys collected from Rift Valley region of Kenya (e.g. Poi, Salabani and Mbechot) and Western region of Cameron (e.g. Bangoulap) had the highest antioxidant (DPPH RSA of 41.52-43.81%) and antimicrobial (MIC (3.125-6.25% w/v) and MBC (6.25-12.5% w/v)) activities. Additionally, the total flavonoid (770-970 mg QE/100 g), phenol (944.79-1047.53 mg GAE/100 g), terpenoid (239.78-320.89 mg LE/100 g) and alkaloid (119.40-266.57 mg CE/100 g) contents reached the highest levels in these bioactive African honeys, which significantly and positively correlated with their bio-functional properties. The functional and phytochemical composition of these bioactive African honeys were similar to or higher than those of the Manuka 5+ honey. Furthermore, gas chromatography-mass spectrometry analysis of African honeys revealed 10 most prominent volatile organic compounds that contribute to their geographical distinction: triacontane, heptacosane, (Z)-9-tricosene, tetracosane, 6-propyl-2,3-dihydropyran-2,4-dione, octacosane, 1,2,4-trimethylcyclohexane, 1,3-bis(1,1-dimethylethyl) benzene, 2-methylheptane and phytol. Overall, our findings suggest that some of the tested African honeys are natural sources of antimicrobial and antioxidant therapies that can be exploited upon further research and commercialized as high value honey.
PubMed: 38778936
DOI: 10.1016/j.heliyon.2024.e30839 -
Clinical Nutrition ESPEN Jun 2024Few studies link vitamin K intake with incident atherosclerotic cardiovascular disease (ASCVD), and the specific mechanism remains uncertain. We aimed to evaluate the...
BACKGROUND AND AIMS
Few studies link vitamin K intake with incident atherosclerotic cardiovascular disease (ASCVD), and the specific mechanism remains uncertain. We aimed to evaluate the relationship between dietary vitamin K and ASCVD.
METHODS
This study used cross-sectional data from people over 20 years old who took part in the National Health and Nutrition Examination Survey (NHANES) between 2013 and 2018. Vitamin K intake was assessed using a 24-h dietary review. The Patient Medical Conditions Questionnaire was used to assess ASCVD. The stability of the outcomes was evaluated using cubic spline models with restricted parameters and logistic regression, while subgroup analyses were also performed.
RESULTS
There were 14,465 participants, with 9.78% (1415/14,465) who diagnosed with ASCVD. Compared with individuals with lower vitamin K intake Q1 (≤39.0 ug/day), the adjusted OR values for dietary vitamin K intake and ASCVD in Q2 (39.1-70.8 ug/day), Q3 (70.9-131.0 mg/day), and Q4 (≥131.1 ug/day) were 0.88 (95% CI: 0.74-1.04, p = 0.134), 0.77(95% CI: 0.65-0.93, p = 0.005), and 0.78 (95% CI: 0.65-0.95, p = 0.013), respectively. The association between dietary vitamin K intake and ASCVD showed an L-shaped curve (nonlinear, p = 0.006). The OR for ASCVD in participants with vitamin K intake <127.1ug/day was 0.996 (95% CI: 0.993-0.998, p = 0.002).
CONCLUSIONS
The relationship between dietary vitamin K intake and ASCVD was L-shaped curve in US adults, the inflection point was roughly 127.1 ug/day.
Topics: Humans; Female; Male; Cross-Sectional Studies; Vitamin K; Atherosclerosis; Nutrition Surveys; Middle Aged; Diet; Adult; Aged; Cardiovascular Diseases; Risk Factors
PubMed: 38777459
DOI: 10.1016/j.clnesp.2024.03.031 -
Renal Failure Dec 2024This review aims to evaluate the safety and efficacy of apixaban vs. vitamin K antagonists (VKAs) in patients on dialysis. (Comparative Study)
Comparative Study Meta-Analysis Review
BACKGROUND
This review aims to evaluate the safety and efficacy of apixaban vs. vitamin K antagonists (VKAs) in patients on dialysis.
METHODS
All types of studies published on PubMed, Embase, CENTRAL, and Web of Science up to 10 September 2023 and comparing outcomes of apixaban vs. VKA in dialysis patients were eligible.
RESULTS
Two randomized controlled trials (RCTs) and six retrospective studies were included. Apixaban treatment was associated with significantly lower risk of major bleeding (RR: 0.61; 95% CI: 0.48, 0.77; = 50%) and clinically relevant non-major bleeding (RR: 0.82, 95% CI: 0.68, 0.98, = 9%) compared to VKA. Meta-analysis also showed that the risk of gastrointestinal bleeding (RR: 0.74, 95% CI: 0.64, 0.85, = 16%) and intracranial bleeding (RR: 0.64, 95% CI: 0.49, 0.84, = 0%) was significantly reduced with apixaban. Meta-analysis showed no difference in the risk of ischemic stroke (RR: 0.40, 95% CI: 0.06, 2.69, = 0%), mortality (RR: 1.26, 95% CI: 0.74, 2.16, = 94%) and recurrent venous thromboembolism (RR: 1.02, 95% CI: 0.87, 1.21, = 0%) between the two groups. Subgroup analysis of RCTs showed no difference in bleeding outcomes.
CONCLUSIONS
Low-quality evidence from a mix of RCTs and retrospective studies shows that apixaban may have better safety and equivalent efficacy as compared to VKA in dialysis patients. Apixaban treatment correlated with significantly reduced risk of major bleeding and clinically relevant nonmajor bleeding in observational studies but not in RCTs. The predominance of retrospective data warrants caution in the interpretation of results.
Topics: Humans; Anticoagulants; Factor Xa Inhibitors; Hemorrhage; Pyrazoles; Pyridones; Randomized Controlled Trials as Topic; Renal Dialysis; Vitamin K
PubMed: 38770962
DOI: 10.1080/0886022X.2024.2349114