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Scientific Reports Feb 2024The application of natural extracts to vegetable plants can increase production, optimize nutrient and water uptake, and mitigate the effects of stress on vegetable... (Randomized Controlled Trial)
Randomized Controlled Trial
The application of natural extracts to vegetable plants can increase production, optimize nutrient and water uptake, and mitigate the effects of stress on vegetable plants by enhancing primary and secondary metabolism. In this study, Acacia saligna (Labill.) H.L.Wendl. fruit aqueous extract (FAE) was applied as a foliar application to assess and demonstrate its effects on growth, productivity, and phytochemicals of coriander (Coriandrum sativum L.) plants. A. saligna FAE (2%, 4%, and 6%), each combined with 50% of the recommended dose of N fertilizer was applied to coriander plants over the course of two successive seasons in the field. These treatments were compared with the control treatment, which used a 100% recommended dose of N. The four tested treatments were set up in a randomized complete block design with three replicates for a total of 12 experimental plots. Each replicate (experimental plot) was 3 m (2 × 1.5 m) in size and included 300 seeds/m. The phytochemicals were examined using chromatographic and spectrophotometric methods, where the essential oils (EOs) extracted from leaves were analyzed by Gas chromatography-mass spectrometry (GC-MS), while the phenolic and flavonoid compounds were analyzed by High Performance Liquid Chromatography (HPLC). With the application of A. saligna FAE (4%) + 50% N fertilizer, the levels of total solid content, total carbohydrates, total protein, total phenols, and total antioxidant activity, as well as chlorophyll a, chlorophyll b, chlorophyll a + b, and carotenoids, were increased at harvest. The treatment A. saligna FAE at 6% + 50% N fertilizer did not observe significant improvement in the growth parameters of coriander plants because of the anticipated allelopathic effects. By GC-MS analysis, the major compounds in the EO from control treatment were 2-octyn-1-ol (23.93%), and 2-butyl-1-octanol (8.80%), in treated plants with 2% of A. saligna FAE + 50% N fertilizer were (E)-2-decen-1-ol (32.00%), and 1-methoxymethoxy-oct-2-yne (13.71%), in treated plants with 4% A. saligna FAE + 50% N fertilizer were E-2-undecen-1-ol (32.70%), and 3,5,5-trimethyl-1-hexene (8.91%), and in the treated plants with A. saligna FAE (6%) + 50% N fertilizer were phytol (80.44%), and (Z)6,(Z)9-pentadecadien-1-ol (13.75%). The flavonoid components 7-hydroxyflavone, naringin, rutin, quercetin, kaempferol, luteolin, apigenin, and catechin were presented with variable concentrations according to the treatments utilized as identified by HPLC analysis from the methanol extracts of the treated plants with the combination treatments of A. saligna FAE (2, 4, and 6%) and N fertilization (50% from the recommended dose) and control coriander plants (100% N recommended dose). The combination of 50% N fertilizer treatment and the biostimulant A. saligna FAE (4%) seems to improve coriander plant growth while simultaneously lowering N fertilizer consumption. Future research will be needed to further study the effectiveness of several concentrations of A. saligna FAE in various conditions and/or species.
Topics: Coriandrum; Chlorophyll A; Acacia; Fertilizers; Fruit; Phytochemicals; Antioxidants; Flavonoids; Plants
PubMed: 38316894
DOI: 10.1038/s41598-024-53378-5 -
Bioorganic & Medicinal Chemistry Letters Mar 2024Since the outbreak of the pandemic, various anti-SARS-CoV-2 drugs have been developed. In particular, 3CL protease (3C-like protease, 3CLpro) is an attractive drug...
Since the outbreak of the pandemic, various anti-SARS-CoV-2 drugs have been developed. In particular, 3CL protease (3C-like protease, 3CLpro) is an attractive drug target because it is an essential enzyme for viral multiplication and is present only in viruses, not in humans. To date, 3CLpro inhibitors against SARS-CoV-2 such as nirmatrelvir and ensitrelvir have been launched as oral drugs in Japan, but there is still no potent drug against SARS-CoV-2, due to issues of in vivo absorption and stability. Recently, vitamin K was reported to show inhibitory activity against 3CLpro of SARS-CoV-2, and the mechanism of action was predicted to be the formation of a covalent bond between the thiol group of cysteine 145, the active center of 3CLpro, and the C-3 position of vitamin K. Therefore, we synthesized derivatives in which the 2-methyl group of the vitamin K was systematically converted to other substituents and examined their inhibitory activity against 3CLpro of SARS-CoV-2. The results showed that the compounds with the sulfide structure showed an approximately 4-fold increase in activity over vitamin K. These results indicated the possibility of creating new inhibitors based on vitamin K and its derivatives.
Topics: Humans; Peptide Hydrolases; SARS-CoV-2; COVID-19; Endopeptidases; Vitamin K; Protease Inhibitors; Antiviral Agents; Molecular Docking Simulation
PubMed: 38310976
DOI: 10.1016/j.bmcl.2024.129642 -
Open Heart Jan 2024Direct-acting oral anticoagulants (DOACs) have, to a substantial degree, replaced vitamin K antagonists (VKA) as treatments for stroke prevention in atrial fibrillation... (Randomized Controlled Trial)
Randomized Controlled Trial Observational Study
AIMS
Direct-acting oral anticoagulants (DOACs) have, to a substantial degree, replaced vitamin K antagonists (VKA) as treatments for stroke prevention in atrial fibrillation (AF) patients. However, evidence on the real-world causal effects of switching patients from VKA to DOAC is lacking. We aimed to assess the empirical incremental cost-effectiveness of switching patients to DOAC compared with maintaining VKA treatment.
METHODS
The target trial approach was applied to the prospective observational Swiss-AF cohort, which enrolled 2415 AF patients from 2014 to 2017. Clinical data, healthcare resource utilisation and EQ-5D-based utilities representing quality of life were collected in yearly follow-ups. Health insurance claims were available for 1024 patients (42.4%). Overall survival, quality-of-life, costs from the Swiss statutory health insurance perspective and cost-effectiveness were estimated by emulating a target trial in which patients were randomly assigned to switch to DOAC or maintain VKA treatment.
RESULTS
228 patients switching from VKA to DOAC compared with 563 patients maintaining VKA treatment had no overall survival advantage over a 5-year observation period (HR 0.99, 95% CI 0.45, 1.55). The estimated gain in quality-adjusted life years (QALYs) was 0.003 over the 5-year period at an incremental costs of CHF 23 033 (€ 20 940). The estimated incremental cost-effectiveness ratio was CHF 425 852 (€ 387 138) per QALY gained.
CONCLUSIONS
Applying a causal inference method to real-world data, we could not demonstrate switching to DOACs to be cost-effective for AF patients with at least 1 year of VKA treatment. Our estimates align with results from a previous randomised trial.
Topics: Humans; Stroke; Cost-Benefit Analysis; Prospective Studies; Quality of Life; Vitamin K; Anticoagulants; Atrial Fibrillation
PubMed: 38302139
DOI: 10.1136/openhrt-2023-002567 -
BMJ Open Jan 2024The objective of the current study is to compare the treatment effects of different vitamins on essential hypertension to provide an initial basis for developing... (Meta-Analysis)
Meta-Analysis
OBJECTIVES
The objective of the current study is to compare the treatment effects of different vitamins on essential hypertension to provide an initial basis for developing evidence-based practices.
DESIGN
Systematic review and network meta-analysis.
DATA SOURCES
Five electronic databases (PubMed, Embase, Web of Science, Cochrane Central Register of Controlled Trials and ClinicalTrials.gov) were searched from their inception to 25 September 2023.
OUTCOMES
The primary outcomes were the difference between the intervention group and the control group in changes in office systolic blood pressure (SBP) and office diastolic blood pressure (DBP) from baseline. The secondary outcomes were the difference between the intervention group and the control group in changes in 24-hour mean ambulatory systolic blood pressure (24 hours SBP), 24-hour mean ambulatory diastolic blood pressure (24 hours DBP) and heart rate (HR) from baseline.
RESULTS
A total of 23 studies comparing five vitamins (vitamin B, vitamin C, vitamin D, vitamin E, folic acid) and involving 2218 participants were included. The included trials were all vitamin versus placebo, so the network was star-shaped. Among the five vitamins, only vitamin E was significantly more effective at reducing SBP (mean difference: -14.14 mm Hg, 95% credible intervals: -27.62 to -0.88) than placebo. In addition, no evidence was found that any of the five vitamins influenced DBP, 24 hours SBP, 24 hours DBP, or HR. The dose of vitamins, geographical region and percentage of males (only SBP) might be sources of heterogeneity. Sensitivity and subgroup analysis revealed that the effect of vitamin intervention on blood pressure varies according to different doses of vitamins.
CONCLUSIONS
According to the results, vitamin E might be an effective measure to reduce SBP, but more research is needed to validate this finding.
PROSPERO REGISTRATION NUMBER
CRD42022352332.
Topics: Adult; Male; Humans; Vitamin D; Ascorbic Acid; Hypertension; Folic Acid; Riboflavin; Vitamin E; Network Meta-Analysis; Vitamins; Essential Hypertension; Blood Pressure; Vitamin A; Vitamin K
PubMed: 38296289
DOI: 10.1136/bmjopen-2023-074511 -
Europace : European Pacing,... Mar 2024A significant proportion of patients who suffer from atrial fibrillation (AF) and are in need of thromboembolic protection are not treated with oral anticoagulation or...
A significant proportion of patients who suffer from atrial fibrillation (AF) and are in need of thromboembolic protection are not treated with oral anticoagulation or discontinue this treatment shortly after its initiation. This undertreatment has not improved sufficiently despite the availability of direct oral anticoagulants which are associated with less major bleeding than vitamin K antagonists. Multiple reasons account for this, including bleeding events or ischaemic strokes whilst on anticoagulation, a serious risk of bleeding events, poor treatment compliance despite best educational attempts, or aversion to drug therapy. An alternative interventional therapy, which is not associated with long-term bleeding and is as effective as vitamin K anticoagulation, was introduced over 20 years ago. Because of significant improvements in procedural safety over the years, left atrial appendage closure, predominantly achieved using a catheter-based, device implantation approach, is increasingly favoured for the prevention of thromboembolic events in patients who cannot achieve effective anticoagulation. This management strategy is well known to the interventional cardiologist/electrophysiologist but is not more widely appreciated within cardiology or internal medicine. This article introduces the devices and briefly explains the implantation technique. The indications and device follow-up are more comprehensively described. Almost all physicians who care for adult patients will have many with AF. This practical guide, written within guideline/guidance boundaries, is aimed at those non-implanting physicians who may need to refer patients for consideration of this new therapy, which is becoming increasingly popular.
Topics: Adult; Humans; Stroke; Left Atrial Appendage Closure; Consensus; Hemorrhage; Anticoagulants; Thromboembolism; Atrial Fibrillation; Physicians; Vitamin K; Atrial Appendage; Treatment Outcome
PubMed: 38291925
DOI: 10.1093/europace/euae035 -
Journal of Nutritional Science 2024Cardiovascular disease (CVD) is one of the most important diseases which controlling its related risk factors, such as metabolic and inflammatory biomarkers, is... (Meta-Analysis)
Meta-Analysis Review
Cardiovascular disease (CVD) is one of the most important diseases which controlling its related risk factors, such as metabolic and inflammatory biomarkers, is necessary because of the increased mortality risk of that. The aim of our meta-analysis is to reveal the general effect of vitamin K supplementation on its related risk factors. Original databases were searched using standard keywords to identify all randomized clinical trials (RCTs) investigating the effects of vitamin K on CVD. Pooled weighted mean difference (WMD) and 95 % confidence intervals (95 % CI) were achieved by random-model effect analysis for the best estimation of outcomes. The statistical heterogeneity was determined using the Cochran's test and statistics. Seventeen studies were included in this systematic review and meta-analysis. The pooled findings showed that vitamin K supplementation can reduce homeostatic model assessment insulin resistance (HOMA-IR) (WMD: -0⋅24, 95 % CI: -0⋅49, -0⋅02, = 0⋅047) significantly compared to the placebo group. However, no significant effect was observed on other outcomes. Subgroup analysis showed a significant effect of vitamin K2 supplementation compared to vitamin K1 supplementation on HOMA-IR. However, no significant effect was observed on other variables. Also, subgroup analysis showed no potential effect of vitamin K supplementation on any outcome and omitting any articles did not affect the final results. We demonstrated that supplementation with vitamin K has no effect on anthropometrics indexes, CRP, glucose metabolism, and lipid profile factors except HOMA-IR.
Topics: Humans; Dietary Supplements; Vitamin K; Blood Glucose; Insulin Resistance; Cardiovascular Diseases
PubMed: 38282652
DOI: 10.1017/jns.2023.106 -
Frontiers in Immunology 2023Mastitis, the inflammatory condition of mammary glands, has been closely associated with immune suppression and imbalances between antioxidants and free radicals in... (Review)
Review
Mastitis, the inflammatory condition of mammary glands, has been closely associated with immune suppression and imbalances between antioxidants and free radicals in cattle. During the periparturient period, dairy cows experience negative energy balance (NEB) due to metabolic stress, leading to elevated oxidative stress and compromised immunity. The resulting abnormal regulation of reactive oxygen species (ROS) and reactive nitrogen species (RNS), along with increased non-esterified fatty acids (NEFA) and β-hydroxybutyric acid (BHBA) are the key factors associated with suppressed immunity thereby increases susceptibility of dairy cattle to infections, including mastitis. Metabolic diseases such as ketosis and hypocalcemia indirectly contribute to mastitis vulnerability, exacerbated by compromised immune function and exposure to physical injuries. Oxidative stress, arising from disrupted balance between ROS generation and antioxidant availability during pregnancy and calving, further contributes to mastitis susceptibility. Metabolic stress, marked by excessive lipid mobilization, exacerbates immune depression and oxidative stress. These factors collectively compromise animal health, productive efficiency, and udder health during periparturient phases. Numerous studies have investigated nutrition-based strategies to counter these challenges. Specifically, amino acids, trace minerals, and vitamins have emerged as crucial contributors to udder health. This review comprehensively examines their roles in promoting udder health during the periparturient phase. Trace minerals like copper, selenium, and calcium, as well as vitamins; have demonstrated significant impacts on immune regulation and antioxidant defense. Vitamin B12 and vitamin E have shown promise in improving metabolic function and reducing oxidative stress followed by enhanced immunity. Additionally, amino acids play a pivotal role in maintaining cellular oxidative balance through their involvement in vital biosynthesis pathways. In conclusion, addressing periparturient mastitis requires a holistic understanding of the interplay between metabolic stress, immune regulation, and oxidative balance. The supplementation of essential amino acids, trace minerals, and vitamins emerges as a promising avenue to enhance udder health and overall productivity during this critical phase. This comprehensive review underscores the potential of nutritional interventions in mitigating periparturient bovine mastitis and lays the foundation for future research in this domain.
Topics: Female; Pregnancy; Cattle; Animals; Humans; Vitamins; Antioxidants; Trace Elements; Amino Acids; Reactive Oxygen Species; Rumen; Vitamin A; Vitamin K; Mastitis; Anti-Inflammatory Agents
PubMed: 38259482
DOI: 10.3389/fimmu.2023.1290044 -
International Journal of Medical... 2024This study aimed to explore the role of connexin 32 (Cx32) in the directional differentiation of induced pluripotent stem cells (iPSCs) into hepatocytes. Urine-derived...
This study aimed to explore the role of connexin 32 (Cx32) in the directional differentiation of induced pluripotent stem cells (iPSCs) into hepatocytes. Urine-derived epithelial cells were collected from the fresh urine of a healthy donor and transducted with reprogramming plasmid mixture to generate iPSCs. The iPSCs were then directionally differentiated into hepatocytes. During the differentiation, the upregulated and downregulated groups were treated with vitamin K2 (VK2) and 2-aminoethoxyboronate diphenylester (2-APB) to increase and inhibit Cx32 expression, respectively. The control group was not treated with the regulatory factor. Expression of Cx32 and hepatocyte-specific markers, including AFP, hepatocyte nuclear factor 4α (HNF-4α), albumin (ALB) and cytokeratin 18 (CK18) were detected. It indicated that Cx32 expression was not observed in iPSCs, but gradually increased during the process of hepatic differentiation from iPSCs. Upregulation of Cx32 expression by VK2 treatment promoted hepatocyte maturation and enhanced the expression of the aforementioned hepatic specific markers, whereas downregulation of Cx32 expression by 2-APB treatment had the opposite effects. In conclusion, urine-derived iPSCs could be directionally differentiated into hepatocytes. Up-regulation of Cx32 improves the efficiency and maturity of differentiation of iPSCs into hepatocytes, and Cx32 may be a promoting factor during the process of hepatic differentiation from iPSCs.
Topics: Cell Differentiation; Down-Regulation; Gap Junction beta-1 Protein; Hepatocytes; Induced Pluripotent Stem Cells; Vitamin K 2; Humans
PubMed: 38250613
DOI: 10.7150/ijms.83973 -
Metabolites Dec 2023The main purpose of this work is to investigate the phytochemical composition of L. non-polar fraction. GC/MS analysis was used to evaluate the plant extract's...
The main purpose of this work is to investigate the phytochemical composition of L. non-polar fraction. GC/MS analysis was used to evaluate the plant extract's saponifiable and unsaponifiable matter. Although L. lipoidal matter saponification produced 30.3% of fatty acid methyl esters and 69.7% of unsaponifiable matter. Phytol was the most dominant substance in the unsaponifiable materials. Notably, marrubiin which is one of the most prominent metabolites of L. was not detected through our adopted GC/MS technique. Thus, further characterization was proceeded through simple and rapid HPTLC analysis which successfully managed to identify marrubiin. Based on the regression equation, the concentration of marrubiin in L. extract was 14.09 mg/g of dry extract. Concerning acetylcholinesterase inhibitory activity, both the crude L. total methanolic extract and the non-polar fraction displayed reasonable inhibitory activity against acetylcholinesterase (AChE), whereas the pure compound marrubiin was considered to be the most effective and potent AChE inhibitor, with an IC value of 52.66 (µM). According to the molecular docking studies, potential sites of interaction between the pure chemical marrubiin and AChE were examined. The results show that Tyr124 on AChE residue was critical to the activity of the aforementioned drug. Based on the depicted marrubin AChE inhibition activity and reported safety profile, this chemical metabolite is considered as a promising lead compound for further pre-clinical investigation as well as drug development and optimization.
PubMed: 38248830
DOI: 10.3390/metabo14010027 -
BMC Microbiology Jan 2024Macrolide antibiotics have been extensively used for the treatment of Staphylococcus aureus infections. However, the emergence of macrolide-resistant strains of S....
BACKGROUND
Macrolide antibiotics have been extensively used for the treatment of Staphylococcus aureus infections. However, the emergence of macrolide-resistant strains of S. aureus has become a major concern for public health. The molecular mechanisms underlying macrolide resistance in S. aureus are complex and diverse, involving both target site modification and efflux pump systems. In this study, we aim to overcome the molecular diversity of macrolide resistance mechanisms in S. aureus by identifying common molecular targets that could be exploited for the development of novel therapeutics.
METHODS
About 300 Staphylococcus aureus different isolates were recovered and purified from 921 clinical specimen including urine (88), blood (156), sputum (264), nasal swabs (168), pus (181) and bone (39) collected from different departments in Tanta University Hospital. Macrolide resistant isolates were detected and tested for Multi Drug Resistant (MDR). Gel electrophoresis was performed after the D test and PCR reaction for erm(A), (B), (C), msr(A), and mph(C) genes. Finally, we tried different combinations of Erythromycin or Azithromycin antibiotics with either vitamin K or vitamin C.
RESULTS
Macrolide resistance S. aureus isolates exhibited 7 major resistance patterns according to number of resistance markers and each pattern included sub patterns or subgroups. The PCR amplified products of different erm genes; analysis recorded different phenotypes of the Staphylococcus aureus isolates according to their different genotypes. In addition, our new tested combinations of Erythromycin and vitamin C, Erythromycin, and vitamin K, Azithromycin and vitamin C and Azithromycin and vitamin K showed significant antibacterial effect when using every antibiotic alone. Our findings provide new insights into the molecular mechanisms of macrolide resistance in S. aureus and offer potential strategies for the development of novel protocols to overcome this emerging public health threat.
Topics: Humans; Anti-Bacterial Agents; Staphylococcus aureus; Macrolides; Methicillin-Resistant Staphylococcus aureus; Vitamins; Lincosamides; Azithromycin; Drug Resistance, Multiple, Bacterial; Drug Resistance, Bacterial; Streptogramin B; Erythromycin; Staphylococcal Infections; Vitamin K; Vitamin A; Microbial Sensitivity Tests; Ascorbic Acid; Genetic Variation
PubMed: 38245680
DOI: 10.1186/s12866-023-03169-1