Vitamin K Research Articles

PPH and Biological Glue and Phytonadione infusion in patients with Cirrhosis and Anticoagulation therapy with high risk of bleeding during and after Stapled Hemorrhoidopexy

Background: Stapled hemorrhoidopexy is a common treatment for grade 3 hemorrhoids. Patients with conditions that increase the risk of bleeding, as cardiac stents usage with clopidogrel bissulfate and liver cirrhosis, should receive an extra care in surgical procedures due to the high risk of bleeding. For this reason and for patients with third degree hemorrhoids we propose the use of stapled hemorrhoidopexy followed by the use of biological glue and the intravenous administration of Phytonadione. Some studies in the literature demonstrate the risks of periprocedural bleeding and post-surgical procedures, generally lasting > 45 minutes and in chemically or pathologically anticoagulated patients as being at high risk of bleeding and death. Aim: Assess surgical outcomes in patients with hemorrhoids and high risk of bleeding submitted to stapled hemorrhoidopexy followed by biological glue. Methods: Between 2005 and 2024 172 patients were analyzed, in a retrospective cohort study. Results: From 86 patients submitted to stapled hemorrhoidopexy followed by the use of biological glue in the local of stapled line, only one (1.16%) presented bleeding in the surgical postoperative (Group 1). Eighty-six patients submitted to PPH procedure and biological glue use, also received 3 days before surgery and 3 days after surgery one dose of 5 mg of Phytonadione (Vitamin K1) per day (Group 2). In this group, no patients presenting rectal bleeding after surgery with the follow up of 3 months. Patients do not have any other complications and pain in the postoperative period. The median (IQR) operative time was 55 min and the median (IQR) length of hospital stay after surgery was 3 days. Conclusion: Patients with high risk of bleeding submitted to stapled hemorrhoidopexy followed by the use of biological glue (Group 1) presented very low rates of bleeding in the postoperative period. The adjuvant administration of vitamin K1 (Group2) at a recommended dose is proven to better prevent bleeding.

Role of connexin 32 in the directional differentiation of induced pluripotent stem cells into hepatocytes.

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.

The effect of vitamin K supplementation on cardiovascular risk factors: a systematic review and meta-analysis.

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 Q test and I2 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, P = 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.

Technoeconomic analysis of fine chemical electrosynthesis: a case study using electrooxidation of 2-methylnaphthelene to vitamin K3

A cerium-mediated electrooxidation method was developed for synthesizing vitamin K3 in a green and efficient manner. A systematic technoeconomic analysis was provided to understand its potential for practical implementation.

Insights from metagenomics into gut microbiome associated with acute coronary syndrome therapy.

Acute coronary syndrome (ACS) is a predominant cause of mortality, and the prompt and precise identification of this condition is crucial to minimize its impact. Recent research indicates that gut microbiota is associated with the onset, progression, and treatment of ACS. To investigate its role, we sequenced the gut microbiota of 38 ACS patients before and after percutaneous coronary intervention and statin therapy at three time points, examining differential species and metabolic pathways. We observed a decrease in the abundance of Parabacteroides, Escherichia, and Blautia in patients after treatment and an increase in the abundance of Gemalla, Klebsiella variicola, Klebsiella pneumoniae, and others. Two pathways related to sugar degradation were more abundant in patients before treatment, possibly correlated with disorders of sugar metabolism and risk factors, such as hyperglycemia, insulin resistance, and insufficient insulin secretion. Additionally, seven pathways related to the biosynthesis of vitamin K2 and its homolog were reduced after treatment, suggesting that ACS patients may gradually recover after therapy. The gut microbiota of patients treated with different statins exhibited notable differences after treatment. Rosuvastatin appeared to promote the growth of anti-inflammatory bacteria while reducing pro-inflammatory bacteria, whereas atorvastatin may have mixed effects on pro-inflammatory and anti-inflammatory bacteria while increasing the abundance of Bacteroides. Our research will provide valuable insights and enhance comprehension of ACS, leading to better patient diagnosis and therapy.

Vitamin D and K Supplementation Is Associated with Changes in the Methylation Profile of U266-Multiple Myeloma Cells, Influencing the Proliferative Potential and Resistance to Bortezomib.

Multiple myeloma (MM) is a plasma cell malignancy that, despite recent advances in therapy, continues to pose a major challenge to hematologists. Currently, different classes of drugs are applied to treat MM, among others, proteasome inhibitors, immunomodulatory drugs, and monoclonal antibodies. Most of them participate in an interplay with the immune system, hijacking its effector functions and redirecting them to anti-MM activity. Therefore, adjuvant therapies boosting the immune system may be potentially beneficial in MM therapy. Vitamin D (VD) and vitamin K (VK) have multiple so called "non-classical" actions. They exhibit various anti-inflammatory and anti-cancer properties. In this paper, we investigated the influence of VD and VK on epigenetic alterations associated with the proliferative potential of MM cells and the development of BTZ resistance. Our results showed that the development of BTZ resistance is associated with a global decrease in DNA methylation. On the contrary, both control MM cells and BTZ-resistant MM cells exposed to VD alone and to the combination of VD and VK exhibit a global increase in methylation. In conclusion, VD and VK in vitro have the potential to induce epigenetic changes that reduce the proliferative potential of plasma cells and may at least partially prevent the development of resistance to BTZ. However, further ex vivo and in vivo studies are needed to confirm the results and introduce new supplementation recommendations as part of adjuvant therapy.

A Potent PDK4 Inhibitor for Treatment of Heart Failure with Reduced Ejection Fraction.

Heart failure with reduced ejection fraction (HFrEF) is characterized not only by reduced left ventricular ejection fraction (EF) but is also combined with symptoms such as dyspnea, fatigue, and edema. Several pharmacological interventions have been established. However, a treatment targeting a novel pathophysiological mechanism is still needed. Evidence indicating that inhibition of pyruvate dehydrogenase kinase 4 (PDK4) may be cardioprotective has been accumulating. Thus, we focused on vitamin K3 and used its framework as a new PDK4 inhibitor skeleton to synthesize new PDK4 inhibitors that show higher activity than the existing PDK4 inhibitor, dichloroacetic acid, and tested their cardioprotective effects on a mouse heart failure model. Among these inhibitors, PDK4 inhibitor 8 improved EF the most, even though it did not reverse cardiac fibrosis or wall thickness. This novel, potent PDK4 inhibitor may improve EF of failing hearts by regulating bioenergetics via activation of the tricarboxylic acid cycle.

Determination of vitamins K1 and K3 in green tea and in pharmaceutical supplements by capillary micellar electrokinetic chromatography

A method based on capillary micellar electrokinetic chromatography (MEKC) was developed for vitamin K1 and K3 determination. Experimental and instrumental parameters optimized for electrophoretic separation with better peak efficiency were: borate buffer at 0.05 mol L−1, pH 8.5, cetyltrimethylammonium bromide (CTAB) at 0.05 mol L−1, acetonitrile 20 % v/v, 25 °C and a negative potential difference of 30 kV. Sample introduction was made by hydrodynamic at 50 mbar for 15 s. Migration times for vitamins K1 and K3 were (5.2 ± 0.1) and (3.4 ± 0.1) min respectively. Limits of detection and quantification were on the order of 10−5 g L−1 and 10−4 g L−1. For vitamin K1, the precision was between 2 and 7 % for the peak area. Recoveries were 101 ± 2 % and 103 ± 2 % for green tea and vitamin supplement samples, respectively. For vitamin K3, recoveries were 99 ± 3 % for vitamin supplement. Comparative tests were performed with the reference method based on liquid chromatography with agreement of results. The uncertainty and the contribution of the relevant sources was carefully evaluated. The method was found adequate to enable reliable and sensitive measurements of different forms of vitamin K with low consumption of solvents and less generation of waste.

Enhancing menaquinone-7 biosynthesis through strengthening precursor supply and product secretion.

Menaquinone-7 (MK-7) is an important class of vitamin K2 that is essential in human health and can prevent osteoporosis and cardiovascular disease. However, due to the complex synthesis pathway, the synthesis efficiency is low. The main objective of this study was to explore the effect of enhanced supply of precursors in Bacillus natto. Three precursors of pyruvate, shikimic acid, and sodium glutamate were chosen to investigate the effect of enhanced supply of precursors on MK-7 synthesis. Then, the optimal concentrations, different combinations, and different adding times were systematically studied, respectively. Results showed that the combination of shikimic acid and sodium glutamate could boost MK-7 production by 2 times, reaching 50mg/L of MK-7 titer and 0.52mg/(L·h) of MK-7 productivity. Furthermore, adding shikimic acid and sodium glutamate initially and feeding pyruvate at 48h and 72h increased MK-7 production to 58mg/L. At the same time, the expression of the three related genes was also significantly upregulated. Subsequently, a new fermentation strategy combining the precursors enhancement and product secretion was proposed to enhance MK-7 yield and MK-7 productivity to 63mg/L and 0.45mg/(L·h). This study proposed a new fermentation regulation strategy for the enhancement of vitamin K2 biosynthesis.

Amyloidogenic and Neuroinflammatory Molecular Pathways Are Contrasted Using Menaquinone 4 (MK4) and Reduced Menaquinone 7 (MK7R) in Association with Increased DNA Methylation in SK-N-BE Neuroblastoma Cell Line.

Besides its role in coagulation, vitamin K seems to be involved in various other mechanisms, including inflammation and age-related diseases, also at the level of gene expression. This work examined the roles of two vitamin K2 (menaquinones) vitamers, namely, menaquinone-4 (MK4) and reduced menaquinone-7 (MK7R), as gene modulator compounds, as well as their potential role in the epigenetic regulation of genes involved in amyloidogenesis and neuroinflammation. The SK-N-BE human neuroblastoma cells provided a "first-line" model for screening the neuroinflammatory and neurodegenerative molecular pathways. MK7R, being a new vitamin K form, was first tested in terms of solubilization, uptake and cell viability, together with MK4 as an endogenous control. We assessed the expression of key factors in amyloidogenesis and neuroinflammation, observing that the MK7R treatment was associated with the downregulation of neurodegeneration- (PSEN1 and BACE1) and neuroinflammation- (IL-1β and IL-6) associated genes, whereas genes retaining protective roles toward amiloidogenesis were upregulated (ADAM10 and ADAM17). By profiling the DNA methylation patterns of genes known to be epigenetically regulated, we observed a correlation between hypermethylation and the downregulation of PSEN1, IL-1β and IL-6. These results suggest a possible role of MK7R in the treatment of cognitive impairment, giving a possible base for further preclinical experiments in animal models of neurodegenerative disease.

The inhibitory effect of vitamins on O micron virus via targeting the ACE2 receptor. In silico analysis

ObjectivesThe wide and rapid spread of epidemics like COVID 19, highlighted the need for the rapid development of effective solutions. In the present work, a therapeutic approach based on the use of vitamins against the Omicron variant spike was investigated through bioinformatics tools. MethodsThe inhibitory effect of vitamins A, B2, B3, C, E, D, K1 and K7 were tested in silico through a molecular docking and molecular dynamic simulation against four ACE2 grid boxes binding specifically the Omicron proteins 7T9K, 7T9L, 7WBL and 7WBP. ResultsThe docking study showed that vitamins K1, A, D and E bind strongly and efficiently to ACE2 receptor. High docking scores with low binding energies and strong interactions with crucial amino acids residues were generally noted for these four vitamins. The dynamic simulation analysis for 100 ns of the best docked complexes using Gromacs tools at a temperature of 300 K allowed screening vitamin A-grid2, vitamin E- grid4, vitamin K1-grid2 and vitamin D-grid 2 as the most stable complexes compared to rest of systems. ConclusionThese findings indicate that vitamins could interact directly with ACE2 receptor blocking in this way the Omicron binding to its host.

Multivitamin complex-loaded electrospun polyvinyl alcohol core/shell structure fibers for transdermal delivery system: In-silico and experimental studies

Transdermal delivery systems offer a controlled and targeted environment for releasing drugs compared to other delivery systems. This study presents the fabrication of polyvinyl alcohol (PVA) fibers with a multivitamin complex (MV) using the electrospinning technique (ES). The research focuses on understanding how various fiber structures, such as core/shell, simple fibers, and ES parameters, affect the MC release mechanism and cell viability behavior.The vitamin complexes were uniformly encapsulated within the polymeric chains in all structure fibers. PVA simple fibers with and without the vitamin complex don't significantly differ in diameter size. However, the core/Shell fiber has a notable decrease in fiber diameter of 45 %.The fiber with a core/shell structure resulted in a slower release rate of the vitamin complex than simple fiber. According to the Korsmeyer-Peppas model, the release mechanism observed in our study for the simple fibers is classical Fickian diffusion. Instead, core/shell fibers indicate a more anomalous or non-Fickian behavior.The structural configurations of the fibers do not result in statistically significant differences in cell viability. This could be attributed to the identical nature of materials used, including the polymer and MV, across all cases.Finally, a computational chemistry study was used to examine the interaction between polyvinyl alcohol (PVA) and vitamins K3 and B3, like a model of MV. The analysis showed four strong hydrogen bonds between PVA and vitamin B3, whereas the interaction between PVA and vitamin K3 only had one hydrogen bond. Furthermore, the PVA and vitamin B3 interaction had higher energy and was more exothermic and spontaneous than the PVA-vitamin K3 interaction. On the other hand, the PVA-vitamin K4 interaction displayed higher reactivity due to its lower separation energy. In contrast, the PVA-vitamin B3 interaction was more stable.

Supramolecular Interactions between Reduced Vitamin K1 and Dissolved CO2 and H2o in Aprotic Solvents

Vitamin K1 is a naphthoquinone (NQ) that can be electrochemically reduced at negative potentials in two one-electron steps in aprotic organic solvents. The first electron transfer at potential E 1 forms the anion radical (NQ• –) and the second electron transfer process at potential E 2 results in the formation of the dianion (NQ2–). If a hydrogen bond donor (H-D) such as water or an alcohol is progressively added to the aprotic organic solvent, both E 1 and E 2 shift towards more positive potentials. The shifts in potential are much greater for E 2 compared to E 1 as the hydrogen bond donor is added, so that a sufficiently high donor concentration, E 2 merges with E 1 and only one voltammetric wave is observed at potential E 3 due to the transfer of two-electrons. The shifts in potential with added hydrogen bond donors can be rationalized by supramolecular interactions between the strongly electronegative oxygen atoms in the quinone anions (especially the dianions) and the donor hydrogen atoms, and can be modelled according to an electrochemical square-scheme mechanism involving multiple electron transfer and chemical bonding steps. NQ + e– ⇌ NQ• – E 1 NQ• – + e– ⇌ NQ2– E 2 NQ + 2e– + nH-D ⇌ [NQ(H-D)n]2– E 3 NQ + 2e– + nCO2 ⇌ [NQ(CO2)n]2– E 4 In addition to H-bonding interactions, reduced forms of NQ also undergo supramolecular interactions with CO2(g) when it is purged into solution. Similar to the situation seen for H-bonding, when CO2 is purged into solution, the two one-electron processes merge into one two-electron process at less negative potentials (E 4). The mechanism can be considered analogous to the H-bonding case where the electronegative oxygen atoms in the reduced quinones interact with the electropositive carbon atoms in CO2. However, the supramolecular interactions appear to be stronger with CO2 than with water, since substantially less CO2 needs to be added to cause the two one-electron reduction processes of NQ to merge into one two-electron process. Controlled potential electrolysis experiments were conducted to determine the chemical reversibility of the supramolecular interactions. It was found that, (i) fully reducing NQ under a CO2 atmosphere and then applying an oxidizing potential resulted in the 100% conversion back to the starting material and, (ii) reducing NQ under a CO2 atmosphere and then purging the solution with argon resulted in the CO2 being released as CO2(g) or CO2 • – to leave NQ in its neutral form or as NQ2–. Figure 1. Cyclic voltammograms for 1,4-naphthoquinone in acetonitrile containing 0.2 M Bu4NPF6 at a scan rate of 0.1 V s–1 at a 1 mm diameter planar Pt electrode in the presence and absence of CO2. Figure 1

Effect of Anionic, Cationic, and Non-Ionic Surfactants on the Structural Stability and Morphology of Perfluorinated Sulfonic Acid Membranes

Redox flow batteries (RFB) are a critical technology for stationary grid-scale energy storage, with potential usage with intermittent power sources, such as wind and solar. RFBs are attractive for long-duration energy storage because the anolyte and catholyte are stored separately external to the electrochemical reactor, which allows the RFBs to be modular and stationary. Separating the electrolytes and the electrochemical cell decouples energy and power densities, unlike batteries that store charge in the solid-state, such as Li-ion, Pb-acid, or Ni-Cd. A standard RFB chemistry is the all-vanadium redox flow battery (VRFB), which utilizes the four oxidation states of vanadium, with V2+, V3+, V4+, and V5+. Recently, new electrolytes are being studied in energy storage devices. Such as the first redox flow battery to utilize microemulsions as the electrolyte.Microemulsions are a breakthrough electrolyte for energy storage (BEES) that is emerging as an alternative to traditional RFB electrolytes because they produce thermodynamically stable, homogeneous solutions of polar and non-polar molecules. The stabilization of oil and water solutions allows microemulsion electrolytes to accommodate organic redox species with fast electron transfer rates that are not soluble in the aqueous phase while still offering the high conductivity of an aqueous salt electrolyte. Microemulsions consist of two immiscible phases stabilized by a surfactant, a non-polar "oil" phase, solubilizing the redox material, and the polar phase, which typically consists of an aqueous brine that provides charge balance and conductivity. Additionally, if the redox molecule was a non-polar liquid, it could serve as the entire oil phase, maximizing the energy density. An attractive property of a microemulsion electrolyte is that each component can be environmentally and biologically safe. For example, the aqueous phase only contains salt and water, and surfactants are found in many household, personal, and food products. Furthermore, some redox materials investigated in our lab are vitamins such as menadione (vitamin K3) and tocopherol (vitamin E).This talk describes the structural, mechanical, and morphological studies of surfactants' effects on perfluorinated sulfonic acid membranes. Small-angle X-ray scattering monitored the morphological changes as a function of surfactant concentration and soaking time, revealing how the surfactant penetrated and altered the polymer membrane. FTIR and NMR spectroscopy are also employed, providing insight into any polymer membrane degradation or dissolution. We demonstrate that surfactant choice is not only crucial to the stability of the microemulsion used as an electrolyte but can ultimately destroy the separator in a redox flow battery.This work was supported as part of the Breakthrough Electrolytes for Energy Storage and Systems (BEES2), an Energy Frontier Research Center funded by the U.S. Department of Energy, Office of Science, Basic Energy Sciences under Award # DE-SC0019409.

The mediation effect of vitamin A and vitamin D supplement in the association between serum vitamin K levels and musculoskeletal disorders in preschool children.

Vitamin K deficiency may elevate the incidence of musculoskeletal disorders (MSD), whereas it lacks validation for pediatric populations and has uncertain dose recommendations. In this context, we hypothesized that serum vitamin K levels are associated with MSD in preschool children, and the widely used vitamin A and vitamin D supplements may mediate these associations based on potential mechanisms, which expects to provide guidance for future practice. A cross-sectional study was conducted in Sichuan province in southwestern China, from January 2021 to May 2022. Serum levels of vitamin K1/K2 and 25(OH)D were determined using the high-performance liquid chromatography method, and the diagnosis of MSD was executed by clinicians. Overall and stratified logistic regression analysis based on categorized 25(OH)D levels were conducted to assess association between serum vitamin K levels and MSD prevalence after adjusting for confounders. Mediation analysis was further performed and vitamin A and D supplementation was regressed as the mediator. A total of 6,368 children aged 0-6 years old were enrolled. MSD was identified in 1179 (18.51%) of the children, while 5,189 (81.49%) of them did not present such disorder. After adjusting confounders, a significant difference was found in serum vitamin K1 level between children in MSD and Non-MSD group (OR = 0.802, 95%CI 0.745-0.864). No significant difference was found in serum vitamin K2 level between the two groups (OR = 0.975, 95%CI 0.753-1.261). The association between vitamin K1 level and MSD prevalence was partly (36.8%) mediated by vitamin A and D supplementation. A low serum vitamin K1 level is connected with an increased risk of MSD among children, highlighting that vitamin A and D supplementation is a helpful intervention to prevent MSD in children with vitamin K deficiency.

Vitamin K1 intake is associated with lower risk for all-cause and cardiovascular disease mortality in community-dwelling older Australian women

Background and aimsAssessing the relationship between vitamin K1 intakes, using region-specific food databases, with both all-cause, and cardiovascular disease (CVD) mortality warrants further investigation to inform future preventative strategies. Consequently, we examined the aforementioned associations in the Perth Longitudinal Study of Ageing Women (PLSAW). Methods and results1436 community-dwelling older Australian women (mean ± SD age 75.2 ± 2.7 years) completed a validated food frequency questionnaire at baseline (1998). Vitamin K1 intake was calculated based on an Australian vitamin K food database, supplemented with published data. All-cause and CVD mortality data was obtained from linked health records. Associations were examined using restricted cubic splines within Cox-proportional hazard models, adjusted for a range of cardiovascular and lifestyle related risk factors. Over 15 years of follow-up, 601 (41.9%) women died, with 236 deaths (16.4%) due to CVD. Compared to women with the lowest vitamin K1 intakes (Quartile 1, median 49.1 μg/day), those with the highest intakes (Quartile 4, median 119.3 μg/day) had lower relative hazards for all-cause mortality (HR 0.66 95%CI 0.51–0.86) and CVD mortality (HR 0.61 95%CI 0.41–0.92). A plateau in the inverse association was observed from vitamin K1 intakes of approximately ≥80 μg/day. ConclusionHigher vitamin K1 intakes were associated with lower risk for both all-cause and CVD mortality in community-dwelling older women, independent of CVD related risk factors. A higher intake of vitamin K1 rich foods, such as leafy green vegetables, may support cardiovascular health.

DETERMINATION OF BIOLOGICALLY ACTIVE COMPOUNDS IN LIQUID EXTRACT OF PLANTS POLYGONUM HIDROPIPER L., BURSA PASTORIS, CALENDULAE OFFICINALIS AND URTICA DIOICA L.

Methods have been developed for the quantitative determination of biologically active compounds - flavonoids and vitamin K1 in the liquid extract "Extradent" obtained from the aerial part of the knotweed (Polygonum hidropiper L.), shepherd's purse (Bursa pastoris), calendula flowers (Calendulae officinalis) and nettle leaves (Urtica dioica). L.), by high performance liquid chromatography (HPLC). As a result, components corresponding to the retention time of standard samples of robinin, rutin, and quercetin were found on the chromatogram of the extract. It was revealed that the content of robinin was 0.37%, rutin 0.014%, quercetin 0.00045%, and vitamin K1 0.005%. The same method of mass spectrometry with inductively coupled plasma (ICP-MS) was used to determine the quantitative content of macro- and microelements of the liquid extract "Extradent". The highest content of macroelements is in the proportion of potassium (0.65%), phosphorus (0.2%), and among the microelements of iron is 15.716 mg/l, selenium – 0.046 mg/l. The content of heavy metal salts in the liquid extract is within the normal range and totals 1.155 mg/l. Of these, the main content is zinc and copper.

Menahydroquinone-4 may play a key role in regulating CCL5 expression induced by epidermal growth factor receptor inhibitors

Epidermal growth factor receptor (EGFR) inhibitors frequently cause severe skin rash as a side effect, which is a critical burden for patients who continuously receive drug treatments. Several recent clinical trials have shown that vitamin K is effective against these side effects; however, the underlying mechanisms remain unclear. EGFR inhibitors induce C–C motif chemokine ligand 5 (CCL5) in dermopathy. We hypothesized that menahydroquinone-4 (MKH), the active form of menaquinone-4 (MK-4, vitamin K2(20)), supplied by biosynthesis or external delivery, is essential for the suppressive effect on CCL5. The aim of this study was to explore the underlying mechanisms governing the relieving effects of MKH against skin rashes caused by EGFR inhibitors. The responses generated by EGFR inhibitors and the effect of MKH derivatives (two ester derivatives and MK-4) on them were evaluated using human skin cell lines (HaCaT and HSC-1). EGFR inhibitors downregulated UbiA prenyltransferase domain-containing protein-1 (UBIAD1, MKH synthetase) expression and MKH biosynthesis. Knockdown of UBIAD1 or γ-glutamyl carboxylase and treatment with warfarin upregulated CCL5 expression. MKH derivatives suppressed the CCL5 expression induced by EGFR inhibitors. Our data strongly suggest that MKH is involved in suppressing CCL5 expression and alleviating the skin damage caused by EGFR inhibitors.

An assessment of immediate newborn care readiness and availability in Nepal

ABSTRACT Background Global neonatal mortality necessitates access to immediate newborn care interventions. In Nepal, disparities persist in the readiness and availability of newborn care services within health facilities. Objective This study aimed to assess this status and compare facilities that had implemented an intensive newborn resuscitation capacity building and retention programme in the past five years with those that had not. Methods Our observational cross-sectional study involved 154 health facilities across Nepal. Through on-site inspections and maternal log reviews, we evaluated the immediate newborn care readiness and availability. Results The mean immediate newborn care intervention availability score of 52.8% (SE = 21.5) and the readiness score averaged 79.6% (SE = 12.3). Encouragingly, 96% of facilities ensured newborns were dried and wrapped for warmth, and 69.9% provided newborn resuscitation. Practices such as delayed cord clamping (42.0%), skin-to-skin contact (28.6%), and early breastfeeding (63.5%) showed room for improvement. Only 16.1% of health facilities administered Vitamin K1 prophylaxis.Domain-specific scores demonstrated a high level of facility readiness in infrastructure (97.5%), medicine, equipment, and supplies (90.6%), and staff training (90.9%), but a lower score for neonatal resuscitation aids (28.8%). Disparities in readiness and availability were evident, with rural areas and the Madhesh province reporting lower scores. Variations among health facility types revealed provincial and private hospitals outperforming local-level facilities. A positive association was observed between the LDSC/SSN mentoring programme and both the readiness and availability of immediate newborn care services. Conclusion This study highlights the gap between healthcare facility readiness and the actual availability of immediate newborn care interventions in Nepal. Addressing disparities and barriers, particularly in rural areas and local-level facilities, is crucial for improving neonatal survival. The positive link between the LDSC/SSN programme and service availability and facility readiness emphasises the significance of targeted training and mentorship programmes in enhancing newborn care across Nepal.

Modulating Effects of Vitamin K2 on Oxidative Stress Induced Organelle Damage in Alzheimer’s Disease

AbstractBackgroundCurrent treatment strategies for AD are either involved in an improved amyloid‐beta precursor protein (APP) processing via inhibition and/or activation of enzymatic machinery. Whereas, others drug regimen includes the use of putative tau kinase inhibitors, microtubule stabilizers and tau immunotherapies. Moreover, therapies to combat oxidative stress are currently being devised because oxidative stress plays a major role innneurodegeneration. Interestingly, current studies are being focused on the screening of bioactive compounds for their effect on prevention of Aβ formation, oxidative stress reduction and targeting organelle dysfunction, which will potentiate the use of bioactive compounds to prevent AD in early stages. Vitamin K2 is one of the bioactive compounds which has gained importance for its role as an antioxidant.MethodTo understand the neuroprotective effect of vitamin K2 during metabolic complications, SH‐SY5Y cells were treated with streptozotocin for 24 h and menadione for 2 h in a dose dependent manner, followed by the post treatment of vitamin K2 for 5 h. Modulating effects of vitamin K2 on cell viability, Lactate Dehydrogenase release, reactive oxygen species (ROS), mitochondrial membrane potential, ER stress marker (CHOP), an indicator of unfolded protein response (UPR) p‐IRE1α, GSK 3α/β, total tau and Aβ 42 were studied.ResultVitamin K2 significantly reduced the neuronal cell death by inhibiting the cytotoxicity, ROS levels and helped in the retainment of mitochondrial membrane potential. Moreover, vitamin K2 significantly decreased the expression of CHOP protein along with the levels and the nuclear localization of p‐IRE1 α, thus showing its significant role in inhibiting chronic ER stress mediated UPR and eventually apoptosis. In addition, Vitamin K2 significantly downregulated the expression of GSK 3 α/β together with the levels of total tau protein, with petite effect on secreted Aβ 42 levels.ConclusionVitamin K2 ameliorated mitochondrial damage, ER stress and tauopathy mediated neuronal cell death, highlighting its role as a novel antioxidative therapeutics targeting related cellular processes.