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ELife May 2024Alterations in the function of K channels such as the voltage- and Ca-activated K channel of large conductance (BK) reportedly promote breast cancer (BC) development and...
Alterations in the function of K channels such as the voltage- and Ca-activated K channel of large conductance (BK) reportedly promote breast cancer (BC) development and progression. Underlying molecular mechanisms remain, however, elusive. Here, we provide electrophysiological evidence for a BK splice variant localized to the inner mitochondrial membrane of murine and human BC cells (mitoBK). Through a combination of genetic knockdown and knockout along with a cell permeable BK channel blocker, we show that mitoBK modulates overall cellular and mitochondrial energy production, and mediates the metabolic rewiring referred to as the 'Warburg effect', thereby promoting BC cell proliferation in the presence and absence of oxygen. Additionally, we detect mitoBK and BK transcripts in low or high abundance, respectively, in clinical BC specimens. Together, our results emphasize, that targeting mitoBK could represent a treatment strategy for selected BC patients in future.
Topics: Humans; Animals; Mice; Breast Neoplasms; Cell Line, Tumor; Cell Proliferation; Mitochondria; Large-Conductance Calcium-Activated Potassium Channel alpha Subunits; Mitochondrial Membranes; Female; Energy Metabolism
PubMed: 38808578
DOI: 10.7554/eLife.92511 -
RSC Advances May 2024Prismatic crystals of partially potassium substituted lead fluorapatite PbCaK(PO)F were grown through a solid-state reaction. The structural study conducted by...
Prismatic crystals of partially potassium substituted lead fluorapatite PbCaK(PO)F were grown through a solid-state reaction. The structural study conducted by single-crystal X-ray diffraction revealed that the compound crystallizes in the hexagonal 6/ space group, with unit cell parameters = = 9.7190(5) Å, = 7.1700(6) Å and = 587.37(7) Å( = 1), as well as final values amounting to and w of 0.0309 and 0.0546, respectively. The structural refinement demonstrated that Pb occupies both the (6 and (4) structural sites of hexagonal fluorapatite, K occupies the (6) site, and Ca is placed on the (4) site. Powder X-ray diffraction study indicated the absence of additional phases or impurities. Chemical analysis using atomic absorption spectrometry and energy-dispersive X-ray spectroscopy confirmed the expected chemical formula. The electrical conductivity measured over a wide temperature range was found to be governed by the ion mobility mechanism in the tunnel along the axis (probably attributed to the fluorine ion located there). We, therefore, could infer from the analysis of the complex impedance spectra that the electrical conductivity of our apatite depends essentially on the temperature and frequency, which produces a relaxation phenomenon and semiconductor-like behavior. Moreover, the strong absorption in the UV-Visible region was substantiated through studies of the optical properties of the developed sample. Fluorescence spectra exhibited emissions in the orange regions when excited at 375 nm. The findings of the phenomena resulting from the emission and conduction of the apatite in question suggest its potential for application in various technological fields such as photovoltaic cells, optoelectronics, photonics, LED applications, catalysis and batteries.
PubMed: 38799221
DOI: 10.1039/d4ra01014k -
BioRxiv : the Preprint Server For... May 2024Thrombosis is a major cause of myocardial infarction and ischemic stroke. The sodium/potassium ATPase (NKA), comprising α and β subunits, is crucial in maintaining...
BACKGROUND
Thrombosis is a major cause of myocardial infarction and ischemic stroke. The sodium/potassium ATPase (NKA), comprising α and β subunits, is crucial in maintaining intracellular sodium and potassium gradients. However, the role of NKA in platelet function and thrombosis remains unclear.
METHODS
We utilized wild-type (WT, α ) and NKA α1 heterozygous (α ) mice, aged 8 to 16 weeks, of both sexes. An intravital microscopy-based, FeCl -induced carotid artery injury thrombosis model was employed for in vivo thrombosis assessment. Platelet transfusion assays were used to evaluate platelet NKA α1 function on thrombosis. Human platelets isolated from healthy donors and heart failure patients treated with/without digoxin were used for platelet function and signaling assay. Complementary molecular approaches were used for mechanistic studies.
RESULTS
NKA α1 haplodeficiency significantly reduced its expression on platelets without affecting sodium homeostasis. It significantly inhibited 7.5% FeCl -induced thrombosis in male but not female mice without disturbing hemostasis. Transfusion of α , but not α , platelets to thrombocytopenic WT mice substantially prolonged thrombosis. Treating WT mice with low-dose ouabain or marinobufagenin, both binding NKA α1 and inhibiting its ion-transporting function, markedly inhibited thrombosis in vivo. NKA α1 formed complexes with leucine-glycine-leucine (LGL)-containing platelet receptors, including P2Y12, PAR4, and thromboxane A2 receptor. This binding was significantly attenuated by LGL>SFT mutation or LGL peptide. Haplodeficiency of NKA α1 in mice or ouabain treatment of human platelets notably inhibited ADP-induced platelet aggregation. While not affecting 10% FeCl -induced thrombosis, NKA α1 haplodeficiency significantly prolonged thrombosis time in mice treated with an ineffective dose of clopidogrel.
CONCLUSION
NKA α1 plays an essential role in enhancing platelet activation through binding to LGL-containing platelet GPCRs. NKA α1 haplodeficiency or inhibition with low-dose ouabain and marinobufagenin significantly inhibited thrombosis and sensitized clopidogrel's anti-thrombotic effect. Targeting NKA α1 emerges as a promising antiplatelet and antithrombotic therapeutic strategy.
PubMed: 38798556
DOI: 10.1101/2024.05.13.593923 -
Plants (Basel, Switzerland) May 2024Polyploid plants often exhibit enhanced stress tolerance. Switchgrass is a perennial rhizomatous bunchgrass that is considered ideal for cultivation in marginal lands,...
Polyploid plants often exhibit enhanced stress tolerance. Switchgrass is a perennial rhizomatous bunchgrass that is considered ideal for cultivation in marginal lands, including sites with saline soil. In this study, we investigated the physiological responses and transcriptome changes in the octoploid and tetraploid of switchgrass ( L. 'Alamo') under salt stress. We found that autoploid 8× switchgrass had enhanced salt tolerance compared with the amphidiploid 4× precursor, as indicated by physiological and phenotypic traits. Octoploids had increased salt tolerance by significant changes to the osmoregulatory and antioxidant systems. The salt-treated 8× Alamo plants showed greater potassium (K) accumulation and an increase in the K/Na ratio. Root transcriptome analysis for octoploid and tetraploid plants with or without salt stress revealed that 302 upregulated and 546 downregulated differentially expressed genes were enriched in genes involved in plant hormone signal transduction pathways and were specifically associated with the auxin, cytokinin, abscisic acid, and ethylene pathways. Weighted gene co-expression network analysis (WGCNA) detected four significant salt stress-related modules. This study explored the changes in the osmoregulatory system, inorganic ions, antioxidant enzyme system, and the root transcriptome in response to salt stress in 8× and 4× Alamo switchgrass. The results enhance knowledge of the salt tolerance of artificially induced homologous polyploid plants and provide experimental and sequencing data to aid research on the short-term adaptability and breeding of salt-tolerant biofuel plants.
PubMed: 38794454
DOI: 10.3390/plants13101383 -
Materials (Basel, Switzerland) May 2024This work is focused on a novel, promising low temperature phase change material (PCM), based on the eutectic Glauber's salt composition. To allow phase transition...
This work is focused on a novel, promising low temperature phase change material (PCM), based on the eutectic Glauber's salt composition. To allow phase transition within the refrigeration range of temperatures of +5 °C to +12 °C, combined with a high repeatability of melting-freezing processes, and minimized subcooling, the application of three variants of sodium carboxymethyl cellulose (Na-CMC) with distinct molecular weights (700,000, 250,000, and 90,000) is considered. The primary objective is to optimize the stabilization of this eutectic PCM formulation, while maintaining the desired enthalpy level. Preparation methods are refined to ensure repeatability in mixing components, thereby optimizing performance and stability. Additionally, the influence of Na-CMC molecular weight on stabilization is examined through differential scanning calorimetry (DSC), T-history, and rheology tests. The PCM formulation of interest builds upon prior research in which borax, ammonium chloride, and potassium chloride were used as additives to sodium sulfate decahydrate (Glauber's salt), prioritizing environmentally responsible materials. The results reveal that CMC with molecular weights of 250 kg/mol and 90 kg/mol effectively stabilize the PCM without phase separation issues, slowing crystallization kinetics. Conversely, CMC of 700 kg/mol proved ineffective due to the disruption of gel formation at its low gel point, hindering higher concentrations. Calculations of ionic concentration indicate higher Na ion content in PCM stabilized with 90 kg/mol CMC, suggesting increased ionic interactions and gel strength. A tradeoff is discovered between the faster crystallization in lower molecular weight CMC and the higher concentration required, which increases the amount of inert material that does not participate in the phase transition. After thermal cycling, the best formulation had a latent heat of 130 J/g with no supercooling, demonstrating excellent performance. This work advances PCM's reliability as a thermal energy storage solution for diverse applications and highlights the complex relationship between Na-CMC molecular weight and PCM stabilization.
PubMed: 38793509
DOI: 10.3390/ma17102442 -
Medicina (Kaunas, Lithuania) May 2024: episodes of acute decompensation in chronic heart failure (ADHF), a common health problem for the growing elderly population, pose a significant socio-economic burden...
: episodes of acute decompensation in chronic heart failure (ADHF), a common health problem for the growing elderly population, pose a significant socio-economic burden on the public health systems. Limited knowledge is available on both the endothelial function in and the cardio-metabolic health profile of old adults hospitalized due to ADHF. This study aimed to investigate the connection between asymmetric dimethylarginine (ADMA)-a potent inhibitor of nitric oxide-and key health biomarkers in this category of high-risk patients. : this pilot study included 83 individuals with a known ADHF history who were admitted to the ICU due to acute cardiac decompensation. Selected cardiovascular, metabolic, haemogram, renal, and liver parameters were measured at admission to the ICU. Key renal function indicators (serum creatinine, sodium, and potassium) were determined again at discharge. These parameters were compared between patients stratified by median ADMA (114 ng/mL). : high ADMA patients showed a significantly higher incidence of ischemic cardiomyopathy and longer length of hospital stay compared to those with low ADMA subjects. These individuals exhibited significantly higher urea at admission and creatinine at discharge, indicating poorer renal function. Moreover, their lipid profile was less favorable, with significantly elevated levels of total cholesterol and HDL. However, no significant inter-group differences were observed for the other parameters measured. : the present findings disclose multidimensional, adverse ADMA-related changes in the health risk profile of patients with chronic heart failure hospitalized due to recurrent decompensation episodes.
Topics: Humans; Heart Failure; Arginine; Male; Female; Aged; Pilot Projects; Biomarkers; Hospitalization; Aged, 80 and over; Middle Aged
PubMed: 38792995
DOI: 10.3390/medicina60050813 -
Molecules (Basel, Switzerland) May 2024The aim of this work was to assess the chemical composition and physico-chemical, techno-functional, and in vitro antioxidant properties of flours obtained from the peel...
The aim of this work was to assess the chemical composition and physico-chemical, techno-functional, and in vitro antioxidant properties of flours obtained from the peel and flesh of pitahaya () to determine their potential for use as ingredients for food enrichment. The chemical composition, including total betalains, mineral content, and polyphenolic profile, was determined. The techno-functional properties (water holding, oil holding, and swelling capacities) were also evaluated. For the antioxidant capacity, four different methodologies, namely ferrous ion-chelating ability assay, ferric-reducing antioxidant power assay; 1,1-Diphenyl-2-picrylhydrazyl radical scavenging ability assay, and 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) radical assay, were used. Pitahaya-peel flour had higher values for protein (6.72 g/100 g), ash (11.63 g/100 g), and dietary fiber 56.56 g/100 g) than pitahaya-flesh flour, with values of 6.06, 3.63, and 8.22 g/100 g for protein, ash, and dietary fiber, respectively. In the same way, pitahaya peel showed a higher content of minerals, betalains, and polyphenolic compounds than pitahaya-flesh flour, with potassium (4.43 g/100 g), catechin (25.85 mg/g), quercetin-3-rhamnoside (11.66 mg/g) and myricetrin (12.10 mg/g) as principal compounds found in the peel. Again, pitahaya-peel flour showed better techno-functional and antioxidant properties than pitahaya-flesh flour. The results obtained suggest that the flours obtained from the peel and pulp of pitahaya () constitute a potential material to be utilized as an ingredient in the food industry due to the high content of bioactive compounds such as betalains, phenolic acids, and flavonoids, with notable antioxidant capacity.
Topics: Cactaceae; Antioxidants; Fruit; Flour; Polyphenols; Betalains; Plant Extracts
PubMed: 38792103
DOI: 10.3390/molecules29102241 -
Molecules (Basel, Switzerland) May 2024The objective of this study is to develop a remediation technology for composited heavy metal-contaminated soil. Biochars (BC300, BC400, and BC500) derived from corn...
Adsorption Potential, Speciation Transformation, and Risk Assessment of Hg-, Cd-, and Pb-Contaminated Soils Using Biochar in Combination with Potassium Dihydrogen Phosphate.
The objective of this study is to develop a remediation technology for composited heavy metal-contaminated soil. Biochars (BC300, BC400, and BC500) derived from corn were combined with potassium dihydrogen phosphate (KHPO) to immobilize and remove heavy metal ions, including mercury (Hg), cadmium (Cd), and lead (Pb). The adsorption kinetics of metal ions in aqueous solutions with different concentrations was tested, and the fitting effects of the two models were compared. The findings demonstrate that the joint application of biochar and KHPO could markedly enhance the immobilization efficacy of Pb, whereas the utilization of KHPO on its own exhibited a more pronounced immobilization impact on Cd. Furthermore, the present study underscores the shortcomings of various remediation techniques that must be taken into account when addressing heavy metal-contaminated soils. It also emphasizes the value of comprehensive remediation techniques that integrate multiple remediation agents. This study offers a novel approach and methodology for addressing the intricate and evolving challenges posed by heavy metal contamination in soil. Its practical value and potential for application are significant.
Topics: Charcoal; Soil Pollutants; Cadmium; Lead; Adsorption; Mercury; Phosphates; Potassium Compounds; Environmental Restoration and Remediation; Risk Assessment; Soil; Metals, Heavy; Kinetics
PubMed: 38792066
DOI: 10.3390/molecules29102202 -
International Journal of Molecular... May 2024Recent advancements in understanding the intricate molecular mechanisms underlying immunological responses have underscored the critical involvement of ion channels in...
Recent advancements in understanding the intricate molecular mechanisms underlying immunological responses have underscored the critical involvement of ion channels in regulating calcium influx, particularly in inflammation. Nootkatone, a natural sesquiterpenoid found in and various citrus species, has gained attention for its diverse pharmacological properties, including anti-inflammatory effects. This study aimed to elucidate the potential of nootkatone in modulating ion channels associated with calcium signaling, particularly CRAC, K1.3, and K3.1 channels, which play pivotal roles in immune cell activation and proliferation. Using electrophysiological techniques, we demonstrated the inhibitory effects of nootkatone on CRAC, K1.3, and K3.1 channels in HEK293T cells overexpressing respective channel proteins. Nootkatone exhibited dose-dependent inhibition of channel currents, with IC values determined for each channel. Nootkatone treatment did not significantly affect cell viability, indicating its potential safety for therapeutic applications. Furthermore, we observed that nootkatone treatment attenuated calcium influx through activated CRAC channels and showed anti-proliferative effects, suggesting its role in regulating inflammatory T cell activation. These findings highlight the potential of nootkatone as a natural compound for modulating calcium signaling pathways by targeting related key ion channels and it holds promise as a novel therapeutic agent for inflammatory disorders.
Topics: Humans; T-Lymphocytes; Polycyclic Sesquiterpenes; HEK293 Cells; Calcium Signaling; Intermediate-Conductance Calcium-Activated Potassium Channels; Cell Proliferation; Calcium Release Activated Calcium Channels; Calcium; Kv1.3 Potassium Channel; Cell Survival; Lymphocyte Activation; Sesquiterpenes
PubMed: 38791278
DOI: 10.3390/ijms25105240 -
Biology May 2024Potassium deficiency is one of the important factors restricting cucumber growth and development. This experiment mainly explored the effect of () on cucumber seedling...
Potassium deficiency is one of the important factors restricting cucumber growth and development. This experiment mainly explored the effect of () on cucumber seedling growth and the photosynthetic system under different potassium levels, and the rhizosphere bacteria (PGPR) that promote plant growth were used to solubilize potassium in soil, providing theoretical support for a further investigation of the effect of biological bacteria fertilizer on cucumber growth and potassium absorption. "Xinjin No. 4" was used as the test material for the pot experiment, and a two-factor experiment was designed. The first factor was potassium application treatment, and the second factor was bacterial application treatment. The effects of different treatments on cucumber seedling growth, photosynthetic characteristics, root morphology, and chlorophyll fluorescence parameters were studied. The results showed that potassium and had obvious promotion effects on the cucumber seedling growth and the photosynthesis of leaves. Compared with the blank control, the treatment had obvious effects on the cucumber seedling height, stem diameter, leaf area, total root length, total root surface area, total root volume, branch number, crossing number, g, WUE, Ci, and A; the dry weight of the shoot and root increased significantly ( ≤ 0.05). Potassium application could significantly promote cucumber growth, and the effect of and potassium application was greater than that of potassium application alone, and the best effect was when 0.2 g/pot and were applied. In conclusion, potassium combined with could enhance the photosynthesis of cucumber leaves and promote the growth of cucumber.
PubMed: 38785830
DOI: 10.3390/biology13050348