Search Results (149)

Hypomagnesemia is a frequent and often underrecognized electrolyte disturbance with important clinical consequences, especially in hospitalized and critically ill patients. This multifactorial condition arises from impaired intestinal absorption, renal magnesium wasting, and the effects of various medications. Magnesium, the second most abundant intracellular cation, is crucial in enzymatic and physiological processes; its deficiency is associated with neuromuscular, cardiovascular, and metabolic complications. This narrative review focuses on the mechanisms and clinical consequences of drug-induced hypomagnesemia, highlighting the major drug classes involved such as diuretics, antibiotics, antineoplastic agents, and immunosuppressants. Management strategies include magnesium supplementation and adjunctive therapies like amiloride and SGLT2 inhibitors to reduce renal magnesium losses. Recognizing and addressing drug-induced hypomagnesemia is essential to improve patient outcomes and prevent long-term complications. Full article

Background: Up to one-third of patients with gastroesophageal reflux disease (GERD) have persistent symptoms despite proton-pump inhibitor (PPI) therapy. E-Gastryal^® + MgAlg (Aurora Biofarma, Italy) is a mucosal protective agent that enhances barrier function against acid and non-acidic reflux. This study assessed its efficacy in combination with omeprazole versus omeprazole alone and as maintenance therapy. Methods: Patients with symptomatic GERD and Grade A reflux esophagitis confirmed by endoscopy were randomized to receive omeprazole 20 mg plus E-Gastryal^® + MgAlg or omeprazole 20 mg alone. The primary endpoint was the number of rescue medications used over 28 days. Secondary endpoints included symptom relief and quality-of-life assessments using the Reflux Symptom Index (RSI), Gastroesophageal Reflux Disease Impact Scale (GIS), GERD-Health-Related Quality of Life (GERD-HRQL), and Global Assessment of Performance (IGAP). Results: Ninety-six patients were included. The combination group used significantly fewer rescue medications (mean: 21 vs. 40.9 tablets; p = 0.002). At week 4, the combination group showed greater improvement in RSI, GIS, and GERD-HRQL scores (p < 0.001). Symptom relief was sustained during weeks 5–26 with E-Gastryal^® + MgAlg alone. Conclusions: E-Gastryal^® + MgAlg combined with omeprazole improves symptom control compared to PPI monotherapy. Continued use as maintenance therapy supports its role in long-term GERD management (NCT04130659). Full article

Tan sheep outperform Dorper sheep in meat-quality traits, including muscle fiber characteristics and fatty acid composition, while Dorper sheep excel in carcass weight. However, the molecular mechanisms underlying these breed-specific traits, especially gut microbiota–bile acid (BA) interactions, remain poorly understood. As host–microbiota co-metabolites, BAs are converted by colonic microbiota via bile salt hydrolase (BSH) and dehydroxylases into secondary BAs, which activate BA receptors to regulate host lipid and glucose metabolism. This study analyzed colonic BA profiles in 8-month-old Tan and Dorper sheep, integrating microbiome and longissimus dorsi muscle transcriptome data to investigate the gut–muscle axis in meat-quality and carcass trait regulation. Results showed that Tan sheep had 1.6-fold higher secondary BA deoxycholic acid (DHCA) levels than Dorper sheep (p < 0.05), whereas Dorper sheep accumulated conjugated primary BAs glycocholic acid (GCA) and tauro-α-muricholic acid (p < 0.05). Tan sheep exhibited downregulated hepatic BA synthesis genes, including cholesterol 7α-hydroxylase (CYP7A1) and 27-hydroxylase (CYP27A1), alongside upregulated transport genes such as bile salt export pump (BSEP), sodium taurocholate cotransporting polypeptide (NTCP), and ATP-binding cassette subfamily B member 4 (ABCB4), with elevated gut BSH activity (p < 0.05). DHCA was strongly correlated with g_Ruminococcaceae_UCG-014, ENSOARG00000001393, and ENSOARG00000016726, muscle fiber density, diameter, and linoleic acid (C18:2n6t) (|r| > 0.5, p < 0.05). In contrast, GCA was significantly associated with g_Lachnoclostridium_10, g_Rikenellaceae_RC9_gut_group, ENSOARG0000001232, carcass weight, and net meat weight (|r| > 0.5, p < 0.05). In conclusion, breed-specific colonic BA profiles were shaped by host–microbiota interactions, with DHCA potentially promoting meat quality in Tan sheep via regulation of muscle fiber development and fatty acid deposition, and GCA influencing carcass traits in Dorper sheep. This study provides novel insights into the gut microbiota–bile acid axis in modulating ruminant phenotypic traits. Full article

Carbonate geothermal reservoirs, characterized by widespread distribution, a high discharge capacity, and favorable reinjection conditions, have become a key target for geothermal resource development. However, the karst geothermal reservoir system in the Juancheng geothermal field exhibits significant heterogeneity, leading to substantial disparities in productivity among multiple geothermal wells and severely restricting efficient regional exploitation. This study systematically investigates the hydraulic characteristics and development potential of the karst geothermal reservoir in the Juancheng geothermal field using sodium fluorescein tracing experiment technology. The results reveal that the reservoir system contains multiple flow channels with distinct permeability differences. The dominant flow pathways, controlled by fault structures, exhibit an apparent velocity of up to 10.98 m/h, significantly higher than other regions in the study area. In contrast, low-permeability zones, influenced by the burial depth of the Ordovician strata, show poor connectivity due to limited karst development, with the lowest apparent velocity of only 1.03 m/h. By integrating pumping test data and tracer response characteristics, the dominant flow direction (northeast) demonstrates a stronger recharge capacity and water abundance, offering a higher development value. Conversely, the southeast low-permeability zone has weaker water production and constrained recharge conditions, resulting in a relatively limited development potential. Additionally, it is recommended that the direction of future geothermal well placement in the Juancheng geothermal field should avoid being parallel to the fault strike to prolong the thermal breakthrough arrival time. In regions with deeper Ordovician strata burial, denser well network deployment is suggested to enhance the reservoir utilization efficiency. Full article

Progressive familial intrahepatic cholestasis type 2 (PFIC2) is a severe hepatocellular cholestasis due to biallelic variations in the ABCB11 (ATP-binding cassette B11) gene encoding the canalicular bile salt export pump (BSEP). Some missense variants identified in patients with PFIC2 do not traffic properly to the canalicular membrane. However, 4-phenybutyrate (4-PB) has been shown in vitro to partially correct the mis-trafficking of selected variants, resulting in an improvement of the medical conditions of corresponding PFIC2 patients. Herein, we report the ability of 4-PB analogous or homologous drugs and of non-4-PB related chemical correctors to rescue the canalicular expression and the activity of the folding-defective Abcb11^R1128C variant. New compounds, either identified by screening a chemical library or designed by structural homology with 4-PB (or its metabolites) and synthesized, were evaluated in vitro for their ability to (i) correct the canalicular localization of Abcb11^R1128C after transfection in hepatocellular polarized cell lines; (ii) restore the ³H-taurocholate transport of the Abcb11^R1128C protein in Madin–Darby canine kidney (MDCK) cells stably co-expressing Abcb11 and the sodium taurocholate co-transporting polypeptide (Ntcp/Slc10A1). Glycerol phenylbutyrate (GPB), phenylacetate (PA, the active metabolite of 4-PB), 3-hydroxy-2-methyl-4-phenylbutyrate (HMPB, a 4-PB metabolite analog chemically synthesized in our laboratory) and 4-oxo-1,2,3,4-tetrahydro-naphthalene-carboxylate (OTNC, from the chemical library screening) significantly increased the proportion of canalicular Abcb11^R1128C protein. GPB, PA, ursodeoxycholic acid (UDCA), alone or in combination with 4-PB, suberoylanilide hydroxamic acid (SAHA), C18, VX-445, and/or VX-661, significantly corrected both the traffic and the activity of Abcb11^R1128C. Such correctors could represent new pharmacological insights for improving the condition of patients with ABCB11 deficiency due to missense variations affecting the transporter’s traffic. Full article

Exposure to aflatoxin (AF) triggers the production of inflammatory molecules and free radicals, leading to chronic inflammation, cancer, and neurodegenerative diseases. This systematic review evaluated the effects of AFB1 on the nervous system, particularly focusing on Alzheimer’s disease (AD). A comprehensive search was conducted in Scopus, Cochrane Library, PubMed, and Web of Science databases up to 1 June 2024, without restrictions. From 993 records retrieved, 16 articles were included in the systematic review. AFB1 participates in various biochemical processes and pathological conditions. The study highlights that AFB1 contributes to AD by inducing DNA damage, oxidative stress, and endoplasmic reticulum (ER) stress, impairing DNA repair mechanisms. This results in neuronal damage, cognitive decline, and neurodegeneration. AFB1 also affects key signaling pathways, reduces sodium–potassium pump activity, and disrupts cell cycle regulation involving p53, leading to neurotoxicity, inflammation, and the formation of amyloid-beta (Aβ) plaques and neurofibrillary tangles. Additionally, network analysis revealed 309 genes associated with AD, inflammation, angiopathy, and aflatoxin B1 (AFB1). Among these, ESR1 exhibited the highest number of direct connections to other nodes within the network. The gene TP53 played a pivotal role in mediating communication among genes, while the EP300 gene significantly influenced the overall network structure. Additionally, KEGG enrichment analysis demonstrated that these 309 genes are substantially involved in pathways related to cancer, the FoxO signaling pathway, apoptosis, and AD. In summary, the study highlights that AFB1 causes DNA damage and stress, leading to cognitive decline and neurodegeneration. It disrupts signaling pathways, damages neurons, and affects DNA repair, contributing to neurotoxicity and inflammation. PROSPERO registration number: CRD420250651007. Full article

Background: Exposure to antimicrobials and Proton Pump Inhibitors (PPIs) are modifiable risk factors for nosocomial Clostridiodes difficile infection (CDI). We investigated the association between these agents and nosocomial CDI over five years. Methods: Nosocomial CDI from January 2017 to December 2021 were included. Consumption trends were analyzed using a simple linear regression model. A correlation analysis was performed using Spearman’s test in two ways: without a time interval and with 1-month interval matching. An interrupted time-series method to evaluate the impact of three key temporal breakpoints on CDI incidence rate was performed using the Poisson regression model. Results: A downward trend for cephalexin, ceftriaxone, clindamycin, gentamicin, macrolides, metronidazole, and penicillin sodium was identified. In contrast, an upward trend was recognized for amoxicillin, ceftazidime/avibactam, ertapenem, fluconazole, ketoconazole, levofloxacin, and tigecycline. Among the antimicrobials that showed a positive association between consumption and the incidence of CDI are clindamycin and cephalosporins after immediate consumption. Moreover, macrolides and metronidazole presented a positive correlation, in both immediate and delayed consumption. PPIs consumption did not show changes and was not associated with nosocomial CDI incidence. The interrupted time series analysis showed no changes at the breakpoints selected. Conclusions: Consumption of clindamycin, cephalosporins, and macrolides showed positive association with CDI, despite having a downtrend in consumption. Specific events, such as the COVID-19 pandemic and the implementation of ASP, have had no correlation with CDI. Further analysis is required in Latin America to advance our understanding of risk factors associated with CDI. Full article

This study investigates groundwater flow patterns in a landslide area above the settlement of Koroška Bela in NW Slovenia using a series of tracer tests with sodium chloride (NaCl) and fluorescein (uranine). The tracer experiments, using a combination of pumping tests and continuous groundwater observations, reveal two distinct groundwater flow horizons within the landslide body: a prevailing shallower flow within highly permeable gravel layers and a slower deep flow in the weathered low-permeability clastic layers. Uranine injections suggest longer retentions, indicating complex hydrogeological conditions. Groundwater is recharged by the infiltration of precipitation and subsurface inflow from the upper-lying carbonate rocks. In the upper landslide, highly permeable gravel layers accelerate flow, especially during heavy rainfall, while downstream interactions between permeable gravel and less permeable clastic materials create local aquifers and springs. These groundwater dynamics significantly influence landslide stability, as rapid infiltration during intense precipitation events can lead to transient increases in pore water pressure, reducing shear strength and potentially triggering slope movement. Meanwhile, slow deep flows contribute to prolonged saturation of critical failure surfaces, which may weaken the landslide structure over time. The study emphasizes the region’s geological heterogeneity and landslide stability, providing valuable insights into the groundwater dynamics of this challenging environment. By integrating hydrogeological assessments with engineering measures, the study provides supportive information for mitigating landslide risks and improving groundwater management strategies. Full article

A microfluidic system for detecting sodium ions (Na⁺) has been developed, incorporating a micro finger-pump chip and a micro-spectrometer platform to measure Na⁺ concentration in human serum. A small volume (10 μL) of serum sample is introduced into the microchip and reacted with a preloaded reagent mixture through a two-step finger-pump actuation process. The resulting purple complex is directed into the detection area of the chip and analyzed using the micro-spectrometer at wavelengths of 555 and 666 nm. The Na⁺ concentration is then inversely derived from the measured A₅₅₅/A₆₆₆ absorbance ratio using self-written software installed on a Raspberry Pi. The entire detection process is completed in just 3 min, offering a significant advantage in meeting clinical needs compared to the traditional reporting turnaround time of several hours in medical institutions. The experimental results indicate a linear relationship between the measured absorbance ratio and Na⁺ concentration within the range of 1–200 mM, with a correlation coefficient of R² = 0.9989. Additionally, the detection results from 60 serum samples collected from chronic kidney disease (CKD) patients showed a strong agreement with those obtained using the conventional indirect ion-selective electrode (ISE) method, achieving a correlation coefficient of R² = 0.9885 and an average recovery rate of 99.4%. In summary, the proposed system provides a practical, affordable, and rapid alternative to conventional Na⁺ detection methods, making it highly promising for point-of-care (POC) testing applications. Full article

With the growing interest in reducing CO₂ emissions to combat climate change, humanity is turning to green or renewable sources of electricity. There are numerous issues associated with the development of these sources. One of the key aspects of renewable energy sources is their problematic controllability, namely the control of energy production over time. Renewable sources are also associated with issues of recycling, utilization in different geographical zones, environmental impact within the required area, and so on. One of the most discussed issues today, however, is the question of efficient use of the energy produced from these sources. There are several different approaches to storing renewable energy, e.g., supercapacitors, flywheels, batteries, PCMs, pumped-storage hydroelectricity, and flow batteries. In the commercial sector, however, mainly due to acquisition costs, these options are narrowed down to only one concept: storing energy using an electrochemical storage device—batteries. Nowadays, lithium-ion batteries (LIBs) are the most widespread battery type. Despite many advantages of LIB technology, the availability of materials needed for the production of these batteries and the associated costs must also be considered. Thus, this battery type is not very ideal for large-scale stationary energy storage applications. Sodium-ion batteries (SIBs) are considered one of the most promising alternatives to LIBs in the field of stationary battery storage, as sodium (Na) is the most abundant alkali metal in the Earth’s crust, and the cell manufacturing process of SIBs is similar to that of LIBs. Unfortunately, considering the physical and electrochemical properties of Na, different electrode materials, electrolytes, and so on, are required. SIBs have come a long way since they were discovered. This review discusses the latest developments regarding the materials used in SIB technology. Full article

The inherent acidic nature of the stratum corneum (SC), the so-called “acid mantle”, has a multitude of effects on skin barrier integrity owing to its (patho)physiological role in skin homeostasis, antimicrobial defense, and inflammation. Several salient SC acidifying mechanisms, including the breakdown of FLG (filaggrin) protein, lipid processing, and the activity of the sodium proton pump SLC9A1/NHE1, are indispensable for the structural and functional integrity and cohesion of the SC as they contribute immensely to the origin, generation, maintenance, and overall SC acidification of the skin surface pH (pHss). As many endogenous and exogenous factors can affect the pHss, the pHss can inevitably deviate from its optimum. The elevation of the pHss is often accompanied by abnormalities in SC lipid metabolism and organization, SC cohesion, and SC integrity and is commonly observed in eczema, which is associated with symptoms of dry skin, inflammation, pruritus, and infection. In psoriasis, it seems that the pHss is altered as well; however, in this case, it is likely to be lower than the physiological pHss. Due to the negative effects of an altered pHss in both eczema and psoriasis, it has been suggested to maintain the pHss at physiological levels by utilizing pH-balanced topical cleansers and moisturizers that can improve the skin’s structural and functional integrity by benefiting skin moisturization and the regeneration and organization of the SC barrier. The principal aim of this review is to gather an understanding of the existing research and to stimulate critical thinking and inspire innovative ideas about ‘known unknowns’, considering the origin, intricate nature, and prime role of the pHss in human skin health, as well as the pathogenesis of eczema and psoriasis. Full article

Background: Ouabain is a steroid hormone that binds to the sodium pump (Na⁺, K⁺-ATPase) at physiological (nanomolar) concentrations, activating different signaling pathways. This interaction has been shown to prevent the axotomy-induced death of retinal ganglion cells (RGCs), although the underlying mechanisms remain unclear. Objective: In this study, we investigated potential mechanisms by which ouabain promotes RGC survival using primary cultures of rat neural retina. Results: Our findings indicate that ouabain regulates brain-derived neurotrophic factor (BDNF) signaling in retinal cells via matrix metalloproteinase-9-mediated processing of proBDNF to mature BDNF (mBDNF) and by increasing the phosphorylation of the mBDNF receptor, tropomyosin-related receptor kinase B. Ouabain also enhances the maturation of interleukin (IL)-1β through the increased activation of caspase-1, which mediates the processing of proIL-1β into IL-1β, and transiently upregulates both IL-1 receptor and IL-1 receptor antagonist (IL-1Ra). Treatment using either IL-1β or IL-1Ra alone is sufficient to enhance RGC survival similarly to that achieved with ouabain. Finally, we further show that ouabain prevents RGC death through a complex signaling mechanism shared by BDNF and IL-1β, which includes the activation of the Src and protein kinase C pathways. Conclusions: Collectively, these results suggest that ouabain stimulates the maturation and signaling of both BDNF and IL-1β, which act as key mediators of RGC survival. Full article

The ability of a cell to keep its volume constant irrespective of intra- and extracellular conditions is essential for cellular homeostasis and survival. The purpose of this study is to elaborate a theoretical model of cell volume homeostasis and to apply it to a simulation of human aqueous humor (AH) production. The model assumes a cell with a spherical shape and only radial deformation satisfying the property that the cell volume in rest conditions equals that of the cell couplets constituting the ciliary epithelium of the human eye. The cytoplasm is described as a homogeneous mixture containing fluid, ions, and neutral solutes whose evolution is determined by net production mechanisms occurring in the intracellular volume and by water and solute exchange across the membrane. Averaging the balance equations over the cell volume leads to a coupled system of nonlinear ordinary differential equations (ODEs) which are solved using the $\theta$-method and the Matlab function ode15s. Simulation tests are conducted to characterize the set of parameters corresponding to baseline conditions in AH production. The model is subsequently used to investigate the relative importance of (a) impermeant charged proteins; (b) sodium–potassium (Na+/K+) pumps; (c) carbonic anhydrase (CA) in the AH production process; and (d) intraocular pressure. Results suggest that (a) and (b) play a role; (c) lacks significant weight, at least for low carbon dioxide values; and (d) plays a role for the elevated values of intraocular pressure. Model results describe a higher impact from charged proteins and Na+/K+ ATPase than CA on AH production and cellular volume. The computational virtual laboratory provides a method to further test in vivo experiments and machine learning-based data analysis toward the prevention and cure of ocular diseases such as glaucoma. Full article

Multidrug-resistant tuberculosis (MDR-TB) patients are treated with a standardised, short World Health Organization (WHO) regimen which includes clofazimine (CFZ) and bedaquiline (BDQ) antibiotics. These two antibiotics lead to the development of QT prolongation in patients, inhibiting potassium (K⁺) uptake by targeting the voltage-gated K⁺ (Kv)11.1 (hERG) channel of the cardiomyocytes (CMs). However, the involvement of these antibiotics to regulate other K⁺ transporters of the CMs, as potential mechanisms of QT prolongation, has not been explored. This study determined the effects of CFZ and BDQ on sodium, potassium–adenosine triphosphatase (Na⁺,K⁺-ATPase) activity of CMs using rat cardiomyocytes (RCMs). These cells were treated with varying concentrations of CFZ and BDQ individually and in combination (1.25–5 mg/L). Thereafter, Na⁺,K⁺-ATPase activity was determined, followed by intracellular adenosine triphosphate (ATP) quantification and cellular viability determination. Furthermore, molecular docking of antibiotics with Na⁺,K⁺-ATPase was determined. Both antibiotics demonstrated dose–response inhibition of Na⁺,K⁺-ATPase activity of the RCMs. The greatest inhibition was demonstrated by combinations of CFZ and BDQ, followed by BDQ alone and, lastly, CFZ. Neither antibiotic, either individually or in combination, demonstrated cytotoxicity. Molecular docking revealed an interaction of both antibiotics with Na⁺,K⁺-ATPase, with BDQ showing higher protein-binding affinity than CFZ. The inhibitory effects of CFZ and BDQ, individually and in combination, on the activity of Na⁺,K⁺-ATPase pump of the RCMs highlight the existence of additional mechanisms of QT prolongation by these antibiotics. Full article

Adsorption heat pumps (AHPs) have garnered significant attention due to their efficient use of low-grade thermal energy, eco-friendly nature, and cost-effectiveness. However, a significant challenge lies in developing adsorbent materials that can achieve a high uptake capacity, rapid adsorption rates, and efficient reversible release of refrigerants, such as ammonia (NH₃). Herein, we developed and synthesized a novel salt-embedded covalent organic framework (COF) composite material designed for enhanced NH₃ capture. This material was prepared by encapsulating sodium bromide (NaBr) within a porous and densely functionalized sulfonic acid-based COF. The COF was synthesized through a Schiff base (imine) condensation reaction, providing a robust platform for effective NaBr impregnation. The COF-based aerogel composite powder was investigated for its potential in ammonia-based AHPs, benefiting from both the porous, highly functionalized COF structure and the strong NH₃ affinity of the impregnated NaBr. The composite adsorbent demonstrates an impressive NH₃ adsorption capacity, adsorption rate, and stability. The exceptional NH₃ adsorption performance of the COF-based aerogel composite powder is primarily attributed to the uniformly dispersed NaBr within the COF, the coordination of NH₃ molecules with Na⁺ ions, and the hydrogen bonding interaction between NH₃ and Br- ions. These findings highlight the potential of the salt-embedded COF composite for use in NH₃-based AHPs, gas separation, and other related applications. Full article