Search Results (5,590)

In vitro cartilage explant culture has been used to assess nutraceuticals on cartilage responses to inflammatory stimuli. However, applying extracts of nutraceuticals directly to cartilage explants does not account for effects of digestion and hepatic biotransformation, or selective exclusion of product metabolites from joint fluid by the synovial membrane. The current study produced a simulated biological extract of a common nutraceutical (glucosamine; G_sim) by exposing it to a simulated upper gastrointestinal tract digestion, hepatic biotransformation by liver microsomes, and purification to a molecular weight cut-off of 50 kDa. This extract was then used to condition cartilage explants cultured for 120 h in the presence or absence of an inflammatory stimulus (lipopolysaccharide). Media samples were analyzed for prostaglandin E₂ (PGE₂), glycosaminoglycan (GAG), and nitric oxide (NO). Tissue was digested and analyzed for GAG content and stained for viability. Conditioning of explants with G_sim significantly reduced media GAG in stimulated and unstimulated explants and reduced nitric oxide production in unstimulated explants. These data provide evidence for the value of glucosamine in protecting cartilage from deterioration following an inflammatory challenge, and the model improves applicability of these in vitro data to the in vivo setting. Full article

This study investigated white wastewater (WW) as a potential source of antimicrobial peptides, employing hydrolysis with Pronase E followed by separation through electrodialysis with ultrafiltration membranes (EDUF) to increase the value of dairy components within a circular economy framework. The WW hydrolysate was divided into two key fractions: the cationic recovery compartment (CRC) and the anionic recovery compartment (ARC). The EDUF process effectively separated peptides, with peptide migration rates reaching 6.83 ± 0.59 g/m²·h for CRC and 6.19 ± 0.66 g/m²·h for ARC. Furthermore, relative energy consumption (REC) increased from 1.15 Wh/g to 2.05 Wh/g over three hours, in line with trends observed in recent studies on electrodialysis energy use. Although 29 peptides were statistically selected from the CRC (20) and ARC (9) compartments, no antibacterial activity was exhibited against Clostridium tyrobutyricum and Pseudomonas aeruginosa; however, antifungal activity was observed in the feed and ARC compartments. Peptides from the ARC demonstrated activity against Mucor racemosus (MIC = 0.156 mg/mL) and showed selective antifungal effects against Penicillium commune (MIC = 0.156 mg/mL). This innovative approach paves the way for improving the recovery of anionic peptides through further optimization of the EDUF process. Future perspectives include synthesizing selected peptides and evaluating their antifungal efficacy against these and other microbial strains, offering exciting potential for applications in food preservation and beyond. Full article

This paper presents a theoretical model of a thin, penny-shaped piezoelectric actuator bonded to an isotropic thermo-elastic substrate under coupled electrical-thermal-diffusive loading. The problem is assumed to be axisymmetric, and the peeling stress of the film is neglected in accordance with membrane theory, yielding a simplified equilibrium equation for the piezoelectric film. By employing potential theory and the Hankel transform technique, the surface strain of the substrate is analytically derived. Under the assumption of perfect bonding, a governing integral equation is established in terms of interfacial shear stress. The solution to this integral equation is obtained numerically using orthotropic Chebyshev polynomials. The derived results include the interfacial shear stress, stress intensity factors, as well as the radial and hoop stresses within the system. Finite element analysis is conducted to validate the theoretical predictions. Furthermore, parametric studies elucidate the influence of material mismatch and actuator geometry on the mechanical response. The findings demonstrate that, the performance of the piezoelectric actuator can be optimized through judicious control of the applied electrical-thermal-diffusive loads and careful selection of material and geometric parameters. This work provides valuable insights for the design and optimization of piezoelectric actuator structures in practical engineering applications. Full article

Background Plasma membrane proteins (PMPs) play key roles in cell signalling, adhesion, and trafficking, and are attractive therapeutic targets in cancer due to their surface accessibility. However, their typically low abundance limits detection by conventional proteomic approaches. Methods: To improve PMP detection, we employed a surface proteomics workflow combining cell surface biotinylation and affinity purification prior to LC-MS/MS analysis in cervical (SiHa) and bladder (UMUC3) cancer cell lines cultured under normoxic (21% O₂) or hypoxic (0.1% O₂) conditions. Results: In SiHa cells, 43 hypoxia-upregulated proteins were identified exclusively in the biotin-enriched fraction, including ITGB2, ITGA7, AXL, MET, JAG2, and CAV1/CAV2. In UMUC3 cells, 32 unique upregulated PMPs were detected, including CD55, ADGRB1, SLC9A1, NECTIN3, and ACTG1. These proteins were not observed in corresponding whole-cell lysates and are associated with extracellular matrix remodelling, immune modulation, and ion transport. Biotinylation enhanced the detection of membrane-associated pathways such as ECM organisation, integrin signalling, and PI3K–Akt activation. Protein–protein interaction analysis revealed links between membrane receptors and intracellular stress regulators, including mitochondrial proteins. Conclusions: These findings demonstrate that surface biotinylation improves the sensitivity and selectivity of plasma membrane proteomics under hypoxia, revealing hypoxia-responsive proteins and pathways not captured by standard whole-cell analysis. Full article

Background/Objectives: Male infertility is a major health concern with a complex etiopathology, yet a substantial proportion of cases remain idiopathic. Mitochondrial dysfunction and non-coding RNA (ncRNA) deregulation have both been implicated in impaired spermatogenesis, but their interplay remains poorly understood. This study aimed to identify infertility-specific variants in ncRNAs that affect mitochondrial dynamics and homeostasis and to explore their roles. Methods: Whole-genome sequencing (WGS) was performed on genomic DNA samples from teratozoospermic, asthenozoospermic, oligozoospermic, and normozoospermic men. Variants uniquely present in infertile individuals and mapped to ncRNAs that affect mitochondrial dynamics were selected and prioritized using bioinformatics tools. An independent transcriptomic validation was conducted using RNA-sequencing data from testicular biopsies of men with non-obstructive azoospermia (NOA) to determine whether the ncRNAs harboring WGS-derived variants were transcriptionally altered. Results: We identified several infertility-specific variants located in lncRNAs known to interact with mitochondrial regulators, including GAS5, HOTAIR, PVT1, MEG3, and CDKN2B-AS1. Transcriptomic analysis confirmed significant deregulation of these lncRNAs in azoospermic testicular samples. Bioinformatic analysis also implicated the disruption of lncRNA–miRNA–mitochondria networks, potentially contributing to mitochondrial membrane potential loss, elevated reactive oxygen species (ROS) production, impaired mitophagy, and germ cell apoptosis. Conclusions: Our integrative genomic and transcriptomic analysis highlights lncRNA–mitochondrial gene interactions as a novel regulatory layer in male infertility, while the identified lncRNAs hold promise as biomarkers and therapeutic targets. However, future functional studies are warranted to elucidate their mechanistic roles and potential for clinical translation in reproductive medicine. Full article

It has long been accepted that breathing gases that are physiologically inert include helium (He), neon (Ne), nitrogen (N₂), argon (Ar), krypton (Kr), xenon (Xe), and hydrogen (H₂). The term “inert gas” has been used to describe them due to their unusually high chemical stability. However, as investigations have advanced, many have shown that inert gas can have specific biological impacts when exposed to high pressure or atmospheric pressure. Additionally, different inert gases have different effects on intracellular signal transduction, ion channels, and cell membrane receptors, which are linked to their anesthetic and cell protection effects in normal or pathological processes. Through a selective analysis of the representative literature, this study offers a concise overview of the state of research on the biological impacts of inert gas and their molecular mechanisms. Full article

The escalating global challenges of antimicrobial resistance (AMR) and cancer necessitate innovative therapeutic solutions from natural sources. This study investigated the multifaceted therapeutic potential of pigment-enriched plant extracts. We screened diverse plant extracts for antimicrobial and antibiofilm activity against multidrug-resistant bacteria and fungi. Hibiscus sabdariffa emerged as the most promising, demonstrating potent broad-spectrum antimicrobial and significant antibiofilm activity. Sub-inhibitory concentrations of H. sabdariffa robustly downregulated essential bacterial virulence genes and suppressed aflatoxin gene expression. Comprehensive chemical profiling via HPLC identified major anthocyanin glucosides, while GC-MS revealed diverse non-pigment bioactive compounds, including fatty acids and alcohols. Molecular docking suggested favorable interactions of key identified compounds (Cyanidin-3-O-glucoside and 1-Deoxy-d-arabitol) with E. coli outer membrane protein A (OmpA), indicating potential antiadhesive and antimicrobial mechanisms. Furthermore, H. sabdariffa exhibited selective cytotoxicity against MCF-7 breast cancer cells. These findings establish H. sabdariffa pigment-enriched extract as a highly promising, multi-functional source of novel therapeutics, highlighting its potential for simultaneously addressing drug resistance and cancer challenges through an integrated chemical, biological, and computational approach. Full article

Fungicides are compounds with potentially toxic effects on the human body, but the molecular mechanisms of their action have not yet been explained. The effect of cyprodinil on cell viability, apoptosis level, cell membrane function, cell morphology and expression of antioxidant enzyme genes in the A-375 and DLD-1 cell lines was examined. The cell lines were selected because they can be an excellent in vitro model of neoplastic changes occurring in the skin and large intestine after exposure to a fungicide. The fungicide selected for the study is commonly used in Poland to protect crops against fungi. Our results showed that the tested compound increased cell viability and proliferation, probably activated by mechanisms related to oxidative stress. Cyprodinil caused an increase in glutathione level (in A-375 by about 37% and in DLD-1 by about 28%) and oxidative stress enzymes activity, but not in apoptosis level. Its membrane interactions and its penetration into cells was concentration dependent. It is worth emphasizing that the novelty of our work lies in the use of non-traditional toxicological methods based on molecular analyses using human cell lines. This allowed us to demonstrate not only the toxicity of a single substance but also its behavior within cellular structures. Our findings suggest that cyprodinil may have tumor-promoting properties in skin and colorectal cancer cells. Full article

The matrix metalloproteinase (MMP) family includes several membrane-bound enzymes. Membrane-type 5 matrix metalloproteinase (MT5-MMP) is unique amongst the MMP family in being primarily expressed in the brain and during development. It is proposed to contribute to synaptic plasticity and is implicated in several pathologies, including multiple cancers and Alzheimer’s disease. In cancer, MT5-MMP expression has been correlated to cancer progression, but a distinct mechanistic role has yet to be uncovered. In Alzheimer’s disease, MT5-MMP exhibits pro-amyloidogenic activity, functioning as an η-secretase that cleaves amyloid precursor protein (APP), ultimately generating two synaptotoxic fragments, Aη-α and Aη-β. Several intracellular binding partners for MT5-MMP have been identified, and of these, N4BP2L1, EIG121, BIN1, or TMX3 binding to MT5-MMP results in a significant increase in MT5-MMP η-secretase activity. Beyond direct effects on APP, MT5-MMP may also facilitate APP trafficking to endosomal/lysosomal compartments and enhance proinflammatory responses. Overall, the substrate profile of MT5-MMP has not been well defined, and selective inhibitors of MT5-MMP have not been described. These advances will be needed for further consideration of MT5-MMP as a therapeutic target in Alzheimer’s disease and other pathologies. Full article

Metal–Organic Frameworks (MOFs) have emerged as advanced porous crystalline materials due to their highly ordered structures, ultra-high surface areas, fine-tunable pore sizes, and massive chemical diversity. These features, arising from the coordination between an almost unlimited number of metal ions/clusters and organic linkers, have resulted in significant interest in MOFs for applications in gas storage, catalysis, sensing, energy, and biomedicine. Beyond their stand-alone properties and applications, recent research has increasingly explored the integration of MOFs with other substrates, particularly electrodes, polymeric thin films, and glass surfaces, to create synergistic effects that enhance material performance and broaden application potential. Coating MOFs onto these substrates can yield significant benefits, including, but not limited to, improved sensitivity and selectivity in electrochemical sensors, enhanced mechanical and separation properties in membranes, and multifunctional coatings for optical and environmental applications. This review provides a comprehensive and up-to-date summary of recent advances (primarily from the past 3–5 years) in MOF coating techniques, including layer-by-layer assembly, in situ growth, and electrochemical deposition. This is followed by a discussion of the representative applications arising from MOF-substrate coating and an outline of key challenges and future directions in this rapidly evolving field. This article aims to serve as a focused reference point for researchers interested in both fundamental strategies and applied developments in MOF surface coatings. Full article

Cell culture models are of central importance for the investigation of cellular metabolism, proliferation and stress responses. In this study, the effects of different concentrations of glucose (1 g/L vs. 4.5 g/L) and fetal bovine serum (FBS; 5%, 10%, 15%) on viability, mitochondrial function and autophagy are investigated in four human cell lines: MRC-5, HeLa, Caco-2 and SW-620. Cells were cultured in defined media for 72 h, and viability was assessed by LDH release, mitochondrial membrane potential using Rhodamine 123, ATP content by luminescence and autophagy activity by dual fluorescence staining. The results showed that HeLa and SW-620 cancer cells exhibited increased proliferation and mitochondrial activity under high glucose conditions, while low glucose media resulted in decreased ATP content and increased membrane permeability in HeLa cells. MRC-5 fibroblasts and Caco-2 cells showed greater resilience to nutrient stress, with minimal changes in LDH release and consistent proliferation. Autophagy was activated under all conditions, with a significant increase only in selected cell-medium combinations. These results highlight the importance of medium composition in influencing cellular bioenergetics and stress responses, which has implications for cancer research, metabolic disease modelling and the development of serum-free culture systems for regenerative medicine. Full article

This study was conducted in Armenia and included 32 pregnant women with TV infection and 30 healthy controls. The vaginal virome includes viruses that infect human cells and unicellular eukaryotes such as Trichomonas vaginalis (TV). Among these are Trichomonas vaginalis viruses (TVVs), double-stranded RNA viruses from the Totiviridae family, and giant DNA viruses that replicate in protozoa. This study investigated the presence of TVVs and giant protozoan viruses in pregnant women with trichomoniasis in Armenia and explored their potential associations with adverse pregnancy outcomes. Vaginal and urethral samples were collected from 32 pregnant women with confirmed TV infection and 30 healthy pregnant controls. TVVs and giant viruses (Marseilleviridae, Mimiviridae, Phycodnaviridae) were detected using qRT-PCR. Viral RNA and DNA were extracted from clinical samples and TV cultures, followed by quantification and gene expression analysis. Selected TVVs were visualized via scanning electron microscopy. All TV-positive women carried at least one TVV strain, with 94% harboring multiple TVV types and TVV4 being the most common. TV infection was significantly associated with preterm birth and premature rupture of membranes (PPROM). Giant viruses were identified in all TV-positive cases but in only 40% of controls. Marseilleviridae gene expression was observed in TV cultures, suggesting possible interactions. These findings highlight a potential role for protozoan viruses in reproductive complications and warrant further investigation. Full article

Membranous nephropathy (MN) is the most prevalent cause of nephrotic syndrome (NS) in adults, and it can be primary (idiopathic) with an unknown cause or secondary due to a variety of conditions (lupus, infections, malignancies, medications, etc.). It progresses to chronic kidney disease (CKD) in up to 60% of patients, and 10 to 30% develop end-stage kidney disease (ESKD). This retrospective study examines the importance of specific factors, including baseline demographic and clinical data, kidney biopsy PH findings, and selected biochemical parameters, influencing MN outcomes after 10 years of follow-up. The cohort included 94 individuals in whom a diagnosis of MN was established by percutaneous biopsy of the left kidney’s lower pole at the University Clinical Center of Serbia (UCCS) between 2008 and 2013. According to the outcomes, patients were divided into three groups: the recovery (Rec) group, with complete remission, including normal serum creatinine (Scr) and proteinuria (Prt), the group with development of chronic kidney disease (CKD), and the group with development of end-stage kidney disease (ESKD). Nephropathologists graded pathohistological (PH) results from I to III based on the observed PH findings. During the follow-up period, 33 patients were in the Rec group, CKD developed in 53 patients, and ESKD developed in 8 patients. Baseline creatinine clearance levels (Ccr), Scr, and uric acid (urate) were found to be significantly associated with the outcomes (p < 0.001). The lowest values of baseline Scr and urate were observed in the Rec group. The presence of acute kidney injury (AKI) or CKD at the time of kidney biopsy was associated with the more frequent development of ESKD (p = 0.02). Lower Ccr was associated with a higher likelihood of progressing to CKD (B = −0.021, p = 0.014), whereas older age independently predicted progression to ESKD (B = 0.02, p = 0.032). Based on this study, it was concluded that the most important biochemical and clinical factors that are associated with the outcomes of this disease are the values of Scr, Ccr, and urate and the existence of CKD at the time of kidney biopsy. Unlike most previous studies, the presence of HTN had no statistical significance in the outcome of the disease. Full article

Anion exchange membrane (AEM) water electrolysis is a potentially inexpensive and efficient source of hydrogen production as it uses effective low-cost catalysts. The catalytic activity and performance of nickel iron oxide (NiFeO_x) catalysts for hydrogen production in AEM water electrolyzers were investigated. The NiFeO_x catalysts were synthesized with various iron content weight percentages, and at the stoichiometric ratio for nickel ferrite (NiFe₂O₄). The catalytic activity of NiFeO_x catalyst was evaluated by linear sweep voltammetry (LSV) and chronoamperometry for the oxygen evolution reaction (OER). NiFe₂O₄ showed the highest activity for the OER in a three-electrode system, with 320 mA cm⁻² at 2 V in 1 M KOH solution. NiFe₂O₄ displayed strong stability over a 600 h period at 50 mA cm⁻² in a three-electrode setup, with a degradation rate of 15 μV/h. In single-cell electrolysis using a X-37 T membrane, at 2.2 V in 1 M KOH, the NiFe₂O₄ catalyst had the highest activity of 1100 mA cm⁻² at 45 °C, which increased with the temperature to 1503 mA cm⁻² at 55 °C. The performance of various membranes was examined, and the highest performance of the tested membranes was determined to be that of the Fumatech FAA-3-50 and FAS-50 membranes, implying that membrane performance is strongly correlated with membrane conductivity. The obtained Nyquist plots and equivalent circuit analysis were used to determine cell resistances. It was found that ohmic resistance decreases with an increase in temperature from 45 °C to 55 °C, implying the positive effect of temperature on AEM electrolysis. The FAA-3-50 and FAS-50 membranes were determined to have lower activation and ohmic resistances, indicative of higher conductivity and faster membrane charge transfer. NiFe₂O₄ in an AEM water electrolyzer displayed strong stability, with a voltage degradation rate of 0.833 mV/h over the 12 h durability test. Full article

Background: Veno-arterial extracorporeal membrane oxygenation (V-A ECMO) is increasingly used to support patients with refractory cardiogenic shock or cardiac arrest. While femoral artery cannulation remains the most common arterial access, axillary artery cannulation has emerged as a valuable alternative in selected cases. Objective: This narrative review aims to synthesize current evidence and expert opinion on axillary artery cannulation in V-A ECMO, focusing on its technical feasibility, physiologic implications, and clinical outcomes. Methods: A comprehensive literature search was performed in PubMed and Scopus using relevant keywords related to ECMO, axillary artery, cannulation techniques, and outcomes. Emphasis was placed on prospective and retrospective clinical studies, expert consensus statements, and technical reports published over the past two decades. Results: Axillary cannulation provides antegrade aortic flow, potentially reducing the risk of differential hypoxia and improving upper body perfusion. However, the technique presents unique technical challenges and may carry risks such as hyperperfusion syndrome or arterial complications. Emerging data suggest favorable outcomes in selected patient populations when performed in experienced centers. Conclusions: Axillary cannulation represents a promising arterial access route in V-A ECMO, particularly in cases with contraindications to femoral cannulation or when upper-body perfusion is a concern. Further prospective studies are needed to better define patient selection criteria and long-term outcomes. Full article