Search Results (1,489)

Zearalenone (ZEA) is a common estrogenic mycotoxin in rabbit breeding that causes various toxic effects. Selenomethionine (SeMet) is a feed additive with potent anti-inflammatory and antioxidant properties. To evaluate the protective role and action mechanism of SeMet against ZEA-induced liver injury, 90-day-old rabbits were randomized into five groups: control, ZEA-alone, and SeMet pretreatment at 0.2, 0.35, and 0.5 mg/kg. SeMet was administered for 21 days, followed by continuous intragastric ZEA (1.2 mg/kg B.W.) for 7 days starting on day 15. As a result, ZEA exposure significantly elevated liver function parameters, disrupted lobular architecture, and impaired glycogen synthesis. It also induced liver oxidative stress, thus upregulating expressions of Bax, Cyt C, Caspase-3, and Caspase-9, triggering hepatocyte apoptosis, mitochondrial damage, and mitophagy. SeMet pretreatment activated SIRT1, reduced the acetylated FOXO1/P53 levels, and enhanced CAT and SOD2 expression, mitigating ZEA-induced oxidative stress, apoptosis, and mitophagy. Based on the above findings, SeMet’s alleviating effect might be mediated via the SIRT1-FOXO1/P53 pathway, with 0.35 mg/kg of SeMet exerting the optimal efficacy, highlighting its therapeutic potential for mitigating ZEA-induced hepatotoxicity in rabbits. Full article

Background/Objectives: Motor imagery (MI) is the mental practice of motor actions with temporal dynamics and neural features in common with motor execution (ME). Although MI can improve motor performance, it remains unclear how closely performance-related signatures of MI resemble those of ME during learning, particularly in tasks with intrinsic variability. This study investigated similarities and differences between MI and ME during a probabilistic sequence-learning task. Methods: Participants performed a finger-tapping serial reaction time task in either a motor execution (ME; n = 10) or motor imagery (MI; n = 10) condition. The task consisted of 750 auditory stimuli mapped to right-hand finger movements and generated by a probabilistic sequence with deterministic and variable events. Reaction times were analyzed using ANOVA designs to assess the effects of Group, Block, Event Type, and the Last Variable event. Results: The MI group showed a significant reduction in reaction times across blocks (p < 0.001), indicating learning-related performance improvement, whereas no block-wise improvement was observed in the ME group. Both groups were sensitive to the probabilistic structure of the sequence, with reaction times differing across event types. A significant Group × Event interaction (p < 0.01) indicated distinct performance signatures for MI and ME. In both groups, reaction times were modulated by the last variable event. Conclusions: Motor imagery supported learning in a probabilistic sequence task but was influenced by factors distinct from those governing motor execution, suggesting partially different underlying mechanisms. Full article

In recent years, dietary intervention has garnered significant attention for T2DM prevention and adjunctive treatment. Lentinula edodes (commonly known as shiitake mushroom), a common edible fungus, has been demonstrated to improve T2DM, primarily attributed to its main bioactive components like peptides and polysaccharides, while their synergistic characteristics are still not fully explained. Therefore, this study investigated the anti-T2DM molecular mechanisms of L. edodes peptides and polysaccharides by integrating network pharmacology and molecular docking. First, systematic searches of the PubMed and HERB databases using keywords such as “Lentinula edodes peptides”, “Lentinula edodes polysaccharides” and “T2DM” and “Lentinula edodes/shiitake mushroom” yielded 25 peptides and 14 polysaccharides. Second, network pharmacology analysis revealed 541 common interaction targets between these peptides/polysaccharides and T2DM. Topological analysis further identified nine core targets: ESR1, MAPK1, AKT1, SRC, EGFR, STAT3, JUN, PIK3CA, and PIK3R1. Third, pathway enrichment analysis showed that these core targets were significantly enriched within the PI3K-Akt signaling pathway and the AGE-RAGE signaling pathway in diabetic complications, suggesting potential anti-T2DM effects through regulation of these key pathways. Finally, molecular docking validation ensured strong binding affinities between peptides/polysaccharides and some core targets, with particularly prominent binding capacities observed for peptides VF and LDELEK with EGFR; peptides KIGSRSRFDVT, LDYGKL, and EDLRLP along with polysaccharides D-glucan and β-glucan with PIK3CA; and peptide DVFAHF with PIK3R1. In summary, this study revealed that L. edodes peptides and polysaccharides may exert synergistic anti-T2DM effects via the regulation of key signaling pathways, including the PI3K-Akt signaling pathway, EGFR tyrosine kinase inhibitor resistance, and the AGE-RAGE signaling pathway in diabetic complications, through their actions on critical targets such as ESR1, PIK3CA, and PIK3R1. These results offer a synergistic mechanism for the anti-T2DM effect of L. edodes, which could be helpful for the development of functional foods and drugs derived from L. edodes. Full article

This study examines how psychological safety (PS) relates to employees’ innovation commitment (IC) in private higher education institutions (HEIs) in Egypt by specifying a learning-based mechanism and two enabling boundary conditions. Drawing on organizational learning theory and commitment research, we surveyed 405 academic and administrative staff (faculty members, teaching assistants, and administrators) across six private universities using validated multi-item measures and analyzed the proposed moderated-mediation model using PLS-SEM (SmartPLS 4), alongside procedural checks to mitigate common method bias. Results indicate that psychological safety is positively associated with knowledge sharing (KS) and innovation commitment, and that knowledge sharing partially mediates the relationship between psychological safety and innovation commitment. The findings further show that transformational leadership (TL) strengthens the positive association between psychological safety and knowledge sharing, while digital readiness (DR) strengthens the positive association between knowledge sharing and innovation commitment. The study contributes by clarifying when psychologically safe climates are most likely to be linked to innovation commitment through day-to-day exchange behaviors and by identifying leadership and digital capability conditions that amplify these relationships in private HEIs. Practically, the results underscore the value of institutionalizing psychologically safe dialog, developing transformational leadership behaviors, and investing in digital infrastructure and skills to make knowledge flows more actionable for innovation-related persistence. Full article

IgA nephropathy (IgAN) is the most common primary chronic glomerular disease worldwide. Its clinical features include proteinuria and complement pathway activation, which are the strongest predictors of progression to renal failure. This disease can occur at any age. Approximately 30–40% of IgAN patients progress to end-stage renal disease (ESRD) within 20–25 years after diagnosis, making it one of the major causes of ESRD. As understanding of the autoimmune development of IgA nephropathy (IgAN) grows, research shows that BAFF and APRIL promote B-cell activation by binding to the receptors TACI, BCMA, and BAFF-R. This results in the overproduction of galactose-deficient IgA1 (Gd-IgA1), which helps drive the progression of IgA nephropathy. B-cell and plasma cell-targeted therapies, such as biologics against BAFF/APRIL, can precisely and effectively improve patient symptoms. Corresponding agents have now been successfully developed and are administered via subcutaneous or intravenous injection. Clinical trials have demonstrated the significant effectiveness of this approach, especially in reducing proteinuria, stabilizing eGFR, and lowering Gd-IgA1 levels. Although current trial data for BAFF/APRIL-targeted biologics in IgA nephropathy are promising, these new treatments need ongoing clinical monitoring for long-term infection risks and potential drug resistance. This article focuses on the application of BAFF/APRIL biologics in the treatment of IgA nephropathy, addressing gaps in existing literature. While prior studies have emphasized the mechanisms of action of these drugs in IgA nephropathy, they have lacked a comprehensive summary of the current status of specific drug research and clinical progress. Full article

Background: Mycoplasma pneumoniae pneumonia (MPP) is a common community-acquired pneumonia in children. Increasing drug resistance highlights the need for more effective treatments with fewer side effects. The Qingfei Tongluo Jiedu formula (QTJD) has demonstrated clinical efficacy against MPP; however, its underlying mechanisms remain unclear. This study aimed to explore the mechanism of QTJD on MPP using network pharmacology and in vitro experiments. Methods: Network pharmacology was used to identify the active compounds and signaling pathways of QTJD in MPP. QTJD-containing serum was prepared, and primary mouse lung and bone marrow cells were isolated to examine the effects of QTJD on macrophage polarization through butyric acid. Cell viability assays, flow cytometry, and quantitative reverse transcription-polymerase chain reaction were performed. GPR109^−/− cells were used to confirm the receptor mediating butyric acid’s action, and Western blotting was employed to assess the MAPK signaling pathway. Results: QTJD promoted macrophage polarization and alleviated the inflammatory response caused by Mycoplasma pneumoniae. High-performance liquid chromatography-electrospray ionization mass spectrometry combined with network pharmacology identified 20 active compounds. Protein-protein interaction analysis revealed 10 core target, including JUN and Tumor Necrosis Factor (TNF), while enrichment analysis highlighted pathways such as Mitogen-Activated Protein Kinase (MAPK) and Phosphoinositide 3-Kinase-Protein Kinase B. Experimental validation demonstrated that QTJD reduced M1 markers (CD86, CXCL10) by increasing butyrate levels (p < 0.01) and enhanced M2 markers (CD206, Arg-1, MRC-1), promoting M2 polarization. QTJD inhibited ERK1/2, p38, and JNK1/2 (p < 0.01). In GPR109A^−/− mice macrophages, QTJD suppressed p38 and JNK1/2 (p < 0.01) but showed no effect on ERK1/2 (p > 0.05), confirming involvement of the butyrate-GPR109A-MAPK pathway. Conclusions: QTJD effectively alleviates MPP by regulating macrophage polarization through the butyrate-GPR109A-MAPK pathway. Future studies should explore how QTJD modulates pulmonary immunity through gut microbiota and butyrate production and elucidate its immunoregulatory mechanisms along the gut-lung axis using multi-omics approaches. Full article

Aging and neurodegenerative diseases are characterized by common features involving bioenergetics deficiencies, oxidative stress and alterations of calcium buffering. Mechanisms of mitochondrial-targeted drugs include the modulation of electron transport chain and oxidative phosphorylation, the binding to mitochondrial lipids, free-radical scavenging, calcium signaling, and possible effects on mitochondrial biogenesis and dynamics and on the regulation of mitophagic pathways. One of the main sites of action of mitochondria-targeted drugs is the interaction with respiratory chain components. Mitochondrial-targeted compounds such as Mito-Q, and Mito-apocynin have been developed by conjugating triphenylphosphonium (TPP⁺) lipophilic cation group with natural molecules, therefore obtaining promising drugs for reestablishing the correct functioning of the mitochondrial respiratory chain. Stabilization of cardiolipin at the inner mitochondrial membrane by elamipretide or SkQ1 and mitochondria-targeted ROS scavengers can also offer a therapeutic approach to prevent bioenergetic impairment associated with several diseases. In addition, the modulation of calcium signaling can be achieved using both MCU agonists and antagonists representing another mitochondrial target for drug therapies development. Finally, potential strategies for treating neurodegenerative diseases based on the modulation of mitochondrial biogenesis, dynamics and/or mitophagic pathways are discussed. Full article

Neurodegeneration is closely linked to neuroinflammation and is frequently accompanied by comorbidities with inflammatory features. Tripartite motif (TRIM) proteins are known to play an important role in innate immunity and inflammatory signaling in various tissues and organs of the body, including the central nervous system. Among the main cell types of the brain, TRIMs’ functions in microglia are largely associated with the regulation of intracellular inflammatory signaling, while in neurons they mainly relate to cell survival and oxidative stress. Data concerning TRIMs’ activity in astrocytes remain limited. Many TRIM proteins exert similar pro- or anti-inflammatory effects in neuroinflammation and in other inflammatory disorders in the body, although for some members their roles are reported to be opposite, contradictory, or insufficiently characterized, highlighting the need for further research. The aim of this review was to summarize published data on the common mechanisms of TRIMs’ actions as modulators of inflammation, and compare available reports in the context of neuroinflammation and peripheral inflammatory pathologies. We suggested that such an analysis may be valuable for guiding future research—both by identifying existing gaps in knowledge and by supporting the rational selection of specific TRIM proteins for investigation as therapeutic targets, with careful consideration of their systemic effects. Full article

Steroidal compounds lie at the crossroads of inflammation and cancer, where modulation of common signaling pathways creates opportunities for dual-action therapeutic intervention. Accumulating evidence indicates that their anti-inflammatory and antitumor activities are frequently interconnected, reflecting shared molecular mechanisms that regulate immune signaling, oxidative stress, cell proliferation, and apoptosis. This review provides a critical and comparative analysis of major classes of bioactive steroids—including furanosteroids, neo-steroids, aromatic steroids, α,β-epoxy steroids, peroxy steroids, cyanosteroids, nitro- and epithio steroids, halogenated steroids (fluorinated, chlorinated, brominated, iodinated), and steroid phosphate esters—with emphasis on their dual anti-inflammatory and anticancer potential. More than one thousand steroidal metabolites derived from plants, fungi, marine organisms, bacteria, and synthetic sources are surveyed. While the majority exhibit either anti-inflammatory or antineoplastic activity alone, only a limited subset displays potent activity in both domains. Comparative evaluation highlights the structural features that favor dual functionality, including epoxide, peroxide, nitrile, nitro, halogen, and phosphate ester moieties, as well as rearranged or heteroatom-enriched steroidal frameworks. Where available, biological data from in vitro and in vivo assays (IC₅₀ values, enzyme inhibition, cytokine modulation, and antiproliferative effects) are summarized and critically compared. Special attention is given to rare natural metabolites—such as polyhalogenated marine steroids, phosphorylated sterols, and heteroatom-containing derivatives—as well as synthetic analogues designed to enhance cytotoxic or immunomodulatory efficacy. Mechanistically, steroids exhibiting dual activity commonly modulate convergent signaling pathways, including NF-κB, JAK/STAT, MAPK, PI3K/AKT, redox homeostasis, and apoptosis regulation. Collectively, these findings underscore the potential of structurally optimized steroids as multifunctional therapeutic agents and provide a framework for the rational design of next-generation anti-inflammatory and anticancer drugs. Full article

Breast cancer is a significant cause of death worldwide. Recent research has focused on identifying natural compounds for developing effective cancer treatments. Resiniferatoxin, a transient receptor potential vanilloid 1 (TRPV1) agonist, is a common diterpene in Euphorbia bicolor Engelm. & A. Gray (Euphorbiaceae), a plant native to the southern United States that has not been studied before. We investigated the antiproliferative activities and mechanisms of action of E. bicolor xylene extract in estrogen receptor-positive T47D and triple-negative MDA-MB-231 cell lines. The extract significantly reduced the viability of T47D and MDA-MB-231 cells in a dose-dependent manner. In MDA-MB-231 cells, the extract induced apoptosis via intracellular calcium overload, triggered by TRPV1 activation. This effect was diminished by the TRPV1 antagonist capsazepine and the calcium chelator BAPTA-AM. Intracellular calcium influx was confirmed through Fura-2 AM staining, revealing that E. bicolor phytochemicals activated TRPV1 in MDA-MB-231 cells. Treatment of T47D cells with E. bicolor xylene extract resulted in apoptosis associated with reactive oxygen species (ROS) generation (10-fold higher in T47D cells than in MDA-MB-231 cells) and mitochondrial calcium overload. These effects were significantly blocked when cells were pretreated with N-acetyl-l-cysteine (NAC), a ROS inhibitor. Both cell lines underwent apoptosis via multiple mitochondrial- and endoplasmic reticulum stress–mediated pathways. This was supported by the activation of caspases 3, 8, and 9; increased expression of FAS, XBP1s, and CHOP; upregulation of BAX; and downregulation of BCL-2. In addition, PI3K, AKT, and pAKT protein expressions were also reduced in both cell lines, indicating downregulation of PI3K/Akt signaling pathway. Phytochemicals in E. bicolor xylene extract could become promising ingredients for developing breast cancer therapeutics. Full article

This study evaluates the chemical profile and antifungal efficacy of essential oils from Piper glabratum, Piper friedrichsthalii, and Piper cumanense against the cocoa pathogens Moniliophthora roreri and Phytophthora palmivora. Microwave-assisted hydrodistillation followed by GC-MS analysis identified 80 constituents, predominantly monoterpenes and sesquiterpenes, which exhibited significant mycelial inhibition comparable to commercial fungicides. Beyond basic characterization, a comprehensive chemoinformatic analysis was conducted to elucidate the molecular mechanisms driving this bioactivity. The computed physicochemical landscape reveals a dominant lipophilic profile (average LogP 3.4) and low polarity (TPSA 11.5 Ų), characteristics essential for effective fungal membrane penetration. Structural mining identified conserved benzene and cyclohexene scaffolds alongside specific 1,3-benzodioxole moieties, while Maximum Common Substructure (MCS) analysis uncovered high similarity clusters among phenylpropanoids and sesquiterpenes. These findings suggest a synergistic mode of action where conserved structural backbones and interchangeable diastereomers facilitate membrane destabilization and ion leakage. Consequently, the integrative chemoinformatic profiling elucidates the molecular basis of this efficacy, positioning these Piper essential oils not merely as empirical alternatives, but as sources of rationally defined synergistic scaffolds for next-generation sustainable fungicides. Full article

Background/Objective: Current treatments for peripheral nerve injury (PNI) lack robust evidence to suggest complete recovery; hence, alternative therapeutics offer new opportunities to develop more effective protocols. Mushroom species and their related components are considered potential candidates for peripheral nerve repair, but their specific effects and underlying mechanisms are not fully understood. This systematic review presents the available evidence on the use of mushroom species for PNI therapy, including the bioactive components and mechanisms of action. Methodology: A comprehensive literature search in three databases (PubMed, Scopus, and Google Scholar) led to the synthesis of 11 records published between 2010 and 2024. Qualitative analysis revealed the neuroregenerative potential of four mushrooms: Amanita muscaria (n = 2), Hericium erinaceus (n = 5), Lignosus rhinocerotis (n = 3), and Flammulina velutipes (n = 1), with aqueous extracts as the most common type of ingredients used (n = 4) relative to specific components such as muscimol, polysaccharide, Erinacine S, and nerve-guided conduits (NGCs). Results: These mushroom-derived treatments enhanced the migration of Schwann cells mainly via the FGF-2 signalling and MAPK pathway. In vivo studies also revealed the ability of H. erinaceus, A. muscaria, and L. rhinocerotis to promote peripheral nerve repair and functional recovery, with evidence suggesting the role of neurotrophic factors, anti-apoptotic signalling, and pro-inflammatory substances. H. erinaceus was identified as the most promising for potential clinical applications, given the stronger evidence-based data and its relatively safer components compared to A. muscuria and other mushroom species. Conclusions: Despite presenting the potential use of mushrooms in managing PNIs, the existing approaches need to be subjected to clinical research to accelerate the development of future therapeutics and preventive measures for PNIs. Full article

Staphylococcus aureus (S. aureus) is a common pathogen that threatens healthcare and food safety. Vine tea extract (VTE) and its major active component, dihydromyricetin (DMY), show antibacterial activity. However, their mechanisms of action are not fully understood. In this study, we combined proteomics and lipidomics, with RT–qPCR validation of selected differentially expressed genes, to investigate how DMY and VTE affect S. aureus. Proteomics identified 210 and 535 differentially expressed proteins (DEPs) in the DMY-treated and VTE-treated groups, respectively. These DEPs were mainly enriched in cell wall- and membrane-associated pathways. DMY markedly increased proteins involved in fatty acid degradation, glyceride metabolism, and cell wall synthesis. In contrast, VTE increased proteins related to heme/iron acquisition and cell wall degradation. In addition, VTE altered proteins involved in pyrimidine metabolism and aminoacyl-tRNA biosynthesis, suggesting that non-DMY components in VTE may contribute to the antibacterial activity through additional pathways. Lipidomics further indicated membrane lipid remodeling, including increased fatty acid unsaturation and shorter acyl chain length. Collectively, DMY and VTE may inhibit S. aureus growth by remodeling membrane lipids and disturbing cell wall–cell membrane homeostasis. These findings provide mechanistic support for further development of DMY and VTE as natural antimicrobial candidates. Full article

Informal settlements are widely present and important urban spaces, providing valuable living spaces for many migrant populations, low-income groups, and indigenous peoples. However, urbanization faces a common challenge: the transformation of informal settlements often destroys social structures and belongingness. Despite its importance, few studies have examined how redevelopment is correlated with original residents’ belongingness. To address this gap, this study proposes a research framework of belongingness structured along the logical chain of “network–node–subject”. Social network analysis (SNA) is employed to identify the existing outdoor activity space network and its key nodes. Exploratory factor analysis (EFA) is then conducted to determine the key environmental features of outdoor activity spaces that influence original residents’ belongingness. Furthermore, K-means clustering is applied to explore the correlation mechanism between space and belongingness across different age groups. This study identifies differentiated and universal elements by analyzing the clustered conflict factors, in order to provide precise policy insights. The findings provide actionable insights for enhancing residents’ belongingness during the redevelopment of informal settlements in cities. Full article

This study presents a statistically robust quality-engineering evaluation of an industrial cathodic electrodeposition (CED) process applied to large electric-charging station components. In contrast to predominantly laboratory-scale studies, the analysis is based on 1250 thickness measurements, enabling reliable assessment of process uniformity, positional effects, and long-term stability under real production conditions. The mean coating thickness was specified at 21.84 µm with a standard deviation of 3.14 µm, fully within the specified tolerance window of 15–30 µm. One-way ANOVA revealed statistically significant but technologically small inter-station differences (F(49, 1200) = 3.49, p < 0.001), with an effect size of η² ≈ 12.5%, indicating that most variability originates from inherent within-station common causes. Shewhart X^¯–R–S control charts confirmed process stability, with all subgroup means and dispersions well inside the control limits and no evidence of special-cause variation. Distribution tests (χ², Kolmogorov–Smirnov, Shapiro–Wilk, Anderson–Darling) detected deviations from perfect normality, primarily in the tails, attributable to the superposition of slightly heterogeneous station-specific distributions rather than fundamental non-Gaussian behaviour. Capability and performance indices were evaluated using Statistica and PalstatCAQ according to ISO 22514; the results (Cp = 0.878, Cpk = 0.808, Pp = 0.797, Ppk = 0.726) classify the process as conditionally capable, with improvement potential mainly linked to reducing positional effects and centering the mean closer to the target thickness. To complement the statistical findings, an AIAG–VDA FMEA was conducted across the entire value stream. The highest-risk failure modes—surface contamination, incorrect bath chemistry, and improper hanging—corresponded to the same mechanisms identified by SPC and ANOVA as contributors to thickness variability. Proposed corrective actions reduced RPN values by 50–62.5%, demonstrating strong potential for capability improvement. A predictive machine-learning model was implemented to estimate layer thickness and successfully reproduced the global trend while filtering process-related noise, offering a practical tool for future predictive quality control. Full article