Search Results (29,782)

Chronic neuroinflammation driven by microglial activation is a pathological hallmark of neurodegenerative diseases, and the NF-$\kappa$B/iNOS signaling axis plays a central role in propagating this damage. NF-$\kappa$B-mediated iNOS transcription generates excessive nitric oxide, causing oxidative neuronal injury. The medicinal mushroom Hericium erinaceus produces cyathane diterpenoid erinacines and isoindolinone erinacerins, both reported to attenuate neuroinflammation; however, the molecular basis of their interactions with iNOS and NF-$\kappa$B remains poorly characterized. We screened 21 erinacerins and 18 erinacines against both targets using validated molecular docking, then subjected top-ranked candidates and negative controls to 100 ns molecular dynamics simulations, MM-PBSA binding free energy calculations (±SEM), per-residue energy decomposition, backbone RMSD, and ligand–protein minimum distance analyses, with quercetin as reference. The analysis revealed scaffold-dependent target selectivity: erinacerins exhibited preferential stability with iNOS (erinacerin L: RMSD 0.185 nm), whereas erinacines formed more stable complexes with NF-$\kappa$B (erinacines G and J: RMSD < 0.36 nm). Minimum-distance monitoring confirmed that the elevated ligand RMSD in iNOS predominantly reflected surface relocation rather than dissociation. Erinacine S emerged as the most promising dual-target candidate ($\Delta G_{bind}$: −24.31 ± 0.16 and −14.24 ± 0.11 kcal/mol for iNOS and NF-$\kappa$B, respectively), over twofold stronger than quercetin for iNOS. Negative controls revealed that docking-based ranking was target-dependent in its discriminative capacity, underscoring the need for MD-based refinement. These results identify erinacine S as a priority candidate for experimental validation. Full article

Healing skin wounds is still difficult in many clinical situations, especially when the wounds are chronic or infected. These wounds often stay inflamed for long periods, and the risk of bacterial invasion is high. Oxidative stress tends to increase as well, while the formation of new blood vessels is often inadequate. Because of these factors, wound repair depends on the proper coordination of several biological events. These include basic antimicrobial activities, the control and resolution of inflammation, protection against oxidative damage, the rebuilding of collagen structures, and the development of new vascular networks. Traditional Chinese Medicine (TCM) provides many active compounds. These compounds work on many targets and through different pathways. They show good potential in wound treatment. But many TCM compounds have poor solubility in water. They are also unstable, have low bioavailability, and do not pass through the skin easily. These problems limit their use in clinical settings. Nanotechnology offers new ways to solve these problems. Nanodelivery systems can improve the solubility and stability of active compounds. They can also help the compounds enter the skin and stay in the wound area. Many types of nanocarriers have been developed, such as liposomes, polymer nanoparticles, nanogels, and inorganic nanomaterials. These systems can also provide controlled release or release that responds to the wound environment. This can make the treatment more accurate. In this review, we summarize how major TCM-derived compounds support wound repair and describe the biological mechanisms behind their effects. We also discuss recent nanodelivery approaches that aim to strengthen these therapeutic actions. These combinations can improve antibacterial performance, shape the immune response, reduce reactive oxygen species, and help the skin close more quickly. We also point out several challenges, such as concerns about material safety, the need for more consistent herbal extraction methods, gaps in mechanistic understanding, and the difficulty of producing these formulations on a large scale. Taken together, these points suggest that nanodelivery approaches using TCM-derived compounds still need more careful study and steady improvement before they can be used more widely in wound care. Full article

Microphysiological systems (MPS) that recapitulate human organ functions have gained attention as alternatives to animal experiments in drug discovery, regenerative medicine, and toxicity assessments. However, preserving MPS with adherent cells remains a significant challenge. In this study, we developed a supercooling preservation method that enables the low-temperature storage of human-derived adherent cells without freezing. Using human hepatic sinusoidal endothelial cells (TMNK-1), we optimized the preservation conditions by assessing the temperature, cooling and rewarming rates, and preservation solutions. Under optimized conditions (preservation at −4 °C, −0.028 °C/min cooling, and +1.0 °C/min rewarming), high cell viability and preserved morphology were maintained for up to 7 days. When these conditions were applied to both two- and three-dimensional MPS containing TMNK-1 or HepG2 cells, post-preservation viability remained high, and no cell death or cytoskeletal disruption was observed. This supercooling preservation method has the potential to serve as a practical strategy for the temporary storage of MPS. Full article

Flammulina filiformis is a significant edible and medicinal fungus; however, its industrial expansion has been limited by traditional cultivation practices, highlighting an urgent need for resource-efficient and environmentally friendly alternative substrates. This study investigated the partial replacement of traditional substrates with Cenchrus fungigraminus. Utilizing the simplex-lattice method for optimization, we identified an optimal cultivation formulation, composed primarily of 20% C. fungigraminus and 28% corncobs. This formulation achieved a biological efficiency of 131.92% and enhanced the nutritional content of the fruiting bodies. Monitoring dynamic enzyme activity revealed that the yield was positively correlated with post-primordium cellulase activity, whereas mycelial growth was negatively correlated with cellulase activity during the vegetative stage. Transcriptomic analysis further indicated that key genes involved in carbohydrate metabolism and cellular processes were significantly upregulated in the optimized formulation. These results suggest that the addition of C. fungigraminus enhances nutrient conversion efficiency by regulating the expression of genes associated with carbon and nitrogen metabolism, ultimately leading to an approximately 15% increase in the biological efficiency of fruiting bodies, and a profit increase of 379.37 Chinese Yuan (CNY) per ton of cultivation substrate, demonstrating substantial economic benefits. In summary, this study provides a theoretical and technical foundation for cultivating F. filiformis using C. fungigraminus, contributing to the advancement of the industry toward resource conservation and environmental sustainability. Full article

Background/Objectives: Ganoderma lucidum (Curtis) P. Karst. (commonly known as reishi mushroom), a well-characterized medicinal fungus, contains diverse bioactive metabolites. This study aimed to fractionate, characterize and identify the biologically active inhibitors present in G. lucidum and to evaluate their antioxidant, antimicrobial, and antidiabetic activities. Methods: The ethanol extract of G. lucidum was fractionated using column chromatography, yielding ten distinct fractions (designated as A, B, E, F, K, L, M, N, O, and P based on their elution order and visual characteristics). Liquid Chromatography–Mass Spectrometry (LC-MS) analysis identified 46 bioactive compounds, including terpenoids, alkaloids, flavonoids, and polysaccharides. Results: Among the fractions, Fraction L exhibited the strongest antioxidant activity, with an IC₅₀ of 1.59 mg/mL. Fraction O displayed significant antibacterial activity against Escherichia coli ATCC 25922 (24.4 ± 0.238 mm), Klebsiella pneumoniae ATCC 13883 (20.5 ± 0.035 mm), Bacillus subtilis ATCC 6633 (8 ± 0.176 mm), and Staphylococcus warneri ATCC 10209 (20 ± 0.080 mm). Regarding antidiabetic activity, Fraction B demonstrated the strongest inhibition of α-amylase (IC₅₀ 1.69 ± 0.03 mg/mL), while Fraction E showed the strongest α-glucosidase inhibition (IC₅₀ = 1.69 ± 0.02 mg/mL), demonstrating reciprocal selectivity between enzyme targets. Conclusions: These results establish that chromatographic fractionation concentrates specific bioactivities into distinct fractions, supporting its potential for the development of novel therapeutic agents with enhanced specificity and efficacy. Full article

Background: Adipose-derived mesenchymal stem/stromal cells (ADSCs) are gaining recognition in regenerative medicine for their potential for adipogenic, osteogenic, and chondrogenic differentiation, as well as their immunomodulatory properties. However, ADSC-based therapies focus either on differentiation for tissue replacement or on counteracting unrestrained inflammation to prevent tissue destruction and initiate regeneration. Here, we aim to examine the immunomodulatory potential of osteogenically differentiated ADSCs by analyzing their proteomic profile. Methods: Using LC-MS/MS, we generated the proteomic profiles of differentiated and undifferentiated ADSCs and compared them with the Reactome database. Transcriptomic analysis was also performed and compared with the proteomic profile. Results: Comparison of the proteomic (499 up-regulated; 355 down-regulated) and transcriptomic (212 up-regulated; 232 down-regulated) profiles showed 60.1% concordance—both proteins and transcripts showed the same trend. Significantly upregulated proteins in differentiating ADSCs (−log₁₀ p > 5 and >10) were grouped into four categories: propensity for osteogenic differentiation; immunomodulation/immune/inflammatory response; cell senescence; and cell cycle regulation. Among those proteins, thirteen were reported to play roles in processes such as immunomodulation, inflammatory signaling, or transplant rejection. Conclusions: We observed that differentiating ADSCs might still exert immunomodulatory effects, which could be used in the treatment of, e.g., bone defects. Full article

The prevalence of osteoporosis, a skeletal disorder characterized by reduced bone mass, microarchitectural deterioration, and increased fracture risk, poses a substantial global healthcare burden. Although animal models and two-dimensional cell cultures have been used to advance bone research, they do not completely replicate the multicellular interactions, extracellular matrix organization, and biomechanical environment of human bone, limiting their translational relevance. This review provides a critical synthesis of recent advances in bone organoid technology, emphasizing biological complexity, technical innovation, and relevance to osteoporosis modeling. Beyond summarizing progress, we distinguish validated capabilities from aspirational claims and identify the methodological gaps that must be addressed before bone organoids can reliably support drug screening, regenerative medicine, and precision approaches. Advances in stem cell biology, tissue engineering, and three-dimensional culture systems have enabled the use of self-organizing, multicellular organoids that reproduce key physiological and pathological features of bone. These systems model estrogen-deficiency-induced bone loss, glucocorticoid-associated osteoporosis, aging-related degeneration, and genetic susceptibility. By integrating osteogenic and endothelial components within biomimetic matrices, bone organoids can support mechanistic studies and pharmacological testing. However, their incomplete vascularization, limited mechanical fidelity, instability, and lack of standardized benchmarks restrict their translational readiness. Overcoming these barriers requires technological refinement, quantitative metrics, and regulatory alignment. Full article

Background/Objectives: Obstetrics and gynecology healthcare represents a global health concern requiring coordinated, accessible services across diverse populations. The Saudi Medical Referrals Centre (MRC) functions as a comprehensive digital health surveillance and coordination platform managing nationwide obstetrics and gynecology (OB/GYN) services. This study characterizes national OB/GYN e-referral patterns coordinated through the MRC platform to describe subspecialty utilization and inform capacity planning, and examines temporal trends in referral direction over the study period. Methods: A retrospective descriptive analysis of the MRC’s digital coordination platform examined 39,526 OB/GYN referrals across Saudi Arabia’s healthcare system (2023–2024). Descriptive statistics, chi-square tests, and one-way ANOVA tests were used to analyze patient demographics, subspecialty distribution, referral types, bed requirements, acceptance rates, geographic patterns, and multivariable logistic regression examined temporal trends in referral direction. Results: The platform achieved 91.81% overall acceptance rates. Platform surveillance revealed referral request distribution by subspecialty: general OB/GYN (60.68%), obstetrics and fetal medicine (16.37%), and reproductive endocrinology and infertility (14.94%). Most referral requests were for outpatient care (71.35%), though obstetrics and fetal medicine demonstrated relatively high NICU utilization (55.62%). Urgent referral requests constituted 22.05% of cases. Internal referral odds increased 1.7% monthly over the study period (OR = 1.017; p < 0.001). Conclusions: This nationwide descriptive analysis of 39,526 OB/GYN e-referrals reveals distinct subspecialty-specific referral patterns, with high overall acceptance rates and predominantly internal referral coordination. These system-level findings provide a baseline for future studies within digital referral platforms. Full article

Fibroblasts are mesenchymal cells which physiologically possess numerous functions and belong to basic cellular components necessary to maintain tissue homeostasis and are essential for extracellular matrix formation and maintenance. In addition, fibroblasts are of paramount importance in regeneration and wound healing as they interact with the immune system. These unique properties determine their great utility in cell therapies in the field of regenerative medicine. This review summarizes the mechanisms of action and clinical applications of fibroblast-based therapies as well as highlighting the future perspectives including the use of allogeneic cells. Full article

Plant-derived saponins have attracted significant interest for their potential to promote apoptotic cell death and enhance antitumor immune responses through immunogenic cell death (ICD). Akebia quinata, a saponin-rich medicinal plant, exhibits diverse pharmacological properties; however, studies on its seeds are limited, and their immunomodulatory activity in cancer remains largely unexplored. In this study, A. quinata seeds were extracted using 70% ethanol, and the phytochemical profile was characterized using UHPLC–QTOF MS/MS. We investigated the anticancer properties of A. quinata seed extract (AQSE), focusing on its role in inducing apoptosis and ICD in non-small cell lung cancer (NSCLC). In human NSCLC cell lines (A549 and H460), AQSE exhibited potent cytotoxic effects in a dose-dependent manner. Flow cytometric analysis confirmed the induction of apoptosis, evidenced by a significant increase in Annexin V-positive cells and an elevated sub-G1 population. Mechanistically, AQSE treatment induced cell death by simultaneously inhibiting the survival-promoting MEK/ERK/CREB axis and activating the stress-responsive JNK pathway. Furthermore, AQSE triggered hallmark features of ICD, characterized by surface exposure of calreticulin and the release of extracellular HMGB1 and ATP. Most importantly, an in vivo vaccination assay using a syngeneic mouse model demonstrated that immunization with AQSE-treated dying cells significantly suppressed tumor growth upon rechallenge, confirming the establishment of antitumor immunological memory. Additionally, bioassay-guided fractionation revealed that the anticancer activity was primarily concentrated in the ethyl acetate fraction. These findings suggest that AQSE exerts anticancer effects via the induction of apoptosis and ICD, highlighting its potential as a promising natural candidate for the development of novel therapeutic strategies against NSCLC. Full article

Antibiotic resistance among bacteria represents a major challenge in modern medicine. The absence of antibiotics effective against multidrug-resistant pathogens triggers interest in reviving older antibiotics. This review aims to provide a focused and updated perspective on the reintroduction of polymyxin antibiotics, with a particular emphasis on colistin, a cyclic oligopeptide initially used in the 1950s and 1960s. We analyze colistin from multiple perspectives, including (i) its historical and contemporary clinical applications, (ii) pharmacokinetic and pharmacodynamic properties, and (iii) use in veterinary medicine and animal husbandry. Key unresolved issues are highlighted, such as colistin toxicity, challenges in susceptibility testing, the emergence of resistance, including the mcr gene variants, and inconsistent clinical evidence supporting combination therapy. By integrating historical background with current data, this review provides a comprehensive overview of the therapeutic relevance, limitations, and ongoing challenges associated with colistin in the era of multidrug-resistant Gram-negative infections. Full article

The management of multiple sclerosis (MS) is shifting from a phenotype-based framework toward a biologically driven precision medicine model, as conventional magnetic resonance imaging (MRI) inadequately captures smoldering inflammation and progression independent of relapse activity (PIRA). This systematic review aimed to synthesize current evidence on the diagnostic and prognostic utility of fluid biomarkers in distinguishing acute inflammatory injury from chronic neurodegeneration. A comprehensive search of Web of Science, PubMed, and Scopus (January 2020–September 2025) identified 28 eligible studies including 7775 participants (6365 MS patients and 1410 controls). Biomarkers derived from serum, plasma, cerebrospinal fluid (CSF), and stool were evaluated in relation to clinical disability measured using the Expanded Disability Status Scale (EDSS) and magnetic resonance imaging (MRI) outcomes. Neurofilament light chain (NfL) consistently predicted acute inflammatory activity, gadolinium-enhancing lesions, and relapse-associated worsening, but levels were reduced by high-efficacy therapies and did not reliably predict PIRA. In contrast, glial fibrillary acidic protein (GFAP) was associated with astrogliosis, disability progression, and retinal thinning, even in patients with low inflammatory activity. Additional CSF, metabolic, and immunologic markers correlated with neurodegeneration and disease severity. Nevertheless, broader clinical use will require greater assay standardization, improved consistency across cohorts, and validation in prospective longitudinal studies. These findings compel a shift toward a multi-biomarker model to guide personalized therapeutic strategies and develop targeted neuroprotective treatments for progressive multiple sclerosis. Full article

Background: Obstructive sleep apnea (OSA) is a complex and diverse disorder affecting almost one billion individuals worldwide. Severity of untreated OSA, measured by the apnea–hypopnea index (AHI), is noted to be associated with an increased all-cause and cardiovascular mortality. Although widely used, AHI insufficiently captures disease variability as there is a poor correlation of symptoms with the AHI. There lies individual susceptibility to the effects of OSA and that parameter alone poorly predicts cardiovascular outcomes without considering intermittent hypoxia and the hemodynamic effects of OSA. Recognition of clinical, polysomnographic, and neurophysiological phenotypes offers an opportunity to refine diagnosis, prognosis, and management strategies. Methods: We conducted a narrative synthesis of the literature involving 70 articles, focusing on quantitative and qualitative (Q2) clinical traits, polysomnographic parameters, and mechanistic insights that enable subclassification of OSA beyond AHI. Evidence from large cohorts, animal models, and pathophysiological studies were reviewed. Results: Phenotyping based on a Q2 analysis of polysomnographic respiratory event predominance, event duration, positional and REM dependence, hypoxic burden, and arousal characteristics reveals significant heterogeneity in risk profiles and therapeutic response. Apnea-predominant OSA correlates with a higher oxygen desaturation index and Epworth sleepiness scale. Hypopnea-predominant OSA correlates with a cardiometabolic disease burden and may show a more favorable response to surgical therapies. The duration of respiratory events is related to cardiovascular risk, and REM-predominant OSA independently predicts hypertension and adverse cardiovascular outcomes. Supine-predominant OSA demonstrates treatment responsiveness to auto-positive airway pressure and positional therapy. Respiratory effort–related arousals (RERAs), RERA-predominant OSA and the broader respiratory disturbance index (RDI) provide neurophysiological insight often missed by AHI-based classifications. Hypoxic burden, rather than AHI, emerged as a superior predictor of cardiovascular events and mortality. Finally, arousal frequency and periodic limb movements independently predict cardiovascular morbidity. Conclusions: Employing Q2-based phenotyping that incorporates clinical, polysomnographic, and neurophysiological markers improves risk stratification, prognosis, and individualized management of OSA. Future investigations should prioritize integrating phenotypic subclassification into diagnostic criteria and treatment planning to advance precision medicine in sleep apnea care. Full article

Lower-limb exoskeleton robots play a pivotal role in rehabilitation medicine and assistive augmentation, where precise dynamic modelling and trajectory tracking control are fundamental to effective assistance. Existing models predominantly focus on hip and knee rotational degrees of freedom, with insufficient attention to ankle dynamics and pelvic translation. To address these limitations, this paper establishes a sagittal-plane dynamic model comprising nine generalised coordinates, treating the human lower limb and exoskeleton as an integrated coupled system. A seven-segment kinematic model encompassing the trunk, bilateral thighs, shanks, and feet is constructed via a modified Denavit–Hartenberg parameter method, and dynamic equations are derived using Lagrangian formulation. Three control strategies—PD control, PD with gravity compensation, and the computed torque method—are designed and evaluated through simulations using gait data from five subjects (two self-collected, three from a public dataset) acquired via Vicon motion capture. Results demonstrate that the computed torque method achieves a joint angle tracking root mean square error (RMSE) of 0.59°, representing an 86.3% improvement over conventional PD control, while maintaining a low control torque RMS of 4.44 N·m. The controller exhibits stable tracking performance across walking speeds of 0.4–1.45 m/s, validating the effectiveness of the proposed model and control strategies. Full article

Brosimum alicastrum Swartz is a forest species with substantial potential for animal and human nutrition. However, its nutritional attributes and commercial applications are poorly disseminated and structurally underdeveloped. This study examines the relationship between scientific research and the commercialization of Brosimum alicastrum products in Mexico, integrating bibliometric analysis with a value network approach to identify market constraints and opportunities. Scientific publications indexed in Scopus from 1961 to 2024 were analyzed to characterize research trends, documented uses, and the geographic distribution of knowledge production. In parallel, companies commercializing Brosimum alicastrum-based products in Mexico were surveyed during 2024 using a value network approach (suppliers, customers, complementors, and competitors). A SWOT analysis was conducted to assess the structural strengths and vulnerabilities affecting market development. The results show that research in Mexico has primarily focused on the species’ properties as a functional food. At the same time, limited attention has been given to silviculture, commercialization strategies, and value-chain governance. Although Brosimum alicastrum products are currently positioned within premium market segments, business continuity is constrained by unstable supply systems that rely almost exclusively on seasonal wild collection from natural distribution areas. Both the value network and the SWOT analysis identified supply instability as the main factor limiting market expansion. Therefore, advancing research on the silviculture of Brosimum alicastrum is essential to support the establishment of managed production systems and commercial plantations capable of ensuring a stable, year-round supply of raw material. These developments would facilitate access to new market niches and enhance the biocultural and ethnobotanical value of Brosimum alicastrum as a functional and medicinal food resource within Mexico’s emerging bioeconomy. Full article