Search Results (18,589)

Background: Ketamine and magnesium sulfate are commonly used perioperatively to prevent shivering, a frequent and clinically relevant complication of spinal and general anesthesia. Although their hypothermic effects are well documented, the neurotransmitter mechanisms underlying these effects remain insufficiently understood. This study examines whether serotonergic, adrenergic (α₂), and GABAergic (GABA_A) systems contribute to hypothermia induced by ketamine and a ketamine–magnesium sulfate combination. Methods: Body temperature was measured in Wistar rats after administration of ketamine (10 mg/kg) or the ketamine (5 mg/kg)–magnesium sulfate (5 mg/kg) combination. To assess neurotransmitter involvement, animals received yohimbine (α₂ antagonist), methysergide (non-selective 5-HT antagonist), or bicuculline (GABA_A antagonist) prior to ketamine or the drug combination. Data were analyzed using two-way repeated measures ANOVA followed by Tukey’s post hoc test. Results: Yohimbine at 0.5 and 1 mg/kg significantly potentiated ketamine-induced hypothermia, while only 3 mg/kg enhanced the effect of the ketamine–magnesium sulfate combination. Methysergide had a bidirectional influence: 1 mg/kg methysergide deepened ketamine-induced hypothermia, whereas 0.5 mg/kg methysergide attenuated the hypothermic effect of the ketamine–magnesium sulfate combination. Bicuculline (1–2 mg/kg) did not alter the hypothermic responses to ketamine or the combination. Conclusions: These findings indicate that ketamine- and ketamine–magnesium sulfate-induced hypothermia is primarily modulated by serotonergic and adrenergic mechanisms, whereas GABA_A receptor-dependent pathways do not appear to play a major role under the experimental conditions used. These results provide new mechanistic insights into NMDA antagonist–related thermoregulation and may help inform anesthetic strategies for shivering prevention and maintenance of perioperative thermal stability. Full article

Berberine, a benzyl isoquinoline alkaloid, is used in food for its diverse spectrum of biological activities. Inflammatory bowel disease (IBD) is a widespread condition characterized by frequent occurrence and limited therapeutic success. Berberine has been shown to alleviate colitis through enhancement of the intestinal barrier and modulation of gut microbial balance. However, the further mutualistic balance mechanism between microbes and the mucus of berberine in alleviating IBD still needs to be clarified. Our findings demonstrated a strong association between berberine’s therapeutic efficacy and alterations in the gut microbiota. This includes enhancements in the level of IgA-coated bacteria, Zg16, Reg3g, and Pla2g2a, all of which contribute to microbiota homeostasis. Moreover, the beneficial effect on gut barrier function of berberine was mostly attributed to Akkermansiam and Bacteriodes-associated mucin–SCFA metabolism. This study lays a critical groundwork for the development of berberine-based functional food additives that harness its nutraceutical potential. Full article

Background/Objectives: Exercise-induced fatigue is a fundamental component of running performance and training, yet it is also implicated in altered movement mechanics and increased injury risk. While numerous studies have examined fatigue-related biomechanical changes during running, findings remain fragmented across biomechanical domains and fatigue modalities. The purpose of this systematic review was to synthesize contemporary evidence on the effects of fatigue on lower-limb biomechanics during running and to interpret the potential injury relevance of these adaptations. Methods: A systematic literature search was conducted in PubMed, Scopus, and Web of Science for original empirical studies published between January 2010 and December 2025. Eligible studies involved human participants performing running or running-related tasks, applied an explicit fatigue protocol, and reported quantitative lower-limb biomechanical outcomes. Study selection followed PRISMA 2020 guidelines. Data extraction included participant characteristics, fatigue protocols, biomechanical measures, instrumentation, and key findings. Methodological quality was assessed using the Cochrane Risk of Bias 2 (RoB-2) tool. Due to substantial methodological heterogeneity, findings were synthesized narratively. Results: Twenty-four studies met the inclusion criteria. Across studies, fatigue consistently altered spatiotemporal parameters, joint kinematic and kinetic variables, spring-mass behavior, impact loading, coordination variability, neuromuscular output, and inter-limb symmetry. Common adaptations included increased ground contact time, reduced ankle joint power and stiffness, increased joint range of motion, elevated impact loading, and greater movement variability. These changes reflected reduced mechanical efficiency and a redistribution of mechanical load from distal to proximal joints, particularly toward the knee and hip. Similar fatigue-related biomechanical patterns were observed in both laboratory-based and real-world endurance running conditions. Conclusions: Exercise-induced fatigue produces systematic and injury-relevant alterations in lower-limb biomechanics during running. These adaptations may preserve short-term performance but create mechanical conditions associated with increased susceptibility to overuse and non-contact injuries. Integrating fatigue-aware biomechanical assessment, neuromuscular conditioning, and individualized load management strategies may help mitigate adverse fatigue-related adaptations. Full article

HER2 testing represents a cornerstone of the treatment algorithm in advanced gastric and gastroesophageal junction adenocarcinoma (GC), yet its evaluation remains complex due to tumor heterogeneity and methodological variability. Unlike breast cancer, HER2 expression in GC is often incomplete and heterogeneous, resulting in discordant results between biopsies, resections, and metastatic sites. Both spatial and temporal HER2 heterogeneity are key determinants of testing reproducibility, diagnostic accuracy, and treatment selection and response in GC. Optimizing sampling through multiple, well-targeted biopsies, standardizing IHC/ISH protocols, and reassessing HER2 status at progression may be crucial steps to ensure diagnostic accuracy. The recognition of HER2-low disease introduces a new pathological and clinical subgroup of GC with potential sensitivity to antibody–drug conjugates, while emerging techniques such as circulating tumor DNA analysis are increasingly applied to detect HER2 amplification and co-existing genetic alterations. Integrating molecular tools and standardized reassessment strategies can enhance HER2 testing reliability and enable more precise treatment strategies, with the potential to minimize HER2 resistance mechanisms. This review provides a practice-oriented guide on the interpretation and optimization of HER2 testing in gastric cancer, while providing insight into the underlying molecular mechanisms driving heterogeneity and resistance. Full article

Oxidative stress-induced lipid peroxidation products (LPPs), particularly 4-hydroxy-nonenal (4-HNE) and 4-oxo-nonenal (4-ONE), have recently gained attention for their direct regulation of ion channels essential for pain signaling. In this study, we investigated how these two LPPs affect the electrophysiological properties of neurons, specifically voltage-gated sodium (Na_V) channels, thereby influencing sensory neuron excitability and pain pathways. Using human neuroblastoma (SH-SY5Y) and ND7/23 cells (a fusion cell line exhibiting partial sensory neuron properties), we measured changes in Na_V channel-mediated sodium currents following treatment with 4-HNE or 4-ONE. Whole-cell patch-clamp experiments showed that 4-ONE (10 µM) and 4-HNE (100 µM) did not significantly alter the peak sodium current amplitude in SH-SY5Y cells. However, in ND7/23 cells, both 4-HNE and 4-ONE induced a negative shift in Na_V channel activation voltage dependence, enabling sodium channel activation at lower membrane potentials. Furthermore, current-clamp recordings in primary mouse dorsal root ganglion neurons demonstrated that treatment with 4-ONE and 4-HNE reduced the current threshold required to elicit action potentials and significantly increased action potential firing frequency. These findings indicate that LPPs enhance pain sensitivity by modulating Na_V channels, which play a crucial role in pain transmission. In conclusion, 4-HNE and 4-ONE shift the voltage-dependent activation of sodium channels toward more negative potentials, thereby increasing the excitability of primary sensory neurons and amplifying pain signals. This study provides molecular insights into how oxidative stress-related lipid peroxidation contributes to sensory mechanisms and offers potential avenues for developing new treatments for oxidative stress- or inflammation-associated pain. Full article

Endometriosis is a chronic, estrogen-dependent inflammatory disorder that is increasingly recognized as a systemic condition with profound implications for female reproductive potential. In addition to pelvic distortion and impaired folliculogenesis, growing evidence indicates that intrinsic alterations in oocyte morphology, mitochondrial function, and developmental competence contribute to infertility. The disease is driven by a multifactorial interplay of somatic mutations, epigenetic remodeling, immune dysregulation, and aberrant steroid signaling, which together create a pro-inflammatory, oxidative, and fibrotic microenvironment. Elevated cytokines, reactive oxygen species, and disrupted granulosa-cell function within the follicular niche impair meiotic progression, cytoplasmic maturation, and mitochondrial integrity, potentially accelerating oocyte aging and diminishing reproductive longevity. Epigenetic and post-transcriptional disturbances—including altered DNA methylation, histone modifications, and RNA-splicing defects—further reinforce estrogen dominance, progesterone resistance, and impaired decidualization, with downstream consequences for ovarian–endometrial communication. Although morphological abnormalities have been documented in oocytes from women with endometriosis, clinical outcomes remain heterogeneous, highlighting the need for integrative models that connect molecular alterations to functional reproductive endpoints. A deeper understanding of these mechanisms is essential for identifying biomarkers of oocyte competence and modifiable strategies—ranging from nutritional optimization to reduction of environmental risk factors—in clinical care to safeguard the reproductive potential of women with endometriosis. Full article

The residential building sector is a significant source of global energy consumption and carbon emissions, especially in rapidly changing rural areas. In China, the shift from vernacular courtyard dwellings to modern rural housing has altered the relationship among architectural form, thermal comfort (TC), and energy use. Vernacular dwellings in northern China employ passive strategies, such as courtyard-centred layouts, high thermal-mass envelopes, and natural ventilation, to achieve summer comfort with minimal energy input. In contrast, modern dwellings (brick–concrete) depend more on mechanical cooling and consume more electricity. This study investigates how dwelling type, spatial configuration, building materials, courtyard configuration, thermal comfort, and housing satisfaction interact to shape residential environmental adaptability in rural Handan, Hebei Province. A questionnaire survey of 383 households was analysed using Partial Least Squares Structural Equation Modelling (PLS-SEM). To supplement perceptual data, summer electricity consumption was monitored in 20 typical dwellings from June to August 2025, and on-site measurements of air temperature, relative humidity, and courtyard air velocity were conducted in six representative cases. The results indicate that dwelling type significantly affects spatial configuration and courtyard form, while spatial configuration and courtyard characteristics together influence material performance. Thermal comfort is identified as a key mediating variable with a strong direct impact on housing satisfaction. Field measurements confirm that vernacular dwellings have lower summer electricity consumption, more stable thermal conditions, improved humidity regulation, and higher courtyard air velocity, indicating superior passive cooling potential. These findings provide empirical evidence that incorporating vernacular passive design principles into contemporary rural housing can improve thermal comfort and reduce energy dependence, thereby supporting climate-responsive, low-carbon rural revitalization strategies. Full article

Serrated adenocarcinoma (SAC) represents a molecularly heterogeneous subtype of colorectal carcinoma (CRC) linked to the serrated pathway. It is aimed to clarify the molecular mechanisms underlying SAC development. Digital slides from The Cancer Genome Atlas (TCGA) colorectal adenocarcinoma Firehose Legacy dataset (632 cases) were reviewed, and cases were classified as SAC, partial-SAC, or classical CRC. Genomic alterations, mRNA expression, and DNA hypermethylation were compared using cBioPortal. Enrichment analyses were performed via WebGestalt, and protein–protein interaction (PPI) networks with hub genes were identified using STRING and Cytoscape. Statistical significance was defined as p < 0.05 and q < 0.05. The results revealed that the groups showed significant differences in the expression of 327 genomic alterations, 20 mRNAs, and 21 methylated genes (p < 0.0001, q < 0.0001). Hub genes were PSMC1, FLT3LG, SNW1, H3C2, H1-2, H2BC14, H1-5, RPS16, SUPT5H, and MYOD1. The pathways associated with differently expressed genes were the following: cell structure and morphology (phagocytic vesicle, microvillus, endocytosis, and immobile cilium), protein kinase activity (particularly MAPK), and immunological mechanisms. The hub genes act as molecular bridges connecting the observed genomic and epigenetic variations, particularly driving chromatin-related regulation and MAPK signaling pathways. In particular, PSMC1, SNW1, H3C2, H1-2, and H2BC14 genes offer promising molecular targets for future therapeutic approaches in SACs. Full article

The tumor microenvironment plays a critical role in cancer progression, with oxidative stress, autophagy, angiogenesis, and cell migration acting as tightly interconnected processes. Natural bioactive compounds have emerged as promising modulators of these pathways; however, their cell type-specific effects within the TME remain poorly understood. In this study, we investigate the effects of punicalin on triple-negative breast cancer and endothelial cells, with a focus on redox homeostasis and autophagy as upstream regulatory mechanisms. Punicalin reduced oxidative stress in MDA-MB-231 cells under basal conditions and strongly attenuated hydrogen peroxide-induced stress, whereas HMEC-1 cells exhibited concentration- and condition-dependent reactive oxygen species (ROS) modulation. Autophagy assays revealed no significant modulation in tumor cells, while a consistent and pronounced decrease in autophagic activity was observed in endothelial cells under both basal and nutrient-deprivation conditions. Functionally, punicalin decreased tumor cell migration and impaired HMEC-1 migration, while HUVEC migration remained largely unaffected. Tube formation assays demonstrated significant inhibition of angiogenic capacity. Taken together, these findings demonstrate that punicalin selectively modulates oxidative stress and autophagy, leading to functional alterations in migration and angiogenesis. By highlighting its selective impact on microvascular endothelial cells while sparing normal endothelium, this study provides a strong rationale for further preclinical evaluation of punicalin. Full article

Bacillus thuringiensis (Bt) is one of the most extensively used microbial insecticides, attributed to the action of insecticidal crystal proteins (ICPs), primarily Cry toxins, which mediate damage to the insect midgut epithelium. Recent evidence suggests that Bt toxicity is also strongly influenced by its physiological state and interactions with the host gut environment. Biofilm formation represents an important adaptive strategy that enhances bacterial stress tolerance and may modulate insecticidal performance, although the underlying mechanisms remain unclear. However, it is still unclear how Bt in the biofilm state alters host responses at the structural and transcriptomic levels. Using the tea plantation pest Ectropis grisescens as a model, we systematically evaluated the insecticidal efficacy of biofilm-state Bt formulations and their synergistic effects with a biofilm inducer system composed of Tween-80, tea saponin, matrine, and tea polyphenols. Bioassays showed that the biofilm-state Bt supplemented with composite inducers achieved the highest corrected mortality and reduced the LC₅₀ against neonate larvae by 2.88-fold compared with conventional planktonic Bt. Histopathological, biochemical, and transcriptomic analyses further revealed that biofilm-state Bt caused more severe midgut damage and induced extensive remodeling of detoxification- and stress-response-related pathways. These findings highlight Bt physiological state as a critical determinant of formulation efficacy and provide a novel framework for Bt optimization through microbial physiological regulation. Full article

Type 2 diabetes mellitus (T2DM) is a globally prevalent chronic metabolic disorder that poses severe public health risks. Synthetic hypoglycemic agents are susceptible to inducing adverse reactions, thus driving the development of natural, safe and highly effective plant-derived hypoglycemic active compounds as a research hotspot. Inhibiting the activity of α-glucosidase and α-amylase represents an effective strategy to regulate postprandial blood glucose levels. This study investigated the synergistic hypoglycemic activity of a composite (PS-PP) formed by polysaccharide (PS) and polyphenols (PP) from Ziziphus jujuba Mill. cv. Muzao and elucidated the structural basis underlying this synergistic effect. First, MPS and MPP were isolated and purified, followed by the in vitro assembly to prepare PS-PP. The hypoglycemic activities of MPS, MPP and MPS-PP were evaluated via in vitro enzyme inhibition assays, while structural characterization was conducted using GPC-MALLS, FT-IR and SEM techniques. Results demonstrated that PS-PP exerted the strongest activity under optimal conditions (0.75 mg/mL concentration, pH 4.0, 1:2 mass ratio), with IC₅₀ values of 1.14 μg/mL and 0.82 μg/mL against the two enzymes, which were superior to those of polysaccharides (15.10 and 36.06 μg/mL) and polyphenols (1.18 and 46.24 μg/mL). Structural analysis revealed that the interaction between PS and PP was primarily mediated by hydrogen bonds. PS-PP exhibited significant differences from single-component compounds in molecular weight distribution, functional group binding and surface morphology. These structural alterations were identified as the key factors contributing to its enhanced hypoglycemic efficacy. This study clarifies the synergistic hypoglycemic mechanism of MPP-PS and lays a scientific foundation for the development of natural hypoglycemic preparations and functional foods. Full article

Ovarian cancer (OC) is a particularly lethal gynecological malignancy with few treatment options due to its late-stage diagnosis, extensive genetic heterogeneity, and frequent development of resistance to existing therapies. Immunotherapy has revolutionized the management and clinical outcome of numerous solid tumors, but its clinical benefit for OC has been limited, in part due to an extremely immunosuppressive tumor microenvironment (TME) and diverse, overlapping immune evasion mechanisms. In this review, we present a comprehensive and timely synthesis of next-generation immunotherapeutic approaches for ovarian cancer, emphasizing strategies that overcome the immunosuppressive tumor microenvironment and improve clinical responsiveness. We describe the emerging molecular mechanisms of immune evasion in OC, including altered antigen presentation, inhibition of T-cell activation (e.g., via immunological checkpoints, metabolic reprogramming), polarization of tumor-associated macrophages (TAMs), and dysfunction of natural killer (NK) cells. We also critically examine several emerging therapeutic approaches, including combination immune checkpoint blockade (ICB), bispecific T-cell engagers (BiTEs), neoantigen-based vaccines, chimeric antigen receptor (CAR)-T- and CAR-NK-cell therapies, oncolytic viruses (OVs), and nanoparticle-mediated immunomodulation. In addition, we highlight recent advances in tumor microenvironment–targeted therapies for ovarian cancer, focusing on strategies that modulate non-lymphoid components such as cancer-associated fibroblasts (CAFs), hypoxia-driven signaling, and the PI3K/AKT/mTOR axis to enhance antitumor immune responsiveness. Finally, we discuss how predictive biomarkers, multi-omics systems, and patient-derived organoid models are accelerating the development and deployment of precision immunotherapies for OC. We would like to highlight the translational promise of next-generation immunotherapies and identify novel molecular targets that may be leveraged to achieve durable responses in OC. Full article

Post-COVID syndrome comprises persistent neuropsychiatric manifestations for more than 12 weeks after recovery from acute SARS-CoV-2 infection, yet its underlying pathophysiology is unclear. Ferroptosis, an iron-dependent form of cell death with three hallmarks, iron dysregulation, antioxidant failure, and lipid peroxidation, seems to be involved in COVID-19/post-COVID-19 pathophysiology. Here, we administered the SARS-CoV-2 spike protein S1 subunit intranasally to K18-hACE2 transgenic mice and quantified ferroptotic marker protein expression in four brain regions (hippocampus, prefrontal cortex, cerebellum, and olfactory bulb) at 2, 6, and 12 weeks post-administration, alongside ultrastructural assessment by transmission electron microscopy (TEM) that was limited to the hippocampus and prefrontal cortex. Two-way ANOVA revealed region- and time-dependent modulation of iron-handling, antioxidant, and lipid peroxidation markers. In the hippocampus, FPN1 was significantly increased at 2 weeks, while TFR1 showed a time-dependent pattern without significant week-specific differences. In the prefrontal cortex, DMT1 significantly increased at 2 weeks, and GPx4 showed an overall treatment effect with a trend of increase at 6 weeks. The cerebellum exhibited early increases in FPN1 and GPx4 and a delayed increase in MDA-conjugated proteins. In the olfactory bulb, FPN1 increased at 12 weeks, with GPx4 showing an overall treatment effect and an early trend of decrease. TEM identified ferroptosis-consistent features in the hippocampus and prefrontal cortex at all time points. These findings suggest that spike protein exposure may be associated with time-dependent and brain-region-specific alterations of ferroptosis-related markers. These preliminary findings are based on a limited sample size, which needs further research to elucidate the clinical implication and to study the mechanism in more depth as well as future validation with pharmacological inhibitors. Full article

Objective: To synthesize current evidence on the relationships between adolescent idiopathic scoliosis (AIS), stress-related mechanisms, neuroanatomical asymmetry, and mental disorders, and to propose an integrative conceptual framework describing their interaction. Materials and Methods: A comprehensive literature review was conducted using the PubMed, Web of Science, and Scopus databases. Search terms targeted the etiology and pathogenesis of adolescent idiopathic scoliosis, hemispheric lateralization, stress responses, body schema disturbances, and associated mental disorders. The review was reported in accordance with PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) recommendations. A structured qualitative synthesis of 225 relevant publications was performed. Results: The analyzed studies revealed several complementary conceptual approaches to AIS pathogenesis. Emerging evidence suggests that atypical hemispheric lateralization, potentially associated with right-hemisphere (RH) dysfunction, may contribute to susceptibility to AIS. Such patterns of lateralization have been linked to specific stress-related coping strategies, including harm avoidance, as well as to disturbances of body schema and an increased prevalence of certain mental disorders. Gender-related differences in stress responses and in the development and progression of AIS were consistently reported across studies. Collectively, these findings support the hypothesis that neuropsychological and stress-related mechanisms, including phenomena described as the “distorting mirror effect”, may contribute to the persistence and progression of spinal deformity in vulnerable individuals. Conclusions: AIS appears to be a multifactorial condition in which atypical neuroanatomical asymmetry, stress-related processes, and altered body representation interact. This integrative perspective generates hypotheses suggesting that prevention and treatment strategies for AIS could benefit from incorporating approaches aimed at modulating stress responses and enhancing brain neuroplasticity. Further interdisciplinary studies integrating clinical, neuroimaging, and neurobiological methods are warranted to clarify underlying mechanisms. Full article

Migraine and epilepsy are common neurological disorders that share overlapping symptoms, such as visual disturbances and altered consciousness, making accurate diagnosis challenging. Although their underlying mechanisms differ, both conditions involve recurrent irregular brain activity, and traditional EEG-based diagnosis relies heavily on clinical interpretation, which may be subjective and insufficient for clear differentiation. To address this challenge, this study introduces an automated EEG classification framework combining Dual Tree Complex Wavelet Transform (DTCWT) for feature extraction with a Random Subspace Ensemble Classifier for multi-class discrimination. EEG data recorded under photic and nonphotic stimulation were analyzed to capture both temporal and frequency characteristics. DTCWT proved effective in modeling the non-stationary nature of EEG signals and extracting condition-specific features, while the ensemble classifier improved generalization by training multiple models on diverse feature subsets. The proposed system achieved an average accuracy of 99.50%, along with strong F-measure, AUC, and Kappa scores. Notably, although previous studies suggest heightened EEG activity in migraine patients during flash stimulation, findings here indicate that flash stimulation alone does not reliably distinguish migraine from epilepsy. Overall, this research highlights the promise of advanced signal processing and machine learning techniques in enhancing diagnostic precision for complex neurological disorders. Full article