Search Results (7,948)

Antioxidative neuroprotection is effective at preventing ischemic stroke (IS). Ferulic acid (FA) offers benefits in the treatment of many diseases, mostly due to its antioxidant activities. In this study, a glycosylated ferulic acid conjugate (FA-Glu), with 1,2,3-triazole as a linker and bioisostere between glucose at the C6 position and FA at the C4 position, was designed and synthesized. The hydrophilicity and chemical stability of FA-Glu were tested. FA-Glu’s protection against DNA oxidative cleavage was tested using pBR322 plasmid DNA under the Fenton reaction. The cytotoxicity of FA-Glu was examined via the PC12 cell and bEnd.3 cell tests. Antioxidative neuroprotection was evaluated, in vitro, via a H₂O₂-induced PC12 cell test, measuring cell viability and ROS levels. Antioxidative alleviation of cerebral ischemia–reperfusion injury (CIRI), in vivo, was evaluated using a rat middle cerebral artery occlusion (MCAO) model. The results indicated that FA-Glu was water-soluble (LogP −1.16 ± 0.01) and chemically stable. FA-Glu prevented pBR322 plasmid DNA cleavage induced via •OH radicals (SC% 88.00%). It was a non-toxic agent based on PC12 cell and bEnd.3 cell tests results. FA-Glu significantly protected against H₂O₂-induced oxidative damage in the PC12 cell (cell viability 88.12%, 100 μM) and inhibited excessive cell ROS generation (45.67% at 100 μM). FA-Glu significantly reduced the infarcted brain areas measured using TTC stain observation, quantification (FA-Glu 21.79%, FA 28.49%, I/R model 43.42%), and H&E stain histological observation. It sharply reduced the MDA level (3.26 nmol/mg protein) and significantly increased the GSH level (139.6 nmol/mg protein) and SOD level (265.19 U/mg protein). With superior performance to FA, FA-Glu is a safe agent with effective antioxidative DNA and neuronal protective actions and an ability to alleviate CIRI, which should help in the prevention of IS. Full article

Background: Acute mountain sickness (AMS) is a prevalent and potentially life-threatening condition caused by rapid exposure to high-altitude hypoxia, affecting pulmonary and neurological functions. Tongqiao Jiuxin Oil (TQ), a traditional Chinese medicine formula composed of aromatic and resinous ingredients such as sandalwood, agarwood, frankincense, borneol, and musk, has been widely used in the treatment of cardiovascular and cerebrovascular disorders. Clinical observations suggest its potential efficacy against AMS, yet its pharmacological mechanisms remain poorly understood. Methods: The chemical profile of TQ was characterized using UHPLC-Q-Exactive Orbitrap HRMS. Network pharmacology was applied to predict the potential targets and pathways involved in AMS. A rat model of AMS was established by exposing animals to hypobaric hypoxia (~10% oxygen), simulating an altitude of approximately 5500 m. TQ was administered at varying doses. Physiological indices, oxidative stress markers (MDA, SOD, GSH), histopathological changes, and the expression of hypoxia- and apoptosis-related proteins (HIF-1α, VEGFA, EPO, Bax, Bcl-2, Caspase-3) in lung and brain tissues were assessed. Results: A total of 774 chemical constituents were identified from TQ. Network pharmacology predicted the involvement of multiple targets and pathways. TQ significantly improved arterial oxygenation and reduced histopathological damage in both lung and brain tissues. It enhanced antioxidant activity by elevating SOD and GSH levels and reducing MDA content. Mechanistically, TQ downregulated the expression of HIF-1α, VEGFA, EPO, and pro-apoptotic markers (Bax/Bcl-2 ratio, Caspase-3), while upregulated Bcl-2, the anti-apoptotic protein expression. Conclusions: TQ exerts protective effects against AMS-induced tissue injury by improving oxygen homeostasis, alleviating oxidative stress, and modulating hypoxia-related and apoptotic signaling pathways. This study provides pharmacological evidence supporting the potential of TQ as a promising candidate for AMS intervention, as well as the modern research method for multi-component traditional Chinese medicine. 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

Background/Objectives: Senecio scandens Buch.-Ham. is a flavonoid-rich traditional medicinal plant with established immunomodulatory properties. However, the mechanisms underlying the immunoregulatory and intestinal protective effects of its flavonoid extract (Senecio scandens flavonoids—SSF) remain unclear. This study characterized SSF’s bioactive components and evaluated its efficacy against cyclophosphamide (CTX)-induced immunosuppression and intestinal injury. Methods: The constituents of SSF were identified using UHPLC/Q-Orbitrap/HRMS. Mice with CTX-induced immunosuppression were treated with SSF (80, 160, 320 mg/kg) for seven days. Immune parameters (organ indices, lymphocyte proliferation, cytokine, and immunoglobulin levels) and gut barrier integrity markers (ZO-1, Occludin, Claudin-1 protein expression; sIgA secretion; microbiota composition) were assessed. Network pharmacology combined with functional assays elucidated the underlying regulatory mechanisms. Results: Twenty flavonoids were identified in SSF, with six prototype compounds detectable in the blood. The SSF treatment significantly ameliorated CTX-induced weight loss and atrophy of the thymus and spleen. It enhanced splenic T- and B-lymphocyte proliferation by 43.6% and 29.7%, respectively; normalized the CD4⁺/CD8⁺ ratio (1.57-fold increase); and elevated levels of IL-2, IL-6, IL-10, TNF-α, IFN-γ, IgM, and IgG. Moreover, SSF reinforced the intestinal barrier by upregulating tight junction protein expression and sIgA levels while modulating the gut microbiota, enriching beneficial taxa (e.g., the Lachnospiraceae_NK4A136_group, Akkermansia) and suppressing pathogenic Alistipes. Mechanistically, SSF activated the TLR/MyD88/NF-κB pathway, with isoquercitrin identified as a pivotal bioactive constituent. Conclusions: SSF effectively mitigates CTX-induced immunosuppression and intestinal damage. These findings highlight SSF’s potential as a dual-functional natural agent for immunomodulation and intestinal protection. Subsequent research should validate isoquercitrin’s molecular targets and assess SSF’s clinical efficacy. Full article

Chronic kidney disease (CKD) has now reached epidemic proportions in many parts of the world, primarily due to the high incidence of diabetes and hypertension. By 2040, CKD is predicted to be the fifth-leading cause of years of life lost. Developing strategies to prevent CKD and to reduce its progression to kidney failure is thus of great public health significance. Hypertension is known to be both a cause and a consequence of kidney damage and an eminently modifiable risk factor. An increased risk of hypertension, especially among women, has been linked to chronic exposure to the ubiquitous food contaminant cadmium (Cd). The mechanism is unclear but is likely to involve its action on the proximal tubular cells (PTCs) of the kidney, where Cd accumulates. Here, it leads to chronic tubular injury and a sustained drop in the estimated glomerular filtration rate (eGFR), a common sequela of ischemic acute tubular necrosis and acute and chronic tubulointerstitial inflammation, all of which hinder glomerular filtration. The present review discusses exposure levels of Cd that have been associated with an increased risk of hypertension, albuminuria, and eGFR ≤ 60 mL/min/1.73 m² (low eGFR) in environmentally exposed people. It highlights the potential role of 20-hydroxyeicosatetraenoic acid (20-HETE), the second messenger produced in the kidneys, as the contributing factor to gender-differentiated effects of Cd-induced hypertension. Use of GFR loss and albumin excretion in toxicological risk calculation, and derivation of Cd exposure limits, instead of β₂-microglobulin (β₂M) excretion at a rate of 300 µg/g creatinine, are recommended. Full article

Background: Nigella sativa, known as black cumin, is traditionally used to treat various illnesses. Objective: The current study aims to investigate the potential hepatoprotective and nephroprotective effect of black cumin fractions via per os route in CCl₄-intoxicated Wistar rats. This study used a computational approach to assess the interaction of bioactive compounds with key proteins (CYP P450 3E1, TNF-α, and Cox-2). Methods: Wistar rats were treated with CCl₄ to induce liver injury and with different Nigella sativa fractions (250 mg/Kg) or Sylimarin (50 mg/Kg). Liver and kidney functions were assessed through biochemical markers, hepatic glycogen, malondialdehyde levels, molecular docking, and ADMET analysis to evaluate drug-likeliness. Results: The results revealed that intoxication with CCl₄ induced an elevation in different liver and kidney biochemical parameters such as (ALT, AST, creatinine, urea...) indicating kidney and hepatic toxicity. However, treatment with different Nigella sativa fractions showed a significant improvement in animal body weight and significant amelioration of biochemical markers indicating a protective potential of these fractions against CCl₄-induced intoxication. Furthermore, the molecular docking approach demonstrated high binding affinity with the target proteins. Conclusions: These current findings shed light on the therapeutic potential of Nigella sativa fractions as a promising protective agent of the liver and kidney against CCl₄ intoxication. Full article

Background: Metabolic syndrome (MetS) is a complex clinical condition characterized by the coexistence of interrelated metabolic abnormalities that significantly increase the risk of cardiovascular diseases and type 2 diabetes mellitus. Endocan—an endothelial cell-specific molecule—is considered a biomarker of endothelial dysfunction and inflammation. This study aimed to evaluate the relationship between serum endocan levels and the severity of MetS, assessed using the MetS-Z score. Methods: This study included 120 patients with MetS and 50 healthy controls. MetS was diagnosed according to the NCEP-ATP III criteria. MetS-Z scores were calculated using the MetS Severity Calculator. Serum levels of endocan, sICAM-1, and sVCAM-1 were measured using the ELISA method. Results: Serum levels of endocan, sICAM-1, and sVCAM-1 were significantly higher in the MetS group compared to the control group (all p < 0.001). When the MetS group was divided into tertiles based on MetS-Z scores, stepwise and statistically significant increases were observed in the levels of endocan and other endothelial markers from the lowest to highest tertile (p < 0.0001). Correlation analysis revealed a strong positive association between the MetS-Z score and serum endocan levels (r = 0.584, p < 0.0001). ROC curve analysis showed that endocan has high diagnostic accuracy for identifying MetS (AUC = 0.967, p = 0.0001), with a cutoff value of >88.0 ng/L. Conclusions: Circulating levels of endocan were significantly increased in MetS and were associated with the severity of MetS, suggesting that endocan may play a role in the cellular response to endothelial dysfunction-related injury in patients with MetS. Full article

Hydrogen-rich water (HRW) has shown neuroprotective effects in acute brain injury, but its role in chronic radiation-induced brain injury (RIBI) remains unclear. This study investigated the long-term efficacy of HRW in mitigating cognitive impairment and neuronal damage caused by chronic RIBI. Fifty male Sprague Dawley rats were randomly divided into five groups: control, irradiation (IR), IR with memantine, IR with HRW, and IR with combined treatment. All but the control group received 20 Gy whole-brain X-ray irradiation, followed by daily interventions for 60 days. Behavioral assessments, histopathological analyses, oxidative stress measurements, ¹⁸F-FDG PET/CT imaging, transcriptomic sequencing, RT-qPCR, Western blot, and serum ELISA were performed. HRW significantly improved anxiety-like behavior, memory, and learning performance compared to the IR group. Histological results revealed that HRW reduced neuronal swelling, degeneration, and loss and enhanced dendritic spine density and neurogenesis. PET/CT imaging showed increased hippocampal glucose uptake in the IR group, which was alleviated by HRW treatment. Transcriptomic and molecular analyses indicated that HRW modulated key genes and proteins, including CD44, CD74, SPP1, and Wnt1, potentially through the MIF, Wnt, and SPP1 signaling pathways. Serum CD44 levels were also lower in treated rats, suggesting its potential as a biomarker for chronic RIBI. These findings demonstrate that HRW can alleviate chronic RIBI by preserving neuronal structure, reducing inflammation, and enhancing neuroplasticity, supporting its potential as a therapeutic strategy for radiation-induced cognitive impairment. Full article

Civil aviation safety remains a critical concern globally, with continuous efforts aimed at reducing accidents and fatalities. This paper focuses on the comprehensive evaluation of civil aviation safety in the Slovak Republic over the past several years, with the main objective of identifying prevailing trends and key risk factors. A comprehensive analysis of 155 accidents and incidents was conducted based on selected operational parameters. Logistic regression was applied to identify potential causal factors influencing various levels of injury severity in aviation accidents. Moreover, the prediction model can also be used to predict the probability of specific injury severity for accidents with given parameter values. The results indicate a clear declining trend in the annual number of aviation safety events; however, the fatality rate has stagnated or slightly increased in recent years. Human error, particularly mistakes and intentional violations of procedures, was identified as the dominant causal factor across all sectors of civil aviation, including flight operations, airport management, maintenance, and air navigation services. Despite technological advancements and regulatory improvements, human-related failures persist as a major safety challenge. The findings highlight the critical need for targeted strategies to mitigate human error and enhance overall aviation safety in the Slovak Republic. Full article

Posterior capsule opacification (PCO), a frequent complication of cataract surgery, arises from dysregulated wound healing and fibrotic transformation of residual lens epithelial cells. While transcriptomic and machine learning (ML) approaches have elucidated fibrosis-related pathways in other tissues, the molecular divergence between regenerative and fibrotic outcomes in the lens remains unclear. Here, we used an ex vivo chick lens injury model to simulate post-surgical conditions, collecting RNA from lenses undergoing either regenerative wound healing or fibrosis between days 1–3 post-injury. Bulk RNA sequencing data were normalized, log-transformed, and subjected to univariate filtering prior to training LASSO, SVM, and RF ML models to identify discriminatory gene signatures. Each model was independently validated using a held-out test set. Distinct gene sets were identified, including fibrosis-associated genes (VGLL3, CEBPD, MXRA7, LMNA, gga-miR-143, RF00072) and wound-healing-associated genes (HS3ST2, ID1), with several achieving perfect classification. Gene Set Enrichment Analysis revealed divergent pathway activation, including extracellular matrix remodeling, DNA replication, and spliceosome associated with fibrosis. RT-PCR in independent explants confirmed key differential expression levels. These findings demonstrate the utility of supervised ML for discovering lens-specific fibrotic and regenerative gene features and nominate biomarkers for targeted intervention to mitigate PCO. Full article

Background/Objectives: The simulation of human movement offers transformative potential for the design of medical devices, particularly in understanding the cause–effect dynamics in individuals with neurological or musculoskeletal impairments. This study presents a simulation-driven framework to determine the optimal ankle–foot orthosis (AFO) stiffness for mitigating the risk of ankle sprains due to excessive subtalar inversion during high-impact activities, such as landing from a free fall. Methods: We employed biomechanical simulations to assess the influence of translational stiffness on subtalar inversion control, given that inversion angles exceeding 25 degrees are strongly correlated with injury risk. Simulations were conducted using a musculoskeletal model with and without a passive AFO; the stiffness varied in three anatomical directions. A Design of Experiments (DoE) approach was utilized to capture nonlinear interactions among stiffness parameters. Results: The results indicated that increased translational stiffness significantly reduced inversion angles to safer levels, though direction–dependent effects were noted. Based on these insights, we developed a 4D visualization tool that integrates simulation data with an interactive color–coded interface to depict ”safe design” zones for various AFO stiffness configurations. This tool supports clinicians in selecting stiffness values that optimize both safety and functional performance. Conclusions: The proposed framework enhances clinical decision-making and engineering processes by enabling more accurate and individualized AFO designs. Full article

Background: Acetaminophen (APAP) is a popular and safe pain reliever. Due to its widespread availability, it is commonly implicated in intentional or unintentional overdoses, which result in severe liver impairment. Pristimerin (Prist) is a natural triterpenoid that has potent antioxidant and anti-inflammatory properties. Our goal was to explore the protective effects of Prist against APAP-induced acute liver damage. Method: Mice were divided into six groups: control, Prist control, N-acetylcysteine (NAC) + APAP, APAP, and two Prist + APAP groups. Prist (0.4 and 0.8 mg/kg) was given for five days and APAP on day 5. Liver and blood samples were taken 24 h after APAP administration and submitted for different biochemical and molecular assessments. Results: Prist counteracted APAP-induced acute liver damage, as it decreased general liver dysfunction biomarkers, and attenuated APAP-induced histopathological lesions. Prist decreased oxidative stress and enforced hepatic antioxidants. Notably, Prist significantly reduced the genetic and protein expressions of inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-II), p-phosphatidylinositol-3-kinase (p-PI3K), p-protein kinase B (p-AKT), and the inflammatory cytokines: nuclear factor kappa B (NF-κB), tumor necrosis factor-α (TNF-α), and interleukins-(IL-6 and IL-1β) in hepatic tissues. Additionally, the m-RNA and protein levels of the apoptotic Bcl2-associated X protein (BAX) and caspase-3 were lowered and the anti-apoptotic B-cell leukemia/lymphoma 2 (BCL-2) was increased upon Prist administration. Conclusion: Prist ameliorated APAP-induced liver injury in mice via its potent anti-inflammatory/antioxidative and anti-apoptotic activities. These effects were mediated through modulation of NF-κB/iNOS/COX-II/cytokines, PI3K/AKT, and BAX/BCL-2/caspase-3 signaling pathways. Full article

As Thailand transitions into a super-aged society, falls are a rising public health issue. However, limited research focuses specifically on independent older adults in rural areas. This study examined intrinsic and extrinsic factors associated with falls among independent older adults in a rural district of southern Thailand, contributing to localized fall prevention strategies. A cross-sectional study was conducted using multi-stage probabilistic sampling with 325 older adults aged 60–79 years residing in Nakhon Si Thammarat. Data were collected through structured interviews, and multivariate logistic regression was used to identify fall predictors. A fall was defined as an unintended fall to a lower level within the previous 12 months. The fall prevalence was 29.8%, with the majority resulting in minor injuries. Multivariate analysis revealed protective factors, including sociodemographic factors such as higher monthly income (adjusted OR = 0.47; 95% CI: 0.30–0.74) and agricultural employment (adjusted OR = 0.50; 95% CI: 0.27–0.95), as well as the extrinsic factor of pet ownership (adjusted OR = 0.53; 95% CI: 0.35–0.81), were significantly associated with reduced fall risk. The study highlights context-specific protective factors that could inform community-based interventions. Future research should assess causality and intervention effectiveness in broader populations. Full article

Background: Midfacial fractures are common outcomes of facial trauma. While younger individuals typically sustain these injuries through high-energy events like assaults and traffic or sports accidents, elderly patients increasingly present with fractures from low-energy mechanisms, primarily falls. Purpose: The aim of this study was to analyze age- and gender-specific patterns in midfacial fractures over a 10-year period, with emphasis on elderly individuals and low-energy trauma. Methods: A retrospective review was performed of proven midfacial fractures between 2013 and 2022 at the Department of Oral and Maxillofacial Surgery (University of Pécs, Hungary). The patients were stratified by age (<65 vs. ≥65 years) and gender. The variables included the injury mechanism, fracture localization, the dental status, hospitalization, and the presence of associated injuries. Bivariate analyses were performed, and the significance level was set to p < 0.05. Results: A total of 957 radiologically confirmed midfacial fracture cases were evaluated, of whom 344 (35.9%) were ≥65 years old. In the elderly group, females had a 19-fold higher risk for midfacial trauma than younger females (OR: 19.1, 95%CI: 9.30–39.21). In the older group, a fall was significantly the most frequent injury mechanism (OR: 14.5; 95%CI: 9.9–21.3), responsible for 89.5% of the cases, while hospitalization (OR: 0.36; 95%CI: 0.23–0.56) was less characteristic. Most of the fractures occurred in the zygomatic bone, in the zygomaticomaxillary complex, or in the anterior wall of the maxilla. Associated injuries in the elderly group included mostly lower limb injuries—particularly pertrochanteric femoral fractures in females—and upper limb injuries, with a slight male dominance. Conclusions: Low-energy falls are the primary cause of midfacial fractures in elderly patients, particularly in women. Tailored prevention and management strategies are essential for improving the outcomes in this growing demographic group. Full article

Background/Objectives: Blunt cardiac injury (BCI) is a severe medical condition that may arise as a result of various traumas, including motor vehicle accidents and falls. The main objective of this study was to explore the role and underlying mechanisms of the TRPV4 gene in BCI. Elucidating the function of TRPV4 in BCI may reveal potential novel therapeutic targets for the treatment of this condition. Methods: Rats in each group, including the SD control group (SDCON), the SD blunt-trauma group (SDBT), the TRPV4 gene-knockout control group (KOCON), and the TRPV4 gene-knockout blunt-trauma group (KOBT), were all freely dropped from a fixed height with a weight of 200 g and struck in the left chest with a certain energy, causing BCI. After the experiment, the levels of serum IL-6 and IL-1β were detected to evaluate the inflammatory response. The myocardial tissue structure was observed by HE staining. In addition, cardiac transcriptome analysis was conducted to identify differentially expressed genes, and metabolomics studies were carried out using UHPLC-Q-TOF/MS technology to analyze metabolites. The results of transcriptomics and metabolomics were verified by qRT-PCR and Western blot analysis. Results: Compared with the SDCON group, the levels of serum IL-6 and IL-1β in the SDBT group were significantly increased (p < 0.001), while the levels of serum IL-6 and IL-1β in the KOBT group were significantly decreased (p < 0.001), indicating that the deletion of the TRPV4 gene alleviated the inflammation induced by BCI. HE staining showed that myocardial tissue injury was severe in the SDBT group, while myocardial tissue structure abnormalities were mild in the KOBT group. Transcriptome analysis revealed that there were 1045 upregulated genes and 643 downregulated genes in the KOBT group. These genes were enriched in pathways related to inflammation, apoptosis, and tissue repair, such as p53, apoptosis, AMPK, PPAR, and other signaling pathways. Metabolomics studies have found that TRPV4 regulates nucleotide metabolism, amino-acid metabolism, biotin metabolism, arginine and proline metabolism, pentose phosphate pathway, fructose and mannose metabolism, etc., in myocardial tissue. The combined analysis of metabolic and transcriptional data reveals that tryptophan metabolism and the protein digestion and absorption pathway may be the key mechanisms. The qRT-PCR results corroborated the expression of key genes identified in the transcriptome sequencing, while Western blot analysis validated the protein expression levels of pivotal regulators within the p53 and AMPK signaling pathways. Conclusions: Overall, the deletion of the TRPV4 gene effectively alleviates cardiac injury by reducing inflammation and tissue damage. These findings suggest that TRPV4 may become a new therapeutic target for BCI, providing new insights for future therapeutic strategies. Full article