Search Results (26,917)

Herpes simplex virus type 1 (HSV-1) is a leading cause of infectious corneal blindness worldwide. Human donor corneal transplantation remains the primary treatment for scarred corneas resulting from herpes simplex keratitis (HSK), a severe inflammatory corneal disease caused by HSV-1 infection, despite a high risk of re-infection or immune rejection of the allografts. As possible alternatives to donor grafting for HSK, we developed cell-free, regeneration-stimulating corneal implants designed to work even under adverse inflammatory situations such as severe infections. The implants comprised short, fully synthetic collagen-like peptides conjugated to polyethylene glycol (CLP-PEG) and crosslinked using carbodiimide chemistry. Being cell-free, they lacked the cellular targets that an already activated immune system would encounter in these inflamed corneas. We tested the performance of these implants in guinea pig and rabbit models of HSK. Three different HSV-1 strains were used to create experimental HSK in rabbits and guinea pigs. There were no overall statistically significant species differences or species–strain differences in virus-induced mortality. At three months post-operation, all treated corneas showed tissue regeneration, but with haze or neovascularization. The initially cell-free CLP-PEG implants allowed for repopulation by ingrowing cells to regenerate neocorneal tissue, despite the inflammation. However, they did not prevent HSV-1 reactivation nor re-infection, as neovascularization and disorganization were observed within the neocorneas. A detailed histopathological examination revealed viral strain differences, but only KOS infection showed interspecies neovascularization differences. A more detailed examination with larger numbers of animals is merited to fully elucidate the effects of the different viral strains on rabbits versus guinea pigs. Full article

Corn is one of the most widely cultivated cereal crops and is rich in antioxidant compounds, especially phenolics. However, many of these are bound to cell wall components, requiring pre-treatment for release. Solid-state fermentation (SSF) with Rhizopus oryzae has been used to enhance antioxidant capacity in grains and legumes, though its application in pigmented corn (PC) has not been reported. This study evaluated R. oryzae growth on PC via SSF and its effect on phenolic compound release and antioxidant capacity (AC). Variables such as temperature, pH, inoculum, and medium salts were tested for their influence on phenolic release and AC. Nutrient changes in PC due to SSF were also examined. HPLC-MS was used to analyze the phenolic compounds’ profile. R. oryzae grew effectively on PC, increasing total phenolic content (TPC) and AC by 131 and 50%, respectively. The pH was found to negatively impact phenolic release. The SSF also raised protein content by 10% and reduced carbohydrates and fiber by 3 and 8%. Thirteen phenolic compounds were identified, including Feruloyl tartaric acid ester and p-Coumaroyl tartaric acid glycosidic ester, with known anti-inflammatory properties. This process offers a sustainable method for enhancing the functional properties of pigmented corn. Full article

Objective: Morphine is a widely used analgesic for severe pain, but tolerance is a major challenge in long-term pain management. This study examined the potential of Daflon^® to enhance morphine’s pain-relieving effects and to reduce tolerance in a rat model with neuropathic pain induced by partial sciatic nerve transection (PSNT). Methods: Male Wistar rats were divided into five groups: (1) Sham + Saline, (2) PSNT + Saline, (3) PSNT + morphine, (4) PSNT + Daflon, and (5) PSNT + morphine + Daflon. Morphine tolerance was induced through continuous intrathecal infusion (15 µg/µL/h, i.t.) for 7 days, starting on day 7 post-PSNT, while Daflon was administered orally (50 mg/kg/day, oral) for 7 days. Pain relief was assessed using tail-flick and paw withdrawal on days 1, 4, and 7 after osmotic pump implantation. Spinal cords were collected for immunohistochemistry to analyze glial expression, and serum biomarkers (TNF-α, IL-1β, IL-6, and IL-10) were measured to evaluate neuroinflammation. Results: The results showed that oral Daflon significantly enhanced morphine’s analgesic effects, evidenced by improved pain thresholds in all behavioral tests. Moreover, Daflon reduced morphine tolerance. Mechanistically, Daflon upregulated the expression of nuclear factor erythroid 2-related factor 2 (Nrf2) and activated heme oxygenase-1 (HO-1), reducing oxidative stress and modulating neuroinflammation through glial regulation. Combining morphine and Daflon reduces pro-inflammatory cytokines (TNF-α, IL-1β, and IL-6) and enhances anti-inflammatory IL-10 serum level, showing a synergistic effect in managing neuropathic pain with greater efficacy and lower drug dependence. Histology and immunohistochemistry evaluations further confirmed that morphine and Daflon co-treatment substantially reduced mononuclear cell infiltration, astrocyte activation (as indicated by GFAP expression), and microglial activation (as indicated by Iba-1 expression) compared to single treatment. Conclusions: Our findings suggest that dual therapy synergistically targets both oxidative stress and inflammatory pathways, leading to stronger neuroprotection and pain relief. Importantly, the combination approach may allow for lower opioid dosages, minimizing the risks of opioid-related side effects. Overall, morphine and Daflon co-administration offers a promising and safer strategy for managing neuropathic pain and preserving spinal cord integrity. Full article

Background/Objectives: Nivolumab has significantly improved outcomes in patients with metastatic non-small cell lung cancer (NSCLC); however, reliable prognostic biomarkers remain an unmet need. To address this gap, we developed the SUVmax-IPI, a novel prognostic index combining maximum standardized uptake value (SUVmax) from ¹⁸F-fluorodeoxyglucose positron emission tomography (FDG-PET) with systemic inflammatory markers. This study aimed to evaluate the prognostic value of SUVmax-IPI in patients with NSCLC receiving nivolumab therapy. Methods: This multicenter retrospective analysis included 187 patients with metastatic NSCLC receiving nivolumab across 5 tertiary institutions. The SUVmax-IPI incorporated pretreatment SUVmax and laboratory-based inflammatory prognostic index (IPI) parameters. Survival outcomes were evaluated using Kaplan–Meier analysis with log-rank testing and multivariate cox regression. Results: Receiver operating characteristic (ROC) analysis established an optimal SUVmax-IPI cut-off of 241.9. Patients with SUVmax-IPI ≤ 241.9 had significantly better survival outcomes: median overall survival (OS) was 35 versus 15 months (p = 0.002). For progression-free survival (PFS), although a numerical difference favored patients with SUVmax-IPI ≤ 241.9 (median: 15 vs. 8 months), this did not reach statistical significance (log-rank p = 0.175). Multivariate analysis confirmed SUVmax-IPI as an independent predictor of survival (p = 0.002). Conclusions: The SUVmax-IPI represents a promising prognostic tool for patients with metastatic NSCLC who received at least 3 months of nivolumab, integrating metabolic and inflammatory parameters to predict survival outcomes. Full article

The deposition of amyloid beta (Aβ) in the human brain is a hallmark of Alzheimer’s disease (AD). Aβ has been shown to exert a wide range of effects on neurons in cell and animal models. Here, we take advantage of differentiated neurons from iPSC-derived neural stem cells of human donors to examine its effects on human neurons. Specifically, we employed two types of neurons from genetically distinct donors: one male carrying APO E2/E2 (M E2/E2) and one female carrying APO E3/E3 (F E3/E3). Genome-wide RNA-sequencing analysis identified 64 and 44 genes that were induced by Aβ in M E2/E2 and F E3/E3 neurons, respectively. GO and pathway analyses showed that Aβ-induced genes in F E3/E3 neurons do not constitute any statistically significant pathways whereas Aβ-induced genes in M E2/E2 neurons constitute a complex network of activated pathways. These pathways include those promoting inflammatory responses, such as IL1β, IL4, and TNF, and those promoting cell migration and movement, such as chemotaxis, migration of cells, and cell movement. These results strongly suggest that the effects of Aβ on neurons are highly dependent on their genetic background and that Aβ can promote strong responses in inflammation and cell migration in some, but not all, neurons. Full article

Ischemic stroke is now widely recognized as a disease with a strong inflammatory profile. Cerebral vascular damage is both preceded and followed by a chain of molecular events involving immune cells and inflammatory markers, irrespective of the etiology of the ischemic injury. Over time, an increasingly comprehensive understanding of these markers has led to a better insight into the mechanisms behind the vascular event and recovery following ischemic stroke. However, to date, there are still no available circulating or tissue biomarkers for early diagnosis or prognostic stratification, making ischemic stroke diagnosis contingent on clinical and instrumental investigations. However, neurological and internal medicine research is progressing in identifying markers that could potentially take on this role. This manuscript, therefore, aims to review the most recent and innovative results of medical advances, summarising the current state of the art and future perspectives. If ischaemic stroke is an inflammatory disease, it is also true that it is not just a singular condition, but a group of entities with their own neuroinflammatory features. Thus, given that, in ischemic cerebral vascular damage, “time is brain,” tracking increasingly accurate markers in the diagnosis of ischemic stroke is a valuable tool that will potentially enable earlier recognition of this disease and, hopefully, make it less disabling and more widely treated. Full article

Background/Objectives: This study aimed to develop an advanced oral delivery platform for Salvia officinalis (S. officinalis) extract by co-encapsulating it with inulin and pectin in alginate-based microbeads, formulated via ionic gelation. Methods: The microbeads were comprehensively characterized, including the assessment of morphology, particle size, encapsulation efficiency, swelling behavior, in vitro dissolution, and enzymatic stability, and Caco-2 cell-based assays for cytocompatibility, permeability, and transepithelial electrical resistance. Antioxidant capacity and anti-inflammatory effects were also evaluated. Results: The resulting microbeads (~275 µm) achieved > 90% encapsulation efficiency and exhibited pronounced swelling (~90%). The release of S. officinalis constituents displayed pH sensitivity, with sustained release in simulated intestinal fluid, alongside significant enhancement of enzymatic stability. Encapsulation led to markedly improved permeability of bioactive compounds across Caco-2 monolayers, attributable to reversible modulation of tight junctions. Encapsulated extract retained potent antioxidant activity and significantly reduced pro-inflammatory cytokines. The formulation, across various concentrations, further promoted the growth and viability of Lactobacillus strains. Conclusions: Collectively, these findings demonstrate that alginate–inulin–pectin microbeads provide a multifunctional system for stabilizing S. officinalis extract, enabling controlled release, enhanced intestinal absorption, and maintained bioefficacy. Importantly, the formulation also promoted Lactobacillus viability, indicating a prebiotic effect and offering considerable potential for improved oral therapeutic applications. Full article

Autoimmune diseases result from dysregulated immune responses that mistakenly attack the body’s own tissues, causing chronic inflammation and progressive damage. Macrophages, with their remarkable plasticity, play key roles in both promoting and resolving inflammation, with pro-inflammatory M1 and anti-inflammatory M2 states shaping disease outcomes. Macrophage-derived exosomes have emerged as important mediators of intercellular communication, reflecting the functional state of their parent cells while influencing recipient cell behavior. Exosomes from M1 macrophages amplify inflammation through cytokines and microRNAs, whereas M2-derived exosomes support tissue repair and immune regulation. Studies in rheumatoid arthritis, lupus, multiple sclerosis, inflammatory bowel disease, type 1 diabetes, and psoriasis highlight their dual roles in pathology and resolution. In addition, macrophage exosomes can be engineered to deliver targeted therapeutic molecules, offering cell-free interventions with advantages in specificity, biocompatibility, and immunomodulation. This review summarizes current insights into macrophage-derived exosomes, their role in autoimmune pathogenesis, and emerging strategies to harness their therapeutic potential, highlighting their promise as precision-guided treatments for autoimmune diseases. Full article

Bladder dysfunction, particularly overactive bladder (OAB), is increasingly recognized as a clinical concern in patients with sickle cell disease (SCD), yet its pathophysiological mechanisms remain poorly understood. This study investigated the relationship between oxidative stress, inflammation, and bladder dysfunction in the Townes transgenic SCD mouse model. Cystometric analysis revealed that SCD mice exhibit an OAB phenotype, characterized by increased frequencies of voiding and non-voiding contractions and reduced bladder compliance. In vitro functional assays demonstrated detrusor hypocontractility in SCD mice, associated with a significant reduction in carbachol- and EFS-induced contractions and downregulation of muscarinic M3 receptor expression. Purinergic signaling and calcium-dependent contractility remained preserved. Molecular analyses showed increased mRNA expression of NOX-2 and IL-1β, and elevated protein levels of 3-nitrotyrosine and myeloperoxidase (MPO) activity, indicating redox imbalance and chronic inflammation in bladder tissue. Together, these changes suggest that oxidative and nitrosative stress, combined with inflammation, contribute to bladder remodeling and dysfunction in SCD. This is the first study to characterize bladder alterations in Townes SCD mice, establishing this model as a valuable tool for investigating lower urinary tract complications in SCD. Our findings provide mechanistic insight into the genitourinary manifestations of SCD and identify redox and inflammatory pathways as potential therapeutic targets for bladder dysfunction in affected individuals. Full article

In children under 4, septic arthritis of the hip (SAH) caused by Kingella kingae (SAH-KK) can be misdiagnosed, as it does not meet classic septic joint criteria (fever > 38.5°, pain, limited range of motion, and inability to bear weight). The objective of this study was to report clinical and paraclinical characteristics in a large cohort of children with confirmed SAH-KK and to evaluate the reliability of the Kocher (KC) and Caird criteria (CC) in predicting SAH-KK. Medical records of 140 children with confirmed SAH-KK were collected. Data on sex, age, temperature on admission, weight-bearing status, white blood cell (WBC) count, platelet count, C-reactive protein (CRP) value, and erythrocyte sedimentation rate (ESR) were extracted. The study focused on the sensitivity of KC (body temperature, refusal to bear weight, leukocytosis, and ESR) and CC (KC criteria plus CRP level). All patients had bacteriologically confirmed SAH-KK; most had mild symptoms and near-normal inflammatory markers. CRP (76.2%) had the highest sensitivity, followed by weight-bearing status (73.8%) and WBC count (69.6%). Body temperature and ESR exceeded cutoff values in less than 50% of cases. Among 77 patients fulfilling all KC, 49 (63.5%) had less than a 40% probability of SAH. Of 50 children with complete CC, 20 (40%) had a 62.4% or lower probability of SAH. KC and CC are not sufficiently accurate to confidently exclude SAH-KK in preschool-aged children due to heterogeneous clinical presentations. Further studies are needed to redefine diagnostic criteria based on patient age and causative pathogens. Full article

Autophagy is a conserved process that involves the degradation of damaged proteins and organelles to restore cellular homeostasis. Autophagy plays a critical role in cell differentiation, immune responses, and protection against pathogens, as well as the development and progression of allergic inflammation. Crosstalk between autophagy and signaling pathways modulates immune responses to inflammatory signals. Here, we discuss the regulatory roles of autophagy in allergic inflammation. Autophagy can promote allergic inflammation by enhancing the secretion of inflammatory mediators. Impaired autophagy resulting from the accumulation of autophagosomes can exacerbate allergic inflammation. Mast cell degranulation and activation require energy provided by mitochondrial respiration. Mast cell activation is accompanied by morphological changes and mitochondrial fragmentation. Mitochondrial fragmentation (mitophagy) induced by oxidative stress involves the degradation of defective mitochondria. Therefore, we discuss the relationship between mitophagy and allergic inflammation. Targeting autophagy and oxidative stress can be a strategy for developing anti-allergy therapeutics. In this review, we also discuss future research directions to better understand allergic diseases with respect to autophagy and develop effective anti-allergy drugs. Full article

Diabetic kidney disease (DKD), as one of the most serious microvascular complications of diabetes, is the main cause of end-stage renal disease in the world. Lipid peroxidation plays a crucial role in the development and progression of DKD. Under conditions of high glucose and insulin resistance, renal lipid metabolism disorders result in abnormal accumulation of polyunsaturated fatty acids (PUFAs), which undergo lipid peroxidation via free radical chain reactions to generate reactive aldehydes. These substances not only directly damage the cell structure but can also be used as signaling molecules that activate pathways related to inflammation, fibrosis, and ferroptosis, eventually leading to glomerular sclerosis and tubulointerstitial fibrosis. Natural products have shown considerable application prospects in the treatment of DKD due to their multi-functional properties, including anti-inflammatory, antioxidant, and lipid-metabolism-regulating effects. To elucidate this, we conducted a systematic review of the literature available in electronic databases (including PubMed, Web of Science, and Scopus, and Google Scholar) from January 2000 to May 2025. This study further discusses the therapeutic effect and mechanism of natural products targeting lipid peroxidation in DKD. The results indicate that natural products are promising anti-lipid peroxidation drugs. Further clinical trials will be necessary to verify the safety and effectiveness of these natural compounds in clinical applications, thereby laying the foundation for developing novel treatment strategies for DKD. Full article

(1) Background: The present study investigated the effects of extracellular vesicles (EVs), derived from adipose tissue stem cells (ADSCs) and bone marrow mesenchymal stem cells (BMMSCs), on atherosclerosis-associated cardiac hypertrophy. (2) Methodology: The experiments were performed on hamsters divided into the following groups: control (C) fed with a standard diet; hypertensive–hyperlipidemic (HH) generated by combining a diet enriched with 3% cholesterol, 15% butter, and by gavage with 8% NaCl on a daily basis; HH groups injected with EVs (ADSCs) or EVs (BMMSCs), either transfected with Smad2/3 siRNAs or not (HH-EVs (ADSCs), HH-EVs (BMMSCs), HH-EVs (ADSCs) + Smad2/3siRNA, HH-EVs (BMMSCs) + Smad2/3siRNA); and HH group injected with Smad2/3 siRNAs (HH-Smad2/3siRNA). (3) Results: In comparison with the HH group, the findings demonstrated that treatment using EVs (ADSCs or BMMSCs), either with or without Smad2/3 siRNAs, resulted in several significant improvements in the following aspects: the plasma levels of cholesterol, LDL, triglycerides, TGF-β1, and Ang II were decreased; the left ventricular structure and function were recovered; inflammatory markers, ROS, COL1A, α-SMA, Cx43, MIF, ANF, and M1/M2 macrophages, were reduced; the level of key protein NF-κB p50 was diminished. (4) Conclusions: These findings underscore the therapeutic potential of mesenchymal stem cell-derived EVs in atherosclerosis-associated cardiac hypertrophy. Full article

Endothelial dysfunction is an early driver of atherosclerosis, yet the direct impact of endogenous crystals such as cholesterol crystals and monosodium urate on endothelial activation remains incompletely understood. In this study, we examine how crystalline stimuli modulate human umbilical vein endothelial cells by assessing inflammatory signaling, mitochondrial respiration, and neutrophil recruitment. Using dose- and time-controlled experiments, we show that CC and MSU are internalized by endothelial cells, activating NF-κB and STAT3 signaling pathways and inducing a robust pro-inflammatory cytokine profile. Notably, CC caused marked mitochondrial dysfunction, evidenced by impaired respiratory capacity and loss of membrane potential, revealing a novel bioenergetic vulnerability in endothelial cells. Both direct crystal stimulation and exposure to crystal-primed conditioned media triggered endothelial adhesion molecule expression and promoted neutrophil adhesion, indicating that soluble mediators released upon crystal stimulation can propagate vascular inflammation. These findings demonstrate that crystalline stimuli are potent vascular danger signals capable of driving endothelial inflammation, mitochondrial impairment, and immune cell engagement, which are hallmarks of early atherogenesis. By elucidating these multifaceted endothelial responses, this study provides important mechanistic insights into how crystal-induced signals may contribute to vascular dysfunction and the early stages of atherogenesis. Full article

Cerebral ischemia/reperfusion (I/R) injury remains a significant contributor to adult neurological morbidity, primarily due to exacerbated neuroinflammation and cell apoptosis. These processes amplify brain damage through the release of various pro-inflammatory cytokines and pro-apoptotic mediators. Although long non-coding RNAs (lncRNAs) are increasingly recognized for their involvement in regulating diverse biological pathways, their precise role in cerebral I/R injury has not been fully elucidated. In the current study, transcriptomic profiling was conducted using a rat model of focal cerebral I/R, leading to the identification of lncRNA-1810026B05Rik—also referred to as CHASERR—as a novel lncRNA responsive to ischemic conditions. The elevated expression of this lncRNA was observed in mouse brain tissues subjected to middle cerebral artery occlusion followed by reperfusion (MCAO/R), as well as in primary cortical neurons derived from rats exposed to oxygen-glucose deprivation and subsequent reoxygenation (OGD/R). The results suggested that lncRNA-1810026B05RiK mediates the activation of the nuclear factor-kappaB (NF-κB) signaling pathway by physically binding to NF-kappa-B inhibitor alpha (IκBα) and promoting its phosphorylation, thus leading to neuroinflammation and neuronal apoptosis during cerebral ischemia/reperfusion. In addition, lncRNA-1810026B05Rik knockdown acts as an NF-κB inhibitor in the OGD/R and MCAO/R pathological processes, suggesting that lncRNA-1810026B05Rik downregulation exerts a protective effect on cerebral I/R injury. In summary, the lncRNA-1810026B05Rik has been identified as a critical regulator of neuronal apoptosis and inflammation through the activation of the NF-κB signaling cascade. This discovery uncovers a previously unrecognized role of 1810026B05Rik in the molecular mechanisms underlying ischemic stroke, offering valuable insights into disease pathology. Moreover, its involvement highlights its potential as a novel therapeutic target, paving the way for innovative treatment strategies for stroke patients. Full article