Search Results (387)

Neuropathic pain (NP) is driven by neuroimmune interactions where in activated microglia release pro-inflammatory mediators that sustain central sensitization. Platelet-rich plasma (PRP) is a promising therapy, but its efficacy depends on its biochemical composition. This study aimed to evaluate how modifying the molecular profile of PRP influences its capacity to modulate neuroinflammation in a human-derived co-culture model. We compared standard PRP (sPRP) and balanced protein-concentrate plasma (BPCP), enriched in extraplatelet molecules, using an iPSC direct co-culture of sensory neurons (hSNs) and microglia (hMG). Neuroinflammation was induced for 24 h with serum-free (SF) or 10% sPRP or BPCP supplementation. Neuroinflammation, microglial activation, apoptosis, and neuronal plasticity were analyzed via RT-qPCR and Luminex. Both formulations attenuated pro-inflammatory mediators. However, BPCP demonstrated superior suppressive efficacy, reducing the levels of major cytokines (IL-1β, TNF-α, IL-6, IL-8) by half as compared to sPRP. BPCP significantly decreased IL-6, IL-8, and MCP-1 protein levels; kept microglial activation markers (CD86, CTSS) downregulated; and downregulated the apoptotic cascade (BAX, CASP9, CASP3). Conversely, sPRP displayed a distinct pro-resolving and neuroprotective trend, upregulating IL-10 and TGF-β1 and rescuing the expression of SLC12A5 (KCC2), which regulates neuronal excitability. sPRP and BPCP modulated neuroinflammation via complementary mechanisms. BPCP acted as an immunomodulatory shield suppressing macro-inflammation, while sPRP drove inflammation resolution and neuroplastic rescue. Full article

Currently, emerging pharmaceutical contaminants (EPCs) pose a significant risk to aquatic biodiversity on both a global and regional scale. Their accumulation in the environment presents several challenges to both human health and ecological integrity. Among EPCs, cyclophosphamide (COP), a widely used alkylating cytotoxic and immunosuppressive drug in human and veterinary oncology, has become one of the most frequently detected environmental contaminants. It has been reported to impair the immune system, induce oxidative stress, and exhibit genotoxic and cytotoxic effects in various fish species. However, limited research has evaluated its toxicity in the Siamese fighting fish (Betta splendens), an endemic significant aquatic species in Thailand. This study evaluated the acute toxicity of COP in Betta splendens by assessing systemic oxidative stress responses, alterations in gene expression, and localized histopathological changes within both hepatic and renal tissues. The 96 h of median lethal concentration (LC₅₀) value for COP in Betta splendens was determined to be 793.4 mg/L. High-concentration exposure (800 mg/L) induced severe systemic oxidative stress, evidenced by a significant reduction in superoxide dismutase (SOD) activity and a marked elevation in malondialdehyde (MDA) levels across both liver and kidney. At the transcriptomic level, acute COP exposure significantly upregulated pro-inflammatory (interleukin-1β, IL-1β and tumor necrosis factor, TNF-α), cellular stress (heat shock protein 70, HSP70), and apoptotic (caspase-3, Casp3) genes. Semi-quantitative histopathological evaluation revealed severe concentration-dependent structural damage. Hepatic lesions peaked at 800 mg/L characterized by diffuse vacuolation, vascular congestion, and extensive necrosis. Similarly, severe renal damage occurred at 800 mg/L, featuring marked vascular congestion, melanomacrophage aggregation, and widespread tubular necrosis. Overall, these findings demonstrate that acute waterborne COP exposure induces severe hepatotoxicity and nephrotoxicity in Betta splendens driven by oxidative stress, pro-inflammatory signaling, and apoptotic pathways. This study provides essential baseline toxicity thresholds and highlights the physiological risks COP spills pose to tropical freshwater labyrinth fish. Full article

Background/Objectives: Autoimmune hepatitis (AIH) is a liver injury characterized by the dysregulation of immune responses. Current options for AIH have limitations that highlight the urgent need to investigate alternative or adjunct therapeutic strategies for its management. We aimed to explore the protective effects of fasudil against concanavalin A (Con A)-induced AIH in mice. Con A resulted in significant hepatic damage, evidenced by dysregulation in liver function biomarkers, marked inflammatory cell infiltration, and hepatocellular degeneration. Methods: The pretreatment of mice with fasudil (10 and 25 mg/kg, intraperitoneally) for 7 days resulted in a significant ameliorative effect on these alterations in a dose-dependent manner. Fasudil treatment was associated with suppression of the RhoA/Rho-associated coiled-coil-containing protein kinase (ROCK) pathway and concomitant downregulation of toll-like receptor 4 (TLR4)/Nuclear factor-κB (NF-κB). Results: These changes were accompanied by reduced macrophage activation and the reduction of pro-inflammatory cytokines, as evidenced by decreased nitric oxide synthase (iNOS), tumor necrosis factor alpha (TNF-α), interleukin-6 (IL-6), interferon gamma (INF-γ), and interleukin-17A (IL-17A). Moreover, it significantly limited the cluster of differentiation (CD)4⁺ and CD8⁺ T cell infiltration, thereby modulating adaptive immune amplification. Conclusions: Accordingly, fasudil restored redox homeostasis and mitigated hepatocellular death by rebalancing apoptotic regulators, normalizing the expression of B cell lymphoma 2 (BCL-2) while reducing the expression of BCL-2-associated X protein (BAX) and caspase-3 activation. Subsequently, fasudil improved liver function profiles and preserved hepatic architecture. Our results demonstrate that fasudil has potent immunomodulatory, anti-inflammatory, antioxidant, and anti-apoptotic effects in AIH. Its protective effects are associated with the suppression of RhoA/ROCK and TLR4/NF-κB signaling, supporting further investigation into the contribution of these pathways to the therapeutic actions of fasudil in AIH. Full article

Gastric cancer (GC) remains a major global health challenge, ranking among the most lethal malignancies due to late diagnosis, high tumor heterogeneity, and limited treatment efficacy. The search for safer, nutritionally based adjuncts to conventional therapies is therefore a research priority. Donkey milk (DM), traditionally used as a hypoallergenic substitute for infants, is emerging as a functional food with remarkable bioactivity. Its composition closely resembles human milk, with high levels of bioactive proteins, a favorable polyunsaturated lipid profile, antioxidant vitamins, and immune-supportive minerals. Despite its growing nutraceutical appeal, the anticancer potential of DM in GC has not yet been explored. This study represents the first investigation of DM in human gastric adenocarcinoma (AGS) cells. Using increasing concentrations of whole DM (25–100%), a dose-dependent inhibition of cell viability and migration was observed. Mechanistic insights reveal that DM induces mitochondrial oxidative stress, disrupts cell cycle progression (S/G2 accumulation at 75%, G2 arrest at 100%), and unexpectedly triggers a pro-inflammatory gene signature suggesting stress-driven immunostimulation rather than canonical apoptosis. These findings highlight a non-classical, context-dependent cytotoxic mechanism that distinguishes DM from conventional pro-apoptotic agents. DM may represent a promising nutraceutical candidate for GC management, bridging traditional food resources with modern oncology. By inhibiting hallmark cancer traits while engaging unique immunological pathways, DM offers a sustainable, low-toxicity approach with translational potential. Future studies will focus on the characterization of active components, validation in organoid and animal models, and exploring clinical applications of DM-derived bioactive components in cancer prevention and therapy. Full article

Diabetes mellitus (DM) induces significant endocrine disruption and oxidative stress (OS) within the testes, resulting in impaired spermatogenesis, increased sperm abnormalities, and compromised reproductive function. This study aimed to evaluate the combined protective effects of Semaglutide (SEM) combined with Carica papaya (papaya) juice against type 2 diabetes-induced testicular damage in rats. Forty adult male albino rats were divided into four experimental groups: a control group, a Streptozotocin (STZ)-induced diabetic group, a diabetic group treated with SEM (0.3 mg/kg), and a diabetic group treated with SEM (0.3 mg/kg) in combination with 10% papaya juice, administered for eight weeks. Statistically significant superiority over SEM alone was observed for selected endpoints; the findings primarily support the potential of papaya as a dose-sparing adjunct rather than demonstrating uniformly enhanced efficacy. They significantly improved systemic metabolic parameters, as evidenced by reduced fasting blood glucose (FBG) and glycated hemoglobin (HbA_1c) levels and restoration of the lipid profile. Importantly, it also attenuated diabetes-induced testicular injury, as demonstrated by improved reproductive hormone levels, enhanced sperm parameters, restoration of antioxidant defenses, modulation of inflammatory and apoptotic signaling, and marked histopathological recovery of seminiferous tubular architecture. Antioxidant markers revealed a notable reduction in malondialdehyde (MDA) and cytochrome P450 2E1 (CYP2E1), along with significant increases in reduced glutathione, catalase (CAT), and superoxide dismutase (SOD). Furthermore, a marked modulation of key pro-inflammatory and pro-apoptotic mediators was observed, including forkhead box protein O1 (FOXO1), microRNA-155 (miR-155), tumor necrosis factor-alpha (TNF-α), nuclear factor kappa B cell subunit 1 (NF-κB1), interleukin-6 (IL-6), caspase-3 (CASP3), and BCL2-Associated X Apoptosis Regulator (Bax), while a significant upregulation of sirtuin-1 (SIRT1), microRNA-34c (miR-34c), and B-cell lymphoma-2 (Bcl-2) was also detected. Histopathological assessments confirmed the restoration of normal testicular architecture in the treated groups. These findings indicate that the combination strategy may have the potential to achieve dose savings while maintaining efficacy comparable to the standard-dose SEM, through the enhancement of the antioxidant defenses, modulation of inflammation, and apoptosis, specifically via the modulation of the miR-34c/miR-155 and SIRT1/FOXO1 signaling. Full article

Background: Geraniol is an acyclic monoterpene widely distributed in the essential oils of aromatic species such as Cymbopogon citratus, Pelargonium graveolens, and Rosa damascena, It is known for its antioxidant, anti-inflammatory, neuroprotective, and antitumor activities. Methods: This study aimed to investigate, through network pharmacology and computational ADMET modeling, the molecular mechanisms and pharmacological potential of geraniol, integrating drug-likeness parameters, toxicity prediction, and multitarget interactions. Results: A total of 25 core targets were identified, mainly involved in inflammation, oxidative stress, apoptosis, and transcriptional regulation. Geraniol exhibited a favorable drug-likeness profile, high predicted intestinal absorption, and low systemic toxicity, supporting its pharmaceutical applicability. Mechanistically, it modulates the Nrf2/HO-1 ↔ NF-κB axis, reducing reactive oxygen species, pro-inflammatory cytokines (TNF-α, IL-1β, IL-6), and apoptotic markers (caspases, Bax), while enhancing antioxidant enzymes (SOD, CAT, GPx) and antiapoptotic proteins (Bcl-2). Conclusions: These findings confirm its multitarget and pleiotropic nature, highlighting its potential as a therapeutic candidate for inflammatory, metabolic, and neurodegenerative disorders. Furthermore, this study provides a robust mechanistic rationale for future in vitro and in vivo validation, as well as for the design of nanostructured formulations to improve geraniol’s bioavailability and therapeutic safety. Full article

Decoy receptor 3 (DcR3) is a pleiotropic soluble factor that modulates cellular functions through both decoy and non-decoy mechanisms. DcR3 has been reported to exert anti-apoptotic and anti-inflammatory effects in humans, particularly in cancers and inflammatory diseases. In the present study, we investigated the role of DcR3 in TLR4-mediated innate immune responses in macrophages. Because the DcR3 gene is absent in the mouse genome, we generated myeloid-specific DcR3 knock-in mice and isolated bone marrow-derived macrophages (BMDMs) for functional analyses. Our results showed that DcR3 did not significantly affect LPS-induced expression of COX-2, iNOS, NLRP3, or pro-IL-1β. Aggresome-like induced structures (ALIS), which consist of aggregates of ubiquitinated proteins, are stress-induced cytoplasmic compartments implicated in MHC class I antigen presentation. We found that DcR3 suppressed LPS-induced ALIS formation by attenuating cellular reactive oxygen species production and p38 MAPK activation. In addition to LPS stimulation, DcR3 also reduced the accumulation of ubiquitinated proteins induced by HO-1 inhibitor ZnPP, lysosomal inhibitor bafilomycin A1, and proteasomal inhibitor MG132. Consistent with a role for autophagy in ALIS regulation, rapamycin reduced LPS-induced ALIS formation, whereas bafilomycin A1 induced comparable LC3-II accumulation in both wild-type and DcR3-expressing macrophages. Furthermore, DcR3 expression did not significantly alter LPS-induced p62 or HO-1 expression. Collectively, although DcR3 does not markedly influence LPS-induced inflammatory responses in BMDMs, our findings reveal a previously unrecognized role for DcR3 in suppressing ALIS formation and the accumulation of ubiquitinated proteins in macrophages, thereby suggesting a novel function for DcR3 in maintaining intracellular protein homeostasis under stress conditions. Full article

Jellyfish stings are the most common type of marine life injuries. However, at present, the treatment measures against jellyfish stings are mostly empirical and supportive, with uncertain therapeutic outcomes, and there is a lack of specific antidotes based on the toxic mechanism of jellyfish venom in clinical practice. In our previous study, polyphenol epigallocatechin-3-gallate (EGCG) was found to neutralize the toxicity of jellyfish Nemopilema nomurai venom (NnV) in vivo and in vitro. Herein we further demonstrated that EGCG exerted its antagonistic effect against NnV through inhibiting the oxidative stress, pro-apoptotic proteins, and systemic inflammatory responses. Subsequently, we constructed a polyethylene glycol (PEG)-EGCG/tetracycline hydrochloride (HTC) co-loaded micellar nanocomplex in order to enhance the stability and bioavailability of EGCG in vivo, which successfully integrated the membrane-repair function of PEG, the enzyme inhibitory effect of HTC and the antioxidant properties of EGCG. Notably, this micellar nanocomplex demonstrated significant protective effects against both functional damage and pathological alterations in a non-lethal NnV-envenomed mouse model. When administered 1 h after NnV envenomation, EGCG (40 mg/kg), HTC and PEG-EGCG (containing 40 mg/kg EGCG) only partially improved abnormal blood biochemical indicators and moderately alleviated histopathologic damage, and PEG-EGCG/HTC containing merely 8 mg/kg EGCG completely mitigated the toxic reactions in envenomed mice. In the preventive regimen, the administration of EGCG, HTC or PEG-EGCG 30 min before exposure showed no significant improvement in abnormal blood biochemical indicators and histopathologic damage, while PEG-EGCG/HTC could still significantly improve the functional impairments and histopathologic damage of the heart and liver in NnV-envenomed mice. These findings suggest the clinical translational potential of PEG-EGCG/HTC against jellyfish envenomation. Full article

Background/Objectives: Tordylium trachycarpum Boiss. (Apiaceae) is traditionally used in Kurdish ethnomedicine for the management of gastrointestinal disorders; however, its pharmacological efficacy and safety profile remain insufficiently investigated. This study evaluated, for the first time, the gastroprotective activity and associated antioxidant, inflammatory, and apoptotic responses of the methanolic extract of T. trachycarpum using an ethanol-induced gastric ulcer model in Sprague–Dawley rats. Methods: Preliminary phytochemical screening revealed the presence of phenolics, flavonoids, terpenoids, tannins, coumarins, and glycosides. Acute oral toxicity testing demonstrated no signs of toxicity at doses up to 5 g/kg. Gastric ulceration was induced by absolute ethanol, and animals were pretreated with the extract (250 and 500 mg/kg) or omeprazole (20 mg/kg). Results: The extract significantly decreased the gastric lesion area from 258.50 ± 6.38 mm² in the ulcer control group to 143.70 ± 0.76 mm² and 115.50 ± 0.76 mm², corresponding to ulcer inhibition rates of 44.41% and 55.31%. Additionally, the extract increased mucus production, maintained mucosal structure, and raised stomach pH. Biochemical analysis showed a significant increase in antioxidant enzymes [superoxide dismutase (SOD) and catalase (CAT)] and a reduction in malondialdehyde (MDA) levels, indicating attenuation of oxidative stress. In addition, the extract modulated pro-inflammatory cytokines (TNF-α, IL-1β, IL-6, and IL-10). Blood-based ELISA analysis demonstrated increased expression of heat shock protein 70 (HSP70) and reduced Bax levels, suggesting anti-apoptotic activity. Conclusions: These findings indicate that T. trachycarpum exerts significant gastroprotective activity through antioxidant, anti-inflammatory, and anti-apoptotic mechanisms, supporting its traditional use and highlighting its potential as a natural therapeutic candidate for the management of gastric ulcers. Full article

Coordinated responses of intestinal epithelial and immune cells are essential for maintaining barrier integrity and immune homeostasis in dogs, yet our mechanistic understanding of probiotic-derived metabolites remains limited due to reliance on non-canine experimental models, highlighting the need for studies in canine-derived systems. Here, we investigated the effects of metabolites derived from Limosilactobacillus reuteri strain ATCC PTA6127 (Lr6127), delivered as a cell-free supernatant (CFS), on canine epithelial MCA-B1 cells and macrophage-like DH82 cells subjected to lipopolysaccharide (LPS)-induced inflammatory stress. Lr6127 CFS significantly reduced epithelial permeability, decreasing FITC–dextran leakage to 94.9 ± 1.9% (normalized relative to LPS-treated control, which was set as 100%) (p < 0.001), despite no detectable transcriptional changes in tight junction, adherens junction, or mucin genes. Barrier effects were instead associated with changes in markers of cellular stress responses, with heme oxygenase expression decreasing from 0.9 ± 0.1 to 0.7 ± 0.1 (p < 0.05). In DH82 immune cells, Lr6127-derived metabolites altered LPS-induced stress- and inflammation-related gene expression patterns; enhanced anti-apoptotic responses, as reflected by the increased BCL2 expression (1.4 ± 0.1 vs. 1.0 ± 0.0; p < 0.01) and elevated BCL2/BAX ratios (p < 0.01); and reduced expression of pro-inflammatory mediators including IL-6 and CCL2 (p < 0.05–0.001). Proteomic analysis corroborated that Lr6127-derived metabolites reduced the abundance of inflammatory and STAT-associated signaling proteins under LPS challenge, while indicating context-dependent changes in immune-related protein profiles under resting condition. Collectively, these results suggest that Lr6127-derived metabolites improved epithelial barrier function, which was accompanied by coordinated changes in cellular stress-related and inflammatory pathways, highlighting their potential to positively influence host responses. Full article

Carbon monoxide (CO) is a gasotransmitter generated by heme oxygenase (HO) isoforms during heme catabolism. The inducible HO-1 produces CO under conditions of redox imbalance, such as oxidative stress and inflammation. On the other hand, HO-2 constitutively generates CO, primarily during the physiological turnover of heme. Extensive evidence indicates that CO exerts autocrine effects by targeting hemoproteins, including soluble guanylyl cyclase, cyclooxygenase, and cytochromes. Furthermore, CO regulates many biological processes within the brain, including mitochondrial biogenesis, potassium channel activity, mitogen-activated protein kinase and phosphatidylinositol-3-kinase/Akt signaling. It also controls the activity of transcription factors, such as hypoxia-inducible factor-1 and peroxisome proliferator-activated receptor-γ. Through these mechanisms, CO modulates inflammatory gene expression, promotes anti-apoptotic signaling, and contributes to local stress responses. Conversely, CO produced in the hypothalamus inhibits the stress-induced release of corticotropin-releasing hormone and arginine vasopressin under pro-inflammatory conditions, resulting in reduced adrenocorticotropin hormone release and cortisol secretion from the anterior pituitary and adrenal cortex, respectively. Moreover, hypothalamic CO acts in a paracrine manner to modulate glucocorticoid release during psychological stress, including restraint or water deprivation. Together, these findings support the view that endogenous CO is a key modulator of the stress axis, exerting pleiotropic effects that integrate neuroendocrine, immune, and metabolic responses. Full article

Background/Objectives: Myocardial infarction (MI) remains a leading cause of death worldwide, primarily resulting from abrupt coronary occlusion that induces severe hypoxia and extensive cardiomyocyte loss. Hypoxia triggers mitochondrial dysfunction, oxidative stress, inflammation, and apoptosis, ultimately compromising cardiac function and promoting adverse cardiac remodeling. MicroRNAs (miRNAs) have emerged as critical regulators of cardiomyocyte survival and stress responses under ischemic conditions; however, the functional roles and molecular mechanisms of many hypoxia-responsive miRNAs remain insufficiently defined. Methods: In this study, we focused on miR-30c-1-3p, which is markedly downregulated during the early phase of MI, and investigated its functional role in hypoxia-induced cardiomyocyte injury. We identified trinucleotide repeat-containing 6A (Tnrc6a), a key component of the miRNA-induced silencing complex, as a potential downstream target. Using primary neonatal rat cardiomyocytes, we performed gain- and loss-of-function experiments, luciferase reporter assays, and Tnrc6a knockdown analyses to evaluate apoptosis, inflammatory cytokine secretion, and release of myocardial injury-related proteins. Results: Restoration of miR-30c-1-3p significantly attenuated hypoxia-induced pro-apoptotic signaling, reduced inflammatory cytokine release, and decreased myocardial injury markers. These protective effects were associated with regulation of the miR-30c-1-3p/Tnrc6a axis. Conclusions: Collectively, our findings identify a previously unappreciated functional role of the miR-30c-1-3p/Tnrc6a axis in hypoxia-induced cardiomyocyte injury and highlight its potential relevance in myocardial stress adaptation. Full article

The present investigation was designed to assess how perinatal contact with the pyrethroid insecticide cyfluthrin (CY) influences cognitive performance in developing rat progeny and to clarify the contributing cellular events through examination of neuroinflammatory processes alongside pyroptotic and apoptotic pathways. An experimental framework involving CY administration during gestation was implemented using Sprague–Dawley (SD) dams, with subsequent monitoring of placental parameters and neonatal outcomes. Once offspring reached postnatal day twenty-one, their behavior was characterized via a battery consisting of the open field paradigm, novel object recognition task, and the Morris water navigation test. Hippocampal tissue architecture and fine structural details were visualized by employing hematoxylin–eosin (HE) staining and Nissl substance labeling. Protein and transcript abundances for pro-inflammatory mediators (TNF-α, IL-6), synaptic constituents (postsynaptic density protein-95, PSD-95; synaptophysin, SYP), and pyroptotic machinery components (NLRP3, GSDMD, Caspase-1) within hippocampal homogenates were quantified through immunoblotting and real-time quantitative PCR procedures, and the spatial distribution of these molecules was validated via immunohistochemical detection. Neuronal apoptosis was assessed by TUNEL staining. The results demonstrated that gestational CY exposure led to reduced placental weight and diameter, decreased blood sinus area in the labyrinth zone, lower offspring birth weight, and impaired catch-up growth. Behavioral tests revealed that CY-exposed offspring exhibited diminished spontaneous locomotor activity, impaired novel object recognition memory, and significant deficits in spatial learning and memory. Pathological analysis showed disorganized neuronal arrangement and reduced Nissl bodies in the hippocampal CA1 region. Compared to the control group, CY exposure markedly upregulated the protein expression of TNF-α and IL-6, downregulated PSD-95 and SYP, activated the NLRP3/GSDMD/Caspase-1-mediated pyroptotic pathway, and increased the expression of the apoptotic protein Caspase-3, culminating in a significant increase in hippocampal neuronal apoptosis. In conclusion, early-life exposure to cyfluthrin impairs cognitive function in offspring, an effect closely associated with the induction of hippocampal neuroinflammation and the activation of pyroptotic and apoptotic pathways. These findings provide novel toxicological evidence for a more comprehensive assessment of the potential health risks posed by CY exposure in human populations. Full article

Background/Objectives: Arsenic (ARS) exposure is a major cause of kidney injury, driven by oxidative stress, inflammation, fibrosis, and apoptosis. This study evaluated the renoprotective effects of morin (MOR) and morin-loaded PLGA nanoparticles (MOR–PGNPs) against ARS-induced nephrotoxicity in rats. Methods: Sixty male Sprague Dawley rats were randomly allocated into six groups (n = 10 per group). The control group received corn oil. The MOR group received MOR (100 mg/kg), and the MOR–PGNPs group received the same dose of MOR encapsulated in PLGA nanoparticles. ARS was administered at 10 mg/kg for 14 days. Co-treated groups received ARS together with either MOR or MOR–PGNPs, with a 28 min interval between administrations. Renal function markers (serum urea, creatinine, uric acid, renal KIM-1), oxidative stress and antioxidant parameters (Nrf2/HO-1, CAT, SOD, GPx, ROS, MDA), inflammatory mediators (TLR4/NF-κB, TNF-α, IL-6, IL-1β), fibrotic markers (TGF-β1, fibronectin), and apoptotic proteins (caspase-3, caspase-8, Bax, Bcl-2) were assessed, alongside histopathological and ultrastructural evaluations. Results: ARS exposure significantly impaired renal function, increased KIM-1, suppressed Nrf2/HO-1 signaling, reduced antioxidant enzyme activities, and elevated ROS and MDA levels. It also activated TLR4/NF-κB signaling, upregulated pro-inflammatory cytokines and fibrotic markers, and increased pro-apoptotic proteins while downregulating Bcl-2. MOR co-treatment partially ameliorated these alterations. MOR–PGNPs produced potentially enhanced protection, restoring kidney function markers, enhancing antioxidant defenses, and markedly attenuating inflammation, fibrosis, and apoptosis. Histopathological and ultrastructural analyses confirmed preservation of glomerular and tubular architecture, mitochondrial integrity, and minimal cytoplasmic vacuolization in the MOR–PGNPs group. Conclusions: MOR–PGNPs at 100 mg/kg effectively mitigated ARS-induced renal damage through antioxidant, anti-inflammatory, antifibrotic, and anti-apoptotic mechanisms, supporting PLGA-based morin nanoparticles as a promising and safe renoprotective strategy. Full article

Nuclear factor-κB (NF-κB) is a critical regulator of inflammation and stress response signaling in acute kidney injury (AKI). Increasing evidence demonstrates that NF-κB signaling is directly related to oxidative stress, autophagy, mitochondrial malfunction, and apoptosis in the process of AKI. Injury-related stimuli, including ischemia–reperfusion, sepsis, nephrotoxins, reactive oxygen species (ROS) and damage-associated molecular patterns (DAMPs), activate canonical and non-canonical NF-κB pathways, resulting in renal inflammation and tubular injury. Recent investigations have shown that TLR4/NF-κB signaling, NLRP3 inflammasome activation, defective autophagy, and mitochondrial dysfunction mediate inflammatory and pro-apoptotic responses in AKI. On the other hand, autophagy-associated proteins such as microtubule-associated protein 1 light chain 3 beta (LC3B) and Beclin-1 may play renoprotective roles through the regulation of NF-κB signaling. This review tries to cover the knowledge regarding NF-κB signaling in AKI and to emphasize the possible function of NF-κB signaling in the control of inflammation, autophagy, and apoptosis. It also seeks to provide some insight into future research directions that may guide the development of more effective therapies for AKI. Full article