Search Results (3,544)

Traditional anti-inflammatory medications—such as corticosteroids, biological agents, and non-steroidal anti-inflammatory drugs—are commonly employed to mitigate inflammation, despite their potential for debilitating side effects. There is a growing need for alternative next-generation therapies for symptomatic, unchecked, and/or detrimental inflammation with more favorable adverse effect profiles. The long history of use of gold salts as anti-inflammatory agents and the more recent exploration of gold nanoparticle (AuNP) formulations for clinical indications suggest that the targeted delivery of nanoparticles to inflammatory sites may be a promising approach worth investigating. Coupled with peptides that specifically target immune cells, AuNPs could potently counteract inflammation. Here, we provide an overview of the selective infiltration of AuNPs into immune cells and summarize their interactions with and impact on these cells. Additionally, we provide a comprehensive mechanistic summary of how AuNPs exert their anti-inflammatory effects. Full article

The prostate gland, a male accessory reproductive organ, is regulated by hormonal inputs and autonomic innervation from the major pelvic ganglion. This study examined the effects of major pelvic ganglion denervation on prostate histology, immune cell infiltration, and systemic levels of prolactin, testosterone, and cytokines in rats. Male Wistar rats (300–350 g) were divided into groups receiving bilateral axotomy of the hypogastric nerve, the pelvic nerve, or both, alongside with a sham-operated control. After 15 days, the animals were killed, and prostate tissue was dissociated in DMEM medium containing DNase I and collagenase. The dissociated cells were stained with fluorochrome-conjugated antibodies, and cell characterization was performed using a flow cytometer. Hematoxylin and eosin (H&E) staining was used to analyze histological characteristics, while testosterone, prolactin, and interleukin levels were measured via ELISA. Histological analysis revealed inflammatory atypical hypertrophy e hiperplasia. Immunological assessments demonstrated increased leukocytes, T lymphocytes (CD4⁺ and CD8⁺), B lymphocytes, and macrophages following double nerve axotomy. Serum analyses showed elevated pro-inflammatory cytokines IL-1β, IL-6, and IFN-γ, as well as anti-inflammatory IL-10, in denervated animals. Hormonal assessments revealed significant increases in serum prolactin and testosterone levels after double axotomy. Loss of neural control may promote pathological prostate changes via inflammation and hormonal dysregulation, offering insights into neuroimmune and neuroendocrine mechanisms underlying prostate pathologies. Full article

Fat embolism is a critical medical emergency often resulting from long bone fractures or amputations, leading to acute respiratory distress syndrome (ARDS). The NOD-like receptor pyrin domain-containing 3 (NLRP3) inflammasome, a key regulator of innate immunity, is activated by reactive oxygen species and tissue damage, contributing to inflammatory responses. This study examines the role of NLRP3 in fat embolism-induced ARDS and evaluates the therapeutic potential of MCC950, a selective NLRP3 antagonist. Fat embolism was induced by fatty micelle injection into the tail vein of Sprague Dawley rats. Pulmonary injury was assessed through lung weight gain as an edema indicator, NLRP3 expression via Western blot, and IL-1β levels using ELISA. Histological damage and macrophage infiltration were evaluated with hematoxylin and eosin staining. Fat embolism significantly increased pulmonary NLRP3 expression, lipid peroxidation, IL-1β release, and macrophage infiltration within four hours, accompanied by severe pulmonary edema. NLRP3 was localized in type I alveolar cells, co-localizing with aquaporin 5. Administration of MCC950 significantly reduced inflammatory responses, lipid peroxidation, pulmonary edema, and histological damage, while attenuating MAPK cascade phosphorylation of ERK and Raf. These findings suggest that NLRP3 plays a critical role in fat embolism-induced acute respiratory distress syndrome, and its inhibition by MCC950 may offer a promising therapeutic approach. Full article

Neuroinflammation is the major contributor to the pathology of neonatal hypoxic–ischemic (HI) brain injury. Our previous studies have demonstrated that microRNA210 (miR210) inhibition with antisense locked nucleic acid (LNA) inhibitor mitigates neuroinflammation and provides neuroprotection after neonatal HI insult. However, the underlying mechanisms remain elusive. In the present study, using miR210 knockout (KO) mice and microglial cultures, we tested the hypothesis that miR210 promotes microglial activation and neuroinflammation through suppressing mitochondrial function in microglia after HI. Neonatal HI brain injury was conducted on postnatal day 9 (P9) wild-type (WT) and miR210 knockout (KO) mouse pups. We found that miR210 KO significantly reduced brain infarct size at 48 h and improved long-term locomotor functions assessed by an open field test three weeks after HI. Moreover, miR210 KO mice exhibited reduced IL1β levels, microglia activation and immune cell infiltration after HI. In addition, in vitro studies of microglia exposed to oxygen–glucose deprivation (OGD) revealed that miR210 inhibition with LNA reduced OGD-induced expression of Il1β and rescued OGD-mediated downregulation of mitochondrial iron–sulfur cluster assembly enzyme (ISCU) and mitochondrial oxidative phosphorylation activity. To validate the link between miR210 and microglia activation, isolated primary murine microglia were transfected with miR210 mimic or negative control. The results showed that miR210 mimic downregulated the expression of mitochondrial ISCU protein abundance and induced the expression of proinflammatory cytokines similar to the effect observed with ISCU silencing RNA. In summary, our results suggest that miR210 is a key regulator of microglial proinflammatory activation through reprogramming mitochondrial function in neonatal HI brain injury. Full article

Classical Hodgkin lymphoma (cHL) is a biologically and clinically unique malignancy characterized by rare Hodgkin and Reed–Sternberg (HRS) cells surrounded by a dense and diverse inflammatory infiltrate. These malignant cells actively reshape the tumor microenvironment (TME) through metabolic reprogramming and immune evasion strategies. This review synthesizes current knowledge on how metabolic alterations contribute to tumor survival, immune dysfunction, and therapeutic resistance in cHL. We discuss novel therapeutic approaches aimed at disrupting these processes and examine the potential of combining metabolic interventions with immune-based strategies—such as immune checkpoint inhibitors (CPIs), epigenetic modulators, bispecific antibodies, and CAR-T/CAR-NK cell therapies—which may help overcome resistance and enhance anti-tumor responses. Several agents are currently under investigation for their ability to modulate immune cell metabolism and restore effective immune surveillance. Altogether, targeting metabolic vulnerabilities within both tumor and immune compartments offers a promising, multifaceted strategy to improve clinical outcomes in patients with relapsed or refractory cHL. Full article

Chronic nasopharyngeal and otic disorders in children represent a significant clinical challenge due to their multifactorial etiology, variable presentation, and frequent resistance to standard therapies. Although often approached from a symptomatic or anatomical perspective, these conditions are deeply rooted in histological and molecular alterations that sustain inflammation, impair mucosal function, and promote recurrence. This narrative review synthesizes the current knowledge on the normal histology of the nasopharynx, Eustachian tube, and middle ear, and explores key pathophysiological mechanisms, including epithelial remodeling, immune cell infiltration, cytokine imbalance, and tissue fibrosis. Special emphasis is placed on the role of immunohistochemistry in defining inflammatory phenotypes, barrier dysfunction, and remodeling pathways. The presence of biofilm, epithelial plasticity, and dysregulated cytokine signaling are also discussed as contributors to disease chronicity. These findings have direct implications for diagnosis, therapeutic stratification, and postoperative monitoring. By integrating histological, immunological, and molecular data, clinicians can better characterize disease subtypes, anticipate treatment outcomes, and move toward a more personalized and biologically informed model of pediatric ENT care. Full article

Feline mammary carcinoma (FMC) exhibits aggressive behavior, with limited treatment options. Given the relevance of the PD-1/PD-L1/PD-L2 axis in human breast cancer immunotherapy, this study assessed PD-1 and its ligands in rare FMC histotypes (n = 48) using immunohistochemistry on tumor cells (TCs), intratumoral lymphocytes (iTILs), and stromal tumor-infiltrating lymphocytes (sTILs). PD-1 was expressed in 13% of TCs, 85% of iTILs, and 94% of sTILs, while PD-L1 was observed in 46% of TCs, 96% of iTILs, and 100% of sTILs. PD-L2 was expressed in 79% of TCs and 100% of both iTILs and sTILs, with PD-L1/PD-L2 co-expression in 42% of TCs. Higher PD-1 IHC scores in TCs were associated with a less aggressive biological behavior; PD-L1 in iTILs was linked to skin ulceration, whereas PD-L2 in TCs was associated with its absence. Our findings highlight the relevance of the PD-1/PD-L1/PD-L2 immune checkpoint in rare FMC subtypes and support further investigation into checkpoint-blockade therapies. Full article

Whether the spongiotic reaction caused by the interaction of keratinocytes, T-lymphocytes, inflammatory dendritic epidermal cells (IDECs), and Langerhans cells (LCs) observed in atopic dermatitis (AD) represents a common feature of spongiosis in various skin diseases remains unclear. We analyzed the characteristics of spongiosis in AD compared with those in other eczematous dermatitis and inflammatory skin diseases by using immunohistochemical methods. Infiltration of IDECs (CD11c+ cells and/or CD206+ cells) and T-lymphocytes, accompanied by degenerated keratinocytes and aggregated LCs (CD207+ cells), was frequently observed as a common feature of spongiosis in multiple conditions. However, IDECs expressing IgE were identified exclusively in IgE-mediated AD. Aggregation of IDECs was predominantly observed in the spongiosis of adaptive immune-mediated eczematous disorders, such as AD and allergic contact dermatitis. These IDEC aggregations constituted the major components of the epidermal dendritic cell clusters seen in AD and other eczematous or eczematoid dermatoses, and may serve as a useful distinguishing marker from Pautrier collections seen in cutaneous T-cell lymphoma. These findings suggest that IDECs, in cooperation with other immune cells, may play a pivotal role in spongiosis formation in AD and various skin diseases, although the underlying immunopathological mechanisms differ among these conditions. Full article

Psoriasis is a chronic inflammatory skin disease characterized by abnormal proliferation of keratinocytes and infiltration of inflammatory cells. Significant challenges remain in developing effective and safe targeted therapies for psoriasis. Here, we reported the discovery of novel cystamine derivatives for the treatment of psoriasis. These compounds effectively attenuated LPS-induced inflammation in vitro, and the optimal candidate CS1 ameliorated imiquimod-induced psoriasis-like inflammation in mice. Mechanistically, CS1 bound and inhibited the deacetylase HDAC6, subsequently inhibited the AKT, MAPK, and STAT3 pathways, attenuated the hyperproliferation and altered differentiation of keratinocytes and reduced the infiltration of immune cells. These findings suggest that HDAC6 may serve as a potential target for drug development in the treatment of psoriasis. Full article

Background: Dyslipidemia and schistosomiasis are major public health challenges, particularly in endemic regions where their coexistence may influence host metabolism and immune responses. This study aimed to evaluate visceral adipose tissue (AT) remodeling in a murine model of acute Schistosoma mansoni infection combined with diet-induced dyslipidemia. Methodology: Female Swiss Webster mice were fed either a standard or high-fat diet (HFD) for 29 weeks and infected with S. mansoni at week 20. Nine weeks after infection, biochemical, morphometric, histopathological, and immunological analyses were performed. Results: The HFD promoted weight gain and dyslipidemia, while S. mansoni infection alone did not alter lipid profiles but partially mitigated the metabolic effects of the HFD. Morphometric analysis revealed adipocyte hypertrophy and reduced cell number in HFD-fed animals. In HFD-fed infected mice, infection partially reversed hypertrophy, suggesting a modulatory effect on AT remodeling. Histopathological examinations showed that while a HFD induced mild inflammation, infection led to intense leukocyte infiltration, hyperemia, and plasma cell degeneration. Peritoneal lavage confirmed a proinflammatory immune profile. Conclusions: These findings indicate that the interaction between a HFD and S. mansoni infection exacerbates adipose tissue inflammation and metabolic alterations, highlighting the complex interplay between parasitic infection, diet, and immune-metabolic regulation. Full article

Background/Objectives: Moschus (musk) has long been used in traditional Tibetan medicine to prevent and treat epidemic febrile illnesses. However, its antiviral mechanisms remain poorly understood. Given the urgent need for effective treatments against viral respiratory tract infections (VRTIs), this study aimed to systematically investigate the molecular targets and pharmacological pathways through which Moschus may exert therapeutic effects. Methods: Based on the identification of bioactive compounds with favorable pharmacokinetics, we applied integrated network pharmacology and multi-omics analyses to systematically identify key therapeutic targets involved in VRTIs. Gene Set Enrichment Analysis (GSEA) and immune infiltration further revealed strong associations with multiple immune cell subsets, reflecting their pivotal roles in immunomodulatory mechanisms during viral infections. Molecular docking confirmed the strong binding affinities between Moschus compounds and these key targets. Results: Notably, testosterone exhibited the strongest and most consistent binding across key targets, suggesting its potential as a pivotal bioactive compound. Importantly, the antiviral effects of Moschus may be mediated in part by the downregulation of the key genes MCL1, MAPK3, and CDK2, which are involved in the regulation of viral replication, apoptosis, and host immune responses. Conclusions: This study provides a comprehensive mechanistic framework supporting the multi-target antiviral potential of Moschus, offering a scientific basis for its further development as a therapeutic agent against VRTIs. Full article

Metabolic dysfunction-associated steatohepatitis (MASH) and atherosclerosis are cardiometabolic twin disorders with shared underlying pathophysiological mechanisms such as insulin resistance and chronic inflammation. This review explores the salient role of carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1) in linking hepatic dysfunction to cardiovascular disease. Findings in mice with genetic modulation of Ceacam1 gene established a critical role for CEACAM1 protein in regulating insulin and lipid metabolism and endothelial integrity and modulating immune response. Loss of CEACAM1 in hepatocytes impairs insulin clearance, causing chronic hyperinsulinemia, a process that ultimately leads to insulin resistance and hepatic and extra-hepatic fat accumulation, which in turn causes inflammatory infiltration. This prompts a paradigm shift that positions impaired hepatic CEACAM1 function as a mechanistic underpinning of the link between insulin resistance, MASH, and atherosclerosis. Full article

Background: Soft tissue sarcomas (STSs) are a rare and heterogeneous group of mesenchymal tumors with limited response to current therapies, particularly in advanced stages. STS tumors were traditionally considered “cold” tumors, characterized by limited immune infiltration and low immunogenicity. However, emerging evidence is challenging this perception, highlighting a potentially critical role for the immune system in STS biology. Objective: Building on our previous findings suggesting impaired natural killer (NK) cell activity in STS patients, we aimed to perform an in-depth characterization of peripheral NK cells in STS. Methods: Peripheral blood samples from STS patients and sex- and age-matched healthy donors were analyzed to assess NK cell degranulation, IFNγ production, and receptor repertoire. Results: Functional assays revealed a notable reduction in both degranulation and IFNγ production in NK cells from STS patients. STS patients also exhibited dysregulated expression of activating and inhibitory NK cell receptors. Principal component analysis (PCA) identified CD27 and NKp44 as critical markers for distinguishing STS patients from healthy donors. Increased CD27 expression represents a shift towards a more regulatory NK cell phenotype, and we found that CD27 expression was negatively correlated with NK cell degranulation and IFNγ production. ROC curve analysis demonstrated strong potential to distinguish between the groups for both CD27 (AUC = 0.85) and NKp44 (AUC = 0.94). Conclusion: In conclusion, STS patients exhibited impaired NK cell function, altered receptor repertoire, and a shift towards a less cytotoxic and more regulatory phenotype. Full article

Background: Choroidal nevi are common, benign tumors. These tumors rarely cause adverse retinal sequalae, but when they do, they can lead to disruption of the outer retina and vision loss. In this paper, we used high-resolution retinal imaging modalities, optical coherence tomography (OCT) and adaptive optics scanning laser ophthalmoscopy (AOSLO), to longitudinally monitor retinal sequelae of a submacular choroidal nevus. Methods: A 31-year-old female with a high-risk choroidal nevus resulting in subretinal fluid (SRF) and a 30-year-old control subject were longitudinally imaged with AOSLO and OCT in this study over 18 and 22 months. Regions of interest (ROI) including the macular region (where SRF was present) and the site of laser photocoagulation were imaged repeatedly over time. The depth of SRF in a discrete ROI was quantified with OCT and AOSLO images were assessed for visualization of photoreceptors and retinal pigmented epithelium (RPE). Cell-like structures that infiltrated the site of laser photocoagulation were measured and their count was assessed over time. In the control subject, images were assessed for RPE visualization and the presence and stability of cell-like structures. Results: We demonstrate that AOSLO can be used to assess cellular-level changes at small ROIs in the retina over time. We show the response of the retina to SRF and laser photocoagulation. We demonstrate that the RPE can be visualized when SRF is present, which does not appear to depend on the height of retinal elevation. We also demonstrate that cell-like structures, presumably immune cells, are present within and adjacent to areas of SRF on both OCT and AOSLO, and that similar cell-like structures infiltrate areas of retinal laser photocoagulation. Conclusions: Our study demonstrates that dynamic, cellular-level retinal responses to SRF and laser photocoagulation can be monitored over time with AOSLO in living humans. Many retinal conditions exhibit similar retinal findings and laser photocoagulation is also indicated in numerous retinal conditions. AOSLO imaging may provide future opportunities to better understand the clinical implications of such responses in vivo. Full article

Cerebral malaria (CM) is the severe progression of an infection with Plasmodium falciparum, causing detrimental damage to brain tissue and is the most frequent cause of Plasmodium falciparum mortality. The critical role of brain-infiltrating CD8⁺ T cells in the pathophysiology of CM having been revealed, our investigation focuses on the role of NR2F6, an established immune checkpoint, as a candidate driver of CM pathology. We employed an experimental mouse model of CM based on Plasmodium berghei ANKA (PbA) infection to compare the relative susceptibility of Nr2f6-knock-out and wild-type C57BL6/N mice. As a remarkable result, Nr2f6 deficiency confers a significant survival benefit. In terms of mechanism, we detected less severe endotheliopathy and, hence, less damage to the blood–brain barrier (BBB), accompanied by decreased sequestered parasites and less cytotoxic T-lymphocytes within the brain, manifesting in a better disease outcome. We present evidence that NR2F6 deficiency renders mice more resistant to experimental cerebral malaria (ECM), confirming a causal and non-redundant role for NR2F6 in the progression of ECM disease. Consequently, pharmacological inhibitors of the NR2F6 pathway could be of use to bolster BBB integrity and protect against CM. Full article