Search Results (60)

Skin cancer is the most common cancer worldwide. The incidence of skin cancer has been increasing worldwide. Nearly 75% of all skin cancers are basal cell carcinomas (BCC), cutaneous squamous cell carcinoma (cSCC) represents approximately 20%, and those remaining are melanomas (4%) or other rare tumors (1%). Given the high cure rates and the ability to histologically confirm tumor clearance, surgical therapy is the gold standard for the treatment of skin cancer. Conventional surgery is the most employed technique for the removal of non-melanoma skin cancer (NMSCs). Mohs Micrographic Surgery (MMS) is the most precise surgical method for the treatment of non-melanoma skin cancer, allowing for 100% margin evaluation, being the gold-standard method for surgical treatment of non-melanoma skin cancer. Whenever it is possible to obtain wide margins (4 to 6 mm), cure rates vary from 70% to 99%. Imiquimod, a synthetic imidazoquinolinone amine, is a topical immune response modifier approved by the U.S. Food and Drug Administration (FDA) for the treatment of external anogenital warts, actinic keratosis (AK), and superficial basal cell carcinoma (sBCC). The efficacy of imiquimod is primarily attributed to its ability to modulate both innate and adaptive immune responses, as well as its direct effects on cancer cells. Imiquimod exerts its immunomodulatory effects by activating Toll-like receptors 7 and 8 (TLR7/8) on various immune cells, including dendritic cells, macrophages, and natural killer (NK) cells. Upon binding to these receptors, imiquimod triggers the MyD88-dependent signaling pathway, leading to the activation of nuclear factor kappa B (NF-κB) and interferon regulatory factors (IRFs). This cascade leads to the production of pro-inflammatory cytokines, including interferon-alpha (IFN-α), tumor necrosis factor-alpha (TNF-α), interleukin-12 (IL-12), and interleukin-6 (IL-6). These cytokines enhance local inflammation, recruit additional immune cells to the tumor site, and stimulate antigen presentation, thereby promoting an anti-tumor immune response. Radiation therapy (RTh) may be employed as a primary treatment to BCC. It may also be employed as an adjuvant treatment to surgery for SCC and aggressive subtypes of BCC. RTh triggers both direct and indirect DNA damage on cancer cells and generates reactive oxygen species (ROS) within cells. ROS trigger oxidative damage to DNA, proteins, and lipids, exacerbating the cellular stress and contributing to tumor cell death. Recently, immunotherapy emerged as a revolutionary treatment for all stages of SCC. Cemiplimab is a human programmed cell death 1 (PD-1)-blocking antibody that triggers a response to over 50% of patients with locally advanced and metastatic SCC. A randomized clinical trial (RCT) published in 2022 revealed that cemiplimab was highly effective in the neoadjuvant treatment of large SCCs. The drug promoted a significant tumor size decrease, enabling organ-sparing operations and a much better cosmetic effect. A few months ago, a RCT of cemiplimab on adjuvant therapy for locally aggressive SCC was published. Interestingly, cemiplimab was administered to patients with local or regional cutaneous squamous cell carcinoma after surgical resection and postoperative radiotherapy, at high risk for recurrence owing to nodal features, revealed that cemiplimab led to much lower risks both of locoregional recurrence and distant recurrence. Full article

Systemic lupus erythematosus (SLE) is characterized by autoimmune dysregulation, elevated autoantibody production, and persistent inflammation, predisposing patients to atherosclerosis (AS). Atherogenesis is dependent on lipid homeostasis and inflammatory processes, with the formation of lipid-laden, macrophage-derived foam cells (MDFC) essential for atherosclerotic lesion progression. Elevated cholesterol levels within lipid rafts trigger heightened pro-inflammatory responses in macrophages via Toll-like receptor 9 (TLR9). Artesunate (ART), an artemisinin derivative sourced from Artemisia annua, exhibits therapeutic potential in modulating inflammation and autoimmune conditions. Nonetheless, its impact and mechanisms in SLE-associated AS (SLE-AS) remain largely unexplored. Our investigation demonstrated that ART could effectively ameliorate lupus-like symptoms and atherosclerotic plaque development in SLE-AS mice. Moreover, ART enhanced cholesterol efflux from MDFC by upregulating ABCA1, ABCG1, and SR-B1 both in vivo and in vitro. Moreover, ART reduced cholesterol accumulation in bone marrow-derived macrophages (BMDMs), thereby diminishing TLR9 recruitment to lipid rafts. ART also suppressed TLR9 expression and its downstream effectors in the kidney and aorta of SLE-AS mice, attenuating the TLR9-mediated inflammatory cascade in CPG2395 (ODN2395)-stimulated macrophages. Through bioinformatics analysis and experimental validation, PPARγ was identified as a pivotal downstream mediator of ART in macrophages. Depleting PPARγ levels reduced the expression of ABCA1, ABCG1, and SR-B1 in macrophages, consequently impeding cholesterol efflux. In conclusion, these findings suggest that ART ameliorates SLE-AS by restoring cholesterol homeostasis through the PPARγ-ABCA1/ABCG1/SR-B1 pathway and suppressing lipid raft-driven TLR9/MyD88 inflammation. Full article

The immunomodulatory polysaccharide CPP-3a, purified from Chlorella pyrenoidosa, was investigated for its effects on RAW264.7 macrophages and underlying mechanisms, revealing that CPP-3a significantly enhanced phagocytic capacity and nitric oxide production while upregulating pro-inflammatory cytokines TNF-α and IL-6 and elevating the co-stimulatory molecule CD86, collectively driving robust M1 polarization. Mechanistically, TLR4-, TLR2-specific inhibitors, and TLR4-knockout cells confirmed TLR4 as the primary receptor for CPP-3a, with TLR2 playing a secondary role in cytokine modulation. CPP-3a activated NF-κB and p38 MAPK signaling pathways via the MyD88-dependent pathway, evidenced by phosphorylation of NF-κB/p65 with its nuclear translocation and increased phosphorylation of p38 MAPK, with these signaling activations further validated by specific pathway inhibitors that abolished M1 polarization phenotypes. Collectively, CPP-3a emerges as a potent TLR4-targeted immunomodulator with adjuvant potential for inflammatory and infectious diseases. Full article

Probiotics have recently gained attention as modulators of the gut–brain axis in neurodegenerative diseases such as Alzheimer’s disease. In this study, we identified probiotic strains with neuroprotective effects and investigated their mechanisms and safety. We screened strains based on their ability to inhibit acetylcholinesterase (AChE) activity and protect cells against H₂O₂-induced damage. The cell-free supernatants (CFS) of Lactobacillus gasseri MG4247 and Lacticaseibacillus rhamnosus MG4644 inhibited AChE activity and reduced cell damage and reactive oxygen species generation. These effects were mediated through inhibition of the MyD88/NF-κB pathway and modulation of the JNK/Bax-dependent apoptotic pathway in neuronal cells treated with H₂O₂. Whole-genome sequencing and antibiotic susceptibility testing confirmed the identity and safety of both strains. These findings suggest that MG4247 and MG4644, as probiotics, may help protect neuronal cells from oxidative stress and inflammation. Full article

Polyphenols are compounds derived from plant-based food possessing numerous biological activities, including inhibiting oxidative stress, suppressing inflammation, and regulating gut microbiota. In this study, we investigated the effects of quinic acid, a phenolic acid from millet, on the regulation of gut microbiota and intestinal inflammation and further discussed the possible mechanism. The results showed that quinic acid could improve the microbiota composition of the feces of patients with inflammatory bowel disease (IBD) by in vitro anaerobic fermentation by increasing the abundance of beneficial genera including Bifidobacterium, Weissella, etc., and decreasing that of harmful genera like Escherichia-Shigella. Quinic acid treatment could alleviate the symptoms of dextran sodium sulfate (DSS)-induced colitis in mice, maintain the intestinal barrier, down-regulate the expression of inflammatory factors such as IL-1β and TNF-α, and inhibit the activation of the MyD88/NF-κB signaling pathway. In addition, quinic acid also improved the diversity of gut microbiota in mice with colitis. Furthermore, pseudo-germ-free colitis mice proved that the effect of quinic acid on intestinal inflammation was diminished after removing most gut microbiota by antibiotic treatment, suggesting that gut microbiota play important roles during the regulation of colitis by quinic acid. In a word, our study verified the regulatory effects of quinic acid on intestinal inflammation, depending on gut microbiota regulation and NF-κB signaling suppression. Full article

Background: Sparstolonin B (SsnB), a natural compound with anti-inflammatory and anti-proliferative properties, was investigated for its effects on cell viability, apoptosis, and inflammatory pathways in human colorectal cancer cells (HCT-116) and healthy human fibroblasts (BJ). Phorbol 12-myristate 13-acetate (PMA), a tumor promoter and inflammatory activator, was used to stimulate proliferation and inflammatory pathways. Methods: HCT-116 and BJ cells were treated with SsnB (3.125–50 μM) or PMA (1–10 nM) for 12–18 h. Cell viability was assessed using MTT analysis, while apoptosis was evaluated through cleaved caspase-3 staining, terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL), and flow cytometry. Proliferation was analyzed through proliferating cell nuclear antigen (PCNA) staining. Toll-like receptor (TLR) signaling, cytokine expression, and sphingolipid levels were measured using immunofluorescence, enzyme-linked immunosorbent assay (ELISA), and mass spectrometry, respectively. Results: SsnB reduced HCT-116 cell viability in a dose- and time-dependent manner with minimal effects on BJ cells. SsnB (25 μM, 12 h) decreased HCT-116 viability 0.6-fold, while PMA (10 nM, 12 h) increased it 2-fold (p < 0.01). No significant change was observed in BJ cells. PCNA fluorescence staining increased 2-fold with PMA and decreased 0.4-fold with SsnB (p < 0.001). PMA upregulated TLR2 and TLR4 mRNA and protein levels, with MyD88, p-ERK, and pNF-κB fluorescence increasing 2.1-, 1.5-, and 1.7-fold, respectively (p < 0.001). PMA elevated TNF-α, IL-1β, and IL-6 levels (p < 0.01). SsnB suppressed PMA-induced effects and promoted apoptosis, increasing cleaved caspase-3 levels by 1.5-fold and TUNEL staining by 1.9-fold (p < 0.01). Flow cytometry confirmed a significant increase in early and late apoptotic cells in the SsnB group. SsnB also increased ceramide (C18, C20, C22, and C24) levels (1.3- to 2.5-fold, p < 0.01) while reducing PMA-induced S1P and C1P increases (p < 0.01). Conclusions: SsnB selectively inhibits proliferation, induces apoptosis, and modulates inflammatory and sphingolipid pathways in colorectal cancer cells, with minimal toxicity to healthy fibroblasts, supporting its potential as a targeted therapeutic agent. Full article

TNF and IFN-γ are key proinflammatory cytokines implicated in the pathophysiology of COVID-19. Toll-like receptor (TLR)7 and TLR8 are known to recognize SARS-CoV-2 and induce TNF and IFN-γ production. However, it is unclear whether TNF and IFN-γ levels are altered through TLR-dependent pathways and whether these pathways mediate disease severity during COVID-19. This study aimed to investigate the association between TNF/IFN-γ levels and immune cell activation to understand their role in disease severity better. We enrolled 150 COVID-19 patients, who were classified by their systemic TNF and IFN-γ levels (high (H) or normal–low (N-L)) as TNF^HIFNγ^H, TNF^HIFNγ^N-L, TNF^N-LIFNγ^H, and TNF^N-LIFNγ^N-L. Compared to patients with TNF^N-LIFNγ^N-L, patients with TNF^HIFNγ^H had high systemic levels of pro- and anti-inflammatory cytokines and cytotoxic molecules, and their T cells and monocytes expressed TNF receptor 1 (TNFR1). Patients with TNF^HIFNγ^H presented the SNP rs3853839 to TLR7 and increased levels of MYD88, NFκB, and IRF7 (TLR signaling), FADD, and TRADD (TNFR1 signaling). Moreover, critical patients were observed in the four COVID-19 groups, but patients with TNF^HIFNγ^H or TNF^HIFNγ^N-L most required invasive mechanical ventilation. We concluded that increased TNF/IFN-γ levels are associated with hyperactive immune cells, whereas normal/low levels are associated with hypoactivity, suggesting a model to explain that the pathophysiology of critical COVID-19 may be mediated through different pathways depending on TNF and IFN-γ levels. These findings highlight the potential for exploring the modulation of TNF and IFN-γ as a therapeutic strategy in severe COVID-19. Full article

As new pollutants, microplastics (MPs) have attracted much attention worldwide because they cause serious environmental pollution and pose potential health risks to humans. However, the toxic effects of MPs are still unclear. In this study, we analysed the inflammatory effects of 0.1 μm polystyrene microplastics (PS-MPs) on mouse and human liver cell lines. After 28 days of exposure to PS-MPs, the mice presented decreased liver index values and increased AST/ALT values. HL7702 and HepG2 were treated with PS-MPs for 24 h, and the cytotoxicity, the expression levels of inflammatory factors, and the phosphorylation of proteins in inflammation related pathways were confirmed. Compared with the control, the cell viability of these two cells significantly decreased after exposure to the PS-MPs at 1000 μm/cm², and the BMD model also exhibited a similar dose. LDH leakage and AST also increased in a dose-dependent increase after PS-MPs exposure. The relative levels of chemokines such as GM-CSF, IL-6, IL-8, and IL-12p70 were significantly greater than those in the control. Furthermore, the PS-MPs can increase the expression levels of TLR4, MyD88, and NF-κB and activate the phosphorylation of NF-κB and STATs. Based on these results, exposure to PS-MPs can stimulate liver inflammation and activate the TLR4/MyD88/NF-κB and JAK-STAT pathways. Full article

Background: The genetic background of Toll-like receptor 4 (TLR4) proved to be important in the induction of immune protection against Bordetella pertussis infection in humans. Currently, the evaluation of the acellular pertussis (aP) vaccine depends largely on using different mouse strains, while the TLR4 genotype of different mouse strains in response to pertussis toxin (PT) is not carefully determined. The current study was designed to determine the differences in TLR4 genotype and TLR4 pathway-related cytokines in response to PT stimulation among mouse strains of ICR, NIH, and BALB/c. Method: We first determined the single-nucleotide polymorphisms (SNPs) in the TLR4 gene by using first-generation sequencing. Then, the cellular response, including the TLR4 mRNA expression and TLR4 signaling-related cytokines, of immune cells from different mouse strains after PT stimulation was determined. Result: Three missense mutation sites (rs13489092, rs13489093, rs13489097) of the TLR4 gene were found. ICR mice were homozygous without mutation, NIH mice were partially heterozygous, and BALB/c mice were homozygous with a missense mutation. The expression of TLR4 was repressed while the downstream cytokines were upregulated after PT stimulation differently among mouse strains. The IFN-β cytokine of the TRIF pathway was significantly increased in ICR mice (p < 0.05). The IL-6 cytokine of the MyD88-dependent pathway was significantly increased in BALB/c mice (p < 0.05). The identified SNPs of the TLR4 gene in different mouse strains might account for the differences in cytokines levels determined after PT stimulation. Conclusions: Our studies might provide useful referees to reduce the mouse-derived difference in the determination of vaccine titer and increase the comparability of the vaccine from different origins, as different mouse strains were used for vaccine development in different countries. Full article

Rabies is a fatal neurological infectious disease caused by rabies virus (RABV), which invades the central nervous system (CNS). RABV with varying virulence regulates chemokine expression, and the mechanisms of signaling pathway activation remains to be elucidated. The relationship between Toll-like receptors (TLRs) and immune response induced by RABV has not been fully clarified. Here, we investigated the role of TLR7 in the immune response induced by RABV, and one-way analysis of variance (ANOVA) was employed to evaluate the data. We found that different RABV strains (SC16, HN10, CVS-11) significantly increased CCL2, CXCL10 and IL-6 production. Blocking assays indicated that the TLR7 inhibitor reduced the expression of CCL2, CXCL10 and IL-6 (p < 0.01). The activation of the Myd88 pathway in BV-2 cells stimulated by RABV was TLR7-dependent, whereas the inhibition of Myd88 activity reduced the expression of CCL2, CXCL10 and IL-6 (p < 0.01). Meanwhile, the RABV stimulation of BV-2 cells resulted in TRL7-mediated activation of NF-κB and induced the nuclear translocation of NF-κB p65. CCL2, CXCL10 and IL-6 release was attenuated by the specific NF-κB inhibitor used (p < 0.01). The findings above demonstrate that RABV-induced expression of CCL2, CXCL10 and IL-6 involves Myd88 and NF-κB pathways via the TLR7 signal. Full article

The Pulsatilla decoction is a well-known herbal remedy used in clinical settings for treating vulvovaginal candidiasis (VVC). However, the specific mechanism that makes it effective is still unclear. Recent studies have shown that in cases of VVC, neutrophils recruited to the vagina, influenced by heparan sulfate (HS), do not successfully engulf Candida albicans (C. albicans). Instead, they release many inflammatory factors that cause damage to the vaginal mucosa. This study aims to understand the molecular mechanism by which the n-butanol extract of Pulsatilla decoction (BEPD) treats VVC through transcriptomics. High-performance liquid chromatography was used to identify the primary active components of BEPD. A VVC mouse model was induced using an estrogen-dependent method and the mice were treated daily with BEPD (20 mg/kg, 40 mg/kg, and 80 mg/kg) for seven days. The vaginal lavage fluid of the mice was analyzed for various experimental indices, including fungal morphology, fungal burden, degree of neutrophil infiltration, and cytokines. Various assessments were then performed on mouse vaginal tissues, including pathological assessment, immunohistochemistry, immunofluorescence, Western blot (WB), quantitative real-time PCR, and transcriptome assays. Our results showed that BEPD reduced vaginal redness and swelling, decreased white discharge, inhibited C. albicans hyphae formation, reduced neutrophil infiltration and fungal burden, and attenuated vaginal tissue damage compared with the VVC model group. The high-dose BEPD group even restored the damaged vaginal tissue to normal levels. The medium- and high-dose groups of BEPD also significantly reduced the levels of IL-1β, IL-6, TNF-α, and LDH. Additionally, transcriptomic results showed that BEPD regulated several chemokine (CXCL1, CXCL3, and CXCL5) and S100 alarmin (S100A8 and S100A9) genes, suggesting that BEPD may treat VVC by affecting chemokine- and alarmin-mediated neutrophil chemotaxis. Finally, we verified that BEPD protects the vaginal mucosa of VVC mice by inhibiting neutrophil recruitment and chemotaxis in an animal model of VVC via the TLR4/MyD88/NF-κB pathway. This study provides further evidence to elucidate the mechanism of BEPD treatment of VVC. Full article

Aging is characterized by increased reactive species, leading to redox imbalance, oxidative damage, and senescence. The adverse effects of alcohol consumption potentiate aging-associated alterations, promoting several diseases, including liver diseases. Nucleoredoxin (NXN) is a redox-sensitive enzyme that targets reactive oxygen species and regulates key cellular processes through redox protein–protein interactions. Here, we determine the effect of chronic alcohol consumption on NXN-dependent redox interactions in the liver of aged mice. We found that chronic alcohol consumption preferentially promotes the localization of NXN either into or alongside senescent cells, declines its interacting capability, and worsens the altered interaction ratio of NXN with FLII, MYD88, CAMK2A, and PFK1 proteins induced by aging. In addition, carbonylated protein and cell proliferation increased, and the ratios of collagen I and collagen III were inverted. Thus, we demonstrate an emerging phenomenon associated with altered redox homeostasis during aging, as shown by the declining capability of NXN to interact with partner proteins, which is enhanced by chronic alcohol consumption in the mouse liver. This evidence opens an attractive window to elucidate the consequences of both aging and chronic alcohol consumption on the downstream signaling pathways regulated by NXN-dependent redox-sensitive interactions. Full article

Pyocyanin (PCN) is an extracellular toxin secreted by Pseudomonas aeruginosa (PA), which has redox capacity and disrupts the redox balance of host cells, affecting cell function and leading to cell death. The aim of this experiment was to compare the degree of apoptosis, inflammation, and oxidative stress of bovine mammary epithelium cells (bMECs) induced by lipopolysaccharide (LPS) and pyocyanin (PCN) and to examine whether PCN can promote the apoptosis, inflammation, and oxidative stress of bMECs induced by LPS. In this study, 1 µg/mL LPS and 1 µg/mL PCN were finally selected for subsequent experiments through dose-dependent experiments. In this study, cells were not given any treatment and were used as the control group (NC). The cells were treated with PCN or LPS individually for 6 h as the PCN group (PCN) or the LPS group (LPS), and the combination of LPS and PCN challenge for 6 h as the LPS + PCN (LPS + PCN) group. Compared with the control and LPS groups, PCN resulted in a significantly upregulated expression of genes related to pro-inflammatory (IL-6, TNF-α, MyD88), apoptotic (Bax, Caspase3, Caspase9), as well as protein expression of components in the TLR4/NF-κB signaling pathway (TLR4, p-p65, p65), and p53 signaling pathway (p-p53, p53, Caspase9) (p < 0.05). Moreover, the expression of genes and proteins was significantly upregulated after PCN treatment combined with LPS compared to either LPS or PCN challenge alone (p < 0.05). The stimulation of PCN combined with LPS significantly increased reactive oxygen species (ROS) and malondialdehyde (MDA) production in bovine mammary epithelial cells (bMECs), as well as decreased glutathione peroxidase (GSH-Px) and total antioxidant capacity (T-AOC). Moreover, cells in the LPS + PCN group aggravated oxidative stress and antioxidant inhibition in cells. In addition, the expression of the corresponding genes and proteins related to the Nrf2 pathway (Nrf2, HO-1) was significantly down-regulated in the PCN group as compared to the control group (p < 0.05). Altogether, PCN stimulation exacerbates inflammatory reactions, apoptosis, and oxidative stress reactions, as well as when combined with LPS challenge in bMECs. Therefore, this study indicates that PCN manifests a role in promoting apoptosis, inflammation, and oxidative stress and interacting with LPS to enhance more serious biological stress responses. Full article

The spleen and small intestines are the primary immune organs that provide important immunity against various diseases. Artemisia ordosica polysaccharide (AOP) could be used as an immunologic enhancer to boost immunity in response to infection. This study was performed to explore the effects of the dietary supplementation of AOP on the growth performance and spleen and small intestine immune function in broilers. A total of 288 AA broilers (1 day old) were randomly assigned into six dietary groups. Each group included six replicates of eight broilers per cage. The broilers were fed with a basal diet supplemented with 0 mg/kg (CON), 50 mg/kg chlortetracycline (CTC), 250, 500, 750, and 1000 mg/kg AOP for 42 d. The results showed that dietary AOP supplementation affected broiler growth performance, with 750 and 1000 mg/kg of AOP being able to significantly improve broiler BWG, and 750 mg/kg of AOP was able to significantly reduce the FCR. The dietary AOP supplementation increased the levels of IgA, IgG, IgM, IL-1β, IL-2, and IL-4 in the spleen and small intestine in a dose-dependent manner (p < 0.05). Meanwhile, we found that AOP can promote the mRNA expression of TLR4/MAPK/NF-κB signaling-pathway-related factors (TLR4, MyD88, P38 MAPK, JNK, NF-κB p50, and IL-1β). In addition, the dietary supplementation of 750 mg/kg AOP provides better immunity in the tissue than the CON group but showed no significant difference from the CTC group. Therefore, AOP has an immunoregulatory action and can modulate the immune function of broilers via the TLR4/ NF-ΚB/MAPK signal pathway. In conclusion, dietary supplementation with 750 mg/kg AOP may be alternatives to antibiotics for enhancing broilers’ health, immunity, and growth performance. Full article

Ethanol induces neuroinflammation, which is believed to contribute to the pathogenesis of alcohol use disorder (AUD). Toll-like receptors (TLRs) are a group of pattern recognition receptors (PRRs) expressed on both immune cells, including microglia and astrocytes, and non-immune cells in the central nervous system (CNS). Studies have shown that alcohol activates TLR4 signaling, resulting in the induction of pro-inflammatory cytokines and chemokines in the CNS. However, the effect of alcohol on signaling pathways downstream of TLR4, such as MyD88 and TRIF (TICAM) signaling, has not been evaluated extensively. In the current study, we treated male wild-type, TLR4-, MyD88-, and TRIF-deficient mice using a chronic plus binge mouse model of AUD. Evaluation of mRNA expression by qRT-PCR revealed that ethanol increased IL-1β, TNF-α, CCL2, COX2, FosB, and JunB in the cerebellum in wild-type and TRIF-deficient mice, while ethanol generally did not increase the expression of these molecules in TLR4- and MyD88-deficient mice. Furthermore, IRF3, IRF7, and IFN-β1, which are associated with the TRIF-dependent signaling cascade, were largely unaffected by alcohol. Collectively, these results suggest that the TLR4 and downstream MyD88-dependent signaling pathways are essential in ethanol-induced neuroinflammation in this mouse model of AUD. Full article