Histological evaluation of the alpaca (Vicugna pacos) vomeronasal organ.

Little is known about the neuronal structure of the vomeronasal organ (VNO), a receptor organ responsible for pheromone perception, in the alpaca (Vicugna pacos). This study was performed to determine the localization of neuronal elements, including protein gene product 9.5 (PGP 9.5), a pan-neuronal marker, olfactory marker protein (OMP), a marker of mature olfactory receptor cells, and phospholipase C beta 2 (PLC-ß2), a marker of solitary chemoreceptor cells (SCCs), in the VNO. OMP was identified in receptor cells of the vomeronasal sensory epithelium (VSE), while PGP 9.5 and PLC-ß2 were localized in both the VSE and vomeronasal non-sensory epithelium. Collectively, these results suggested that the alpaca VNO possesses SCCs and olfactory receptor cells, which recognize both harmful substances and pheromones.

Eugenol ameliorates uveitis in mice with experimental autoimmune encephalomyelitis through the suppression of key inflammatory genes.

Visual impairment associated with uveitis is among the potential complications in multiple sclerosis (MS) and its animal model, experimental autoimmune encephalomyelitis (EAE). Bioinformatics analyses have shown that some hub genes are closely associated with the molecular mechanisms underlying uveitis in EAE. This study evaluated whether 4-allyl-2-methoxyphenol (eugenol) can mitigate the pathogenesis of uveitis in EAE through the interruption of key uveitogenic gene expression. Myelin oligodendrocyte glycoprotein35-55 (MOG) peptide-immunized C57BL/6 mice were injected intraperitoneally with eugenol. The eyeballs and spinal cords of EAE mice with or without eugenol treatment were collected simultaneously and immunohistochemical and molecular biological analyses were conducted. Eugenol treatment significantly ameliorated hindlimb paralysis. Ionized calcium-binding adapter molecule 1 (Iba-1) immunohistochemistry showed that the inflammatory response was significantly reduced in the uvea of eugenol-treated EAE mice compared with vehicle-treated controls. Eugenol also significantly reduced the expression of key uveitogenic genes including C1qb and Tyrobp. The suppressive effect of eugenol on inflammation was also observed in the spinal cord, as determined by the suppression of Iba-1-positive microglial cells. Together, these results suggest that the ameliorative effect of eugenol against EAE uveitis is associated with the suppression of key proinflammatory genes, which may represent targets for the treatment of uveitis.

Key Genes in Olfactory Disorder in Experimental Autoimmune Encephalomyelitis Identified by Transcriptomic Analysis of the Olfactory Bulbs.

Experimental autoimmune encephalomyelitis (EAE) is an animal model of multiple sclerosis that shows demyelination in the central nervous system and functional deficits, including olfactory impairment. However, the genes related to olfactory impairment in EAE are unknown. We evaluated hub genes of the olfactory bulb in EAE mice. Differentially expressed genes (cut-offs, fold change > 2 and adjusted p < 0.05) and their related pathways in olfactory bulbs were subjected to gene ontology (GO) pathway analysis, gene set enrichment analysis (GSEA). Protein-protein interactions with selected genes were evaluated using the Search Tool for the Retrieval of Interacting Genes/Proteins. Gene regulatory networks (GRNs) which were constructed at the post-transcriptional level, including the genes-transcription factors (TFs) and gene-microRNAs (miRNAs) interaction networks. Twelve hub genes were found, three of which (Ctss, Itgb2, and Tlr2) were validated by RT-qPCR to be related to GO pathways such as immune response and regulation of immune response. GSEA showed that neuron-related genes-including Atp6v1g2, Egr1, and Gap43-and their pathways were significantly downregulated. GRNs analysis of six genes (Ctss, Itgb2, Tlr2, Atp6v1g2, Egr1, and Gap43) revealed 37 TFs and 84 miRNAs were identified as potential regulators of six genes, indicating significant interaction among six genes, TFs, and miRNAs. Collectively, these results suggest that transcriptomic analysis of the olfactory bulb of EAE mice can provide insight into olfactory dysfunction and reveal therapeutic targets for olfactory impairment.

Eugenol alleviates the symptoms of experimental autoimmune encephalomyelitis in mice by suppressing inflammatory responses.

Eugenol is a principal compound in essential clove oil, known for its anti-inflammatory and antioxidant properties. While recent studies have demonstrated its neuroprotective effects on central nervous system (CNS) injuries, such as brain ischemia/reperfusion injuries, but its potential impact on multiple sclerosis (MS), an autoimmune disease of the CNS, has not yet been explored. We evaluated the therapeutic effects of eugenol on experimental autoimmune encephalomyelitis (EAE), an established animal model of MS. EAE was induced in C57BL/6 mice using the myelin oligodendrocyte glycoprotein (MOG)35-55 peptide. Clinical symptoms, including paralysis, were monitored daily, and levels of pro-inflammatory mediators were evaluated using real-time quantitative polymerase chain reaction, Western blot analyses, and immunohistochemistry. Daily oral administration of eugenol to MOG-induced EAE mice led to a notable decline in the severity of clinical symptoms. Eugenol inhibited EAE-related immune cell infiltration and the production of pro-inflammatory mediators. Histological examinations confirmed its ability to mitigate inflammation and demyelination in the spinal cord post-EAE induction. Eugenol alleviates neuroinflammation in the spinal cords of EAE-induced mice, primarily through anti-inflammatory action.

Glycoconjugate-Specific Developmental Changes in the Horse Vomeronasal Organ.

The vomeronasal organ (VNO) is a tubular pheromone-sensing organ in which the lumen is covered with sensory and non-sensory epithelia. This study used immunohistochemistry and lectin histochemistry techniques to evaluate developmental changes, specifically of the glycoconjugate profile, in the horse VNO epithelium. Immunostaining analysis revealed PGP9.5 expression in some vomeronasal non-sensory epithelium (VNSE) cells and in the vomeronasal receptor cells of the vomeronasal sensory epithelium (VSE) in fetuses, young foals, and adult horses. Olfactory marker protein expression was exclusively localized in receptor cells of the VSE in fetuses, young foals, and adult horses and absent in VNSE. To identify the glycoconjugate type, lectin histochemistry was performed using 21 lectins. Semi-quantitative analysis revealed that the intensities of glycoconjugates labeled with WGA, DSL, LEL, and RCA120 were significantly higher in adult horse VSE than those in foal VSE, whereas the intensities of glycoconjugates labeled with LCA and PSA were significantly lower in adult horse VSE. The intensities of glycoconjugates labeled with s-WGA, WGA, BSL-II, DSL, LEL, STL, ConA, LCA, PSA, DBA, SBA, SJA, RCA120, jacalin, and ECL were significantly higher in adult horse VNSE than those in foal VNSE, whereas the intensity of glycoconjugates labeled with UEA-I was lower in adult horse VNSE. Histochemical analysis of each lectin revealed that various glycoconjugates in the VSE were present in the receptor, supporting, and basal cells of foals and adult horses. A similar pattern of lectin histochemistry was also observed in the VNSE of foals and adult horses. In conclusion, these results suggest that there is an increase in the level of N-acetylglucosamine (labeled by WGA, DSL, LEL) and galactose (labeled by RCA120) in horse VSE during postnatal development, implying that they may influence the function of VNO in adult horses.

Antibody-Conjugated Magnetic Nanoparticle Therapy for Inhibiting T-Cell Mediated Inflammation.

Tolerance induction is critical for mitigating T cell-mediated inflammation. Treatments based on anti-CD3 monoclonal antibody (mAb) play a pivotal role in inducing such tolerance. Anti-CD3 mAb conjugated with dextran-coated magnetic nanoparticles (MNPs) may induce inflammatory tolerance is posited. MNPs conjugated with anti-CD3 mAb (Ab-MNPs) are characterized using transmission and scanning electron microscopy, and their distribution is assessed using a nanoparticle tracking analyzer. Compared to MNPs, 90% of Ab-MNPs increased in size from 54.7 ± 0.5 to 71.7 ± 2.7 nm. The in vitro and in vivo studies confirmed the therapeutic material as nontoxic and biocompatible. Mice are administered various dosages of Ab-MNPs before receiving concanavalin-A (ConA), an inflammation inducer. Preadministration of Ab-MNPs, as opposed to MNPs or anti-CD3 mAb alone, significantly reduced the serum levels of interferon-γ and interleukin-6 in ConA-treated mice. Additionally, the transdermal stamp patch as an effective delivery system for Ab-MNPs is validated. This study demonstrates the utility of the Ab-MNP complex in pathologies associated with T cell-mediated hyperinflammation, such as organ transplantation and COVID-19.

Antioxidant effects of phenolic compounds in through the distillation of Lonicera japonica & Chenpi extract and anti-inflammation on skin keratinocyte.

The phenolic compounds in Lonicera japonica & Chenpi distillation extract (LCDE) were thoroughly examined for their antioxidant and anti-inflammatory properties. Phenolic compounds in LCDE were analyzed for five peaks using high-performance liquid chromatography (HPLC) combined with mass spectrometry (MS) and determined. Five phenolic compounds were identified from the samples and MS data. Ultrafiltration with LC analysis was used to investigate the ability of bioactive compounds to target DPPH. As a result, it was confirmed that the major compounds exhibited a high binding affinity to DPPH and could be regarded as antioxidant-active compounds. In addition, the anti-inflammatory effect of LCDE was confirmed in vitro, and signal inhibition of anti-inflammation cytokines, MAPK and NF-kB pathways was confirmed. Finally, Molecular docking analysis supplements the anti-inflammatory effect through the binding affinity of selected compounds and inflammatory factors. In conclusion, the phenolic compounds of the LCDE were identified and potential active compounds for antioxidant and anti-inflammatory activities were identified. Additionally, this study will be utilized to provide basic information for the application of LCDE in the pharmaceutical and pharmaceutical cosmetics industries along with information on efficient screening techniques for other medicinal plants.

Potential Joint Protective and Anti-Inflammatory Effects of Integrin αvß3 in IL-1ß-Treated Chondrocytes Cells.

In osteoarthritis (OA), the articular cartilage covering the articular surface of the bone wears out, exposing the subchondral bone, and the synovial membrane surrounding the joint becomes inflamed, causing pain and deformity. OA causes pain, stiffness, and swelling, and discomfort in the knee when climbing stairs is a typical symptom. Although drug development studies are conducted to treat these inflammatory joint diseases, it is difficult to find conclusive research results which could reduce inflammation and slow cartilage tear. The development of drugs to relieve inflammatory pain often utilizes inflammatory triggers. Interleukins, one of the proteins in the limelight as pro-inflammatory factors, are immune-system-stimulating factors that promote the body's fight against harmful factors such as bacteria. In this study, inflammation was induced in Chondrocytes cells (Chon-001 cells) with IL-1ß and then treated with integrin αvß3 to show anti-inflammatory and chondrogenesis effects. Integrin αvß3 was not toxic to Chon-001 cells in any concentration groups treated with or without IL-1ß. COX-2 and iNOS, which are major markers of inflammation, were significantly reduced by integrin αvß3 treatment. Expressions of p-ERK, p-JNK, and p-p38 corresponding to the MAPKs signaling pathway and p-IκBα and p-p65 corresponding to the NF-κB signaling pathway were also decreased in a dose-dependent manner upon integrin αvß3 treatment, indicating that inflammation was inhibited, whereas treatment with integrin αvß3 significantly increased the expression of ALP, RUNX2, BMP2, BMP4, Aggrecan, SOX9, and COL2A1, suggesting that osteogenesis and chondrogenesis were induced. These results suggest that integrin αvß3 in-duces an anti-inflammatory effect, osteogenesis, and chondrogenesis on IL-1ß-induced Chon-001 cells.

Potential Antioxidant and Anti-Inflammatory Effects of Lonicera japonica and Citri Reticulatae Pericarpium Polyphenolic Extract (LCPE).

Dermatitis is an inflammatory condition of the outer layer of the skin that causes itching, blisters, redness, swelling, and often exudation, scabs, and peeling. Among them, purulent inflammation is a symptom that often occurs on the skin and appears in the form of boils and acne. Various studies are being conducted to treat these inflammatory diseases. Accordingly, Lonicera japonica and Citri Reticulatae Pericarpium Polyphenolic Extract (LCPE), which uses herbal preparations such as Lonicera japonica, Citri Reticulatae Pericarpium, and Glycyrrhiza uralensis, has been used to suppress inflammation since ancient times, and its anti-inflammatory effect can be observed in skin keratinocytes after inducing inflammation. In this study, the major polyphenolic compounds in LCPE were quantitatively determined by analyzing the data through peak values using high-performance chromatography (HPLC-MS/MS) coupled with mass spectrometry. Additionally, bioactive compounds targeting 2,2-diphenyl-1-picrylhydrazyl (DPPH) were analyzed by ultrafiltration integrated with LC. Several compounds with the most significant effects were selected (chlorogenic acid, narirutin, and isorhamnetin). Skin keratinocytes induced by lipopolysaccharide (LPS) were treated with LCPE to show its anti-inflammatory effects. After LCPE treatment, inflammation-mediating cytokines such as cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) were decreased. In addition, nuclear factor kappa (NF-кB) and mitogen-activated protein kinase (MAPK) were inhibited in important pathways related to inflammation. Lastly, molecular modeling was performed to determine binding scores with inflammation-related proteins using molecular docking for the selected compounds. According to these results, LCPE is effective in treating keratinocytes induced by LPS and reducing inflammation and has potential antioxidant effects, and the polyphenol components have been identified.

Mechanistic Action of Cell Cycle Arrest and Intrinsic Apoptosis via Inhibiting Akt/mTOR and Activation of p38-MAPK Signaling Pathways in Hep3B Liver Cancer Cells by Prunetrin-A Flavonoid with Therapeutic Potential.

Hepatocellular carcinoma (HCC) has a poor prognosis and a low survival rate. Drugs without side effects are desperately needed since chemotherapy has a negative effect on the host cells. Previous research has firmly established that plant-based compounds have significant bioactivities without a negative impact on the host. Flavonoids, in particular, are a class of compounds with both anti-inflammatory and anti-cancer properties. Prunetrin (PUR) is a glycosyloxyisoflavone (Prunetin 4'-O-glucoside) derived from Prunus sp., and its other form, called prunetin, showed optimistic results in an anti-cancerous study. Hence, we aimed to discover the anti-cancer ability of prunetrin in liver cancer Hep3B cells. Our cytotoxicity results showed that PUR can decrease cell viability. The colony formation assay confirms this strongly and correlates with cell cytotoxicity results. Prunetrin, in a dose-dependent manner, arrested the cell cycle in the G2/M phase and decreased the expression of cyclin proteins such as Cyclin B1, CDK1/CDC2, and CDC25c. Prunetrin treatment also promoted the strong cleavage of two important apoptotic hallmark proteins called PARP and caspase-3. It also confirms that apoptosis occurs through the mitochondrial pathway through increased expression of cleaved caspase-9 and increased levels of the pro-apoptotic protein Bak. Bak was significantly increased with the declining expression of the anti-apoptotic protein Bcl-xL. Next, it inhibits the mTOR/AKT signaling pathways, proving that prunetrin includes apoptosis and decreases cell viability by suppressing these pathways. Further, it was also observed that the activation of p38-MAPK was dose-dependent. Taken together, they provide evidence that prunetrin has an anti-cancerous ability in Hep3B liver cancer cells by arresting the cell cycle via p38 and inhibiting mTOR/AKT.

Inhibition of Cell Proliferation and Cell Death by Apigetrin through Death Receptor-Mediated Pathway in Hepatocellular Cancer Cells.

Epidemiologic research recommends using flavonoids in the diet due to their overall health benefits. Apigetrin (Apigenin 7-O-glucoside) is a glycoside phytonutrient found in fruits and vegetables and known for different biological activities such as antioxidant and anti-inflammatory properties. Hepatocellular cancer (HCC) is a major health concern because of its adverse prognosis and side effects of chemotherapeutic agents. In the present study, we determine the impact of apigetrin on HepG2 cells and its cell death mechanism. Apigetrin reduced HepG2 cell proliferation with morphological changes and floating cells in treated cells. Colony formation and wound healing assays showed a reduced cell number in treatment groups. Further, we checked for the cell cycle through flow cytometry to understand the cell death mechanism. Apigetrin induced G2/M phase arrest in HepG2 cells by regulating Cyclin B1 and CDK1 protein levels in HepG2 cells. Annexin V and propidium iodide (PI) staining was performed to confirm the apoptotic cell population in treated groups. At the higher concentration, apigetrin showed a late apoptotic population in HepG2 cells. Chromatin condensation was also found in the treatment groups. Western blot analysis showed an increased expression of extrinsic apoptotic proteins such as FasL, Cleaved caspase 8, Cleaved caspase 3, and cleavage of PARP. In comparison, intrinsic apoptotic pathway markers showed no changes in Bax, Bcl-xL, and Cleaved caspase 9. Altogether, these findings strongly indicate that apigetrin causes cell death in HepG2 cells through the extrinsic apoptotic pathway, and that the intrinsic/mitochondrial pathway is not involved.

Flavones: The Apoptosis in Prostate Cancer of Three Flavones Selected as Therapeutic Candidate Models.

Cancer is a widespread but dangerous disease that can strike anyone and is the second 1leading cause of death worldwide. Prostate cancer, in particular, is a prevalent cancer that occurs in men, and much research is being done on its treatment. Although chemical drugs are effective, they have various side effects, and accordingly, anticancer drugs using natural products are emerging. To date, many natural candidates have been discovered, and new drugs are being developed as drugs to treat prostate cancer. Representative candidate compounds that have been studied to be effective in prostate cancer include apigenin, acacetin and tangeretin of the flavone family among flavonoids. In this review, we look at the effects of these three flavones on prostate cancer cells via apoptosis in vitro and in vivo. Furthermore, in addition to the existing drugs, we suggest the three flavones and their effectiveness as natural anticancer agents, a treatment model for prostate cancer.

Hepatoprotective effects of norgalanthamine on carbon tetrachloride induced-hepatotoxicity in mice.

Norgalanthamine is a major component of Crinum asiaticum var. japonicum that exhibits several biological activities. This study evaluated the anti-inflammatory and anti-oxidative properties of norgalanthamine in mice with carbon tetrachloride (CCl4)-induced liver injury. Norgalanthamine (1 and 10 mg/kg) was orally administered to mice for 7 or 14 days, after which liver injury was induced by CCl4 (1.5 ml/kg, i.p.). The vehicle and positive controls consisted of phosphate-buffered saline and silymarin (100 mg/kg), respectively. In CCl4-injured mice, norgalanthamine pretreatment significantly reversed the increases in serum alanine aminotransferase, aspartate aminotransferase, and total bilirubin levels, and the decrease in the serum glucose level. In the liver, norgalanthamine restored the activities of the antioxidant enzymes superoxide dismutase and catalase, while reducing lipid accumulation and, concurrently, the expression of genes involved in lipid synthesis, including peroxisome proliferator-activated receptor γ and adipocyte protein-2. Norgalanthamine also ameliorated inflammation by down-regulating the expression of the pro-inflammatory mediators, TNF-α, IL-1ß, and MCP-1, and up-regulating the Nrf2/HO-1 pathway. In addition, norgalanthamine decreased collagen deposition in liver tissue as shown on picrosirius red staining by down-regulating expression of the fibrosis-related genes αSMA and fibronectin. Collectively, these findings imply that norgalanthamine mitigates CCl4-induced hepatic injury by increasing anti-oxidative activity, down-regulating pro-inflammatory mediators and fibrosis-related genes in the liver.HighlightsNorgalanthamine ameliorated the hepatotoxicity after CCl4 injury.Norgalanthamine suppressed the activation of Kupffer cells and macrophages.Norgalanthamine down-regulated pro-inflammatory mediators.Norgalanthamine increased anti-oxidative activity via the Nrf2/HO-1 pathway.Norgalanthamine downregulated fibrosis-related genes in the liver.

Blood-retina barrier dysfunction in experimental autoimmune uveitis: the pathogenesis and therapeutic targets.

Experimental autoimmune uveitis (EAU), an animal model of human uveitis, is characterized by infiltration of autoimmune T cells in the uvea as well as in the retina of susceptible animals. EAU is induced by the immunization of uveitogenic antigens, including either retinal soluble-antigen or interphotoreceptor retinoid-binding proteins, in Lewis rats. The pathogenesis of EAU in rats involves the proliferation of autoimmune T cells in peripheral lymphoid tissues and breakdown of the blood-retinal barrier, primarily in the uvea and retina, finally inducing visual dysfunction. In this review, we describe recent EAU studies to facilitate the design of a therapeutic strategy through the interruption of uveitogenic factors during the course of EAU, which will be helpful for controlling human uveitis.

Unmet informatics needs of nurses regarding the use of personal smartphones in the workplace.

AIMS: This study aimed to investigate the differences in practices, policies, and perceptions of nurses regarding work-related utilization of smartphones in acute-care settings. BACKGROUND: Mobile devices utilizing emerging technology are widely used in acute-care settings; however, concerns such as potential distraction, improper use, and negative impact on the nursing image in clinical practice remain valid. METHODS: Nurse managers (n = 8) and nurses (n = 181) were enrolled from eight academic tertiary hospitals that have comprehensive electronic medical record systems and mobile versions. Between October 2018 and February 2019, participants completed a questionnaire designed to explore their use of smartphones. The reporting guide for self-administered surveys of clinicians was applied. RESULTS: Approximately 80% of nurses carried personal smartphones while working, with 70% using their devices for work. The prevalence of work-related smartphone use ranged from 3% to 43% by functionality, which was lower than that estimated by managers. Frequent uses included taking pictures/videos and internet browsing. Nurses were more positive than managers about the benefits of smartphone use and less burdened by related concerns. Novice and junior nurses were more optimistic than senior nurses. Only one hospital had a policy on nurses' use of personal devices at work. CONCLUSION: Two unmet needs in the current clinical information system were identified: information supporting task-related knowledge at the bedside and security of data capture and communication. IMPLICATION FOR NURSING POLICY: The unintended perception gaps between nurses and managers regarding work-related smartphone use can be closed by nursing leadership. Unmet nursing informatics, particularly for information-seeking purposes, can be addressed in the context of quality assurance. Nurse leaders can advocate secure and proper use of smartphones in clinical practice.

Osteopontin is a biomarker for early autoimmune uveoretinitis.

Osteopontin (OPN) is an extracellular matrix protein with a diverse range of functions, including roles in cell adhesion, migration, and immunomodulation, which are associated with the modulation of neuroinflammation in the central nervous system. The present study was performed to evaluate the involvement of OPN in the eyes of an experimental autoimmune uveoretinitis (EAU) model. The EAU model was developed by immunization of Lewis rats with interphotoreceptor retinoid-binding protein. The results showed the OPN level was remarkably upregulated in the eye of EAU rats on day 9 post-immunization. The level of CD44, a ligand of OPN, was increased in the ciliary body of EAU rats. Furthermore, OPN was also detected in the ciliary body and activated microglia/macrophages in the EAU retina. The results suggest that OPN was significantly upregulated in the eyes of EAU rats, and that it may be useful as an early biomarker of ocular autoimmune diseases. All animal experiments were approved by the Institutional Animal Care and Use Committee of Jeju National University (approval No. 2020-0012) on March 11, 2020.

Identification of Kynurenic Acid-Induced Apoptotic Biomarkers in Gastric Cancer-Derived AGS Cells through Next-Generation Transcriptome Sequencing Analysis.

Understanding the triggers and therapeutic targets for gastric cancer, one of the most common cancers worldwide, can provide helpful information for the development of therapeutics. RNA sequencing technology can be utilized to identify complex disease targets and therapeutic applications. In the present study, we aimed to establish the pharmacological target of Kynurenic acid (KYNA) for gastric cancer AGS cells and to identify the biological network. RNA sequencing identified differentially expressed genes (DEGs) between KYNA-treated and untreated cells. A total of 278 genes were differentially expressed, of which 120 genes were up-regulated, and 158 genes were down-regulated. Gene ontology results confirmed that KYNA had effects such as a reduction in genes related to DNA replication and nucleosome organization on AGS cells. Protein-protein interaction was confirmed through STRING analysis, and it was confirmed that cancer cell growth and proliferation were inhibited through KEGG, Reactome, and Wiki pathway analysis, and various signaling pathways related to cancer cell death were induced. It was confirmed that KYNA treatment reduced the gene expression of cancer-causing AP-1 factors (Fos, Jun, ATF, and JDP) in AGS cell lines derived from gastric cancer. Overall, using next-generation transcriptome sequencing data and bioinformatics tools, we confirmed that KYNA had an apoptosis effect by inducing changes in various genes, including factor AP-1, in gastric cancer AGS cells. This study can identify pharmacological targets for gastric cancer treatment and provide a valuable resource for drug development.

Attenuation of Experimental Autoimmune Uveitis in Lewis Rats by Betaine.

Experimental autoimmune uveitis (EAU) is an animal model of human autoimmune uveitis that is characterized by the infiltration of autoimmune T cells with concurrent increases in pro-inflammatory cytokines and reactive oxygen species. This study aimed to assess whether betaine regulates the progression of EAU in Lewis rats. EAU was induced via immunization with the interphotoreceptor retinoid-binding protein (IRBP) and oral administration of either a vehicle or betaine (100 mg/kg) for 9 consecutive days. Spleens, blood, and retinas were sampled from the experimental rats at the time of sacrifice and used for the T cell proliferation assay, serological analysis, real-time polymerase chain reaction, and immunohistochemistry. The T cell proliferation assay revealed that betaine had little effect on the proliferation of splenic T cells against the IRBP antigen in an in vitro assay on day 9 post-immunization. The serological analysis showed that the level of serum superoxide dismutase increased in the betainetreated group compared with that in the vehicle-treated group. The anti-inflammatory effect of betaine was confirmed by the downregulation of pro-inflammation-related molecules, including vascular cell adhesion molecule 1 and interleukin-1ß in the retinas of rats with EAU. The histopathological findings agreed with those of ionized calcium-binding adaptor molecule 1 immunohistochemistry, further verifying that inflammation in the retina and ciliary bodies was significantly suppressed in the betaine-treated group compared with the vehicle-treated group. Results of the present study suggest that betaine is involved in mitigating EAU through anti-oxidation and anti-inflammatory activities.