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Nitric Oxide : Biology and Chemistry Apr 2024Neuronal differentiation of adipose tissue-derived stem cells (ASCs) is greatly promoted by valproic acid (VPA) with cAMP elevating agents thorough NO signaling...
Neuronal differentiation of adipose tissue-derived stem cells (ASCs) is greatly promoted by valproic acid (VPA) with cAMP elevating agents thorough NO signaling pathways, but its mechanism is not fully understood. In the present study, we investigate the involvement of protein S-nitrosylation in the VPA-promoted neuronal differentiation of ASCs. The whole amount of S-nitrosylated protein was increased by the treatment with VPA alone for three days in ASCs. An inhibitor of thioredoxin reductase (TrxR), auranofin, further increased the amount of S-nitrosylated protein and enhances the VPA-promoted neuronal differentiation in ASCs. On the contrary, another inhibitor of TrxR, dinitrochlorobenzene, inhibited the VPA-promoted neuronal differentiation in ASCs even with cAMP elevating agents, which was accompanied by unexpectedly decreased S-nitrosylated protein. It was considered from these results that increased protein S-nitrosylation is involved in VPA-promoted neuronal differentiation of ASCs. By the proteomic analysis of S-nitrosylated protein in VPA-treated ASCs, no identified proteins could be specifically related to VPA-promoted neuronal differentiation. The identified proteins, however, included those involved in the metabolism of substances regulating neuronal differentiation, such as aspartate and glutamate.
Topics: Valproic Acid; Neurons; Proteomics; Stem Cells; Adipose Tissue
PubMed: 38382865
DOI: 10.1016/j.niox.2024.02.004 -
Biomedicine & Pharmacotherapy =... Mar 2024Atopic dermatitis (AD) is a chronic inflammatory skin condition primarily driven by T helper 2 (Th2) cytokines, resulting in skin barrier defects, angiogenesis, and...
Atopic dermatitis (AD) is a chronic inflammatory skin condition primarily driven by T helper 2 (Th2) cytokines, resulting in skin barrier defects, angiogenesis, and inflammatory responses. The marine natural product excavatolide B (EXCB), isolated from the Formosan Gorgonian coral Briareum stechei, exhibits anti-inflammatory and analgesic properties. To enhance solubility, EXCB is chemically modified into the derivatives EXCB-61 salt and EXCB-79. The study aims to investigate the therapeutic effects of these compounds on dinitrochlorbenzene (DNCB)-induced skin damage and to elucidate the underlying anti-inflammatory and anti-angiogenesis mechanism. In vitro, using lipopolysaccharide (LPS)-induced RAW 264.7 cells, all compounds at 10 μM significantly inhibited expression of inflammatory proteins (inducible nitric oxide synthase and cyclooxygenase-2), vascular endothelial growth factor (VEGF), and cytokines (interleukin (IL)-1β, IL-6, and IL-17A). In vivo, topical application of these compounds on DNCB-induced AD mice alleviated skin symptoms, reduced serum levels of IgE, IL-4, IL-13, IL-17, and interferon-γ, and moderated histological phenomena such as hyperplasia, inflammatory cell infiltration, and angiogenesis. The three compounds restored the expression of skin barrier-related proteins (loricrin, filaggrin, and claudin-1) and reduced the expression of angiogenesis-related proteins (VEGF and platelet endothelial cell adhesion molecule-CD31) in the tissues. This is the first study to indicate that EXCB, EXCB-61 salt, and EXCB-79 can treat AD disease by reducing inflammation and angiogenesis. Hence, they may be considered potential candidates for the development of new drugs for AD.
Topics: Animals; Mice; Dermatitis, Atopic; Angiogenesis Inhibitors; Vascular Endothelial Growth Factor A; Dinitrochlorobenzene; Cytokines; Angiogenic Proteins; Anti-Inflammatory Agents; Diterpenes
PubMed: 38368838
DOI: 10.1016/j.biopha.2024.116279 -
Environmental Toxicology May 2024Yin chai hu (Radix Stellariae) is a root medicine that is frequently used in Chinese traditional medicine to treat fever and malnutrition. In modern medicine, it has...
Supercritical CO fluid extract from Stellariae Radix ameliorates 2,4-dinitrochlorobenzene-induced atopic dermatitis by inhibit M1 macrophages polarization via AMPK activation.
Yin chai hu (Radix Stellariae) is a root medicine that is frequently used in Chinese traditional medicine to treat fever and malnutrition. In modern medicine, it has been discovered to have anti-inflammatory, anti-allergic, and anticancer properties. In a previous study, we were able to extract lipids from Stellariae Radix using supercritical CO extraction (SRE), and these sterol lipids accounted for up to 88.29% of the extract. However, the impact of SRE on the development of atopic dermatitis (AD) has not yet been investigated. This study investigates the inhibitory effects of SRE on AD development using a 2,4-dinitrochlorobenzene (DNCB)-induced AD mouse model. Treatment with SRE significantly reduced the dermatitis score and histopathological changes compared with the DNCB group. The study found that treatment with SRE resulted in a decrease of pro-inflammatory cytokines TNF-α, CXC-10, IL-12, and IL-1β in skin lesions. Additionally, immunohistochemical analysis revealed that SRE effectively suppressed M1 macrophage infiltration into the AD lesion. Furthermore, the anti-inflammatory effect of SRE was evaluated in LPS + INF-γ induced bone marrow-derived macrophages (BMDMs) M1 polarization, SRE inhibited the production of TNF-α, CXC-10, IL-12, and IL-1β and decreased the expression of NLRP3. Additionally, SRE was found to increase p-AMPK, but had no effect on total AMPK expression, after administration of the AMPK inhibitor Compound C, the inhibitory effect of SRE on M1 macrophages was partially reversed. The results indicate that SRE has an inhibitory effect on AD, making it a potential therapeutic agent for this atopic disorder.
Topics: Animals; Mice; Dermatitis, Atopic; Dinitrochlorobenzene; AMP-Activated Protein Kinases; Carbon Dioxide; Tumor Necrosis Factor-alpha; Cytokines; Macrophages; Anti-Inflammatory Agents; Interleukin-12; Lipids; Mice, Inbred BALB C; Skin
PubMed: 38356236
DOI: 10.1002/tox.24145 -
Nutrients Feb 2024Atopic dermatitis (AD) is a persistent inflammatory skin condition resulting from an intricate interplay among genetic, immunological, and environmental factors. (EA),...
Atopic dermatitis (AD) is a persistent inflammatory skin condition resulting from an intricate interplay among genetic, immunological, and environmental factors. (EA), an annual winter plant belonging to the family Asteraceae, possesses anti-inflammatory, cytoprotective, and antioxidant activities. In this study, we hypothesized that extract (EAE) could be an effective agent for ameliorating AD-like symptoms. To confirm this hypothesis in vitro, we used HO-stimulated human keratinocytes (HaCaT cells) to demonstrate that pre-treatment with EAE protected against oxidative stress. HaCaT cells pretreated with EAE and stimulated with HO showed decreased intracellular malondialdehyde content, increased superoxide dismutase activity, and reduced intracellular reactive oxygen species accumulation. To verify the in vivo hypothesis based on the intracellular results, an AD disease mouse model was induced with 1-chloro-2,4-dinitrobenzene (DNCB), and EAE was orally administered at a non-toxic concentration according to the toxicity evaluation results. The results showed that AD disease models in BALB/c mice exhibited reduced ear epidermal thickness, scratching behavior, and mast cell infiltration. In conclusion, our results indicate that EAE has the potential to improve AD by upregulating the nuclear factor erythroid 2-related factor 2 (Nrf2)/heme oxygenase-1 (HO-1) signaling pathway.
Topics: Humans; Animals; Mice; Dermatitis, Atopic; Skin; Dinitrochlorobenzene; Erigeron; NF-E2-Related Factor 2; Dinitrobenzenes; Heme Oxygenase-1; Hydrogen Peroxide; Tumor Necrosis Factor-alpha; Mice, Inbred BALB C; Cytokines
PubMed: 38337735
DOI: 10.3390/nu16030451 -
Journal of Biomedical Materials... Feb 2024In vivo skin sensitization tests are required to evaluate the biological safety of medical devices in contact with living organisms to provide safe medical care to...
In vivo skin sensitization tests are required to evaluate the biological safety of medical devices in contact with living organisms to provide safe medical care to patients. Negative and positive reference materials have been developed for biological tests of cytotoxicity, implantation, hemolysis, and in vitro skin irritation. However, skin sensitization tests are lacking. In this study, polyurethane sheets containing 1 wt/wt % 2,4-dinitrochlorobenzene (DNCB-PU) were developed and evaluated as a positive reference material for skin sensitization tests. DNCB-PU sheet extracts prepared with sesame oil elicited positive sensitization responses for in vivo sensitization potential in the guinea pig maximization test and the local lymph node assay. Furthermore, DNCB-PU sheet extracts prepared with water and acetonitrile, 10% fetal bovine serum-containing medium, or sesame oil elicited positive sensitization responses as alternatives to animal testing based on the amino acid derivative reactivity assay, human cell line activation test, and epidermal sensitization assay, respectively. These data suggest that the DNCB-PU sheet is an effective extractable positive reference material for in vivo and in vitro skin sensitization testing in medical devices. The formulation of this reference material will lead to the development of safer medical devices that contribute to patient safety.
Topics: Humans; Animals; Guinea Pigs; Dinitrochlorobenzene; Proof of Concept Study; Sesame Oil; Skin; Epidermis
PubMed: 38334720
DOI: 10.1002/jbm.b.35386 -
The Journal of Investigative Dermatology Feb 2024This study investigated the role of CD226 in a 2,4-dinitrochlorobenzene (DNCB)-induced mouse model of atopic dermatitis. The results showed that the lack of CD226...
This study investigated the role of CD226 in a 2,4-dinitrochlorobenzene (DNCB)-induced mouse model of atopic dermatitis. The results showed that the lack of CD226 (global and CD4 T-cell specific) significantly increased ear thickness, reddening, swelling, and scaling of the skin as well as inflammatory cell and mast cell infiltration. RT-qPCR results demonstrated that the mRNA expressions of atopic dermatitis-related inflammatory cytokines and chemokines were markedly increased in the draining lymph nodes and lesioned ear skin tissues of global and CD4 T-cell-specific CD226-deficient mice compared with that in control mice. In vitro assessment revealed that CD226 directly modulates TGFβ-mediated regulatory T (Treg) cell differentiation and proliferation. Notably, Treg cell-specific deletion of CD226 (Cd226Foxp3 mice) resulted in more severe dermatitis and epidermal thickening than those observed in littermate mice upon DNCB treatment. Subsequent analysis showed that the infiltration of Treg cells in ear lesions and the number of Tregs in the spleen were significantly reduced in Cd226Foxp3 mice after DNCB treatment. In addition, the lack of CD226 induced apoptosis of Treg cells through the activation of caspase 3. Therefore, these results suggest that CD226 has potential efficacy in atopic dermatitis, correlating with Treg cell inhibition.
PubMed: 38325579
DOI: 10.1016/j.jid.2024.01.022 -
Current Medicinal Chemistry Jan 2024Nepetin is a type of O-methylated flavone (6-hydroxy luteolin) and has been found in many herbal medicines that exhibit various pharmacological properties, including...
Nepetin is a type of O-methylated flavone (6-hydroxy luteolin) and has been found in many herbal medicines that exhibit various pharmacological properties, including anti-inflammatory responses. Here, we aimed to investigate the efficacy of nepetin in attenuating inflammatory responses in cultured keratinocytes and 2,4-dinitrochlorobenzene (DNCB)-induced atopic dermatitis (AD) in BALB/c mice. Various assay methods including cell viability, flow cytometry, fluorometry, confocal microscopy, western blot, ELISA techniques, staining methods, score and scratch frequency assessment, etc. were employed to explore the mechanisms. LPS-treated keratinocytes showed a significant increase in inflammatory mediators (iNOS, COX-2, PGES2, and NO) and cytokines (IL-1β, IL-6, and TNF-α) in a dose-dependent manner. Treatment with nepetin prevented LPS-induced cell death and inhibited inflammatory mediators and the production of cytokines in cultured keratinocytes. This inhibition was achieved by nepetin, which inhibited LPS-induced ROS production and the translocation of NF-κB in the cultures, thereby inhibiting the generation of inflammatory mediators and/or cytokines. In a mouse model of AD, treatment with nepetin reduced skin inflammation symptoms in a dose-dependent manner, as evidenced by the significant reduction of inflammation- related cytokines, skin lesions, and behavior scores. Based on the present in vitro and in vivo study, nepetin is the safest bioactive compound with potential therapeutic applications for AD-related skin lesions and adverse skin reactions.
PubMed: 38310399
DOI: 10.2174/0109298673244967231101114033 -
Journal of Cutaneous Medicine and... 2024Prurigo nodularis (PN) is a skin disease characterized by firm, itchy, erythematous lesions. Treatment consists of systemic and non-systemic modes of therapy.... (Review)
Review
Prurigo nodularis (PN) is a skin disease characterized by firm, itchy, erythematous lesions. Treatment consists of systemic and non-systemic modes of therapy. Non-systemic forms of treatment are first-line and include topical corticosteroids, topical steroid-sparing agents, and phototherapy. The objective was to review the efficacy of non-systemic treatment used to treat PN. A systematic search was conducted in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines and registered with PROSPERO (CRD42023412012). The search consisted of keywords and Medical Subject Heading (MeSH) terms and translated to Ovid MEDLINE, Embase, and Scopus. Google Scholar was also searched for the first 200 articles. Article quality of evidence was scored using GRADE criteria. The search yielded 1151 results; 37 met criteria for inclusion. There were 14 studies on phototherapy, and 11 studies on topical corticosteroids, most of which were also combined with topical antihistamines, antipruritics, and/or phototherapy. There were 2 studies each on topical antipruritics used in isolation, vitamin D analogues, and intralesional triamcinolone acetonide. There was 1 study each on topical pimecrolimus, tacrolimus, 2% dinitrochlorobenzene, cryotherapy, acupuncture, and the Paul Gerson Unna boot. Most were case reports and case series, although 2 randomized controlled trials on phototherapy and topical pimecrolimus were included. Corticosteroids had varying levels of positive response in patients and appeared more effective when used in combination or under occlusive dressing. Phototherapy is likely effective, but the risk of relapse is high. Cryotherapy may also be a lesion-directed agent to circumvent challenges to adherence and avoidance of systemic medication.
Topics: Humans; Antipruritics; Prurigo; Tacrolimus; Dermatologic Agents; Adrenal Cortex Hormones
PubMed: 38291823
DOI: 10.1177/12034754241227634 -
Marine Drugs Jan 2024This study investigated the antioxidant, antimicrobial, and anti-atopic dermatitis (AD) effects of a novel peptide (CP) derived from a by-product hydrolysate. Alcalase,...
This study investigated the antioxidant, antimicrobial, and anti-atopic dermatitis (AD) effects of a novel peptide (CP) derived from a by-product hydrolysate. Alcalase, Flavourzyme, Neutrase, and Protamex enzymes were used to hydrolyze the by-product protein, and the 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) radical-scavenging activity was measured. Alcalase hydrolysate exhibited the highest ABTS radical-scavenging activity, leading to the selection of Alcalase for further purification. The CHAO-1-I fraction, with the highest ABTS activity, was isolated and further purified, resulting in the identification of the peptide CP with the amino acid sequence Ala-Gln-Val-Met-Lys-Leu-Pro-His-Arg-Met-Gln-His-Ser-Gln-Ser. CP demonstrated antimicrobial activity against , inhibiting its growth. In a 2,4-dinitrochlorobenzene (DNCB)-induced AD-like skin model in mice, CP significantly alleviated skin lesions, reduced epidermal and dermal thickness, and inhibited mast cell infiltration. Moreover, CP suppressed the elevated levels of interleukin-6 (IL-6) in the plasma of DNCB-induced mice. These findings highlight the potential of CP as a therapeutic agent for AD and suggest a novel application of this by-product in the fish processing industry.
Topics: Animals; Mice; Dermatitis, Atopic; Hydrolysis; Antioxidants; Dinitrochlorobenzene; Anti-Bacterial Agents; Peptides; Perciformes; Subtilisins; Sulfonic Acids; Benzothiazoles
PubMed: 38248669
DOI: 10.3390/md22010044 -
Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi =... Jan 2024Objective To explore the significance of interleukin-17C(IL-17C)-mediated follicular helper T cell (Tfh) differentiation in atopic dermatitis (AD) model. Methods BALB/c...
Objective To explore the significance of interleukin-17C(IL-17C)-mediated follicular helper T cell (Tfh) differentiation in atopic dermatitis (AD) model. Methods BALB/c mice were divided into control group, AD model group, low-dose MOR106 (anti-IL-17C huIgG1)(MDR106-L)treatment group and high-dose MOR106 (MOR106-H) treatment group, 8 mice in each group. Except for the control group, all the other groups were treated with 2, 4- dinitrochlorobenzene (DNCB) to establish AD models. The low-dose and high-dose MOR106 groups were treated with 5 mg/kg or 10 mg/kg MOR106 respectively. The differentiation of Tfh cell subsets in peripheral blood of mice was analyzed by flow cytometry, and the expression of Janus kinase 2/signal transducer and activator of transcription 3(JAK2/STAT3) signal pathway protein in skin tissue was detected by Western blot analysis. Results Compared with the control group, the dermatitis severity score, mass difference between two ears, spleen mass and spleen index of DNCB group increased significantly, while those of MOR106-L group and MOR106-H group decreased significantly. Compared with the control group, the Tfh subgroup of AD mice showed deregulated differentiation, resulting in a significant increase in the percentage of CD4CXCR5IFN-γTfh1 cells, CD4CXCR5IL-17ATfh17 and CD4CXCR5IL-21Tfh21 cells, and a significant decrease in the percentage of CD4CXCR5IL-10Tfh10 cells and CD4CXCR5FOXP3Tfr cells in peripheral blood. The protein levels of phosphorylated JAK2(p-JAK2) and p-STAT3 were significantly increased. MOR106 effectively reversed these changes of Tfh1, Tfh10, Tfh17, Tfh21 and Tfr cells in peripheral blood of AD mice. Compared with AD group, the levels of p-JAK2 and p-STAT3 protein in low-dose and high-dose MOR106 treatment groups decreased significantly. Conclusion MOR106 can reduce the inflammatory response of AD mice by blocking JAK2/STAT3 signaling pathway and inhibiting the differentiation of Tfh cells mediated by IL-17C.
Topics: Animals; Mice; Dermatitis, Atopic; Interleukin-17; T Follicular Helper Cells; Janus Kinase 2; Dinitrochlorobenzene; Inflammation; Cell Differentiation; Signal Transduction
PubMed: 38246174
DOI: No ID Found