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Gut Jun 1975This review set out to answer several questions related to tumour immunology and the gut. It is evident that in patients with gastrointestinal cancer there is a general... (Review)
Review
This review set out to answer several questions related to tumour immunology and the gut. It is evident that in patients with gastrointestinal cancer there is a general depression of the immune response and this seems to be correlated with the stage of the disease. Paradoxically a specific immune response against definable tumour antigens can be demonstrated, both cellular and humoral mechanisms being involved although the complexities of this paradox require further analysis. Immunotherapy has been employed in gastrointestinal tumours in a sporadic way. The results suggest that gastrointestinal neoplasms may respond at least as well as other tumours. A firm conclusion awaits the results of controlled trials in which the bulk of the tumour has been effectively dealt with by other means or where combined immunochemotherapy is being used.
Topics: Animals; Antibody Formation; Antigens, Neoplasm; BCG Vaccine; Carcinoembryonic Antigen; Colonic Neoplasms; Cricetinae; Dinitrochlorobenzene; Gastrointestinal Neoplasms; Humans; Immunity, Cellular; Immunosuppression Therapy; Immunotherapy; Leukocyte Count; Lymph Nodes; Lymphocyte Activation; Mice; Neoplasms, Experimental; Nutritional Physiological Phenomena; Rats; Skin Tests; alpha-Fetoproteins
PubMed: 50255
DOI: 10.1136/gut.16.6.490 -
International Journal of Molecular... Aug 2023Atopic dermatitis (AD) is a common skin disease worldwide. The major causes of AD are skin barrier defects, immune dysfunction, and oxidative stress. In this study, we...
Atopic dermatitis (AD) is a common skin disease worldwide. The major causes of AD are skin barrier defects, immune dysfunction, and oxidative stress. In this study, we investigated the anti-oxidation and anti-inflammation effects of extract (CAE) and its regulation of the skin barrier and immune functions in AD. In vitro experiments revealed that CAE decreased the reactive oxygen species levels and inhibited the translocation of nuclear factor-κB (NF-κB), further reducing the secretion of interleukin (IL)-1β and IL-6 induced by interferon-γ (IFN-γ)/tumor necrosis factor-α (TNF-α). Moreover, CAE decreased IFN-γ/TNF-α-induced NLR family pyrin domain-containing 3 (NLRP3), caspase-1, high-mobility group box 1 (HMGB1), and receptor for advanced glycation end products (RAGE) expression levels. It also restored the protein levels of skin barrier function-related markers including filaggrin and claudin-1. In vivo experiments revealed that CAE not only reduced the redness of the backs of mice caused by 2,4-dinitrochlorobenzene (DNCB) but also reduced the levels of pro-inflammatory factors in their skin. CAE also reduced transepidermal water loss (TEWL) and immune cell infiltration in DNCB-treated mice. Overall, CAE exerted anti-oxidation and anti-inflammation effects and ameliorated skin barrier dysfunction, suggesting its potential as an active ingredient for AD treatment.
Topics: Mice; Animals; Dermatitis, Atopic; Inflammasomes; NLR Family, Pyrin Domain-Containing 3 Protein; Coffea; Tumor Necrosis Factor-alpha; Dinitrochlorobenzene; Skin; Antioxidants; Cytokines; Mice, Inbred BALB C
PubMed: 37569742
DOI: 10.3390/ijms241512367 -
The Journal of Investigative Dermatology Jul 1976Significant developments during the last 25 years are discussed and interpreted. The following areas of delayed hypersensitivity are included: the mode of active... (Review)
Review
Significant developments during the last 25 years are discussed and interpreted. The following areas of delayed hypersensitivity are included: the mode of active sensitization to simple allergenic chemicals; evidence for anamnestic responses; cell types and cell-cell interactions via lymphokines; function of skin and lymphatics, and the role of the carrier in initial sensitization to allergenic chemicals; acquired tolerance; transfer factor. Some prognostications for the future are attempted.
Topics: Amino Acids; Animals; B-Lymphocytes; Dermatitis, Atopic; Dermatitis, Contact; Dinitrochlorobenzene; Dinitrophenols; Freund's Adjuvant; Haptens; Humans; Hypersensitivity, Delayed; Immune Tolerance; Immunization; Immunologic Memory; Lymphatic System; Macrophages; Picryl Chloride; Skin; Skin Tests; T-Lymphocytes; Transfer Factor
PubMed: 778286
DOI: 10.1111/1523-1747.ep12513002 -
Molecules (Basel, Switzerland) Dec 2022Atopic dermatitis (AD) is a common chronic inflammatory skin disease. Bisdemethoxycurcumin (BDMC) is an ingredient from the rhizome of the traditional Chinese herbal...
Atopic dermatitis (AD) is a common chronic inflammatory skin disease. Bisdemethoxycurcumin (BDMC) is an ingredient from the rhizome of the traditional Chinese herbal medicine turmeric. BDMC has been reported to have important pharmacological properties, such as anti-inflammatory, antioxidant, antitumor and antiproliferative activities. However, its effect on atopic dermatitis has not been reported. The purpose of our study was to demonstrate the effectiveness of BDMC on TNF-α/IFNγ-stimulated HaCaT cells and on 2,4-dinitrochlorobenzene (DNCB)-induced AD mice. Our studies showed in vitro that BDMC was able to significantly inhibit the mRNA expression of chemokines and cytokines in TNF-α/IFN-γ-stimulated HaCaT cells and alleviate their inflammatory response. Our studies found in vivo that BDMC was able to significantly improve the symptoms of DNCB-induced AD skin lesions, decrease the number of scratches, ear thickness, and spleen index, improve inflammatory cells and mast cell infiltration and decrease skin thickness. Moreover, it was also able to inhibit the mRNA expression levels of chemokines and inflammatory cytokines and the activation of the MAPK and NF-κB signaling pathways. Thus, the results indicated that BDMC can improve atopic dermatitis in mice and that further clinical studies are warranted on its treatment of AD.
Topics: Animals; Mice; Dermatitis, Atopic; Dinitrochlorobenzene; Keratinocytes; Tumor Necrosis Factor-alpha; Skin; Cytokines; Chemokines; NF-kappa B; RNA, Messenger; Mice, Inbred BALB C
PubMed: 36615486
DOI: 10.3390/molecules28010293 -
Free Radical Biology & Medicine Dec 2013Ligand/receptor stimulation of cells promotes protein carbonylation that is followed by the decarbonylation process, which might involve thiol-dependent reduction (C.M....
Ligand/receptor stimulation of cells promotes protein carbonylation that is followed by the decarbonylation process, which might involve thiol-dependent reduction (C.M. Wong et al., Circ. Res. 102:301-318; 2008). This study further investigated the properties of this protein decarbonylation mechanism. We found that the thiol-mediated reduction of protein carbonyls is dependent on heat-labile biologic components. Cysteine and glutathione were efficient substrates for decarbonylation. Thiols decreased the protein carbonyl content, as detected by 2,4-dinitrophenylhydrazine, but not the levels of malondialdehyde or 4-hydroxynonenal protein adducts. Mass spectrometry identified proteins that undergo thiol-dependent decarbonylation, which include peroxiredoxins. Peroxiredoxin-2 and -6 were carbonylated and subsequently decarbonylated in response to the ligand/receptor stimulation of cells. siRNA knockdown of glutaredoxin inhibited the decarbonylation of peroxiredoxin. These results strengthen the concept that thiol-dependent decarbonylation defines the kinetics of protein carbonylation signaling.
Topics: Aldehydes; Animals; Cells, Cultured; Dinitrochlorobenzene; Glutaredoxins; Humans; Male; Malondialdehyde; Mercaptoethanol; Oxidative Stress; Peroxiredoxins; Phenylhydrazines; Protein Carbonylation; RNA Interference; RNA, Small Interfering; Rats; Rats, Sprague-Dawley; Reactive Oxygen Species; Sulfhydryl Compounds; Thioredoxins
PubMed: 24044890
DOI: 10.1016/j.freeradbiomed.2013.09.005 -
Animal Models and Experimental Medicine Jun 2023Amarogentin (AMA) is a secoiridoid glycoside extracted from Swertia and Gentiana roots and exhibits many biological effects such as antioxidative, anti-inflammatory, and...
BACKGROUND
Amarogentin (AMA) is a secoiridoid glycoside extracted from Swertia and Gentiana roots and exhibits many biological effects such as antioxidative, anti-inflammatory, and antitumor activities. Atopic dermatitis (AD) is a chronic inflammatory skin disease caused by disorders in the regulation of multiple inflammatory cytokines. No effective cure has been found for AD now.
METHODS
We constructed the HaCat and splenocyte model and tested the inhibitory effect of AMA on IL-4, IL-6, and IL-13 secretions using enzyme-linked immunosorbent assay (ELISA). The AD mouse model was constructed and treated with AMA, the severity of skin lesions was observed, epidermal tissue was collected, and epidermal thickness and mast cell infiltration were observed using hematoxylin and eosin and toluidine blue staining, respectively. The expression of kallikrein-related peptidase 7 (KLK7) and filaggrin (FLG) was detected using immunostaining and Western blot analysis. The mRNA expression of KLK7 and FLG was detected using quantitative polymerase chain reaction (qPCR). Blood immunoglobulin E (IgE) secretion was detected.
RESULTS
AMA inhibited IL-6 secreted by tumor necrosis factor (TNF)-α-induced HaCaT cells and reduced IL-4 and IL-13 secreted by phytohemagglutinin (PHA)-induced primary cells in the mice spleen. It was found that the treatment of AMA with 2,4-dinitrochlorobenzene-induced AD-like mice could promote the recovery of dermatitis, reduce the score of dermatitis severity and the scratching frequency, treat the skin lesions, reduce the epidermal thickness, decrease the infiltration of mast cells, reduce the IgE level in serum, decrease the expression levels of AD-related cytokines, increase protein and mRNA expression of FLG, and reduce the protein and mRNA expression of KLK7 in the skin tissues of AD-like mice.
CONCLUSION
In conclusion, AMA inhibits inflammatory response at the cellular level, and AMA reduces the validation response of specific dermatitis mice, relieves pruritus, and repairs the damaged skin barrier.
Topics: Animals; Mice; Humans; Dermatitis, Atopic; Dinitrochlorobenzene; Interleukin-13; Interleukin-6; HaCaT Cells; Interleukin-4; Cytokines; Tumor Necrosis Factor-alpha; Anti-Inflammatory Agents; Immunoglobulin E; RNA, Messenger
PubMed: 36131559
DOI: 10.1002/ame2.12260 -
International Journal of Trichology Jan 2010Alopecia Areata (AA) is a common non-scarring alopecia directed against the anagenic hair follicle. Various treatment modalities have been used for the treatment of...
Alopecia Areata (AA) is a common non-scarring alopecia directed against the anagenic hair follicle. Various treatment modalities have been used for the treatment of severe AA. Topical immunotherapy is the best documented treatment so far for severe and refractory AA. Dinitrochlorobenzene (DNCB), squaric acid dibutylester (SADBE), and diphencyprone (DPCP) are the contact allergens used for this purpose. DNCB has been found to be mutagenic by the Ames test and is largely replaced by DPCP and SADBE. DPCP and SADBE are both known to be non-mutagenic compounds and have comparable efficacy results and relapse rates. SADBE requires special solvents and additives to maintain its potency and is more expensive than the rest. DPCP has a response rate varying from 60% in severe Alopecia Areata to 17% in patients with alopecia totalis or universalis, and shows about 88 to 100% high response rate in patients with patchy Alopecia Areata.
PubMed: 21188022
DOI: 10.4103/0974-7753.66911 -
Zhong Nan Da Xue Xue Bao. Yi Xue Ban =... Jan 2023Ozone is widely applied to treat allergic skin diseases such as eczema, atopic dermatitis, and contact dermatitis. However, the specific mechanism remains unclear. This...
OBJECTIVES
Ozone is widely applied to treat allergic skin diseases such as eczema, atopic dermatitis, and contact dermatitis. However, the specific mechanism remains unclear. This study aims to investigate the effects of ozonated oil on treating 2,4-dinitrochlorobenzene (DNCB)-induced allergic contact dermatitis (ACD) and the underling mechanisms.
METHODS
Besides the blank control (Ctrl) group, all other mice were treated with DNCB to establish an ACD-like mouse model and were randomized into following groups: a model group, a basal oil group, an ozonated oil group, a FcεRI-overexpressed plasmid (FcεRI-OE) group, and a FcεRI empty plasmid (FcεRI-NC) group. The basal oil group and the ozonated oil group were treated with basal oil and ozonated oil, respectively. The FcεRI-OE group and the FcεRI-NC group were intradermally injected 25 µg FcεRI overexpression plasmid and 25 µg FcεRI empty plasmid when treating with ozonated oil, respectively. We recorded skin lesions daily and used reflectance confocal microscope (RCM) to evaluate thickness and inflammatory changes of skin lesions. Hematoxylin-eosin (HE) staining, real-time PCR, RNA-sequencing (RNA-seq), and immunohistochemistry were performed to detct and analyze the skin lesions.
RESULTS
Ozonated oil significantly alleviated DNCB-induced ACD-like dermatitis and reduced the expressions of IFN-γ, IL-17A, IL-1β, TNF-α, and other related inflammatory factors (all P<0.05). RNA-seq analysis revealed that ozonated oil significantly inhibited the activation of the DNCB-induced FcεRI/Syk signaling pathway, confirmed by real-time PCR and immunohistochemistry (all P<0.05). Compared with the ozonated oil group and the FcεRI-NC group, the mRNA expression levels of IFN-γ, IL-17A, IL-1β, IL-6, TNF-α, and other inflammatory genes in the FcεRI-OE group were significantly increased (all P<0.05), and the mRNA and protein expression levels of FcεRI and Syk were significantly elevated in the FcεRI-OE group as well (all P<0.05).
CONCLUSIONS
Ozonated oil significantly improves ACD-like dermatitis and alleviated DNCB-induced ACD-like dermatitis via inhibiting the FcεRI/Syk signaling pathway.
Topics: Animals; Mice; Dinitrochlorobenzene; Skin; Cytokines; Interleukin-17; Tumor Necrosis Factor-alpha; Dermatitis, Allergic Contact; Dermatitis, Atopic; Signal Transduction; RNA, Messenger; Mice, Inbred BALB C
PubMed: 36935172
DOI: 10.11817/j.issn.1672-7347.2023.220082 -
Molecular Medicine Reports May 2021Atopic dermatitis (AD) is a chronic inflammatory skin disease that seriously affects quality of life. Quinine is a bitter taste receptor agonist that exhibits...
Atopic dermatitis (AD) is a chronic inflammatory skin disease that seriously affects quality of life. Quinine is a bitter taste receptor agonist that exhibits antimalarial effects. The aim of the present study was to examine the therapeutic effects of quinine in AD‑like mice. AD was induced with 2,4‑dinitrochlorobenzene, and the mice were treated with 10 mg/kg quinine for 1, 4 and 7 days. A total of 60 BALB/c mice were divided into the following groups: Healthy, AD‑like, AD‑like + quinine and healthy + quinine, with 1, 4 and 7 days groups for each treatment. Blood was extracted from all mice and ELISA was performed to detect immunoglobulin E (IgE) levels. H&E‑stained tissue sections were prepared from skin lesions on the backs of the mice and pathological changes were observed. Cytokines were detected via ELISA, and the filaggrin (FLG) and kallikrein‑7 (KLK7) proteins were detected via western blotting and immunohistochemistry. IKKα and NF‑κB mRNA were analyzed via reverse transcription‑quantitative PCR. Quinine ameliorated skin damage in the AD‑like mice, reduced IgE expression in the blood, inhibited expression of IKKα and NF‑κB, reduced cytokine secretion, reduced KLK7 expression, reduced scratching frequency, increased FLG expression and repaired the skin barrier. These results suggested that quinine exhibited therapeutic effects in AD‑like mice.
Topics: Animals; Cytokines; Dermatitis, Atopic; Dinitrochlorobenzene; Disease Models, Animal; I-kappa B Kinase; Immunoglobulin E; Kallikreins; Male; Mice, Inbred BALB C; NF-KappaB Inhibitor alpha; NF-kappa B; Quinine; Receptor, Fibroblast Growth Factor, Type 1; Signal Transduction; Skin; Mice
PubMed: 34240224
DOI: 10.3892/mmr.2021.11952 -
BioMed Research International 2022and scopoletin are widely used in oriental Eastern medicine and are often consumed as teas. In this study, proinflammatory cytokines expressed in human keratinocytes...
and scopoletin are widely used in oriental Eastern medicine and are often consumed as teas. In this study, proinflammatory cytokines expressed in human keratinocytes (HaCaT) were induced by skin diseases caused by 2,4-dinitrochlorobenzene (DNCB) and tumor necrosis factor alpha (TNF-)/interferon gamma (IFN-). The inhibitory activity of EtOH extract (LBE) and scopoletin on proinflammatory cytokines and chemokines was investigated. In the DNCB-induced animal model, oral administration of LBE inhibited skin lesions and proinflammatory cytokines and chemokines and showed inhibitory effects . Additionally, as a result of examining the efficacy of scopoletin isolated from , scopoletin in HaCaT cells showed inhibitory effects on proinflammatory cytokines and chemokines. It shows promise in the treatment of chronic skin diseases.
Topics: Animals; Anti-Inflammatory Agents; Chemokines; Cytokines; Dermatitis, Atopic; Dinitrochlorobenzene; Humans; Inflammation; Interferon-gamma; Lycium; Mice; Mice, Inbred BALB C; Plant Extracts; Scopoletin; Skin; Tumor Necrosis Factor-alpha
PubMed: 36158872
DOI: 10.1155/2022/2475699