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Frontiers in Pharmacology 2022Atopic dermatitis (AD) is a chronic and recurrent skin disease. At present, there is a lack of sufficiently effective and safe medicines that can be used for a...
Atopic dermatitis (AD) is a chronic and recurrent skin disease. At present, there is a lack of sufficiently effective and safe medicines that can be used for a prolonged time and reduce the recurrence of AD. The Gu-Ben-Hua-Shi (AESS) formula has been used for many years with a good clinical effect on AD but its specific treatment mechanism is unknown. The main components of AESS were analyzed using ultra-high performance liquid chromatography (UPLC). The composition of AESS compounds in the serum from rats was analyzed using ultra-high performance liquid chromatography-mass spectrometry. An AD mouse model was constructed using 2,4-dinitrofluorobenzene stimulation in Balb/C mice and the effect on the reduction of skin lesions and Th1/Th2/Th17/Treg balance after AESS administration were measured. The effects of AESS serum on the proliferation and apoptosis of keratinocyte cell line HaCaT and adhesion of HaCaT to human monocyte cell line THP-1 were detected in an IFN-γ/TNF-α stimulated AD-like inflammatory cell model. The effects of Yes-associated protein (YAP) expression on the therapeutic effect and a related signaling pathway were also investigated. In total, 10 components were confirmed using UPLC, namely five organic acids, three flavonoids, and two chromogenic ketones. Additionally, the similarity of the three batches of samples (S1-3) was above 0.98, indicating that the formula samples have good uniformity. These 10 compounds were also detected in rat serum, suggesting that they are absorbed into rat blood as prototype components. Furthermore, AESS effectively reduced the skin lesions in the AD mouse model, regulated the Th1/Th2/Th17/Treg imbalance, improved the proliferation ability of the AD-like cell model, and inhibited HaCaT apoptosis and adhesion to THP-1 cells. It also reduced the expression of YAP in Th17 and Treg cells of the mouse spleen and increased YAP expression in the skin. The change in YAP expression in keratinocytes weakened the curative effect of AESS, and AESS exerted its effects through the NF-κB signaling pathway. AESS may play a role in the treatment of AD by affecting the expression of YAP. These findings can be used to promote its use as an alternative medication for prolonged use with fewer side effects.
PubMed: 36313294
DOI: 10.3389/fphar.2022.929580 -
Frontiers in Pharmacology 2022Numerous clinical studies have shown that atopic dermatitis (AD) is often associated with mental disorders. This could contribute to the overall burden of atopic...
Numerous clinical studies have shown that atopic dermatitis (AD) is often associated with mental disorders. This could contribute to the overall burden of atopic dermatitis. However, the underlying mechanism of mental health symptoms in AD has not been fully elucidated. An AD mouse was induced by 2,4-dinitrofluorobenzene (DNFB), which was repeatedly applied to the back skin of the BALB/C mice to establish an atopic dermatitis mental disorder model. The role of neuroinflammation in the pathogenesis of atopic dermatitis mental disorders was then explored. After the stimulation of DNFB for 35 days, the skin lesions, the HE staining of skin lesions, and the behavioral experiments (including elevated plus maze assay and tail suspension test) suggested that the AD mental disorder mouse model was successfully replicated. The expression of neuroinflammatory factors in the hippocampus was then investigated through Western blotting. The results showed a significant increase in the protein expression of NLRP3, caspase-1, and IL-1β. Mental disorders in AD might be related to the neuroinflammatory response in the hippocampus. An alternative yet essential approach to promoting AD recovery could be through reducing neuroinflammation and improving mental disorders.
PubMed: 36267291
DOI: 10.3389/fphar.2022.966279 -
International Journal of Molecular... Sep 2022Atopic dermatitis (AD) is a chronic and recurrent inflammatory skin disease, characterized by severe itching and recurrent skin lesions. We hypothesized that a novel...
Atopic dermatitis (AD) is a chronic and recurrent inflammatory skin disease, characterized by severe itching and recurrent skin lesions. We hypothesized that a novel treatment involving calcium-based antimicrobial peptide compounds (CAPCS), a combination of natural calcium extracted from marine shellfish, and a variety of antimicrobial peptides, may be beneficial for AD. We established a dinitrofluorobenzene (DNFB)-induced AD model in BALB/c mice to test our hypothesis. We observed mouse behavior and conducted histopathological and immunohistochemical analyses on skin lesions before and after CAPCS treatment. We also characterized the changes in the levels of cytokines, inflammatory mediators, and Toll-like receptors (TLRs) in plasma and skin lesions. The results showed that (i) topical application of CAPCS ameliorated AD-like skin lesions and reduced scratching behavior in BALB/c mice; (ii) CAPCS suppressed infiltration of inflammatory cells and inhibited the expression of inflammatory cytokines in AD-like skin lesions; (iii) CAPCS reduced plasma levels of inflammatory cytokines; and (iv) CAPCS inhibited TLR2 and TLR4 protein expression in skin lesions. Topical application of CAPCS exhibits a therapeutic effect on AD by inhibiting inflammatory immune responses via recruiting helper T cells and engaging the TLR2 and TLR4 signaling pathways. Therefore, CAPCS may be useful for the treatment of AD.
Topics: Animals; Antimicrobial Peptides; Calcium; Cytokines; Dermatitis, Atopic; Dinitrofluorobenzene; Inflammation Mediators; Mice; Mice, Inbred BALB C; Skin; T-Lymphocytes, Helper-Inducer; Toll-Like Receptor 2; Toll-Like Receptor 4
PubMed: 36232673
DOI: 10.3390/ijms231911371 -
Bioengineering & Translational Medicine Sep 2022Vascularized lymph node transplantation (VLNT) has shown inspiring results for the treatment of lymphedema. Nevertheless, it remains unclear how VLNT restores lymphatic...
Vascularized lymph node transplantation (VLNT) has shown inspiring results for the treatment of lymphedema. Nevertheless, it remains unclear how VLNT restores lymphatic drainage and whether or not immunity recovers after surgery. Hindlimb lymphedema model was created using rats with extensive groin and popliteal lymph node removable following with radiotherapy, and the lymphedema was confirmed using indocyanine green (ICG) lymphangiography and micro-computer tomography for volume measurement. VLNT was performed 1 month later. Volume measurement, ICG lymphangiography, histology, and immune reaction were done 1 month after surgery. VLNT successfully reduced the volume of the lymphedema hindlimb, restored lymphatic drainage function with proven lymphatic channel, and reduced lymphedema-related inflammation and fibrosis. It promotes lymphangiogenesis shown from ICG lymphangiography, histology, and enhanced lymphangiogenesis gene expression. Dendritic cell trafficking via the regenerated lymphatic channels was successfully restored, and maintained systemic immune response was proved using dinitrofluorobenzene sensitization and challenge. VLNT effectively reduces lymphedema and promotes lymphatic regeneration in the capillary lymphatic but not the collecting lymphatic vessels. Along with the re-established lymphatic system was the restoration of immune function locally and systemically. This correlated to clinical experience regarding the reduction of swelling and infection episodes after VLNT in lymphedema patients.
PubMed: 36176614
DOI: 10.1002/btm2.10301 -
Frontiers in Physiology 2022Atopic dermatitis (AD) is a chronic inflammatory skin disease with a high prevalence worldwide. Increasing evidence suggests that the gut microbiota plays an important...
Atopic dermatitis (AD) is a chronic inflammatory skin disease with a high prevalence worldwide. Increasing evidence suggests that the gut microbiota plays an important role in the pathogenesis of AD. In this study, we sought to verify the effect of polysaccharides (DCP) on AD induced by 2,4-Dinitrofluorobenzene (DNFB) in Balb/c mice regarding its impact on the intestinal microbiome. We found that 2-week oral administration of DCP improved AD-like symptoms and histological damage of skin, reduced mast cell infiltration, down-regulated the level of serum total IgE and the expression of pro-inflammatory cytokines such as TNF-α, IFN-γ, IL-4 and IL-6, and increased the expression level of anti-inflammatory cytokine IL-10. The beneficial effect of DCP was attributed to the restoration of the intestinal microbiome composition and the unbalance of the intestinal homeostasis. Our results indicated that DCP might be used as a promising novel microbiota-modulating agent for the treatment of AD.
PubMed: 36160845
DOI: 10.3389/fphys.2022.976421 -
Scientific Reports Sep 2022With its antimicrobial and immunomodulating properties, the cathelicidin (LL37) plays an important role in innate immune system. Here, we attempted to alleviate...
With its antimicrobial and immunomodulating properties, the cathelicidin (LL37) plays an important role in innate immune system. Here, we attempted to alleviate chemically induced colitis using a lactococci strain that either directly expressed the precursor to LL37, hCAP18 (LL-pSEC:hCAP18), or delivered hCAP18 cDNA to host cells under the control of the cytomegalovirus promoter (LL-Probi-H1:hCAP18). We also investigated whether the alleviation of symptoms could be explained through modification of the gut microbiota by hCAP18. Mice were administered daily doses of LL-pSEC:hCAP18 or LL-Probi-H1:hCAP18. On day 7, colitis was induced by DNBS. During autopsy, we assessed macroscopic tissue damage in the colon and collected tissue samples for the characterization of inflammation markers and histological analysis. Feces were collected at day 7 for 16S DNA sequencing. We also performed a fecal transplant experiment in which mice underwent colon washing and received feces from Lactococcus lactis-treated mice before DNBS-colitis induction. Treatment with LL-Probi-H1:hCAP18 reduced the severity of colitis symptoms. The protective effects were accompanied by increased levels of IL17A and IL10 in mesenteric lymph node cells. L. lactis administration altered the abundance of Lachnospiraceae and Muribaculaceae. However, fecal transplant from L. lactis-treated mice did not improve DNBS-induced symptoms in recipient mice.
Topics: Animals; Cathelicidins; Colitis; Cytokines; DNA, Complementary; Dinitrofluorobenzene; Interleukin-10; Interleukin-17; Lactococcus lactis; Mice; Mice, Inbred C57BL
PubMed: 36123355
DOI: 10.1038/s41598-022-19455-3 -
Frontiers in Pharmacology 2022Atopic dermatitis (AD), characterized by severe pruritus, immune imbalance, and skin barrier dysfunction, has a high incidence worldwide. Recent evidence has shown that...
Atopic dermatitis (AD), characterized by severe pruritus, immune imbalance, and skin barrier dysfunction, has a high incidence worldwide. Recent evidence has shown that the modulation of gut microbiota is crucial for alleviating clinical symptoms of AD. Tremella fuciformis polysaccharides (TFPS) have been demonstrated to have a variety of biological activities such as immunomodulatory, anti-tumor, antioxidant, anti-inflammatory, neuroprotective, hypoglycemic and hypolipidemic effects. However, their effects on AD treatment have never been investigated. In this study, we compared the therapeutic effects of topical or oral administration of TFPS on AD in dinitrofluorobenzene (DNFB)-induced AD mice. Both topical application and oral administration of TFPS led to improvement on transdermal water loss, epidermal thickening, and ear edema in AD mice, but the oral administration showed significantly better efficacy than the topical application. The TFPS treatment increased the proportion of CD4 (+) CD25 (+) Foxp3 (+) regulatory T cells in mesenteric lymph nodes. Additionally, the non-targeted metabolomics and sequencing of 16S rDNA amplicons were performed, revealing metabolite modulation in feces and changed composition of gut microbiota in mice, which were induced for AD-like disorder and treated by oral administration of TFPS. Collectively, these data suggest that the oral administration of TFPS may constitute a novel effective therapy for AD, with underlying mechanisms associated with the regulation of immune response, and improvement of both metabolism and the composition of intestinal microbiota.
PubMed: 36091780
DOI: 10.3389/fphar.2022.944801 -
Biomolecules Aug 2022Similar to canine inflammatory enteropathy, inflammatory bowel disease (IBD) is a chronic idiopathic condition characterized by remission periods and recurrent flares in...
Similar to canine inflammatory enteropathy, inflammatory bowel disease (IBD) is a chronic idiopathic condition characterized by remission periods and recurrent flares in which diarrhea, visceral pain, rectal bleeding/bloody stools, and weight loss are the main clinical symptoms. Intestinal barrier function alterations often persist in the remission phase of the disease without ongoing inflammatory processes. However, current therapies include mainly anti-inflammatory compounds that fail to promote functional symptoms-free disease remission, urging new drug discoveries to handle patients during this step of the disease. ALIAmides (ALIA, autacoid local injury antagonism) are bioactive fatty acid amides that recently gained attention because of their involvement in the control of inflammatory response, prompting the use of these molecules as plausible therapeutic strategies in the treatment of several chronic inflammatory conditions. N-palmitoyl-D-glucosamine (PGA), an under-researched ALIAmide, resulted in being safe and effective in preclinical models of inflammation and pain, suggesting its potential engagement in the treatment of IBD. In our study, we demonstrated that micronized PGA significantly and dose-dependently reduces colitis severity, improves intestinal mucosa integrity by increasing the tight junction proteins expression, and downregulates the TLR-4/NLRP3/iNOS pathway via PPAR-α receptors signaling in DNBS-treated mice. The possibility of clinically exploiting micronized PGA as support for the treatment and prevention of inflammation-related changes in IBD patients would represent an innovative, effective, and safe strategy.
Topics: Animals; Dogs; Mice; Colitis; Dinitrofluorobenzene; Glucosamine; Inflammation; Inflammatory Bowel Diseases; NLR Family, Pyrin Domain-Containing 3 Protein; PPAR alpha; Toll-Like Receptor 4
PubMed: 36009057
DOI: 10.3390/biom12081163 -
Frontiers in Immunology 2022Cold atmospheric plasma has been widely applied in medical treatment clinically, especially skin diseases. However, the mechanism of cold atmospheric plasma on the...
Cold atmospheric plasma has been widely applied in medical treatment clinically, especially skin diseases. However, the mechanism of cold atmospheric plasma on the treatment of skin diseases is still undefined. In this study, dinitrofluorobenzene-induced atopic dermatitis mice model was constructed. Cold atmospheric plasma was able to decrease skin cells apoptosis, relieve skin inflammation, ER stress and oxidative stress caused by dinitrofluorobenzene stimulation, which was mediated by cold atmospheric plasma-induced MANF expression. In terms of mechanism, hypoxia-inducible factor-1α expression was increased intracellularly after cold atmospheric plasma treatment, which further bound to the promoter region of gene and enhanced MANF transcriptional expression. This study reveals that cold atmospheric plasma has a positive effect on atopic dermatitis treatment, also demonstrates the regulatory mechanism of cold atmospheric plasma on MANF expression HIF-1α, which indicates the potential medical application of cold atmospheric plasma for atopic dermatitis treatment.
Topics: Animals; Dermatitis, Atopic; Dinitrofluorobenzene; Endoplasmic Reticulum Stress; Hypoxia-Inducible Factor 1, alpha Subunit; Mice; Nerve Growth Factors; Plasma Gases
PubMed: 35911675
DOI: 10.3389/fimmu.2022.941219 -
Biological & Pharmaceutical Bulletin 2022We have previously reported that swellings caused by haptens, such as 2,4,6-trinitrochlorobenzene (TNCB), may be associated with the extracellular signal-regulated...
We have previously reported that swellings caused by haptens, such as 2,4,6-trinitrochlorobenzene (TNCB), may be associated with the extracellular signal-regulated kinase (ERK)-induced proliferation pathway. However, the involvement of the Spred/Sprouty family as critical negative regulators of the Ras/Raf/ERK signaling pathway at disease sites is not well-established. Thus, in the present study, the effects of hapten-challenge on the expression levels of genes and proteins associated with the Spred/Sprouty family in the ear of mice were investigated. The activation of ERK and epidermal growth factor receptor (EGFR) tyrosine kinase was inhibited by their selective inhibitors, namely, U0126 and PD168393, respectively. Twenty-four hours after the final challenge by the haptens TNCB, 2,4-dinitrofluorobenzene, or oxazolone, ear thickness was augmented by challenge with all haptens and the gene expression levels of Spred1, Spred2, Sprouty1, and Sprouty2 in swelling induced by all haptens were significantly decreased. Furthermore, Spred2, Sprouty1, and Sprouty2 genes were decreased in the epidermis and dermis of the TNCB-challenged ear. In conclusion, it is possible that the mechanism of hapten-challenge-induced skin thickening involves not only the enhancement of cell proliferative functions via the activation of ERK by EGFR tyrosine kinase activation but also the decreases expression of Spred/Sprouty family members.
Topics: Animals; Dermatitis, Contact; ErbB Receptors; Extracellular Signal-Regulated MAP Kinases; Mice; Picryl Chloride; Protein-Tyrosine Kinases; Repressor Proteins
PubMed: 35908904
DOI: 10.1248/bpb.b22-00279