1,2-Bis[(3-Methoxyphenyl)Methyl]Ethane-1,2-Dicarboxylic Acid Reduces UVB-Induced Photodamage In Vitro and In Vivo

This study investigated the effects and mechanisms of 1,2-bis[(3-methoxyphenyl)methyl]ethane-1,2-dicarboxylic acid (S4), a sesamin derivative, on anti-inflammation and antiphotoaging in vitro and in vivo. Human skin fibroblasts were treated with S4 and did not show cytotoxicity under concentrations of 5–50 µM. In addition, S4 also reduced ultraviolet (UV)B-induced intracellular reactive oxygen species (ROS) production. Additionally, S4 inhibited UVB-induced phosphorylation of mitogen-activated protein (MAP) kinases, activator protein-1 (AP-1), and matrix metalloproteinases (MMPs) overexpression. Furthermore, S4 also inhibited UVB-induced Smad7 protein expression and elevated total collagen content in human dermal fibroblasts. For anti-inflammatory activity, S4 inhibited UVB-induced nitric oxide synthase (i-NOS) and cyclooxygenase (COX)-2 protein expression and inhibited nuclear factor-kappaB (NF-ĸB) translocation into the nucleus. S4 ameliorated UVB-induced erythema and wrinkle formation in hairless mice. On histological observation, S4 also ameliorated UVB-induced epidermal hyperplasia and collagen degradation. S4 reduced UVB-induced MMP-1, interleukin (IL)-6, and NF-ĸB expression in the mouse skin. The results indicated that S4 had antiphotoaging and anti-inflammatory activities, protecting skin from premature aging.

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Extracellular SPARC cooperates with TGF-β signalling to induce pro-fibrotic activation of systemic sclerosis patient dermal fibroblasts

Rheumatology ◽

10.1093/rheumatology/kez583 ◽

2019 ◽

Vol 59 (9) ◽

pp. 2258-2263 ◽

Cited By ~ 3

Author(s):

Tiago Carvalheiro ◽

Beatriz Malvar Fernández ◽

Andrea Ottria ◽

Barbara Giovannone ◽

Wioleta Marut ◽

...

Keyword(s):

Protein Expression ◽

Therapeutic Target ◽

Dermal Fibroblasts ◽

Dependent Manner ◽

Healthy Controls ◽

Multiple Organs ◽

Extracellular Matrix Components ◽

Mrna And Protein Expression

Abstract Objectives SSc is an autoimmune disease characterized by inflammation, vascular injury and excessive fibrosis in multiple organs. Secreted protein acidic and rich in cysteine (SPARC) is a matricellular glycoprotein that regulates processes involved in SSc pathology, such as inflammation and fibrosis. In vivo and in vitro studies have implicated SPARC in SSc, but it is unclear if the pro-fibrotic effects of SPARC on fibroblasts are a result of intracellular signalling or fibroblast interactions with extracellular SPARC hampering further development of SPARC as a potential therapeutic target. This study aimed to analyse the potential role of exogenous SPARC as a regulator of fibrosis in SSc. Methods Dermal fibroblasts from both healthy controls and SSc patients were stimulated with SPARC alone or in combination with TGF-β1, in the absence or presence of a TGF receptor 1 inhibitor. mRNA and protein expression of extracellular matrix components and other fibrosis-related mediators were measured by quantitative PCR and western blot. Results Exogenous SPARC induced mRNA and protein expression of collagen I, collagen IV, fibronectin 1, TGF-β and SPARC by dermal fibroblasts from SSc patients, but not from healthy controls. Importantly, exogenous SPARC induced the activation of the tyrosine kinase SMAD2 and pro-fibrotic gene expression induced by SPARC in SSc fibroblasts was abrogated by inhibition of TGF-β signalling. Conclusion These results indicate that exogenous SPARC is an important pro-fibrotic mediator contributing to the pathology driving SSc but in a TGF-β dependent manner. Therefore, SPARC could be a promising therapeutic target for reducing fibrosis in SSc patients, even in late states of the disease.

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Anti-Inflammatory Effects of Alnus Sibirica Extract on In Vitro and In Vivo Models

Molecules ◽

10.3390/molecules25061418 ◽

2020 ◽

Vol 25 (6) ◽

pp. 1418

Author(s):

Jeongyoon Choi ◽

Sunghee Moon ◽

Hyemi Bae ◽

Young-Won Kim ◽

Yelim Seo ◽

...

Keyword(s):

Immunoglobulin E ◽

Skin Inflammation ◽

Skin Lesions ◽

Dermal Fibroblasts ◽

In Vivo Model ◽

Necrosis Factor Alpha ◽

In Vivo Models ◽

Anti Inflammatory

Alnus sibirica extracts (ASex) have long been used in Oriental medicine to treat various conditions. To provide a scientific basis for this application and the underlying mechanism, we investigated the anti-inflammatory effects of ASex in vitro and in vivo. The in vitro model was established using human dermal fibroblasts (HDFs) treated with inflammatory stimulants (lipopolysaccharide, tumor necrosis factor-alpha, interferon-gamma). Lactate dehydrogenase and reverse transcription-polymerase chain reaction showed that ASex inhibited the increased expression of acute-phase inflammatory cytokines. The in vivo model was established by inducing skin inflammation in NC/Nga mice via the repeated application of house dust mite (HDM) ointment to the ears and back of the mice for eight weeks. HDM application increased the severity of skin lesions, eosinophil/mast cell infiltration, and serum immunoglobulin E levels, which were all significantly decreased by ASex treatment, demonstrating the same degree of protection as hydrocortisone. Overall, ASex showed excellent anti-inflammatory effects both in vitro and in vivo, suggesting its potential as an excellent candidate drug to reduce skin inflammation.

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Protective Effects of Sesamin Against UVB-Induced Skin Inflammation and Photodamage In Vitro and In Vivo

Biomolecules ◽

10.3390/biom9090479 ◽

2019 ◽

Vol 9 (9) ◽

pp. 479 ◽

Cited By ~ 6

Author(s):

Lin ◽

Wu ◽

Hou ◽

Chien ◽

Chang ◽

...

Keyword(s):

Protein Expression ◽

Map Kinase ◽

Human Fibroblasts ◽

Mouse Skin ◽

P38 Map Kinase ◽

Dermal Fibroblasts ◽

Tissue Inhibitor Of Metalloproteinase ◽

Protective Effects ◽

Cox 2

Ultraviolet (UV) exposure has been demonstrated as the most critical factor causing extrinsic skin aging and inflammation. This study explored the protective effects and mechanisms of sesamin against skin photodamage. Sesamin reduced intracellular reactive oxygen species production after UVB irradiation in human dermal fibroblasts. The sesamin treatment attenuated mitogen-activated protein (MAP) kinase phosphorylation and matrix metalloproteinase (MMPs) overexpression induced by UVB exposure, and it significantly enhanced the tissue inhibitor of metalloproteinase-1 protein expression. Sesamin also elevated the total collagen content in human fibroblasts by inhibiting UVB-induced mothers against decapentaplegic homolog 7 (Smad7) protein expression. Sesamin reduced UVB-induced inducible nitric oxide synthase (i-NOS) and cyclooxygenase-2 (COX-2) overexpression and inhibited nuclear factor-kappa B (NF-κB) translocation. Moreover, sesamin may regulate the c-Jun N-terminal kinases (JNK) and p38 MAP kinase pathways, which inhibit COX-2 expression. Sesamin could reduce UVB-induced inflammation, epidermal hyperplasia, collagen degradation, and wrinkle formation in hairless mice. It also reduced MMP-1, interleukin (IL-1), i-NOS, and NF-κB in the mouse skin. These results demonstrate that sesamin had antiphotodamage and anti-inflammatory activities. Sesamin has potential for use as a skin protection agent in antiphotodamage and skin care products.

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Human acellular amniotic membrane incorporating exosomes from adipose-derived mesenchymal stem cells promotes diabetic wound healing

10.21203/rs.3.rs-151677/v1 ◽

2021 ◽

Author(s):

Shune Xiao ◽

Chunfang Xiao ◽

Yong Miao ◽

Jin Wang ◽

Ruosi Chen ◽

...

Keyword(s):

Wound Healing ◽

Amniotic Membrane ◽

Mouse Skin ◽

Skin Wound ◽

Dermal Fibroblasts ◽

Diabetic Wound ◽

Wound Model ◽

Diabetic Wound Healing

Abstract Background: Diabetic wounds threaten the health and quality of life of patients and their treatment remains challenging. ADSC-derived exosomes have shown encouraging results in enhancing diabetic wound healing. However, the common method of exosome administration is subcutaneous injection at several sites around the wound, causing further damage and preventing direct contact between the exosomes and the injury site. Methods: A diabetic mouse skin wound model was established. ADSC-derived exosomes (ADSC-Exos) were isolated and in vitro application of exosomes was evaluated using human umbilical vein endothelial cells (HUVECs) and human dermal fibroblasts (HDFs). After preparation and characterization of a scaffold of human acellular amniotic membrane (hAAM) loaded with ADSC-Exos in vitro , they were transplanted into wounds in vivo and wound healing phenomena were observed by histological and immunohistochemical analyses to identify the wound healing mechanism of the exosome-hAAM composites. Results: The hAAM scaffold dressing was very suitable for the delivery of exosomes. ADSC-Exos enhanced the proliferation and migration of HDFs and promoted proliferation and tube formation of HUVECs in vitro . In vivo results from a diabetic skin wound model showed that the hAAM-Exos dressing accelerated wound healing by regulating inflammation, stimulating vascularization and promoting the production of extracellular matrix. Conclusion: Exosome-incorporated hAAM scaffolds showed great potential in promoting diabetic skin wound healing, while also providing strong evidence for the future clinical applications of ADSC-derived exosomes.

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Modulation of Skin Inflammatory Response by Active Components of Silymarin

Molecules ◽

10.3390/molecules24010123 ◽

2018 ◽

Vol 24 (1) ◽

pp. 123 ◽

Cited By ~ 6

Author(s):

Jana Juráňová ◽

Juliette Aury-Landas ◽

Karim Boumediene ◽

Catherine Baugé ◽

David Biedermann ◽

...

Keyword(s):

Wound Healing ◽

Prolonged Exposure ◽

Dermal Fibroblasts ◽

Enzyme Linked Immunosorbent Assay ◽

Activator Protein 1 ◽

Human Dermal Fibroblasts ◽

Active Components ◽

Mobility Shift ◽

Anti Inflammatory

In this study, we compared selected silymarin components, such as quercetin (QE), 2,3-dehydrosilybin (DHS) and silybin (SB), with the anti-inflammatory drug indomethacin (IND) in terms of their wound healing potential. In view of the fact that pathological cutaneous wound healing is associated with persistent inflammation, we studied their anti-inflammatory activity against inflammation induced by bacterial lipopolysaccharide (LPS). We investigated the regulation of crucial pro-inflammatory transcription factors—nuclear factor kappa-B (NF-κB) and activator protein 1 (AP-1)—as well as the expression of downstream inflammatory targets by Western blotting, real-time PCR (RT-PCR), electrophoretic mobility shift assay (EMSA), and/or enzyme-linked immunosorbent assay (ELISA) in vitro using primary normal human dermal fibroblasts (NHDF). We demonstrated the greater ability of DHS to modulate the pro-inflammatory cytokines production via the NF-κB and AP-1 signaling pathways when compared to other tested substances. The prolonged exposure of LPS-challenged human dermal fibroblasts to DHS had both beneficial and detrimental consequences. DHS diminished interleukin-6 (IL-6) and interleukin-8 (IL-8) secretion but induced the significant upregulation of IL-8 mRNA associated with NF-κB and AP-1 activation. The observed conflicting results may compromise the main expected benefit, which is the acceleration of the healing of the wound via a diminished inflammation.

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Human acellular amniotic membrane incorporating exosomes from adipose-derived mesenchymal stem cells promotes diabetic wound healing

Stem Cell Research & Therapy ◽

10.1186/s13287-021-02333-6 ◽

2021 ◽

Vol 12 (1) ◽

Author(s):

Shune Xiao ◽

Chunfang Xiao ◽

Yong Miao ◽

Jin Wang ◽

Ruosi Chen ◽

...

Keyword(s):

Wound Healing ◽

Amniotic Membrane ◽

Mouse Skin ◽

Skin Wound ◽

Dermal Fibroblasts ◽

Diabetic Wound ◽

Wound Model ◽

Diabetic Wound Healing

Abstract Background Diabetic wounds threaten the health and quality of life of patients and their treatment remains challenging. ADSC-derived exosomes have shown encouraging results in enhancing diabetic wound healing. However, how to use exosomes in wound treatment effectively is a problem that needs to be addressed at present. Methods A diabetic mouse skin wound model was established. ADSC-derived exosomes (ADSC-Exos) were isolated, and in vitro application of exosomes was evaluated using human umbilical vein endothelial cells (HUVECs) and human dermal fibroblasts (HDFs). After preparation and characterization of a scaffold of human acellular amniotic membrane (hAAM) loaded with ADSC-Exos in vitro, they were transplanted into wounds in vivo and wound healing phenomena were observed by histological and immunohistochemical analyses to identify the wound healing mechanism of the exosome-hAAM composites. Results The hAAM scaffold dressing was very suitable for the delivery of exosomes. ADSC-Exos enhanced the proliferation and migration of HDFs and promoted proliferation and tube formation of HUVECs in vitro. In vivo results from a diabetic skin wound model showed that the hAAM-Exos dressing accelerated wound healing by regulating inflammation, stimulating vascularization, and promoting the production of extracellular matrix. Conclusion Exosome-incorporated hAAM scaffolds showed great potential in promoting diabetic skin wound healing, while also providing strong evidence for the future clinical applications of ADSC-derived exosomes.

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