International Journal of Molecular Sciences

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18 pages, 10599 KiB

Open AccessArticle

Anti-Inflammatory Effects of Spirodela polyrhiza (L.) S_CHLEID. Extract on Contact Dermatitis in Mice—Its Active Compounds and Molecular Targets

by Kukhwa Kim, Daniel Lee, Han-Young Kim, Soyeon Kim, Ji-Hyo Lyu, Sujung Park, Young-Chul Park and Hyungwoo Kim

Int. J. Mol. Sci. 2023, 24(17), 13271; https://doi.org/10.3390/ijms241713271 - 26 Aug 2023

Viewed by 1159

Abstract

Spirodela polyrhiza (L.) S_CHLEID. has been used to treat epidemic fever, dysuria, and various skin ailments, such as measles eruptions, eczema, and pruritus, in China, Japan, and Korea. In this study, the active compounds in S. polyrhiza and their target genes [...] Read more.

Spirodela polyrhiza (L.) S_CHLEID. has been used to treat epidemic fever, dysuria, and various skin ailments, such as measles eruptions, eczema, and pruritus, in China, Japan, and Korea. In this study, the active compounds in S. polyrhiza and their target genes were identified by network-based analysis. Moreover, the study evaluated the effects of a 70% ethanolic extract of S. polyrhiza (EESP) on skin lesions, histopathological changes, inflammatory cytokines, and chemokines in mice with contact dermatitis (CD) induced by 1-fluoro-2,4-dinitrobenzene (DNFB), and examined the inhibitory effects of EESP on mitogen-activated protein kinase (MAPK) signalling pathways. In our results, 14 active compounds and 29 CD-related target genes were identified. Among them, tumour necrosis factor (TNF) and interleukin 6 (IL-6) were identified as hub genes, and luteolin and apigenin showed a strong binding affinity with TNF (<−8 kcal/mol) and IL-6 (<−6 kcal/mol). Our in vivo studies showed that topical EESP ameliorated DNFB-induced skin lesions and histopathological abnormalities, and reduced the levels of TNF-α, interferon (IFN)-ɣ, IL-6, and monocyte chemotactic protein (MCP)-1 in inflamed tissues. In conclusion, our findings suggest the potential for dermatological applications of S. polyrhiza and suggest that its anti-dermatitis action is related to the inhibition of TNF and IL-6 by luteolin and luteolin glycosides. Full article

(This article belongs to the Special Issue Advanced Research on Wound Healing)

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15 pages, 3248 KiB

Open AccessArticle

KY19382 Accelerates Cutaneous Wound Healing via Activation of the Wnt/β-Catenin Signaling Pathway

by Minguen Yoon, Eunhwan Kim, Seol Hwa Seo, Geon-Uk Kim and Kang-Yell Choi

Int. J. Mol. Sci. 2023, 24(14), 11742; https://doi.org/10.3390/ijms241411742 - 21 Jul 2023

Viewed by 1333

Abstract

The Wnt/β-catenin signaling pathway plays important roles in the multi-phases of wound healing: homeostasis, inflammation, proliferative, and remodeling phases. However, there are no clinically available therapeutic agents targeting the Wnt/β-catenin pathway. In this study, we tested the effect of 5, 6-dichloroindirubin-3′-methoxime (KY19382), a [...] Read more.

The Wnt/β-catenin signaling pathway plays important roles in the multi-phases of wound healing: homeostasis, inflammation, proliferative, and remodeling phases. However, there are no clinically available therapeutic agents targeting the Wnt/β-catenin pathway. In this study, we tested the effect of 5, 6-dichloroindirubin-3′-methoxime (KY19382), a small molecule that activates the Wnt/β-catenin pathway via interference with the function of the negative feedback regulator CXXC5, on cutaneous wound healing. KY19382 significantly enhanced cell migration of human keratinocytes and dermal fibroblasts with increased levels of β-catenin, phalloidin, Keratin 14, proliferating cell nuclear antigen (PCNA), Collagen I, and alpha-smooth muscle actin (α-SMA) by activating the Wnt/β-catenin signaling pathway without causing significant cytotoxicity. In addition, levels of Collagen I, Keratin 14, PCNA, and stem cell markers were significantly increased by KY19382 in a cutaneous murine wound healing model. Moreover, KY19382 treatment accelerated re-epithelialization and neo-epidermis formation with collagen deposition and stem cell activation at an early stage of cutaneous wound healing. Overall, KY19382 accelerates wound healing via activating the Wnt/β-catenin pathway, and may have the potential to be used for the development of a new wound healing agent. Full article

(This article belongs to the Special Issue Advanced Research on Wound Healing)

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14 pages, 3883 KiB

Open AccessArticle

Adipose Tissue-Derived Mesenchymal Stem Cell-Derived Exosomes Promote Wound Healing and Tissue Regeneration

by Jun Ho Lee, Yu Jin Won, Hail Kim, Minji Choi, Esther Lee, Bumsik Ryoou, Seok-Geun Lee and Byong Seung Cho

Int. J. Mol. Sci. 2023, 24(13), 10434; https://doi.org/10.3390/ijms241310434 - 21 Jun 2023

Cited by 12 | Viewed by 4189

Abstract

Wound healing is a complex process involving cell proliferation, migration, and extracellular matrix (ECM) remodeling. Extracellular vesicles (EVs) or exosomes derived from adipose tissue-derived stem cells (ASCs) are emerging as promising alternatives to cell therapy for advanced wound healing. Hyaluronic acid (HA), a [...] Read more.

Wound healing is a complex process involving cell proliferation, migration, and extracellular matrix (ECM) remodeling. Extracellular vesicles (EVs) or exosomes derived from adipose tissue-derived stem cells (ASCs) are emerging as promising alternatives to cell therapy for advanced wound healing. Hyaluronic acid (HA), a major component of the skin ECM, is widely utilized in wound dressings and dermal fillers. This study aimed to investigate the effects of ASC-derived exosomes (ASC-EXOs) on human dermal fibroblasts (HDFs) and their potential combination with HA in in vivo wound healing and dermal filler models. In HDFs, ASC-EXOs increased cell proliferation and migration. ASC-EXOs also upregulated the expression of genes involved in cell proliferation and wound healing while stimulating collagen production in HDFs. In a porcine wound healing model, topical treatment with a combination of HA and ASC-EXOs led to higher wound closure rates compared to HA alone. Histological examination showed increased re-epithelialization and collagen type III deposition in wounds treated with the combination of HA and ASC-EXOs. In a mouse dermal filler model, tissues injected with the combination of HA and ASC-EXOs exhibited thicker tissue layers, increased vascularization, enhanced infiltration of myofibroblasts, and higher levels of collagen III and collagen fiber content compared to HA alone. These findings suggest that ASC-EXOs have beneficial effects on cell proliferation, migration, and gene expression related to wound healing, and they may accelerate wound closure and promote tissue regeneration. Furthermore, the combination of HA and ASC-EXOs may enhance wound healing and tissue remodeling, indicating its potential for both clinical and regenerative aesthetic applications in skin repair and regeneration. Full article

(This article belongs to the Special Issue Advanced Research on Wound Healing)

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33 pages, 5542 KiB

Open AccessArticle

Drug Target Identification and Drug Repurposing in Psoriasis through Systems Biology Approach, DNN-Based DTI Model and Genome-Wide Microarray Data

by Yu-Ping Zhan and Bor-Sen Chen

Int. J. Mol. Sci. 2023, 24(12), 10033; https://doi.org/10.3390/ijms241210033 - 12 Jun 2023

Cited by 3 | Viewed by 1522

Abstract

Psoriasis is a chronic skin disease that affects millions of people worldwide. In 2014, psoriasis was recognized by the World Health Organization (WHO) as a serious non-communicable disease. In this study, a systems biology approach was used to investigate the underlying pathogenic mechanism [...] Read more.

Psoriasis is a chronic skin disease that affects millions of people worldwide. In 2014, psoriasis was recognized by the World Health Organization (WHO) as a serious non-communicable disease. In this study, a systems biology approach was used to investigate the underlying pathogenic mechanism of psoriasis and identify the potential drug targets for therapeutic treatment. The study involved the construction of a candidate genome-wide genetic and epigenetic network (GWGEN) through big data mining, followed by the identification of real GWGENs of psoriatic and non-psoriatic using system identification and system order detection methods. Core GWGENs were extracted from real GWGENs using the Principal Network Projection (PNP) method, and the corresponding core signaling pathways were annotated using the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways. Comparing core signaling pathways of psoriasis and non-psoriasis and their downstream cellular dysfunctions, STAT3, CEBPB, NF-κB, and FOXO1 are identified as significant biomarkers of pathogenic mechanism and considered as drug targets for the therapeutic treatment of psoriasis. Then, a deep neural network (DNN)-based drug-target interaction (DTI) model was trained by the DTI dataset to predict candidate molecular drugs. By considering adequate regulatory ability, toxicity, and sensitivity as drug design specifications, Naringin, Butein, and Betulinic acid were selected from the candidate molecular drugs and combined into potential multi-molecule drugs for the treatment of psoriasis. Full article

(This article belongs to the Special Issue Advanced Research on Wound Healing)

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32 pages, 34952 KiB

Open AccessArticle

Beneficial Effects of Dinitrosyl Iron Complexes on Wound Healing Compared to Commercial Nitric Oxide Plasma Generator

by Alexandra Igrunkova, Alexey Fayzullin, Natalia Serejnikova, Tatiana Lipina, Alexandr Pekshev, Anatoly Vanin, Victoria Zaborova, Elena Budanova, Dmitry Shestakov, Igor Kastyro and Anatoly Shekhter

Int. J. Mol. Sci. 2023, 24(5), 4439; https://doi.org/10.3390/ijms24054439 - 23 Feb 2023

Cited by 6 | Viewed by 1596

Abstract

Nitric oxide (NO) is a gaseous molecule which plays a key role in wound healing. Previously, we identified the optimal conditions for wound healing strategies using NO donors and an air plasma generator. The aim of this study was to compare the wound [...] Read more.

Nitric oxide (NO) is a gaseous molecule which plays a key role in wound healing. Previously, we identified the optimal conditions for wound healing strategies using NO donors and an air plasma generator. The aim of this study was to compare the wound healing effects of binuclear dinitrosyl iron complexes with glutathione (B-DNIC-GSH) and NO-containing gas flow (NO-CGF) at their optimal NO doses (0.04 mmol for B-DNIC-GSH and 1.0 mmol for NO-CGF per 1 cm²) in a rat full-thickness wound model over a 3-week period. Excised wound tissues were studied by light and transmission electron microscopy and immunohistochemical, morphometrical and statistical methods. Both treatments had an identical stimulating impact on wound healing, which indicated a higher dosage effectiveness of B-DNIC-GSH compared to the NO-CGF. B-DNIC-GSH spray application reduced inflammation and promoted fibroblast proliferation, angiogenesis and the growth of granulation tissue during the first 4 days after injury. However, prolonged NO spray effects were mild compared to NO-CGF. Future studies should determine the optimal B-DNIC-GSH solution course for a more effective wound healing stimulation. Full article

(This article belongs to the Special Issue Advanced Research on Wound Healing)

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19 pages, 2795 KiB

Open AccessArticle

Secretome of Adipose-Derived Stem Cells Cultured in Platelet Lysate Improves Migration and Viability of Keratinocytes

by Maike Hermann, Ajay Peddi, Alexander Gerhards, Rafael Schmid, Deborah Schmitz, Andreas Arkudas, Volker Weisbach, Raymund E. Horch and Annika Kengelbach-Weigand

Int. J. Mol. Sci. 2023, 24(4), 3522; https://doi.org/10.3390/ijms24043522 - 9 Feb 2023

Cited by 2 | Viewed by 2181

Abstract

Chronic wounds depict a silent epidemic challenging medical professionals worldwide. Regenerative medicine uses adipose-derived stem cells (ADSC) in promising new therapies. In this study, platelet lysate (PL) as a xenogen-free substitute for foetal bovine serum (FBS) in ADSC culture was used to create [...] Read more.

Chronic wounds depict a silent epidemic challenging medical professionals worldwide. Regenerative medicine uses adipose-derived stem cells (ADSC) in promising new therapies. In this study, platelet lysate (PL) as a xenogen-free substitute for foetal bovine serum (FBS) in ADSC culture was used to create an ADSC secretome containing cytokines for optimal wound healing conditions. The ADSC secretome was tested on keratinocytes for migrational behaviour and viability. Therefore, human ADSC were characterized under FBS (10%) and PL (5% and 10%) substitution, regarding morphology, differentiation, viability, gene and protein expression. ADSC were then cultured in 5% PL and their secretome was used for stimulation of keratinocyte migration and viability. To enhance the effect, ADSC were treated with Epithelial Growth Factor (EGF, 100 ng/mL) and hypoxia (1% O₂). In both PL and FBS groups, ADSC expressed typical stem cell markers. PL induced a significantly higher increase in cell viability compared to FBS substitution. ADSC secretome contained various beneficial proteins which enhance the wound healing capacity of keratinocytes. This could be optimized treating ADSC with hypoxia and EGF. In conclusion, the study shows that ADSC cultivated in 5% PL can effectively support wound healing conditions and can be considered as a promising new therapy for individual treatment of chronic wound disorders. Full article

(This article belongs to the Special Issue Advanced Research on Wound Healing)

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16 pages, 2853 KiB

Open AccessArticle

Efficacy of Polydeoxyribonucleotide in Promoting the Healing of Diabetic Wounds in a Murine Model of Streptozotocin-Induced Diabetes: A Pilot Experiment

by Jiyoung Yun, SaeGwang Park, Ha Young Park and Kyung Ah Lee

Int. J. Mol. Sci. 2023, 24(3), 1932; https://doi.org/10.3390/ijms24031932 - 18 Jan 2023

Viewed by 1696

Abstract

We assessed the efficacy of polydeoxyribonucleotide (PDRN) in accelerating the healing of diabetic wounds in a murine model of streptozotocin (STZ)-induced diabetes. After the creation of diabetic wounds, the mice of the PDRN SC, PDRN IP and PBS groups received a subcutaneous, an [...] Read more.

We assessed the efficacy of polydeoxyribonucleotide (PDRN) in accelerating the healing of diabetic wounds in a murine model of streptozotocin (STZ)-induced diabetes. After the creation of diabetic wounds, the mice of the PDRN SC, PDRN IP and PBS groups received a subcutaneous, an intra-peritoneal injection of PDRN and a subcutaneous injection of PBS, respectively. After euthanasia, time-dependent changes in the wound diameter and histologic scores were measured and vascular endothelial growth factor (VEGF), transforming growth factor-β1 (TGF-β1) and collagen types I and III were assessed for their expression levels. The PDRN SC and the PDRN IP groups showed a significantly smaller diameter of diabetic wounds, significantly higher histologic scores, a significantly greater expression of VEGF, a significantly lower expression of TGF-β1 and a significantly greater expression of collagen types I and III as compared with the PBS group (p < 0.05 or 0.0001). In conclusion, PDRN might be effective in promoting the healing of diabetic wounds in a murine model of STZ-induced diabetes. Full article

(This article belongs to the Special Issue Advanced Research on Wound Healing)

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12 pages, 3354 KiB

Open AccessArticle

Effect of Baicalin on Wound Healing in a Mouse Model of Pressure Ulcers

by Eunbin Kim, Seoyoon Ham, Bok Ki Jung, Jin-Woo Park, Jihee Kim and Ju Hee Lee

Int. J. Mol. Sci. 2023, 24(1), 329; https://doi.org/10.3390/ijms24010329 - 25 Dec 2022

Cited by 7 | Viewed by 2825

Abstract

One of the most frequent comorbidities that develop in chronically ill or immobilized patients is pressure ulcers, also known as bed sores. Despite ischemia-reperfusion (I/R)-induced skin lesion having been identified as a primary cause of pressure ulcers, wound management efforts have so far [...] Read more.

One of the most frequent comorbidities that develop in chronically ill or immobilized patients is pressure ulcers, also known as bed sores. Despite ischemia-reperfusion (I/R)-induced skin lesion having been identified as a primary cause of pressure ulcers, wound management efforts have so far failed to significantly improve outcomes. Baicalin, or 5,6,7-trihydroxyflavone, is a type of flavonoid which has been shown to possess a variety of biological characteristics, including antioxidative and anti-inflammatory effects and protection of I/R injury. In vitro wound scratch assay was first used to assess the function of baicalin in wound healing. We established a mouse model of advanced stage pressure ulcers with repeated cycles of I/R pressure load. In this model, topically applied baicalin (100 mg/mL) induced a significant increase in the wound healing process measured by wound area. Histological examination of the pressure ulcer mouse model showed faster granulation tissue formation and re-epithelization in the baicalin-treated group. Next, baicalin downregulated pro-inflammatory cytokines (IL-6 and IL-1β), while upregulating the anti-inflammatory IL-10. Additionally, baicalin induced an increase in several growth factors (VEGF, FGF-2, PDGF-β, and CTGF), promoting the wound healing process. Our results suggest that baicalin could serve as a promising agent for the treatment of pressures ulcers. Full article

(This article belongs to the Special Issue Advanced Research on Wound Healing)

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