140 Alpha-Mangostin Inhibits Proliferation, Promotes Apoptosis, and Modulates Fibrotic Gene Expression in Normal and Keloid Fibroblasts In Vitro

2021 ◽  
Vol 42 (Supplement_1) ◽  
pp. S93-S94
Author(s):  
Dorothy M Supp ◽  
Kevin L McFarland ◽  
Jennifer M Hahn ◽  
Kelly A Combs
Keyword(s):  
Gene Expression ◽  
Healing Process ◽  
Antioxidant Properties ◽  
Dermal Fibroblasts ◽  
Enzyme Linked Immunosorbent Assay ◽  
Wound Healing Process ◽  
Type I ◽  
Matrix Metalloproteinase 1 ◽  
Keloid Fibroblasts

Abstract Introduction Keloids are disfiguring lesions that result from an abnormal wound healing process. Despite the availability of numerous therapeutic options, keloids remain challenging to treat and often recur after therapy. α-Mangostin, a natural xanthone isolated from the fruit of the Mangosteen tree, has been used for centuries in many Southeast Asian nations for medicinal purposes, and has gained attention more recently due to its anti-inflammatory, antimicrobial, and antioxidant properties, with numerous studies suggesting possible anticarcinogenic activities. Hypothetically, α-mangostin may have therapeutic value for keloid suppression. To investigate this hypothesis, the effects of α-mangostin on fibroblast proliferation, apoptosis, and gene expression in vitro were analyzed. Methods Dermal fibroblasts were isolated and cultured from normal human skin and excised keloid lesions (3 donors each), and were treated with multiple doses (0–10 µm) of α-mangostin in vitro. Proliferation was measured using an MTT assay, gene expression was measured using quantitative real-time PCR (qPCR), and protein levels in culture media were measured by enzyme-linked immunosorbent assay (ELISA). Apoptosis was assessed by measuring expression of C/EBP homologous protein (CHOP), which mediates endoplasmic reticulum stress-induced apoptosis, by qPCR. Results Dose-dependent decreases in proliferation of keloid and normal fibroblasts were observed following treatment with α-mangostin. The α-mangostin treated fibroblasts displayed significantly increased expression of CHOP, indicating increased apoptosis. In addition, numerous changes in gene expression were observed in α-mangostin-treated keloid fibroblasts, including decreased expression of collagen type I alpha 1 chain (COL1A1) and increased expression of matrix metalloproteinase 1 (MMP1), MMP3, and MMP13. Secretion of pro-collagen I was decreased, and secretion of MMP1 and MMP3 proteins were increased, in α-mangostin-treated fibroblasts. Conclusions The results suggest that α-mangostin may exhibit antiproliferative, proapoptotic, and antifibrotic activities in keloid and normal fibroblasts.

scholarly journals Wound Healing Promotion by Hyaluronic Acid: Effect of Molecular Weight on Gene Expression and In Vivo Wound Closure

2021 ◽  
Vol 14 (4) ◽  
pp. 301
Author(s):  
Yayoi Kawano ◽  
Viorica Patrulea ◽  
Emmanuelle Sublet ◽  
Gerrit Borchard ◽  
Takuya Iyoda ◽  
...  
Keyword(s):  
Gene Expression ◽  
Molecular Weight ◽  
Wound Healing ◽  
Hyaluronic Acid ◽  
Healing Process ◽  
Dermal Fibroblasts ◽  
Water Soluble ◽  
Wound Healing Process ◽  
And Migration ◽  
Proliferation And Migration

Hyaluronic acid (HA) has been known to play an important role in wound healing process. However, the effect of molecular weight (MW) of exogenously administered HA on the wound healing process has not been fully understood. In this study, we investigated HA with different MWs on wound healing process using human epidermal keratinocytes and dermal fibroblasts. Cell proliferation and migration ability were assessed by water soluble tetrazolium (WST) assay and wound scratch assay. We examined the effect of HA addition in a full-thickness wound model in mice and the gene expression related to wound healing. Proliferation and migration of HaCaT cells increased with the increase of MW and concentration of HA. Interleukin (IL-1β), IL-8 and vascular endothelial growth factor (VEGF) as well as matrix metalloproteinase (MMP)-9 and MMP-13 were significantly upregulated by high molecular weight (HMW) HA in keratinocytes. Together with VEGF upregulation and the observed promotion of HaCaT migration, HA with the MW of 2290 kDa may hold potential to improve re-epithelialization, a critical obstacle to heal chronic wounds.

Investigation of the effects of prostaglandin E2 on equine superficial digital flexor tendon fibroblasts in vitro

2010 ◽  
Vol 23 (06) ◽  
pp. 417-423 ◽  
Author(s):  
J. M. Cissell ◽  
S. C. Milton ◽  
L. A. Dahlgren
Keyword(s):  
Gene Expression ◽  
Matrix Protein ◽  
Collagen Type ◽  
Flexor Tendon ◽  
Cell Metabolism ◽  
Collagen Type I ◽  
Type I ◽  
Matrix Metalloproteinase 1 ◽  
Superficial Digital Flexor Tendon

Summary Objectives: To evaluate the effects of pros-taglandin E2 (PGE2) treatment on the metabolism of equine tendon fibroblasts in vitro to aid in investigating the response of tendon fibroblasts to injury and novel therapeutics. Methods: Superficial digital flexor tendon fibroblasts isolated via collagenase digestion from six young adult horses were grown in monolayer in four concentrations of PGE2 (0, 10, 50, 100 ng/ml) for 48 hours. Cells and medium were harvested for gene expression (collagen types I and III, cartilage oligomeric matrix protein [COMP], decorin, and matrix metalloproteinase-1, –3, and –13), biochemical analysis (glycosaminoglycan, DNA, and collagen content), and cytological staining. Results: Gene expression for collagen type I was significantly increased at 100 ng/ml PGE2 compared to 10 and 50 ng/ml. There were not any significant differences detected for gene expression of collagen type III, COMP or dec-orin or for biochemical content and cell morphology. Clinical significance: Under the conditions investigated, exogenous treatment of equine tendon fibroblasts with PGE2 failed to alter cell metabolism in a manner useful as a model of tendon injury. A model that applies cyclic strain to a three dimensional construct seeded with tendon fibroblasts may prove to be a more useful model and merits further investigation for this purpose. The ability to assess cellular responses in an environment where the cells are supported within the extracellular matrix may prove beneficial.

scholarly journals Effect of Hypoxia on Gene Expression in Cell Populations Involved in Wound Healing

2019 ◽  
Vol 2019 ◽  
pp. 1-20 ◽  
Author(s):  
Sarah D’Alessandro ◽  
Andrea Magnavacca ◽  
Federica Perego ◽  
Marco Fumagalli ◽  
Enrico Sangiovanni ◽  
...  
Keyword(s):  
Gene Expression ◽  
Wound Healing ◽  
Endothelial Cells ◽  
Current Knowledge ◽  
Expression Profiles ◽  
Healing Process ◽  
Critical Role ◽  
Dermal Fibroblasts ◽  
Cell Populations ◽  
Wound Healing Process

Wound healing is a complex process regulated by multiple signals and consisting of several phases known as haemostasis, inflammation, proliferation, and remodelling. Keratinocytes, endothelial cells, macrophages, and fibroblasts are the major cell populations involved in wound healing process. Hypoxia plays a critical role in this process since cells sense and respond to hypoxic conditions by changing gene expression. This study assessed the in vitro expression of 77 genes involved in angiogenesis, metabolism, cell growth, proliferation and apoptosis in human keratinocytes (HaCaT), microvascular endothelial cells (HMEC-1), differentiated macrophages (THP-1), and dermal fibroblasts (HDF). Results indicated that the gene expression profiles induced by hypoxia were cell-type specific. In HMEC-1 and differentiated THP-1, most of the genes modulated by hypoxia encode proteins involved in angiogenesis or belonging to cytokines and growth factors. In HaCaT and HDF, hypoxia mainly affected the expression of genes encoding proteins involved in cell metabolism. This work can help to enlarge the current knowledge about the mechanisms through which a hypoxic environment influences wound healing processes at the molecular level.

Activation of peroxisome proliferator-activated receptor-γ contributes to the inhibitory effects of curcumin on rat hepatic stellate cell growth

2003 ◽  
Vol 285 (1) ◽  
pp. G20-G30 ◽  
Author(s):  
Jianye Xu ◽  
Yumei Fu ◽  
Anping Chen
Keyword(s):  
Gene Expression ◽  
Liver Injury ◽  
Hepatic Fibrosis ◽  
Stellate Cell ◽  
Healing Process ◽  
Wound Healing Process ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Ppar Γ

Hepatic fibrogenesis occurs as a wound-healing process after many forms of chronic liver injury. Hepatic fibrosis ultimately leads to cirrhosis if not treated effectively. During liver injury, quiescent hepatic stellate cells (HSC), the most relevant cell type, become active and proliferative. Oxidative stress is a major and critical factor for HSC activation. Activation of peroxisome proliferator-activated receptor-γ (PPAR-γ) inhibits the proliferation of nonadipocytes. The level of PPAR-γ is dramatically diminished along with activation of HSC. Curcumin, the yellow pigment in curry, is a potent antioxidant. The aims of this study were to evaluate the effect of curcumin on HSC proliferation and to begin elucidating underlying mechanisms. It was hypothesized that curcumin might inhibit the proliferation of activated HSC by inducing PPAR-γ gene expression and reviving PPAR-γ activation. Our results indicated that curcumin significantly inhibited the proliferation of activated HSC and induced apoptosis in vitro. We demonstrated, for the first time, that curcumin dramatically induced the gene expression of PPAR-γ and activated PPAR-γ in activated HSC. Blocking its trans-activating activity by a PPAR-γ antagonist markedly abrogated the effects of curcumin on inhibition of cell proliferation. Our results provide a novel insight into mechanisms underlying the inhibition of activated HSC growth by curcumin. The characteristics of curcumin, including antioxidant potential, reduction of activated HSC growth, and no adverse health effects, make it a potential antifibrotic candidate for prevention and treatment of hepatic fibrosis.

scholarly journals Eremostachys Binalodensis, A Potential Therapeutic Choice for Gingival Inflammatory Wounds

2021 ◽  
Vol 7 (3) ◽  
Keyword(s):  
Wound Healing ◽  
Methanol Extract ◽  
Healing Process ◽  
Enzyme Linked Immunosorbent Assay ◽  
Wound Healing Process ◽  
Gingival Fibroblasts ◽  
Wound Induction ◽  
Therapeutic Choice ◽  
Tnf Α

Objectives: In this study we aimed to evaluate the effect of E. binalodensis on gingival inflammatory wounds. Methods: In-vitro wound was induced by scratching the surface layer of human gingival fibroblasts (hGFs). Cells were pretreated with 1,10,100,1000 µg/ml of E. binalodensis methanol extract prior to 1µg/ml LPS stimulation. hGFs proliferation was assessed by MTT test. Also levels of critical inflammatory cytokines such as IL-1𝛽, IL-6 and TNF-𝛼 were determined by enzyme-linked immunosorbent assay (ELISA). Results: Wound induction was associated with secretion of IL-1β, IL-6 and TNF-α from hGFs. E. binalodensis enhanced the hGFs proliferation besides reducing the level of IL-1β, IL-6 and TNF-α in LPS-scratch-stimulated hGFs. Conclusions: Regarding anti-inflammatory and proliferative effects of E. binalodensis on hGFs, availability and safety of it, it is suggested for enhancing the wound healing process in gingival inflammatory wounds.

scholarly journals Anti-aging Effect of Mixed Extract from Medicinal Herbs

2021 ◽  
Vol 19 (4) ◽  
pp. 679-692
Author(s):  
Soyoun Lee ◽  
Hongyan An ◽  
Woosoo Kim ◽  
Xinxin Lu ◽  
Hyanghwa Jeon ◽  
...  
Keyword(s):  
Collagen Synthesis ◽  
Aging Effect ◽  
Dermal Fibroblasts ◽  
Herbal Extract ◽  
Type I ◽  
Mrna Levels ◽  
Protein Levels ◽  
Matrix Metalloproteinase 1 ◽  
Crow’S Feet

Purpose: This study was conducted to confirm the applicability of a mixed herbal extract (MHE) as an anti-aging cosmetic ingredient by investigating its skin anti-aging activities in vitro and in vivo.Methods: In this study, we prepared MHE using an ultrasonic extraction containing Forsythiae fructus, Tribuli fructus, Solomon’s seal, Siberian ginseng, Ponciri fructus and Ginseng. We investigated the anti-aging effect of the MHE for skin in dermal fibroblasts. The anti-aging activity was determined by the type I collagen synthesis levels. Matrix metalloproteinase-1 (MMP1) and tissue inhibitor of metalloproteinases 1 (TIMP1) mRNA levels were measured by qRT-PCR. MMP1 protein levels were evaluated by blotting analysis. Clinical tests of skin moisture, elasticity, texture, and wrinkles were performed using cosmetics containing 1% MHE.Results: The MHE induced the upregulation of pro-collagen type I synthesis and TIMP1 mRNA expression. The MHE led to the downregulation of MMP1 mRNA levels and protein levels. Furthermore, after skin application of cosmetics containing 1% MHE, skin hydration, elasticity, texture, and crow’s feet were improved 4 weeks after the treatment.Conclusion: MHE has an anti-aging effect by promoting collagen synthesis and suppressing MMP1 gene expression in vitro, and it has a skin improvement effect in vivo. Therefore, the MHE was shown to have value as a functional cosmetic ingredient.

scholarly journals The effect of fish bone bioactive peptides on the wound healing process: an in vitro study on keratinocytes

2021 ◽  
Vol 26 (3) ◽  
pp. 2692-2699
Author(s):  
ANDREEA IOSAGEANU ◽  
◽  
ANCA OANCEA ◽  
DANIELA ILIE ◽  
ELENA DANIELA ANTON ◽  
...  
Keyword(s):  
Wound Healing ◽  
Bioactive Peptides ◽  
High Efficiency ◽  
Healing Process ◽  
Silver Carp ◽  
Fish Bone ◽  
Wound Healing Process ◽  
Type I ◽  
And Migration

Fish bones mainly contain type I collagen and hydroxyapatite, and despite of their potential for applications in biotechnology and biomedicine, they represent one of the major source of waste generated by fish processing industry. The present study was focused on the interaction of bioactive peptides extracted from silver carp (H. molitrix) bones with human keratinocytes in culture. The potential of fish bone bioactive peptides to influence cell viability, proliferation and migration was evaluated in different experimental models in vitro. The results demonstrated a high efficiency and bioactivity of the enzymatically extracted fish bone peptides in several processes involved in cutaneous wound healing, in particular stimulation of keratinocytes metabolism and migration. In conclusion, they present a huge potential for applications in skin tissue engineering, but also in the biomedical and cosmetic fields.

Hydrogels: A Versatile Drug Delivery Carrier Systems

1970 ◽  
Vol 5 (3) ◽  
pp. 1745-1756
Author(s):  
L H Baldaniya ◽  
Sarkhejiya N A
Keyword(s):  
Drug Delivery ◽  
Protein Delivery ◽  
Structural Integrity ◽  
Healing Process ◽  
Polymer Chains ◽  
Wound Healing Process ◽  
Aqueous Environment ◽  
Preparation Methods ◽  
Control Drug

Hydrogels are the material of choice for many applications in regenerative medicine due to their unique properties including biocompatibility, flexible methods of synthesis, range of constituents, and desirable physical characteristics. Hydrogel (also called Aquagel) is a network of polymer chains that are hydrophilic, sometimes found as a colloidal gel in which water is the dispersion medium. Hydrogels are highly absorbent (contain ~99.9% water), natural or synthetic polymers. Hydrogel also possess a degree of flexibility very similar to natural tissue, due to its significant water content. It can serve as scaffolds that provide structural integrity to tissue constructs, control drug and protein delivery to tissues and cultures. Also serve as adhesives or barriers between tissue and material surfaces. The positive effect of hydrogels on wounds and enhanced wound healing process has been proven. Hydrogels provide a warm, moist environment for wound that makes it heal faster in addition to its useful mucoadhesive properties. Moreover, hydrogels can be used as carriers for liposomes containing variety of drugs, such as antimicrobial drugs. Hydrogels are water swollen polymer matrices, with a tendency to imbibe water when placed in aqueous environment. This ability to swell, under biological conditions, makes it an ideal material for use in drug delivery and immobilization of proteins, peptides, and other biological compounds. Hydrogels have been extensively investigated for use as constructs to engineer tissues in vitro. This review describes the properties, classification, preparation methods, applications, various monomer used in formulation and development of hydrogel products.

scholarly journals Development of a Topical Insulin Polymeric Nanoformulation for Skin Burn Regeneration: An Experimental Approach

2021 ◽  
Vol 22 (8) ◽  
pp. 4087
Author(s):  
Maria Quitério ◽  
Sandra Simões ◽  
Andreia Ascenso ◽  
Manuela Carvalheiro ◽  
Ana Paula Leandro ◽  
...  
Keyword(s):  
Wound Healing ◽  
Healing Process ◽  
In Vitro Release ◽  
Peptide Hormone ◽  
Plga Nanoparticles ◽  
Wound Healing Process ◽  
Target Area ◽  
Encapsulation Process

Insulin is a peptide hormone with many physiological functions, besides its use in diabetes treatment. An important role of insulin is related to the wound healing process—however, insulin itself is too sensitive to the external environment requiring the protective of a nanocarrier. Polymer-based nanoparticles can protect, deliver, and retain the protein in the target area. This study aims to produce and characterize a topical treatment for wound healing consisting of insulin-loaded poly-DL-lactide/glycolide (PLGA) nanoparticles. Insulin-loaded nanoparticles present a mean size of approximately 500 nm and neutral surface charge. Spherical shaped nanoparticles are observed by scanning electron microscopy and confirmed by atomic force microscopy. SDS-PAGE and circular dichroism analysis demonstrated that insulin preserved its integrity and secondary structure after the encapsulation process. In vitro release studies suggested a controlled release profile. Safety of the formulation was confirmed using cell lines, and cell viability was concentration and time-dependent. Preliminary safety in vivo assays also revealed promising results.

scholarly journals STING and cGAS gene expressions were downregulated among HIV-1-infected persons after antiretroviral therapy

2021 ◽  
Vol 18 (1) ◽  
Author(s):  
Lorena Leticia Peixoto de Lima ◽  
Allysson Quintino Tenório de Oliveira ◽  
Tuane Carolina Ferreira Moura ◽  
Ednelza da Silva Graça Amoras ◽  
Sandra Souza Lima ◽  
...  
Keyword(s):  
Gene Expression ◽  
Viral Load ◽  
T Cell ◽  
Antiretroviral Therapy ◽  
Cell Count ◽  
Enzyme Linked Immunosorbent Assay ◽  
Type I ◽  
Α Level ◽  
The Impact ◽  
Hiv 1

Abstract Background The HIV-1 epidemic is still considered a global public health problem, but great advances have been made in fighting it by antiretroviral therapy (ART). ART has a considerable impact on viral replication and host immunity. The production of type I interferon (IFN) is key to the innate immune response to viral infections. The STING and cGAS proteins have proven roles in the antiviral cascade. The present study aimed to evaluate the impact of ART on innate immunity, which was represented by STING and cGAS gene expression and plasma IFN-α level. Methods This cohort study evaluated a group of 33 individuals who were initially naïve to therapy and who were treated at a reference center and reassessed 12 months after starting ART. Gene expression levels and viral load were evaluated by real-time PCR, CD4+ and CD8+ T lymphocyte counts by flow cytometry, and IFN-α level by enzyme-linked immunosorbent assay. Results From before to after ART, the CD4+ T cell count and the CD4+/CD8+ ratio significantly increased (p < 0.0001), the CD8+ T cell count slightly decreased, and viral load decreased to undetectable levels in most of the group (84.85%). The expression of STING and cGAS significantly decreased (p = 0.0034 and p = 0.0001, respectively) after the use of ART, but IFN-α did not (p = 0.1558). Among the markers evaluated, the only markers that showed a correlation with each other were STING and CD4+ T at the time of the first collection. Conclusions ART provided immune recovery and viral suppression to the studied group and indirectly downregulated the STING and cGAS genes. In contrast, ART did not influence IFN-α. The expression of STING and cGAS was not correlated with the plasma level of IFN-α, which suggests that there is another pathway regulating this cytokine in addition to the STING–cGAS pathway.

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