scholarly journals Cytotoxicity and Epidermal Barrier Function Evaluation of Common Antiseptics for Clinical Use in an Artificial Autologous Skin Model

2021 ◽  
Vol 10 (4) ◽  
pp. 642
Author(s):  
María I. Quiñones-Vico ◽  
Ana Fernández-González ◽  
Elena Pérez-Castejón ◽  
Trinidad Montero-Vílchez ◽  
Salvador Arias-Santiago
Keyword(s):  
Cell Viability ◽  
Barrier Function ◽  
Structural Integrity ◽  
Dermal Fibroblasts ◽  
Histological Evaluation ◽  
Suitable Model ◽  
Chlorhexidine Digluconate ◽  
Epidermal Barrier ◽  
Antiseptic Treatment ◽  
The Impact

Bioengineered artificial skin substitutes (BASS) are the main treatment used in addition to autografts when skin injuries involve a large body surface area. Antiseptic/antibiotic treatment is necessary to prevent infections in the BASS implant area. This study aims to evaluate the effect of antiseptics and antibiotics on cell viability, structural integrity, and epidermal barrier function in BASS based on hyaluronic acid during a 28 day follow-up period. Keratinocytes (KTs) and dermal fibroblasts (DFs) were isolated from skin samples and used to establish BASS. The following antibiotic/antiseptic treatment was applied every 48 h: colistin (1%), chlorhexidine digluconate (1%), sodium chloride (0.02%), and polyhexanide (0.1%). Cell viability (LIVE/DEAD® assay), structural integrity (histological evaluation), and epidermal barrier function (trans-epidermal water loss, (TEWL), Tewameter®) were also evaluated. Cell viability percentage of BASS treated with chlorhexidine digluconate was significantly lower (p ≤ 0.001) than the other antiseptics at day 28. Compared to other treatments, chlorhexidine digluconate and polyhexanide significantly affected the epithelium. No significant differences were found regarding epidermal barrier. These results may be useful for treatment protocols after implantation of BASS in patients and evaluating them in clinical practice. BASS represent a suitable model to test in vitro the impact of different treatments of other skin wounds.

The Impact of Ultraviolet Radiation on Barrier Function in Human Skin: Molecular Mechanisms and Topical Therapeutics

2019 ◽  
Vol 25 (40) ◽  
pp. 5503-5511 ◽  
Author(s):  
Abdulaziz Alhasaniah ◽  
Michael J. Sherratt ◽  
Catherine A. O'Neill
Keyword(s):  
Ultraviolet Radiation ◽  
Barrier Function ◽  
Molecular Mechanisms ◽  
Transepidermal Water Loss ◽  
Protective Effects ◽  
Barrier Dysfunction ◽  
Epidermal Barrier ◽  
Positive Effects ◽  
Terrestrial Mammals ◽  
The Impact

A competent epidermal barrier is crucial for terrestrial mammals. This barrier must keep in water and prevent entry of noxious stimuli. Most importantly, the epidermis must also be a barrier to ultraviolet radiation (UVR) from the sunlight. Currently, the effects of ultraviolet radiation on epidermal barrier function are poorly understood. However, studies in mice and more limited work in humans suggest that the epidermal barrier becomes more permeable, as measured by increased transepidermal water loss, in response UVR, at doses sufficiently high to induce erythema. The mechanisms may include disturbance in the organisation of lipids in the stratum corneum (the outermost layer of the epidermis) and reduction in tight junction function in the granular layer (the first living layer of the skin). By contrast, suberythemal doses of UVR appear to have positive effects on epidermal barrier function. Topical sunscreens have direct and indirect protective effects on the barrier through their ability to block UV and also due to their moisturising or occlusive effects, which trap water in the skin, respectively. Some topical agents such as specific botanical extracts have been shown to prevent the loss of water associated with high doses of UVR. In this review, we discuss the current literature and suggest that the biology of UVR-induced barrier dysfunction, and the use of topical products to protect the barrier, are areas worthy of further investigation.

scholarly journals Nitric Oxide as a Potential Adjuvant Therapeutic for Neuroblastoma: Effects of NO on Murine N2a Cells

2020 ◽  
Vol 7 (2) ◽  
pp. 51
Author(s):  
Jenna L. Gordon ◽  
Melissa M. Reynolds ◽  
Mark A. Brown
Keyword(s):  
Nitric Oxide ◽  
Cell Viability ◽  
Pediatric Cancer ◽  
Clinical Management ◽  
Colony Formation ◽  
Neuroblastoma Cells ◽  
Dermal Fibroblasts ◽  
Cell Analysis ◽  
Monosodium Salt ◽  
The Impact

Neuroblastoma, the most common extracranial solid tumor in children, accounts for 15% of all pediatric cancer deaths. Pharmaceutical applications of S-Nitrosylation, which, under normal conditions is involved with a host of epigenetic and embryological development pathways, have exhibited great potential for use as adjuvant therapeutics in the clinical management of cancer. Herein, an evaluation of the impact of nitric oxide (NO) as a potent anticancer agent on murine neuroblastoma cells is presented. Excitingly cell viability, colony formation, and non-carcinogenic cell analysis illustrate the significance and practicality of NO as a cytotoxic anticancer therapeutic. Resazurin, WST-8 (2-(2-methoxy-4-nitrophenyl)-3-(4-nitrophenyl)-5-(2,4-disulfophenyl)-2H-tetrazolium, monosodium salt), and MTT (3-(4,5-Dimethylthiazol-2-yl)-2,5-diphyltetrazolium bromide) assays consistently displayed a moderate, ~20–25% reduction in cell viability after exposure to 1 mM S-Nitrosoglutathione (GSNO). A colony formation assay demonstrated that treated cells no longer exhibited colony formation capacity. Identically GSNO-treated Adult Human Dermal Fibroblasts (HDFa) exhibited no decrease in viability, indicating potential discrimination between neoplastic and normal cells. Collectively, our findings indicate a potential application for NO as an adjuvant therapeutic in the clinical management of neuroblastoma.

scholarly journals Study of Skin Barrier Function in Psoriasis: The Impact of Emollients

Life ◽  
2021 ◽  
Vol 11 (7) ◽  
pp. 651
Author(s):  
Daniel Maroto-Morales ◽  
Trinidad Montero-Vilchez ◽  
Salvador Arias-Santiago
Keyword(s):  
Barrier Function ◽  
Skin Barrier ◽  
Transepidermal Water Loss ◽  
Psoriatic Skin ◽  
Skin Barrier Function ◽  
Epidermal Barrier ◽  
Stratum Corneum Hydration ◽  
Systemic Inflammatory Disease ◽  
Water Based ◽  
The Impact

Psoriasis is a chronic multi-systemic inflammatory disease that affects the epidermal barrier. Emollients can be used as a coadjutant therapy for psoriasis management, but little is known about how the epidermal barrier function in psoriatic patients is modified by moisturizers. The objective of this study is to evaluate the effect of Vaseline jelly and a water-based formula on epidermal barrier function in psoriatic patients. Thirty-one patients with plaque-type psoriasis and thirty-one gender and age-matched healthy controls were enrolled in the study. Temperature, transepidermal water loss (TEWL), stratum corneum hydration (SCH), pH, elasticity and the erythema index were measured using non-invasive tools before and after applying Vaseline jelly and a water-based formula. TEWL was higher in psoriatic plaques than uninvolved psoriatic skin (13.23 vs. 8.54 g·m−2·h−1; p < 0.001). SCH was lower in psoriatic plaques than uninvolved psoriatic skin and healthy skin (13.44 vs. 30.55 vs. 30.90 arbitrary units (AU), p < 0.001). In psoriatic plaques, TEWL decreased by 5.59 g·m−2·h−1 (p = 0.001) after applying Vaseline Jelly, while it increased by 3.60 g·m−2·h−1 (p = 0.006) after applying the water-based formula. SCH increased by 9.44 AU after applying the water-based formula (p = 0.003). The use of emollients may improve epidermal barrier function in psoriatic patients. TEWL is decreased by using Vaseline, and SCH is increased by using the water-based formula.

The impact of stress on epidermal barrier function: an evidence‐based review

2019 ◽  
Vol 181 (6) ◽  
pp. 1129-1137 ◽  
Author(s):  
M. Maarouf ◽  
C.L. Maarouf ◽  
G. Yosipovitch ◽  
V.Y. Shi
Keyword(s):  
Barrier Function ◽  
Evidence Based ◽  
Epidermal Barrier ◽  
The Impact

VDAC1 Mediated Anticancer Activity of Gallic Acid in Human Lung Adenocarcinoma A549 Cells

2018 ◽  
Vol 18 (2) ◽  
pp. 255-262 ◽  
Author(s):  
Aikebaier Maimaiti ◽  
Amier Aili ◽  
Hureshitanmu Kuerban ◽  
Xuejun Li
Keyword(s):  
Western Blot ◽  
Cell Viability ◽  
Gallic Acid ◽  
Molecular Mechanisms ◽  
A549 Cells ◽  
Dependent Manner ◽  
Lung Carcinoma Cells ◽  
Induced Apoptosis ◽  
The Impact

Aims: Gallic acid (GA) is generally distributed in a variety of plants and foods, and possesses cell growth-inhibiting activities in cancer cell lines. In the present study, the impact of GA on cell viability, apoptosis induction and possible molecular mechanisms in cultured A549 lung carcinoma cells was investigated. Methods: In vitro experiments showed that treating A549 cells with various concentrations of GA inhibited cell viability and induced apoptosis in a dose-dependent manner. In order to understand the mechanism by which GA inhibits cell viability, comparative proteomic analysis was applied. The changed proteins were identified by Western blot and siRNA methods. Results: Two-dimensional electrophoresis revealed changes that occurred to the cells when treated with or without GA. Four up-regulated protein spots were clearly identified as malate dehydrogenase (MDH), voltagedependent, anion-selective channel protein 1(VDAC1), calreticulin (CRT) and brain acid soluble protein 1(BASP1). VDAC1 in A549 cells was reconfirmed by western blot. Transfection with VDAC1 siRNA significantly increased cell viability after the treatment of GA. Further investigation showed that GA down regulated PI3K/Akt signaling pathways. These data strongly suggest that up-regulation of VDAC1 by GA may play an important role in GA-induced, inhibitory effects on A549 cell viability.

Bone tissue engineering in the greater omentum with computer-aided design/computer-aided manufacturing scaffolds is enhanced by a periosteum transplant

2020 ◽  
Author(s):  
Hendrik Naujokat ◽  
Klaas Loger ◽  
Juliane Schulz ◽  
Yahya Açil ◽  
Jörg Wiltfang
Keyword(s):  
Bone Formation ◽  
Bone Tissue ◽  
Computer Aided Design ◽  
Bone Tissue Regeneration ◽  
Histological Evaluation ◽  
Greater Omentum ◽  
Collagen Membrane ◽  
Computer Aided ◽  
3D Printed ◽  
The Impact

Aim: This study aimed to evaluate two different vascularized bone flap scaffolds and the impact of two barrier membranes for the reconstruction of critical-size bone defects. Materials & methods: 3D-printed scaffolds of biodegradable calcium phosphate and bioinert titanium were loaded with rhBMP-2 bone marrow aspirate, wrapped by a collagen membrane or a periosteum transplant and implanted into the greater omentum of miniature pigs. Results: Histological evaluation demonstrated significant bone formation within the first 8 weeks in both scaffolds. The periosteum transplant led to enhanced bone formation and a homogenous distribution in the scaffolds. The omentum tissue grew out a robust vascular supply. Conclusion: Endocultivation using 3D-printed scaffolds in the greater omentum is a very promising approach in defect-specific bone tissue regeneration.

scholarly journals Potential and limitations of finite element modelling in assessing structural integrity of coralline algae under future global change

2015 ◽  
Vol 12 (19) ◽  
pp. 5871-5883 ◽  
Author(s):  
L. A. Melbourne ◽  
J. Griffin ◽  
D. N. Schmidt ◽  
E. J. Rayfield
Keyword(s):  
Climate Change ◽  
Finite Element ◽  
Structural Integrity ◽  
Geometric Model ◽  
Algal Growth ◽  
Coralline Algae ◽  
Rocky Shores ◽  
Element Analysis ◽  
Scan Data ◽  
The Impact

Abstract. Coralline algae are important habitat formers found on all rocky shores. While the impact of future ocean acidification on the physiological performance of the species has been well studied, little research has focused on potential changes in structural integrity in response to climate change. A previous study using 2-D Finite Element Analysis (FEA) suggested increased vulnerability to fracture (by wave action or boring) in algae grown under high CO2 conditions. To assess how realistically 2-D simplified models represent structural performance, a series of increasingly biologically accurate 3-D FE models that represent different aspects of coralline algal growth were developed. Simplified geometric 3-D models of the genus Lithothamnion were compared to models created from computed tomography (CT) scan data of the same genus. The biologically accurate model and the simplified geometric model representing individual cells had similar average stresses and stress distributions, emphasising the importance of the cell walls in dissipating the stress throughout the structure. In contrast models without the accurate representation of the cell geometry resulted in larger stress and strain results. Our more complex 3-D model reiterated the potential of climate change to diminish the structural integrity of the organism. This suggests that under future environmental conditions the weakening of the coralline algal skeleton along with increased external pressures (wave and bioerosion) may negatively influence the ability for coralline algae to maintain a habitat able to sustain high levels of biodiversity.

scholarly journals Inhibition of p38 Mitogen-Activated Protein Kinase Impairs Mayaro Virus Replication in Human Dermal Fibroblasts and HeLa Cells

Viruses ◽  
2021 ◽  
Vol 13 (6) ◽  
pp. 1156
Author(s):  
Madelaine Sugasti-Salazar ◽  
Yessica Y. Llamas-González ◽  
Dalkiria Campos ◽  
José González-Santamaría
Keyword(s):  
Protein Expression ◽  
Hela Cells ◽  
Plaque Assay ◽  
Dermal Fibroblasts ◽  
Dependent Manner ◽  
Human Dermal Fibroblasts ◽  
Mitogen Activated Protein ◽  
Mayaro Virus ◽  
The Impact ◽  
Dose Dependent

Mayaro virus (MAYV) hijacks the host’s cell machinery to effectively replicate. The mitogen-activated protein kinases (MAPKs) p38, JNK, and ERK1/2 have emerged as crucial cellular factors implicated in different stages of the viral cycle. However, whether MAYV uses these MAPKs to competently replicate has not yet been determined. The aim of this study was to evaluate the impact of MAPK inhibition on MAYV replication using primary human dermal fibroblasts (HDFs) and HeLa cells. Viral yields in supernatants from MAYV-infected cells treated or untreated with inhibitors SB203580, SP600125, U0126, or Losmapimod were quantified using plaque assay. Additionally, viral protein expression was analyzed using immunoblot and immunofluorescence. Knockdown of p38⍺/p38β isoforms was performed in HDFs using the PROTACs molecule NR-7h. Our data demonstrated that HDFs are highly susceptible to MAYV infection. SB203580, a p38 inhibitor, reduced MAYV replication in a dose-dependent manner in both HDFs and HeLa cells. Additionally, SB203580 significantly decreased viral E1 protein expression. Similarly, knockdown or inhibition of p38⍺/p38β isoforms with NR-7h or Losmapimod, respectively, affected MAYV replication in a dose-dependent manner. Collectively, these findings suggest that p38 could play an important role in MAYV replication and could serve as a therapeutic target to control MAYV infection.

scholarly journals Impact of RARα and miR-138 on retinoblastoma etoposide resistance

Tumor Biology ◽  
2021 ◽  
Vol 43 (1) ◽  
pp. 11-26
Author(s):  
Maike Busch ◽  
Natalia Miroschnikov ◽  
Jaroslaw Thomas Dankert ◽  
Marc Wiesehöfer ◽  
Klaus Metz ◽  
...  
Keyword(s):  
Cell Viability ◽  
Cell Lines ◽  
Cancer Progression ◽  
Treated Patient ◽  
Luciferase Reporter ◽  
Luciferase Reporter Gene ◽  
Gene Assay ◽  
The Impact

BACKGROUND: Retinoblastoma (RB) is the most common childhood eye cancer. Chemotherapeutic drugs such as etoposide used in RB treatment often cause massive side effects and acquired drug resistances. Dysregulated genes and miRNAs have a large impact on cancer progression and development of chemotherapy resistances. OBJECTIVE: This study was designed to investigate the involvement of retinoic acid receptor alpha (RARα) in RB progression and chemoresistance as well as the impact of miR-138, a potential RARα regulating miRNA. METHODS: RARα and miR-138 expression in etoposide resistant RB cell lines and chemotherapy treated patient tumors compared to non-treated tumors was revealed by Real-Time PCR. Overexpression approaches were performed to analyze the effects of RARα on RB cell viability, apoptosis, proliferation and tumorigenesis. Besides, we addressed the effect of miR-138 overexpression on RB cell chemotherapy resistance. RESULTS: A binding between miR-138 and RARα was shown by dual luciferase reporter gene assay. The study presented revealed that RARα is downregulated in etoposide resistant RB cells, while miR-138 is endogenously upregulated. Opposing RARα and miR-138 expression levels were detectable in chemotherapy pre-treated compared to non-treated RB tumor specimen. Overexpression of RARα increases apoptosis levels and reduces tumor cell growth of aggressive etoposide resistant RB cells in vitro and in vivo. Overexpression of miR-138 in chemo-sensitive RB cell lines partly enhances cell viability after etoposide treatment. CONCLUSIONS: Our findings show that RARα acts as a tumor suppressor in retinoblastoma and is downregulated upon etoposide resistance in RB cells. Thus, RARα may contribute to the development and progression of RB chemo-resistance.

scholarly journals Codon harmonization reduces amino acid misincorporation in bacterially expressed P. falciparum proteins and improves their immunogenicity

AMB Express ◽  
2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Neeraja Punde ◽  
Jennifer Kooken ◽  
Dagmar Leary ◽  
Patricia M. Legler ◽  
Evelina Angov
Keyword(s):  
Protein Structure ◽  
Amino Acid ◽  
Codon Usage ◽  
Dna Sequences ◽  
Structural Integrity ◽  
Host Cells ◽  
Loss Of Function ◽  
Species Specific ◽  
And Function ◽  
The Impact

Abstract Codon usage frequency influences protein structure and function. The frequency with which codons are used potentially impacts primary, secondary and tertiary protein structure. Poor expression, loss of function, insolubility, or truncation can result from species-specific differences in codon usage. “Codon harmonization” more closely aligns native codon usage frequencies with those of the expression host particularly within putative inter-domain segments where slower rates of translation may play a role in protein folding. Heterologous expression of Plasmodium falciparum genes in Escherichia coli has been a challenge due to their AT-rich codon bias and the highly repetitive DNA sequences. Here, codon harmonization was applied to the malarial antigen, CelTOS (Cell-traversal protein for ookinetes and sporozoites). CelTOS is a highly conserved P. falciparum protein involved in cellular traversal through mosquito and vertebrate host cells. It reversibly refolds after thermal denaturation making it a desirable malarial vaccine candidate. Protein expressed in E. coli from a codon harmonized sequence of P. falciparum CelTOS (CH-PfCelTOS) was compared with protein expressed from the native codon sequence (N-PfCelTOS) to assess the impact of codon usage on protein expression levels, solubility, yield, stability, structural integrity, recognition with CelTOS-specific mAbs and immunogenicity in mice. While the translated proteins were expected to be identical, the translated products produced from the codon-harmonized sequence differed in helical content and showed a smaller distribution of polypeptides in mass spectra indicating lower heterogeneity of the codon harmonized version and fewer amino acid misincorporations. Substitutions of hydrophobic-to-hydrophobic amino acid were observed more commonly than any other. CH-PfCelTOS induced significantly higher antibody levels compared with N-PfCelTOS; however, no significant differences in either IFN-γ or IL-4 cellular responses were detected between the two antigens.

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