Human Skin Fibroblast Cell Line Research Articles

Synthesis and Cytotoxicity Evaluation of Spirocyclic Bromotyrosine Clavatadine C Analogs.

Marine-originated spirocyclic bromotyrosines are considered as promising scaffolds for new anticancer drugs. In a continuation of our research to develop potent and more selective anticancer compounds, we synthesized a library of 32 spirocyclic clavatadine analogs by replacing the agmatine, i.e., 4-(aminobutyl)guanidine, side chain with different substituents. These compounds were tested for cytotoxicity against skin cancer using the human melanoma cell line (A-375) and normal human skin fibroblast cell line (Hs27). The highest cytotoxicity against the A-375 cell line was observed for dichloro compound 18 (CC50 0.4 ± 0.3 µM, selectivity index (SI) 2). The variation of selectivity ranged from SI 0.4 to reach 2.4 for the pyridin-2-yl derivative 29 and hydrazide analog of 2-picoline 37. The structure–activity relationships of the compounds in respect to cytotoxicity and selectivity toward cancer cell lines are discussed.

Abstract 2090: TP73 expression may be influenced by DNA methylation in human tumorigenesis

Abstract Epigenetic events that cause alterations in gene expression are common in human cancers. The connection between TP73 expression and its epigenetic functionality in tumorigenesis has scarcely been explored. As a transcription factor, TP73 (aka, p73) like its cousin, p53, is activated in response to DNA damage and regulates the expression of downstream genes involved in cell cycle arrest and apoptosis. However, there are other compounding functions of this gene that reflect its non-tumor-related characteristics, thus making it very difficult to assess its specific role in tumorigenesis. Our previous work showed that DNA methylation activates TP73 expression in hepatocellular carcinoma (HCC) and gastrointestinal cancer. In this study, we determined TP73 expression in normal human mammary epithelial cells (HMECs), human non-cancerous Li-Fraumeni Syndrome (LFS) skin fibroblast cells, human breast cancer cell lines (MCF7, MDA-MB-231 & MDA-MB-468), prostate cancer cell lines (LNCaP & MDA-PCa2b), lung cancer cell lines (A549 & NCI-H596), neuroblastoma cell lines (IMR32 & SK-N-SH) and normal human skin fibroblast cell line (HS27). The results show that TP73 was expressed solely in cancer cells. Subsequent immunohistochemical analyses of TP73 expression in cancerous and adjacent non-cancerous liver tissues of HCC patients clearly showed that TP73 expression was exclusively evident in cancerous tissues but not in the adjacent normal liver tissues. Mechanistically, methylation-specific PCR and bisulfite sequencing studies revealed that TP73 promoter is activated only in cancer cells and this activation occurs via DNA methylation. Moreover, ChIP assays demonstrated that a CTCF (a chromosomal networking protein CCCTC binding factor) and tumor protein p53 (TP53) bind to TP73 promoter and regulate TP73 expression. Our observations demonstrate that a positive correlation in tumorigenesis exists between TP73 expression and DNA methylation in promoter regions of TP73. These findings suggest that TP73's role in carcinogenesis may prove to be pivotal for the development of future diagnostic and therapeutic applications. Citation Format: Zhixing Yao, David R. Yao, William Yu, Ahmed Malki, Zaki A. Sherif. TP73 expression may be influenced by DNA methylation in human tumorigenesis [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 2090.

Encapsulation of folic acid (vitamin B9) into sporopollenin microcapsules: Physico-chemical characterisation, in vitro controlled release and photoprotection study

Folic acid (FA) is a crucial vitamin for all living creatures. However, it is susceptible to degradation under pH, heat, ultraviolet (UV) and day sunlight conditions, resulting in lowering its bioavailability. Therefore, a versatile protective encapsulation system for FA is highly required to overcome its inherent instability. We report the use of the robust Lycopodium clavatum sporopollenin (LCS) microcapsules, extracted from their natural micrometer-sized raw spores, for FA microencapsulation. The physico-chemical characterisation of the LCS microcapsules are comprehensively investigated before and after the microencapsulation using SEM, elemental, CLSM, FTIR, TGA/DTG and XRD analyses, revealing a successful FA encapsulation within the LCS in an amorphous form. The phenylpropanoid acids, responsible for the UV protection and the autofluorescence of the LCS, were found in the LCS as evidenced by FTIR analysis. TGA/DTG results revealed that the hemi-cellulose and cellulose are the major component of the LCS. A controlled and sustained release of FA from FA-loaded LCS were achieved where the release profile of FA-loaded LCS was found to be pH-dependent. The percentages of cumulative FA released after 10 h at 37 ± 0.5 °C were 45.5% and 76.1% in pH 1.2 and 7.4, respectively, ensuring controlled and slow release in simulated physiological conditions. The FA release kinetic studies indicated the prevalence of the Fickian diffusion mechanism in pH 1.2, while anomalous non-Fickian transport was ascribed for FA release in pH 7.4. The in vitro cytotoxicity assay revealed that the obtained formulations were biocompatible against the human skin fibroblast (HSF) cell line. The versatile LCS microcapsules exhibited intriguing photostability for FA under UV or sunlight irradiation. Concretely, the obtained FA sustained delivery and photoprotection properties of these LCS microcapsules validate their multifunctional characteristics, opening up intriguing applications in oral and topical drug delivery as well as in food industry.

4-thiazolidinone-based derivatives rosiglitazone and pioglitazone affect the expression of antioxidant enzymes in different human cell lines

PPARγ regulate the expression of genes involved in peripheral insulin sensitivity, adipogenesis, and glucose homeostasis. Moreover, PPARγ agonists, such as pioglitazone and rosiglitazone, are used in the treatment of various diseases, e.g. diabetes (type II), atherosclerosis, inflammatory skin disease, and some types of cancers. PPARγ agonists have also been found to reduce oxidative-stress (OS) and OS-induced apoptosis. Therefore, the aim of the present study was to evaluate the impact of 4-thiazolidinone-based derivatives Les-2194, Les-3377, and Les-3640 on the expression of antioxidant enzymes in human squamous cell carcinoma (SCC-15), lung carcinoma (A549), colon adenocarcinoma (CACO-2), and skin fibroblast (BJ) cell lines. After 24 h of exposure, Les-2194 caused an increase in ROS production in the SCC-15 and CACO-2 cell lines; however, no changes in caspase-3 activity and metabolic activity were observed. Nevertheless, the Ki67 level was significantly decreased. Les-3377 was able to increase ROS production in all tested cell lines, but no impact on metabolic activity and caspase-3 activity were noticed. In turn, Les-3640 was able to induce ROS overproduction in BJ, SCC-15, and CACO-2 and did not affect metabolic activity. However, an increase in caspase-3 activity was observed at the 10 µM concentration in all tested cell lines. All tested compounds were able to influence CAT and SOD1 expression and decreased (Les-2194 in the BJ cells) or increased (Les-3640 in the SCC-15 and CACO-2 cells) PPARγ expression.

Quinoline-sulfamoyl carbamates/sulfamide derivatives: Synthesis, cytotoxicity, carbonic anhydrase activity, and molecular modelling studies

Carbonic anhydrase (CA) IX, and XII isoforms are known to be highly expressed in various human tissues and malignancies. CA IX is a prominent target for some cancers because it is overexpressed in hypoxic tumors and this overexpression leads to poor prognosis. Novel twenty-seven compounds in two series (sulfamoylcarbamate-based quinoline (2a-2o) and sulfamide-based quinoline (3a-3l)) were synthesized and characterized by means of IR, NMR, and mass spectra. Their inhibitory activities were evaluated against CA I, CA II, CA IX, and CA XII isoforms. 2-Phenylpropyl (N-(quinolin-8-yl)sulfamoyl)carbamate (2m) exhibited the highest hCA IX inhibition with the Ki of 0.5 µM. In addition, cytotoxic effects of the synthesized compounds on human colorectal adenocarcinoma (HT-29; HTB-38), human breast adenocarcinoma (MCF7; HTB-22), human prostate adenocarcinoma (PC3; CRL-1435) and human healthy skin fibroblast (CCD-986Sk; CRL-1947) cell lines were examined. The cytotoxicity results showed that 2j, 3a, 3e, 3f are most active compounds in all cell lines (HT-29, MCF7, PC3, and CCD-986Sk).

Stable copper nanoparticles as potential antibacterial agent against aquaculture pathogens and human fibroblast cell viability

The developments of green nanotechnology are generating interest of researchers towards synthesis of copper nanoparticles due to their increasing application towards the biomedical field. The utilization of phytochemicals in plant extracts have become a valuable trend in the synthesis of nanoparticles as they possess dual nature of reducing and stabilizing agents. In this work a simple and rapid biosynthesis route for producing stable fenugreek copper nanoparticles (FCuNPs) using Trigonella foenum-graecum is demonstrated and assessed its antibacterial activity against gram negative Vibrio species. The characterization of synthesized FCuNPs was carried out using UV–vis spectrophotometer and the SPR of FCuNPs is observed at 350 nm. TEM, HRTEM –SAED analysis was done to evaluate the morphology and size of FCuNPs. FTIR spectra of both the plant extract and FCuNPs were recorded in order to study the interaction of phytochemicals with FCuNPs. The antibacterial activity of biosynthesized FCuNPs was tested against V. vulnificus, V. harveyi and V. parahaemolyticus using agar well diffusion technique. Since this method of synthesizing copper nanoparticles does not involve any harmful chemicals, the FCuNPs produced are more biocompatible and were used to evaluate human skin fibroblast cell line by Alamar Blue reduction assay. The outcomes of this report will surely provide a new path in the field of nanotechnology and nano medicine where there is a significant need of antibacterial and cell viability studies. Hence, FCuNPs can be powerful therapeutic materials in numerous biomedical applications, which are to be discovered in the near prospective.

Anti-bacterial and biocompatibility properties of green synthesized silver nanoparticles using Parkia biglandulosa (Fabales:Fabaceae) leaf extract

The biosynthesis of silver nanoparticles is considered to be a feasible, green, and eco-friendly method. Silver nanoparticles (AgNPs) were synthesized using badminton ball tree (Parkia biglandulosa) leaf extract and their significant physiochemical properties were characterized. The aqueous extract of the leaf of P. biglandulosa act as a reducing as well as capping agent for the reduction of Ag+ ​ions. FTIR analysis was conducted to find out the compounds that were liable for the bio-reduction of silver ions and to study the functional groups present in P. bigalandulosa leaf extract. The biologically reduced silver nanoparticles showed a surface plasmon resonance at 439 ​nm as studied from the UV–visible absorption spectrum. TEM studies confirmed the shape of the nanoparticles to be spherical with an average diameter of 15 ​nm. The anti-bacterial properties of the prepared nanoparticles were tested against Bacillus cereus by well plate method. Biosynthesized silver nanoparticles (PbAgNPs) at 0.02 ​M concentration showed the most antibacterial activity with a zone of inhibition of 7 ​mm. The high biocompatibility of the PbAgNPs by using human skin fibroblast cell line was evaluated by Alamar Blue reduction assay. The PbAgNPs had shown the highest cell viability when compared to native nanoparticles, meanwhile, a significant increase in cell viability was noted for the nanoparticles. The biosynthetic approach for synthesis was found to be a facile, rapid, single-step, safe, and effective alternative to the conventional physical/chemical methods.

Study on proanthocyanidins crosslinked collagen membrane for guided bone tissue regeneration.

The goal of this study is to understand the ability of a newly developed barrier membrane to enhance bone tissue regeneration. Here in this study we present the in vitro characterization of the barrier membrane made from type I collagen and crosslinked by oligomeric proanthocyanidins (OPCs). The effects of the membrane (P-C film) on cell cycle, proliferation, alkaline phosphatase activity, and mineralization were evaluated using the human osteoblast cell line MG-63, while the barrier ability was examined using MG-63 cells, as well as the human skin fibroblast cell line WS-1. The pore size is one of the factors that plays a key role in tissue regeneration, therefore, we evaluated the pore size of the membrane using a capillary flow porometer. Our results showed that the mean pore size of the P-C film was approximately 7-9 µm, the size known to inhibit cell migration across the membrane. The P-C film also demonstrated excellent cell viability and good biocompatibility, since the cell number increased with time, with MG-63 cells proliferating faster on the P-C film than in the cell culture flask. Furthermore, the P-C film promoted osteoblast differentiation, resulting in higher alkaline phosphatase activity and mineralization. Therefore, our results suggest that this P-C film has a great potential to be used in guided bone regeneration during periodontal regeneration and bone tissue engineering.

The Cytotoxic Effect of Gold Polyacrylate (Aurumacryl) on Human Skin Fibroblasts

The cytotoxic effect of the potential antitumor drug aurumacryl (gold polyacrylate) on human skin fibroblast cell line hFB-hTERT6 has been studied in vitro. It has been found that aurumacryl exhibits substantial cytotoxicity to human skin fibroblasts. The maximum cytotoxic effect (75% cell death) is observed at an aurumacryl concentration of 0.125 mg/mL. The inhibitory concentration of aurumacryl that causes 50% human skin fibroblast death (IC50) is 0.09 mg/mL.

Characterization of exopolysaccharide produced from marine-derived Aspergillus terreus SEI with prominent biological activities

Four fungal isolates were obtained from marine sediments collected from El-Max shore of Alexandria City, Egypt. The four isolates were screened for exopolysaccharide (EPS) production. The most promising isolate SEI that provided the highest EPS yield (4.98 g/L) was identified morphologically and genetically using 18S rRNA gene sequence analysis as Aspergillus terreus (A. terreus). Physio-chemical analysis using UV–Vis estimated the carbohydrate contents to be ~ 70.7%. As well, HPLC analysis indicated that it composed of O-glucosamine 59.2%, D-fucose 1.27%, D-glucose 0.88% and D-galactose 0.56%. Further, NMR showed the abundance of α-type monosaccharides over β-anomers, existed mainly in the pyranose form. The SEC estimated the molar mass (Mw-) to be ~ 5.0 x 104 g/mol. The SEM revealed irregular blocks-like structure with smooth surface. The anticoagulant activity of SEI-EPS was investigated for the first time using activated partial thromboplastin time (APTT) assay. The current results displayed that the SEI-EPS had successfully increased the APTT from 33 s to 56 s and 251 s at concentrations of 10 and 100 mg/mL, respectively. Moreover, SEI-EPS showed cytotoxic effects against breast cancer and human skin fibroblast cell lines (IC50 > 100 µg/mL and IC50 ~ 47 µg/mL, respectively). To the best of our knowledge, this is the first time to report the anticoagulant and cytotoxic activities of A. terreus EPS.

Amygdalin Decreases Adhesion and Migration of MDA-MB-231 and MCF-7 Breast Cancer Cell Lines.

Cell adhesion, as dynamic interactions between cell-cell and cell-matrix, has an essential role in cancer cell migration. Integrins as cell membrane receptors are involved in cell adhesion and signal transduction. Aberrant expression of integrins is associated with the cancer cell adhesion. Targeting the process of cell adhesion and migration could be helpful to prevent cancer cell metastasis. Amygdalin is a cyanoglycoside compound with anti-cancer properties, while its effect on cancer cell adhesion is not completely clear. The cytotoxic effect of amygdalin on breast cancer cell lines (MCF-7 and MDA-MB- 231) and human skin fibroblast cell line as a normal cell, was evaluated through MTT assay. The cell adhesion assay and wound healing assay were performed to determine amygdalin effects on adhesion and migration of cancer cells. Further analysis was carried out to evaluate integrin α and β levels through real-time PCR. We demonstrated that amygdalin diminished the cell viability of both cell lines in a time and dose-dependent manner, while amygdalin did not have any toxicity on the human skin fibroblast cell line in the same dosages. Following amygdalin treatment, the adhesion of both studied cell lines to fibronectin and collagen I decrease, and this reduction is significantly greater in the case of binding to fibronectin compared to binding to collagen. The MDA-MB-231 cell migration was decreased greater than MCF-7 cells. The levels of α and β integrin were differentially regulated by amygdalin in both cancer cell lines. These results suggest that depending on cancer cell lines, amygdalin affects cancer cell adhesion and migration.

Electrospun poly(vinyl alcohol)/reduced graphene oxide nanofibrous scaffolds for skin tissue engineering

Graphene is composed of a two-dimensional (2D) layer of carbon atoms arranged in a honeycomb lattice configuration. In this paper, we adopted a green synthetic method of producing reduced graphene oxide using glucose as a reducing and stabilizing agent. We also investigated the fabrication of electrospun nanofibers of glucose-reduced graphene oxide (GRGO) (0–1.0 wt%) reinforced with polyvinyl alcohol (PVA) as (PG) scaffolds, and chemically crosslinked with acidic glutaraldehyde (GA) in acetone medium to mimic the extracellular matrix (ECM) for skin tissue engineering applications. These PG scaffolds were evaluated for morphology, mechanical strength, surface wettability, thermal properties, hemocompatibility, and biocompatibility. Field emission-scanning electron microscopy (FE-SEM) revealed an increase in the thickness of nanofibers in PG scaffolds with an increase in the concentration of GRGO. X-ray diffraction and attenuated total reflectance-infrared and Raman spectra showed the GRGO was incorporated in the PVA nanofibrous matrix. As the concentration of GRGO was increased in PG scaffolds, tensile strengths and elongations at break decreased, whereas thermal properties increased. The biological activities of PG scaffolds were evaluated using in vitro hemolysis, using CCD-986Sk (a human skin fibroblast cell line) viability and proliferation assays, and by live/dead cell imaging. Results showed GRGO inclusion in PVA nanofibers caused a slight hydrophilic to hydrophobic shift. PG scaffolds did not cause hemolysis of red blood cells even at a GRGO loading of 1.0 wt%, and PG-1.0 scaffold (with a GRGO loading of 1.0 wt%) exhibited excellent compatibility with fibroblasts and significantly increased metabolic activity after culture for 21 days as compared with PG-0 controls. DAPI staining and live/dead imaging assays showed that all PG scaffolds increased fibroblast proliferation and viability, indicating the potential for skin tissue engineering applications.

Screening of Antioxidant Potentials and Bioactive Properties of the Extracts Obtained from Two Centaurea L. Species (C. kroumirensis Coss. and C. sicula L. subsp sicula)

Herbal medicines, dietary supplements, or infusions with health promoting effects can note strong consumer demand. Hence, researchers and scientists have been increasingly focusing on the promotion of medicinal plants. In this respect, the present study has the evaluation of the biological properties of different extracts (hexane, chloroform, methanol, ultrasonic, essential oil, and supercritical) obtained from two Centaurea species (C. kroumirensis (Coss.) and C. sicula L. subsp sicula) as purpose. Antioxidative activities were assessed by in vitro assays including total phenolic content, free radical scavenging assay and ferric ion reducing power. Among the fourteen extracts examined, the highest total phenolic content (TPC) and antioxidant abilities were recorded in ultrasonic ethanol extracts of both Centaurea species. Additionally, these extracts exhibited a noticeable strong protective effect of the human skin fibroblast cell line (HS-68) that was exposed to oxidative stress induced by hydrogen peroxide. According to our results, the sonication with ethanol might be an ideal, rapid, and eco-friendly extraction method for obtaining a polyphenol-rich extract that exhibited high antioxidant activity. The results presented herein suggest that Centaurea species could be promoted as an antioxidant resource that could be exploited for the development of nutraceuticals or in pharmacology industry.

ЦИТОТОКСИЧЕСКОЕ ДЕЙСТВИЕ ПОЛИАКРИЛАТА ЗОЛОТА (АУРУМАКРИЛ) НА ФИБРОБЛАСТЫ КОЖИ ЧЕЛОВЕКА

The cytotoxic effect of the potential antitumor drug aurumacryl (aurum polyacrylate) on the hFB-hTERT6 human skin fibroblast cell line has been studied in vitro. It has been established that aurumacril exhibits substantial cytotoxicity to human skin fibroblasts. The maximum of cytotoxic effect (75% cell death) was observed when the concentration of aurumacryl was 0.125 mg/ml. The inhibitory concentration of aurumacryl causing 50% human skin fibroblast death (IC50) was 0.09 mg/ml.

Aluminium and calcium lake pigments of Lac natural dye

This work presents the physicochemical properties of the prepared lac lakes. The study revealed the stability, cytotoxicity and use of lac lake pigment as a cosmetic colorant. SEM, XRD and DSC were used to study the characteristics of the lac lakes.. The color stability of lac dye and its lakes was investigated at ambient temperature and at 45 °C, in sunlight,fluorescent light and darkness, for 3 months. Cytotoxicity on human dermal skin fibroblast cell lines was tested using MTT assay and the use of the lakes as a colorant in lip color product was studied. Different metal salts resulted in lac lakes of different shades and appearance. SEM, XRD and DSC results indicated that the morphology and structure of lac dye were changed after reacting with metal salts which support the coordination of metal ion with lac dye. The lac lakes were not cytotoxic to human dermal skin fibroblast cells (0.78-100 µg/mL). Lac lakes exhibited less alteration of color shade over acidic and basic conditions when compared with the lac dye itself. Additionally, the lake pigments displayed better color stability than lac dye and produced an orange-brown shade of lip color product. The results suggest that lac lake pigments have good potential for use as cosmetic colorant.

Evaluation of wound healing activity of ethanol extract of Annona reticulata L. leaf both in vitro and in diabetic mice model

Background and aimThe leaves of AnnonareticulataLinn (牛心果niú x ınguǒ; Bullock’s heart), a member of Annonaceae family, have been used extensively in folk medicine; however, its wound healing potential is yet to be explored. Our aim was to investigate the wound healing ability of A. reticulataleaf extract in vitro and in streptozotocin induced diabetic mice model. Material and methodsWe observed the plant extract induced proliferation and migration of primary human dermal fibroblast (HDF), human skin fibroblast cell line (GM00637) and human keratinocyte cell line (HACAT). The expression of transforming growth factor beta (TGF-β), connective tissue growth factor (CTGF), vascular endothelial growth factor (VEGF), alpha smooth muscle actin (α-SMA), matrix metalloproteinases (MMP-2, MMP-9), collagen-1, collagen-3, focal adhesion kinase (FAK) were evaluated by Western blot and gelatin zymography. Excisional diabetic wound model was used for in vivo wound healing assay. Furthermore, we processed wound tissue for histological and immunohistochemical study. ResultA. reticulata L. leaf extract stimulates proliferation and migration of HDF, skin fibroblast and keratinocyte significantly in a dose dependent manner; expression of TGF-β, CTGF, VEGF, α-SMA, MMP-2, MMP-9, collagen-1, collagen-3, FAK increased. Additionally, an enhanced expression of phospho-SMAD2, phospho-SMAD3 in the treated cells indicated the activation of TGF-β signal transduction pathway, similarly increased expression of phospho-AkT suggested activation of PI3/AkT pathway. Expression of CTGF and α-SMA was also increased significantly in wound tissue. Mass spectrometric analysis revealed that mainly two compounds to be present in the extract: quercetin and β-sitosterol. ConclusionCollective data suggest that A.reticulata leaf extract may have a stimulatory effect in diabetic wound healing.

Pharmacology Study of the Multiple Angiogenesis Inhibitor RC28-E on Anti-Fibrosis in a Chemically Induced Lung Injury Model.

Background: Disease-related injury in any organ triggers a complex cascade of cellular and molecular responses that culminate in tissue fibrosis, inflammation, and angiogenesis simultaneously. Multiple cell angiogenesis is an essential part of the tissue damage response, which is involved in fibrosis development. RC28-E is a novel recombinant dual decoy receptor lgG1 Fc-fusion protein that can block vascular endothelial growth factor (VEGFA), platelet-derived growth factor (PDGF), and fibroblast growth factor-2 (FGF-2) simultaneously. This protein has stepped into clinical trials (NCT03777254) for the treatment of pathological neovascularization-related diseases. Here, we report on the role of RC28-E during anti-fibrosis and its potential multitarget function in regulating fibrosis. Methods: A bleomycin-induced pulmonary fibrosis C57BL/6 mouse model was established. Hematoxylin and eosin staining (HE) and Masson staining (Masson’s) were performed to evaluate the pulmonary fibrosis based on the scoring from, Ashcroft score. Fibrosis related factors and inflammatory cytokines including HYP, α-SMA, procollagen, ICAM, IL-6, IL-1, and TNF-α were also determined at the protein and mRNA levels to characterize the fibrosis. Both mRNA and protein levels of VEGF, FGF, and transforming growth factor (TGF)-β were detected by quantitative real-time PCR (qRT-PCR) and immunohistochemical (IHC) analysis, respectively. Pulmonary fibrosis and related cytokines were re-evaluated in vivo after 3 doses of RC28-E (5 mg/kg, 15 mg/kg, and 50 mg/kg, ip. Tiw × 9) in comparison with a mono-target antagonist treatment (VEGF or FGF blocking). RC28-E attenuated the activation of TGF-β induced fibroblasts in vitro. Expression levels of α-SMA and collagen I, as well as proliferation and migration, were determined with the human skin fibroblast cell line Detroit 551 and primary murine pulmonary fibroblast cells. The mechanism of RC28-E via the TGF-β/Smad pathway was also investigated. Results: RC28-E exhibits significant anti-fibrosis effects on Idiopathic pulmonary fibrosis (IPF) in vivo. Moreover, TGF-β induced fibroblast activation in vitro via the inhibition of the TGF-β downstream Smad pathway, thus providing potential therapeutics for clinical disease-related fibrosis-like IPF as well as chemotherapy-induced fibrosis in cancer therapy.

Evaluation of stability and in vitro wound healing potential of melatonin loaded (lipid enriched) chitosan based microspheres.

The aim of this study was to evaluate long-term stability and assess the wound healing potential of the innovative melatonin-loaded lipid-enriched hybrid system compared to conventional melatonin-loaded chitosan microspheres. The hybrid system contained nanostructured lipid carrier incorporated in the chitosan matrix, in order to modify melatonin release and alter physicochemical characteristics of the delivery system. Stability testing was performed during a six-month period under two conditions: refrigerated (5 ± 3 °C) and at room temperature (25 ± 2 °C/60 ± 5 % RH). Samples stored at both conditions were analyzed in terms of particle size, zeta potential, moisture content and thermal properties. At the end of testing, drug content was determined in all samples. Dressings wound healing potential was assessed by in vitro scratch test using human skin fibroblast cell line. Although both systems showed good stability characteristics, the addition of lipids in the system has improved its wound healing potential.

Safety Assessment of Natural Color Foundation for Atopy

Purpose: As a therapeutic makeup product, foundation is used to reduce the anxiety and unease associated with appearance in people with atopic skin problems. The aim of the present study was to prepare and evaluate the safety of natural color foundation for atopy. Methods: Color foundations containing organic kaolin and zinc oxide were prepared. Safety of color foundation was evaluated by MTT cell viability assay (CCD-986sk human skin fibroblast cell line), and human repeat insult patch test for atopic dermatits. Results: Results of the MTT cell viability assay showed that the growth activity of human skin fibroblast cells was over 88% in all concentrations of the natural color foundations (sample C and D). Patch test revealed that the natural color foundations were safe. While two cases showed weak positive reactions (+) to sample A and B (general foundation on the market). Conclusion: Natural color foundation with kaolin and zinc oxide was verified safe for atopic dermatitis and it appears to be beneficial for use as a foundation for atopy.

Biocomposites conductive scaffold based on PEDOT:PSS/nHA/chitosan/PCL: Fabrication and characterization

Biomaterial-based scaffolds with suitable characteristics are highly desired in tissue engineering (TE) application. Biocomposites based on polymer and ceramics increase the chance for modulating the properties of scaffold. In recent years, researchers have considered conductive polymers to be used in TE application, due to their conductivity. This property has a good impact on tissue regeneration. A suitable design for bone substitute that consists of considerations such as material component, fabrication technique and mechanical properties. The previous studies on PEDOT:PSS/nHA/CS showed high wettability rate but low mechanical properties. Polycaprolactone (PCL) is a biodegradable and biocompatible polymer with a low wettability. The incorporation of PCL inside biocomposite can lead to the decrement in wettability and increment in mechanical property. In addition, this paper would examine the feasibility of blending of PCL and chitosan to fabricate PEDOT:PSS/nHA/CS composite scaffold. The fabrication technique of freezing/ lyophilization was used in this study. The scaffolds were characterized morphologically using scanning electron microscopy (SEM). Wettability was studied using a contact angle instrument. The attenuated total reflectance fourier transform infrared spectroscopy (ATR-FTIR) spectra interpreted the presence of polymeric ingredients within composite scaffold. Conductivity of the scaffolds was measured using a Digital Multimeter. In-vitro biological evaluation of the scaffolds was studied using human skin Fibroblast (HSF) cell line. The morphological study of biocomposite PEDOT:PSS/nHA/CS/PCL scaffold revealed random pore sizes and 66% porosity. Contact angle of the scaffold was increased and the swelling property and pore sizes were decreased after blending of PCL polymer. The viability of HSF cells on biocomposite PEDOT:PSS/nHA/CS/PCL scaffold was 85%. After 7 days, SEM analysis revealed the presence of cells on the surface of scaffold. In conclusion, the results suggested that PEDOT:PSS/nHA/CS/PCL biocomposite scaffold was non-toxic to cells and has suitable properties.