Biocompatibility and Antioxidant Capabilities of Carbon Dots Obtained from Tomato (Solanum lycopersicum)

Since their discovery in 2004, carbon dots have attracted strong interest in the scientific community due to their characteristic properties, particularly their luminescence and their ease of synthesis and derivatization. Carbon dots can be obtained from different carbon sources, including natural products, resulting in a so-called ’green synthesis’. In this work, we obtain carbon dots from tomato juice in order to obtain nanoparticles with the antioxidant capabilities of the natural antioxidants present in that fruit. The obtained material is characterized regarding nanoparticle size distribution, morphology, surface functional groups and optic properties. Antioxidant properties are also evaluated through the DPPH method and their cytotoxicity is checked against human dermal fibroblast and A549 cell-lines. The results indicate that carbon dots obtained from tomato have a higher antioxidant power than other already-published antioxidant carbon dots. The bandgap of the synthesized materials was also estimated and coherent with the literature values. Moreover, carbon dots obtained from tomato juice are barely toxic for healthy cells up to 72 h, while they induce a certain cytotoxicity in A549 lung carcinoma cells.

Evaluation of Polycaprolactone Electrospun Nanofiber-Composites for Artificial Skin Based on Dermal Fibroblast Culture

The study’s aim was to develop a dermal equivalent scaffold that can mimic the architecture and biological performance of the human dermis. Poly ε-caprolactone (PCL) electrospun nanofiber material (ENF) was assembled with polyethylene glycol diacrylate (PEGDA), sodium alginate (SA) and type I collagen (CG1) to develop three groups of dermal equivalent scaffolds. These scaffolds were named PEGDA-PCL, SA-PCL and CG1-PCL. Scanning electron microscopy (SEM) images of cell-free scaffolds’ top and cross-sectional surface were collected and analyzed to examine internal morphology, specifically the adhesiveness of PCL fibers with the different scaffolds. Human dermal fibroblasts were cultured on each of the scaffolds. Cell viability studies including cell adhesion, cell differentiation and stress fiber production were conducted on each scaffold. Furthermore, the architectural integrity of each scaffold was verified by degradation analysis for 2 weeks by soaking each scaffold in phosphate-buffered saline (PBS) solution. Finally, we conducted rheological characteristics of each scaffold. Based on our results from the above analysis, the study concluded that CG1-PCL is best suitable for the dermal equivalent model and has potential to be used as a graft for skin repair.

Imination of Microporous Chitosan Fibers—A Route to Biomaterials with “On Demand” Antimicrobial Activity and Biodegradation for Wound Dressings

Microporous chitosan nanofibers functionalized with different amounts of an antimicrobial agent via imine linkage were prepared by a three-step procedure including the electrospinning of a chitosan/PEO blend, PEO removal and acid condensation reaction in a heterogeneous system with 2-formylphenylboronic acid. The fibers’ characterization was undertaken keeping in mind their application to wound healing. Thus, by FTIR and 1H-NMR spectroscopy, it was confirmed the successful imination of the fibers and the conversion degree of the amine groups of chitosan into imine units. The fiber morphology in terms of fiber diameter, crystallinity, inter- and intra-fiber porosity and strength of intermolecular forces was investigated using scanning electron microscopy, polarized light microscopy, water vapor sorption and thermogravimetric analysis. The swelling ability was estimated in water and phosphate buffer by calculating the mass equilibrium swelling. The fiber biodegradation was explored in five media of different pH, corresponding to different stages of wound healing and the antimicrobial activity against the opportunistic pathogens inflicting wound infection was investigated according to standard tests. The biocompatibility and bioadhesivity were studied on normal human dermal fibroblast cells by direct contact procedure. The dynamic character of the imine linkage of the functionalized fibers was monitored by UV-vis spectroscopy. The results showed that the functionalization of the chitosan microporous nanofibers with antimicrobial agents via imine linkage is a great route towards bio-absorbable wound dressings with “on demand” antimicrobial properties and biodegradation rate matching the healing stages.

Anti-Inflammatory and Antiproliferative Properties of Sweet Cherry Phenolic-Rich Extracts

Cherries have largely been investigated due to their high content in phenolics in order to fully explore their health-promoting properties. Therefore, this work aimed to assess, for the first time, the anti-inflammatory potential of phenolic-targeted fractions of the Saco cherry, using RAW 264.7 macrophages stimulated with lipopolysaccharide. Additionally, the cytotoxic effects on gastric adenocarcinoma (AGS), neuroblastoma (SH-SY5Y) and normal human dermal fibroblast (NHDF) cells were evaluated, as well as the ability to protect these cellular models against induced oxidative stress. The obtained data revealed that cherry fractions can interfere with cellular nitric oxide (NO) levels by capturing NO radicals and decreasing inducible nitric oxide synthase and cyclooxygenase-2 expression. Furthermore, it was observed that all cherry fractions exhibited dose-dependent cytotoxicity against AGS cells, presenting cytotoxic selectivity for these cancer cells when compared to SH-SY5Y and NHDF cells. Regarding their capacity to protect cancer cells against oxidative injury, in most assays, the total cherry extract was the most effective. Overall, this study reinforces the idea that sweet cherries can be incorporated into new pharmaceutical products, smart foods and nutraceuticals.

Modulation by 17,20S(OH)2pD of Fibrosis-Related Mediators in Dermal Fibroblast Lines from Healthy Donors and from Patients with Systemic Sclerosis

We previously demonstrated that the non-calcemic pregnacalciferol (pD) analog 17,20S (OH)2pD suppressed TGF-β1-induced type I collagen production in cultured normal human dermal fibroblasts. In the present studies, we examined fibroblasts cultured from the lesional skin of patients with systemic sclerosis (scleroderma (SSc)) and assessed the effects of 17,20S(OH)2pD on fibrosis-related mediators. Dermal fibroblast lines were established from skin biopsies from patients with SSc and healthy controls. Fibroblasts were cultured with either 17,20S(OH)2pD or 1,25(OH)2D3 (positive control) with/without TGF-β1 stimulation and extracted for protein and/or mRNA for collagen synthesis and mediators of fibrosis (MMP-1, TIMP-1, PAI-1, BMP-7, PGES, GLI1, and GLI2). 1 7,20S(OH)2pD (similar to 1,25(OH)2D3) significantly suppressed net total collagen production in TGF-β1-stimulated normal donor fibroblast cultures and in cultures of SSc dermal fibroblasts. 17,20S(OH)2pD (similar to 1,25(OH)2D3) also increased MMP-1, BMP-7, and PGES and decreased TIMP-1 and PAI1 expression in SSc fibroblasts. Although 17,20S(OH)2pD had no effect on Gli1 or Gli2 in SSc fibroblasts, it increased Gli2 expression when cultured with TGF-β1 in normal fibroblasts. These studies demonstrated that 17,20S(OH)2pD modulates mediators of fibrosis to favor the reduction of fibrosis and may offer new noncalcemic secosteroidal therapeutic approaches for treating SSc and fibrosis.

A Study of Vanadate Group Substitution into Nanosized Hydroxyapatite Doped with Eu3+ Ions as a Potential Tissue Replacement Material

In this study, nanosized vanadate-substituted hydroxyapatites doped with 1 mol% and 2 mol% Eu3+ ions were obtained via the precipitation method. To evaluate the structure and morphology of the obtained compounds, the XRPD (X-ray powder diffraction) technique, Rietveld refinement, SEM-EDS (scanning electron microscopy-energy-dispersive spectrometry) and TEM (transmission electron microscopy) techniques as well as FTIR (Fourier transform infrared) spectroscopy were performed. Moreover, the chemical formula was confirmed using the ICP-OES (Inductively coupled plasma optical emission spectroscopy spectroscopy). The calculated average grain size for powders was in the range of 25 to 90 nm. The luminescence properties of vanadium-substituted hydroxyapatite were evaluated by recording emission spectra and excitation spectra as well as luminescence kinetics. The crucial step of this research was the evaluation of the biocompatibility of the synthesized nanomaterials. Therefore, the obtained compounds were tested toward sheep red blood cells and normal human dermal fibroblast to confirm the nontoxicity and biocompatibility of new nanosized Eu3+ ion-doped vanadate-hydroxyapatite. Moreover, the final step of the research allowed us to determine the time dependent ion release to the simulated body fluid environment. The study confirmed cytocompatibility of vanadium hydroxyapatite doped with Eu3+ ions.

Sequential Four-Component Synthesis And Antitumor Activity Screening of Spiro[chromene-indolo[2,1-b]quinazoline] And Spiro[indolo[2,1-b]Quinazoline-pyrano[3,2-c]chromene]

Chemotherapy is one of the most common types of treatment among cancer patients and by using potent chemicals and agents, tumor promotion was inhibited. Despite the usage of many chemical agents in cancer therapy, cancer is still incurable. It seems that the synthesis of new compounds with high efficiency on cancer cells and low side effects on normal cells will remain a critical challenge among researchers in this area. In the present work, a fast and straightforward process for the transformations involving tryptanthrins, malononitrile, some types of CH-acids such as 1,3-cyclohexanedione, dimedone, and 4-hydroxycumarin resulting in preparing spiro[chromene-indolo[2,1-b]quinazoline] and spiro[indolo[2,1-b]quinazoline-pyrano[3,2-c]chromene] derivatives through sequential Knoevenagel/Michael/intramolecular cyclization sequences was reported. at room temperature. This protocol benefits some notable advantages including short reaction time, mild reaction condition, and simple purification, which make it interesting. Furthermore, it was carried out at room temperature, so it is according to green chemistry procedures. Also, antitumor screening of our new synthetic compounds (4a-i) was evaluated on pancreatic cancer cells (Panc1), breast cancer cells (MDA-MB-231), prostate cancer cells (PC3), and normal human adult dermal fibroblast cells (HDF) by using MTT assay using etoposide as a positive control. We found that 50% growth inhibitory concentration (IC50) values of our synthetic compounds were not lower than etoposide against three cancer cell lines.

Insilico and Invitro optimization of Naringin and rutin molecules targeting DNA damage in breast cancer cells

Discovering the molecular mechanisms of DNA damage response pathways has led to new therapeutic approaches in oncology. Our study optimized DNA damage-targeting molecules naringin and rutin in breast cancer cells. Our study involved MTT assays for detection of its toxicity and proliferative activity in breast cancer cells and normal cancer cells. Our studies determined the molecules' antioxidant properties using the DPPH assay. The role in reducing free radicals has been evaluated using a variety of free radical scavenging activity assays. Further evaluation of the molecules was carried out by high alkaline comet assay (pH>13) to test for genotoxicity. Human Dermal Fibroblast cells (2DD) (1x105 cells/ml) and breast cancer cells (MDA-MB-231) were pre-incubated with Naringin and Rutin (10 microMolar) for one hour. In normal cells, rutin and naringin molecules do not cause genotoxicity, but they cause DNA damage in breast cancer cells when they are diluted to 10microMolar. The results from our study indicate that both molecules cause 60-70% DNA damage in breast cancer cells.

Human Metabolites of Hamaforton™ (Hamamelis virginiana L. Extract) Modulates Fibroblast Extracellular Matrix Components in Response to UV-A Irradiation

Hamamelis virginiana L. a rich source of both condensed and hydrolyzable tannins, utilized to treat dermatological disorders. Since no experimental and clinical data is available for its use as oral formulation in skin related disorders, the purpose of this study was to investigate the effects of Hamaforton™ (Hamamelis virginiana extract) metabolites on gene dysregulation induced by ultraviolet A radiation in cultured human dermal fibroblasts. A combination of in vivo and ex vivo experimental designs has been exploited in order to take into account the polyphenol metabolic transformation that occurs in humans. 12 healthy volunteers received either a capsule of Hamaforton™ or a placebo in a randomized, blinded crossover trial. After Hamaforton™ ingestion, the kinetic of appearance of galloyl derivatives was measured in plasma. Then, in the ex vivo experiment, the serum isolated after supplementation was used as a source of Hamaforton™ metabolites to enrich the culture medium of dermal fibroblasts exposed to ultraviolet A radiation. Three different gallic acid metabolites (4-O-methyl gallic acid, 4-O-methyl gallic acid sulphate and trimethyl gallic acid glucuronide) were identified in volunteer plasma. While, ultraviolet A irradiation of dermal fibroblasts affected the expression of extracellular matrix genes, the presence of Hamaforton™ metabolites in the culture media did not affect the expression of most of those genes. However, the activation of the expression of 10 different genes involved in repair processes for the maintenance of skin integrity, suggest that the metabolites can play a role in damage recovery. To our knowledge, this is the first study that demonstrates the bioavailability of Hamaforton™ phenolic compounds, and the effects of its metabolites on cultured dermal fibroblast response to ultraviolet A irradiation.