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.

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.

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

Cherries have been largely investigated due to their high content in phenolics in order to fully ex-plore their health-promoting properties. Therefore, this work aimed to assess, for the first time, the anti-inflammatory potential of phenolic-targeted fractions of Saco cherry, using RAW 264.7 mac-rophages stimulated with lipopolysaccharide. Additionally, the cytotoxic effects on gastric ade-nocarcinoma (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 cyclooxygen-ase-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 sweet cherries incorporation in new pharmaceutical products, smart foods and nutraceuticals.

Physically Crosslinked Chitosan/PVA Hydrogels Containing Honey and Allantoin with Long-Term Biocompatibility for Skin Wound Repair: An In Vitro and In Vivo Study

Chitosan/PVA hydrogel films crosslinked by the freeze–thaw method and containing honey and allantoin were prepared for application as wound dressing materials. The effects of the freeze–thaw process and the addition of honey and allantoin on the swelling, the gel content and the mechanical properties of the samples were evaluated. The physicochemical properties of the samples, with and without the freeze–thaw process, were compared using FTIR, DSC and XRD. The results showed that the freeze–thaw process can increase the crystallinity and thermal stability of chitosan/PVA films. The freeze–thaw process increased the gel content but did not have a significant effect on the tensile strength. The presence of honey reduced the swelling and the tensile strength of the hydrogels due to hydrogen bonding interactions with PVA and chitosan chains. Long-term cell culture experiments using normal human dermal fibroblast (NHDF) cells showed that the hydrogels maintained their biocompatibility, and the cells showed extended morphology on the surface of the hydrogels for more than 30 days. The presence of honey significantly increased the biocompatibility of the hydrogels. The release of allantoin from the hydrogel was studied and, according to the Korsmeyer–Peppas and Weibull models, the mechanism was mainly diffusional. The results for the antimicrobial activity against E. coli and S. aureus bacteria showed that the allantoin-containing samples had a more remarkable antibacterial activity against S. aureus. According to the wound healing experiments, 98% of the wound area treated by the chitosan/PVA/honey hydrogel was closed, compared to 89% for the control. The results of this study suggest that the freeze–thaw process is a non-toxic crosslinking method for the preparation of chitosan/PVA hydrogels with long term biocompatibility that can be applied for wound healing and skin tissue engineering.

A Biological Study of Anisotropic Silver Nanoparticles and Their Antimicrobial Application for Topical Use

The excessive use of antibiotics in both human and veterinary medicine has contributed to the development and rapid spread of drug resistance in bacteria. Silver nanoparticles (AgNPs) have become a tool of choice that can be used to treat these resistant bacteria. Several studies have shown that AgNPs have antibacterial and wound healing properties. In this study, we evaluated the biological activity of anisotropic AgNPs to develop an antimicrobial gel formulation for treating wound infections. We showed that some anisotropic AgNPs (S2) have an effective antibacterial activity against bacterial pathogens and low cytotoxicity to keratinocytes and fibroblasts in vitro. The MIC and MBC values were in the range of 2–32 µg/mL, and cytotoxicity had IC50 values of 68.20 ± 9.71 µg/mL and 68.65 ± 10.97 µg/mL against human keratinocyte and normal human dermal fibroblast cells, respectively. The anisotropic AgNPs (S2) were used as a gel component and tested for antibacterial activity, including long-term protection, compared with povidone iodine, a common antiseptic agent. The results show that the anisotropic AgNPs can inhibit the growth of most tested bacterial pathogens and provide protection longer than 48 h, whereas povidone iodine only inhibits the growth of some bacteria. This study suggests that anisotropic AgNPs could be used as an alternative antimicrobial agent for treating bacterial skin infection and as a wound healing formulation.

Antioxidant Activity and Anti-Photoaging Effects on UVA-Irradiated Human Fibroblasts of Rosmarinic Acid Enriched Extract Prepared from Thunbergia laurifolia Leaves

The current study investigated the inhibiting effect on reactive oxygen species (ROS), reactive nitrogen species (RNS), and matrix metalloproteinase-1 (MMP-1) production in a cell-based study of standardized rosmarinic acid enriched extract (SRAEE) prepared from Thunbergia laurifolia leaves. HPLC chromatogram revealed that rosmarinic acid is a major component in prepared SRAEE, followed by caffeic acid. SRAEE exhibited antioxidant activity both in vitro and cell-based studies. SRAEE showed scavenging effects on nitric oxide and superoxide anion and inhibition effects on lipid peroxidation in vitro. SRAEE also inhibited ROS and MMP-1 production in normal human dermal fibroblast cells induced by H2O2 and UVA, respectively, without exerted cytotoxicity. Additionally, collagen degradation was protected by SRAEE induced by UVA. Nitric oxide and inducible nitric oxide synthase (iNOS) productions were also inhibited by SRAEE in RAW264.7 mouse macrophage cells induced by combined lipopolysaccharide (LPS)-interferon-γ (IFN-γ). The results indicated that SRAEE is a potential candidate as a natural pharmaceutical active ingredient for cosmeceutical product application.

Perfusable System Using Porous Collagen Gel Scaffold Actively Provides Fresh Culture Media to a Cultured 3D Tissue

Culturing three-dimensional (3D) tissues with an appropriate microenvironment is a critical and fundamental technology in broad areas of cutting-edge bioengineering research. In addition, many technologies have engineered tissue functions. However, an effective system for transporting nutrients, waste, or oxygen to affect the functions of cell tissues has not been reported. In this study, we introduce a novel system that employs diffusion and convection to enhance transportation. To demonstrate the concept of the proposed system, three layers of normal human dermal fibroblast cell sheets are used as a model tissue, which is cultured on a general dish or porous collagen scaffold with perfusable channels for three days with and without the perfusion of culture media in the scaffold. The results show that the viability of the cell tissue was improved by the developed system. Furthermore, glucose consumption, lactate production, and oxygen transport to the tissues were increased, which might improve the viability of tissues. However, mechanical stress in the proposed system did not cause damage or unintentional functional changes in the cultured tissue. We believe that the introduced culturing system potentially suggests a novel standard for 3D cell cultures.

Therapeutic Effects of Dipterocarpus tuberculatus with High Antioxidative Activity Against UV-Induced Photoaging of NHDF Cells and Nude Mice

To investigate the therapeutic effects of methanol extracts of Dipterocarpus tuberculatus Roxb. (MED) against UV-induced photoaging, we assessed for alterations in the antioxidant activity, anti-apoptotic effects, ECM modulation, skin appearances, and anti-inflammatory response in normal human dermal fibroblast (NHDF) cells and nude mice orally treated with MED. High levels of tannin content and high free radical scavenging activity to DPPH were determined in MED, while seven active components, namely, gallic acid, bergenin, ellagic acid, ε-viniferin, asiatic acid, oleanolic acid, and 2α-hydroxyursolic acid, were identified using LC–MS analyses. UV-induced alterations in the NO concentration, SOD activity, and Nrf2 expression were remarkably recovered in MED-treated NHDF cells. Moreover, the decreased number of apoptotic cells and G2/M phase arrest were observed in the UV + MED-treated groups. Similar recoveries were detected for β-galactosidase, MMP-2/9 expression, and intracellular elastase activity. Furthermore, MED treatment induced suppression of the COX-2-induced iNOS mediated pathway, expression of inflammatory cytokines, and inflammasome activation in UV-radiated NHDF cells. The anti-photoaging effects observed in NHDF cells were subsequently evaluated and validated in UV + MED-treated nude mice through skin phenotypes and histopathological structure analyses. Taken together, these results indicate that MED exerts therapeutic effects against UV-induced photoaging and has the potential for future development as a treatment for photoaging.

Lumenato protects normal human dermal fibroblasts from neutrophil-induced collagen-3 damage in co-cultures

Collagen is the major structural protein in the extracellular matrix of skin produced by fibroblasts. UV exposure results in infiltration of neutrophils within the epidermis and dermis, inducing collagen damage and contributing to the process of photo-aging. Collagen-3 is an integral structural component with collagen-1, and is an important regulator of collagen-1 fibrillogenesis. Addition of neutrophils activated with TNFα to normal human dermal fibroblast cultures, but not their supernatant, caused significant collagen-3 damage. To study whether Lumenato can protect from collagen-3 damage, it was added to co-cultures of Normal human dermal fibroblasts and neutrophils activated with TNFα. Lumenato prevented collagen-3 damage induced by activated neutrophils in a dose-dependent manner in the co-cultures. Lumenato also induced a low rate of collagen-3 synthesis in a dose-dependent manner detected by pro-collagen-3 secretion, but did not affect fibroblast cell number. Although Lumenato inhibited MMP-8, MMP-9, and elastase secreted from neutrophils, its main effect was in inhibiting both NADPH oxidase-producing superoxides and MPO activity-producing halides in a dose-dependent manner that correlated with protection from collagen-3 damage. In conclusion, the results suggest that Lumenato induces low levels of collagen-3 that may contribute for skin health and is very effective in defending the co-cultures from collagen-3 damage by inhibiting free radicals secreted from neutrophils, thus, indicating Lumenato's possible potential for skin protection.

Synthesis and Characterization of Chitosan-Based Nanodelivery Systems to Enhance the Anticancer Effect of Sorafenib Drug in Hepatocellular Carcinoma and Colorectal Adenocarcinoma Cells

The formation of two nanodelivery systems, Sorafenib (SF)-loaded chitosan (SF-CS) and their folate-coated (SF-CS-FA) nanoparticles (NPs), were developed to enhance SF drug delivery on human Hepatocellular Carcinoma (HepG2) and Colorectal Adenocarcinoma (HT29) cell lines. The ionic gelation method was adopted to synthesize the NPs. The characterizations were performed by DLS, FESEM, TEM, XRD, TGA, FTIR, and UV-visible spectroscopy. It was found that 83.7 ± 2.4% and 87.9 ± 1.1% of encapsulation efficiency; 18.2 ± 1.3% and 19.9 ± 1.4% of loading content; 76.3 ± 13.7 nm and 81.6 ± 12.9 nm of hydrodynamic size; 60–80 nm and 70–100 nm of TEM; and FESEM sizes of near-spherical shape were observed, respectively, for SF-CS and SF-CS-FA nanoparticles. The SF showed excellent release from the nanoparticles under pH 4.8 PBS solution, indicating a good delivery system for tumor cells. The cytotoxicity study revealed their better anticancer action towards HepG2 and HT29 cell lines compared to the free sorafenib. Moreover, both NPs systems showed negligible toxicity to normal Human Dermal Fibroblast adult cells (HDFa). This is towards an enhanced anticancer drug delivery system with sustained-release properties for better cancer management.