Biocompatibility and Antimicrobial Profile of Acid Usnic-Loaded Electrospun Recycled Polyethylene Terephthalate (PET)-Magnetite Nanofibers.

The highest amount of the world's polyethylene terephthalate (PET) is designated for fiber production (more than 60%) and food packaging (30%) and it is one of the major polluting polymers. Although there is a great interest in recycling PET-based materials, a large amount of unrecycled material is derived mostly from the food and textile industries. The aim of this study was to obtain and characterize nanostructured membranes with fibrillar consistency based on recycled PET and nanoparticles (Fe3O4@UA) using the electrospinning technique. The obtained fibers limit microbial colonization and the development of biofilms. Such fibers could significantly impact modern food packaging and the design of improved textile fibers with antimicrobial effects and good biocompatibility. In conclusion, this study suggests an alternative for PET recycling and further applies it in the development of antimicrobial biomaterials.

Adipose-Derived Stem Cells (ADSCs) Supplemented with Hepatocyte Growth Factor (HGF) Attenuate Hepatic Stellate Cell Activation and Liver Fibrosis by Inhibiting the TGF-ß/Smad Signaling Pathway in Chemical-Induced Liver Fibrosis Associated with Diabetes.

Liver fibrosis can develop on the background of hyperglycemia in diabetes mellitus. However, xenobiotic-related factors may accelerate diabetes-associated liver fibrosis. In this study, we aimed to assess the antfibrotic effect of ADSC and HGF therapy and to establish the cellular and molecular mechanisms through in vitro and in vivo experiments. In vitro, TGF-ß1-activated hepatic stellate cells (HSCs) were cocultured with ADSCs or HGF, and the expression of several fibrosis markers was investigated. The antifibrotic effect of the ADSCs, HGF, and ADSCs supplemented with HGF was further assessed in vivo on diabetic mice with liver fibrosis experimentally induced. In vitro results showed the inhibition of HSC proliferation and decrease in fibrogenesis markers. Coadministration of ADSCs and HGF on diabetic mice with liver fibrosis enhanced antifibrotic effects confirmed by the downregulation of Col I, α-SMA, TGF-ß1, and Smad2, while Smad7 was upregulated. Moreover, stem cell therapy supplemented with HGF considerably attenuated inflammation and microvesicular steatosis, decreased collagen deposits, and alleviated liver fibrosis. In conclusion, the HGF-based ADSC therapy might be of interest for the treatment of liver fibrosis in diabetic patients, consecutive aggression exerts by different environmental factors.

Systemic Beta-Hydroxybutyrate Affects BDNF and Autophagy into the Retina of Diabetic Mice.

Background: Diabetic retinopathy (DR) is a neurovascular disease, characterized by a deficiency of brain-derived neurotrophic factor (BDNF), a regulator of autophagy. Beta-hydroxybutyrate (BHB), previously reported as a protective agent in DR, has been associated with BDNF promotion. Here, we investigated whether systemic BHB affects the retinal levels of BDNF and local autophagy in diabetic mice with retinopathy; Methods: C57BL/6J mice were administered with intraperitoneal (i.p.) streptozotocin (STZ) (75 mg/kg) injection to develop diabetes. After 2 weeks, they received i.p. injections of BHB (25−50−100 mg/kg) twice a week for 10 weeks. Retinal samples were collected in order to perform immunofluorescence, Western blotting, and ELISA analysis; Results: BHB 50 mg/kg and 100 mg/kg significantly improved retinal BDNF levels (p < 0.01) in diabetic mice. This improvement was negatively associated with autophagosome−lysosome formations (marked by LC3B and ATG14) and to higher levels of connexin 43 (p < 0.01), a marker of cell integrity. Moreover, BHB administration significantly reduced M1 microglial activation and autophagy (p < 0.01); Conclusions: The systemic administration of BHB in mice with DR improves the retinal levels of BDNF, with the consequent reduction of the abnormal microglial autophagy. This leads to retinal cell safety through connexin 43 restoration.

Silk ProteinsEnriched Nanocomposite Hydrogels Based on Modified MMT Clay and Poly(2-hydroxyethyl methacrylate-co-2-acrylamido-2-methylpropane Sulfonic Acid) Display Favorable Properties for Soft Tissue Engineering.

Due to their remarkable structures and properties, three-dimensional hydrogels and nanostructured clay particles have been extensively studied and have shown a high potential for tissue engineering as solutions for tissue defects. In this study, four types of 2-hydroxyethyl methacrylate/2-acrylamido-2-methylpropane sulfonic acid/montmorillonite (HEMA/AMPSA/MMT) hydrogels enriched with sericin, and fibroin were prepared and studied in the context of regenerative medicine for soft tissue regenerative medicine. Our aim was to obtain crosslinked hydrogel structures using modified montmorillonite clay as a crosslinking agent. In order to improve the in vitro and in vivo biocompatibility, silk proteins were further incorporated within the hydrogel matrix. Fourier transform infrared spectroscopy with attenuated total reflectance (FTIR-ATR) were performed to prove the chemical structures of the modified MMT and nanocomposite hydrogels. Swelling and rheological measurements showed the good elastic behavior of the hydrogels due to this unique network structure in which modified MMT acts as a crosslinking agent. Hydrogel biocompatibility was assessed by MTT, LDH and LIVE/DEAD assays. The hydrogels were evaluated for their potential to support adipogenesis in vitro and human stem cells isolated from adipose tissue were seeded in them and induced to differentiate. The progress was assessed by evaluation of expression of adipogenic markers (ppar-γ2, perilipin) evaluated by qPCR. The potential of the materials to support tissue regeneration was further evaluated on animal models in vivo. All materials proved to be biocompatible, with better results on the 95% HEMA 5% AMPSA enriched with sericin and fibroin material. This composition promoted a better development of adipogenesis compared to the other compositions studied, due the addition of sericin and fibroin. The results were confirmed in vivo as well, with a better progress of soft tissue regeneration after implantation in mice. Therefore, hydrogel 95% HEMA 5% AMPSA enriched with sericin as well as fibroin showed the best results that recommend it for future soft tissue engineering application.

Graphene-Oxide Porous Biopolymer Hybrids Enhance In Vitro Osteogenic Differentiation and Promote Ectopic Osteogenesis In Vivo.

Over the years, natural-based scaffolds have presented impressive results for bone tissue engineering (BTE) application. Further, outstanding interactions have been observed during the interaction of graphene oxide (GO)-reinforced biomaterials with both specific cell cultures and injured bone during in vivo experimental conditions. This research hereby addresses the potential of fish gelatin/chitosan (GCs) hybrids reinforced with GO to support in vitro osteogenic differentiation and, further, to investigate its behavior when implanted ectopically. Standard GCs formulation was referenced against genipin (Gp) crosslinked blend and 0.5 wt.% additivated GO composite (GCsGp/GO 0.5 wt.%). Pre-osteoblasts were put in contact with these composites and induced to differentiate in vitro towards mature osteoblasts for 28 days. Specific bone makers were investigated by qPCR and immunolabeling. Next, CD1 mice models were used to assess de novo osteogenic potential by ectopic implantation in the subcutaneous dorsum pocket of the animals. After 4 weeks, alkaline phosphate (ALP) and calcium deposits together with collagen synthesis were investigated by biochemical analysis and histology, respectively. Further, ex vivo materials were studied after surgery regarding biomineralization and morphological changes by means of qualitative and quantitative methods. Furthermore, X-ray diffraction and Fourier-transform infrared spectroscopy underlined the newly fashioned material structuration by virtue of mineralized extracellular matrix. Specific bone markers determination stressed the osteogenic phenotype of the cells populating the material in vitro and successfully differentiated towards mature bone cells. In vivo results of specific histological staining assays highlighted collagen formation and calcium deposits, which were further validated by micro-CT. It was observed that the addition of 0.5 wt.% GO had an overall significant positive effect on both in vitro differentiation and in vivo bone cell recruitment in the subcutaneous region. These data support the GO bioactivity in osteogenesis mechanisms as being self-sufficient to elevate osteoblast differentiation and bone formation in ectopic sites while lacking the most common osteoinductive agents.

Regenerative Potential of Mesenchymal Stem Cells' (MSCs) Secretome for Liver Fibrosis Therapies.

Chronic liver injuries lead to liver fibrosis and then to end-stage liver cirrhosis. Liver transplantation is often needed as a course of treatment for patients in critical conditions, but limitations associated with transplantation prompted the continuous search for alternative therapeutic strategies. Cell therapy with stem cells has emerged as an attractive option in order to stimulate tissue regeneration and liver repair. Transplanted mesenchymal stem cells (MSCs) could trans-differentiate into hepatocyte-like cells and, moreover, show anti-fibrotic and immunomodulatory effects. However, cell transplantation may lead to some uncontrolled side effects, risks associated with tumorigenesis, and cell rejection. MSCs' secretome includes a large number of soluble factors and extracellular vesicles (EVs), through which they exert their therapeutic role. This could represent a cell-free strategy, which is safer and more effective than MSC transplantation. In this review, we focus on cell therapies based on MSCs and how the MSCs' secretome impacts the mechanisms associated with liver diseases. Moreover, we discuss the important therapeutic role of EVs and how their properties could be further used in liver regeneration.

Fingolimod and Diabetic Retinopathy: A Drug Repurposing Study.

This study aimed to investigate the interactions between fingolimod, a sphingosine 1-phosphate receptor (S1PR) agonist, and melanocortin receptors 1 and 5 (MCR1, MCR5). In particular, we investigated the effects of fingolimod, a drug approved to treat relapsing-remitting multiple sclerosis, on retinal angiogenesis in a mouse model of diabetic retinopathy (DR). We showed, by a molecular modeling approach, that fingolimod can bind with good-predicted affinity to MC1R and MC5R. Thereafter, we investigated the fingolimod actions on retinal MC1Rs/MC5Rs in C57BL/6J mice. Diabetes was induced in C57BL/6J mice through streptozotocin injection. Diabetic and control C57BL/6J mice received fingolimod, by oral route, for 12 weeks and a monthly intravitreally injection of MC1R antagonist (AGRP), MC5R antagonist (PG20N), and the selective S1PR1 antagonist (Ex 26). Diabetic animals treated with fingolimod showed a decrease of retinal vascular endothelial growth factor A (VEGFA) and vascular endothelial growth factor receptors 1 and 2 (VEGFR1 and VEGFR2), compared to diabetic control group. Fingolimod co-treatment with MC1R and MC5R selective antagonists significantly (p < 0.05) increased retinal VEGFR1, VEGFR2, and VEGFA levels compared to mice treated with fingolimod alone. Diabetic animals treated with fingolimod plus Ex 26 (S1PR1 selective blocker) had VEGFR1, VEGFR2, and VEGFA levels between diabetic mice group and the group of diabetic mice treated with fingolimod alone. This vascular protective effect of fingolimod, through activation of MC1R and MC5R, was evidenced also by fluorescein angiography in mice. Finally, molecular dynamic simulations showed a strong similarity between fingolimod and the MC1R agonist BMS-470539. In conclusion, the anti-angiogenic activity exerted by fingolimod in DR seems to be mediated not only through S1P1R, but also by melanocortin receptors.

Genotoxicity and Gene Expression in the Rat Lung Tissue following Instillation and Inhalation of Different Variants of Amorphous Silica Nanomaterials (aSiO2 NM).

Several reports on amorphous silica nanomaterial (aSiO2 NM) toxicity have been questioning their safety. Herein, we investigated the in vivo pulmonary toxicity of four variants of aSiO2 NM: SiO2_15_Unmod, SiO2_15_Amino, SiO2_7 and SiO2_40. We focused on alterations in lung DNA and protein integrity, and gene expression following single intratracheal instillation in rats. Additionally, a short-term inhalation study (STIS) was carried out for SiO2_7, using TiO2_NM105 as a benchmark NM. In the instillation study, a significant but slight increase in oxidative DNA damage in rats exposed to the highest instilled dose (0.36 mg/rat) of SiO2_15_Amino was observed in the recovery (R) group. Exposure to SiO2_7 or SiO2_40 markedly increased oxidative DNA lesions in rat lung cells of the exposure (E) group at every tested dose. This damage seems to be repaired, since no changes compared to controls were observed in the R groups. In STIS, a significant increase in DNA strand breaks of the lung cells exposed to 0.5 mg/m3 of SiO2_7 or 50 mg/m3 of TiO2_NM105 was observed in both groups. The detected gene expression changes suggest that oxidative stress and/or inflammation pathways are likely implicated in the induction of (oxidative) DNA damage. Overall, all tested aSiO2 NM were not associated with marked in vivo toxicity following instillation or STIS. The genotoxicity findings for SiO2_7 from instillation and STIS are concordant; however, changes in STIS animals were more permanent/difficult to revert.

Sex and Age-Related Differences in Neuroinflammation and Apoptosis in Balb/c Mice Retina Involve Resolvin D1.

(1) Background: The pro-resolving lipid mediator Resolvin D1 (RvD1) has already shown protective effects in animal models of diabetic retinopathy. This study aimed to investigate the retinal levels of RvD1 in aged (24 months) and younger (3 months) Balb/c mice, along with the activation of macro- and microglia, apoptosis, and neuroinflammation. (2) Methods: Retinas from male and female mice were used for immunohistochemistry, immunofluorescence, transmission electron microscopy, Western blotting, and enzyme-linked immunosorbent assays. (3) Results: Endogenous retinal levels of RvD1 were reduced in aged mice. While RvD1 levels were similar in younger males and females, they were markedly decreased in aged males but less reduced in aged females. Both aged males and females showed a significant increase in retinal microglia activation compared to younger mice, with a more marked reactivity in aged males than in aged females. The same trend was shown by astrocyte activation, neuroinflammation, apoptosis, and nitrosative stress, in line with the microglia and Müller cell hypertrophy evidenced in aged retinas by electron microscopy. (4) Conclusions: Aged mice had sex-related differences in neuroinflammation and apoptosis and low retinal levels of endogenous RvD1.

Nano Selenium-Enriched Probiotics as Functional Food Products against Cadmium Liver Toxicity.

Since cadmium is a toxic metal that can cause serious health problems for humans, it is necessary to find bioremediation solutions to reduce its harmful effects. The main goal of our work was to develop a functional food based on elemental selenium nanoparticles (SeNPs) obtained by green synthesis using Lactobacillus casei and to validate their ability to annihilate the hepatic toxic effects induced by cadmium. The characterization of SeNPs was assessed by UV-Vis spectroscopy, FTIR, XRD, DLS and TEM. In order to investigate the dose-dependent protective effects of SeNPs on Cd liver toxicity, mice were assigned to eight experimental groups and fed by gavage, with 5 mg/kg b.w. cadmium, respectively, with co-administration with SeNPs or lacto-SeNPs (LSeNPs) in 3 doses (0.1, 0.2 and 0.4 mg/kg b.w.) for 30 days. The protective effect was demonstrated by the restoration of blood hepatic markers (AST, ALT, GGT and total bilirubin) and antioxidant enzymes, such as catalase (CAT) and glutathione peroxidase (GPx). Moreover, the antioxidant capacity of mice plasma by the FRAP assay, revealed the highest antioxidant capacity for the 0.2 mg/kg LSeNPs group. Histopathological analysis demonstrated the morphological alteration in the group that received only cadmium and was restored after the administration of SeNPs or LSeNPs, while the immunohistochemical analysis of the bcl family revealed anti-apoptotic effects; the Q-PCR analysis showed an upregulation of hepatic inflammatory markers for the group exposed to Cd and a decreased value for the groups receiving oral SeNPs/ LSeNPs in a dose-dependent manner. The best protective effects were obtained for LSeNPs. A functional food that includes both probiotic bacteria and elemental SeNPs could be successfully used to annihilate Cd-induced liver toxicity, and to improve both nutritional values and health benefits.

Corrigendum: Changes in Retinal Structure and Ultrastructure in the Aged Mice Correlate with Differences in the Expression of Selected Retinal miRNAs.

[This corrects the article DOI: 10.3389/fphar.2020.593514.].

Complexation with Random Methyl-ß-Cyclodextrin and (2-Hidroxypropyl)-ß-Cyclodextrin Enhances In Vivo Anti-Fibrotic and Anti-Inflammatory Effects of Chrysin via the Inhibition of NF-κB and TGF-ß1/Smad Signaling Pathways and Modulation of Hepatic Pro/Anti-Fibrotic miRNA.

Chrysin (CHR) is a natural flavonoid with a wide range of pharmacological activities, including hepatoprotection, but poor water solubility. By including water-soluble hydroxypropyl (HPBCD) and randomly methylated (RAMEB) ß-cyclodextrin, we aimed to increase its biodisponibility and the effectiveness of the antifibrotic effects of chrysin at oral administration. Liver fibrosis in mice was induced in 7 weeks by CCl4 i.p. administration, and afterwards treated with 50 mg/kg of CHR-HPBCD, CHR-RAMEB, and free chrysin. CCl4 administration increased hepatic inflammation (which was augmented by the upregulation of nuclear factor kappa-light-chain enhancer of activated B cells (NF-kB), tumor necrosis factor (TNF)-α, and interleukin 6 (IL-6) and induced fibrosis, as determined using histopathology and electron microscopy. These results were also confirmed by the upregulation of Collagen I (Col I) and matrix metalloproteinase (MMP) expression, which led to extracellular fibrotic matrix proliferation. Moreover, the immunopositivity of alpha-smooth muscle actin (a-SMA) in the CCl4 group was evidence of hepatic stellate cell (HSC) activation. The main profibrotic pathway was activated, as confirmed by an increase in the transforming growth factor- ß1 (TGF-ß1) and Smad 2/3 expression, while Smad 7 expression was decreased. Treatment with CHR-HPBCD and CHR-RAMEB considerably reduced liver injury, attenuated inflammation, and decreased extracellular liver collagen deposits. CHR-RAMEB was determined to be the most active antifibrotic complex. We conclude that both nanocomplexes exert anti-inflammatory effects and antifibrotic effects in a considerably stronger manner than for free chrysin administration.

A novel experimental approach to evaluate guided bone regeneration (GBR) in the rat femur using a 3D-printed CAD/CAM zirconia space-maintaining barrier.

INTRODUCTION: Obtaining a certain bone volume is an important goal in implantology or orthopedics. Thus, after tooth extraction, quite a lot of horizontal and vertical alveolar bone is lost in time and can be detrimental to the implant treatment outcome, while the treatment of critical bone defects is a considerable challenge for surgery. OBJECTIVES: In this study we designed a new in vivo model as an useful experimental tool to assess guided bone regeneration (GBR) using a computer-aided design/manufacturing (CAD-CAM) space-maintaining barrier. METHODS: The barrier was 3D printed with three progressive heights, surgically placed on rat femur, and GBR results were analyzed at 2, 4, and 8 weeks by X-ray and bone mineral density analysis, histology/morphometry and by immunofluorescence and immunohistochemistry for osteogenesis and angiogenesis evaluation. RESULTS: The obtained results show that the proposed experimental model provides a real-time useful information on progressive bone tissue formation, which depends on the volume of isolated space created for GBR and on molecular events that lead to satisfactory vertical and horizontal bone augmentation and osteointegration. CONCLUSION: In conclusion, the proposed customized three-dome space-maintaining barrier is suitable as an experimental tool to assess the potential of using the designed barriers in dentistry and orthopedics to promote the formation of new bone and determine their space- and time-dependent limitations. Meanwhile, guided bone augmentation for dentistry requires subsequent evaluation on an alveolar bone preclinical model followed by clinical implementation.

Qualifying Osteogenic Potency Assay Metrics for Human Multipotent Stromal Cells: TGF-ß2 a Telling Eligible Biomarker.

Potency assays are critical for regenerative medicine, addressing the known challenge of functional heterogeneity among human multipotent stromal cells (hMSC). Necessary laboratory cell expansion allows analysis before implantation in the patient. Levels of induction of five signature gene biomarkers, ALPL, COL1A2, DCN, ELN and RUNX2, constituted a previously reported proof-of-principle osteogenic potency assay. We tested assay modification to enhance reproducibility using six consistent bone marrow derived hBM-MSC and explored applicability to three adipose tissue derived hAT-MSC. Using a potent proprietary osteogenic induction factor, the GUSB/YWAHZ reference gene pair provided real time PCR consistency. The novel assay conditions supported the concept that genes encoding extracellular matrix proteins one week after osteogenic induction were informative. Nonetheless, relatively low induction of COL1A2 and ELN encouraged search for additional biomarkers. TGFB2 mRNA induction, important for osteogenic commitment, was readily quantifiable in both hBM-MSC and hAT-MSC. Combined with DCN, TGFB2 mRNA induction data provided discriminatory power for resolving donor-specific heterogeneity. Histomorphometric decorin and TGF-ß2 protein expression patterns in eight-week heterotopic bone implants also discriminated the two non-bone-forming hMSC. We highlight progress towards prompt osteogenic potency assays, needed by current clinical trials to accelerate improved intervention with enhanced stem cell therapy for serious bone fractures.

Comprehensive Appraisal of Graphene-Oxide Ratio in Porous Biopolymer Hybrids Targeting Bone-Tissue Regeneration.

The bone-tissue engineering (BTE) field is continuously growing due to a major need for bone substitutes in cases of serious traumas, when the bone tissue has reduced capacity for self-regeneration. So far, graphene oxide (GO)-reinforced natural materials provide satisfactory results for BTE, for both in vitro and in vivo conditions. In this study, we aimed to evaluate the biocompatibility of a new biocomposite consisting of chitosan and fish gelatin crosslinked with genipin and loaded with various concentrations of GO (0.5, 1, 2, 3 wt.%) for prospective BTE applications. Scaffold characterizations revealed a constant swelling degree and good resistance to enzyme degradation. The composites presented a porous structure with pores of similar size, thus mimicking the bone structure. In vitro biocompatibility assays demonstrated an overall beneficial interaction between preosteoblasts, and these particular composites, particularly with 0.5 wt.% GO, reinforced composition. Next, the materials were implanted subcutaneously in 6-week old CD1 mice for in vivo evaluation of biocompatibility and inflammatory activity. Immunohistochemical staining revealed maximal cell infiltration and minimal inflammatory reaction for fish gelatin/chitosan/genipin with 0.5 wt.% GO scaffold, thus demonstrating the best biocompatibility for this particular composition, confirming the in vitro results. This study revealed the potential use of fish gelatin/chitosan GO composites for further implementation in the BTE field.

Effects of Dietary Inclusion of Bilberry and Walnut Leaves Powder on the Digestive Performances and Health of Tetra SL Laying Hens.

The purpose of this study was to examine the effects of dietary inclusion of two additives at the final concentration of 0.5% bilberry (E1) and 1% walnut (E2) leaves powder in the basal diet on digestive health of hens. A total number of 90 Tetra SL hens were divided into two experimental groups (E1 and E2) and one control group (C) consisting of 30 hens each. After four weeks, 10 hens of each group were sacrificed and tissue samples and intestinal content were taken from the duodenum, jejunum, and cecum in order to perform histological, enzymatic, and microbiota analyses. In groups E1 and E2, the histological analysis showed a significant increase of villus height, resulting probably in increased absorption of nutrients in duodenum and jejunum. A decrease in the specific activity of alpha-amylase and trypsin in E1 and E2 for both duodenum and jejunum compared to the control one was also recorded. In addition, the maltase and invertase specific activity in duodenum increased, a tendency that was kept for maltase but not for invertase in jejunum. The cecal microbiota of E1 and E2 individuals was characterized by an increase of Firmicutes and Lactobacilli and a decrease of Enterobacteriaceae. In conclusion, our results indicate that bilberry and walnut leaves additives in feed may improve the health status of the poultry gastrointestinal tract.

Release of the Non-Steroidal Anti-Inflammatory Drug Flufenamic Acid by Multiparticulate Delivery Systems Promotes Adipogenic Differentiation of Adipose-Derived Stem Cells.

Engineered tissue-like structures often instigate an inflammatory response in the host that can inhibit wound healing and ultimately lead to the rejection of the implant. In our previous study, we have characterized the properties and biocompatibility of novel multiparticulate drug delivery systems (MDDS), based on collagen matrix with gradual release of anti-inflammatory drug flufenamic acid, we evaluated their anti-inflammatory potential and demonstrated their efficiency against burns and soft tissue lesions. In addition to these results, FA was previously described as a stimulant for adipogenesis, therefore we hypothesized that MDDS might also be appropriate for adipose tissue engineering. After the cell-scaffold constructs were obtained, cell morphology, adhesion and spreading on the systems were highlighted by scanning electron microscopy, immunostaining and confocal microscopy. The effect of FA-enriched materials on adipogenesis was evaluated at gene and protein level, by RT-qPCR, confocal microscopy and immunohistochemistry. Our current work indicates that flufenamic acid plays a beneficial role in adipocyte differentiation, with a direct effect upon the gene and protein expression of important early and late markers of adipogenesis, such as PPARγ2 and perilipin.

The morphological changes of the colonic goblet cells and mucin profile in oncohematological patients under Epirubicin-based chemotherapy.

Changes in the lining of the small intestine following chemotherapy have been extensively studied, although also occurs in the large intestine. The aim of this study was to assess the consequences of Epirubicin-based therapy on goblet cells (GCs) and mucus production on colonic mucosa, immediately and after short-time of chemotherapy administration to oncohematological patients, by clinical and histopathological analysis. We assessed the mucus production, composition, and distribution by Alcian Blue (pH 2.5)-Periodic Acid-Schiff (PAS) staining, alongside with the immunoexpression of mucin (MUC)2, MUC4 and inflammatory markers in a series of oncohematological patients, immediately and after short-time of Epirubicin-based chemotherapy cumulative therapy cessation. We showed that GCs number decrease slightly at 48 hours, while mucous secretion became mixed (with a few neutral) after three weeks. Overall, the secretion was increased immediately after the Epirubicin administration, due to the activation of inflammatory pathways, assessed by increased immunostaining of tumor necrosis factor-alpha (TNF-α) at 48 hours. The MUC2 and MUC4 showed a decreased immunoexpression at 48 hours after the Epirubicin administration compared to controls and partially restored three weeks after the cessation. Overall, it is highly plausible that all these key players revolve around the chemotherapy-induced mucositis in oncohematological patients and highlights the morphofunctional particularities of the GCs, which further modulates the clinical outcome of the patient.

Changes in Retinal Structure and Ultrastructure in the Aged Mice Correlate With Differences in the Expression of Selected Retinal miRNAs.

Age and gender are two important factors that may influence the function and structure of the retina and its susceptibility to retinal diseases. The aim of this study was to delineate the influence that biological sex and age exert on the retinal structural and ultrastructural changes in mice and to identify the age-related miRNA dysregulation profiles in the retina by gender. Experiments were undertaken on male and female Balb/c aged 24 months (approximately 75-85 years in humans) compared to the control (3 months). The retinas were analyzed by histology, transmission electron microscopy, and age-related miRNA expression profile analysis. Retinas of both sexes showed a steady decline in retinal thickness as follows: photoreceptor (PS) and outer layers (p < 0.01 for the aged male vs. control; p < 0.05 for the aged female vs. control); the inner retinal layers were significantly affected by the aging process in the males (p < 0.01) but not in the aged females. Electron microscopy revealed more abnormalities which involve the retinal pigment epithelium (RPE) and Bruch's membrane, outer and inner layers, vascular changes, deposits of amorphous materials, and accumulation of lipids or lipofuscins. Age-related miRNAs, miR-27a-3p (p < 0.01), miR-27b-3p (p < 0.05), and miR-20a-5p (p < 0.05) were significantly up-regulated in aged male mice compared to the controls, whereas miR-20b-5p was significantly down-regulated in aged male (p < 0.05) and female mice (p < 0.05) compared to the respective controls. miR-27a-3p (5.00 fold; p < 0.01) and miR-27b (7.58 fold; p < 0.01) were significantly up-regulated in aged male mice vs. aged female mice, whereas miR-20b-5p (-2.10 fold; p < 0.05) was significantly down-regulated in aged male mice vs. aged female mice. Interestingly, miR-27a-3p, miR-27b-3p, miR-20a-5p, and miR-20b-5p expressions significantly correlated with the thickness of the retinal PS layer (p < 0.01), retinal outer layers (p < 0.01), and Bruch's membrane (p < 0.01). Our results showed that biological sex can influence the structure and function of the retina upon aging, suggesting that this difference may be underlined by the dysregulation of age-related mi-RNAs.

Electrospun Polyethylene Terephthalate Nanofibers Loaded with Silver Nanoparticles: Novel Approach in Anti-Infective Therapy.

Polyethylene terephthalate (PET) is a major pollutant polymer, due to its wide use in food packaging and fiber production industries worldwide. Currently, there is great interest for recycling the huge amount of PET-based materials, derived especially from the food and textile industries. In this study, we applied the electrospinning technique to obtain nanostructured fibrillary membranes based on PET materials. Subsequently, the recycled PET networks were decorated with silver nanoparticles through the chemical reduction method for antimicrobial applications. After the characterization of the materials in terms of crystallinity, chemical bonding, and morphology, the effect against Gram-positive and Gram-negative bacteria, as well as fungal strains, was investigated. Furthermore, in vitro and in vivo biocompatibility tests were performed in order to open up potential biomedical applications, such as wound dressings or implant coatings. Silver-decorated fibers showed lower cytotoxicity and inflammatory effects and increased antibiofilm activity, thus highlighting the potential of these systems for antimicrobial purposes.