Induction of Drug-Resistance and Production of a Culture Medium Able to Induce Drug-Resistance in Vinblastine Untreated Murine Myeloma Cells.

Cancer therapies use different compounds of synthetic and natural origin. However, despite some positive results, relapses are common, as standard chemotherapy regimens are not fully capable of completely eradicating cancer stem cells. While vinblastine is a common chemotherapeutic agent in the treatment of blood cancers, the development of vinblastine resistance is often observed. Here, we performed cell biology and metabolomics studies to investigate the mechanisms of vinblastine resistance in P3X63Ag8.653 murine myeloma cells. Treatment with low doses of vinblastine in cell media led to the selection of vinblastine-resistant cells and the acquisition of such resistance in previously untreated, murine myeloma cells in culture. To determine the mechanistic basis of this observation, we performed metabolomic analyses of resistant cells and resistant drug-induced cells in a steady state, or incubation with stable isotope-labeled tracers, namely, 13C 15N-amino acids. Taken together, these results indicate that altered amino acid uptake and metabolism could contribute to the acquisition of vinblastine resistance in blood cancer cells. These results will be useful for further research on human cell models.

Ozone gas as a storage treatment to control Gnomoniopsis castanea, preserving chestnut quality.

BACKGROUND: Chestnuts are gluten-free, low-fat, cholesterol-free products. Postharvest decay reduces chestnut shelf life and can cause severe economic losses. In this study we investigated the effect of ozone (O3 ) gaseous treatment on chestnut rot caused by Gnomoniopsis castanea and the quality parameters of chestnuts. RESULTS: The results showed that ozone treatment (150 ppb during the day, and 300 ppb during the night) reduced the decay of chestnuts and had a fungistatic effect on isolates of G. castanea. The exposure of chestnuts to ozone did not alter weight losses, sugar content and titratable acidity. The concentration of total phenolics decreased during the storage period, both for treated and untreated nuts. However, after 150 days of treatment the polyphenol content of the chestnuts exposed to ozone was significantly higher than in control nuts. CONCLUSIONS: Our results suggested that ozone is an appropriate and economical tool to maximize the quality of chestnut shelf life, enabling it to be stored for long periods. © 2019 Society of Chemical Industry.

Implant-supported prostheses esthetic outcomes after socket preservation technique.

Bone and soft tissue remodeling after tooth extraction may have dramatic effects. The socket preservation technique has demonstrated to be effective in maintaining volume before implant placement. The Pink Esthetic Score (PES) is an easy and complete evaluation of esthetic parameters. The aim of this study was to compare the PES index of anterior teeth needing to be replaced and the correspondent implant-supported prostheses after the socket preservation technique with 1 year of follow-up. Twenty-four patients were enrolled in this study. Eighteen maxillary central incisors and 6 maxillary lateral incisors were extracted, and then, every alveolar site was treated with the socket preservation technique and filled with Bio-Oss, mixed with fibrin glue, and covered with a collagen sponge. After 6 months of undisturbed healing, implants were placed and left healing for 4 months. After they were regularly loaded and at 1 year of follow-up, peri-implant PESs were recorded. All implants integrated successfully. No dropouts were recorded. Comparing PES results before extraction (mean, 12.25) and after implant loading (mean, 12.35), those around implants are similar if not better, and there are no statistically significant differences as analyzed with the t-test. The socket preservation technique combined with delayed implant placement and a standard healing time before implant loading has demonstrated to be effective in maintaining volumes and also esthetic values around implants compared with PES values before tooth extraction.

Oral mucosa produces cytokines and factors influencing osteoclast activity and endothelial cell proliferation, in patients with osteonecrosis of jaw after treatment with zoledronic acid.

OBJECTIVES: The intravenous injection of bisphosphonates, currently used as treatment for osteoporosis, bone Paget's disease, multiple myeloma, or bone metastases, can cause jaw bone necrosis especially in consequence of trauma. The present research aimed to clarify the mechanisms underlying bone necrosis, exploring involvement of the oral mucosa "in vivo." PATIENTS AND METHODS: Specimens of oral mucosa were removed from bisphosphonate-treated patients with or without jaw bone necrosis. In mucosa specimens, expression was evaluated of: cytokines involved in the inflammatory process, factors involved in osteoclast activity, i.e., receptor activator of nuclear factor kappa-B ligand (RANKL) and osteoprotegerin, a factor involved in cell proliferation, namely hydroxymethylglutaryl coenzyme A reductase, and a factor involved in angiogenesis, namely vascular endothelial growth factor (VEGF). RESULTS: Interleukin (IL)-6 and the RANK/osteoprotegerin ratio were significantly elevated in mucosa from patients with versus without jaw necrosis, whereas hydroxymethylglutaryl coenzyme A reductase and VEGF were significantly decreased. CONCLUSIONS: Our results suggest that mucosa, stimulated by bisphosphonate released from the bone, can contribute to the development of jaw necrosis, reducing VEGF, and producing IL-6 in consequence of hydroxymethylglutaryl coenzyme A reductase reduction. In turn, IL-6 stimulates osteoclast activity, as shown by the increased RANKL/osteoprotegerin ratio. CLINICAL RELEVANCE: The results of this study suggest the importance of evaluating during bisphosphonate treatment the production of IL-6, RANKL, osteoprotegerin, and VEGF, in order to monitor the jaw osteonecrosis onset. To avoid repeated mucosa excisions, the determination of these factors could be carried out in crevicular fluid.

Alveolar Ridge Preservation with a Novel Cross-Linked Collagen Sponge: Histological Findings from a Case Report.

Alveolar ridge preservation (ARP) is a well-documented procedure to maintain bone volume after tooth extraction in order to place implants. However, at the end of the healing process, the residual biomaterial that is not reabsorbed remains embedded in the bone over time. Ribose cross-linked biomaterials demonstrated their ability to promote osteoconduction and complete resorption. The aim of this study was to evaluate the histological healing pattern of a novel ribose cross-linked collagen sponge used as a grafting material left exposed in human sockets at the time of tooth extraction. On a single patient, non-restorable lower first molars were extracted on both sides, and a ribose cross-linked collagen sponge was placed bilaterally in the cavities and left uncovered at the end of the surgery. After six months, core biopsies were taken immediately prior to implant placement; after the sample preparation, a histological analysis was performed. The results are very promising for substitution with newly formed bone and the amount of residual material. Ribose cross-linked collagen sponge could represent a valid alternative to conventional biomaterials for ARP procedures with no need for flap advancement and/or the addition of a membrane to cover the graft, reducing the invasiveness, complexity, and costs of the treatment.

Laurus nobilis, Salvia sclarea and Salvia officinalis Essential Oils and Hydrolates: Evaluation of Liquid and Vapor Phase Chemical Composition and Biological Activities.

Laurus nobilis, Salvia officinalis and Salvia sclarea essential oils (EOs) and hydrolates (HYs) were investigated to define their chemical compositions and biological properties. Gas-chromatography/Mass-spectrometry (GC/MS) and Headspace-GC/MS (HS-GC/MS) techniques were used to characterize the liquid and vapor phase chemical composition of EOs and HYs. 1,8-Cineole (42.2%, 33.5%) and α-pinene (16.7%, 39.0%) were the main compounds of L. nobilis EO; 1,8-cineole (30.3%, 48.4%) and camphor (17.1%, 8.7%) were for S. officinalis EO; linalyl acetate (62.6%, 30.1%) and linalool (11.1%, 28.9%) were for S. sclarea EO for the liquid and vapor phase, respectively. Chemical profile of HYs was characterized by 1,8-cineole (65.1%, 61.4%) as a main constituent of L. nobilis and S. officinalis HYs, while linalool (89.5%) was the main constituent of S. sclarea HY. The antioxidant activity of EOs and HYs was carried out by DPPH and ABTS assays and antimicrobial properties were also investigated by microdilution and the disc diffusion method for liquid and vapor phase against five different bacterial strains such as Escherichia coli ATCC 25922, Pseudomonas fluorescens ATCC 13525 and Acinetobacter bohemicus DSM 102855 among Gram-negative and Bacillus cereus ATCC 10876 and Kocuria marina DSM 16420 among Gram-positive. L. nobilis and S. officinalis EOs demonstrated considerable antibacterial activity, while S. sclarea EO proved to be less effective. Agar diffusion method and vapor phase test showed the EOs activity with the biggest halo inhibition diameters against A. bohemicus and B. cereus. A remarkably high antioxidant activity was determined for L. nobilis showing low EC50 values and also for S. sclarea; good EO results were obtained in both of the used assays. S. officinalis EC50 values were slightly higher to which corresponds to a lower antioxidant activity. Concerning the HYs, the EC50 values for L. nobilis, S. officinalis and S. sclarea were remarkably high corresponding to an extremely low antioxidant activity, as also obtained by expressing the values in Trolox equivalent antioxidant capacity (TEAC).