Search Results (10)

Background/Objectives: Considering the large number of candidates in vaccine-testing studies against different pathogens and the amount of time spent in the preclinical and clinical trials, there is a pressing need to develop an improved in vivo system to quickly screen vaccine candidates. The model of a polyester–polyurethane sponge implant provides a rapid analysis of the specific stimulus–response, allowing the study of a compartmentalized microenvironment. The sponge implant’s defined measurements were standardized as a compartment to assess the immune response triggered by the vaccinal antigen. The LBSap vaccine (composed of Leishmania braziliensis antigens associated with saponin adjuvant) was used in the sponge model to assess the antigen-specific immunological biomarker, including memory generation after initial contact with the antigen. Methods: Mice strains (Swiss, BALB/c, and C57BL/6) were previously immunized using LBSap vaccine, followed by an antigenic booster performed inside the sponge implant. The sponge implants were assessed after 72 h, and the immune response pattern was analyzed according to leukocyte immunophenotyping and cytokine production. Results: After LBSap vaccination, the innate immune response of the antigenic booster in the sponge implants demonstrated higher levels in the Ly+ neutrophils and CD11c+ dendritic cells with reduced numbers of F4/80+ macrophages. Moreover, the adaptive immune response in Swiss mice demonstrated a high CD3+CD4+ T-cell frequency, consisting of an effector memory component, in addition to a cytoxicity response (CD3+CD8+ T cells), displaying the central memory biomarker. The major cell surface biomarker in the BALB/c mice strain was related to CD3+CD4+ effector memory, while the increased CD3+CD8+ effector memory was highlighted in C57/BL6. The cytokine profile was more inflammatory in Swiss mice, with the highest levels of IL-6, TNF, IFN-g, and IL-17, while the same cytokine was observed in in C57BL/6 yet modulated by enhanced IL-10 levels. Similar to Swiss mice, BALB/c mice triggered an inflammatory environment after the antigenic booster in the sponge implant with the increased levels in the ILL-6, TNF, and IFN-g. Conclusions: The findings emphasized the impact of genetic background on the populations engaged in immune responses, suggesting that this model can be utilized to enhance and track both innate and adaptive immune responses in vaccine candidates. Consequently, these results may inform the selection of the most suitable experimental model for biomolecule testing, taking into account how the unique characteristics of each mouse strain affect the immune response dynamics. Full article

Recently, film materials based on the combination of noble metals have showed promising results for surface modification of medical implants, allowing both to improve biocompatibility and to acquire the increased antibacterial effect. An important challenge here is to combine the developed coating morphology, which is favorable for biological response, with a high protective function, which, on the contrary, requires a compact coating microstructure. In this work, we aimed to solve this problem with respect to the TiNi implant material. We have tested two types of compact thin sublayers: Iridium (Ir’), formed by metal-organic chemical vapor deposition (MOCVD), and gold (Au), formed by physical vapor deposition (PVD). Subsequently these sublayers were coated with a developed-columnar-iridium (Ir) by MOCVD. Features of the microstructure, chemical and phase composition of all these film materials were studied using powder X-ray diffraction (XRD), scanning electron microscopy (SEM) and X-ray photoelectron spectroscopy (XPS). The changes in the characteristics of TiNi martensitic transformation due to MOCVD experiments were also studied by differential scanning calorimetry (DSC). The biocompatibility of Ir’/TiNi, Au/TiNi, Ir/Ir’/TiNi, Ir/Au/TiNi samples was assessed by cytoxicity testing (Man-1 cells) and measuring of nickel content in the biological extracts. The application of both sublayers effectively reduces the release of nickel, which was previously shown for Ir/TiNi samples. This prevents the toxic effect. Note that the Ir’ sublayer better protects against nickel release, while the Au sublayer promotes cell proliferation. Full article

For centuries, macroalgae, or seaweeds, have been a significant part of East Asian diets. In Europe, seaweeds are not considered traditional foods, even though they are increasingly popular in Western diets in human food applications. In this study, a biological processing method based on semi-solid fermentation was optimized for the treatment of the seaweed Gracilaria gracilis. For the first time, selected lactic acid bacteria and non-conventional coagulase-negative staphylococci were used as starter preparations for driving a bio-processing and bio-stabilization of raw macroalga material to obtain new seaweed-based food prototypes for human consumption. Definite food safety and process hygiene criteria were identified and successfully applied. The obtained fermented products did not show any presence of pathogenic or spoilage microorganisms, thereby indicating safety and good shelf life. Lactobacillus acidophilus-treated seaweeds revealed higher α-amylase, protease, lipase, endo-cellulase, and endo-xylanase activity than in the untreated sample. This fermented sample showed a balanced n-6/n-3 fatty acid ratio. SBM-11 (Lactobacillus sakei, Staphylococcus carnosus and Staphylococcus xylosus) and PROMIX 1 (Staphylococcus xylosus) treated samples showed fatty acid compositions that were considered of good nutritional quality and contained relevant amounts of isoprenoids (vitamin E and A). All the starters improved the nutritional value of the seaweeds by significantly reducing the insoluble indigestible fractions. Preliminary data were obtained on the cytocompatibility of G. gracilis fermented products by in vitro tests. This approach served as a valid strategy for the easy bio-stabilization of this valuable but perishable food resource and could boost its employment for newly designed seaweed-based food products. Full article

Cutaneous melanoma is the deadliest type of skin cancer and current treatment is still inadequate, with low patient survival rates. The polyphenol xanthohumol has been shown to inhibit tumourigenesis and metastasization, however its physicochemical properties restrict its application. In this work, we developed PLGA nanoparticles encapsulating xanthohumol and tested its antiproliferative, antitumour, and migration effect on B16F10, malignant cutaneous melanoma, and RAW 264.7, macrophagic, mouse cell lines. PLGA nanoparticles had a size of 312 ± 41 nm and a PdI of 0.259, while achieving a xanthohumol loading of about 90%. The viability study showed similar cytoxicity between the xanthohumol and xanthohumol-loaded PLGA nanoparticles at 48 h with the IC50 established at 10 µM. Similar antimigration effects were observed for free and the encapsulated xanthohumol. It was also observed that the M1 antitumor phenotype was stimulated on macrophages. The ultimate anti-melanoma effect emerges from an association between the viability, migration and macrophagic phenotype modulation. These results display the remarkable antitumour effect of the xanthohumol-loaded PLGA nanoparticles and are the first advance towards the application of a nanoformulation to deliver xanthohumol to reduce adverse effects by currently employed chemotherapeutics. Full article

The increased use of biostimulants in conventional agriculture and organic farming requires the implementation of rapid tests to determine their effectiveness in enhancing plant growth and protection against abiotic stresses. However, their innocuity to plant health has rarely been demonstrated. We used the Vicia faba Micronucleus Assay, as described by the standard AFNOR EN ISO 29200(2020-05) to reveal biostimulant, genotoxic and cytotoxic effects of four commercialized wood-based products by comparing mitotic indices and micronucleus frequencies with respect to the controls. Neither genotoxicity, as measured by micronucleus frequency (MN), nor cytotoxicity, assessed by Mitotic index counts, was observed. Additionally, one of these stimulants (BHS^®) conferred protective effects against contaminants (maleic hydrazide or lead nitrate). We describe that plotting micronuclei frequency against mitotic indices allows discrimination between cytotoxic/genotoxic effects from growth levels. Vicia faba experiments were successfully transposed to other agronomical important crops such as corn and sunflower. This technique can be valuable to industrials, to assess growth, potential cytoxicity and genotoxicity effects of any new biostimulant or organic. Full article

Background: KDM5 enzymes are H3K4 specific histone demethylases involved in transcriptional regulation and DNA repair. These proteins are overexpressed in different kinds of cancer, including breast, prostate and bladder carcinomas, with positive effects on cancer proliferation and chemoresistance. For these reasons, these enzymes are potential therapeutic targets. Methods: In the present study, we analyzed the effects of three different inhibitors of KDM5 enzymes in MCF-7 breast cancer cells over-expressing one of them, namely KDM5B/JARID1B. In particular we tested H3K4 demethylation (western blot); radio-sensitivity (cytoxicity and clonogenic assays) and damage accumulation (COMET assay and kinetics of H2AX phosphorylation). Results: we show that all three compounds with completely different chemical structures can selectively inhibit KDM5 enzymes and are capable of increasing sensitivity of breast cancer cells to ionizing radiation and radiation-induced damage. Conclusions: These findings confirm the involvement of H3K4 specific demethylases in the response to DNA damage, show a requirement of the catalytic function and suggest new strategies for the therapeutic use of their inhibitors. Full article

The dried fruits of Forsythia viridissima have been prescribed to relive fever, pain, vomiting, and nausea in traditional medicine. Oxaliplatin (LOHP) is used to treat advanced colorectal cancer; however, it frequently induces peripheral neuropathies. This study was done to evaluate the neuroprotective effects of an aqueous extract of Forsythia viridissima fruits (EFVF) and its major constituents. Chemical constituents from EFVF were characterized and quantified with the UHPLC-diode array detector method, and three major constituents were identified as arctiin, matairesinol, and arctigenin. The in vitro cytotoxicity was measured by the Ez-cytox viability assay, and the in vivo neuroprotection activity was evaluated by a von Frey test in two rodent animal models that were administered LOHP. EFVF significantly alleviated the LOHP-induced mechanical hypersensitivity in the induction model. EFVF also prevented the induction of mechanical hyperalgesia by LOHP in the pre- and co-treatment of LOHP and EFVF. Consistently, EFVF exerted protective effects against LOHP-induced neurotoxicity as well as inhibited neurite outgrowths in PC12 and dorsal root ganglion cells. Among the major components of EFVF, arctigenin and matairesinol exerted protective effects against LOHP-induced neurotoxicity. Therefore, EFVF may be useful for relieving or preventing LOHP-induced peripheral neuropathy in cancer patients undergoing chemotherapy with LOHP. Full article

The venom peptide bicarinalin, previously isolated from the ant Tetramorium bicarinatum, is an antimicrobial agent with a broad spectrum of activity. In this study, we investigate the potential of bicarinalin as a novel agent against Helicobacter pylori, which causes several gastric diseases. First, the effects of synthetic bicarinalin have been tested against Helicobacter pylori: one ATCC strain, and forty-four isolated from stomach ulcer biopsies of Peruvian patients. Then the cytoxicity of bicarinalin on human gastric cells and murine peritoneal macrophages was measured using XTT and MTT assays, respectively. Finally, the preventive effect of bicarinalin was evaluated by scanning electron microscopy using an adherence assay of H. pylori on human gastric cells treated with bicarinalin. This peptide has a potent antibacterial activity at the same magnitude as four antibiotics currently used in therapies against H. pylori. Bicarinalin also inhibited adherence of H. pylori to gastric cells with an IC₅₀ of 0.12 μg·mL⁻¹ and had low toxicity for human cells. Scanning electron microscopy confirmed that bicarinalin can significantly decrease the density of H. pylori on gastric cells. We conclude that Bicarinalin is a promising compound for the development of a novel and effective anti-H. pylori agent for both curative and preventive use. Full article

Chemically diverse heterocyclic chalcones were prepared and evaluated for cytotoxicity, aiming to push forward potency and selectivity. They were tested against rhabdomyosarcoma (RMS) and noncancerous cell line (LLC-PK1). The influence of heteroaryl patterns on rings A and B was studied. Heterocycle functionalities on both rings, such as phenothiazine, thiophene, furan and pyridine were evaluated. Notably, the introduction of three methoxy groups at positions 3, 4, 5 on ring B appears to be critical for cytotoxicity. The best compound, with potent and selective cytotoxicity (IC₅₀ = 12.51 μM in comparison with the value 10.84 μM of paclitaxel), contains a phenothiazine moiety on ring A and a thiophene heterocycle on ring B. Most of the potential compounds only show weak cytoxicity on the noncancerous cell line LLC-PK1. Full article

Antimicrobial activity and cytotoxicity of fifty one extracts of different parts of 14 plants were studied. Ethanol, methanol, aqueous, butanol, and n-hexane extracts were tested against three Gram negative, two Gram positive bacteria, and two fungi. Cytotoxicity and phytochemical screening were determined using MTT and TLC assays, respectively. Of the fifty one extracts, twenty two showed activities against different microorganisms with MICs ranging from 62.5 to 1000 µg/mL. The highest activity (100% inhibition) was for a butanol extract of Rosa damascena receptacles against Salmonella typhimurium and Bacillus cereus (MIC of 62.5 and 250 µg/mL) respectively. Butanol extract of Narcissus tazetta aerial parts and aqueous extract of Rosa damascena receptacles were both active against Candida albicans (MIC of 125 µg/mL). Methicillin-resistant Staphylococcus aureus was inhibited by butanol, aqueous extracts of Rosa damascena receptacles and butanol extract of Inula viscosa flowers (MIC of 500, 500, and 250 µg/mL) respectively. Rosa damascena receptacles and Verbascum sinaiticum flowers ethanol extract showed lowest cytoxicity against Vero cell line (IC₅₀ of 454.11and 367.11). Most toxic was the ethanol extract of Ononis hirta aerial parts (IC₅₀ 72.50 µg/mL). Flavonoids and terpenoids were present in all plants. Ononis hirta and Narcissus tazetta contained alkaloids. The results validate the use of these plants and report for the first time bioactivity of Rosa damascena receptacles and further justifies the use of such screening programs in the quest for new drugs. Full article