Murine Fibroblast Cell Research Articles

IPMK Loss Inhibits Cellular Motility and Contractility

Cellular adhesion is dependent on the type of adhesion receptors displayed on the cell surface, and activation of adhesion receptors initiates downstream signaling cascades that are context dependent. Cellular expression of adhesion receptors is modulated by a complex array of extracellular and intracellular signals, and we have found that Inositol Phosphate Multikinase (IPMK) is a transcriptional regulator of integrin β1 protein in murine embryonic fibroblast (MEF) cells. Further, we show that although loss of IPMK dramatically reduces levels of both active and inactive integrin β1 protein, activation of the focal adhesion proteins FAK and Src are increased while total protein levels are unchanged, suggesting that IPMK is a negative regulator of focal adhesion complex activity. Importantly, IPMK regulation of integrin gene expression is activity dependent. Using native extracellular matrix mimicking fibers as substrate, generated using STEP (Spinneret-based Tunable Engineered Parameters) technique, we show that loss of this enzyme inhibits migration (0.68 μm/min in Wild Type cells vs 0.35 μm/min in IPMK Knock-out cells) due to decreased cell-matrix adhesion and reduced cellular contractility. Using nanonet force microscopy (NFM), we calculated the forces of migrating MEF WT cells to be 226.8 nN which was significantly higher than those of the IPMK KO cells (115.6 nN). Attempts to rescue IPMK pharmacologically resulted in increased contractility (154.3 nN) but not to the same degree as that of WT cells. To further elucidate the impact of IPMK on adhesion strength, we stretched the cells suspended between fibers until their adhesion bonds failed and the cells detached from the adhered fibers. WT cells demonstrated higher failure force (45.4 nN) as opposed to KO cells (36.2 nN). Based on these findings, we hypothesize that IPMK modulates cell migration and contractility by regulating gene expression of cell-matrix molecules.

Assessment of Manganese-Zinc Ferrite Nanoparticles as a Novel Magnetic Resonance Imaging Contrast Agent for the Detection of 4T1 Breast Cancer Cells.

Background:The aim of the study was to evaluate the potential of manganese-zinc ferrite nanoparticles (MZF NPs) as a novel negative magnetic resonance imaging (MRI) contrast agents for 4T1 (mouse mammary carcinoma) and L929 (murine fibroblast) cell lines.Methods:MZF NPs and its suitable coating, polyethylene glycol (PEG) via covalent bonding, were investigated under in vitro condition. The cytotoxicity of MZF NPs was tested by 3-(4,5-dimethyl thiazolyl-2)-2,5-diphenyltetrazolium bromide assay after 12 and 24 h of incubation. To evaluate the potential of MZF NPs as T2 MRI nanocontrast agent, images were obtained from phantom containing different Fe concentrations and T2 relaxivity (r2) was measured. The viability of both 4T1 breast cancer and L929 murine fibroblast cell lines incubated with different Fe concentrations.Results:In vitro T2-weighted MRI showed that signal intensity of 4T1 cells was lower than that of L929 as control cells. T2-weighted MRI showed that signal intensity of MZF NPs enhanced with increasing concentration of NPs. The values of 1/T2 relaxivity (r2) for coated MZF NPs with PEG found to be 85.5 mM−1 s−1 which is higher than that of commercially clinical used (Sinerem) MRI contrast agent.Conclusion:The results showed that MZF NPs have potential to detect breast cancer cells (4T1) and also have high contrast resolution between normal (L929) and cancerous cells (4T1) which is a suitable nanoprobe for T2-weighted MR imaging contrast agents.

Evaluation of the Toxicity of Silver/Silica and Titanium Dioxide Particles in Mammalian Cells

ABSTRACT The increasing concern over the spread of diseases has lead to a high consumption of antimicrobial additives in the medical and industrial fields. Since these particles can lixiviate from loaded materials, the contact between this additive and mammalian cells can occur during manufacture, use and disposal of the products. Silver on fumed silica (AgNP_SiO2) and titanium dioxide (TiO2) can be used as antimicrobial additives that are applied in polymeric formulation. While these additives can inhibit bacteria, fungus and virus proliferation; they may also be harmful to humans. Standard toxicological studies were undertaken using the MTT (3-(4,5-dimethylthiazol-2-yl)-2,5 diphenyltetrazolium bromide), CBPI (cytokinesis-block proliferation index) and micronucleus assay using different sets of additive concentrations. The nanosize of the samples evaluated was confirmed by transmission electronic microscopy. No significant micronucleus frequency increase or cell viability reduction were observed with the exposure of L-929 murine fibroblast cells to AgNP_SiO2 and TiO2 particles at any of the tested concentrations. The non toxic effect of the analyzed particles can be explained by considering its agglomeration tendency, composition, and crystalline form. Further investigations should be done to understand the interference of agglomeration and how it affects the toxicological study.

Evaluation of in vitro cytotoxicity of superparamagnetic poly(thioether-ester) nanoparticles on erythrocytes, non-tumor (NIH3T3), tumor (HeLa) cells and hyperthermia studies

Magnetic nanoparticles encapsulated in biocompatible and biodegradable polymeric matrices are promising materials for biomedical applications, such as transport of antitumoral drugs and cancer treatment by hyperthermia. In this study, biobased poly(thioether-ester), PTEe, was obtained by thiol-ene polymerization and superparamagnetic nanoparticles, MNPs, were successfully incorporated in PTEe nanoparticles by miniemulsification followed by solvent evaporation. MNPs-PTEe nanoparticles with average diameter around 150 nm presented superparamagnetic behavior as confirmed by magnetization curves analysis. MNPs-PTEe nanoparticles did not present hemolytic damage on human red blood cells when incubated for 24 h. According to the cell viability assays, nanoparticles did not present any cytotoxic effect on murine fibroblast cell (NIH3T3) and human cervical cancer (HeLa). Hyperthermia assays were applied, demonstrating that AC magnetic field application (110 KHz–500 Oe) for 20 min significantly reduced the cells viability. The morphology evaluation of HeLa showed a hypoxia region one hour after hyperthermia application. Therefore, the results indicated that the superparamagnetic poly(thioether-ester) nanoparticles can be an excellent alternative for the targeted delivery of antitumor drugs and cancer treatment for hyperthermia.

Fabrication of polylysine based antibacterial coating for catheters by facile electrostatic interaction

Despite the development of advanced antibacterial biomedical materials, bacterial infection is still a serious problem for indwelling catheter because it usually induces severe complications. Hence, medical indwelling catheter with the capabilities of antibacterial activity, stability, biocompatibility is urgently needed. In this work, a water-insoluble antibacterial coating based on ε-Poly-ʟ-lysine (PL) was prepared via a facile electrostatic interaction between cation PL and anion surfactant, 1,4-bis(2-ethylhexyl) sodium sulfosuccinate (AOT). The ease and efficacy of the PL-AOT complex preparation render it as antibacterial coating applicable to a variety of medical devices for reduction of bacterial infections. This coating was fabricated on the medical catheter with broad-spectrum antibacterial activity, long-term stability, biocompatibility. The contact-killing oriented strategy for the antibacterial action of this coating was confirmed by high-performance liquid chromatography (HPLC). Almost 100% S. aureus and E. coli as Gram-positive and Gram-negative bacteria model could be killed rapidly by this coating for thermoplastic polyurethane (TPU) film. The antibacterial properties of the coated catheters were also assessed under static and dynamic flow conditions. Regardless of the above conditions, the coated catheters displayed remarkable antibacterial activity compared to the uncoated catheters. In addition, this coating showed better antibacterial stability by mimicking the in vivo environment, that is, the antibacterial efficacy could still maintain even after 31 days immersing. Moreover, the coated catheter exhibited negligible cytotoxicity against L929 murine fibroblasts cells. For in vivo experiment, the coated catheter caused 90% less inflammation in mice and showed more remarkable antibacterial performance. Consequently, this ε-Poly-ʟ-lysine (PL) based coating have a great potential to serve as a safe and multifunctional antibacterial strategy for the medical indwelling devices.

Extracellular biopolymers produced by Dictyosphaerium family - Chemical and immunomodulative properties

Many microalgal species produce a wide range of highly-value products which are interesting for biotechnological applications. Cultivation of microalgal species Dictyosphaerium pulchellum and Dictyosphaerium tetrachotomum, strains Růžicka and Fott resulted yields of 0.2, 0.7 and 1.8 g/L of extracellular biopolymers (EPSs), respectively. All biopolymers were shown to be anionic proteoglycans. The sugar composition analyses of all EPSs showed high contents of hexoses and the presence of partially methylated monosaccharide residues, i.e. hexoses, and deoxy hexoses. The dominant sugar component of all EPSs was found to be galactose. Extracellular microalgal biopolymers were subjected to immunobiological and immunotoxicological evaluation using murine melanoma cancer cells B16, murine fibroblast cell line NIH-3T3, murine macrophages cell line RAW 264.7 and skin construct EpiDerm™ (EPI-200). The EPSs exerted the antiproliferative effectivity; treatment of EPS induced proinflammatory cytokines TNF-α, IL-6, IL-12, IL-1β and IL-17, also engaged in anti-cancer immunity. Immunotoxicological studies revealed their non-toxic character and safe application on EpiDerm™.

IN VITRO ANTIFUNGAL ACTIVITY AND CYTOTOXICITY SCREENING OF DRY CRUDE EXTRACTS FROM BRAZILIAN AMAZONIA PLANTS

Background: Antifungal multidrug resistance has been reported worldwide and has stimulated investigations of plant
 species for the treatment of candidiasis. In particular, in vitro antifungal activities and cytotoxicity of dry extracts from
 Ceasalpinia ferrea (tul.) Martius, Brosimum acutifolium Huber, and Salacia impressifolia (Miers) A.C. Smith were
 evaluated.
 Materials and Methods: Minimum inhibitory concentrations (MIC) and minimum fungicide (MFC) values were
 established according to the protocol M27-A2 of the Clinical and Laboratory Standards Institute (CLSI). Subsequent
 evaluations were performed using strains of Candida albicans from the American Type Culture Collection (ATCC)
 10231, clinical isolated Candida albicans, Candida glabrata (CCT) 0728, Candida krusei (FTI) CCT 1517, and
 Candida guilliermondii (CCT) 1890. Morphological changes were evaluated using scanning electron microscopy
 (SEM), and cytotoxicity was evaluated in murine L929 fibroblast cells after treatment with plant extracts.
 Results: MIC values indicated antifungal potential of all three extracts against the main fungi that causes candidiasis.
 Conclusion: In particular, C. ferrea showed promising antimicrobial potential against all strains. Hence, future studies
 are warranted to investigate pharmacologically active compounds from this extract that could be used as prototypes for
 drug development and/or as a source of raw pharmaceutical materials for the treatment of candidiasis.

Immortalized murine fibroblast cell lines are refractory to reprogramming to pluripotent state

To date different cell types of various mammalian species have been reprogrammed to induced pluripotent stem cells (iPSCs) using Yamanaka's cocktail of transcription factors (Oct4, Klf4, Sox2, and cMyc). It has been shown that several primary human cancer cell lines could be reprogrammed to iPSCs. We sought if immortalized mouse fibroblast cell lines could also be reprogrammed to iPSCs. The approach of generating iPSCs from such cells should be valuable in different experimental settings as it allows clonally derive cell lines carrying mutations whose impact on reprogramming could be next evaluated. Therefore, we investigated reprogramming of widely used immortalized cell lines (NIH3T and STO), as well as of de novo immortalized fibroblast line (tKM) with the use of highly effective lentiviral polycistronic OKSM expression system. Our reprogramming experiments have shown that in contrast to mouse embryonic fibroblasts (MEFs), none of the immortalized cell lines can be reprogrammed to pluripotent state. Contrary to colonies derived from MEFs, those derived from the immortalized cells lines (1) developed much later, (2) contained large round cells, not typical for iPSCs, and (3) were negative for trusted markers of matured iPSCs, Nanog and SSEA1. Immortalized cell lines NIH3T and STO are known to be mostly aneuploid, whereas tKM population includes cells with normal karyotype, however, neither cell type can be reprogrammed. Thus our data argue that aneuploidy per se is not a reason for the observed refractoriness of mouse immortalized cells to reprogramming to pluripotent state.

Phenolic Composition, Antioxidant and Cytotoxic Prospective of three Linum species: A Potential Source of Novel Anticancer Pharmacophores

The therapeutic potential of some Linum species has been reported previously. Nonetheless, several species of this genus warrant further scientific consideration. In this study, the phenolic composition, antioxidant activity (DPPH, phosphomolybdenum, iron chelating, hydroxyl radical and lipid peroxidation assays) and cytotoxicity effect (human rhabdomyosarcoma, human cervix carcinoma, and murine fibroblast cell lines) of ethyl acetate, methanol, and water extracts of three Linum species (Linum austriacum subsp. glaucescens, Linum hirsutum subsp. anatolicum, and Linum tenuifolium) were assessed. High performance liquid chromatography with diode-array detection (HPLC-DAD) analysis revealed the presence of ferulic acid, p-hydroxybenzoic acid, synapic acid, rutin, apigenin-glucoside, quercetin, luteolin, and naringenin in all the extracts. It was observed that the extracts (IC50 ranging from 42.07 to 51.66 µg/mL) showed IC50 significantly (p<0.05) lower than ascorbic and gallic acid (> 1000 and 255.43 µg/mL respectively) against lipid peroxidation. According to the American National Cancer Institute guidelines, the extracts showed low cytotoxicity (IC50 < 30 µg/mL). However, the water extracts showed cytotoxicity effects (IC50 17.43±0.13 to 28.12±0.66 µg/mL) against the studied cell lines as compared to the antineoplastic positive control (Cis-DDP). These findings support the use of these plants in the management of ROS mediated disorders and advocates for the need for further scientific evaluations to confirm the observed in vitro bioactivity. The cytotoxic potential coupled with the antioxidant property of the water extracts of these plant species is of particular interest which can open new avenues in the quest for novel anticancer drugs. Keywords: Linum, antioxidant, phenolic, nutraceuticals, anticancer, cytotoxic, Turkey.

Nontoxic Glucomoringin-Isothiocyanate (GMG-ITC) Rich Soluble Extract Induces Apoptosis and Inhibits Proliferation of Human Prostate Adenocarcinoma Cells (PC-3).

The incidence of prostate cancer malignancy along with other cancer types is increasing worldwide, resulting in high mortality rate due to lack of effective medications. Moringa oleifera has been used for the treatment of communicable and non-communicable ailments across tropical countries, yet, little has been documented regarding its effect on prostate cancer. We evaluated the acute toxicity and apoptosis inducing effect of glucomoringin-isothiocyanate rich soluble extracts (GMG-ITC-RSE) from M. oleifera in vivo and in vitro, respectively. Glucomoringin was isolated, identified, and characterized using fundamental analytical chemistry tools where Sprague-Dawley (SD) rats, murine fibroblast (3T3), and human prostate adenocarcinoma cells (PC-3) were used for acute toxicity and bioassays experiments. GMG-ITC-RSE did not instigate adverse toxic reactions to the animals even at high doses (2000 mg/kg body weight) and affected none of the vital organs in the rats. The extract exhibited high levels of safety in 3T3 cells, where more than 90% of the cells appeared viable when treated with the extract in a time-dependent manner even at high dose (250 µg/mL). GMG-ITC-RSE significantly triggered morphological aberrations distinctive to apoptosis observed under microscope. These findings obviously revealed the putative safety of GMG-ITC-RSE in vivo and in vitro, in addition to its anti-proliferative effect on PC-3 cells.

Electroconductive hyaluronic acid/gelatin/poly(ethylene oxide) polymeric film reinforced by reduced graphene oxide

AbstractNovel electroconductive polymeric films with enhanced mechanical performance were fabricated by encapsulating reduced graphene oxide (RGO) at different concentrations (0–50 vol %) into a hyaluronic acid/gelatin/poly(ethylene oxide) (HyA/Gel/PEO) polymeric structure. The obtained RGO‐reinforced polymeric films were characterized by Fourier transform infrared and scanning electron microscopy analyses. Mechanical performances were measured with a universal mechanical testing machine. The results verified that the RGO reinforcement significantly enhanced the mechanical performances of the films. To determine the biocompatibility of the polymeric films, L929 (murine fibroblast) cell lines were used. The water uptake capacities were measured using swelling tests. A four‐probe method was used to measure conductivity characteristics. The conductivity results indicated that HyA/Gel/PEO film containing 20 vol % RGO has the highest average electrical conductivity (1.832 × 10−6S/cm). All of the results demonstrated that the obtained electroconductive films could be used in biomedical fields in the future, especially in controlled drug release systems and tissue engineering. © 2018 Wiley Periodicals, Inc. J. Appl. Polym. Sci.2019,136, 46905.

Nano-topography: Quicksand for cell cycle progression?

The 3-D spatial and mechanical features of nano-topography can create alternative environments, which influence cellular response. In this paper, murine fibroblast cells were grown on surfaces characterized by protruding nanotubes. Cells cultured on such nano-structured surface exhibit stronger cellular adhesion compared to control groups, but despite the fact that stronger adhesion is generally believed to promote cell cycle progression, the time cells spend in G1 phase is doubled. This apparent contradiction is solved by confocal microscopy analysis, which shows that the nano-topography inhibits actin stress fiber formation. In turn, this impairs RhoA activation, which is required to suppress the inhibition of cell cycle progression imposed by p21/p27. This finding suggests that the generation of stress fibers, required to impose the homeostatic intracellular tension, rather than cell adhesion/spreading is the limiting factor for cell cycle progression. Indeed, nano-topography could represent a unique tool to inhibit proliferation in adherent well-spread cells.

PO-508 Detection and role of novel fusion oncogenes in paediatric cancers

IntroductionPaediatric cancers (PC) represent the 1 st cause of death by disease in children as 20% of patients still die from a recurrence of the malignancy. PC differ from adult cancers regarding their aetiology, cellular origin or mutational rate. Improving the knowledge on the biology of the relapsed tumours and identifying new targets are needed to provide new treatments. Fusion genes are responsible for ~20% of cancers and are the consequence of the juxtaposition of two previously separate genes which can activate proto-oncogenes or inactivate tumour suppressor genes. They are of great interest in clinics as they can be used as therapeutic targets or biomarkers. Our aim is to explore new fusion genes in relapsing/resistant paediatric patients through bioinformatics analysis of the NGS data from the molecular profiling program MOSCATO-01, and to study their function and oncogenic potential.Material and methodsWe developed an approach to optimise the detection of fusion transcripts in RNA-seq data. A biological validation of selected candidates was performed by RT-qPCR in patients’ tumour samples and available cell lines. A fusion never previously described found in a Ewing’s sarcoma (EWS) patient retained our attention, therefore we established 2 cellular models in order to assess the effect of this transcript on proliferation, migration, sensitivity to anticancer agents, gene expression in vitro and tumorigenicity in mice.Results and discussionsOur in-house pipeline ChimComp allowed the detection of 118 new potentially oncogenic fusions. Following the validation by RT-qPCR, we showed that ChimComp could be reliable at ~90%. A new fusion, LMO3-BORCS5, was found in a patient with EWS and in 12 cell lines from different origins suggesting that it is not an isolated event. Then, we explored the function and oncogenic potential of LMO3-BORCS5. Until now, we show that the stable transfection of this fusion into A673 Ewing’s sarcoma and NIH3T3 murine fibroblasts cell lines, leads to an increase of cell proliferation and an increase or an induction of tumorigenicity after injection in mice, as well as a decrease of sensitivity to anticancer drugs vincristine and camptothecin in A673 cells.ConclusionThese results suggest that LMO3-BORCS5 could play a key role in tumorigenesis and in response to treatment and could be used as a therapeutic target for patients where LMO3-BORCS5 is detected. More broadly, this study emphasises the key role of fusion genes in disease progression and their clinical interest in personalised medicine.

Cold atmospheric Plasma Jet-Generated Oxidized Derivatives of Tryptophan and Their Selective Effects on Murine Melanoma and Fibroblast Cells

Cold atmospheric pressure plasma is widely used in research for biomedical applications and is a promising therapy to selectively eradicate cancer cells. However, fundamental information related to the plasma modification of biomolecules in aqueous solution remains elusive. In this work, we studied the chemical basis of tryptophan (Trp) oxidation using an Ar plasma jet and investigated the effects of plasma-treated tryptophan (PTT) on cell viability. The results show that the main product of the Trp of plasma induced oxidation is a mixture of hydroxyl derivatives and hydroperoxides in aqueous form. The products result primarily from the hydroxyl radical (·OH) attacking the Trp, which can be explained by the interaction with both the aromatic and the pyrrole rings. We observed that the PTT has a different proliferation effect between the growth of the B16 melanoma cells and the L929 fibroblast cells. The experimental results indicated that the effect of the PTT is dose-dependent in the B16 cells, ranging from cell proliferation to cytotoxic damage with apoptosis. Furthermore, we examined the intracellular changes in hydrogen peroxide (H2O2) and superoxide radicals ( $${\text{O}}_{2}^{{\bar{ \cdot }}}$$ ) following the Trp-derived treatment using the fluorescence probe method. Rigorous identification of the reactive oxygen species (ROS) produced by PTT in cells as $${\text{O}}_{2}^{{\bar{ \cdot }}}$$ and H2O2 helped establish the cellular source of ROS. It is shown that the intracellular H2O2 might originate from the activation of NADPH. These results suggested that the amino acid and protein hydroperoxides may play a crucial role in the action of plasma on the biologic target.

Synthesis and Evaluation of New Potential Benzo[a]phenoxazinium Photosensitizers for Anticancer Photodynamic Therapy.

The use of photodynamic therapy (PDT) and development of novel photosensitizers (PSs) for cancer treatment have received more and more attention nowadays. In the present work, five benzo[a]phenoxazinium derivatives have been prepared and evaluated for their in vitro anticancer photodynamic activity for the first time. They are red light absorbers and show low fluorescence quantum yield. Of these compounds, PS4 exhibited a higher quantum yield for reactive oxygen species (ROS) generation. The assays with cells in vitro showed that PS1 and PS4 were not significantly toxic in the dark, but was robustly toxic against the murine breast adenocarcinoma cells 4T1 and normal murine fibroblast cells NIH-3T3 upon photoactivation. More interestingly, PS5 was particularly selective towards 4T1 cancer cells and nearly non-phototoxic to non-cancerous NIH-3T3 cells. The results described in this report suggest that these new benzo[a]phenoxazinium derivatives are potential candidates as PSs for anticancer PDT. Further investigation of benzo[a]phenoxaziniums for anticancer PDT is warranted.

2213 Tumor suppressors p53 and ARF control oncogenic potential of triple-negative breast cancer cells by regulating RNA editing enzyme ADAR1

OBJECTIVES/SPECIFIC AIMS: Triple-negative breast cancer (TNBC) accounts for one-fifth of the breast cancer patient population. The heterogeneous nature of TNBC and lack of options for targeted therapy make its treatment a constant adventure. The deficiency of tumor suppressors p53 and ARF is one of the known genetic signatures enriched in TNBC. Crucial questions remain about how TNBC is regulated by these genetic alterations. METHODS/STUDY POPULATION: In order to address this issue, we established p53/ARF-defective murine embryonic fibroblast and mammary epithelial cell to study the molecular and phenotypic consequences. Moreover, transgenic mice were generated to investigate the effect of p53/ARF deficiency on mammary tumor development in vivo. RESULTS/ANTICIPATED RESULTS: Increased proliferation and transformation capability were observed in p53/ARF-defective cells, and an aggressive form of mammary tumor was also seen in p53−/−ARF−/− mice. Gene expression profiling and knock-down experiments using shRNAs were conducted to identify inflammatory marker ISG15 and RNA-editing enzyme ADAR1 as potential culprits for the elevated oncogenic potential. Interestingly, we found that the overexpression of ISG15 and ADAR1 is also prevalent in human TNBC cell lines. Reducing ADAR1 expression abrogated the oncogenic potential of human TNBC cell lines, while non-TNBC cells are less susceptible. DISCUSSION/SIGNIFICANCE OF IMPACT: These results indicate critical roles played by the tumor suppressors p53 and ARF in the pathogenesis of TNBC, likely through regulating ADAR1-mediated RNA modifications. Further understanding of this pathway promises to shed light on genetics-driven vulnerabilities of TNBC and inform development of more effective therapeutic strategies.

Fabrication and investigation of silica nanofibers via electrospinning

Electrospinning is a versatile and cost-effective method for fabricating nanofibers of different materials suitable for various applications. In this work, silica nanofibers have produced using the electrospinning method followed by the heat treatment. To fabricate silica nanofibers, polyvinylpyrrolidone (PVP), tetraethyl orthosilicate (TEOS) and Butanol were used to prepare the dope solutions. The optimized concentration for polymer in the dope solutions was then measured at 0.1 g/ml. The electrospinning process was conducted under the optimum circumstances of voltage, injection flow, tip to collector distance, ambient temperature (25 °C) and the humidity of 47%. Having conducted the thermal analysis (TG/DTA), electrospun fibers were exposed to thermal analysis in three different temperatures of 500, 700, and 1000 °C for 5 h. Following this, the morphology and the diameter of the fibers, as well as the chemical composition and the crystallinity of each sample were analyzed using scanning electron microscopy (SEM), Fourier transform infrared spectrometer (FT-IR), and x-ray diffractometry (XRD), respectively. The noteworthy conditions of 700 °C and 5 h of heat treatment (i.e., calcination) have provided satisfactory results in terms of silica nanofibers morphology and fibers; diameter, i.e., 110 and 600 nm. For cytotoxicity assay, murine fibroblast cells L929 were cultured on a mat of as-spun silica nanofibers. After 24 h and 48 h cultivation time, samples showed no evidence of cytotoxicity effect, which will be a promising result.

Catalytic Double Cyclization Process for Antitumor Agents against Breast Cancer Cell Lines

SummaryThe development of efficient synthetic strategies for the discovery of novel antitumor molecules is a major goal in current research. In this context, we report here a catalytic double cyclization process leading to bicyclic heterocycles with significant antitumor activity on different human breast cancer (BC) cell lines. The products, 6,6a-dihydrofuro[3,2-b]furan-2(5H)-ones, were obtained in one step, starting from simple substrates (4-yne-1,3-diols, CO, and O2), under the catalytic action of PdI2 in conjunction with KI. These compounds have significant antiproliferative activity in vitro on human BC cell lines, both hormone receptor positive (MCF-7) and triple negative (triple-negative breast cancer [TNBC]; MDA-MB-231 and MDAMB-468), while exhibiting practically no effects on normal MCF-10A (human mammary epithelial) and 3T3-L1 (murine fibroblasts) cells. Thus, these compounds have the potential to expand the therapeutic options against BC, and in particular, against its most aggressive forms (TNBCs). Moreover, the present synthetic approach may provide an economic benefit for their production.

Anti-inflammatory, antiproliferative and cytoprotective potential of the Attalea phalerata Mart. ex Spreng. pulp oil.

The anti-inflammatory, antiproliferative and cytoprotective activity of the Attalea phalerata Mart. ex Spreng pulp oil was evaluated by in vitro and in vivo methods. As for the chemical profile, the antioxidant activity was performed by spectrophotometry, and the profile of carotenoids and amino acids by chromatography. Our data demonstrated that A. phalerata oil has high carotenoid content, antioxidant activity and the presence of 5 essential amino acids. In the in vitro models of inflammation, the oil demonstrated the capacity to inhibit COX1 and COX2 enzymes, the production of nitric oxide and also induces macrophages to spreading. In the in vivo models of inflammation, the oil inhibited edema and leukocyte migration in the Wistar rats. In the in vitro model of antiproliferative and cytoprotective activity, the oil was shown inactive against the kidney carcinoma and prostate carcinoma lineage cells and with cytoprotective capacity in murine fibroblast cells, inhibiting the cytotoxic action of doxorubicin. Therefore, it is concluded that A. phalerata pulp oil has anti-inflammatory effects with nutraceutical properties potential due to the rich composition. Moreover, the oil also has cytoprotective activity probably because of its ability to inhibit the action of free radicals.

Biosynthesis of silver nanoparticles using Caesalpinia ferrea (Tul.) Martius extract: physicochemical characterization, antifungal activity and cytotoxicity.

BackgroundGreen synthesis is an ecological technique for the production of well characterized metallic nanoparticles using plants. This study investigated the synthesis of silver nanoparticles (AgNPs) using a Caesalpinia ferrea seed extract as a reducing agent.MethodsThe formation of AgNPs was identified by instrumental analysis, including ultraviolet–visible (UV–Vis) spectroscopy, scanning electron microscopy (SEM), X-ray diffraction (XRD) of the AgNPs, and surface-enhanced Raman scattering (SERS) spectra of rhodamine-6G (R6G). We studied the physicochemical characterization of AgNPs, evaluated them as an antifungal agent against Candida albicans, Candida kruzei, Candida glabrata and Candida guilliermondii, and estimated their minimum inhibitory concentration (MIC) and minimum fungicidal concentration (MFC) values. Lastly, this study evaluated the cytotoxicity of the AgNPs in murine L929 fibroblasts cells using an MTT assay.ResultsThe UV–Vis spectroscopy, SERS, SEM and XRD results confirmed the rapid formation of spheroidal 30–50 nm AgNPs. The MIC and MFC values indicated the antifungal potential of AgNPs against most of the fungi studied and high cell viability in murine L929 fibroblasts. In addition, this study demonstrated that C. ferrea seed extracts may be used for the green synthesis of AgNPs at room temperature for the treatment of candidiasis.