Novel Iron Oxide Nanoparticles Induce Ferroptosis in a Panel of Cancer Cell Lines

The use of nanomaterials rationally engineered to treat cancer is a burgeoning field that has reported great medical achievements. Iron-based polymeric nano-formulations with precisely tuned physicochemical properties are an expanding and versatile therapeutic strategy for tumor treatment. Recently, a peculiar type of regulated necrosis named ferroptosis has gained increased attention as a target for cancer therapy. Here, we show for the first time that novel iron oxide nanoparticles coated with gallic acid and polyacrylic acid (IONP–GA/PAA) possess intrinsic cytotoxic activity on various cancer cell lines. Indeed, IONP–GA/PAA treatment efficiently induces ferroptosis in glioblastoma, neuroblastoma, and fibrosarcoma cells. IONP–GA/PAA-induced ferroptosis was blocked by the canonical ferroptosis inhibitors, including deferoxamine and ciclopirox olamine (iron chelators), and ferrostatin-1, the lipophilic radical trap. These ferroptosis inhibitors also prevented the lipid hydroperoxide generation promoted by the nanoparticles. Altogether, we report on novel ferroptosis-inducing iron encapsulated nanoparticles with potent anti-cancer properties, which has promising potential for further in vivo validation.     

Inclusion Complex between Local Anesthetic/2-hydroxypropyl-β-cyclodextrin in Stealth Liposome

The drugs delivery system in the treatment of diseases has advantages such as reduced toxicity, increased availability of the drug, etc. Therefore, studies of the supramolecular interactions between local anesthetics (LAs) butamben (BTB) or ropivacaine (RVC) complexed with 2-hydroxypropyl-β-cyclodextrin (HP-βCD) and carried in Stealth liposomal (SL) are performed. ¹H-NMR nuclear magnetic resonance (DOSY and STD) were used as the main tools. The displacements observed in the ¹H-NMR presented the complexion between LAs and HP-βCD. The diffusion coefficients of free BTB and RVC were 7.70 × 10⁻¹⁰ m² s⁻¹ and 4.07 × 10⁻¹⁰ m² s⁻¹, and in the complex with HP-βCD were 1.90 × 10⁻¹⁰ m² s⁻¹ and 3.64 × 10⁻¹⁰ m² s⁻¹, respectively, which indicate a strong interaction between the BTB molecule and HP-βCD (98.3% molar fraction and Ka = 72.279 L/mol). With STD-NMR, the encapsulation of the BTB/HP-βCD and RVC/HP-βCD in SL vesicles was proven. Beyond the saturation transfer to the LAs, there is the magnetization transfer to the hydrogens of HP-βCD. BTB and RVC have already been studied in normal liposome systems; however, little is known of their behavior in SL.     

Salpianthus macrodontus Extracts,a Novel Source of Phenolic Compounds with Antibacterial Activity against Potentially Pathogenic Bacteria Isolated from White Shrimp

This study aimed to evaluate the antibacterial activity in vitro of Salpianthus macrodontus and Azadirachta indica extracts against potentially pathogenic bacteria for Pacific white shrimp. Furthermore, the extracts with higher inhibitory activity were analyzed to identify compounds responsible for bacterial inhibition and evaluate their effect on motility and biofilm formation. S. macrodontus and A. indica extracts were prepared using methanol, acetone, and hexane by ultrasound. The minimum inhibitory concentration (MIC) of the extracts was determined against Vibrio parahaemolyticus, V. harveyi, Photobacterium damselae and P. leiognathi. The polyphenol profile of those extracts showing the highest bacterial inhibition were determined. Besides, the bacterial swimming and swarming motility and biofilm formation were determined. The highest inhibitory activity against the four pathogens was found with the acetonic extract of S. macrodontus leaf (MIC of 50 mg/mL for Vibrio spp. and 25 mg/mL for Photobacterium spp.) and the methanol extract of S. macrodontus flower (MIC of 50 mg/mL for all pathogens tested). Both extracts affected the swarming and swimming motility and the biofilm formation of the tested bacteria. The main phenolic compounds related to Vibrio bacteria inhibition were naringin, vanillic acid, and rosmarinic acid, whilst hesperidin, kaempferol pentosyl-rutinoside, and rhamnetin were related to Photobacterium bacteria inhibition.     

Sensing the ortho Positions in C6Cl6 and C6H4Cl2 from Cl2− Formation upon Molecular Reduction

The geometrical effect of chlorine atom positions in polyatomic molecules after capturing a low-energy electron is shown to be a prevalent mechanism yielding Cl₂⁻. In this work, we investigated hexachlorobenzene reduction in electron transfer experiments to determine the role of chlorine atom positions around the aromatic ring, and compared our results with those using ortho-, meta- and para-dichlorobenzene molecules. This was achieved by combining gas-phase experiments to determine the reaction threshold by means of mass spectrometry together with quantum chemical calculations. We also observed that Cl₂⁻ formation can only occur in 1,2-C₆H₄Cl₂, where the two closest C–Cl bonds are cleaved while the chlorine atoms are brought together within the ring framework due to excess energy dissipation. These results show that a strong coupling between electronic and C–Cl bending motion is responsible for a positional isomeric effect, where molecular recognition is a determining factor in chlorine anion formation.     

Effect of Bauhinia monandra Kurz Leaf Preparations on Embryonic Stages and Adult Snails of Biomphalaria glabrata (Say, 1818), Schistosoma mansoni Cercariae and Toxicity in Artemia salina

Biomphalaria glabrata snails constitute the main vector of schistosomiasis in Brazil, and Bauhinia monandra Kurz, the leaves of which contain BmoLL lectin with biocidal action, is a plant widely found on continents in which the disease is endemic. This work describes the composition of B. monandra preparations and the effect on embryos and adult snails, their reproduction parameters and hemocytes. We also describe the results of a comet assay after B. glabrata exposure to sublethal concentrations of the preparations. Additionally, the effects of the preparations on S. mansoni cercariae and environmental monitoring with Artemia salina are described. In the chemical evaluation, cinnamic, flavonoid and saponin derivatives were detected in the two preparations assessed, namely the saline extract and the fraction. Both preparations were toxic to embryos in the blastula, gastrula, trochophore, veliger and hippo stages (LC₅₀ of 0.042 and 0.0478; 0.0417 and 0.0419; 0.0897 and 0.1582; 0.3734 and 0.0974; 0.397 and 0.0970 mg/mL, respectively) and to adult snails (LC₅₀ of 6.6 and 0.87 mg/mL, respectively), which were reproductively affected with decreased egg deposition. In blood cell analysis, characteristic cells for apoptosis, micronucleus and binucleation were detected, while for comet analysis, different degrees of nuclear damage were detected. The fraction was able to cause total mortality of the cercariae and did not present environmental toxicity. Therefore, B. monandra preparations are promising in combating schistosomiasis since they can control both the intermediate host and eliminate the infectious agent, besides being safe to the environment.     

“Click handle”-modified 2′-deoxy-2′-fluoroarabino nucleic acid as a synthetic genetic polymer capable of post-polymerization functionalization

The functions of natural nucleic acids such as DNA and RNA have transcended genetic information carriers and now encompass affinity reagents, molecular catalysts, nanostructures, data storage, and many others. However, the vulnerability of natural nucleic acids to nuclease degradation and the lack of chemical functionality have imposed a significant constraint on their ever-expanding applications. Herein, we report the synthesis and polymerase recognition of a 5-(octa-1,7-diynyl)uracil 2′-deoxy-2′-fluoroarabinonucleic acid (FANA) triphosphate. The DNA-templated, polymerase-mediated primer extension using this “click handle”-modified FANA (cmFANA) triphosphate and other FANA nucleotide triphosphates consisting of canonical nucleobases efficiently generated full-length products. The resulting cmFANA polymers exhibited excellent nuclease resistance and the ability to undergo efficient click conjugation with azide-functionalized molecules, thereby becoming a promising platform for serving as a programmable and evolvable synthetic genetic polymer capable of post-polymerization functionalization.

Polymerase-mediated incorporation of a “click handle”-modified fluoroarabinonucleic acid (cmFANA) triphosphate produces a new class of nuclease-resistant, evolvable genetic polymers that can be functionalized with azide-containing molecules.     

Precise Quantification of Molybdate In Vitro by the FRET-Based Nanosensor ‘MolyProbe’

Molybdenum (Mo) is an essential trace element in all kingdoms of life. Mo is bioavailable as the oxyanion molybdate and gains biological activity in eukaryotes when bound to molybdopterin, forming the molybdenum cofactor. The imbalance of molybdate homeostasis results in growth deficiencies or toxic symptoms within plants, fungi and animals. Recently, fluorescence resonance energy transfer (FRET) methods have emerged, monitoring cellular and subcellular molybdate distribution dynamics using a genetically encoded molybdate-specific FRET nanosensor, named MolyProbe. Here, we show that the MolyProbe system is a fast and reliable in vitro assay for quantitative molybdate determination. We added a Strep-TagII affinity tag to the MolyProbe protein for quick and easy purification. This MolyProbe is highly stable, resistant to freezing and can be stored for several weeks at 4 °C. Furthermore, the molybdate sensitivity of the assay peaked at low nM levels. Additionally, The MolyProbe was applied in vitro for quantitative molybdate determination in cell extracts of the plant Arabidopsis thaliana, the fungus Neurospora crassa and the yeast Saccharomyces cerevisiae. Our results show the functionality of the Arabidopsis thaliana molybdate transporter MOT1.1 and indicate that FRET-based molybdate detection is an excellent tool for measuring bioavailable Mo.     

Impact of the Cooking Process on Metabolite Profiling of Acanthocereus tetragonus,a Plant Traditionally Consumed in Mexico

Acanthocereus tetragonus (L.) Hummelinck is used as an alternative food source in some Mexican communities. It has been shown that the young stems of A. tetragonus provide crude protein, fiber, and essential minerals for humans. In this work, we analyzed the phytochemical profile, the total phenolic content (TPC), and the antioxidant activity of cooked and crude samples of A. tetragonus to assess its functional metabolite contribution to humans. The phytochemical profile was analyzed using Ultra-High-Performance Liquid Chromatography coupled to High-Resolution Mass Spectrometry (UHPLC-PDA-HESI-Orbitrap-MS/MS). Under the proposed conditions, 35 metabolites were separated and tentatively identified. Of the separated metabolites, 16 occurred exclusively in cooked samples, 6 in crude samples, and 9 in both crude and cooked samples. Among the detected compounds, carboxylic acids, such as threonic, citric, and malic acids, phenolic acids, and glycosylated flavonoids (luteolin-O-rutinoside) were detected. The TPC and antioxidant activity were analyzed using the Folin–Ciocalteu method and the 2,2-diphenyl-1-picrylhydrazyl (DPPH) free radical inhibition method, respectively. The TPC and antioxidant activity were significantly reduced in the cooked samples. We found that some metabolites remained intact after the cooking process, suggesting that A. tetragonus represents a source of functional metabolites for people who consume this plant species.     

Coffee Chlorogenic Acids Incorporation for Bioactivity Enhancement of Foods: A Review

The demand of foods with high antioxidant capacity have increased and research on these foods continues to grow. This review is focused on chlorogenic acids (CGAs) from green coffee, which is the most abundant source. The main CGA in coffee is 5-O-caffeoylquinic acid (5-CQA). Coffee extracts are currently the most widely used source to enhance the antioxidant activity of foods. Due to the solubility of CGAs, their extraction is mainly performed with organic solvents. CGAs have been associated with health benefits, such as antioxidant, antiviral, antibacterial, anticancer, and anti-inflammatory activity, and others that reduce the risk of cardiovascular diseases, type 2 diabetes, and Alzheimer’s disease. However, the biological activities depend on the stability of CGAs, which are sensitive to pH, temperature, and light. The anti-inflammatory activity of 5-CQA is attributed to reducing the proinflammatory activity of cytokines. 5-CQA can negatively affect colon microbiota. An increase in anthocyanins and antioxidant activity was observed when CGAs extracts were added to different food matrices such as dairy products, coffee drinks, chocolate, and bakery products. The fortification of foods with coffee CGAs has the potential to improve the functionality of foods.     

Effect of Biodegradable Coatings on the Growth of Aspergillus flavus In Vitro,on Maize Grains,and on the Quality of Tortillas during Storage

The fungus Aspergillus flavus causes serious damage to maize grains and its by-products, such as tortilla. Currently, animal and plant derivatives, such as chitosan and propolis, and plant extract residues, respectively, are employed as alternatives of synthetic fungicides. The objective of this research was to evaluate the efficacy of several formulations based on propolis-chitosan-pine resin extract on the in vitro growth of A. flavus, the growth of maize grain plantlets and the quality of stored tortillas at 4 and 28 °C. The most outstanding formulation was that based on 59.7% chitosan + 20% propolis nanoparticles + 20% pine resin extract nanoparticles; since the in vitro conidia germination of A. flavus did not occur, disease incidence on grains was 25–30% and in tortillas, 0% infection was recorded, along with low aflatoxin production (1.0 ppb). The grain germination and seedling growth were markedly reduced by the nanocoating application. The percentage weight loss and color of tortillas were more affected by this coating compared to the control, and the rollability fell within the scale of non-ruptured at 4 °C and partially ruptured at 28 °C. The next step is to evaluate the toxicity of this formulation.