Teriflunomide Preserves Neuronal Activity and Protects Mitochondria in Brain Slices Exposed to Oxidative Stress

Teriflunomide (TFN) limits relapses in relapsing–remitting multiple sclerosis (RRMS) by reducing lymphocytic proliferation through the inhibition of the mitochondrial enzyme dihydroorotate dehydrogenase (DHODH) and the subsequent modulation of de novo pyrimidine synthesis. Alterations of mitochondrial function as a consequence of oxidative stress have been reported during neuroinflammation. Previously, we showed that TFN prevents alterations of mitochondrial motility caused by oxidative stress in peripheral axons. Here, we aimed to validate TFN effects on mitochondria and neuronal activity in hippocampal brain slices, in which cellular distribution and synaptic circuits are largely preserved. TFN effects on metabolism and neuronal activity were investigated by assessing oxygen partial pressure and local field potential in acute slices. Additionally, we imaged mitochondria in brain slices from the transgenic Thy1-CFP/COX8A)S2Lich/J (mitoCFP) mice using two-photon microscopy. Although TFN could not prevent oxidative stress-related depletion of ATP, it preserved oxygen consumption and neuronal activity in CNS tissue during oxidative stress. Furthermore, TFN prevented mitochondrial shortening and fragmentation of puncta-shaped and network mitochondria during oxidative stress. Regarding motility, TFN accentuated the decrease in mitochondrial displacement and increase in speed observed during oxidative stress. Importantly, these effects were not associated with neuronal viability and did not lead to axonal damage. In conclusion, during conditions of oxidative stress, TFN preserves the functionality of neurons and prevents morphological and motility alterations of mitochondria.     

Roles of α-Synuclein and Disease-Associated Factors in Drosophila Models of Parkinson’s Disease

α-Synuclein (αSyn) plays a major role in the pathogenesis of Parkinson’s disease (PD), which is the second most common neurodegenerative disease after Alzheimer’s disease. The accumulation of αSyn is a pathological hallmark of PD, and mutations in the SNCA gene encoding αSyn cause familial forms of PD. Moreover, the ectopic expression of αSyn has been demonstrated to mimic several key aspects of PD in experimental model systems. Among the various model systems, Drosophila melanogaster has several advantages for modeling human neurodegenerative diseases. Drosophila has a well-defined nervous system, and numerous tools have been established for its genetic analyses. The rapid generation cycle and short lifespan of Drosophila renders them suitable for high-throughput analyses. PD model flies expressing αSyn have contributed to our understanding of the roles of various disease-associated factors, including genetic and nongenetic factors, in the pathogenesis of PD. In this review, we summarize the molecular pathomechanisms revealed to date using αSyn-expressing Drosophila models of PD, and discuss the possibilities of using these models to demonstrate the biological significance of disease-associated factors.     

Fetal Undernutrition Modifies Vascular RAS Balance Enhancing Oxidative Damage and Contributing to Remodeling

Fetal stress is known to increase susceptibility to cardiometabolic diseases and hypertension in adult age in a process known as fetal programming. This study investigated the relationship between vascular RAS, oxidative damage and remodeling in fetal programming. Six-month old Sprague-Dawley offspring from mothers that were fed ad libitum (CONTROL) or with 50% intake during the second half of gestation (maternal undernutrition, MUN) were used. qPCR or immunohistochemistry were used to obtain the expression of receptors and enzymes. Plasma levels of carbonyls were measured by spectrophotometry. In mesenteric arteries from MUN rats we detected an upregulation of ACE, ACE2, AT₁ receptors and NADPH oxidase, and lower expression of AT₂, Mas and MrgD receptors compared to CONTROL. Systolic and diastolic blood pressure and plasma levels of carbonyls were higher in MUN than in CONTROL. Vascular morphology evidenced an increased media/lumen ratio and adventitia/lumen ratio, and more connective tissue in MUN compared to CONTROL. In conclusion, fetal undernutrition indices RAS alterations and oxidative damage which may contribute to the remodeling of mesenteric arteries, and increase the risk of adverse cardiovascular events and hypertension.     

Medicated Scaffolds Prepared with Hydroxyapatite/Streptomycin Nanoparticles Encapsulated into Polylactide Microfibers

The preparation, characterization, and controlled release of hydroxyapatite (HAp) nanoparticles loaded with streptomycin (STR) was studied. These nanoparticles are highly appropriate for the treatment of bacterial infections and are also promising for the treatment of cancer cells. The analyses involved scanning electron microscopy, dynamic light scattering (DLS) and Z-potential measurements, as well as infrared spectroscopy and X-ray diffraction. Both amorphous (ACP) and crystalline (cHAp) hydroxyapatite nanoparticles were considered since they differ in their release behavior (faster and slower for amorphous and crystalline particles, respectively). The encapsulated nanoparticles were finally incorporated into biodegradable and biocompatible polylactide (PLA) scaffolds. The STR load was carried out following different pathways during the synthesis/precipitation of the nanoparticles (i.e., nucleation steps) and also by simple adsorption once the nanoparticles were formed. The loaded nanoparticles were biocompatible according to the study of the cytotoxicity of extracts using different cell lines. FTIR microspectroscopy was also employed to evaluate the cytotoxic effect on cancer cell lines of nanoparticles internalized by endocytosis. The results were promising when amorphous nanoparticles were employed. The nanoparticles loaded with STR increased their size and changed their superficial negative charge to positive. The nanoparticles’ crystallinity decreased, with the consequence that their crystal sizes reduced, when STR was incorporated into their structure. STR maintained its antibacterial activity, although it was reduced during the adsorption into the nanoparticles formed. The STR release was faster from the amorphous ACP nanoparticles and slower from the crystalline cHAp nanoparticles. However, in both cases, the STR release was slower when incorporated in calcium and phosphate during the synthesis. The biocompatibility of these nanoparticles was assayed by two approximations. When extracts from the nanoparticles were evaluated in cultures of cell lines, no cytotoxic damage was observed at concentrations of less than 10 mg/mL. This demonstrated their biocompatibility. Another experiment using FTIR microspectroscopy evaluated the cytotoxic effect of nanoparticles internalized by endocytosis in cancer cells. The results demonstrated slight damage to the biomacromolecules when the cells were treated with ACP nanoparticles. Both ACP and cHAp nanoparticles were efficiently encapsulated in PLA electrospun matrices, providing functionality and bioactive properties.     

The Impact of [C16Pyr][Amp] on the Aggressiveness in Breast and Prostate Cancer Cell Lines

Breast (BrCa) and prostate (PCa) cancers are the most common malignancies in women and men, respectively. The available therapeutic options for these tumors are still not curative and have severe side effects. Therefore, there is an urgent need for more effective antineoplastic agents. Herein, BrCa, PCa, and benign cell lines were treated with two ionic liquids and two quinoxalines and functional experiments were performed—namely cell viability, apoptosis, cytotoxicity, and colony formation assays. At the molecular level, an array of gene expressions encompassing several molecular pathways were used to explore the impact of treatment on gene expression. Although both quinoxalines and the ionic liquid [C2OHMIM][Amp] did not show any effect on the BrCa and PCa cell lines, [C16Pyr][Amp] significantly decreased cell viability and colony formation ability, while it increased the apoptosis levels of all cell lines. Importantly, [C16Pyr][Amp] was found to be more selective for cancer cells and less toxic than cisplatin. At the molecular level, this ionic liquid was also associated with reduced expression levels of CPT2, LDHA, MCM2, and SKP2, in both BrCa and PCa cell lines. Hence, [C16Pyr][Amp] was shown to be a promising anticancer therapeutic agent for BrCa and PCa cell lines.     

New Formulation of a Methylseleno-Aspirin Analog with Anticancer Activity Towards Colon Cancer

Aspirin (ASA) has attracted wide interest of numerous scientists worldwide thanks to its chemopreventive and chemotherapeutic effects, particularly in colorectal cancer (CRC). Incorporation of selenium (Se) atom into ASA has greatly increased their anti-tumoral efficacy in CRC compared with the organic counterparts without the Se functionality, such as the promising antitumoral methylseleno-ASA analog (1a). Nevertheless, the efficacy of compound 1a in cancer cells is compromised due to its poor solubility and volatile nature. Thus, 1a has been formulated with native α-, β- and γ-cyclodextrin (CD), a modified β-CD (hydroxypropyl β-CD, HP-β-CD) and Pluronic F127, all of them non-toxic, biodegradable and FDA approved. Water solubility of 1a is enhanced with β- and HP- β-CDs and Pluronic F127. Compound 1a forms inclusion complexes with the CDs and was incorporated in the hydrophobic core of the F127 micelles. Herein, we evaluated the cytotoxic potential of 1a, alone or formulated with β- and HP- β-CDs or Pluronic F127, against CRC cells. Remarkably, 1a formulations demonstrated more sustained antitumoral activity toward CRC cells. Hence, β-CD, HP-β-CD and Pluronic F127 might be excellent vehicles to improve pharmacological properties of organoselenium compounds with solubility issues and volatile nature.     

Acylierung von Heterocyclen mit Kohlensäurederivaten. I. Kinetik und Mechanismus der Reaktion von 2-Aminobenzimidazolen mit Arylcyanaten

Acylation of Heterocycles with Carbonic Acid Derivatives. I. Kinetics and Mechanism of the Reaction of 2-Aminobenzimidazoles with Aryl Cyanates The second order rate constants for the reaction of 2-amino-benzimidazoles (2-ABI) with aryl cyanates forming 2-amino-benzimidazole aryl ester imide 3 have been determined in dependence on substituent effects by u. v. measurements. The results are interpreted by a six-membered cyclic transition state in which the electrophilic attack of the cyanate on the endocyclic N atom is catalyzed by an H bridge interaction of the exocyclic amino group of 2-ABI with the OCN group.     

Vitamins A and E content in infant milk-based powdered formulae after opening the packet

Vitamins A and E were determined by HPLC in 20 starting, milk-based powdered infant formulae from local markets. We traced the evolution of these compounds, once the packets had been opened, during 0, 30 and 70 days of storage at room temperature (≈25 °C; min. 23 °C, max. 25.5 °C). Immediately after opening the packets, vitamin A ranged from 0.55 to 0.94 mg RE/100 g (93.3–183 μg RE/100 kcal) and vitamin E from 6.58 to 27.8 mg α-TE/100 g (1.36–5.39 mg α-TE/100 kcal). All the samples had higher vitamins A and E contents than those declared on the label, vitamin A mean adequacy values: 134% ± 17, min. 98%, max. 162%, and vitamin E 185% ± 47, min. 101%, max. 286%, including values at 0, 30 and 70 days of storage.     

Intracellular silver accumulation in Chlamydomonas reinhardtii upon exposure to carbonate coated silver nanoparticles and silver nitrate

The intracellular silver accumulation ({Ag}(in)) upon exposure to carbonate coated silver nanoparticles (AgNP, 0.5-10 μM, average diameter 29 nm) and silver nitrate (20-500 nM) was examined in the wild type and in the cell wall free mutant of the green alga Chlamydomonas reinhardtii at pH 7.5. The {Ag}(in) was measured over time up to 1 h after a wash procedure to remove silver ions (Ag(+)) and AgNP from the algal cell surface. The {Ag}(in) increased with increasing exposure time and with increasing AgNP and AgNO(3) concentrations in the exposure media, reaching steady-state concentrations between 10(-5) and 10(-3) mol L(cell)(-1). According to estimated kinetic parameters, high Ag(+) bioconcentration factors were calculated (>10(3) L L(cell)(-1)). Higher accumulation rate constants were assessed in the cell wall free mutant, indicating a protective role of the cell wall in limiting Ag(+) uptake. The bioavailability of AgNP was calculated to be low in both strains relative to Ag(+), suggesting that AgNP internalization across the cell membrane was limited.     

The Effect of Food Type (Fish Nuggets or French Fries) on Oil Blend Degradation during Repeated Frying

Abstract: Oil that is reused multiple times for deep frying goes through changes in chemical composition and physical characteristics, affecting the quality of the fried foods. In this study, the effect of the food type (fish nuggets or French fries) on the degradation of an oil blend during the deep‐fat frying of each food at 180°C during 12 days was determined, and the characteristics of the fried products were evaluated. The degradation of oil during repeated use was relatively faster when fish nuggets were fried than when French fries were fried, as higher values of total polar compounds were obtained. Practical Application: The results are useful for producers of French fries and fish nuggets, such as restaurants or fast foods sellers, providing them with practical guidelines within the permitted values established by the regulatory authorities. The studied foods have high economic importance and are different in their composition. Under the studied conditions, the tested oil blend may be used during 4 d (4 h per day) with a daily replenishment, without discarding the oil when frying fish nuggets, and must be discarded after 8 d when French fries are processed. This suggestion allows preparing safe fried foods for consumers.