Solubility enhancement of ibuprofen using tri-ureasil-PPO hybrid: structural,cytotoxic, and drug release investigation

Herein, we used tri-ureasil organic–inorganic hybrid material (tU5000) in order to enhance the solubility of nonsteroidal anti-inflammatory drugs and fine tuning the drug delivery profile. For the first time, we used tU5000 as a film-forming agent in order to provide an alternative vehicle for transdermal drug delivery systems which the cell viability of practically 100 % for the highest and the lowest tested concentrations of pure tU5000 indicated that the material was not cytotoxic. The physicochemical properties of the tU5000 drug carrier and drug-loaded hybrids were systematically studied using powder X-ray diffraction, differential scanning calorimetry, small-angle X-ray scattering, and Fourier-transform infrared spectroscopy. The structural changes of tU5000 as well as the relationships between the drug content and in vitro drug release behaviors were investigated. The results showed that the ibu molecules were homogeneously distributed in the tU5000 xerogels contributing to fine-tuning the drug delivery profile. Considering the ability to incorporated high drug content, simple and mild preparation procedure by one-pot sol–gel route, high stability of the materials, sustained-release property, this class of hybrid based on polymers and inorganic compounds may have potential applications in the design of pharmaceutical formulation as ophthalmic (contact lenses), transdermal (patches) and implantable (soft tissue) drug delivery systems.     

Real‐Time In Vivo Detection of Cellular Senescence through the Controlled Release of the NIR Fluorescent Dye Nile Blue

In vivo detection of cellular senescence is accomplished by using mesoporous silica nanoparticles loaded with the NIR‐FDA approved Nile blue (NB) dye and capped with a galactohexasaccharide ( S3 ). NB emission at 672 nm is highly quenched inside S3 , yet a remarkable emission enhancement is observed upon cap hydrolysis in the presence of β‐galactosidase and dye release. The efficacy of the probe to detect cellular senescence is tested in vitro in melanoma SK‐Mel‐103 and breast cancer 4T1 cells and in vivo in palbociclib‐treated BALB/cByJ mice bearing breast cancer tumor.     

Development and Validation of Multi-Residue Method for Drugs Analysis in Human Feces by Liquid Chromatography–Tandem Mass Spectrometry

The use of veterinary drugs in animal production is a common practice to secure animal and human health. However, residues of administrated drugs could be present in animal food products. Levels of drugs in food of animal origin are regulated within the European Union. In recent years, residues have been detected not only in food, but also in the environmental elements such as water or soil, meaning that humans are involuntarily exposed to these substances. This article presents a multiclass method for the analysis of various therapeutic groups of pharmaceuticals in human feces. Pharmaceuticals are extracted from feces with an acid extraction solvent, and after filtration the extract was analyzed by HPLC–MS/MS. A limit of detection of 10 ng/g was achieved for 9 pharmaceuticals, with linearity over 0.99 and repeatability and reproducibility lower than 20%. The method was satisfactorily applied in 25 feces samples of individuals that had declared not to be under medical treatment for the last two months. Results indicate the presence of six different compounds at concentration between 10 and 456 ng/g. This preliminary study showed the involuntary exposure of human gut microbiota to active substances such as pharmaceuticals     

Bioactive Compounds from Pale Ale Beer Powder Attenuate Experimental Colitis in BALB/c Mice

Phenolic compounds (PCs) present in foods are associated with a decreased risk of developing inflammatory diseases. The aim of this study was to extract and characterize PCs from craft beer powder and evaluate their potential benefits in an experimental model of inflammatory bowel disease (IBD). PCs were extracted and quantified from pure beer samples. BALB/c mice received either the beer phenolic extract (BPE) or beer powder fortified with phenolic extract (BPFPE) of PCs daily for 20 days by gavage. Colon samples were collected for histopathological and immunohistochemical analyses. Dextran sodium sulfate (DSS)-induced mice lost more weight, had reduced colon length, and developed more inflammatory changes compared with DSS-induced mice treated with either BPE or BPFPE. In addition, in DSS-induced mice, the densities of CD4- and CD11b-positive cells, apoptotic rates, and activation of NF-κB and p-ERK1/2 MAPK intracellular signaling pathways were higher in those treated with BPE and BPFPE than in those not treated. Pretreatment with the phenolic extract and BPFPE remarkably attenuated DSS-induced colitis. The protective effect of PCs supports further investigation and development of therapies for human IBD.     

Immunomodulatory Properties of Masticadienonic Acid and 3α-Hydroxy Masticadienoic Acid in Dendritic Cells

Dendritic cells are antigen-presenting cells, which identify and process pathogens to subsequently activate specific T lymphocytes. To regulate the immune responses, DCs have to mature by the recognition of TLR ligands, TNFα or IFNγ. These ligands have been used as adjuvants to activate DCs in situ or in vitro, with toxic effects. It has been shown that some molecules affect the immune system, e.g., Masticadienonic acid (MDA) and 3α-hydroxy masticadienoic acid (3α-OH MDA) triterpenes naturally occurring in several medicinal plants, since they activate the nitric oxide synthase in macrophages and induce T lymphocyte proliferation. The DCs maturation induced by MDA or 3a-OH MDA was determined by incubating these cells with MDA or 3α-OH MDA, and their phenotype was afterwards analyzed. The results showed that only 3α-OH MDA was able to induce DCs maturation. When mice with melanoma were inoculated with DCs/3α-OH MDA, a decreased tumor growth rate was observed along with an extended cell death area within tumors compared to mice treated with DCs incubated with MDA. In conclusion, it is proposed that 3α-OH MDA may be an immunostimulant molecule. Conversely, it is proposed that MDA may be a molecule with anti-inflammatory properties.     

Heartwood of Dalbergia cochinchinensis: 4,7,2′-Trihydroxy-4′-methoxyisoflavanol and 6,4′-Dihydroxy-7-methoxyflavane Reduce Cytokine and Chemokine Expression In Vitro

Dalbergia cochinchinensis has been widely used in traditional medicine because of its flavonoids; however, the impact of the flavonoids to modulate the inflammatory response to oral cells remains to be described. For this aim, we isolated 4,7,2′-trihydroxy-4′-methoxyisoflavanol (472T4MIF) and 6,4′-dihydroxy-7-methoxyflavane (64D7MF) from the heartwood of D. cochinchinensis and confirmed the chemical structure by nuclear magnetic resonance. We show here that both flavonoids are inhibitors of an inflammatory response of murine RAW 264.7 inflammatory macrophages stimulated by LPS. This is indicated by interleukin (IL)1, IL6, and chemokine CCL2 production besides the phosphorylation of p65. Consistently, in primary murine macrophages, both flavonoids decreased the inflammatory response by lowering LPS-induced IL1 and IL6 expression. To introduce oral cells, we have used human gingival fibroblasts and provoked the inflammatory response by exposing them to IL1β and TNFα. Under these conditions, 472T4MIF, but not 64D7MF, reduced the expression of chemokines CXCL1 and CXCL2. Taken together, we identified two flavonoids that can reduce the expression of cytokines and chemokines in macrophages and fibroblastic cells.     

Convolutional Neural Network Approach for Multispectral Facial Presentation Attack Detection in Automated Border Control Systems

Automated border control systems are the first critical infrastructure point when crossing a border country. Crossing border lines for unauthorized passengers is a high security risk to any country. This paper presents a multispectral analysis of presentation attack detection for facial biometrics using the learned features from a convolutional neural network. Three sensors are considered to design and develop a new database that is composed of visible (VIS), near-infrared (NIR), and thermal images. Most studies are based on laboratory or ideal conditions-controlled environments. However, in a real scenario, a subject’s situation is completely modified due to diverse physiological conditions, such as stress, temperature changes, sweating, and increased blood pressure. For this reason, the added value of this study is that this database was acquired in situ. The attacks considered were printed, masked, and displayed images. In addition, five classifiers were used to detect the presentation attack. Note that thermal sensors provide better performance than other solutions. The results present better outputs when all sensors are used together, regardless of whether classifier or feature-level fusion is considered. Finally, classifiers such as KNN or SVM show high performance and low computational level.     

3-MCPD in food other than soy sauce or hydrolysed vegetable protein (HVP)

This review gives an overview of current knowledge about 3-monochloropropane-1,2-diol (3-MCPD) formation and detection. Although 3-MCPD is often mentioned with regard to soy sauce and acid-hydrolysed vegetable protein (HVP), and much research has been done in that area, the emphasis here is placed on other foods. This contaminant can be found in a great variety of foodstuffs and is difficult to avoid in our daily nutrition. Despite its low concentration in most foods, its carcinogenic properties are of general concern. Its formation is a multivariate problem influenced by factors such as heat, moisture and sugar/lipid content, depending on the type of food and respective processing employed. Understanding the formation of this contaminant in food is fundamental to not only preventing or reducing it, but also developing efficient analytical methods of detecting it. Considering the differences between 3-MCPD-containing foods, and the need to test for the contaminant at different levels of food processing, one would expect a variety of analytical approaches. In this review, an attempt is made to provide an up-to-date list of available analytical methods and to highlight the differences among these techniques. Finally, the emergence of 3-MCPD esters and analytical techniques for them are also discussed here, although they are not the main focus of this review.     

Components of Banisteriopsis caapi,a Plant Used in the Preparation of the Psychoactive Ayahuasca,Induce Anti-Inflammatory Effects in Microglial Cells

Banisteriopsis caapi is used to prepare the psychoactive beverage ayahuasca, and both have therapeutic potential for the treatment of many central nervous system (CNS) conditions. This study aimed to isolate new bioactive compounds from B. caapi extract and evaluate their biological activity, and that of the known β-carboline components of the plant (harmine, harmaline, and tetrahydroharmine), in BV-2 microglial cells, the in vivo activation of which is implicated in the physiopathology of CNS disorders. B. caapi extract was fractionated using semipreparative liquid chromatography (HPLC-DAD) and the exact masses ([M + H]⁺ m/z) of the compounds in the 5 isolated fractions were determined by high-resolution LC-MS/MS: F1 (174.0918 and 233.1289), F2 (353.1722), F3 (304.3001), F4 (188.1081), and F5 (205.0785). Harmine (75.5–302 µM) significantly decreased cell viability after 2 h of treatment and increased the number of necrotic cells and production of reactive oxygen species at equal or lower concentrations after 24 h. F4 did not impact viability but was also cytotoxic after 24 h. Most treatments reduced proinflammatory cytokine production (IL-2, IL-6, IL-17, and/or TNF), especially harmaline and F5 at 2.5 µM and higher concentrations, tetrahydroharmine (9.3 µM and higher), and F5 (10.7 µM and higher). The results suggest that the compounds found in B. caapi extract have anti-inflammatory potential that could be explored for the development of treatments for neurodegenerative diseases.