Novel 1,3,5-Triazinyl Aminobenzenesulfonamides Incorporating Aminoalcohol,Aminochalcone and Aminostilbene Structural Motifs as Potent Anti-VRE Agents,and Carbonic Anhydrases I,II, VII,IX, and XII Inhibitors

A series of 1,3,5-triazinyl aminobenzenesulfonamides substituted by aminoalcohol, aminostilbene, and aminochalcone structural motifs was synthesized as potential human carbonic anhydrase (hCA) inhibitors. The compounds were evaluated on their inhibition of tumor-associated hCA IX and hCA XII, hCA VII isoenzyme present in the brain, and physiologically important hCA I and hCA II. While the test compounds had only a negligible effect on physiologically important isoenzymes, many of the studied compounds significantly affected the hCA IX isoenzyme. Several compounds showed activity against hCA XII; (E)-4-{2-[(4-[(2,3-dihydroxypropyl)amino]-6-[(4-styrylphenyl)amino]-1,3,5-triazin-2-yl)amino]ethyl}benzenesulfonamide (31) and (E)-4-{2-[(4-[(4-hydroxyphenyl)amino]-6-[(4-styrylphenyl)amino]-1,3,5-triazin-2-yl)amino]ethyl}benzenesulfonamide (32) were the most effective inhibitors with K_Is = 4.4 and 5.9 nM, respectively. In addition, the compounds were tested against vancomycin-resistant Enterococcus faecalis (VRE) isolates. (E)-4-[2-({4-[(4-cinnamoylphenyl)amino]-6-[(4-hydroxyphenyl)amino]-1,3,5-triazin-2-yl}amino)ethyl]benzenesulfonamide (21) (MIC = 26.33 µM) and derivative 32 (MIC range 13.80–55.20 µM) demonstrated the highest activity against all tested strains. The most active compounds were evaluated for their cytotoxicity against the Human Colorectal Tumor Cell Line (HCT116 p53 +/+). Only 4,4’-[(6-chloro-1,3,5-triazin-2,4-diyl)bis(iminomethylene)]dibenzenesulfonamide (7) and compound 32 demonstrated an IC₅₀ of ca. 6.5 μM; otherwise, the other selected derivatives did not show toxicity at concentrations up to 50 µM. The molecular modeling and docking of active compounds into various hCA isoenzymes, including bacterial carbonic anhydrase, specifically α-CA present in VRE, was performed to try to outline a possible mechanism of selective anti-VRE activity.     

Heparin-Functionalized Adsorbents Eliminate Central Effectors of Immunothrombosis,including Platelet Factor 4, High-Mobility Group Box 1 Protein and Histones

Inflammation and thrombosis are closely intertwined in numerous disorders, including ischemic events and sepsis, as well as coronavirus disease 2019 (COVID-19). Thrombotic complications are markers of disease severity in both sepsis and COVID-19 and are associated with multiorgan failure and increased mortality. Immunothrombosis is driven by the complement/tissue factor/neutrophil axis, as well as by activated platelets, which can trigger the release of neutrophil extracellular traps (NETs) and release further effectors of immunothrombosis, including platelet factor 4 (PF4/CXCL4) and high-mobility box 1 protein (HMGB1). Many of the central effectors of deregulated immunothrombosis, including activated platelets and platelet-derived extracellular vesicles (pEVs) expressing PF4, soluble PF4, HMGB1, histones, as well as histone-decorated NETs, are positively charged and thus bind to heparin. Here, we provide evidence that adsorbents functionalized with endpoint-attached heparin efficiently deplete activated platelets, pEVs, PF4, HMGB1 and histones/nucleosomes. We propose that this elimination of central effectors of immunothrombosis, rather than direct binding of pathogens, could be of clinical relevance for mitigating thrombotic complications in sepsis or COVID-19 using heparin-functionalized adsorbents.     

Human Chorionic Gonadotropin and Early Embryogenesis: Review

Human chorionic gonadotropin (hCG) has four major isoforms: classical hCG, hyperglycosylated hCG, free β subunit, and sulphated hCG. Classical hCG is the first molecule synthesized by the embryo. Its RNA is transcribed as early as the eight-cell stage and the blastocyst produces the protein before its implantation. This review synthetizes everything currently known on this multi-effect hormone: hCG levels, angiogenetic activity, immunological actions, and effects on miscarriages and thyroid function.     

New steering mechanism for wheeled mobile robots

Mobile platform has attracted various researches inrobotic applications such as wheelchair, car-like-robotetc. Different categories of omni-directional mobileplatforms have been presented significantly over the last20 years. Their mechanical structures ar…     

Novel Insights into Autophagy and Prostate Cancer: A Comprehensive Review

Autophagy is a complex process involved in several cell activities, including tissue growth, differentiation, metabolic modulation, and cancer development. In prostate cancer, autophagy has a pivotal role in the regulation of apoptosis and disease progression. Several molecular pathways are involved, including PI3K/AKT/mTOR. However, depending on the cellular context, autophagy may play either a detrimental or a protective role in prostate cancer. For this purpose, current evidence has investigated how autophagy interacts within these complex interactions. In this article, we discuss novel findings about autophagic machinery in order to better understand the therapeutic response and the chemotherapy resistance of prostate cancer. Autophagic-modulation drugs have been employed in clinical trials to regulate autophagy, aiming to improve the response to chemotherapy or to anti-cancer treatments. Furthermore, the genetic signature of autophagy has been found to have a potential means to stratify prostate cancer aggressiveness. Unfortunately, stronger evidence is needed to better understand this field, and the application of these findings in clinical practice still remains poorly feasible.     

Antifungal Activity of Lactic Acid Bacteria Isolated from Peanuts,Gari, and Orange Fruit Juice against Food Aflatoxigenic Molds

This study aims to evaluate the antifungal activity of lactic acid bacteria (LAB) from some Cameroonian food commodities against mycotoxigenic and spoilage molds. Following LAB isolation, the antifungal activity of the isolates was assessed. The organic acids were quantified using high-performance liquid chromatography and the ability of the LAB to reduce mold biomass and aflatoxin production was evaluated. The LAB were identified and the biopreservative potential of strain LO3 was evaluated on tomato paste. Nine percent of the strains isolated showed broad antifungal activity. The activity was due to the effect of organic acids comprising lactic, acetic, 4-hydroxy-3-phenyllactic and 3-phenyllactic acids. Lactobacillus plantarum LO3 exhibiting the highest and broadest antifungal activity was selected and showed the capacity to inhibit fungal growth and aflatoxin production in vitro. Moreover, this strain and its cell-free supernatant showed the ability to prevent aflatoxigenic mold growth in tomato paste without altering its physico-chemical and organoleptic properties.     

Cytotoxicity of CeO2 nanoparticles for Escherichia coli. Physico-chemical insight of the cytotoxicity mechanism

The production of nanoparticles (NPs) is increasing rapidly for applications in electronics, chemistry, and biology. This interest is due to the very small size of NPs which provides them with many interesting properties such as rapid diffusion, high specific surface areas, reactivity in liquid or gas phase, and a size close to biomacromolecules. In turn, these extreme abilities might be a problem when considering a potentially uncontrolled exposure to the environment. For instance, nanoparticles might be highly mobile and rapidly transported in the environment or inside the body through a water or air pathway. Accordingly, the very fast development of these new synthetic nanomaterials raises questions about their impact on the environment and human health. We have studied the impact of a model water dispersion of nanoparticles (7 nm CeO2 oxide) on a Gram-negative bacteria (Escherichia coli). The nanoparticles are positively charged at neutral pH and thus display a strong electrostatic attraction toward bacterial outer membranes. The counting of colony forming units (CFU) after direct contact with CeO2 NPs allows for the defining of the conditions for which the contact is lethal to Escherichia coli. Furthermore, a set of experiments including sorption isotherms, TEM microscopy, and X-ray absorption spectroscopy (XAS) at cerium L3 edge is linked to propose a scenario for the observed toxic contact.     

Processing of tomato: impact on in vitro bioaccessibility of lycopene and textural properties

BACKGROUND: Human studies have demonstrated that processing of tomato can greatly increase lycopene bioavailability. However, the difference between processing methods is not widely investigated. In the current study different thermal treatments of tomato were evaluated with regard to their impact on in vitro bioaccessibility and retention of lycopene and β‐carotene as well as textural properties. Thermal treatments used were low (60 °C) and high (90 °C) temperature blanching followed by boiling. RESULTS: Lycopene was relatively stable during thermal treatment, whereas β‐carotene was significantly (P < 0.05) reduced by all heat treatments except for low temperature blanching. In vitro bioaccessibility of lycopene was significantly increased from 5.1 ± 0.2 to 9.2 ± 1.8 and 9.7 ± 0.6 mg kg^?1 for low and high temperature blanching, respectively. An additional boiling step after blanching did not further improve lycopene bioaccessibility for any treatment, but significantly reduced the consistency of low temperature treated samples. CONCLUSION: Choice and order of processing treatments can have a large impact on both lycopene bioavailability and texture of tomato products. Further investigations are needed, but this study provides one of the first steps towards tomato products tailored to optimise nutritional benefits. Copyright © 2010 Society of Chemical Industry