Antirhea borbonica Aqueous Extract Protects Albumin and Erythrocytes from Glycoxidative Damages

Diabetes constitutes a major health problem associated with severe complications. In hyperglycemic conditions, chronically increased oxidation and glycation of circulating components lead to advanced glycation end-products (AGEs) formation, a key contributor in diabetes complication progression. In line with literature documenting the beneficial properties of herbal teas, this study evaluates the antioxidant/glycant properties of Antirhea borbonica (Ab). Ab aqueous extract effects were tested on human albumin or erythrocytes submitted to methyl glyoxal-mediated glycoxidative damages. By using mass spectrometry, Ab aqueous extracts revealed to be rich in polyphenols. All tested biomarkers of oxidation and glycation, such as AGE, ketoamine, oxidized thiol groups, were decreased in albumin when glycated in the presence of Ab aqueous extract. Ab extract preserve erythrocyte from methylglyoxal (MGO)-induced damages in terms of restored membrane deformability, reduced oxidative stress and eryptosis phenomenon. Antioxidant capacities of Ab extract on erythrocytes were retrieved in vivo in zebrafish previously infused with MGO. These results bring new evidences on the deleterious impacts of glycation on albumin and erythrocyte in diabetes. Furthermore, it reveals antioxidant and antiglycant properties of Ab that could be used for the dietary modulation of oxidative stress and glycation in hyperglycemic situations

Detection of antibacterial activity of essential oil components by TLC-bioautography using luminescent bacteria

The aim of the present study was the chemical characterization of some medically relevant essential oils (tea tree, clove, cinnamon bark, thyme and eucalyptus) and the investigation of antibacterial effect of the components of these oils by use of a direct bioautographic method. Thin layer chromatography (TLC) was combined with biological detection in this process. The chemical composition of the oils was determined by gas chromatography (GC) and gas chromatography-mass spectrometry (GC-MS). Eucalyptol (84.2%) was the main component of the essential oil of eucalyptus, eugenol (83.7%) of clove oil, and trans-cinnamic aldehyde (73.2%), thymol (49.9%) and terpinen-4-ol (45.8%) of cinnamon bark, thyme and tea tree oils, respectively. Antibacterial activity of the separated components of these oils, as well as their pure main components (eucalyptol, eugenol, trans-cinnamic aldehyde and thymol) was observed against the Gram-negative luminescence tagged plant pathogenic bacterium Pseudomonas syringae pv. maculicola (Psmlux) and the Gram-negative, naturally luminescent marine bacterium Vibrio fischeri. On the whole, the antibacterial activity of the essential oils could be related to their main components, but the minor constituents may be involved in this process. Trans-cinnamic aldehyde and eugenol were the most active compounds in TLC-bioautography. The sensitivity of TLC-bioautographic method can be improved with using luminescent test bacteria. This method is more cost-effective and provides more reliable results in comparison with conventional microbiological methods, e.g. disc-diffusion technique

cDC2 plasticity and acquisition of a DC3-like phenotype mediated by IL-6 and PGE2 in a patient-derived colorectal cancer organoids model

Metastatic colorectal cancer (CRC) is highly resistant to therapy and prone to recur. The tumor-induced local and systemic immunosuppression allows cancer cells to evade immunosurveillance, facilitating their proliferation and dissemination. Dendritic cells (DCs) are required for the detection, processing, and presentation of tumor antigens, and subsequently for the activation of antigen-specific T cells to orchestrate an effective antitumor response. Notably, successful tumors have evolved mechanisms to disrupt and impair DC functions, underlining the key role of tumor-induced DC dysfunction in promoting tumor growth, metastasis initiation, and treatment resistance. Conventional DC type 2 (cDC2) are highly prevalent in tumors and have been shown to present high phenotypic and functional plasticity in response to tumor-released environmental cues. This plasticity reverberates on both the development of antitumor responses and on the efficacy of immunotherapies in cancer patients. Uncovering the processes, mechanisms, and mediators by which CRC shapes and disrupts cDC2 functions is crucial to restoring their full antitumor potential. In this study, we use our recently developed 3D DC-tumor co-culture system to investigate how patient-derived primary and metastatic CRC organoids modulate cDC2 phenotype and function. We first demonstrate that our collagen-based system displays extensive interaction between cDC2 and tumor organoids. Interestingly, we show that tumor-corrupted cDC2 shift toward a CD14+ population with defective expression of maturation markers, an intermediate phenotype positioned between cDC2 and monocytes, and impaired T-cell activating abilities. This phenotype aligns with the newly defined DC3 (CD14(+) CD1c(+) CD163(+)) subset. Remarkably, a comparable population was found to be present in tumor lesions and enriched in the peripheral blood of metastatic CRC patients. Moreover, using EP2 and EP4 receptor antagonists and an anti-IL-6 neutralizing antibody, we determined that the observed phenotype shift is partially mediated by PGE2 and IL-6. Importantly, our system holds promise as a platform for testing therapies aimed at preventing or mitigating tumor-induced DC dysfunction. Overall, our study offers novel and relevant insights into cDC2 (dys)function in CRC that hold relevance for the design of therapeutic approaches

Enantioselective Dynamic Process Reduction of α- and β-Tetralone and Stereoinversion of Resulting Alcohols in a Selected Strain Culture

α-Tetralone and β-tetralone were subjected to biotransformation by 14 fungal strains. Enantiomeric purity of the products depended on the reaction time. 3-Day transformation of α-tetralone in Absidia cylindrospora culture gave S-(+)-1,2,3,4-tetrahydro-1-naftol of 92 % ee, whereas longer biotransformation time resulted in decrease of ee value. 3-Day transformation of β-tetralone by the same strain gave predominantly S-(−)-1,2,3,4-tetrahydro-2-naftol, whereas after 9 days of the reaction, the R-enantiomer with 85 % ee was isolated. Transformation of β-tetralone by Chaetomium sp. KCh 6651 gave pure (S)-(−)-1,2,3,4-tetrahydro-2-naftol in high yield at the concentration of 1 g/l. In this process, a non-selective carbonyl reduction was observed, followed by a selective oxidation of the R-alcohol

Updated clinical diagnostic criteria for sporadic Creutzfeldt-Jakob disease

Several molecular subtypes of sporadic Creutzfeldt-Jakob disease have been identified and electroencephalogram and cerebrospinal fluid biomarkers have been reported to support clinical diagnosis but with variable utility according to subtype. In recent years, a series of publications have demonstrated a potentially important role for magnetic resonance imaging in the pre-mortem diagnosis of sporadic Creutzfeldt-Jakob disease. Magnetic resonance imaging signal alterations correlate with distinct sporadic Creutzfeldt-Jakob disease molecular subtypes and thus might contribute to the earlier identification of the whole spectrum of sporadic Creutzfeldt-Jakob disease cases. This multi-centre international study aimed to provide a rationale for the amendment of the clinical diagnostic criteria for sporadic Creutzfeldt-Jakob disease. Patients with sporadic Creutzfeldt-Jakob disease and fluid attenuated inversion recovery or diffusion-weight imaging were recruited from 12 countries. Patients referred as ‘suspected sporadic Creutzfeldt-Jakob disease' but with an alternative diagnosis after thorough follow up, were analysed as controls. All magnetic resonance imaging scans were assessed for signal changes according to a standard protocol encompassing seven cortical regions, basal ganglia, thalamus and cerebellum. Magnetic resonance imaging scans were evaluated in 436 sporadic Creutzfeldt-Jakob disease patients and 141 controls. The pattern of high signal intensity with the best sensitivity and specificity in the differential diagnosis of sporadic Creutzfeldt-Jakob disease was identified. The optimum diagnostic accuracy in the differential diagnosis of rapid progressive dementia was obtained when either at least two cortical regions (temporal, parietal or occipital) or both caudate nucleus and putamen displayed a high signal in fluid attenuated inversion recovery or diffusion-weight imaging magnetic resonance imaging. Based on our analyses, magnetic resonance imaging was positive in 83% of cases. In all definite cases, the amended criteria would cover the vast majority of suspected cases, being positive in 98%. Cerebral cortical signal increase and high signal in caudate nucleus and putamen on fluid attenuated inversion recovery or diffusion-weight imaging magnetic resonance imaging are useful in the diagnosis of sporadic Creutzfeldt-Jakob disease. We propose an amendment to the clinical diagnostic criteria for sporadic Creutzfeldt-Jakob disease to include findings from magnetic resonance imaging scan

Stereoselective Ag-Catalyzed 1,3-Dipolar Cycloaddition of Activated Trifluoromethyl-Substituted Azomethine Ylides

This is the peer reviewed version of the following article: Chemistry – A European Journal 22.14 (2016): 4952 - 4959, which has been published in final form at http://doi.org/10.1002/chem.201504869. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Use of Self-Archived VersionsA silver-catalyzed 1,3-dipolar cycloaddition of fluorinated azomethine ylides and activated olefins is reported. The reaction offers a straightforward and atom-economical procedure for the preparation of fluorinated pyrrolidines. Broad scope and high levels of diastereoselectivity have been achieved simply by using AgOAc/PPh3as the catalyst system. The high efficiency of the cycloaddition relies on the presence of a metal-coordinating group on the imine moiety, such as an ester or heteroaryl group. The asymmetric version of the cycloaddition has been developed by using Taniaphos as a chiral ligandFinancial support of this work by the Ministerio de Economía y Competitividad (MINECO, CTQ2012-35790) is gratefully acknowledge

Evaluation of the antibacterial and anticancer activities of some South African medicinal plants

<p>Abstract</p> <p>Background</p> <p>Several herbs are traditionally used in the treatment of a variety of ailments particularly in the rural areas of South Africa where herbal medicine is mainly the source of health care system. Many of these herbs have not been assessed for safety or toxicity to tissue or organs of the mammalian recipients.</p> <p>Methods</p> <p>This study evaluated the cytotoxicity of some medicinal plants used, inter alia, in the treatment of diarrhoea, and stomach disorders. Six selected medicinal plants were assessed for their antibacterial activities against ampicillin-resistant and kanamycin-resistant strains of <it>Escherichia coli </it>by the broth micro-dilution methods. The cytotoxicities of methanol extracts and fractions of the six selected plants were determined using a modified tetrazolium-based colorimetric assay (3-(4, 5-dimethylthiazol)-2, 5-diphenyl tetrazolium bromide (MTT) assay).</p> <p>Results</p> <p>The average minimum inhibitory concentration (MIC) values of the plants extracts ranged from 0.027 mg/mℓ to 2.5 mg/mℓ after 24 h of incubation. <it>Eucomis autumnalis </it>and <it>Cyathula uncinulata </it>had the most significant biological activity with the least MIC values. The in vitro cytotoxicity assay on human hepatocarcinoma cell line (Huh-7) revealed that the methanol extract of <it>E. autumnalis </it>had the strongest cytotoxicity with IC₅₀of 7.8 μg/mℓ. Ethyl acetate and butanol fractions of <it>C. uncinulata, Hypoxis latifolia, E. autumnalis </it>and <it>Lantana camara </it>had lower cytotoxic effects on the cancer cell lines tested with IC₅₀values ranging from 24.8 to 44.1 μg/mℓ; while all the fractions of <it>Aloe arborescens </it>and <it>A. striatula </it>had insignificant or no cytotoxic effects after 72 h of treatment.</p> <p>Conclusions</p> <p>Our results indicate that the methanol fraction of <it>E. autumnalis </it>had a profound cytotoxic effect even though it possessed very significant antibacterial activity. This puts a query on its safety and hence a call for caution in its usage, thus a product being natural is not tantamount to being entirely safe. However, the antibacterial activities and non-cytotoxic effects of <it>A. arborescens </it>and <it>A. striatula </it>validates their continuous usage in ethnomedicine.</p

Updated clinical diagnostic criteria for sporadic Creutzfeldt-Jakob disease

Several molecular subtypes of sporadic Creutzfeldt–Jakob disease have been identified and electroencephalogram and cerebrospinal fluid biomarkers have been reported to support clinical diagnosis but with variable utility according to subtype. In recent years, a series of publications have demonstrated a potentially important role for magnetic resonance imaging in the pre-mortem diagnosis of sporadic Creutzfeldt–Jakob disease. Magnetic resonance imaging signal alterations correlate with distinct sporadic Creutzfeldt–Jakob disease molecular subtypes and thus might contribute to the earlier identification of the whole spectrum of sporadic Creutzfeldt–Jakob disease cases. This multi-centre international study aimed to provide a rationale for the amendment of the clinical diagnostic criteria for sporadic Creutzfeldt–Jakob disease. Patients with sporadic Creutzfeldt–Jakob disease and fluid attenuated inversion recovery or diffusion-weight imaging were recruited from 12 countries. Patients referred as ‘suspected sporadic Creutzfeldt–Jakob disease’ but with an alternative diagnosis after thorough follow up, were analysed as controls. All magnetic resonance imaging scans were assessed for signal changes according to a standard protocol encompassing seven cortical regions, basal ganglia, thalamus and cerebellum. Magnetic resonance imaging scans were evaluated in 436 sporadic Creutzfeldt–Jakob disease patients and 141 controls. The pattern of high signal intensity with the best sensitivity and specificity in the differential diagnosis of sporadic Creutzfeldt–Jakob disease was identified. The optimum diagnostic accuracy in the differential diagnosis of rapid progressive dementia was obtained when either at least two cortical regions (temporal, parietal or occipital) or both caudate nucleus and putamen displayed a high signal in fluid attenuated inversion recovery or diffusion-weight imaging magnetic resonance imaging. Based on our analyses, magnetic resonance imaging was positive in 83% of cases. In all definite cases, the amended criteria would cover the vast majority of suspected cases, being positive in 98%. Cerebral cortical signal increase and high signal in caudate nucleus and putamen on fluid attenuated inversion recovery or diffusion-weight imaging magnetic resonance imaging are useful in the diagnosis of sporadic Creutzfeldt–Jakob disease. We propose an amendment to the clinical diagnostic criteria for sporadic Creutzfeldt–Jakob disease to include findings from magnetic resonance imaging scans

Cementomimetics—constructing a cementum-like biomineralized microlayer via amelogenin-derived peptides

This is the published version. Copyright 2012 Nature Publishing GroupCementum is the outer-, mineralized-tissue covering the tooth root and an essential part of the system of periodontal tissue that anchors the tooth to the bone. Periodontal disease results from the destructive behavior of the host elicited by an infectious biofilm adhering to the tooth root and left untreated, may lead to tooth loss. We describe a novel protocol for identifying peptide sequences from native proteins with the potential to repair damaged dental tissues by controlling hydroxyapatite biomineralization. Using amelogenin as a case study and a bioinformatics scoring matrix, we identified regions within amelogenin that are shared with a set of hydroxyapatite-binding peptides (HABPs) previously selected by phage display. One 22-amino acid long peptide regions referred to as amelogenin-derived peptide 5 (ADP5) was shown to facilitate cell-free formation of a cementum-like hydroxyapatite mineral layer on demineralized human root dentin that, in turn, supported attachment of periodontal ligament cells in vitro. Our findings have several implications in peptide-assisted mineral formation that mimic biomineralization. By further elaborating the mechanism for protein control over the biomineral formed, we afford new insights into the evolution of protein–mineral interactions. By exploiting small peptide domains of native proteins, our understanding of structure–function relationships of biomineralizing proteins can be extended and these peptides can be utilized to engineer mineral formation. Finally, the cementomimetic layer formed by ADP5 has the potential clinical application to repair diseased root surfaces so as to promote the regeneration of periodontal tissues and thereby reduce the morbidity associated with tooth loss