The impact of the Maillard reaction on the in vitro proteolytic breakdown of bovine lactoferrin in adults and infants

2014 ◽  
Vol 5 (8) ◽  
pp. 1898-1908 ◽  
Author(s):  
Alice M. Moscovici ◽  
Yousef Joubran ◽  
Valerie Briard-Bion ◽  
Alan Mackie ◽  
Didier Dupont ◽  
...  
Keyword(s):  
Maillard Reaction ◽  
Bioactive Peptide ◽  
Bovine Lactoferrin ◽  
Peptide Formation ◽  
The Impact ◽  
First Time

The impact of the Maillard reaction on proteolysis of the bioactive bovine lactoferrin is comparedin vitrobetween adults and infants for the first time, coupling proteomics to elucidate bioactive peptide formation.

scholarly journals Phenotypic Susceptibility to Bevirimat in Isolates from HIV-1-Infected Patients without Prior Exposure to Bevirimat

2010 ◽  
Vol 54 (6) ◽  
pp. 2345-2353 ◽  
Author(s):  
Nicolas A. Margot ◽  
Craig S. Gibbs ◽  
Michael D. Miller
Keyword(s):  
Recombinant Viruses ◽  
Gag Polyprotein ◽  
New Class ◽  
Major Mutation ◽  
Hiv Drugs ◽  
The Impact ◽  
First Time ◽  
Hiv 1

ABSTRACT Bevirimat (BVM) is the first of a new class of anti-HIV drugs with a novel mode of action known as maturation inhibitors. BVM inhibits the last cleavage of the Gag polyprotein by HIV-1 protease, leading to the accumulation of the p25 capsid-small peptide 1 (SP1) intermediate and resulting in noninfectious HIV-1 virions. Early clinical studies of BVM showed that over 50% of the patients treated with BVM did not respond to treatment. We investigated the impact of prior antiretroviral (ARV) treatment and/or natural genetic diversity on BVM susceptibility by conducting in vitro phenotypic analyses of viruses made from patient samples. We generated 31 recombinant viruses containing the entire gag and protease genes from 31 plasma samples from HIV-1-infected patients with (n = 21) or without (n = 10) prior ARV experience. We found that 58% of the patient isolates tested had a >10-fold reduced susceptibility to BVM, regardless of the patient's ARV experience or the level of isolate resistance to protease inhibitors. Analysis of mutants with site-directed mutations confirmed the role of the V370A SP1 polymorphism (SP1-V7A) in resistance to BVM. Furthermore, we demonstrated for the first time that a capsid polymorphism, V362I (CA protein-V230I), is also a major mutation conferring resistance to BVM. In contrast, none of the previously defined resistance-conferring mutations in Gag selected in vitro (H358Y, L363M, L363F, A364V, A366V, or A366T) were found to occur among the viruses that we analyzed. Our results should be helpful in the design of diagnostics for prediction of the potential benefit of BVM treatment in HIV-1-infected patients.

scholarly journals Assessment of Healthy and Harmful Maillard Reaction Products in a Novel Coffee Cascara Beverage: Melanoidins and Acrylamide

Foods ◽  
2020 ◽  
Vol 9 (5) ◽  
pp. 620 ◽  
Author(s):  
Amaia Iriondo-DeHond ◽  
Ana Sofía Elizondo ◽  
Maite Iriondo-DeHond ◽  
Maria Belén Ríos ◽  
Romina Mufari ◽  
...  
Keyword(s):  
Maillard Reaction ◽  
Antioxidant Properties ◽  
Maillard Reaction Products ◽  
Reaction Products ◽  
High Fiber ◽  
Chemical Indicators ◽  
Safety And Health ◽  
Health Promoting ◽  
First Time

Our research aimed to evaluate the formation of Maillard reaction products in sun-dried coffee cascara and their impact on the safety and health promoting properties of a novel beverage called “Instant Cascara” (IC) derived from this coffee by-product. Maillard reaction products in sun-dried coffee cascara have never been reported. “Instant Cascara” (IC) extract was obtained by aqueous extraction and freeze-drying. Proteins, amino acids, lipids, fatty acid profile, sugars, fiber, minerals, and vitamins were analyzed for its nutritional characterization. Acrylamide and caffeine were used as chemical indicators of safety. Colored compounds, also called melanoidins, their stability under 40 °C and in light, and their in vitro antioxidant capacity were also studied. A safe instant beverage with antioxidant properties was obtained to which the following nutritional claims can be assigned: “low fat”, “low sugar” “high fiber” and “source of potassium, magnesium and vitamin C”. For the first time, cascara beverage color was attributed to the presence of antioxidant melanoidins (>10 kDa). IC is a potential sustainable alternative for instant coffee, with low caffeine and acrylamide levels and a healthy composition of nutrients and antioxidants.

scholarly journals 2′-O-Methylation of Ribosomal RNA: Towards an Epitranscriptomic Control of Translation?

Biomolecules ◽  
2018 ◽  
Vol 8 (4) ◽  
pp. 106 ◽  
Author(s):  
Piero Monaco ◽  
Virginie Marcel ◽  
Jean-Jacques Diaz ◽  
Frédéric Catez
Keyword(s):  
Ribosomal Rna ◽  
Translational Control ◽  
Ribosome Biogenesis ◽  
In Vitro Translation ◽  
Ribosome Structure ◽  
Quantitative Mapping ◽  
And Function ◽  
The Impact ◽  
First Time

Ribosomal RNA (rRNA) undergoes post-transcriptional modification of over 200 nucleotides, predominantly 2′-O-methylation (2′-O-Me). 2′-O-Methylation protects RNA from hydrolysis and modifies RNA strand flexibility but does not contribute to Watson-Crick base pairing. The contribution of 2′-O-Me to the translational capacity of ribosomes has been established. Yet, how 2′-O-Me participates in ribosome biogenesis and ribosome functioning remains unclear. The development of 2′-O-Me quantitative mapping methods has contributed to the demonstration that these modifications are not constitutive but rather provide heterogeneity to the ribosomal population. Moreover, recent advances in ribosome structure analysis and in vitro translation assays have proven, for the first time, that 2′-O-Me contributes to regulating protein synthesis. This review highlights the recent data exploring the impact of 2′-O-Me on ribosome structure and function, and the emerging idea that the rRNA epitranscriptome is involved in translational control.

scholarly journals Comparison of the In Vitro and Ex Vivo Permeation of Existing Topical Formulations Used in the Treatment of Facial Angiofibroma and Characterization of the Variations Observed

Pharmaceutics ◽  
2020 ◽  
Vol 12 (11) ◽  
pp. 1060
Author(s):  
Guillaume Le Guyader ◽  
Bernard Do ◽  
Victoire Vieillard ◽  
Karine Andrieux ◽  
Muriel Paul
Keyword(s):  
Ex Vivo ◽  
Thermodynamic Activity ◽  
Physico Chemical ◽  
Ex Vivo Permeation ◽  
Franz Cells ◽  
Great Heterogeneity ◽  
The Impact ◽  
First Time

Rapamycin has been used topically to treat facial angiofibromas associated with tuberous sclerosis for more than a decade. In the absence of a commercial form, a large number of formulations have been clinically tested. However, given the great heterogeneity of these studies, particularly with regard to the response criteria, it was difficult to know the impact and thus to compare the relevance of the formulations used. The objective of this work was therefore to evaluate the link between the diffusion of rapamycin and the physico-chemical characteristics of these different formulations on Strat-M® membranes as well as on human skin using Franz cells. Our results underline the importance of the type of vehicle used (hydrogel > cream > lipophilic ointment), the soluble state of rapamycin and its concentration close to saturation to ensure maximum thermodynamic activity. Thus, this is the first time that a comparative study of the different rapamycin formulations identified in the literature for the management of facial angiofibromas has been carried out using a pharmaceutical and biopharmaceutical approach. It highlights the important parameters to be considered in the development and optimization of topical rapamycin formulations with regard to cutaneous absorption for clinical efficacy.

scholarly journals Quantitative study of alpha-synuclein prion-like spreading in fully oriented reconstructed neural networks reveals non-synaptic dissemination of seeding aggregates

2021 ◽  
Author(s):  
Josquin Courte ◽  
Ngoc Anh Le ◽  
Luc Bousset ◽  
Ronald Melki ◽  
Catherine Villard ◽  
...  
Keyword(s):  
Neural Networks ◽  
Alpha Synuclein ◽  
Transfer Efficiency ◽  
Synaptic Connectivity ◽  
Low Efficiency ◽  
Synaptic Structures ◽  
The Impact ◽  
First Time ◽  
The Brain

The trans-neuronal spread of protein aggregates in a prion-like manner underlies the progression of neuronal lesions in the brain of patients with synucleinopathies such as Parkinson's disease. Despite being studied actively, the mechanisms of alpha-synuclein (aSyn) aggregates propagation remain poorly understood. This hinders the development of therapeutic approaches aiming at preventing the spatial progression of intracellular inclusions in neural networks. To assess the role of synaptic structures and neuron characteristics in the transfer efficiency of aggregates with seeding propensity, we developed a novel microfluidic culture system which allows for the first time to reconstruct in vitro fully oriented and synaptically connected neural networks. This is achieved by filtering axonal growth with unidirectional "axon valves" microchannels. We exposed the presynaptic compartment of reconstructed networks to well characterized human aSyn aggregates differing in size: Fibrils and Oligomers. Both aggregates were transferred to postsynaptic neurons through active axonal transport, albeit with poor efficiency. By manipulating network maturity, we compared the transfer rate of aggregates in networks with distinct levels of synaptic connectivity. Surprisingly, we found that transfer efficiency was lower in mature networks with higher synaptic connectivity. We then investigated the seeding efficiency of endogenous aSyn in the postsynaptic population. We found that exposure to Fibrils, and not Oligomers, resulted in low efficiency trans-neuronal seeding which was restricted to postsynaptic axons. Finally, we assessed the impact of neuron characteristics and aSyn expression on the propagation of aSyn aggregates. By reconstructing chimeric networks, we found that neuron characteristics, such as the brain region from which they originate or aSyn expression levels, did not significantly impact aggregates transfer, and observed no trans-neuronal seeding where the presynaptic population did not express aSyn. Overall, we demonstrate that this novel platform uniquely allows the quantitative interrogation of original aspects of the trans-neuronal propagation of seeding pathogenic entities.

Slo3 K+ channel blocker clofilium extends bull and mouse sperm-fertilizing competence

Reproduction ◽  
2018 ◽  
Vol 156 (6) ◽  
pp. 463-476 ◽  
Author(s):  
Roland Abi Nahed ◽  
Guillaume Martinez ◽  
Jean Pascal Hograindleur ◽  
Emilie Le Blévec ◽  
Sabine Camugli ◽  
...  
Keyword(s):  
Artificial Insemination ◽  
Acrosome Reaction ◽  
Channel Blocker ◽  
Specific Inhibitor ◽  
K Channel ◽  
Sperm Dna ◽  
The Impact ◽  
First Time ◽  
Bovine Species

For artificial insemination (AI) to be successful, it is essential that sperm delivery be perfectly timed relative to ovulation, as sperm lifespan is limited due to oxidative metabolism induced by capacitation. Extending the window of sperm capacitation could therefore increase sperm lifespan, prolong sperm-fertilizing competence and increase AI efficiency. Hyperpolarization of sperm is a crucial step in capacitation and is induced by activation of the potassium calcium-activated channel subfamily U member 1 (KCNU1, also named Slo3 or KSper). Given the essential role played by KCNU1 in capacitation, this study assessed the impact of its pharmacological inhibition on sperm lifespan. We showed that treatment of murine sperm with sub-micromolar concentrations of clofilium, a specific inhibitor of KCNU1, slowed down capacitation, decreased the rate of acrosome reaction and extended the fertilizing competence of capacitated sperm for 12 h. Clofilium also extended fertilizing competence and motility of bovine-capacitated sperm, and increased the rate of fertilization with sperm capacitated for 24 h by 100%, and the rate of blastocyst formation by 150%. Finally, toxicity experiments showed clofilium to have no impact on sperm DNA and no embryotoxicity at the concentration used to extend sperm lifespan. Our results demonstrate that clofilium prolongs fertilizing competence of aging capacitated sperm in vitro in both rodent and bovine species. To our knowledge, this is the first time the duration of sperm-fertilizing competence is shown to be extended by potassium channels blockers.

scholarly journals Molecular Interaction Characterization Strategies for the Development of New Biotherapeutic Antibody Modalities

Antibodies ◽  
2020 ◽  
Vol 9 (2) ◽  
pp. 7
Author(s):  
Xiangdan Wang ◽  
Minh Michael Phan ◽  
Ji Li ◽  
Herman Gill ◽  
Simon Williams ◽  
...  
Keyword(s):  
Molecular Interaction ◽  
Binding Kinetics ◽  
Therapeutic Development ◽  
Dosing Regimens ◽  
Fit For Purpose ◽  
Target Binding ◽  
The Impact ◽  
First Time

The characterization of target binding interactions is critical at each stage of antibody therapeutic development. During early development, it is important to design fit-for-purpose in vitro molecular interaction characterization (MIC) assays that accurately determine the binding kinetics and the affinity of therapeutic antibodies for their targets. Such information enables PK/PD (pharmacokinetics/pharmacodynamics) modeling, estimation of dosing regimens, and assessment of potency. While binding kinetics and affinities seem to be readily obtained, there is little discussion in the literature on how the information should be generated and used in a systematic manner along with other approaches to enable key drug development decisions. The introduction of new antibody modalities poses unique challenges to the development of MIC assays and further increases the need to discuss the impact of developing context-appropriate MIC assays to enable key decision making for these programs. In this paper, we discuss for the first time the challenges encountered when developing MIC assays supporting new antibody modalities. Additionally, through the presentation of several real case studies, we provide strategies to overcome these challenges to enable investigational new drug (IND) filings.

Role of blue light in bactericidal effect against meat-borne pathogens and freshness maintaining of beef

2021 ◽  
Author(s):  
Shuanghua Luo ◽  
Xi Yang ◽  
Shuyan Wu ◽  
Minmin Liu ◽  
Xiujuan Zhang ◽  
...  
Keyword(s):  
Blue Light ◽  
Amino Acid Content ◽  
Bactericidal Effect ◽  
In Vivo Studies ◽  
Dependent Inactivation ◽  
A Minor ◽  
The Impact ◽  
First Time

Beef is rich in various nutrients while easily spoils due to contamination by pathogens, thus it is of great significance to develop a bactericidal method to inactivate meat-borne pathogens and meanwhile maintain the freshness of beef. For the first time, the present study investigated the bactericidal effect of blue light (BL) at 415 nm against four meat-borne pathogens (methicillin-resistant Staphylococcus aureus , Escherichia coli , Salmonella Typhimurium and Listeria monocytogenes ) in vitro and inoculated on the surface of fresh beef, respectively. When the non-illuminated beef was used as control, the population of the four pathogens did not change significantly ( P > 0.05), while BL-illuminated beef showed dose-dependent inactivation effect in both in vitro and in vivo studies. The experiments on beef cuts showed that 109.44 J/cm 2 of BL inactivated 90% of inoculated cells for the tested strains ( P < 0.05), and the impact of BL inactivation could be sustained in 7 days of cold storage. Notably, changes of lipid oxidation rate, water holding capacity and cooking loss value between the control and beef illuminated by 109.44 J/cm 2 at the same time were scarcely detected during the storage. BL had a minor but insignificant influence on surface color and free amino acid content. Moreover, the pH of illuminated beef increased slower ( P < 0.05) than that of non-illuminated beef. The present work demonstrated that BL could be a novel bactericidal and freshness-maintaining method for fresh beef.

scholarly journals Follicular Lymphoma and Macrophages: Impact of Approved and Novel Therapies

2021 ◽  
Author(s):  
Sushanth Gouni ◽  
Mario L. Marques-Piubelli ◽  
Paolo Strati
Keyword(s):  
Follicular Lymphoma ◽  
Novel Therapies ◽  
Antibody Dependent Cellular Cytotoxicity ◽  
Macrophage Phagocytosis ◽  
Cd20 Antibody ◽  
Anti Cd20 ◽  
And Function ◽  
The Impact ◽  
First Time

The survival and proliferation of follicular lymphoma (FL) cells is strongly dependent on macrophages, their presence being necessary for the propagation of FL cells in vitro. To this regard, as shown also for the majority of solid tumors, a high tissue content of tumor-associated macrophages (TAMs), particularly if showing a pro-tumoral phenotype (also called M2) has strongly associated with a poor outcome among FL patients treated with chemotherapy. The introduction of rituximab, an anti-CD20 antibody which can be used by TAMs to performed antibody-dependent cellular cytotoxicity and antibody-dependent cellular phagocytosis, has challenged this paradigm. In the rituximab-era, in fact, clinical studies have yielded conflicting results in FL, showing variable outcomes based on the type of employed regimen. This has highlighted for the first time that the impact of TAM on the prognosis of FL patients may depend on the administered treatment, emphasizing the need to better understand how currently available therapies affect macrophage function in FL. We summarize here the impact of approved and novel therapies for FL on the biology of TAMs, including radiation therapy, chemotherapy, anti-CD20 monoclonal antibodies, lenalidomide, and targeted agents, and describe their effects on macrophage phagocytosis, polarization and function. While novel agents targeting the CD47/SIRPα axis are being developed and showing promising activity in FL, a deeper understanding of macrophage biology and their complex pathways will help to develop novel and safer therapeutic strategies for patients with this type of lymphoma.

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