Simulated gastro-intestinal digestion is widely employed in many fields of food and nutritional sciences, as conducting human trials are often costly, resource intensive, and ethically disputable. As a consequence, in vitro alternatives that determine endpoints such as the bioaccessibility of nutrients and non-nutrients or the digestibility of macronutrients (e.g. lipids, proteins and carbohydrates) are used for screening and building new hypotheses. Various digestion models have been proposed, often impeding the possibility to compare results across research teams. For example, a large variety of enzymes from different sources such as of porcine, rabbit or human origin have been used, differing in their activity and characterization. Differences in pH, mineral type, ionic strength and digestion time, which alter enzyme activity and other phenomena, may also considerably alter results. Other parameters such as the presence of phospholipids, individual enzymes such as gastric lipase and digestive emulsifiers vs. their mixtures (e.g. pancreatin and bile salts), and the ratio of food bolus to digestive fluids, have also been discussed at length. In the present consensus paper, within the COST Infogest network, we propose a general standardised and practical static digestion method based on physiologically relevant conditions that can be applied for various endpoints, which may be amended to accommodate further specific requirements. A frameset of parameters including the oral, gastric and small intestinal digestion are outlined and their relevance discussed in relation to available in vivo data and enzymes. This consensus paper will give a detailed protocol and a line-by-line, guidance, recommendations and justifications but also limitation of the proposed model. This harmonised static, in vitro digestion method for food should aid the production of more comparable data in the future.

https://hal.archives-ouvertes.fr/hal-01209876/document

A standardised static in vitro digestion method suitable for food – an international consensus

The analogs of nitrogen-based heterocycles occupy an exclusive position as a valuable source of therapeutic agents in medicinal chemistry. More than 75% of drugs approved by the FDA and currently available in the market are nitrogen-containing heterocyclic moieties. In the forthcoming decade, a much greater share of new nitrogen-based pharmaceuticals is anticipated. Many new nitrogen-based heterocycles have been designed. The number of novel N-heterocyclic moieties with significant physiological properties and promising applications in medicinal chemistry is ever-growing. In this review, we consolidate the recent advances on novel nitrogen-containing heterocycles and their distinct biological activities, reported over the past one year (2019 to early 2020). This review highlights the trends in the use of nitrogen-based moieties in drug design and the development of different potent and competent candidates against various diseases.

A Review on Recent Advances in Nitrogen-Containing Molecules and Their Biological Applications.

The properties of benzimidazole and its derivatives have been studied over more than one hundred years. Benzimidazole derivatives are useful intermediates/subunits for the development of molecules of pharmaceutical or biological interest. Substituted benzimidazole derivatives have found applications in diverse therapeutic areas such as antiulcer, anticancer agents, and anthelmintic species to name just a few. This work systematically gives a comprehensive review in current developments of benzimidazole-based compounds in the whole range of medicinal chemistry as anticancer, antibacterial, antifungal, anti-inflammatory, analgesic agents, anti-HIV, antioxidant, anticonvulsant, antitubercular, antidiabetic, antileishmanial, antihistaminic, antimalarial agents, and other medicinal agents. This review will further be helpful for the researcher on the basis of substitution pattern around the nucleus with an aim to help medicinal chemists for developing an SAR on benzimidazole drugs/compounds.

Comprehensive Review in Current Developments of Benzimidazole-Based Medicinal Chemistry.

Current research has demonstrated that small cationic amphipathic peptides have strong potential not only as antimicrobials, but also as antibiofilm agents, immune modulators, and anti-inflammatories. Although traditionally termed antimicrobial peptides (AMPs) these additional roles have prompted a shift in terminology to use the broader term host defense peptides (HDPs) to capture the multi-functional nature of these molecules. In this review, we critically examined the role of AMPs and HDPs in infectious diseases and inflammation. It is generally accepted that HDPs are multi-faceted mediators of a wide range of biological processes, with individual activities dependent on their polypeptide sequence. In this context, we explore the concept of chemical space as it applies to HDPs and hypothesize that the various functions and activities of this class of molecule exist on independent but overlapping activity landscapes. Finally, we outline several emerging functions and roles of HDPs and highlight how an improved understanding of these processes can potentially be leveraged to more fully realize the therapeutic promise of HDPs.

/pdf/reassessing-the-host-defense-peptide-landscape-911cd7opw4.pdf

Reassessing the Host Defense Peptide Landscape

Abiotic stressors such as extreme temperatures, drought, flood, light, salt, and heavy metals alter biological diversity and crop production worldwide. Therefore, it is important to know the mechanisms by which plants cope with stress conditions. Polyphenols, which are the largest group of plant-specialized metabolites, are generally recognized as molecules involved in stress protection in plants. This diverse group of metabolites contains various structures, from simple forms consisting of one aromatic ring to more complex ones consisting of large number of polymerized molecules. Consequently, all these molecules, depending on their structure, may show different roles in plant growth, development, and stress protection. In the present review, we aimed to summarize data on how different polyphenol structures influence their biological activity and their roles in abiotic stress responses. We focused our review on phenolic acids, flavonoids, stilbenoids, and lignans.

https://www.mdpi.com/2223-7747/10/1/118/pdf

The Role of Polyphenols in Abiotic Stress Response: The Influence of Molecular Structure

Nanotechnology application in food packaging: A plethora of opportunities versus pending risks assessment and public concerns.

Ellagic acid a multi-target bioactive compound for drug discovery in CNS? A narrative review.

Oxidative stress (OS), triggered by overproduction of reactive oxygen and nitrogen species, is the main mechanism responsible for several human diseases. The available one-target drugs often face such illnesses, by softening symptoms without eradicating the cause. Differently, natural polyphenols from fruits and vegetables possess multi-target abilities for counteracting OS, thus representing promising therapeutic alternatives and adjuvants. Although in several in vitro experiments, ellagitannins (ETs), ellagic acid (EA), and its metabolites urolithins (UROs) have shown similar great potential for the treatment of OS-mediated human diseases, only UROs have demonstrated in vivo the ability to reach tissues to a greater extent, thus appearing as the main molecules responsible for beneficial activities. Unfortunately, UROs production depends on individual metabotypes, and the consequent extreme variability limits their potentiality as novel therapeutics, as well as dietary assumption of EA, EA-enriched functional foods, and food supplements. This review focuses on the pathophysiology of OS; on EA and UROs chemical features and on the mechanisms of their antioxidant activity. A discussion on the clinical applicability of the debated UROs in place of EA and on the effectiveness of EA-enriched products is also included.

https://www.mdpi.com/2076-3921/9/8/707/pdf

Oxidative Stress, Antioxidant Capabilities, and Bioavailability: Ellagic Acid or Urolithins?

Antibiotic resistance has increased markedly in Gram-negative bacteria, causing severe infections intractable with traditional drugs and amplifying mortality and healthcare costs. Consequently, to find novel antimicrobial compounds, active on multidrug resistant bacteria, is mandatory. In this regard, cationic antimicrobial peptides (CAMPs)—able to kill pathogens on contact—could represent an appealing solution. However, low selectivity, hemolytic toxicity and cost of manufacturing, hamper their massive clinical application. In the recent years—starting from CAMPs as template molecules—less toxic and lower-cost synthetic mimics of CAMPs, including cationic peptides, polymers and dendrimers, have been developed. Although the pending issue of hemolytic toxicity and biodegradability is still left not completely solved, cationic antimicrobial polymers (CAPs), compared to small drug molecules, thanks to their high molecular weight, own appreciable selectivity, reduced toxicity toward eukaryotic cells, more long-term activity, stability and non-volatility. With this background, an updated overview concerning the main manufactured types of CAPs, active on Gram-negative bacteria, is herein reported, including synthetic procedure and action’s mechanism. Information about their structures, antibacterial activity, advantages and drawbacks, was reported in the form of tables, which allow faster consultation and quicker learning concerning current CAPs state of the art, in order not to retrace reviews already available.

https://www.mdpi.com/2073-4360/12/5/1195/pdf

Positively Charged Polymers as Promising Devices against Multidrug Resistant Gram-Negative Bacteria: A Review.

The alarming increase in antimicrobial resistance, based on the built-in abilities of bacteria to nullify the activity of current antibiotics, leaves a growing number of bacterial infections untreatable. An appealing approach, advanced in recent decades, concerns the development of novel agents able to interact with the external layers of bacteria, causing irreparable damage. Regarding this, some natural cationic antimicrobial peptides (CAMPs) have been reconsidered, and synthetic cationic polymers, mimicking CAMPs and able to kill bacteria by non-specific detrimental interaction with the negative bacterial membranes, have been proposed as promising solutions. Lately, also dendrimers were considered suitable macromolecules for the preparation of more advanced cationic biomimetic nanoparticles, able to harmonize the typical properties of dendrimers, including nanosize, mono-dispersion, long-term stability, high functionality, and the non-specific mechanism of action of CAMPs. Although cationic dendrimers are extensively applied in nanomedicine for drug or gene delivery, their application as antimicrobial agents is still in its infancy. The state of the art of their potential applications in this important field has therefore been reviewed here, with particular attention to the innovative case studies in the literature including also amino acid-modified polyester-based dendrimers, practically unexplored as membrane-active antimicrobials and able to kill bacteria on contact.

Silvana Alfei

Papers

Nanotechnology application in food packaging: A plethora of opportunities versus pending risks assessment and public concerns.

Ellagic acid a multi-target bioactive compound for drug discovery in CNS? A narrative review.

Oxidative Stress, Antioxidant Capabilities, and Bioavailability: Ellagic Acid or Urolithins?

Positively Charged Polymers as Promising Devices against Multidrug Resistant Gram-Negative Bacteria: A Review.

From Nanobiotechnology, Positively Charged Biomimetic Dendrimers as Novel Antibacterial Agents: A Review.