Exploring the Therapeutic Potential: Bioactive Molecules and Dietary Interventions in Multiple Sclerosis Management.

Multiple sclerosis (MS) is a chronic autoimmune demyelinating disease of the central nervous system, the etiology of which is still unclear. Its hallmarks are inflammation and axonal damage. As a disease primarily impacting younger individuals, the social cost of MS is high. It has been proposed that environmental factors, smoking, and dietary habits acting on a genetic susceptibility play a role in MS. Recent studies indicate that diet can significantly influence the onset and progression of MS. This review delves into the impact of natural bioactive molecules on MS development and explores the dietary interventions that hold promise in managing the disease. Dietary patterns, including ketogenic and Mediterranean diets, are discussed. Theories about the potential mechanistic associations beneath the noted effects are also proposed. Several dietary components and patterns demonstrated the potential for a significant impact on MS. However, extensive prospective clinical trials are necessary to fully understand the role of natural bioactive molecules as disease modifiers in MS.

Development of uniform ribosome display technology enabling easy and efficient identification of full-length proteins that interact with bioactive small and large molecules.

Identifying target proteins that interact with bioactive molecules is indispensable for understanding their mechanisms of action. In this study, we developed a uniform ribosome display technology using equal-length DNAs and mRNAs to improve molecular display principle for target identification. The equal-length DNAs were designed to contain various coding sequences for full-length proteins with molecular weights of up to 130 kDa and were used to synthesize equal-length mRNAs, which allowed the formation of full-length protein-ribosome-equal-length mRNA complexes. Uniform ribosome display selections of dihydrofolate reductase and haloalkane dehalogenase mutant were performed against methotrexate and chlorohexane, respectively. Quantitative changes of proteins after each selection indicated that the target protein-displaying ribosomal complexes were specifically selected through non-covalent or covalent interactions with the corresponding bioactive molecules. Furthermore, selection of full-length proteins interacting with methotrexate or anti-DDX46 antibody from protein pools showed that only the target proteins could be precisely identified even though the molar amounts of equal-length mRNAs encoding them were adjusted to 1/20,000 of the total equal-length mRNAs. Thus, the uniform ribosome display technology enabled efficient identification of target proteins that interact with bioactive small and large molecules through simplified operations without deep sequencing.

Transition-Metal-Catalyzed Transformations for the Synthesis of Marine Drugs.

Transition metal catalysis has contributed to the discovery of novel methodologies and the preparation of natural products, as well as new chances to increase the chemical space in drug discovery programs. In the case of marine drugs, this strategy has been used to achieve selective, sustainable and efficient transformations, which cannot be obtained otherwise. In this perspective, we aim to showcase how a variety of transition metals have provided fruitful couplings in a wide variety of marine drug-like scaffolds over the past few years, by accelerating the production of these valuable molecules.

Statistical Tools to Optimize the Recovery of Bioactive Compounds from Marine Byproducts.

Techniques for extracting important bioactive molecules from seafood byproducts, viz., bones, heads, skin, frames, fins, shells, guts, and viscera, are receiving emphasis due to the need for better valorization. Employing green extraction technologies for efficient and quality production of these bioactive molecules is also strictly required. Hence, understanding the extraction process parameters to effectively design an applicable optimization strategy could enable these improvements. In this review, statistical optimization strategies applied for the extraction process parameters of obtaining bioactive molecules from seafood byproducts are focused upon. The type of experimental designs and techniques applied to criticize and validate the effects of independent variables on the extraction output are addressed. Dominant parameters studied were the enzyme/substrate ratio, pH, time, temperature, and power of extraction instruments. The yield of bioactive compounds, including long-chain polyunsaturated fatty acids, amino acids, peptides, enzymes, gelatine, collagen, chitin, vitamins, polyphenolic constituents, carotenoids, etc., were the most studied responses. Efficiency and/or economic and quality considerations and their selected optimization strategies that favor the production of potential bioactive molecules were also reviewed.

Biomimetic Mineralization for Smart Biostimulant Delivery and Crop Micronutrients Fortification.

Sustainable and precise fortification practices are necessary to ensure food security for the increasing human population. Precision agriculture aims to minimize the use of fertilizers and pesticides by developing smart materials for real-life agricultural practices. Here, we show that biomimetic mineralization can be efficiently employed to encapsulate and controllably release plant biostimulants (MiZax-3) to improve the quality and yield of capsicum (Capsicum annum) crops in field experiments. ZIF-8 encapsulation of MiZax-3 (MiZIFs) could significantly enhance its stability up to around 679 times (6p value = 0.0072) at field conditions. Our results demonstrate that the coordinating Zn ions and the MiZax-3 play a vital role in improving Zn content in the produced fruits by 2-fold, which is the first report of this nature on Zn content in fruits. We envision this platform as a starting point to investigate other biocompatible coordination-based platforms for micronutrient delivery in precision agriculture.

Platelet hyperactivity: a comparison of water-soluble, bioactive compound levels in commercial tomato products and water-soluble tomato concentrate, a supplement with an approved EFSA antiplatelet health effect.

The aim of this study was to evaluate and compare the concentration of water-soluble bioactive compounds in tomato products (polyphenols profile, water-soluble vitamins and nucleophilic substances) with the concentration of the same bioactive molecules existing in a water-soluble patented tomato extract, water-soluble tomato extract (WSTC), commercially available as FruitFlow®. This patented tomato extract has been recognised by EFSA (European Food Safety Authority) in a specific Health Claim declaration as having an "Antiplatelet health effect". More than 100 commercial tomato samples, coming from 18 different processing tomato companies worldwide, were analysed and compared with the FruitFlow® supplement. According to the multivariate statistical analyses applied to the data matrix, it is possible to conclude that the commercial tomato products measured (pastes, purees, others) show a significantly higher concentration of water-soluble bioactive molecules (nucleosides/nucleotides and polyphenols) responsible for an anti-platelet aggregation effect than the FruitFlow® dietary supplement.

Electrospun Nanofibers Encapsulated with Natural Products: A Novel Strategy to Counteract Skin Aging.

The skin is the primary tissue affected by wounds and aging, significantly impacting its protective function. Natural products are widely used in cosmetics, representing a new approach to preventing age-related damage. Nanomedicine combines nanotechnology and traditional treatments to create innovative drugs. The main targets of nanotechnological approaches are wound healing, regeneration, and rejuvenation of skin tissue. The skin barrier is not easily permeable, and the creation of modern nanodevices is a way to improve the passive penetration of substances. In this study, Helichrysum italicum oil (HO) was combined with different types of electrospun nanofibers to study their protective activity on the skin and to evaluate their future application for topical treatments. In the present research, we used biodegradable polymers, including polyvinyl alcohol (PVA) and polyvinylpyrrolidone (PVP), which were characterized by a scanning electron microscope (SEM). All results show a positive trend in cell proliferation and viability of human skin stem cells (SSCs) and BJ fibroblasts pre-treated with combined nanofibers and then exposed to UV stress. Gene expression analysis revealed the activation of a molecular rejuvenation program in SSCs treated with functionalized nanofibers before UV exposure. Understanding the mechanisms involved in skin changes during aging allows for the future application of nanomaterials combined with HO directly to the patients.

Chemical Composition Antioxidant and Anti-Inflammatory Activities of Myrtus communis L. Leaf Extract: Forecasting ADMET Profiling and Anti-Inflammatory Targets Using Molecular Docking Tools.

Compounds derived from natural sources continue to serve as chemical scaffolds for designing prophylactic/therapeutic options for human healthcare. In this study, we aimed to systematically unravel the chemical profile and antioxidant and anti-inflammatory activities of myrtle methanolic extract (MMEx) using in vitro, in vivo, and in silico approaches. High levels of TPC (415.85 ± 15.52 mg GAE/g) and TFC (285.80 ± 1.64 mg QE/g) were observed. Mass spectrophotometry (GC-MS) analysis revealed the presence of 1,8-cineole (33.80%), α-pinene (10.06%), linalool (4.83%), p-dimethylaminobenzophenone (4.21%), thunbergol (4%), terpineol (3.60%), cis-geranyl acetate (3.25%), and totarol (3.30%) as major compounds. MMEx induced pronounced dose-dependent inhibition in all assays, and the best antioxidant activity was found with H2O2, with an IC50 of 17.81 ± 3.67 µg.mL-1. MMEx showed a good anti-inflammatory effect in vivo by limiting the development of carrageenan-induced paw edema. The pharmacokinetic profiles of the active molecules were determined using the SwissADME website, followed by virtual screening against anti-inflammatory targets including phospholipase A2 (PLA-2), cyclooxygenase-2 (COX-2), tumor necrosis factor alpha (TNF-α), interleukin-1ß (IL-1ß), and NF-κB. A pharmacokinetic study revealed that the molecules have good absorption, distribution, and metabolism profiles, with negative organ toxicity. Among the compounds identified by GC-MS analysis, pinostrobin chalcone, cinnamyl cinnamate, hedycaryol, totarol, and p-dimethylaminobenzophenone were observed to have good binding scores, thus appreciable anti-inflammatory potential. Our study reveals that MMEx from Algerian Myrtus communis L. can be considered to be a promising candidate for alleviating many health complaints associated with oxidative stress and inflammation.

Microbial cancer therapeutics: A promising approach.

The success of conventional cancer therapeutics is hindered by associated dreadful side-effects of antibiotic resistance and the dearth of antitumor drugs' selectivity and specificity. Hence, the conceptual evolution of anti-cancerous therapeutic agents that selectively target cancer cells without impacting the healthy cells or tissues, has led to a new wave of scientific interest in microbial-derived bioactive molecules. Such strategic solutions may pave the way to surmount the shortcomings of conventional therapies and raise the potential and hope for the cure of wide range of cancer in a selective manner. This review aims to provide a comprehensive summary of anti-carcinogenic properties and underlying mechanisms of bioactive molecules of microbial origin, and discuss the current challenges and effective therapeutic application of combinatorial strategies to attain minimal systemic side-effects.

Concentration-Dependent Enrichment Identifies Primary Protein Targets of Multitarget Bioactive Molecules.

Multitarget bioactive molecules (MBMs) are of increasing importance in drug discovery as they could produce high efficacy and a low chance of resistance. Several advanced approaches of quantitative proteomics were developed to accurately identify the protein targets of MBMs, but little study has been carried out in a sequential manner to identify primary protein targets (PPTs) of MBMs. This set of proteins will first interact with MBMs in the temporal order and play an important role in the mode of action of MBMs, especially when MBMs are at low concentrations. Herein, we describe a valuable observation that the result of the enrichment process is highly dependent on concentrations of the probe and the proteome. Interestingly, high concentrations of probe and low concentrations of incubated proteome will readily miss the hyper-reactive protein targets and thereby increase the probability of rendering PPTs with false-negative results, while low concentrations of probe and high concentrations of incubated proteome more than likely will capture the PPTs. Based on this enlightening observation, we developed a proof-of-concept approach to identify the PPTs of iodoacetamide, a thiol-reactive MBM. This study will deepen our understanding of the enrichment process and improve the accuracy of pull-down-guided target identification.

A systematic review on endophytic fungi and its role in the commercial applications.

MAIN CONCLUSION: EF have been explored for its beneficial impact on environment and for its commercial applications. It has proved its worth in these sectors and showed an impact on biological properties of plants by producing various bioactive molecules and enzymes. Endophytes are plant mutualists that live asymptomatically within plant tissues and exist in almost every plant species. Endophytic fungi benefit from the host plant nutrition, and the host plant gains improved competitive abilities and tolerance against pathogens, herbivores, and various abiotic stresses. Endophytic fungi are one of the most inventive classes which produce secondary metabolites and play a crucial role in human health and other biotic aspects. This review is focused on systematic study on the biodiversity of endophytic fungi in plants, and their role in enhancing various properties of plants such as antimicrobial, antimycobacterial, antioxidant, cytotoxic, anticancer, and biological activity of secondary metabolites produced by various fungal endophytes in host plants reported from 1994 to 2021. This review emphasizes the endophytic fungal population shaped by host genotype, environment, and endophytic fungi genotype affecting host plant. The impact of endophytic fungi has been discussed in detail which influences the commercial properties of plants. Endophytes also have an influence on plant productivity by increasing parameters such as nutrient recycling and phytostimulation. Studies focusing on mechanisms that regulate attenuation of secondary metabolite production in EF would provide much needed impetus on ensuring continued production of bioactive molecules from a indubitable source. If this knowledge is further extensively explored regarding fungal endophytes in plants for production of potential phytochemicals, then it will help in exploring a keen area of interest for pharmacognosy.

A computational overview of integrase strand transfer inhibitors (INSTIs) against emerging and evolving drug-resistant HIV-1 integrase mutants.

AIDS (Acquired immunodeficiency syndrome) is one of the chronic and potentially life-threatening epidemics across the world. Hitherto, the non-existence of definitive drugs that could completely cure the Human immunodeficiency virus (HIV) implies an urgent necessity for the discovery of novel anti-HIV agents. Since integration is the most crucial stage in retroviral replication, hindering it can inhibit overall viral transmission. The 5 FDA-approved integrase inhibitors were computationally investigated, especially owing to the rising multiple mutations against their susceptibility. This comparative study will open new possibilities to guide the rational design of novel lead compounds for antiretroviral therapies (ARTs), more specifically the structure-based design of novel Integrase strand transfer inhibitors (INSTIs) that may possess a better resistance profile than present drugs. Further, we have discussed potent anti-HIV natural compounds and their interactions as an alternative approach, recommending the urgent need to tap into the rich vein of indigenous knowledge for reverse pharmacology. Moreover, herein, we discuss existing evidence that might change in the near future.

Seed gum-based delivery systems and their application in encapsulation of bioactive molecules.

Now-a-days, the food/pharma realm faces with great challenges for the application of bioactive molecules when applying them in free form due to their instability in vitro/in vivo. For promoting the biological and functional properties of bioactive molecules, efficient delivery systems have played a pivotal role offering a controlled delivery and improved bioavailability/solubility of bioactives. Among different carbohydrate-based delivery systems, seed gum-based vehicles (SGVs) have shown great promise, facilitating the delivery of a high concentration of bioactive at the site of action, a controlled payload release, and less bioactive loss. SGVs are potent structures to promote the bioavailability, beneficial properties, and in vitro/in vivo stability of bioactive components. Here, we offer a comprehensive overview of seed gum-based nano- and microdevices as delivery systems for bioactive molecules. We have a focus on structural/functional attributes and health-promoting benefits of seed gums, but also strategies involving modification of these biopolymers are included. Diverse SGVs (nano/microparticles, functional films, hydrogels/nanogels, particles for Pickering nanoemulsions, multilayer carriers, emulsions, and complexes/conjugates) are reviewed and important parameters for bioactive delivery are highlighted (e.g. bioactive-loading capacity, control of bioactive release, (bio)stability, and so on). Future challenges for these biopolymer-based carriers have also been discussed. HighlightsSeed gum-based polymers are promising materials to design different bioactive delivery systems.Seed gum-based delivery systems are particles, fibers, complexes, conjugates, hydrogels, etc.Seed gum-based vehicles are potent structures to promote the bioavailability, beneficial properties, and in vitro/in vivo stability of bioactive components.

Cocoa bean shells: a review into the chemical profile, the bioactivity and the biotransformation to enhance their potential applications in foods.

During processing, cocoa bean shells (CBS) are de-hulled from the bean and discarded as waste. Undermined by its chemical and bioactive composition, CBS is abundant in dietary fiber and phenolic compounds that may serve the valorization purpose of this by-product material into prebiotic and functional ingredients. In addition, the cell-wall components of CBS can be combined through enzymatic feruloylation to obtain feruloylated oligo- and polysaccharides (FOs), further enhancing the techno-functional properties. FOs have attracted scientific attention due to their prebiotic, antimicrobial, anti-inflammatory and antioxidant functions inherent to their structural features. This review covers the chemical and bioactive compositions of CBS as well as their modifications upon cocoa processing. Physical, chemical, and enzymatic approaches to extract and bio-transform bioactive components from the cell wall matrix of CBS were also discussed. Although nonspecific to CBS, studies were compiled to investigate efforts done to extract and produce feruloylated oligo- and polysaccharides from the cell wall materials.

Environmental effects and interaction of nanoparticles on beneficial soil and aquatic microorganisms.

A steadily increasing production volume of nanoparticles reflects their numerous industrial and domestic applications. These economic successes come with the potential adverse effects on natural systems that are associated with their presence in the environment. Biological activities and effects of nanoparticles are affected by their entry method together with their specificities like their size, shape, charge, area, and chemical composition. Particles can be classified as safe or dangerous depending on their specific properties. As both aquatic and terrestrial systems suffer from organic and inorganic contamination, nanoparticles remain a sink for these contaminants. Researching the sources, synthesis, fate, and toxicity of nanoparticles has advanced significantly during the last ten years. We summarise nanoparticle pathways throughout the ecosystem and their interactions with beneficial microorganisms in this research. The prevalence of nanoparticles in the ecosystem causes beneficial microorganisms to become hazardous to their cells, which prevents the synthesis of bioactive molecules from undergoing molecular modifications and diminishes the microbe population. Recently, observed concentrations in the field could support predictions of ambient concentrations based on modeling methodologies. The aim is to illustrate the beneficial and negative effects that nanoparticles have on aqueous and terrestrial ecosystems, as well as the methods utilized to reduce their toxicity.

Pesticide-tolerant microbial consortia: Potential candidates for remediation/clean-up of pesticide-contaminated agricultural soil.

Reclamation of pesticide-polluted lands has long been a difficult endeavour. The use of synthetic pesticides could not be restricted due to rising agricultural demand. Pesticide toxicity has become a pressing agronomic problem due to its adverse impact on agroecosystems, agricultural output, and consequently food security and safety. Among different techniques used for the reclamation of pesticide-polluted sites, microbial bioremediation is an eco-friendly approach, which focuses on the application of resilient plant growth promoting rhizobacteria (PGPR) that may transform or degrade chemical pesticides to innocuous forms. Such pesticide-resilient PGPR has demonstrated favourable effects on soil-plant systems, even in pesticide-contaminated environments, by degrading pesticides, providing macro-and micronutrients, and secreting active but variable secondary metabolites like-phytohormones, siderophores, ACC deaminase, etc. This review critically aims to advance mechanistic understanding related to the reduction of phytotoxicity of pesticides via the use of microbe-mediated remediation techniques leading to crop optimization in pesticide-stressed soils. The literature surveyed and data presented herein are extremely useful, offering agronomists-and crop protectionists microbes-assisted remedial strategies for affordably enhancing crop productivity in pesticide-stressed soils.

Insights into Metabolic Engineering of Bioactive Molecules in Tetrastigma hemsleyanum Diels & Gilg: A Traditional Medicinal Herb.

Plants are a vital source of bioactive molecules for various drug development processes. Tetrastigma hemsleyanum is one of the endangered medicinal plant species well known to the world due to its wide range of therapeutic effects. Many bioactive molecules have been identified from this plant, including many classes of secondary metabolites such as flavonoids, phenols, terpenoids, steroids, alkaloids, etc. Due to its slow growth, it usually takes 3-5 years to meet commercial medicinal materials for this plant. Also, T. hemsleyanum contains low amounts of specific bioactive compounds, which are challenging to isolate easily. Currently, scientists are attempting to increase bioactive molecules' production from medicinal plants in different ways or to synthesize them chemically. The genomic tools helped to understand medicinal plants' genome organization and led to manipulating genes responsible for various biosynthesis pathways. Metabolic engineering has made it possible to enhance the production of secondary metabolites by introducing manipulated biosynthetic pathways to attain high levels of desirable bioactive molecules. Metabolic engineering is a promising approach for improving the production of secondary metabolites over a short time period. In this review, we have highlighted the scope of various biotechnological approaches for metabolic engineering to enhance the production of secondary metabolites for pharmaceutical applications in T. hemsleyanum. Also, we summarized the progress made in metabolic engineering for bioactive molecule enhancement in T. hemsleyanum. It may lead to reducing the destruction of the natural habitat of T. hemsleyanum and conserving them through the cost-effective production of bioactive molecules in the future.

Marine Natural Products as Innovative Cosmetic Ingredients.

Over the course of the last 20 years, numerous studies have identified the benefits of an array of marine natural ingredients for cosmetic purposes, as they present unique characteristics not found in terrestrial organisms. Consequently, several marine-based ingredients and bioactive compounds are under development, used or considered for skin care and cosmetics. Despite the multitude of cosmetics based on marine sources, only a small proportion of their full potential has been exploited. Many cosmetic industries have turned their attention to the sea to obtain innovative marine-derived compounds for cosmetics, but further research is needed to determine and elucidate the benefits. This review gathers information on the main biological targets for cosmetic ingredients, different classes of marine natural products of interest for cosmetic applications, and the organisms from which such products can be sourced. Although organisms from different phyla present different and varied bioactivities, the algae phylum seems to be the most promising for cosmetic applications, presenting compounds of many classes. In fact, some of these compounds present higher bioactivities than their commercialized counterparts, demonstrating the potential presented by marine-derived compounds for cosmetic applications (i.e., Mycosporine-like amino acids and terpenoids' antioxidant activity). This review also summarizes the major challenges and opportunities faced by marine-derived cosmetic ingredients to successfully reach the market. As a future perspective, we consider that fruitful cooperation among academics and cosmetic industries could lead to a more sustainable market through responsible sourcing of ingredients, implementing ecological manufacturing processes, and experimenting with inventive recycling and reuse programs.

Bioactive Molecules from the Innate Immunity of Ascidians and Innovative Methods of Drug Discovery: A Computational Approach Based on Artificial Intelligence.

The study of bioactive molecules of marine origin has created an important bridge between biological knowledge and its applications in biotechnology and biomedicine. Current studies in different research fields, such as biomedicine, aim to discover marine molecules characterized by biological activities that can be used to produce potential drugs for human use. In recent decades, increasing attention has been paid to a particular group of marine invertebrates, the Ascidians, as they are a source of bioactive products. We describe omics data and computational methods relevant to identifying the mechanisms and processes of innate immunity underlying the biosynthesis of bioactive molecules, focusing on innovative computational approaches based on Artificial Intelligence. Since there is increasing attention on finding new solutions for a sustainable supply of bioactive compounds, we propose that a possible improvement in the biodiscovery pipeline might also come from the study and utilization of marine invertebrates' innate immunity.

Bioactive molecules from fungal endophytes and their applications in pharmaceutical industries: challenges and future scope.

Medicinal plants are an important source of bioactive compounds and have been used to isolate various bioactive compounds having industrial applications. The demand for plants derived bioactive molecules is increasing gradually. However, the extensive use of these plants to extract bioactive molecules has threatened many plant species. Moreover, extracting bioactive molecules from these plants is laborious, costly, and time-consuming. So, some alternative sources and strategies are urgently needed to produce these bioactive molecules similar to that of plant origin. However, the interest in new bioactive molecules has recently shifted from plants to endophytic fungi because many fungi produce bioactive molecules similar to their host plant. Endophytic fungi live in mutualistic association within the healthy plant tissue without causing disease symptoms to the host plant. These fungi are a treasure house of novel bioactive molecules having broad pharmaceutical, industrial, and agricultural applications. The rapid increase in publications in this domain over the last three decades proves that natural product biologists and chemists are paying great attention to the natural bioactive products from endophytic fungi. Though endophytes are source of novel bioactive molecules but there is need of advanced technologies like clustered regularly interspaced short palindromic repeats and CRISPR-associated protein 9 (CRISPR-Cas9) and epigenetic modifiers to enhance the production of compounds having industrial applications. This review provides an overview of the various industrial applications of bioactive molecules produced by endophytic fungi and the rationale behind selecting specific plants for fungal endophyte isolation. Overall, this study presents the current state of knowledge and highlights the potential of endophytic fungi for developing alternative therapies for drug-resistant infections.