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Molecules (Basel, Switzerland) Aug 2014Allicin (diallylthiosulfinate) is a defence molecule from garlic (Allium sativum L.) with a broad range of biological activities. Allicin is produced upon tissue damage... (Review)
Review
Allicin (diallylthiosulfinate) is a defence molecule from garlic (Allium sativum L.) with a broad range of biological activities. Allicin is produced upon tissue damage from the non-proteinogenic amino acid alliin (S-allylcysteine sulfoxide) in a reaction that is catalyzed by the enzyme alliinase. Current understanding of the allicin biosynthetic pathway will be presented in this review. Being a thiosulfinate, allicin is a reactive sulfur species (RSS) and undergoes a redox-reaction with thiol groups in glutathione and proteins that is thought to be essential for its biological activity. Allicin is physiologically active in microbial, plant and mammalian cells. In a dose-dependent manner allicin can inhibit the proliferation of both bacteria and fungi or kill cells outright, including antibiotic-resistant strains like methicillin-resistant Staphylococcus aureus (MRSA). Furthermore, in mammalian cell lines, including cancer cells, allicin induces cell-death and inhibits cell proliferation. In plants allicin inhibits seed germination and attenuates root-development. The majority of allicin's effects are believed to be mediated via redox-dependent mechanisms. In sub-lethal concentrations, allicin has a variety of health-promoting properties, for example cholesterol- and blood pressure-lowering effects that are advantageous for the cardio-vascular system. Clearly, allicin has wide-ranging and interesting applications in medicine and (green) agriculture, hence the detailed discussion of its enormous potential in this review. Taken together, allicin is a fascinating biologically active compound whose properties are a direct consequence of the molecule's chemistry.
Topics: Animals; Anti-Infective Agents; Antineoplastic Agents, Phytogenic; Apoptosis; Arabidopsis; Disulfides; Germination; Humans; Oxidation-Reduction; Plant Roots; Sulfinic Acids
PubMed: 25153873
DOI: 10.3390/molecules190812591 -
Annual Review of Microbiology Sep 2016The ability of bacteria to recognize kin provides a means to form social groups. In turn these groups can lead to cooperative behaviors that surpass the ability of the... (Review)
Review
The ability of bacteria to recognize kin provides a means to form social groups. In turn these groups can lead to cooperative behaviors that surpass the ability of the individual. Kin recognition involves specific biochemical interactions between a receptor(s) and an identification molecule(s). Recognition specificity, ensuring that nonkin are excluded and kin are included, is critical and depends on the number of loci and polymorphisms involved. After recognition and biochemical perception, the common ensuing cooperative behaviors include biofilm formation, quorum responses, development, and swarming motility. Although kin recognition is a fundamental mechanism through which cells might interact, microbiologists are only beginning to explore the topic. This review considers both molecular and theoretical aspects of bacterial kin recognition. Consideration is also given to bacterial diversity, genetic relatedness, kin selection theory, and mechanisms of recognition.
Topics: Bacteria; Bacterial Physiological Phenomena; Bacterial Proteins; Gene Expression Regulation, Bacterial
PubMed: 27359217
DOI: 10.1146/annurev-micro-102215-095325 -
Trends in Immunology Jul 2020How innate immunity gave rise to adaptive immunity in vertebrates remains unknown. We propose an evolutionary scenario beginning with pathogen-associated molecular... (Review)
Review
How innate immunity gave rise to adaptive immunity in vertebrates remains unknown. We propose an evolutionary scenario beginning with pathogen-associated molecular pattern(s) (PAMPs) being presented by molecule(s) on one cell to specific receptor(s) on other cells, much like MHC molecules and T cell receptors (TCRs). In this model, mutations in MHC-like molecule(s) that bound new PAMP(s) would not be recognized by original TCR-like molecule(s), and new MHC-like gene(s) would be lost by neutral drift. Integrating recombination activating gene (RAG) transposon(s) in a TCR-like gene would result in greater recognition diversity, with new MHC-like variants recognized and selected, along with a new RAG/TCR-like system. MHC genes would be selected to present many peptides, through multigene families, allelic polymorphism, and peptide-binding promiscuity.
Topics: Adaptive Immunity; Animals; DNA Transposable Elements; Evolution, Molecular; Genes, RAG-1; Immunity, Innate; Major Histocompatibility Complex; Receptors, Antigen, T-Cell
PubMed: 32467030
DOI: 10.1016/j.it.2020.05.002 -
International Journal of Nanomedicine 2022Bioavailability is an eternal topic that cannot be circumvented by peroral drug delivery. Adequate blood drug exposure after oral administration is a prerequisite for... (Review)
Review
Bioavailability is an eternal topic that cannot be circumvented by peroral drug delivery. Adequate blood drug exposure after oral administration is a prerequisite for effective treatment. Nanovesicles as pleiotropic oral vehicles can solubilize, encapsulate, stabilize an active ingredient and promote the payload absorption via various mechanisms. Vesicular systems with nanoscale size, such as liposomes, niosomes and polymersomes, provide a versatile platform for oral delivery of drugs with distinct nature. The amphiphilicity of vesicles in structure allows hydrophilic and lipophilic molecule(s) either or both to be loaded, being encapsulated in the aqueous cavity or the inner core, respectively. Depending on high oral transport efficiency based on their structural flexibility, gastrointestinal stability, biocompatibility, and/or intestinal epithelial affinity, nanovesicles can markedly augment the oral bioavailability of various poorly absorbed drugs. Vesicular drug delivery systems (VDDSs) demonstrate a lot of preferences and are becoming more prominent of late years in biomedical applications. Equally, these systems can potentiate a drug's therapeutic index by ameliorating the oral absorption. This review devotes to comment on various VDDSs with special emphasis on the peroral drug delivery. The classification of nanovesicles, preparative processes, intestinal transport mechanisms, in vivo fate, and design rationale were expounded. Knowledge on vesicles-mediated oral drug delivery for bioavailability enhancement has been properly provided. It can be concluded that VDDSs with many merits will step into an energetic arena in oral drug delivery.
Topics: Biological Availability; Liposomes; Administration, Oral; Hydrophobic and Hydrophilic Interactions; Excipients
PubMed: 36262189
DOI: 10.2147/IJN.S382192 -
Frontiers in Chemistry 2023Supramolecular containers have long been applied to regulate organic reactions with distinct selectivity, owing to their diverse functions such as the ability to pose a... (Review)
Review
Supramolecular containers have long been applied to regulate organic reactions with distinct selectivity, owing to their diverse functions such as the ability to pose a guest molecule(s) with a certain orientation and conformation. In this review, we try to illustrate how self-assembled coordination cages could achieve this goal. Two representative cage hosts, namely, self-assembled Pd(II)-ligand octahedral coordination cages ([PdL]) and self-assembled Ga(III)-ligand tetrahedral coordination cages ([GaL]) are selected as the pilot hosts that this mini review covers. Representative works in this area are presented here in brief.
PubMed: 37731456
DOI: 10.3389/fchem.2023.1269471 -
Molecules (Basel, Switzerland) Aug 2015Non-covalent derivatives (NCDs) are formed by incorporating one (or more) coformer molecule(s) into the matrix of a parent molecule via non-covalent forces. These forces... (Review)
Review
Non-covalent derivatives (NCDs) are formed by incorporating one (or more) coformer molecule(s) into the matrix of a parent molecule via non-covalent forces. These forces can include ionic forces, Van der Waals forces, hydrogen bonding, lipophilic-lipophilic interactions and pi-pi interactions. NCDs, in both cocrystal and eutectic forms, possess properties that are unique to their supramolecular matrix. These properties include critical product performance factors such as solubility, stability and bioavailability. NCDs have been used to tailor materials for a variety of applications and have the potential to be used in an even broader range of materials and processes. NCDs can be prepared using little or no solvent and none of the reagents typical to synthetic modifications. Thus, NCDs represent a powerfully versatile, environmentally-friendly and cost-effective opportunity.
Topics: Agrochemicals; Cosmetics; Crystallization; Food Additives; Temperature
PubMed: 26287141
DOI: 10.3390/molecules200814833 -
Frontiers in Plant Science 2022The liaison between Nitric oxide (NO) and phytohormones regulates a myriad of physiological processes at the cellular level. The interaction between NO and phytohormones... (Review)
Review
The liaison between Nitric oxide (NO) and phytohormones regulates a myriad of physiological processes at the cellular level. The interaction between NO and phytohormones is mainly influenced by NO-mediated post-translational modifications (PTMs) under basal as well as induced conditions. Protein S-nitrosylation is the most prominent and widely studied PTM among others. It is the selective but reversible redox-based covalent addition of a NO moiety to the sulfhydryl group of cysteine (Cys) molecule(s) on a target protein to form S-nitrosothiols. This process may involve either direct S-nitrosylation or indirect S-nitrosylation followed by transfer of NO group from one thiol to another (transnitrosylation). During S-nitrosylation, NO can directly target Cys residue (s) of key genes involved in hormone signaling thereby regulating their function. The phytohormones regulated by NO in this manner includes abscisic acid, auxin, gibberellic acid, cytokinin, ethylene, salicylic acid, jasmonic acid, brassinosteroid, and strigolactone during various metabolic and physiological conditions and environmental stress responses. S-nitrosylation of key proteins involved in the phytohormonal network occurs during their synthesis, degradation, or signaling roles depending upon the response required to maintain cellular homeostasis. This review presents the interaction between NO and phytohormones and the role of the canonical NO-mediated post-translational modification particularly, S-nitrosylation of key proteins involved in the phytohormonal networks under biotic and abiotic stresses.
PubMed: 35401598
DOI: 10.3389/fpls.2022.865542 -
Pharmacology Research & Perspectives Dec 2019Paul Ehrlich's concept of the magic bullet, by which a induces pharmacological effects by interacting with a has been a strong driving force in pharmacology for a... (Review)
Review
Paul Ehrlich's concept of the magic bullet, by which a induces pharmacological effects by interacting with a has been a strong driving force in pharmacology for a century. It is continually thwarted, though, by the fact that the treated organism is highly dynamic and the target molecule(s) is (are) never static. In this article, we address some of the factors that modify and cause the mobility and plasticity of drug targets and their interactions with ligands and discuss how these can lead to unexpected (lack of) effects of drugs. These factors include genetic, epigenetic, and phenotypic variability, cellular plasticity, chronobiological rhythms, time, age and disease resolution, sex, drug metabolism, and distribution. We emphasize four existing approaches that can be taken, either singly or in combination, to try to minimize effects of pharmacological plasticity. These are firstly, to enhance specificity using target conditions close to those in diseases, secondly, by simultaneously or thirdly, sequentially aiming at multiple targets, and fourthly, in synchronization with concurrent dietary, psychological, training, and biorhythm-synchronizing procedures to optimize drug therapy.
Topics: Epigenesis, Genetic; Gene Expression Regulation; Humans; Ligands; Molecular Targeted Therapy; Pharmacology, Clinical
PubMed: 31768257
DOI: 10.1002/prp2.532 -
Proceedings of the National Academy of... Jul 2013It has recently been recognized that solid-state nanopores in single-atomic-layer graphene membranes can be used to electronically detect and characterize single long...
It has recently been recognized that solid-state nanopores in single-atomic-layer graphene membranes can be used to electronically detect and characterize single long charged polymer molecules. We have now fabricated nanopores in single-layer graphene that are closely matched to the diameter of a double-stranded DNA molecule. Ionic current signals during electrophoretically driven translocation of DNA through these nanopores were experimentally explored and theoretically modeled. Our experiments show that these nanopores have unusually high sensitivity (0.65 nA/Å) to extremely small changes in the translocating molecule's outer diameter. Such atomically short graphene nanopores can also resolve nanoscale-spaced molecular structures along the length of a polymer, but do so with greatest sensitivity only when the pore and molecule diameters are closely matched. Modeling confirms that our most closely matched pores have an inherent resolution of ≤ 0.6 nm along the length of the molecule.
Topics: DNA; Graphite; Microscopy, Electron; Nanopores
PubMed: 23836648
DOI: 10.1073/pnas.1220012110 -
Frontiers in Pharmacology 2022The human microbiota produces molecules that are evolved to interact with the diverse cellular machinery of both the host and microbes, mediating health and diseases.... (Review)
Review
The human microbiota produces molecules that are evolved to interact with the diverse cellular machinery of both the host and microbes, mediating health and diseases. One of the most puzzling microbiome molecules is colibactin, a genotoxin encoded in some commensal and extraintestinal microbes and is implicated in initiating colorectal cancer. The colibactin cluster was discovered more than 15 years ago, and most of the research studies have been focused on revealing the biosynthesis and precise structure of the cryptic encoded molecule(s) and the mechanism of carcinogenesis. In 2022, the Balskus group revealed that colibactin not only hits targets in the eukaryotic cell machinery but also in the prokaryotic cell. To that end, colibactin crosslinks the DNA resulting in activation of the SOS signaling pathway, leading to prophage induction from bacterial lysogens and modulation of virulence genes in pathogenic species. These unique activities of colibactin highlight its ecological role in shaping gut microbial communities and further consequences that impact human health. This review dives in-depth into the molecular mechanisms underpinning colibactin cellular targets in eukaryotic and prokaryotic cells, aiming to understand the fine details of the role of secreted microbiome chemistry in mediating host-microbe and microbe-microbe interactions. This understanding translates into a better realization of microbiome potential and how this could be advanced to future microbiome-based therapeutics or diagnostic biomarkers.
PubMed: 36172175
DOI: 10.3389/fphar.2022.958012