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Annual Review of Physiology Feb 2020Acidic metabolic waste products accumulate in the tumor microenvironment because of high metabolic activity and insufficient perfusion. In tumors, the acidity of the... (Review)
Review
Acidic metabolic waste products accumulate in the tumor microenvironment because of high metabolic activity and insufficient perfusion. In tumors, the acidity of the interstitial space and the relatively well-maintained intracellular pH influence cancer and stromal cell function, their mutual interplay, and their interactions with the extracellular matrix. Tumor pH is spatially and temporally heterogeneous, and the fitness advantage of cancer cells adapted to extracellular acidity is likely particularly evident when they encounter less acidic tumor regions, for instance, during invasion. Through complex effects on genetic stability, epigenetics, cellular metabolism, proliferation, and survival, the compartmentalized pH microenvironment favors cancer development. Cellular selection exacerbates the malignant phenotype, which is further enhanced by acid-induced cell motility, extracellular matrix degradation, attenuated immune responses, and modified cellular and intercellular signaling. In this review, we discuss how the acidity of the tumor microenvironment influences each stage in cancer development, from dysplasia to full-blown metastatic disease.
Topics: Acids; Animals; Humans; Hydrogen-Ion Concentration; Neoplasm Metastasis; Neoplasms; Signal Transduction; Tumor Microenvironment
PubMed: 31730395
DOI: 10.1146/annurev-physiol-021119-034627 -
European Journal of Medicinal Chemistry Jun 2020Research related to boronic acids, from synthetic development to materials to drug discovery, has skyrocketed in the past 20 years. In terms of drug discovery, the... (Review)
Review
Research related to boronic acids, from synthetic development to materials to drug discovery, has skyrocketed in the past 20 years. In terms of drug discovery, the incorporation of boronic acids into medicinal chemistry endeavours has seen a steady increase in recent years. In fact, the Food and Drug Administration (FDA) and Health Canada have thus far approved five boronic acid drugs, three of which were approved in the past four years, and several others are in clinical trials. Boronic acids have several desirable properties that has led to their increased use, including potentially enhancing potency of drugs and/or improving their pharmacokinetics profile. This review explores discovery processes of boronic acid drugs. It begins with a brief scope of boron in natural products and in current drugs, followed by an investigation into the various rationalizations for boronic acid incorporation and the synthetic developments that focused on facilitating their addition into organic compounds. We hope that the knowledge we have assembled in this literature review will encourage medicinal chemists to consider the potential benefits of incorporating boronic acids into their future drug discovery endeavours.
Topics: Boronic Acids; Drug Carriers; Drug Design; Humans
PubMed: 32302879
DOI: 10.1016/j.ejmech.2020.112270 -
Applied Biochemistry and Biotechnology Aug 2022Nanostarch is unique in that it is highly soluble, thermally stable, non-toxic and inexpensive. Hence, it is utilized in numerous well-established applications,... (Review)
Review
Nanostarch is unique in that it is highly soluble, thermally stable, non-toxic and inexpensive. Hence, it is utilized in numerous well-established applications, including drug delivery, cosmetics, textiles, foods, and enhanced oil recovery (EOR). These applications take advantage of the special functions that can be achieved through modifications to the structure and properties of native starch. The most common method for the preparation of nanostarch with a relatively higher crystallinity and stability is acid hydrolysis. Technically, the properties of nanostarch are highly dependent on several factors during the hydrolysis process, such as the acid, concentration of acid, reaction time, reaction temperature, and source of starch. The production of nanostarch with desired properties requires a detailed understanding on each of the factors as they are inevitably affected the physical and chemical properties of nanostarch. Hence, it is vital to incorporate optimization technique into the production process to achieve the full potential of nanostarch. Therefore, the current review comprehensively elaborates on the factors that affect acid hydrolysis as well as the optimization techniques used in the preparation of nanostarch.
Topics: Acids; Hydrolysis; Nanoparticles; Starch; Temperature
PubMed: 35488954
DOI: 10.1007/s12010-022-03932-6 -
Journal of Pharmaceutical Sciences Aug 2020This review provides insight into the use of boric acid as a pharmaceutical, a buffer, and an adjuvant/excipient in pharmaceutical formulations. Boric acid is a Lewis... (Review)
Review
This review provides insight into the use of boric acid as a pharmaceutical, a buffer, and an adjuvant/excipient in pharmaceutical formulations. Boric acid is a Lewis acid with a pKa of 8.92-9.24 that is sensitive to temperature, ionic strength, and concentration. The pKa varies with concentration because of polymerization above 0.02 M. Boric acid reacts reversibly with alcohols, especially 1,2-diols including carbohydrates, with carboxylic acids, thiols, and amines. These esters/adducts, are also Lewis acids with lower pKa values. Boric acid can stabilize some materials while catalyzing the degradation of others. Boric acid is used in various dermal and women's hygiene products because of its mild antibacterial and antifungal activity. In ophthalmic products, it is used as a buffer and in combination with other preservatives to broaden the prservative spectrum. Boric acid has been used reluctantly in parenteral products but appears to be quite safe at low doses. However, at high exposure, toxicity, including death, has been reported in humans, especially in children. Animal toxicities have also been noted, including reductions in male sperm counts. Boric acid is well absorbed on oral dosing. Its biological half-life is about 21 h in humans and has an affinity for some tissues, especially bone.
Topics: Alcohols; Animals; Boric Acids; Child; Esters; Female; Humans; Lewis Acids; Male; Osmolar Concentration
PubMed: 32353453
DOI: 10.1016/j.xphs.2020.04.015 -
Critical Reviews in Biotechnology Mar 2023Acid-resistant bacteria are more and more widely used in industrial production due to their unique acid-resistant properties. In order to survive in various acidic... (Review)
Review
Acid-resistant bacteria are more and more widely used in industrial production due to their unique acid-resistant properties. In order to survive in various acidic environments, acid-resistant bacteria have developed diverse protective mechanisms such as sensing acid stress and signal transduction, maintaining intracellular pH homeostasis by controlling the flow of H, protecting and repairing biological macromolecules, metabolic modification, and cross-protection. Acid-resistant bacteria have broad biotechnological application prospects in the food field. The production of fermented foods with high acidity and acidophilic enzymes are the main applications of this kind of bacteria in the food industry. Their acid resistance modules can also be used to construct acid-resistant recombinant engineering strains for special purposes. However, they can also cause negative effects on foods, such as spoilage and toxicity. Herein, the aim of this paper is to summarize the research progress of molecular mechanisms against acid stress of acid-resistant bacteria. Moreover, their effects on the food industry were also discussed. It is useful to lay a foundation for broadening our understanding of the physiological metabolism of acid-resistant bacteria and better serving the food industry.
Topics: Bacteria; Biotechnology; Acids; Food Industry
PubMed: 35114869
DOI: 10.1080/07388551.2021.2025335 -
International Journal of Sport... Jun 2017Diet composition can affect systemic pH and acid-base regulation, which may in turn influence exercise performance. An acidic environment in the muscle impairs... (Review)
Review
Diet composition can affect systemic pH and acid-base regulation, which may in turn influence exercise performance. An acidic environment in the muscle impairs performance and contributes to fatigue; therefore, current trends in sports nutrition place importance on maximizing the alkalinity of the body with ergogenic aids and dietary strategies. This review examines the evidence on the effects of dietary manipulations on acid load and exercise performance. Ten studies that investigated the effect of high versus low dietary acid loads on athletic performance generally identified that low dietary acid loads increased plasma pH, but did not consistently improve exercise performance at maximal or submaximal exercise intensities. In addition, the few studies conducted have several limitations including lack of female subjects and use of exercise tests exclusive to cycling or treadmill running. Although the research does not strongly support a performance benefit from low dietary acid loads, a more alkaline dietary pattern may be beneficial for overall health, as dietary induced acidosis has been associated with greater risk of cardiovascular disease and bone disease. The review includes dietary recommendations for athletes to reduce dietary acid load while still meeting sports nutrition recommendations.
Topics: Acid-Base Equilibrium; Acidosis; Acids; Athletic Performance; Diet; Exercise Test; Humans; Sports Nutritional Physiological Phenomena
PubMed: 28050921
DOI: 10.1123/ijsnem.2016-0186 -
Molecules (Basel, Switzerland) Oct 2018Amide bonds are the most prevalent structures found in organic molecules and various biomolecules such as peptides, proteins, DNA, and RNA. The unique feature of amide... (Review)
Review
Amide bonds are the most prevalent structures found in organic molecules and various biomolecules such as peptides, proteins, DNA, and RNA. The unique feature of amide bonds is their ability to form resonating structures, thus, they are highly stable and adopt particular three-dimensional structures, which, in turn, are responsible for their functions. The main focus of this review article is to report the methodologies for the activation of the unactivated amide bonds present in biomolecules, which includes the enzymatic approach, metal complexes, and non-metal based methods. This article also discusses some of the applications of amide bond activation approaches in the sequencing of proteins and the synthesis of peptide acids, esters, amides, and thioesters.
Topics: Acids; Amides; Biological Products; Esters; Molecular Conformation
PubMed: 30322008
DOI: 10.3390/molecules23102615 -
International Journal of Molecular... Nov 2021Peptides inherently feature the favorable properties of being easily synthesized, water-soluble, biocompatible, and typically non-toxic. Thus, boronic acid has been... (Review)
Review
Peptides inherently feature the favorable properties of being easily synthesized, water-soluble, biocompatible, and typically non-toxic. Thus, boronic acid has been widely integrated with peptides with the goal of discovering peptide ligands with novel biological activities, and this effort has led to broad applications. Taking the integration between boronic acid and peptide as a starting point, we provide an overview of the latest research advances and highlight the versatile and robust functionalities of boronic acid. In this review, we summarize the diverse applications of peptide boronic acids in medicinal chemistry and chemical biology, including the identification of covalent reversible enzyme inhibitors, recognition, and detection of glycans on proteins or cancer cell surface, delivery of siRNAs, development of pH responsive devices, and recognition of RNA or bacterial surfaces. Additionally, we discuss boronic acid-mediated peptide cyclization and peptide modifications, as well as the facile chemical synthesis of peptide boronic acids, which paved the way for developing a growing number of peptide boronic acids.
Topics: Antineoplastic Agents; Boron Compounds; Boronic Acids; Bortezomib; Drug Design; Enzyme Inhibitors; Glycine; Humans; Peptides; Protease Inhibitors
PubMed: 34884766
DOI: 10.3390/ijms222312958 -
Molecules (Basel, Switzerland) Sep 2019Indole derivatives are associated with a variety of both biological activities and applications in the field of material chemistry. A number of different strategies for... (Review)
Review
Indole derivatives are associated with a variety of both biological activities and applications in the field of material chemistry. A number of different strategies for synthesizing substituted indoles by means of the reactions of indolylboronic acids with electrophilic compounds are considered the methods of choice for modifying indoles because indolylboronic acids are easily available, stable, non-toxic and new reactions using indolylboronic acids have been described in the literature. Thus, the aim of this review is to summarize the methods available for the preparation of indolylboronic acids as well as their chemical transformations. The review covers the period 2010-2019.
Topics: Boronic Acids; Cyclization; Indoles; Metabolic Networks and Pathways; Metals; Models, Chemical; Molecular Structure
PubMed: 31569441
DOI: 10.3390/molecules24193523 -
Current Opinion in Biotechnology Apr 2016Acid mine drainage (AMD) is generated from the oxidative dissolution of metal sulfides when water and oxygen are available largely due to human mining activities. This... (Review)
Review
Acid mine drainage (AMD) is generated from the oxidative dissolution of metal sulfides when water and oxygen are available largely due to human mining activities. This process can be accelerated by indigenous microorganisms. In the last several decades, culture-dependent researches have uncovered and validated the roles of AMD microorganisms in metal sulfides oxidation and acid generation processes, and culture-independent studies have largely revealed the diversity and metabolic potentials and activities of AMD communities, leading towards a full understanding of the microbial diversity, functions and interactions in AMD ecosystems. This review describes the diversity of microorganisms and their functions in AMD ecosystems, and discusses their biotechnological applications in biomining and AMD bioremediation according to their capabilities.
Topics: Acids; Biodegradation, Environmental; Ecosystem; Humans; Mining; Water Microbiology; Water Pollutants, Chemical
PubMed: 26921733
DOI: 10.1016/j.copbio.2016.01.013