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1.
Biological Factors, Metals, and Biomaterials Regulating Osteogenesis through Autophagy.
di Giacomo, V, Cataldi, A, Sancilio, S
International journal of molecular sciences. 2020;(8)
Abstract
Bone loss raises great concern in numerous situations, such as ageing and many diseases and in both orthopedic and dentistry fields of application, with an extensive impact on health care. Therefore, it is crucial to understand the mechanisms and the determinants that can regulate osteogenesis and ensure bone balance. Autophagy is a well conserved lysosomal degradation pathway, which is known to be highly active during differentiation and development. This review provides a revision of the literature on all the exogen factors that can modulate osteogenesis through autophagy regulation. Metal ion exposition, mechanical stimuli, and biological factors, including hormones, nutrients, and metabolic conditions, were taken into consideration for their ability to tune osteogenic differentiation through autophagy. In addition, an exhaustive overview of biomaterials, both for orthopedic and dentistry applications, enhancing osteogenesis by modulation of the autophagic process is provided as well. Already investigated conditions regulating bone regeneration via autophagy need to be better understood for finely tailoring innovative therapeutic treatments and designing novel biomaterials.
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2.
Harnessing Metal Homeostasis Offers Novel and Promising Targets Against Candida albicans.
Hameed, S, Hans, S, Singh, S, Fatima, Z
Current drug discovery technologies. 2020;(4):415-429
Abstract
Fungal infections, particularly of Candida species, which are the commensal organisms of human, are one of the major debilitating diseases in immunocompromised patients. The limited number of antifungal drugs available to treat Candida infections, with the concomitant increasing incidence of multidrug-resistant (MDR) strains, further worsens the therapeutic options. Thus, there is an urgent need for the better understanding of MDR mechanisms, and their reversal, by employing new strategies to increase the efficacy and safety profiles of currently used therapies against the most prevalent human fungal pathogen, Candida albicans. Micronutrient availability during C. albicans infection is regarded as a critical factor that influences the progression and magnitude of the disease. Intracellular pathogens colonize a variety of anatomical locations that are likely to be scarce in micronutrients, as a defense strategy adopted by the host, known as nutritional immunity. Indispensable critical micronutrients are required both by the host and by C. albicans, especially as a cofactor in important metabolic functions. Since these micronutrients are not freely available, C. albicans need to exploit host reservoirs to adapt within the host for survival. The ability of pathogenic organisms, including C. albicans, to sense and adapt to limited micronutrients in the hostile environment is essential for survival and confers the basis of its success as a pathogen. This review describes that micronutrients availability to C. albicans is a key attribute that may be exploited when one considers designing strategies aimed at disrupting MDR in this pathogenic fungi. Here, we discuss recent advances that have been made in our understanding of fungal micronutrient acquisition and explore the probable pathways that may be utilized as targets.
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3.
Allosteric control of metal-responsive transcriptional regulators in bacteria.
Baksh, KA, Zamble, DB
The Journal of biological chemistry. 2020;(6):1673-1684
Abstract
Many transition metals are essential trace nutrients for living organisms, but they are also cytotoxic in high concentrations. Bacteria maintain the delicate balance between metal starvation and toxicity through a complex network of metal homeostasis pathways. These systems are coordinated by the activities of metal-responsive transcription factors-also known as metal-sensor proteins or metalloregulators-that are tuned to sense the bioavailability of specific metals in the cell in order to regulate the expression of genes encoding proteins that contribute to metal homeostasis. Metal binding to a metalloregulator allosterically influences its ability to bind specific DNA sequences through a variety of intricate mechanisms that lie on a continuum between large conformational changes and subtle changes in internal dynamics. This review summarizes recent advances in our understanding of how metal sensor proteins respond to intracellular metal concentrations. In particular, we highlight the allosteric mechanisms used for metal-responsive regulation of several prokaryotic single-component metalloregulators, and we briefly discuss current open questions of how metalloregulators function in bacterial cells. Understanding the regulation and function of metal-responsive transcription factors is a fundamental aspect of metallobiochemistry and is important for gaining insights into bacterial growth and virulence.
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4.
Prospects and applications of plant growth promoting rhizobacteria to mitigate soil metal contamination: A review.
Guo, J, Muhammad, H, Lv, X, Wei, T, Ren, X, Jia, H, Atif, S, Hua, L
Chemosphere. 2020;:125823
Abstract
The rapid increase in world population has generated the issues of hunger, poverty, food insecurity and malnutrition. To meet the challenge of increased food production of better quality, the farmers were compelled to use more chemical fertilizers, especially in developing countries. The higher use of chemical fertilizers interrupts the food chain through eutrophication, the polluting air and soil by incorporating metals. Trace metals have a deleterious effect on soil microbial and plant growth. To minimize metal toxicity and maximize the production of food, there are different approaches that can lead to lessen the use of chemical fertilizers. Plant growth promoting rhizobacteria (PGPR) are capable to enhance the plant growth and can remediate metal contaminated soils. PGPR has the ability to improve food production with diverse attributes e.g. producing siderophores that promote rhizosphere trace metal sequestration and production of organic and inorganic acids thus affecting trace metal bioavailability and plant induced systemic tolerance (IST) to limit the crop metal accumulation. In this review paper, we have discussed the biological approach which is environmentally friendly and cost-effective mean for metal polluted soils and gives some new insights for safety use of PGPR in trace metal contaminated fields.
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5.
Direct and indirect influence of arbuscular mycorrhizae on enhancing metal tolerance of plants.
Janeeshma, E, Puthur, JT
Archives of microbiology. 2020;(1):1-16
Abstract
The acerbic elevation of toxic metal ions in arable lands, enhance the risk of their accumulation and biomagnification in crops as well as in humans. Phytoremediation is an eco-friendly approach to clear metal-contaminated lands by making use of metal accumulation potential of plants; which are referred to as hyperaccumulators. This phytoremediation potential can be enhanced with the symbiotic association between the root of hyperaccumulators and arbuscular mycorrhizae. Modification of root morphology, enhancement of antioxidants biosynthesis, and the increase in shoot biomass are the changes observed in plants as a result of indirect influence of arbuscular mycorrhizae. Direct influence of arbuscular mycorrhizae on enhancing metal tolerance of plants includes immobilization strategies, adsorption of metals on to the hyphal wall and glomalin exudation. Furthermore, we have discussed arbuscular mycorrhizal induced increment in the metal tolerance potential of plants through the alteration in various metabolic processes with special emphasis to the phenylpropanoid pathway.
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6.
Metabolic manipulation by Pseudomonas fluorescens: a powerful stratagem against oxidative and metal stress.
MacLean, A, Bley, AM, Appanna, VP, Appanna, VD
Journal of medical microbiology. 2020;(3):339-346
Abstract
Metabolism is the foundation of all living organisms and is at the core of numerous if not all biological processes. The ability of an organism to modulate its metabolism is a central characteristic needed to proliferate, to be dormant and to survive any assault. Pseudomonas fluorescens is bestowed with a uniquely versatile metabolic framework that enables the microbe to adapt to a wide range of conditions including disparate nutrients and toxins. In this mini-review we elaborate on the various metabolic reconfigurations evoked by this microbial system to combat reactive oxygen/nitrogen species and metal stress. The fine-tuning of the NADH/NADPH homeostasis coupled with the production of α-keto-acids and ATP allows for the maintenance of a reductive intracellular milieu. The metabolic networks propelling the synthesis of metabolites like oxalate and aspartate are critical to keep toxic metals at bay. The biochemical processes resulting from these defensive mechanisms provide molecular clues to thwart infectious microbes and reveal elegant pathways to generate value-added products.
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7.
Current understanding of metal ions in the pathogenesis of Alzheimer's disease.
Wang, L, Yin, YL, Liu, XZ, Shen, P, Zheng, YG, Lan, XR, Lu, CB, Wang, JZ
Translational neurodegeneration. 2020;:10
Abstract
BACKGROUND The homeostasis of metal ions, such as iron, copper, zinc and calcium, in the brain is crucial for maintaining normal physiological functions. Studies have shown that imbalance of these metal ions in the brain is closely related to the onset and progression of Alzheimer's disease (AD), the most common neurodegenerative disorder in the elderly. MAIN BODY Erroneous deposition/distribution of the metal ions in different brain regions induces oxidative stress. The metal ions imbalance and oxidative stress together or independently promote amyloid-β (Aβ) overproduction by activating β- or γ-secretases and inhibiting α-secretase, it also causes tau hyperphosphorylation by activating protein kinases, such as glycogen synthase kinase-3β (GSK-3β), cyclin-dependent protein kinase-5 (CDK5), mitogen-activated protein kinases (MAPKs), etc., and inhibiting protein phosphatase 2A (PP2A). The metal ions imbalances can also directly or indirectly disrupt organelles, causing endoplasmic reticulum (ER) stress; mitochondrial and autophagic dysfunctions, which can cause or aggravate Aβ and tau aggregation/accumulation, and impair synaptic functions. Even worse, the metal ions imbalance-induced alterations can reversely exacerbate metal ions misdistribution and deposition. The vicious cycles between metal ions imbalances and Aβ/tau abnormalities will eventually lead to a chronic neurodegeneration and cognitive deficits, such as seen in AD patients. CONCLUSION The metal ions imbalance induces Aβ and tau pathologies by directly or indirectly affecting multiple cellular/subcellular pathways, and the disrupted homeostasis can reversely aggravate the abnormalities of metal ions transportation/deposition. Therefore, adjusting metal balance by supplementing or chelating the metal ions may be potential in ameliorating AD pathologies, which provides new research directions for AD treatment.
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8.
Metal-Mediated Functionalization of Natural Peptides and Proteins: Panning for Bioconjugation Gold.
Ohata, J, Martin, SC, Ball, ZT
Angewandte Chemie (International ed. in English). 2019;(19):6176-6199
Abstract
Selective modification of natural proteins is a daunting methodological challenge and a stringent test of selectivity and reaction scope. There is a continued need for new reactivity and new selectivity concepts. Transition metals exhibit a wealth of unique reactivity that is orthogonal to biological reactions and processes. As such, metal-based methods play an increasingly important role in bioconjugation. This Review examines metal-based methods as well as their reactivity and selectivity for the functionalization of natural proteins and peptides.
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9.
Additive manufacturing of biodegradable metals: Current research status and future perspectives.
Qin, Y, Wen, P, Guo, H, Xia, D, Zheng, Y, Jauer, L, Poprawe, R, Voshage, M, Schleifenbaum, JH
Acta biomaterialia. 2019;:3-22
Abstract
The combination of biodegradable metals and additive manufacturing (AM) leads to a revolutionary change of metal implants in many aspects including materials, design, manufacturing, and clinical applications. The AM of nondegradable metals such as titanium and CoCr alloys has proven to be a tremendous success in clinical applications. The AM of biodegradable metals including magnesium (Mg), iron (Fe), and zinc (Zn) is still in its infancy, although much progress has been made in the research field. Element loss and porosity are common processing problems for AM of biodegradable metals like Zn and Mg, which are mainly caused by evaporation during melting under a high-energy beam. The resulting formation quality and properties are closely related to material, design, and processing, making AM of biodegradable metals a typical interdisciplinary subject involving biomaterials, mechanical engineering, and medicine. This work reviews the state of research and future perspective on AM of biodegradable metals from extensive viewpoints such as material, processing, formation quality, design, microstructure, and properties. Effects of powder properties and processing parameters on formation quality are characterized in detail. The microstructure and metallurgical defects encountered in the AM parts are described. Mechanical and biodegradable properties of AM samples are introduced. Design principles and potential applications of biodegradable metal implants produced by AM are discussed. Finally, current research status is summarized together with some proposed future perspectives for advancing knowledge about AM of biodegradable metals. STATEMENT OF SIGNIFICANCE Rapid development of research and applications on biodegradable metals and additive manufacturing (AM) has been made in recent years. Customized geometric shapes of medical metals with porous structure can be realized accurately and efficiently by laser powder bed fusion (L-PBF), which is beneficial to achieve reliable stress conduction and balanced properties. This review introduces the development history and current status of AM of biodegradable metals and then critically surveys L-PBF of Mg-, Fe-, and Zn-based metals from multiple viewpoints including materials, processing, formation quality, structural design, microstructure, and mechanical and biological properties. The present findings are summarized together with some proposed future challenges for advancing AM of biodegradable metals into real clinical applications.
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10.
Metal-responsive RNA polymerase extracytoplasmic function (ECF) sigma factors.
Moraleda-Muñoz, A, Marcos-Torres, FJ, Pérez, J, Muñoz-Dorado, J
Molecular microbiology. 2019;(2):385-398
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Abstract
In order to survive, bacteria must adapt to multiple fluctuations in their environment, including coping with changes in metal concentrations. Many metals are essential for viability, since they act as cofactors of indispensable enzymes. But on the other hand, they are potentially toxic because they generate reactive oxygen species or displace other metals from proteins, turning them inactive. This dual effect of metals forces cells to maintain homeostasis using a variety of systems to import and export them. These systems are usually inducible, and their expression is regulated by metal sensors and signal-transduction mechanisms, one of which is mediated by extracytoplasmic function (ECF) sigma factors. In this review, we have focused on the metal-responsive ECF sigma factors, several of which are activated by iron depletion (FecI, FpvI and PvdS), while others are activated by excess of metals such as nickel and cobalt (CnrH), copper (CarQ and CorE) or cadmium and zinc (CorE2). We focus particularly on their physiological roles, mechanisms of action and signal transduction pathways.