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In recent years, new nicotine delivery methods have emerged, and many users are choosing electronic cigarettes (e-cigarettes) over traditional tobacco cigarettes. E-cigarette use is very popular among adolescents, with more than 3.5 million currently using these products in the US. Despite the increased prevalence of e-cigarette use, there is limited knowledge regarding the health impact of e-cigarettes on the general population. Based on published findings by others, E-cigarette is associated with lung injury outbreak, which increased health and safety concerns related to consuming this product. Different components of e-cigarettes, including food-safe liquid solvents and flavorings, can cause health issues related to pneumonia, pulmonary injury, and bronchiolitis. In addition, e-cigarettes contain alarmingly high levels of carcinogens and toxicants that may have long-lasting effects on other organ systems, including the development of neurological manifestations, lung cancer, cardiovascular disorders, and tooth decay. Despite the well- documented potential for harm, e-cigarettes do not appear to increase susceptibility to SARS-CoV- 2 infection. Furthermore, some studies have found that e-cigarette users experience improvements in lung health and minimal adverse effects. Therefore, more studies are needed to provide a definitive conclusion on the long-term safety of e-cigarettes. The purpose of this review is to inform the readers about the possible health-risks associated with the use of e-cigarettes, especially among the group of young and young-adults, from a molecular biology point of view.
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Trivalent organoarsenicals such as methylarsenite (MAs(III)) are considerably more toxic than inorganic arsenate (As(V)) or arsenite (As(III)). In microbial communities MAs(III) exhibits significant antimicrobial activity. Although MAs(III) and other organoarsenicals contribute to the global arsenic biogeocycle, how they exert antibiotic-like properties is largely unknown. To identify possible targets of MAs(III), a genomic library of the gram-negative bacterium, Shewanella putrefaciens 200, was expressed in Escherichia coli with selection for MAs(III) resistance. One clone contained the S. putrefaciens murA gene (SpmurA), which catalyzes the first committed step in peptidoglycan biosynthesis. Overexpression of SpmurA conferred MAs(III) resistance to E. coli. Purified SpMurA was inhibited by MAs(III), phenylarsenite (PhAs(III)) or the phosphonate antibiotic fosfomycin but not by inorganic As(III). Fosfomycin inhibits MurA by binding to a conserved residue that corresponds to Cys117 in SpMurA. A C117D mutant was resistant to fosfomycin but remained sensitive to MAs(III), indicating that the two compounds have different mechanisms of action. New inhibitors of peptidoglycan biosynthesis are highly sought after as antimicrobial drugs, and organoarsenicals represent a new area for the development of novel compounds for combating the threat of antibiotic resistance.
Assuntos
Alquil e Aril Transferases/antagonistas & inibidores , Farmacorresistência Bacteriana/efeitos dos fármacos , Compostos Organometálicos/farmacologia , Peptidoglicano/biossíntese , Shewanella putrefaciens/efeitos dos fármacos , Alquil e Aril Transferases/genética , Farmacorresistência Bacteriana/genética , Escherichia coli/genética , Peptidoglicano/metabolismo , Shewanella putrefaciens/genéticaRESUMO
With advances in medical technology, the number of people over the age of 60 is on the rise, and thus, increasing the prevalence of age-related pathologies within the aging population. Neurodegenerative disorders, cancers, metabolic and inflammatory diseases are some of the most prevalent age-related pathologies affecting the growing population. It is imperative that a new treatment to combat these pathologies be developed. Although, still in its infancy, the CRISPR-Cas9 system has become a potent gene-editing tool capable of correcting gene-mediated age-related pathology, and therefore ameliorating or eliminating disease symptoms. Deleting target genes using the CRISPR-Cas9 system or correcting for gene mutations may ameliorate many different neurodegenerative disorders detected in the aging population. Cancer cells targeted by the CRISPR-Cas9 system may result in an increased sensitivity to chemotherapeutics, lower proliferation, and higher cancer cell death. Finally, reducing gene targeting inflammatory molecules production through microRNA knockout holds promise as a therapeutic strategy for both arthritis and inflammation. Here we present a review based on how the expanding world of genome editing can be applied to disorders and diseases affecting the aging population.
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Massive amounts of methyl [e.g., methylarsenate, MAs(V)] and aromatic arsenicals [e.g., roxarsone (4-hydroxy-3-nitrophenylarsonate, Rox(V)] have been utilized as herbicides for weed control and growth promotors for poultry and swine, respectively. The majority of these organoarsenicals degrade into more toxic inorganic species. Here, we demonstrate that the legume symbiont Sinorhizobium meliloti both reduces MAs(V) to MAs(III) and catalyzes sequential two-step reduction of nitro and arsenate groups in Rox(V), producing the highly toxic trivalent amino aromatic derivative 4-hydroxy-3-aminophenylarsenite (HAPA(III)). The existence of this process suggests that S. meliloti possesses the ability to transform pentavalent methyl and aromatic arsenicals into antibiotics to provide a competitive advantage over other microbes, which would be a critical process for the synthetic aromatic arsenicals to function as antimicrobial growth promoters. The activated trivalent aromatic arsenicals are degraded into less-toxic inorganic species by an MAs(III)-demethylating aerobe, suggesting that environmental aromatic arsenicals also undergo a multiple-step degradation pathway, in analogy with the previously reported demethylation pathway of the methylarsenate herbicide. We further show that an FAD-NADPH-dependent nitroreductase encoded by mdaB gene catalyzes nitroreduction of roxarsone both in vivo and in vitro. Our results demonstrate that environmental organoarsenicals trigger competition between members of microbial communities, resulting in gradual degradation of organoarsenicals and contamination by inorganic arsenic.
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Anti-Infecciosos , Arsenicais , Fabaceae , Herbicidas , Animais , Antibacterianos , Arsênio , Roxarsona , Sinorhizobium meliloti , SuínosRESUMO
Arsenic is a non-essential, environmentally ubiquitous toxic metalloid. In response to this pervasive environmental challenge, organisms evolved mechanisms to confer resistance to arsenicals. Inorganic pentavalent arsenate is taken into most cells adventitiously by phosphate uptake systems. Similarly, inorganic trivalent arsenite is taken into most cells adventitiously, primarily via aquaglyceroporins or sugar permeases. The most common strategy for tolerance to both inorganic and organic arsenicals is by efflux that extrude them from the cytosol. These efflux transporters span across kingdoms and belong to various families such as aquaglyceroporins, major facilitator superfamily (MFS) transporters, ATP-binding cassette (ABC) transporters and potentially novel, yet to be discovered families. This review will outline the properties and substrates of known arsenic transport systems, the current knowledge gaps in the field, and aims to provide insight into the importance of arsenic transport in the context of the global arsenic biogeocycle and human health.
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Arsênio/metabolismo , Arsenicais/metabolismo , Animais , Transporte Biológico , Humanos , Proteínas de Membrana Transportadoras/metabolismoRESUMO
Microbial biotransformations are major contributors to the arsenic biogeocycle. In parallel with transformations of inorganic arsenic, organoarsenicals pathways have recently been recognized as important components of global cycling of arsenic. The well-characterized pathway of resistance to arsenate is reduction coupled to arsenite efflux. Here, we describe a new pathway of arsenate resistance involving biosynthesis and extrusion of an unusual pentavalent organoarsenical. A number of arsenic resistance (ars) operons have two genes of unknown function that are linked in these operons. One, gapdh, encodes the glycolytic enzyme glyceraldehyde-3-phosphate dehydrogenase. The other, arsJ, encodes a major facilitator superfamily (MFS) protein. The two genes were cloned from the chromosome of Pseudomonas aeruginosa. When expressed together, but not alone, in Escherichia coli, gapdh and arsJ specifically conferred resistance to arsenate and decreased accumulation of As(V). Everted membrane vesicles from cells expressing arsJ accumulated As(V) in the presence of purified GAPDH, D-glceraldehylde 3-phosphate (G3P) and NAD(+) . GAPDH forms the unstable organoarsenical 1-arseno-3-phosphoglycerate (1As3PGA). We propose that ArsJ is an efflux permease that extrudes 1As3PGA from cells, where it rapidly dissociates into As(V) and 3-phosphoglycerate (3PGA), creating a novel pathway of arsenate resistance.