Generation Of Metabolites Research Articles

Metabolite Detection and Profiling Using Analytical Methods

To develop effective and safe drugs and to take them to the market in short period of time is the mission of pharmaceutical research companies. A selection of few of the lead compounds are done for the evaluation of safety and their ADMET (absorption, distribution, metabolism, excretion and toxicology) properties are tested in in-vitro (test systems), in-vivo (living organisms) and in-silico (computational methods). From initial stages to final stages of modern drug discovery processes, the vital tool for detecting and characterizing metabolites is MS (Mass spectrometry) hyphenated with other techniques. The methods used for generation of metabolites are in vitro techniques and cell lines (containing expressing drug metabolizing enzymes and heterologous genes). The use of HPLC-MS/UPLC-MS and high resolution MS, enables the in depth metabolite detection and profiling studies and it may also be likely to identify and characterize the site and types of biotransformation.

Persistence and fate of chlortetracycline in the aquatic environment under sub-tropical conditions: generation and dissipation of metabolites

The persistence of chlortetracycline in the aquatic environment, including the generation and dissipation of its metabolites, were investigated over a period of 90 days using microcosm experiments, with a view to establishing the metabolites generated and their persistence under conditions closely resembling the actual aquatic environment in terms of chemical and microbial composition. The concentrations of chlortetracycline and its metabolites were monitored in the water phase as well as the sediment phase. Data are presented showing that the degradation of chlortetracycline in each phase conforms to a triphasic linear rate law, confirming the existence of three speciation forms in each phase, attributed to one free dissolved form, and two colloidal particle adsorbed forms. Data are also presented showing that the two adsorbed forms are the most persistent, with life-times of 204.1 and 20.3 days respectively in the water phase, and 215.1 and 19.8 days respectively in the sediment phase. Life-times of 5.01 and 3.7 days respectively were obtained for the free dissolved forms in the water phase and sediment phase respectively. Data are further presented showing that of the several metabolites of chlortetracycline reported previously, only 4-epi-chlortetracycline and iso-chlortetracycline could be detected, and that these two degradation products undergo microbial mineralization without transformation to other intermediate degradation products in significant or detectable amounts.

Oxidative and/or Inflammatory Thrust Induced by Silver Nanoparticles in Rabbits: Effect of Vitamin E or NSAID Administration on Semen Parameters.

The aim of this research was to evaluate the inflammatory and/or oxidative damage related to silver nanoparticles (AgNPs), which are responsible for negative effects on sperm physiology and metabolism. Thirty New Zealand White rabbit bucks were divided into 5 experimental groups (6 animals/group): Control, treated with 0.9% NaCl; AgNP, treated with a 5 mM AgNP solution; LPS, treated with 50 g/kg b.w. E. coli LPS; AgNPs + NSAID, treated with an anti-inflammatory drug at 0.2 mg/kg b.w. and 5 mM AgNPs; and AgNPs + Vit E, treated with 0.18 mg/kg b.w. vitamin E and 5 mM AgNPs. Sperm quality and oxidative and inflammatory status were assessed at different times (0-60 days). Two statistical models were built: the first evaluated the effects of AgNPs and LPS (vs. Control), whereas the second evaluated the protective effect of an NSAID and vitamin E against AgNP-induced damage. Three principal component analyses were performed: sperm traits (motility, volume), oxidative status (antioxidants, oxidative metabolites, and redox reactions), and cytokines (TNF-α, IL-8, and IL-6). A negative effect on reproductive traits resulted after NP administration. In particular, an inflammatory/oxidative response took place in the reproductive tract during the first 2-3 wks of AgNP administration (cytokine and oxidative metabolite generation); the inflammatory/oxidative thrust impaired the status of rabbit tissues (seminal plasma, sperm, and blood), inducing a response (increased antioxidant enzymes and redox reactions) at 4-7 wks; oxidative stress, if not totally counteracted, likely induced toxicity in the late phases of AgNP administration (8-9 wks). In conclusion, exposure to silver nanoparticles produced a similar but more persistent effect than that of LPS on rabbit reproductive tissues: AgNP administration triggered a proinflammatory response linked to oxidative thrust, worsening many sperm parameters. However, only anti-inflammatory treatment counteracted the negative effects of AgNPs, whereas vitamin E seemed to act as an adjuvant, attenuating the oxidative cascade.

Post-transcriptional control of mitochondrial protein composition in changing environmental conditions.

In fluctuating environmental conditions, organisms must modulate their bioenergetic production in order to maintain cellular homeostasis for optimal fitness. Mitochondria are hubs for metabolite and energy generation. Mitochondria are also highly dynamic in their function: modulating their composition, size, density, and the network-like architecture in relation to the metabolic demands of the cell. Here, we review the recent research on the post-transcriptional regulation of mitochondrial composition focusing on mRNA localization, mRNA translation, protein import, and the role that dynamic mitochondrial structure may have on these gene expression processes. As mitochondrial structure and function has been shown to be very important for age-related processes, including cancer, metabolic disorders, and neurodegeneration, understanding how mitochondrial composition can be affected in fluctuating conditions can lead to new therapeutic directions to pursue.

Oxidative Stress in Cytokine-Induced Dysfunction of the Pancreatic Beta Cell: Known Knowns and Known Unknowns.

Compelling evidence from earlier studies suggests that the pancreatic beta cell is inherently weak in its antioxidant defense mechanisms to face the burden of protecting itself against the increased intracellular oxidative stress following exposure to proinflammatory cytokines. Recent evidence implicates novel roles for nicotinamide adenine dinucleotide phosphate (NADPH) oxidases (Noxs) as contributors to the excessive intracellular oxidative stress and damage under metabolic stress conditions. This review highlights the existing evidence on the regulatory roles of at least three forms of Noxs, namely Nox1, Nox2, and Nox4, in the cascade of events leading to islet beta cell dysfunction, specifically under the duress of chronic exposure to cytokines. Potential crosstalk between key signaling pathways (e.g., inducible nitric oxide synthase [iNOS] and Noxs) in the generation and propagation of reactive molecules and metabolites leading to mitochondrial damage and cell apoptosis is discussed. Available data accrued in investigations involving small-molecule inhibitors and antioxidant protein expression methods as tools toward the prevention of cytokine-induced oxidative damage are reviewed. Lastly, current knowledge gaps in this field, and possible avenues for future research are highlighted.

A role for the succinate dehydrogenase in the mode of action of the redox-active antimalarial drug, plasmodione

Malaria, caused by protozoan parasites, is a major public health issue in subtropical countries. An arsenal of antimalarial treatments is available, however, resistance is spreading, calling for the development of new antimalarial compounds. The new lead antimalarial drug plasmodione is a redox-active compound that impairs the redox balance of parasites leading to cell death. Based on extensive in vitro assays, a model of its mode of action was drawn, involving the generation of active plasmodione metabolites that act as subversive substrates of flavoproteins, initiating a redox cycling process producing reactive oxygen species. We showed that, in yeast, the mitochondrial respiratory chain NADH-dehydrogenases are the main redox-cycling target enzymes. Furthermore, our data supported the proposal that plasmodione is a pro-drug acting via its benzhydrol and benzoyl metabolites. Here, we selected plasmodione-resistant yeast mutants to further decipher plasmodione mode of action. Of the eleven mutants analysed, nine harboured a mutation in the FAD binding subunit of succinate dehydrogenase (SDH). The analysis of the SDH mutations points towards a specific role for SDH-bound FAD in plasmodione bioactivation, possibly in the first step of the process, highlighting a novel property of SDH.

Mutual Interplay of Host Immune System and Gut Microbiota in the Immunopathology of Atherosclerosis.

Inflammation is the key for the initiation and progression of atherosclerosis. Accumulating evidence has revealed that an altered gut microbiome (dysbiosis) triggers both local and systemic inflammation to cause chronic inflammatory diseases, including atherosclerosis. There have been some microbiome-relevant pro-inflammatory mechanisms proposed to link the relationships between dysbiosis and atherosclerosis such as gut permeability disruption, trigger of innate immunity from lipopolysaccharide (LPS), and generation of proatherogenic metabolites, such as trimethylamine N-oxide (TMAO). Meanwhile, immune responses, such as inflammasome activation and cytokine production, could reshape both composition and function of the microbiota. In fact, the immune system delicately modulates the interplay between microbiota and atherogenesis. Recent clinical trials have suggested the potential of immunomodulation as a treatment strategy of atherosclerosis. Here in this review, we present current knowledge regarding to the roles of microbiota in contributing atherosclerotic pathogenesis and highlight translational perspectives by discussing the mutual interplay between microbiota and immune system on atherogenesis.

New Horizons: Novel Approaches to Enhance Healthspan Through Targeting Cellular Senescence and Related Aging Mechanisms.

The elderly population is increasing faster than other segments of the population throughout the world. Age is the leading predictor for most chronic diseases and disorders, multimorbidity, geriatric syndromes, and impaired ability to recover from accidents or illnesses. Enhancing the duration of health and independence, termed healthspan, would be more desirable than extending lifespan merely by prolonging the period of morbidity toward the end of life. The geroscience hypothesis posits that healthspan can be extended by targeting fundamental aging mechanisms, rather than attempting to address each age-related disease one at a time, only so the afflicted individual survives disabled and dies shortly afterward of another age-related disease. These fundamental aging mechanisms include, among others, chronic inflammation, fibrosis, stem cell/ progenitor dysfunction, DNA damage, epigenetic changes, metabolic shifts, destructive metabolite generation, mitochondrial dysfunction, misfolded or aggregated protein accumulation, and cellular senescence. These processes appear to be tightly interlinked, as targeting any one appears to affect many of the rest, underlying our Unitary Theory of Fundamental Aging Mechanisms. Interventions targeting many fundamental aging processes are being developed, including dietary manipulations, metformin, mTOR (mechanistic target of rapamycin) inhibitors, and senolytics, which are in early human trials. These interventions could lead to greater healthspan benefits than treating age-related diseases one at a time. To illustrate these points, we focus on cellular senescence and therapies in development to target senescent cells. Combining interventions targeting aging mechanisms with disease-specific drugs could result in more than additive benefits for currently difficult-to-treat or intractable diseases. More research attention needs to be devoted to targeting fundamental aging processes.

4-methylpyrazole protects against acetaminophen-induced acute kidney injury

Acetaminophen (APAP) hepatotoxicity is the most common cause of acute liver failure in the United States, and while a significant percentage of APAP overdose patients develop kidney injury, molecular mechanisms involved in APAP-induced nephrotoxicity are relatively unknown. We have shown that 4-methylpyrazole (4MP, Fomepizole) protects against APAP-induced liver injury by inhibiting reactive metabolite formation through Cyp2E1, and analysis of data from APAP overdose patients indicated that kidney dysfunction strongly correlated with severe liver injury. Since Cyp2E1 is also expressed in the kidney, this study explored protection by 4MP against APAP-induced nephrotoxicity. Male C57BL/6 J mice were treated with either 300 or 600 mg/kg APAP with or without 4MP for 2, 6 or 24 h, followed by measurement of APAP metabolism and tissue injury. Interestingly, levels of APAP and its non-oxidative metabolites were significantly higher in kidneys when compared to the liver. APAP-protein adducts were present in both tissues within 2 h, but were absent in kidney mitochondria, unlike in the liver. While GSH depletion was seen in both tissues, activation of c-jun N-terminal kinase and its translocation to the mitochondria, which is a critical feature of APAP-induced liver injury, was not detected in the kidney. Treatment with 4MP attenuated APAP oxidative metabolite generation, GSH depletion as well as kidney injury indicating its potential use in protection against APAP-induced nephrotoxicity. In conclusion, since reactive metabolite formation seems to be common in both liver and kidney, 4MP mediated inhibition of Cyp2E1 protects against APAP-induced nephrotoxicity. However, downstream mechanisms of APAP-induced nephrotoxicity seem distinct from the liver.

Integrated omics unveil the secondary metabolic landscape of a basal dinoflagellate

BackgroundSome dinoflagellates cause harmful algal blooms, releasing toxic secondary metabolites, to the detriment of marine ecosystems and human health. Our understanding of dinoflagellate toxin biosynthesis has been hampered by their unusually large genomes. To overcome this challenge, for the first time, we sequenced the genome, microRNAs, and mRNA isoforms of a basal dinoflagellate, Amphidinium gibbosum, and employed an integrated omics approach to understand its secondary metabolite biosynthesis.ResultsWe assembled the ~ 6.4-Gb A. gibbosum genome, and by probing decoded dinoflagellate genomes and transcriptomes, we identified the non-ribosomal peptide synthetase adenylation domain as essential for generation of specialized metabolites. Upon starving the cells of phosphate and nitrogen, we observed pronounced shifts in metabolite biosynthesis, suggestive of post-transcriptional regulation by microRNAs. Using Iso-Seq and RNA-seq data, we found that alternative splicing and polycistronic expression generate different transcripts for secondary metabolism.ConclusionsOur genomic findings suggest intricate integration of various metabolic enzymes that function iteratively to synthesize metabolites, providing mechanistic insights into how dinoflagellates synthesize secondary metabolites, depending upon nutrient availability. This study provides insights into toxin production associated with dinoflagellate blooms. The genome of this basal dinoflagellate provides important clues about dinoflagellate evolution and overcomes the large genome size, which has been a challenge previously.

Integrative Analyses of Genes Associated with Fulminant Type 1 Diabetes.

Objective Fulminant type 1 diabetes (FT1D) is a type of type 1 diabetes, which is characterized by rapid onset of disease and severe metabolic disorders. We intend to screen for crucial genes and potential molecular mechanisms in FT1D in this study. Method We downloaded GSE44314, which includes six healthy controls and five patients with FT1D, from the GEO database. Identification of differentially expressed genes (DEGs) was performed by NetworkAnalyst. The Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses of DEGs were screened by an online tool—Database for Annotation, Visualization, and Integration Discovery (DAVID). Protein-protein interaction (PPI) network and hub genes among DEGs were analyzed by NetworkAnalyst. And we also use NetworkAnalyst to find out the microRNAs (miRNAs) and transcription factors (TFs) which regulate the expression of DEGs. Result We identified 130 DEGs (60 upregulated and 70 downregulated DEGs) between healthy controls and FT1D patients. GO analysis results revealed that DEGs were mostly enriched in generation of precursor metabolites and energy, neurohypophyseal hormone activity, and mitochondrial inner membrane. KEGG pathway analysis demonstrated that DEGs were mostly involved in nonalcoholic fatty liver disease. Results indicated that NCOA1, SRF, ERBB3, EST1, TOP1, UBE2S, INO80, COX7C, ITGAV, and COX6C were the top hub genes in the PPI network. Furthermore, we recognized that LDLR, POTEM, IFNAR2, BAZ2A, and SRF were the top hub genes in the miRNA-target gene network, and SRF, TSPAN4, CD59, ETS1, and SLC25A25 were the top hub genes in the TF-target gene network. Conclusion Our study pinpoints key genes and pathways associated with FT1D by a sequence of bioinformatics analysis on DEGs. These identified genes and pathways provide more detailed molecular mechanisms of FT1D and may provide novel therapeutic targets.

Genome-wide association analysis of natural variation in seed tocochromanols of barley.

Tocochromanols (tocols for short), commonly called Vitamin E, are lipid-soluble plant antioxidants vital for regulating lipid peroxidation in chloroplasts and seeds. Barley (Hordeum vulgare L.) seeds contain all eight different isoforms of tocols; however, the extent of natural variation in their composition and their underlying genetic basis is not known. Tocol levels in barley seeds were quantified in diverse H. vulgare panels comprising 297 wild lines from a diversity panel and 160 cultivated spring-type accessions from the mini-core panel representing the genetic diversity of the USDA barley germplasm collection. Significant differences were observed in the concentration of tocols between the two panels. To identify the genes associated with tocols, genome-wide association analysis was conducted with single nucleotide polymorphisms (SNPs) from Illumina arrays for the mini-core panel and genotyping-by-sequencing for the wild barley panel. Forty unique SNPs in the wild barley and 27 SNPs in the mini-core panel were significantly associated with various tocols. Marker-trait associations (MTAs) were identified on chromosomes 1, 6, and 7 for key genes in the tocol biosynthesis pathway, which have also been reported in other studies. Several novel MTAs were identified on chromosomes 2, 3, 4 and 5 and were found to be in proximity to genes involved in the generation of precursor metabolites required for tocol biosynthesis. This study provides a valuable resource for barley breeding programs targeting specific isoforms of seed tocols and for investigating the physiological roles of these metabolites in seed longevity, dormancy, and germination.

Recent Progress on Activatable Nanomedicines for Immunometabolic Combinational Cancer Therapy

Tumor metabolism generally involves the generation of immunosuppressive metabolites, which contribute to the dysfunction of immune cells. Thus, immunometabolic interventions targeting the metabolic circuits and reducing immunosuppressive metabolites have been developed to invigorate antitumor immunity and attenuate cancer immune evasion. Although several clinical trials have been launched to develop metabolic agents for immunotherapy, they have the issues of potential immune‐related adverse events and low response rate. Smart nanomedicines integrated with physiological stimuli‐activatable action hold great promise to improve the therapeutic effectiveness and reduce systemic side effects for clinical translation. In this review, the recent progress on smart nanosystems for immunometabolic cancer therapy is summarized and their synergistic effects by combining immunometabolic intervention with multiple therapeutic modalities are highlighted, focusing on the molecular design and nanoengineering fabrication of these physiological stimuli‐activatable nanomedicines. These nanomedicines recover their activity of immunometabolic intervention in response to the specific physiological stimuli in the tumor microenvironment. This greatly reinforces their therapeutic action and reduces the off‐target side effects via local reprogramming of tumor metabolism. In addition to highlighting the synergistic therapeutic potential by combining immunometabolic therapy with multiple therapeutic modalities, current challenges and prospects of these activatable nanomedicines are discussed.

IL4I1 Is a Metabolic Immune Checkpoint that Activates the AHR and Promotes Tumor Progression

Aryl hydrocarbon receptor (AHR) activation by tryptophan (Trp) catabolites enhances tumor malignancy and suppresses anti-tumor immunity. The context specificity of AHR target genes has so far impeded systematic investigation of AHR activity and its upstream enzymes across human cancers. A pan-tissue AHR signature, derived by natural language processing, revealed that across 32 tumor entities, interleukin-4-induced-1 (IL4I1) associates more frequently with AHR activity than IDO1 or TDO2, hitherto recognized as the main Trp-catabolic enzymes. IL4I1 activates the AHR through the generation of indole metabolites and kynurenic acid. It associates with reduced survival in glioma patients, promotes cancer cell motility, and suppresses adaptive immunity, thereby enhancing the progression of chronic lymphocytic leukemia (CLL) in mice. Immune checkpoint blockade (ICB) induces IDO1 and IL4I1. As IDO1 inhibitors do not block IL4I1, IL4I1 may explain the failure of clinical studies combining ICB with IDO1 inhibition. Taken together, IL4I1 blockade opens new avenues for cancer therapy.

WRKY1-mediated regulation of tryptophan decarboxylase in tryptamine generation for withanamide production in Withania somnifera (Ashwagandha).

WsWRKY1-mediated transcriptional modulation of Withania somnifera tryptophan decarboxylase gene (WsTDC) helps to regulate fruit-specific tryptamine generation for production of withanamides. Withania somnifera is a highly valued medicinal plant. Recent demonstration of novel indolyl metabolites called withanamides in its fruits (berries) prompted us to investigate its tryptophan decarboxylase (TDC), as tryptophan is invariably a precursor for indole moiety. TDC catalyzes conversion of tryptophan into tryptamine, and the catalytic reaction constitutes a committed metabolic step for synthesis of an array of indolyl metabolites. The TDC gene (WsTDC) was cloned from berries of the plant and expressed in E. coli. The recombinant enzyme was purified and characterized for its catalytic attributes. Catalytic and structural aspects of the enzyme indicated its regulatory/rate-limiting significance in generation of the indolyl metabolites. Novel tissue-wise and developmentally differential abundance of WsTDC transcripts reflected its preeminent role in withanamide biogenesis in the fruits. Transgenic lines overexpressing WsTDC gene showed accumulation of tryptamine at significantly higher levels, while lines silenced for WsTDC exhibited considerably depleted levels of tryptamine. Cloning and sequence analysis of promoter of WsTDC revealed the presence of W-box in it. Follow-up studies on isolation of WsWRKY1 transcription factor and its overexpression in W. somnifera revealed that WsTDC expression was substantially induced by WsWRKY1 resulting in overproduction of tryptamine. The study invokes a key role of TDC in regulating the indolyl secondary metabolites through enabling elevated flux/supply of tryptamine at multiple levels from gene expression to catalytic attributes overall coordinated by WsWRKY1. This is the first biochemical, molecular, structural, physiological and regulatory description of a fruit-functional TDC.

Gut Microbiota-Polyphenol Interactions in Chicken: A Review.

Simple SummaryGut microbiota play crucial roles in digestion of feed and absorption of nutrients in fast growing chickens. Gut microbiota affects feed conversion ratio, body weight gain, apparent metabolizable energy, residual feed intake, and time taken to attain the desired weight, which have direct influence on the health and productivity of chickens. A normal gut microbiota is therefore very important for optimum health. Factors like the environment, heat stress, and housing conditions can cause detrimental changes in the gut resulting in poor health of birds and decreased production performance. Polyphenols can be used to improve gut health due to their established health benefits and strong antioxidant potential. The interaction between polyphenols and the gut microbiota further generates active metabolites, which can modulate the composition of the chicken gut microbiota. Because of the specificities of the gut microbiota-polyphenols interactions, current knowledge in this area is presented.The gastrointestinal tract of the chicken harbors very complex and diverse microbial communities including both beneficial and harmful bacteria. However, a dynamic balance is generally maintained in such a way that beneficial bacteria predominate over harmful ones. Environmental factors can negatively affect this balance, resulting in harmful effects on the gut, declining health, and productivity. This means modulating changes in the chicken gut microbiota is an effective strategy to improve gut health and productivity. One strategy is using modified diets to favor the growth of beneficial bacteria and a key candidate are polyphenols, which have strong antioxidant potential and established health benefits. The gut microbiota-polyphenol interactions are of vital importance in their effects on the gut microbiota modulation because it affects not only the composition of gut bacteria but also improves bioavailability of polyphenols through generation of more bioactive metabolites enhancing their health effects on morphology and composition of the gut microbiota. The object of this review is to improve the understanding of polyphenol interactions with the gut microbiota and highlights their potential role in modulation of the gut microbiota of chicken.

Bioelectricity generation and analysis of anode biofilm metabolites from septic tank wastewater in microbial fuel cells

The microbial fuel cell (MFC) has gained interest among the scientific community due to the feasibility of transforming organic wastes directly into electrical energy through biocatalysis or enzymatic bioelectrochemical reactions. In the present study, an effective coculture system, namely, Serratia marcescens AATB1 and Klebsiella pneumoniae AATB2, was used in the MFC system. The isolated strains, AATB1 and AATB2 were identified as biofilm producing bacteria. The experiments were performed in a two-chambered MFC setup with septic tank wastewater as the substrate in a 5 days batch mode. Pure culture of S. marcescens AATB1 and K. pneumoniae AATB2, and their cocultures were able to produce energy with the maximum current densities of 728.85 ± 36 mA/m2, 642.19 ± 32 mA/m2 and 869.11 ± 43 mA/m2, respectively, and the maximum power densities of 341.65 ± 17 mW/m2, 257.51 ± 12 mW/m2 and 398.69 ± 19 mW/m2, respectively. During the process, cyclic voltammetry analysis has revealed the electrochemical behavior of the anodic biofilm. Approximately, 70.42% ± 3.52% of chemical oxygen demand removal was achieved during the process. Biofilm formation by the adhesion of microbes on the electrode surfaces was visualized by confocal laser scanning microscope and scanning electron microscope. All the three MFC systems were produced by biofilms containing extracellular polymeric substance from S. marcescens AATB1 (55 ± 2.75 μg/cm2 of protein, 61 ± 3.05 μg/cm2 of carbohydrate) and K. pneumoniae AATB2 (46 ± 2.30 μg/cm2 of protein, 53 ± 2.65 μg/cm2 of carbohydrate) and coculture (60 ± 3.00 μg/cm2 of protein, 69 ± 3.45 μg/cm2 of carbohydrate). Furthermore, the anode biofilm metabolites were identified by Gas Chromatography–Mass Spectrometry (GC-MS) and Nuclear Magnetic Resonance NMR spectroscopy.

Microbiologically influenced corrosion behavior of friction stir welded S32654 super austenitic stainless steel in the presence of Acidithiobacillus caldus SM-1 biofilm

The microbiologically influenced corrosion (MIC) susceptibility of friction stir welded (FSW) S32654 super austenitic stainless steel (SASS) in the presence of acid producing bacterium Acidithiobacillus caldus SM-1 was investigated by surface analysis techniques and electrochemical measurements. The average depth of pits shown on the FSW coupon surface was 2.8 ± 0.5 μm after 14 days of immersion in A. caldus SM-1 broth, which was similar to that of the control base metal (BM) coupon (2.7 ± 0.6 μm). The results of electrochemical measurements showed that control BM and FSW coupons had very close corrosion rates in both abiotic and biotic media. The results indicated that the FSW process did not decrease the corrosion resistance of S32654 SASS. In addition, A. caldus SM-l significantly accelerated the general corrosion and pitting corrosion of control BM and FSW coupons. The lowest pH value of A. caldus SM-1 inoculated medium arrived at 1.81 ± 0.09 after 14 days of incubation. The acceleration of corrosion rate may be attributed to the generation and enrichment of aggressive acidic metabolites of A. caldus SM-l underneath the biofilm.

Frog Skin-Derived Peptides Against Corynebacterium jeikeium: Correlation between Antibacterial and Cytotoxic Activities.

Corynebacterium jeikeium is a commensal bacterium that colonizes human skin, and it is part of the normal bacterial flora. In non-risk subjects, it can be the cause of bad body smell due to the generation of volatile odorous metabolites, especially in the wet parts of the body that this bacterium often colonizes (i.e., groin and axillary regions). Importantly, in the last few decades, there have been increasing cases of serious infections provoked by this bacterium, especially in immunocompromised or hospitalized patients who have undergone installation of prostheses or catheters. The ease in developing resistance to commonly-used antibiotics (i.e., glycopeptides) has made the search for new antimicrobial compounds of clinical importance. Here, for the first time, we characterize the antimicrobial activity of some selected frog skin-derived antimicrobial peptides (AMPs) against C. jeikeium by determining their minimum inhibitory and bactericidal concentrations (MIC and MBC) by a microdilution method. The results highlight esculentin-1b(1-18) [Esc(1-18)] and esculentin-1a(1-21) [Esc(1-21)] as the most active AMPs with MIC and MBC of 4–8 and 0.125–0.25 µM, respectively, along with a non-toxic profile after a short- and long-term (40 min and 24 h) treatment of mammalian cells. Overall, these findings indicate the high potentiality of Esc(1-18) and Esc(1-21) as (i) alternative antimicrobials against C. jeikeium infections and/or as (ii) additives in cosmetic products (creams, deodorants) to reduce the production of bad body odor.

Disclosing the redox metabolism of drugs: The essential role of electrochemistry

Abstract Electrochemical methods provide a wide range of strategies to explore the metabolism of drugs. These approaches traditionally encompass preparative aspects viz. the electrochemical generation of potent metabolites or the electrochemical exploration of the reactivity of redox enzymes (or their mimics) toward drugs. More recently, the electroanalytical characterization of the successive redox and redox-coupled reactions was found effective to unravel more complex mechanisms, especially those related to the reactivity of bioorganometallic drugs. This minireview highlights the contribution of these different electrochemical strategies to the determination of drug metabolism through representative recent examples.