Adduct Formation Research Articles

AHR-mediated DNA damage contributes to BaP-induced cardiac malformations in zebrafish

Benzo[a]pyrene (BaP) is a representative polycyclic aromatic hydrocarbon widely present in the environment. We previously reported that the aryl hydrocarbon receptor (AHR) mediates BaP-induced apoptosis and cardiac malformations in zebrafish embryos, but the underlying molecular mechanisms were unclear. Since BaP is a mutagenetic compound, we hypothesize that BaP induces apoptosis and heart defects via AHR-mediated DNA damage. In this study, zebrafish embryos were exposed to BaP at a concentration of 0.1 μM from 2 to 72 h post fertilization, either with or without inhibitors/agonists. AHR activity and levels of reactive oxygen species (ROS) were examined under a fluorescence microscope. mRNA expression levels were quantified by qPCR. DNA damage and apoptosis were detected by immunofluorescence. Our findings revealed that BaP exposure significantly increased BPDE-DNA adducts, mitochondrial damage, apoptosis and heart defects in zebrafish embryos. These effects were counteracted by inhibiting AHR/cyp1a1 using pharmaceutical inhibitors or genetic knockdown. Furthermore, we observed that spironolactone, an antagonist of nucleotide excision repair (NER), significantly enhanced BaP-induced BPDE-DNA adducts, mitochondrial damage, apoptosis and heart malformation rates. Conversely, SRT1720, a SIRT1 agonist, reduced the adverse effects of BaP. Supplementation with spironolactone also enhanced γ-H2AX signals in the heart of zebrafish embryos exposed to BaP. Additional experiments demonstrated that BaP suppressed the expression of SIRT1. We further established that AHR, when activated by BaP, directly inhibited SIRT1 transcription, leading to downregulation of XPC and XPA, which are essential NER genes involved in the recognition and verification steps of the NER process. Taken together, our results indicate that AHR mediates BaP-induced DNA damage in the heart of zebrafish embryos by inducing BPDE-DNA adduct formation via the AHR/Cyp1a1 signalling pathway, as well as suppressing NER via AHR-mediated inhibition of SIRT1.

Comparison of the methylglyoxal scavenging effects of kaempferol and glutathione and the consequences for the toxicity of methylglyoxal in SH-SY5Y cells

This study aimed to characterize the methylglyoxal (MGO) scavenging capacity of glutathione (GSH) and kaempferol in more detail with special emphasis on the possible reversible nature of the adduct formation and their competition for MGO, and the safety consequences of their MGO-scavenging effects. GSH showed immediate and concentration-dependent MGO-scavenging effects, while the scavenging effects by kaempferol appeared concentration- but also time-dependent, with stable adducts formed over time. The GSH adduct gradually disappeared in a competition reaction with kaempferol, and kaempferol became the preferred scavenger over time. Furthermore, the scavenging of MGO by kaempferol provided better protection than GSH against extracellular MGO in SH-SY5Y cells. It is concluded that flavonoids like kaempferol provide better scavengers for food-borne MGO than thiol-based scavengers such as GSH, while, given the endogenous concentrations of both scavengers and the detoxification of the GSH-MGO adduct by the glyoxalase system, GSH will be dominant for intracellular MGO protection.

Autoreactive B cells against malondialdehyde-induced protein cross-links are present in the joint, lung, and bone marrow of rheumatoid arthritis patients

Autoantibodies to malondialdehyde (MDA) proteins constitute a subset of anti-modified protein autoantibodies in rheumatoid arthritis (RA), which is distinct from citrulline reactivity. Serum anti-MDA IgG levels are commonly elevated in RA and correlate with disease activity, CRP, IL6, and TNF-α. MDA is an oxidation-associated reactive aldehyde that together with acetaldehyde mediates formation of various immunogenic amino acid adducts including linear MDA-lysine, fluorescent malondialdehyde acetaldehyde (MAA)-lysine, and intramolecular cross-linking. We used single-cell cloning, generation of recombinant antibodies (n= 356 from 25 donors), and antigen-screening to investigate the presence of class-switched MDA/MAA+ B cells in RA synovium, bone marrow, and bronchoalveolar lavage. Anti-MDA/MAA+ B cells were found in bone marrow plasma cells of late disease and in the lung of both early disease and risk-individuals and in different B cell subsets (memory, double negative B cells). These were compared with previously identified anti-MDA/MAA from synovial memory and plasma cells. Seven out of eight clones carried somatic hypermutations and all bound MDA/MAA-lysine independently of protein backbone. However, clones with somatic hypermutations targeted MAA cross-linked structures rather than MDA- or MAA-hapten, while the germline-encoded synovial clone instead bound linear MDA-lysine in proteins and peptides. Binding patterns were maintained in germline converted clones. Affinity purification of polyclonal anti-MDA/MAA from patient serum revealed higher proportion of anti-MAA versus anti-MDA compared to healthy controls. In conclusion, IgG anti-MDA/MAA show distinct targeting of different molecular structures. Anti-MAA IgG has been shown to promote bone loss and osteoclastogenesis invivo and may contribute to RA pathogenesis.

Antibactericidal Ir(III) and Ru(II) Complexes with Phosphine-Alkaloid Conjugate and Their Interactions with Biomolecules: A Case of N-Methylphenethylamine.

The phosphine ligand (Ph2 PCH2 N(CH3 )(CH2 )2 Ph, PNMPEA) obtained by the reaction of the (hydroxymethyl)diphenylphosphine with naturally occurring alkaloid N-methylphenethylamine, was used to synthesize the half-sandwich iridium(III) (Ir(η5 -Cp*)Cl2 Ph2 PCH2 N(CH3 )(CH2 )2 Ph, IrPNMPEA) and ruthenium(II) (Ru(η6 -p-cymene)Cl2 Ph2 PCH2 N(CH3 )(CH2 )2 Ph, RuPNMPEA) complexes. They were characterized using a vast array of methods, including 1D and 2D NMR, ESI(+)MS spectrometry, elemental analysis, cyclic voltammetry (CV), electron spectroscopy in the UV-Vis range (absorption, fluorescence) and density functional theory (DFT). The initial antimicrobial activity in vitro toward Gram-positive and Gram-negative bacterial strains was examined, indicating that both complexes are selective towards Gram-positive bacteria, e. g., Staphylococcus aureus, where the IrPNMPEA has been more bactericidal compared to RuPNMPEA. Additionally, the interactions of these compounds with various biomolecules, such as DNA (ctDNA, plasmid DNA, 9-ethylguanine (9-EtG), and 9-methyladenine (9-MeA)), nicotinamide adenine dinucleotide (NADH), glutathione (GSH), and ascorbic acid (Asc) were described. The results showed that both Ir(III) and Ru(II) complexes accelerate the oxidation process of NADH, GSH and Asc that appeared to occur by an electron transfer mechanism. Interestingly, only IrPNMPEA leads to the formation of various biomolecule adducts, which can explain its higher activity. Furthermore, RuPNMPEA and IrPNMPEA have been interacting with the DNA through weak noncovalent interactions.

COMPLEXES OF p-METHOXYPHENYLTELLURIUM TRICHLORIDE WITH ALLYL THIOETHERS OF 5-ARYL-1,3,4-OXADIAZOLE

1,3,4-Oxadiazole and its functional derivatives have a wide spectrum of biological activity. There are well-known examples of the use of oxadiazoles in materials science as high-energy molecules. Therefore, the synthesis of new functional derivatives based on them is an urgent problem. This paper describes the synthesis of allylic thioethers of 5-nitrophenyl-1,3,4-oxadiazole by the alkylation reaction of the corresponding thiones with allyl bromide in an alcohol-alkaline medium. Such thioethers were studied in reactions with phenylselentrihalides, as a result of which oxadiazolo[2,3-d][1,3,4]thiaselenazinium halides were synthesized. We investigated the interaction of the tellurium-containing analogue p-methoxyphenyltellurium trichloride with allylic thioethers of 5-nitrophenyl-1,3,4-oxadiazole. It was established that the reaction between p-methoxyphenyl tellurium trichloride and the investigated alkenyl thioethers within 8 hours occurs with the formation of adducts of the substrate-electrophile composition 1:1, regardless of the ratio of reagents. Attempts to change the polarity of the solvent, increase the reaction time, and change the temperature regime did not change the direction of the reaction. Based on the obtained experimental spectral data and elemental analysis data, the structure of the obtained complexes is proposed.
 Keywords: p-methoxyphenyltellurium trichloride; 1,3,4-oxadiazole; allyl thioethers; organotellurium compounds; molecular complexes.

Precarcinogens in food – Mechanism of action, formation of DNA adducts and preventive measures

Food quality and food composition play key roles in human health. Food may contain harmful ingredients apart from the basic ingredients beneficial to our body. A harmful group of substances entering food from the environment are heavy metals and pesticides. Other toxicants, such as mycotoxins are produced during action of microorganisms contaminating food. The second group of compounds, including heterocyclic aromatic amines, nitrosamines, and acrylamide are formed in food during its processing or improper storage. Due to metabolic activation, these substances are transformed into precancerogens, i.e. electrophilic derivatives that finally form DNA adducts. DNA sites susceptible to the action of electrophilic compounds are atoms with a slight negative charge, especially the N7 position of guanine and N3 of adenine. These modifications may result in various mutations, and consequently, may lead to cancer development. This paper presents the general characteristics of main precancerogens, such as mycotoxins, polyaromatic hydrocarbons, heterocyclic aromatic amines, nitrosamines, and acrylamide present in various food products, formation of specific adducts of these substances with DNA, as well as describes biological consequences of adducts formation. Moreover, different strategies for reducing the levels of these contaminants in food material are discussed.

Reactivity Analysis of the [2 + 2] Cycloaddition between Group-6 ≡ Group-14 Triple-Bonded Complexes and Acetylene: Insights from Theoretical Studies.

Theoretical examinations of reactivity for the formal [2 + 2] cycloaddition of Me-C≡C-Ph to Group-6(G6)≡Group-14(G14) triple-bonded organometallic complexes have been carried out using the M06-2X-D3/def2-TZVP level of theory. Our theoretical findings suggest that Me-C≡C-Ph can undergo adduct formation with all G6≡Si complexes, resulting in the generation of four-membered ring structures. However, among the W≡Group-14 complex reactants, only W≡Si-based, W≡Ge-based, and W≡Sn-based organometallic molecules are capable of undergoing a [2 + 2] cycloaddition reaction with Me-C≡C-Ph. Based on energy decomposition analysis, our theoretical investigations demonstrate that the bonding mechanism in such [2 + 2] cycloaddition reactions involves the creation of two dative bonds between singlet fragments (the donor-acceptor model), as opposed to two electron-sharing bonds between triplet fragments. In addition, the examinations based on the activation strain model indicate that the activation barrier of the [2 + 2] cycloaddition reaction is predominantly governed by the geometric deformation energy of the two reactants (G6≡G14-Rea and Me-C≡C-Ph). Our research using the M06-2X method shows that the barrier heights of [2 + 2] cycloaddition reactions between Me-C≡C-Ph and G6≡Si-Rea are dependent on the geometric changes occurring in both fragments during the transition states, consistent with Hammond's postulate.

On the Reactivity of a NHC Nickel Bis-Boryl Complex: Reductive Elimination and Formation of Mono-Boryl Complexes.

The synthesis of the first terminal mono-boryl complexes of nickel, which are not stabilized by a pincer ligand, is reported. The reaction of the nickel bis-boryl complex cis-[Ni(iPr2ImMe)2(Bcat)2] 1 (cat = 1,2-O2C6H4) with the small donor ligand PMe3 led to a complete ligand exchange at nickel with reductive elimination of B2cat2, formation of the bisNHC adduct [B2cat2 · (iPr2ImMe)2] 3 and formation of [Ni(PMe3)4] 2 as the metal-containing species. Electrophilic attack of MeI on complex 1 or ligand dismutation of 1 with trans[Ni(iPr2ImMe)2Br2] led to loss of only one boryl ligand of 1 and afforded the nickel mono-boryl complexes trans-[Ni(iPr2ImMe)2(Bcat)Br] 4a and trans-[Ni(iPr2ImMe)2(Bcat)I] 4b.

Binding of Stimuli-Responsive Ruthenium Aqua Complexes with 9-Ethylguanine.

Stimuli-responsive ruthenium complexes proximal- and distal-[Ru(C10tpy)(C10pyqu) OH2]2+ (proximal-1 and distal-1; C10tpy = 4'-decyloxy-2,2':6',2″-terpyridine and C10pyqu = 2-[2'-(6'-decyloxy)-pyridyl]quinoline) were experimentally studied for adduct formation with a model DNA base. At 303 K, proximal-1 exhibited 1:1 adduct formation with 9-ethylguanine (9-EtG) to yield proximal-[Ru(C10tpy)(C10pyqu)(9-EtG)]2+ (proximal-RuEtG). Rotation of the guanine ligand on the ruthenium center was sterically hindered by the presence of an adjacent quinoline moiety at 303 K. Results from 1H NMR measurements indicated that photoirradiation of a proximal-RuEtG solution caused photoisomerization to distal-RuEtG, whereas heating of proximal-RuEtG caused ligand substitution to proximal-1. The distal isomer of the aqua complex, distal-1, was observed to slowly revert to proximal-1 at 303 K. In the presence of 9-EtG, distal-1 underwent thermal back-isomerization to proximal-1 and adduct formation to distal-RuEtG. Kinetic analysis of 1H NMR measurements showed that adduct formation between proximal-1 and 9-EtG was 8-fold faster than that between distal-1 and 9-EtG. This difference may be attributed to intramolecular hydrogen bonding and steric repulsion between the aqua ligand and the pendant moiety of the bidentate ligand..

The Lipid Metabolism as Target and Modulator of BOLD-100 Anticancer Activity: Crosstalk with Histone Acetylation.

The leading first-in-class ruthenium-complex BOLD-100 currently undergoes clinical phase-II anticancer evaluation. Recently, BOLD-100 is identified as anti-Warburg compound. The present study shows that also deregulated lipid metabolism parameters characterize acquired BOLD-100-resistant colon and pancreatic carcinoma cells. Acute BOLD-100 treatment reduces lipid droplet contents of BOLD-100-sensitive but not -resistant cells. Despite enhanced glycolysis fueling lipid accumulation, BOLD-100-resistant cells reveal diminished lactate secretion based on monocarboxylate transporter 1 (MCT1) loss mediated by a frame-shift mutation in the MCT1 chaperone basigin. Glycolysis and lipid catabolism converge in the production of protein/histone acetylation substrate acetyl-coenzymeA (CoA). Mass spectrometric and nuclear magnetic resonance analyses uncover spontaneous cell-free BOLD-100-CoA adduct formation suggesting acetyl-CoA depletion as mechanism bridging BOLD-100-induced lipid metabolism alterations and histone acetylation-mediated gene expression deregulation. Indeed, BOLD-100 treatment decreases histone acetylation selectively in sensitive cells. Pharmacological targeting confirms histone de-acetylation as central mode-of-action of BOLD-100 and metabolic programs stabilizing histone acetylation as relevant Achilles' heel of acquired BOLD-100-resistant cell and xenograft models. Accordingly, histone gene expression changes also predict intrinsic BOLD-100 responsiveness. Summarizing, BOLD-100 is identified as epigenetically active substance acting via targeting several onco-metabolic pathways. Identification of the lipid metabolism as driver of acquired BOLD-100 resistance opens novel strategies to tackle therapy failure.

Revealing the crucial role of Carbon-Centered radicals in UV/PAA process for trace amounts of organic contaminants removal

Peracetic acid (PAA) is a promising peroxyacid to combine with ultraviolet (UV) to eliminate trace amounts of organic contaminants (TrOCs), with growing importance in water treatment. In spite of a large number of research on UV/PAA process, the underlying mechanism still require further investigation, due to the difficulties in analyzing the carbon-centered radicals. Here we demonstrated the crucial roles of the carbon-centered radicals (namely CH3C(O)OO), via electron paramagnetic resonance (EPR) and kinetic models, with concentration of 4 orders magnitude higher than that of OH. Then, the theoretical calculation using density functional theory (DFT) showed that CH3C(O)OO and OH tended to attack phenol mostly through the route of radical adduct formation. The generated CH3C(O)OO and OH adducts may undergo further reactions to produce catechol and hydroquinone. Further, the environmental applicability of UV/PAA process for TrOC abatement was evaluated, including the effects of pH, PAA dosage, water constituents, as well as the variation of acute toxicity. Different from the OH-dominated process, kinetic analysis revealed that CH3C(O)OO was almost immune to the presence of water constituents, leading to the outperformance of UV/PAA process in actual water samples. Our present study could inform the application of UV/PAA process in water and wastewater treatment.

BPDE-DNA adduct formation and alterations of mRNA, protein, and DNA methylation of CYP1A1, GSTP1, and GSTM1 induced by benzo[a]pyrene and the intervention of aspirin in mice.

Benzo[a]pyrene (B[a]P), one typical environmental pollutant, the toxicity mechanisms, and potential prevention remain perplexing. Available evidence suggests cytochrome P450 1A1 (CYP1A1) and glutathione S-transferases (GSTs) metabolize B[a]P, resulting in metabolic activation and detoxification of B[a]P. This study aimed to reveal the impact of B[a]P exposure on trans-7,8-diol-anti-9,10-epoxide DNA (BPDE-DNA) adduct formation, level of CYP1A1, glutathione S-transferase pi (GSTP1) and glutathione S-transferase mu1 (GSTM1) mRNA, protein and DNA methylation in mice, and the potential prevention of aspirin (ASP). This study firstly determined the BPDE-DNA adduct formation in an acute toxicity test of a large dose in mice induced by B[a]P, which subsequently detected CYP1A1, GSTP1, and GSTM1 at levels of mRNA, protein, and DNA methylation in the organs of mice in a subacute toxicity test at appropriate doses and the potential prevention of ASP, using the methods of real-time quantitative PCR (QPCR), western blotting, and real-time methylation-specific PCR (MSP), respectively. The results verified that B[a]P induced the formation of BPDE-DNA adduct in all the organs of mice in an acute toxicity test, and the order of concentration of which was lung > kidney > liver > brain. In a subacute toxicity test, following B[a]P treatment, mice showed a dose-dependent slowdown in body weight gain and abnormalities in behavioral and cognitive function and which were alleviated by ASP co-treatment. Compared to the controls, following B[a]P treatment, CYP1A1 was significantly induced in all organs in mice at mRNA level (P < 0.05), was suppressed in the lung and cerebrum of mice at protein level, and inhibited at DNA methylation level in the liver, lung, and cerebrum, whereas GSTP1 and GSTM1 at mRNA, protein, and DNA methylation levels showed organ-specific changes in mice following B[a]P treatment, which was generally alleviated by ASP intervention. In conclusion, B[a]P induced BPDE-DNA adduct formation in all organs in mice and altered the mRNA, protein, and DNA methylation levels in CYP1A1, GSTP1, and GSTM1 in an organ-dependent pattern, which could be related to the organ toxicity and mechanism of B[a]P. ASP intervention may be an effective measure to prevent B[a]P toxicity. The findings provide scientific evidence for further study on the organ toxicity and mechanisms of B[a]P.

Dose-response formation of N7-(3-benzo[1,3]dioxol-5-yl-2-hydroxypropyl)guanine in liver and urine correlates with micronucleated reticulocyte frequencies in mice administered safrole oxide

Safrole oxide (SAFO), a metabolite of naturally occurring hepatocarcinogen safrole, is implicated in causing DNA adduct formation. Our previous study first detected the most abundant SAFO-induced DNA adduct, N7-(3-benzo[1,3] dioxol-5-yl-2-hydroxypropyl)guanine (N7γ-SAFO-G), in mouse urine using a well-developed isotope-dilution high-performance liquid chromatography-electrospray ionization tandem mass spectrometry (ID-HPLC-ESI-MS/MS) method. This study further elucidated the genotoxic mode of action of SAFO in mice treated with SAFO 30, 60, 90, or 120 mg/kg for 28 days. The ID-HPLC-ESI-MS/MS method detected N7γ-SAFO-G with excellent sensitivity and specificity in mouse liver and urine of SAFO-treated mice. Our data provide the first direct evidence of SAFO-DNA adduct formation in rodent tissues. N7γ-SAFO-G levels in liver were significantly increased by SAFO 120 mg/kg compared with SAFO 30 mg/kg, suggesting rapid spontaneous or enzymatic depurination of N7γ-SAFO-G in tissue DNA. Urinary N7γ-SAFO-G exhibited a sublinear dose response. Moreover, the micronucleated peripheral reticulocyte frequencies increased dose-dependently and significantly correlated with N7γ-SAFO-G levels in liver (r = 0.8647; p < 0.0001) and urine (r = 0.846; p < 0.0001). Our study suggests that safrole-mediated genotoxicity may be caused partly by its metabolic activation to SAFO and that urinary N7γ-SAFO-G may serve as a chemically-specific cancer risk biomarker for safrole exposure.

Distribution and Mobility of Amines Confined in Porous Silica Supports Assessed via Neutron Scattering, NMR, and MD Simulations: Impacts on CO2 Sorption Kinetics and Capacities.

ConspectusSolid-supported amines are a promising class of CO2 sorbents capable of selectively capturing CO2 from diverse sources. The chemical interactions between the amine groups and CO2 give rise to the formation of strong CO2 adducts, such as alkylammonium carbamates, carbamic acids, and bicarbonates, which enable CO2 capture even at low driving force, such as with ultradilute CO2 streams. Among various solid-supported amine sorbents, oligomeric amines infused into oxide solid supports (noncovalently supported) are widely studied due to their ease of synthesis and low cost. This method allows for the construction of amine-rich sorbents while minimizing problems, such as leaching or evaporation, that occur with supported molecular amines.Researchers have pursued improved sorbents by tuning the physical and chemical properties of solid supports and amine phases. In terms of CO2 uptake, the amine efficiency, or the moles of sorbed CO2 per mole of amine sites, and uptake rate (CO2 capture per unit time) are the most critical factors determining the effectiveness of the material. While structure-property relationships have been developed for different porous oxide supports, the interaction(s) of the amine phase with the solid support, the structure and distribution of the organic phase within the pores, and the mobility of the amine phase within the pores are not well understood. These factors are important, because the kinetics of CO2 sorption, particularly when using the prototypical amine oligomer branched poly(ethylenimine) (PEI), follow an unconventional trend, with rapid initial uptake followed by a very slow, asymptotic approach to equilibrium. This suggests that the uptake of CO2 within such solid-supported amines is mass transfer-limited. Therefore, improving sorption performance can be facilitated by better understanding the amine structure and distribution within the pores.In this context, model solid-supported amine sorbents were constructed from a highly ordered, mesoporous silica SBA-15 support, and an array of techniques was used to probe the soft matter domains within these hybrid materials. The choice of SBA-15 as the model support was based on its ordered arrangement of mesopores with tunable physical and chemical properties, including pore size, particle lengths, and surface chemistries. Branched PEI─the most common amine phase used in solid CO2 sorbents─and its linear, low molecular weight analogue, tetraethylenepentamine (TEPA), were deployed as the amine phases. Neutron scattering (NS), including small angle neutron scattering (SANS) and quasielastic neutron scattering (QENS), alongside solid-state NMR (ssNMR) and molecular dynamics (MD) simulations, was used to elucidate the structure and mobility of the amine phases within the pores of the support. Together, these tools, which have previously not been applied to such materials, provided new information regarding how the amine phases filled the support pores as the loading increased and the mobility of those amine phases. Varying pore surface-amine interactions led to unique trends for amine distributions and mobility; for instance, hydrophilic walls (i.e., attractive to amines) resulted in hampered motions with more intimate coordination to the walls, while amines around hydrophobic walls or walls with grafted chains that interrupt amine-wall coordination showed recovered mobility, with amines being more liberated from the walls. By correlating the structural and dynamic properties with CO2 sorption properties, novel relationships were identified, shedding light on the performance of the amine sorbents, and providing valuable guidance for the design of more effective supported amine sorbents.

Comprehensive Review of Red Meat Consumption and the Risk of Cancer.

Red and processed meat consumption rates are increasing in the United States. In this review, we present the current evidence that links red meat consumption and cancer development. A literature search was conducted in the PubMed and Google Scholar databases to review red meat consumption and its association with breast cancer and gastrointestinal cancer. Due to the presence of heme iron, which triggers oxidative reactions that eventually result in tumor formation, red meat consumption is strongly associated with the development of breast cancer. Ingestion of red meat increases Helicobacter pylori infections, resulting in enhanced expression of the CagA gene and the secretion of pro-inflammatory cytokines. This is the leading cause of gastric cancer. There is a strong correlation between heterocyclic amines and polycyclic aromatic hydrocarbons in red meat and the development of pancreatic cancer. However, additional research is necessary to confirm this finding. Adult colorectal cancer is caused by the formation of heterocyclic amines and DNA adducts due to the intake of red and processed meats cooked at higher temperatures. The consumption of poultry is associated with a reduced risk of breast and gastrointestinal cancers, but the results are inconsistent. The evidence is strong for the association between red meat and breast cancer and most gastric cancers. The presence of aromatic hydrocarbons, heterocyclic amines, and heme iron in red meat has been found to be behind tumorigenesis. Poultry has been shown to have a low association with cancer, but additional research is needed.

Short Survey on the Protein Modifications in Plasma during SARS-CoV-2 Infection.

Although the COVID-19 pandemic has ended, it is important to understand the pathology of severe SARS-CoV-2 infection associated with respiratory failure and high mortality. The plasma proteome, including protein modification by lipid peroxidation products in COVID-19 survivors (COVID-19; n = 10) and deceased individuals (CovDeath; n = 10) was compared in samples collected upon admission to the hospital, when there was no difference in their status, with that of healthy individuals (Ctr; n = 10). The obtained results show that COVID-19 development strongly alters the expression of proteins involved in the regulation of exocytosis and platelet degranulation (top 20 altered proteins indicated by analysis of variance; p-value (False Discovery Rate) cutoff at 5%). These changes were most pronounced in the CovDeath group. In addition, the levels of 4-hydroxynonenal (4-HNE) adducts increased 2- and 3-fold, whereas malondialdehyde (MDA) adducts increased 7- and 2.5-fold, respectively, in COVID-19 and CovDeath groups. Kinases and proinflammatory proteins were particularly affected by these modifications. Protein adducts with 15-deoxy-12,14-prostaglandin J2 (15d-PGJ2) were increased 2.5-fold in COVID-19 patients, including modifications of proteins such as p53 and STAT3, whereas CovDeath showed a decrease of approximately 60% compared with Ctr. This study for the first time demonstrates the formation of lipid metabolism products-protein adducts in plasma from survived and deceased COVID-19 patients, significantly distinguishing them, which may be a predictor of the course of SARS-CoV-2 infection.

Analysis of Pesticide Residues on Fruit Using Swab Spray Ionization Mass Spectrometry.

The vast quantity and high variety of pesticides globally used in agriculture entails considerable risks for the environment and requires ensuring the safety of food products. Therefore, powerful analytical tools are needed to acquire qualitative and quantitative data for monitoring pesticide residues. The development of ambient ionization mass spectrometry methods in the past two decades has demonstrated numerous ways to generate ions under atmospheric conditions and simultaneously to reduce the need for extended sample preparation and circumvent chromatographic separation prior to mass analysis. Swab spray ionization enables the generation of ions directly from swabs via the application of high voltage and solvent flow. In this study, swab sampling of fruit surfaces and subsequent ionization directly from the swab in a modified electrospray ion source was employed for the screening and quantitation of pesticide residues. Aspects regarding sample collection, sampling efficacy on different surfaces, and swab background are discussed. The effect of solvent composition on pesticide-sodium adduct formation and the suppression of ionization by the background matrix have been investigated. Furthermore, a novel approach for the quantitation of pesticide residues based on depletion curve areas is presented. It is demonstrated that swab spray ionization is an effective and quick method for spectral library-based identification and the quantitative analysis of polar contact pesticide residues on food.

Antiglycation, antifibrillation and antioxidative effects of para coumaric acid and vitamin D; an in-vitro and in-silico comparative-cum-synergistic approach

Diabetes Mellitus is a metabolic disorder that results in impaired utilization of carbohydrates, lipids, and proteins. Severe hyperglycemia is its principal clinical symptom. Human serum albumin (HSA) is used as a model protein since it is viewed as a sign of glycaemic management because it is more likely to get glycated in diabetic people than other proteins. Para-coumaric acid (pCA), a phenolic acid, and Vitamin D (vit-D) are used as protective agents. In the present work, we deduce a synergistic-cum-comparative effect of pCA and vit-D, expecting some improvement in the efficacy of pCA when combined with vit-D. Methods employed are DPPH radical scavenging activity, In-vitro glycation of HSA, UV–vis spectroscopy, fluorescence analysis, and circular dichroism measurement. After treatment, increasein the absorbance and fluorescence intensity were reduced along with normalization of CD value. . The glycation-mediated fibrillation assessed by Congo-Red and Thioflavin T (ThT) were found to be diminishedwhen HSA was treated with equimolar concentration of p-CA and vit-D- treatment. Fructosamine adduct formation and lysine modificationwas also decreased, while inhibition to hemolysis and lipid peroxidation was found to increase upon treatment. The reactive oxygen species generation detection was also performed in lymphocytes treated with various protein samples. Docking results further confirmed theblocking some glycation-prone amino acids by both compounds. The study shows that the combination in the ratio of 1:1 has provided higher overall protection comparable to aminoguanidine (AG), the molecule which is utilized as a positive control.

A reaction-based carbazole-dicyanovinyl conjugated colorimetric and ratiometric fluorescent probe for selective detection of cyanide ions

In the present work, 4-(9′-hexylcarbazol-3′-yl)benzylidenemalononitrile 5 (probe L) was tested as a colorimetric and ratiometric fluorescent probe in dimethyl sulfoxide (DMSO) medium towards anions, cations and neutral molecules. The sensing properties of probe L were investigated by using UV–Vis absorption and fluorescence spectroscopy techniques. Probe L showed selectivity and sensitivity towards cyanide ions (CN–) in the presence of analytes used. Upon the addition of CN–, intramolecular charge transfer (ICT) band at 425 nm in UV spectrum disappeared. In addition, ICT emission intensity at 593 nm decreased and ligand-centred (LC) emission intensity at 480 nm increased. These findings indicate that nucleophilic conjugate addition of CN– to the dicyanovinyl group of probe L successfully occurs, hence forming a new adduct between probe L and CN–. In this adduct, π-conjugation was partially blocked, and the ICT transfer was hindered. Adduct formation was proved by Job’s plot, 1H NMR and FT-IR analysis. Probe L showed very low limit of detection (LOD) value of 1.467 nM towards CN–. Probe L was also applied to the CN– detection in real-world water samples by the spike and recovery method. The maximum relative standard deviation (RSD) value was 4.24, indicating this method works successfully. Therefore, probe L could find a potential use in detection of CN– in liquid media.

Continuous Flow Oxidation of Alcohols Using TEMPO/NaOCl for the Selective and Scalable Synthesis of Aldehydes.

A simple and benign continuous flow oxidation protocol for the selective conversion of primary and secondary alcohols into their respective aldehyde and ketone products is reported. This approach makes use of catalytic amounts of TEMPO in combination with sodium bromide and sodium hypochlorite in a biphasic solvent system. A variety of substrates are tolerated including those containing heterocycles based on potentially sensitive nitrogen and sulfur moieties. The flow approach can be coupled with inline reactive extraction by formation of the carbonyl-bisulfite adduct which aids in separation of remaining substrate or other impurities. Process robustness is evaluated for the preparation of phenylpropanal at decagram scale, a trifluoromethylated oxazole building block as well as a late-stage intermediate for the anti-HIV drug maraviroc which demonstrates the potential value of this continuous oxidation method.