Reactive Carbonyl Research Articles

Exploring the impact of malondialdehyde and 4-hydroxy-2-nonena on myofibrillar protein structure: A proteomic analysis

In this investigation, the impacts of malondialdehyde (MDA), 4-hydroxy-2-nonena (HNE), and their combinations on the structural characteristics of myofibrillar proteins (MP) were examined using endogenous fluorescence, Fourier transform infrared spectrum (FTIR) and Sodium Dodecyl Sulfate Polyacrylamide Gel Electrophoresis (SDS-PAGE). The potential binding mechanisms were also explored using LC-MS/MS and proteomics techniques. The findings indicated that various reactive carbonyl compounds (RCCs) displayed distinct oxidation performances in the oxidation of myofibrillar proteins. Samples containing HNE (HMP and MHMP groups) exhibited a more pronounced ability to oxidize MP than those containing MDA, as evidenced by their higher carbonyl content and lower sulfhydryl content. The MHMP group demonstrated the greatest surface hydrophobicity and Schiff base content but the lowest fluorescence intensity, suggesting that MDA and HNE synergistically altered MP conformation. Moreover, the alteration by RCCs notably modified the secondary structure of MP. Among these, HMP triggered the unfolding of MP molecules, resulting in the lowest α-helix and highest β-sheet ratio. The SDS‒PAGE results suggested that MDA oxidation promoted the crosslinking of MP molecules. At the same time, HNE caused the degradation of MP, as indicated by the decrease in the intensity of the high-molecular-weight bands. Proteomic analysis suggested that lysine residues distributed in the tail region of myosin were the main binding sites for MDA, whereas HNE preferentially modified methionine located at the myosin head. Additionally, HNE-induced protein degradation dominated RCC-induced oxidation reactions. These findings provide deeper insights into the mechanisms underlying quality changes induced by lipid oxidation products in MP-based food systems.

Molecular dynamics of structural effects of reactive carbonyl species derivate of lipid peroxidation on bovine serum albumin

BackgroundSerum albumin is the most abundant protein in the Mammalia blood plasma at where plays a decisive role in the transport wide variety of hydrophobic ligands. BSA undergoes oxidative modifications like the carbonylation by the reactive carbonyl species (RCSs) 4-hydroxy-2-nonenal (HNE), 4 hydroxy-2-hexenal (HHE), malondialdehyde (MDA) and 4-oxo-2-nonenal (ONE), among others. The structural and functional changes induced by protein carbonylation have been associated with the advancement of neurodegenerative, cardiovascular, metabolic and cancer diseases. MethodsTo elucidate structural effects of protein carbonylation with RCSs on BSA, parameters for six new non-standard amino acids were designated and molecular dynamics simulations of its mono‑carbonylated-BSA systems were conducted in the AMBER force field. Trajectories were evaluated by RMSD, RMSF, PCA, RoG and SASA analysis. ResultsAn increase in the conformational instability for all proteins modified with local changes were observed, without significant changes on the BSA global three-dimensional folding. A more relaxed compaction level and major solvent accessible surface area for modified systems was found. Four regions of high molecular fluctuation were identified in all modified systems, being the subdomains IA and IIIB those with the most remarkable local conformational changes. Regarding essential modes of domain movements, it was evidenced that the most representatives were those related to IA subdomain, while IIIB subdomain presented discrete changes. ConclusionsRCSs induces local structural changes on mono‑carbonylated BSA. Also, this study extends our knowledge on how carbonylation by RCSs induce structural effects on proteins.

Ginsenoside Re protects against kainate-induced neurotoxicity in mice by attenuating mitochondrial dysfunction through activation of the signal transducers and activators of transcription 3 signaling

It was demonstrated that ginsenosides exert anti-convulsive potentials and interleukin-6 (IL-6) is protective from excitotoxicity induced by kainate (KA), a model of temporal lobe epilepsy. Ginsenosides-mediated mitochondrial recovery is essential for attenuating KA-induced neurotoxicity, however, little is known about the effects of ginsenoside Re (GRe), one of the major ginsenosides. In this study, GRe significantly attenuated KA-induced seizures in mice. KA-induced redox changes were more evident in mitochondrial fraction than in cytosolic fraction in the hippocampus of mice. GRe significantly attenuated KA-induced mitochondrial oxidative stress (i.e. increases in reactive oxygen species, 4-hydroxynonenal, and protein carbonyl) and mitochondrial dysfunction (i.e. the increase in intra-mitochondrial Ca2+ and the decrease in mitochondrial membrane potential). GRe or mitochondrial protectant cyclosporin A restored phospho-signal transducers and activators of transcription 3 (STAT3) and IL-6 levels reduced by KA, and the effects of GRe were reversed by the JAK2 inhibitor AG490 and the mitochondrial toxin 3-nitropropionic acid (3-NP). Thus, we used IL-6 knockout (KO) mice to investigate whether the interaction between STAT3 and IL-6 is involved in the GRe effects. Importantly, KA-induced reduction of manganese superoxide dismutase (SOD-2) levels and neurodegeneration (i.e. astroglial inhibition, microglial activation, and neuronal loss) were more prominent in IL-6 KO than in wild-type (WT) mice. These KA-induced detrimental effects were attenuated by GRe in WT and, unexpectedly, IL-6 KO mice, which were counteracted by AG490 and 3-NP. Our results suggest that GRe attenuates KA-induced neurodegeneration via modulating mitochondrial oxidative burden, mitochondrial dysfunction, and STAT3 signaling in mice.

Effect of levan polysaccharide on chronological aging in the yeast Saccharomyces cerevisiae

Levan is a fructose-based biopolymer with diverse applications in the medicinal, pharmaceutical, and food industries. However, despite its extensive biological and pharmacological actions, including antioxidant, anti-inflammatory, and antidiabetic properties, research on its anti-aging potential is limited. This study explored levan's impact on the chronological lifespan (CLS) of yeast Saccharomyces cerevisiae for the first time. The results show that levan treatment significantly extended the CLS of wild-type (WT) yeast by preventing the accumulation of oxidative stress markers (reactive oxygen species, malondialdehyde, and protein carbonyl content) and ameliorating apoptotic features such as reduced mitochondrial membrane potential, loss of plasma membrane integrity, and externalization of phosphatidylserine. By day 40 of the CLS, a significant increase in yeast viability of 6.8 % (p < 0.01), 11.9 % (p < 0.01), and 20.8 % (p < 0.01) was observed at 0.25, 0.5, and 1 mg/mL of levan concentrations, respectively, compared to control (0 %). This study's results indicate that levan treatment substantially modulates the expression of genes involved in the TORC1/Sch9 pathway. Moreover, levan treatment significantly extended the CLS of yeast antioxidant-deficient mutant sod2Δ and antiapoptotic gene-deficient mutant pep4Δ. Levan also extended the CLS of signaling pathway gene-deficient mutants such as pkh2Δ, rim15Δ, atg1, and ras2Δ, while not affecting the CLS of tor1Δ and sch9Δ.

Aflatoxin B1 decreased flesh flavor and inhibited muscle development in grass carp (Ctenopharyngodon idella)

In nature, aflatoxins, especially aflatoxin B1 (AFB1), are the common mycotoxins, which cause serious health problems for humans and animals. This paper aimed to study the effects of AFB1 on flesh flavor and muscle development of grass carp (Ctenopharyngodon idella) and its mechanism. There were 1440 individual fish in total, with 6 treatments and each treatment replicated 3 times. The 6 treatments were fed a control diet with different doses of AFB1 (0.04, 29.48, 58.66, 85.94, 110.43 and 146.92 μg/kg diet) for 60 d. AFB1 increased myofiber diameter, as well as decreased myofiber density of grass carp muscle (P < 0.05). The contents of free amino acid decreased gradually (P < 0.05) as dietary AFB1 increased in the muscle of grass carp. The levels of reactive oxygen species, malonaldehyde and protein carbonyl (PC) were increased (P < 0.05) with the dietary AFB1 increased. The levels of antioxidant enzyme (glutathione peroxidase, glutathione, glutathione reductase, total antioxidant capacity, anti-superoxide anion, and anti-hydroxyl radical) were decreased (P < 0.05) with the dietary AFB1 increased. In addition, dietary AFB1 decreased the content of collagen, and downregulated the mRNA and protein levels of transforming growth factor-β (TGF-β)/Smads signaling pathway in grass carp muscle (P < 0.05). The mRNA and protein levels of myogenic regulatory factors were downregulated in grass carp muscle (P < 0.05). Furthermore, the activities of matrix metalloproteinase-2 (MMP-2) and matrix metalloproteinase-9 (MMP-9) were increased (P < 0.05), and the protein levels of phosphorylate-38 mitogen-activated protein kinase (p-p38MAPK), phosphorylate-c-Jun N-terminal kinase, urokinase-type plasminogen activator (uPA), MMP-2 and MMP-9 were upregulated (P < 0.05), but collagen Ⅰ, laminin β1 and fibronectin were downregulated (P < 0.05) with the dietary AFB1 increased in the muscle of grass carp. Based on the results of this study, we can draw the following conclusion: dietary AFB1 might damage flesh flavor and inhibit the muscle development through MAPK/uPA/MMP/extracellular matrix (ECM) signaling pathway in grass carp. Moreover, the recommended safe limit of AFB1 in feed is no more than 26.77 μg/kg diet according to the PC levels in grass carp muscle.

Динаміка показників оксидантно-антиоксидантних реакцій у післяопераційному періоді у хворих на поширений перитоніт

Purpose - to determine the effect of the developed treatment of patients with peritonitis on the dynamics of indicators of oxidant-antioxidant reactions and to justify the need for the use of the proposed drugs in the complex treatment of peritonitis. Matherials and methods. The study included 124 patients with toxic and terminal stages of peritonitis, who were divided into 3 groups: the Group I included 39 patients in whose complex treatment we included cytochrome C; the Group II included 41 patients whose complex treatment included cytochrome C and a solution containing levocarnitine and arginine hydrochloride; the Comparison group included 44 patients in whom the specified drugs were not used. The content of diene conjugates, reactive oxygen species (ROS), S-nitrosothiols, superoxide dismutase (SOD), carbonyl groups, and sodium nitrite was determined in the patients. Statistical processing of the study results was performed using the Statistical software EZR v. 1.64. Results. In patients of the Group I and the Group II, the use of the proposed treatment contributed to the optimization of oxidant-antioxidant reactions: a decrease in the production of diene conjugates, ROS, S-nitrosothiols, carbonyl groups, sodium nitrite during the study, optimization of SOD production, especially in the Group II. In patients of the Comparison group, decompensation in oxidant-antioxidant reactions was determined, associated with a significant increase in the production of diene conjugates, ROS, S-nitrosothiols and a decrease in SOD during the entire period. These trends developed against the background of an increase in the content of nitric oxide products and the activation of processes associated with the oxidative modification of blood plasma proteins. Conclusions. The use of cytochrome C and a solution containing levocarnitine and arginine hydrochloride in the complex treatment of patients with disseminated peritonitis helps to optimize oxidant-antioxidant reactions, which leads to a decrease in the manifestations of inflammation. The research was carried out in accordance with the principles of the Helsinki Declaration. The study protocol was approved by the Local Ethics Committee of all participating institutions. The informed consent of the patient was obtained for conducting the studies. No conflict of interests was declared by the authors.

Building an Understanding of Proteostasis in Reproductive Cells: The Impact of Reactive Carbonyl Species on Protein Fate.

Significance: Stringent regulation of protein homeostasis pathways, under both physiological and pathological conditions, is necessary for the maintenance of proteome fidelity and optimal cell functioning. However, when challenged by endogenous or exogenous stressors, these proteostasis pathways can become dysregulated with detrimental consequences for protein fate, cell survival, and overall organism health. Most notably, there are numerous somatic pathologies associated with a loss of proteostatic regulation, including neurodegenerative disorders, type 2 diabetes, and some cancers. Recent Advances: Lipid oxidation-derived reactive carbonyl species (RCS), such as 4-hydroxynonenal (4HNE) and malondialdehyde, are relatively underappreciated purveyors of proteostatic dysregulation, which elicit their effects via the nonenzymatic post-translational modification of proteins. Emerging evidence suggests that a subset of germline proteins can serve as substrates for 4HNE modification. Among these, prevalent targets include succinate dehydrogenase, heat shock protein A2 and A-kinase anchor protein 4, all of which are intrinsically associated with fertility. Critical Issues: Despite growing knowledge in this field, the RCS adductomes of spermatozoa and oocytes are yet to be comprehensively investigated. Furthermore, the manner by which RCS-mediated adduction impacts protein fate and drives cellular responses, such as protein aggregation, requires further examination in the germline. Given that RCS-protein adduction has been attributed a role in infertility, there has been sparked research investment into strategies to prevent lipid peroxidation in germ cells. Future Directions: An increased depth of knowledge regarding the mechanisms and substrates of RCS-mediated protein modification in reproductive cells may reveal important targets for the development of novel therapies to improve fertility and pregnancy outcomes for future generations.

Reactive Carbonyl Species Scavenger: Epigallocatechin-3-Gallate.

Epigallocatechin-3-gallate (EGCG), a prominent polyphenol found abundantly in tea, has garnered significant attention for its potential in preventing and ameliorating a wide range of diseases. Its remarkable antioxidant properties and ability to capture reactive carbonyl species make it a key player among tea's polyphenolic components. This paper delves into the synthesis and origins of both EGCG and reactive carbonyl species (RCS), emphasizing the toxicity of RCS in various food sources and their formation during food processing. Understanding EGCG's capability to capture and metabolize RCS is crucial for harnessing its health benefits. Thus, this paper explores the underlying mechanisms of EGCG for RCS inhibition and its role in capturing these compounds to generate EGCG-RCS adducts. And the absorption and metabolism of EGCG-RCS adducts is also discussed.

(+)-Catechin mitigates impairment in insulin secretion and beta cell damage in methylglyoxal-induced pancreatic beta cells.

The formation of advanced glycation end products (AGEs) is the central process contributing to diabetic complications in diabetic individuals with sustained and inconsistent hyperglycemia. Methylglyoxal, a reactive carbonyl species, is found to be a major precursor of AGEs, and its levels are elevated in diabetic conditions. Dysfunction of pancreatic beta cells and impairment in insulin secretion are the hallmarks of diabetic progression. Exposure to methylglyoxal-induced AGEs alters the function and maintenance of pancreatic beta cells. Hence, trapping methylglyoxal could be an ideal approach to alleviate AGE formation and its influence on beta cell proliferation and insulin secretion, thereby curbing the progression of diabetes to its complications. In the present study, we have explored the mechanism of action of (+)-Catechin against methylglyoxal-induced disruption in pancreatic beta cells via molecular biology techniques, mainly western blot. Methylglyoxal treatment decreased insulin synthesis (41.5%) via downregulating the glucose-stimulated insulin secretion pathway (GSIS). This was restored upon co-treatment with (+)-Catechin (29.9%) in methylglyoxal-induced Beta-TC-6 cells. Also, methylglyoxal treatment affected the autocrine function of insulin by disrupting the IRS1/PI3k/Akt pathway. Methylglyoxal treatment suppresses Pdx-1 and Maf A levels, which are responsible for beta cell maintenance and cell proliferation. (+)-Catechin could significantly augment the levels of these transcription factors. This is the first study to examine the impact of a natural compound on methylglyoxal with the insulin-mediated autocrine and paracrine activities of pancreatic beta cells. The results indicate that (+)-Catechin exerts a protective effect against methylglyoxal exposure in pancreatic beta cells and can be considered a potential anti-glycation agent in further investigations on ameliorating diabetic complications.

The Chemical Reactivity of Membrane Lipids.

It is well-known that aqueous dispersions of phospholipids spontaneously assemble into bilayer structures. These structures have numerous applications across chemistry and materials science and form the fundamental structural unit of the biological membrane. The particular environment of the lipid bilayer, with a water-poor low dielectric core surrounded by a more polar and better hydrated interfacial region, gives the membrane particular biophysical and physicochemical properties and presents a unique environment for chemical reactions to occur. Many different types of molecule spanning a range of sizes, from dissolved gases through small organics to proteins, are able to interact with membranes and promote chemical changes to lipids that subsequently affect the physicochemical properties of the bilayer. This Review describes the chemical reactivity exhibited by lipids in their membrane form, with an emphasis on conditions where the lipids are well hydrated in the form of bilayers. Key topics include the following: lytic reactions of glyceryl esters, including hydrolysis, aminolysis, and transesterification; oxidation reactions of alkenes in unsaturated fatty acids and sterols, including autoxidation and oxidation by singlet oxygen; reactivity of headgroups, particularly with reactive carbonyl species; and E/Z isomerization of alkenes. The consequences of reactivity for biological activity and biophysical properties are also discussed.

The effects of using sheep tail fat and cooking time on carboxymethyl-lysine formation and some quality characteristics of heat-treated sucuk.

The study's aim was to determine the effect of using sheep tail fat (STF) on carboxymethyl-lysine (CML) content and other properties of heat-treated sucuk (HTS), a type of semi-dry fermented sausage. Three mixtures were prepared: 100% beef fat (BF), 50% BF + 50% STF, and 100% STF. After production (fermentation, heat treatment, and drying), the samples were cooked at 180°C for 0, 1, 3, and 5 min to determine the effect of cooking time on CML, thiobarbituric acid reactive substance (TBARS), total sulfhydryl, and carbonyl contents. The lowest pH value (5.50) was observed in the presence of STF. The most oleic acid (46.02%) was observed in the 100% STF group. The score of taste and general acceptability decreased with increasing STF. Using STF had no significant effect on TBARS, total sulfhydryl, carbonyl, or CML content. These parameters were affected by cooking time. The mean CML content increased from 55.77 to 72.90 μg/g after 5 min of cooking. CML correlated more strongly with TBARS than sulfhydryl or carbonyl.

Reactive Carbonyl Species and Protein Lipoxidation in Atherogenesis.

Atherosclerosis is a multifactorial disease of medium and large arteries, characterized by the presence of lipid-rich plaques lining the intima over time. It is the main cause of cardiovascular diseases and death worldwide. Redox imbalance and lipid peroxidation could play key roles in atherosclerosis by promoting a bundle of responses, including endothelial activation, inflammation, and foam cell formation. The oxidation of polyunsaturated fatty acids generates various lipid oxidation products such as reactive carbonyl species (RCS), including 4-hydroxy alkenals, malondialdehyde, and acrolein. RCS covalently bind to nucleophilic groups of nucleic acids, phospholipids, and proteins, modifying their structure and activity and leading to their progressive dysfunction. Protein lipoxidation is the non-enzymatic post-translational modification of proteins by RCS. Low-density lipoprotein (LDL) oxidation and apolipoprotein B (apoB) modification by RCS play a major role in foam cell formation. Moreover, oxidized LDLs are a source of RCS, which form adducts on a huge number of proteins, depending on oxidative stress intensity, the nature of targets, and the availability of detoxifying systems. Many systems are affected by lipoxidation, including extracellular matrix components, membranes, cytoplasmic and cytoskeletal proteins, transcription factors, and other components. The mechanisms involved in lipoxidation-induced vascular dysfunction are not fully elucidated. In this review, we focus on protein lipoxidation during atherogenesis.

Protective Effect of Quercetin against Paraquat-induced Brain Mitochondrial Disruption in Mice.

Paraquat is a highly toxic quaternary ammonium herbicide widely used in agriculture. It is an agent that induces pulmonary toxicity via the redox cyclic reaction. The present study investigated the protective effect of quercetin against paraquatinduced brain mitochondria disruption in mice. Paraquat (1.25 mg/kg, intraperitoneally) was administered to the mice, and then quercetin (50, 100, 200 mg/kg) was injected i.p. Oxidative damage biomarkers such as reactive oxygen species, protein carbonyl, lipid peroxidation, glutathione content, and mitochondrial function were assessed in the brain mitochondria. The results showed that paraquat significantly (P < 0.001) increased the reactive oxygen species, protein carbonyl, and lipid peroxidation and significantly (P < 0.0001) decreased the glutathione content and mitochondrial function in the brain cells. Administration of the quercetin at doses of 50, 100, and 200 mg/kg significantly reduced reactive oxygen species, lipid peroxidation, and protein carbonyl and improved mitochondrial function and glutathione content in the mice brain mitochondrial compared to the paraquat group. Quercetin at 200 mg/kg dose had better effectiveness than 50 and 100 mg/kg doses. Our results suggest that quercetin in a dose-dependent manner has neuroprotective effects, probably by free radicals scavenging or enhancing the antioxidant mechanisms in the brain mitochondria. It seems that quercetin could modulate protein and lipid oxidation and improve oxidative damage induced by paraquat in the early stages.

Methyl vinyl ketone and its analogs covalently modify PI3K and alter physiological functions by inhibiting PI3K signaling

Reactive carbonyl species (RCS), which are abundant in the environment and are produced in vivo under stress, covalently bind to nucleophilic residues such as cysteine (Cys) in proteins. Disruption of protein function by RCS exposure is predicted to play a role in the development of various diseases such as cancer and metabolic disorders, but most studies on RCS have been limited to simple cytotoxicity validation, leaving their target proteins and resulting physiological changes unknown. In this study, we focused on methyl vinyl ketone (MVK), which is one of the main RCS found in cigarette smoke and exhaust gas. We found that MVK suppressed phosphatidylinositol-3 kinase (PI3K)–Akt signaling, which regulates processes involved in cellular homeostasis, including cell proliferation, autophagy, and glucose metabolism. Interestingly, MVK inhibits the interaction between the epidermal growth factor (EGF) receptor and PI3K. Cys656 in the SH2 domain of the PI3K p85 subunit, which is the covalently binding site of MVK, is important for this interaction. Suppression of PI3K–Akt signaling by MVK reversed EGF-induced negative regulation of autophagy, and attenuated glucose uptake. Furthermore, we analyzed the effects of the 23 RCS compounds with structures similar to MVK and showed that their analogs also suppressed PI3K–Akt signaling in a manner that correlated with their similarities to MVK. Our study demonstrates the mechanism of MVK and its analogs in suppressing PI3K–Akt signaling and modulating physiological functions, providing a model for future studies analyzing environmental reactive species.

Zinc oxide nanoparticles decrease acrylamide cytotoxicity and oxidative stress in HepG2 cells

Purpose Acrylamide (AA) is predominantly used as a synthetic substance within various industries. However, AA is also recognized as a carcinogen. Zinc oxide nanoparticles (ZnO-NPs) are becoming increasingly attractive as medical agents. However, to the knowledge, the effects of ZnO-NPs on preventing cytotoxicity with AA have not been reported. Therefore, this study aims to determine the protective effects of ZnO-NPs against the cytotoxicity caused by AA. Design/methodology/approach MTT assay was used to determine the cytotoxicity. Reactive oxygen species (ROS) formation, carbonyl protein, malondialdehyde (MDA) and glutathione (GSH) were measured and analyzed statistically. Findings The findings observed that the presence of 200 µM AA led to a substantial reduction in cell viability (p &lt; 0.001). However, ZnO-NPs restored cell viability at 50 and 100 µM concentrations (p = 0.0121 and p = 0.0011, respectively). The levels of ROS were significantly reduced (p = 0.001 and p = &lt; 0.001) to 518 ± 47.57 and 364 ± 47.79, respectively, compared to the AA group. The levels of GSH were significantly increased (p = 0.004 and p = 0.002) to 16.9 ± 1.3 and 17.6 ± 0.5, respectively, compared to the AA group. The levels of MDA were significantly decreased (p = 0.005, p &lt; 0.001 and p &lt; 0.001) when compared to the AA group, as were the levels of carbonyl protein (p = 0.009 and p &lt; 0.002) in comparison to the AA group. Originality/value In summary, the outcomes of this research indicate that ZnO-NPs played a role in inhibiting AA-induced oxidative stress and cytotoxicity.

Friedel–Crafts Acylation for Accessing Multi‐Bridge‐Functionalized Large Pillar[n]arenes

AbstractPillar[n]arenes can be constructed using a Friedel–Crafts alkylation process. However, due to the reversible nature of the alkylation, mixture of large pillar[n]arenes (n≥7) are obtained as minor products, and thus laborious purification are necessary to isolate the larger pillar[n]arenes. Moreover, inert methylene bridges are introduced during the alkylation process, and the multi‐functionalization of the bridges has never been investigated. Herein, an irreversible Friedel–Crafts acylation is used to prepare pillar[n]arenes. Due to the irreversible nature of the acylation, the reaction of precursors bearing carboxylic acids and electron‐rich arene rings results in a size‐exclusive formation of pillar[n]arenes, in which the ring‐size is determined by the precursor length. Because of this size‐selective formation, laborious separation of undesired macrocycles is not necessary. Moreover, the bridges of pillar[n]arenes are selectively installed with reactive carbonyl groups using the acylation method, whose positions are determined by the precursor used. The carbonyl bridges can be easily converted into versatile functional groups, leading to various laterally modified pillar[n]arenes, which cannot be accessed by the alkylation strategy.

Friedel-Crafts Acylation for Accessing Multi-Bridge-Functionalized Large Pillar[n]arenes.

Pillar[n]arenes can be constructed using a Friedel-Crafts alkylation process. However, due to the reversible nature of the alkylation, mixture of large pillar[n]arenes (n≥7) are obtained as minor products, and thus laborious purification are necessary to isolate the larger pillar[n]arenes. Moreover, inert methylene bridges are introduced during the alkylation process, and the multi-functionalization of the bridges has never been investigated. Herein, an irreversible Friedel-Crafts acylation is used to prepare pillar[n]arenes. Due to the irreversible nature of the acylation, the reaction of precursors bearing carboxylic acids and electron-rich arene rings results in a size-exclusive formation of pillar[n]arenes, in which the ring-size is determined by the precursor length. Because of this size-selective formation, laborious separation of undesired macrocycles is not necessary. Moreover, the bridges of pillar[n]arenes are selectively installed with reactive carbonyl groups using the acylation method, whose positions are determined by the precursor used. The carbonyl bridges can be easily converted into versatile functional groups, leading to various laterally modified pillar[n]arenes, which cannot be accessed by the alkylation strategy.

Effects of mango and partridge tea extracts on microbial, physical, and chemical properties of tilapia fillets treated with in-package cold plasma during refrigerator storage

Abstract Objectives The effect of natural extracts on the oxidative quality of cold plasma (CP)-treated tilapia fillets during 9 d refrigerator storage was explored by adding mango and partridge tea extracts as natural antioxidants. Materials and Methods The effects of mango and partridge tea extracts on the fish during storage were evaluated using the total viable count (TVC), total volatile basic nitrogen (TVB-N), thiobarbituric acid reactive substance (TBARS), carbonyl values, and color. Results The results showed that on the ninth day, the TVC of the mango extract (ME)-CP group was 3.52±0.08 log colony-forming units/g, which was significantly (P&amp;lt;0.05) lower than that of the other groups, while the TBARS of ME-CP and partridge tea extract (MOE)-CP was similar. The TVB-N values in the ME-CP and MOE-CP groups were 10.21±0.7 mg/100 g and 14.27±0.31 mg/100 g, respectively, which were within the acceptable values. The sulfhydryl and carbonyl contents in ME-CP were lower than those in MOE-CP; however, no significant variation was detected in texture. No significant changes were observed in the L* values among the treatment groups, while the b* values in the MOE-CP group were significantly increased (P&amp;lt;0.05). Conclusions Therefore, the addition of ME combined with CP treatment can inhibit microbial growth, lipid oxidation, and protein oxidation in tilapia fillets without significantly impacting their color.

The Protection of EGCG Against 6-OHDA-Induced Oxidative Damage by Regulating PPARγ and Nrf2/HO-1 Signaling.

6-Hydroxydopamine (6-OHDA) is a classic neurotoxin that has been widely used in Parkinson's disease research. 6-OHDA can increase intracellular reactive oxygen species (ROS) and can cause cell damage, which can be attenuated with (-)-Epigallocatechin-3-gallate (EGCG) treatment. However, the mechanism by which EGCG alters the 6-OHDA toxicity remains unclear; In this study, we found 6-OHDA (25 μM) alone increased intracellular ROS concentration in N27 cells, which was attenuated by pretreating with EGCG (100 μM). We evaluated the intracellular oxidative damage by determining the level of thiobarbituric acid reactive substances (TBARS) and protein carbonyl content. 6-OHDA significantly increased TBARS by 82.7% (P < .05) and protein carbonyl content by 47.8 (P < .05), compared to the control. Pretreatment of EGCG decreased TBARS and protein carbonyls by 36.4% (P < .001) and 27.7% (P < .05), respectively, compared to 6-OHDA alone treatment. Antioxidant effect was tested with E2-related factor 2 (Nrf2), heme oxygenase-1(HO-1) and peroxisome-proliferator activator receptor γ (PPARγ) expression. 6-OHDA increased Nrf2 expression by 69.6% (P < .001), HO-1 by 173.3% (P < .001), and PPARγ by 122.7% (P < .001), compared with untreatment. EGCG pretreatment stabilized these alterations induced by 6-OHDA. Our results suggested that the neurotoxicity of 6-OHDA in N27 cells was associated with ROS pathway, whereas pretreatment of EGCG suppressed the ROS generation and deactivated the Nrf2/HO-1 and PPARγ expression.

PH-Responsive self-assembled polymer-photosensitizer conjugate for activable photodynamic therapy.

This paper reports synthesis, aqueous self-assembly and relevance of the pH-triggered activable photodynamic therapy of amphiphilic polyurethane (P1S) functionalized with a heavy-atom free organic photosensitizer. Condensation polymerization between 1,4-diisocyanatobutane and two different dihydroxy monomers (one having a pendant hydrophilic wedge and the other having 1,3-dihydroxypropan-2-one with a reactive carbonyl group) in the presence of a measured amount of (S)-2-methylbutan-1-ol (chain-stopper) and DABCO catalyst produces a reactive pre-polymer P1. Hydrazide-functionalized thionated-naphthalenemonoimide (NMIS), which acts as a photosensitizer, reacted with the carbonyl-functionality of P1 to obtain the desired polymer-photosensitizer conjugate P1S in which the dye was attached to the polymer backbone via an acid-labile hydrazone linker. In water, P1S adopted an intra-chain H-bonding stabilized folded structure, which further assembled to produce a polymersome structure (Dh ≈ 200 nm), in which the hydrophobic membrane consists of aggregated NMIS and trialkoxy-benzene chromophores, as evident from UV/vis, CD and small-angle X-ray diffraction studies. In the aggregated state, NMIS loses its reactive oxygen species (ROS) generation ability and remains in a dormant state. However, under acidic conditions (pH 5.5), the photosensitizer is detached (presumably because of the cleavage of the hydrazone linker) and regains its full ROS-generation activity under photoirradiation, as evidenced from the standard DCFH assay. To test the possibility of such pH-activable intra-cellular ROS generation, P1S was treated with HeLa cells, as it is known that cancer cells are more acidic than normal cells. Indeed, photoirradiation-induced intra-cellular ROS generation was evident by the DCFH assay, resulting in efficient cell killing.