Trans-Cinnamaldehyde Inhibition of Pyruvate Dehydrogenase: Effects on Streptococcus mutans Carbohydrate Metabolism.

Dental caries is a chronic oral infectious disease, and Streptococcus mutans (S. mutans) plays an important role in the formation of dental caries. Trans-cinnamaldehyde (CA) exhibits broad-spectrum antibacterial activity; however, its target and mechanism of action of CA on S. mutans needs to be further explored. In this study, it was verified that CA could inhibit the growth and biofilm formation of S. mutans. Further proteomic analysis identified 33, 55, and 78 differentially expressed proteins (DEPs) in S. mutans treated with CA for 1, 2, and 4 h, respectively. Bioinformatics analysis showed that CA interfered with carbohydrate metabolism, glycolysis, pyruvate metabolism, and the TCA cycle, as well as amino acid metabolism of S. mutans. Protein interactions suggested that pyruvate dehydrogenase (PDH) plays an important role in the antibacterial effect of CA. Moreover, the upstream and downstream pathways related to PDH were verified by various assays, and the results proved that CA not only suppressed the glucose and sucrose consumption and inhibited glucosyltransferase (GTF) and lactate dehydrogenase (LDH) activities but also decreased the ATP production. Interestingly, the protein interaction, qRT-PCR, and molecular docking analysis showed that PDH might be the target of CA to fight S. mutans. In summary, the study shows that CA interferes with the carbohydrate metabolism of bacteria by inhibiting glycolysis and the tricarboxylic acid (TCA) cycle via binding to PDH, which verifies that PDH is a potential target for the development of new drugs against S. mutans.

Acrolein Induces Changes in Cell Membrane and Cytosol Proteins of Erythrocytes.

High concentrations of acrolein (2-propenal) are found in polluted air and cigarette smoke, and may also be generated endogenously. Acrolein is also associated with the induction and progression of many diseases. The high reactivity of acrolein towards the thiol and amino groups of amino acids may cause damage to cell proteins. Acrolein may be responsible for the induction of oxidative stress in cells. We hypothesized that acrolein may contribute to the protein damage in erythrocytes, leading to the disruption of the structure of cell membranes. The lipid membrane fluidity, membrane cytoskeleton, and osmotic fragility were measured for erythrocytes incubated with acrolein for 24 h. The levels of thiol, amino, and carbonyl groups were determined in cell membrane and cytosol proteins. The level of non-enzymatic antioxidant potential (NEAC) and TBARS was also measured. The obtained research results showed that the exposure of erythrocytes to acrolein causes changes in the cell membrane and cytosol proteins. Acrolein stiffens the cell membrane of erythrocytes and increases their osmotic sensitivity. Moreover, it has been shown that erythrocytes treated with acrolein significantly reduce the non-enzymatic antioxidant potential of the cytosol compared to the control.

Theanine Capture of Reactive Carbonyl Species in Humans after Consuming Theanine Capsules or Green Tea.

Acrolein (ACR), methylglyoxal (MGO), and glyoxal (GO) are a class of reactive carbonyl species (RCS), which play a crucial role in the pathogenesis of chronic and age-related diseases. Here, we explored a new RCS inhibitor (theanine, THE) and investigated its capture capacity on RCS in vivo by human experiments. After proving that theanine could efficiently capture ACR instead of MGO/GO by forming adducts under simulated physiological conditions, we further detected the ACR/MGO/GO adducts of theanine in the human urine samples after consumption of theanine capsules (200 and 400 mg) or green tea (4 cups, containing 200 mg of theanine) by using ultraperformance liquid chromatography-time-of-flight-high-resolution mass spectrometry. Quantitative assays revealed that THE-ACR, THE-2ACR-1, THE-MGO, and THE-GO were formed in a dose-dependent manner in the theanine capsule groups; the maximum value of the adducts of theanine was also tested. Furthermore, besides the RCS adducts of theanine, the RCS adducts of catechins could also be detected in the drinking tea group. Whereas, metabolite profile analysis showed that theanine could better capture RCS produced in the renal metabolic pathway than catechins. Our findings indicated that theanine could reduce RCS in the body in two ways: as a pure component or contained in tea leaves.

Visualization of Acrolein Upregulation during Ferroptosis by a Ratiometric Fluorescent Probe.

Ferroptosis is a pattern of cell death caused by iron-dependent accumulation of lipid peroxides and is closely associated with the occurrence and development of multiple diseases. Acrolein (ACR), one of the final metabolites of lipid peroxidation, is a reactive carbonyl species with strong biotoxicity. Effective detection of ACR is important for understanding its role in the progression of ferroptosis and studying the specific mechanisms of ferroptosis-mediated diseases. However, visualization detection of ACR during ferroptosis has not yet been reported. In this work, the first ratiometric fluorescent probe (HBT-SH) based on 2-(2'-hydroxyphenyl) benzothiazole (HBT) was designed for tracing endogenous ACR with an unprecedented regiospecific ACR-induced intramolecular cyclization strategy, which employs 2-aminoethanethiol as an ACR-selective recognition receptor. The experimental results showed that HBT-SH has excellent selectivity, high sensitivity (LOD = 0.26 µM) and good biocompatibility. More importantly, the upregulation of ACR levels was observed during ferroptosis in HeLa cells and zebrafish, indicating that ACR may be a specific active molecule that plays an essential biological role during ferroptosis or may serve as a potential marker of ferroptosis, which has great significance for studying the pathological process and treatment options of ferroptosis-related diseases.

Identification of a cinnamoyl-CoA reductase from Cinnamomum cassia involved in trans-cinnamaldehyde biosynthesis.

MAIN CONCLUSION: The identification of a functional cinnamoyl-CoA reductase enzyme from Cinnamomum cassia involved in trans-cinnamaldehyde biosynthesis offers the potential for enhancing trans-cinnamaldehyde production through genetic engineering. A significant accumulation of trans-cinnamaldehyde has been found in the bark tissues of C. cassia, used in traditional Chinese medicine. trans-Cinnamaldehyde exhibits various pharmacological properties such as anti-inflammatory, analgesic, and protection of the stomach and the digestive tract. However, further elucidation and characterization of the biosynthetic pathway for trans-cinnamaldehyde is required. In this study, we conducted an integrated analysis of trans-cinnamaldehyde accumulation profiles and transcriptomic data from five different C. cassia tissues to identify the genes involved in its biosynthesis. The transcriptome data we obtained included nearly all genes associated with the trans-cinnamaldehyde pathway, with the majority demonstrating high abundance in branch barks and trunk barks. We successfully cloned four C. cassia cinnamoyl-CoA reductases (CcCCRs), a key gene in trans-cinnamaldehyde biosynthesis. We found that the recombinant CcCCR1 protein was the only one that more efficiently converted cinnamoyl-CoA into trans-cinnamaldehyde. CcCCR1 exhibited approximately 14.7-fold higher catalytic efficiency (kcat/Km) compared to the Arabidopsis thaliana cinnamoyl-CoA reductase 1 (AtCCR1); therefore, it can be utilized for engineering higher trans-cinnamaldehyde production as previously reported. Molecular docking studies and mutagenesis experiments also validated the superior catalytic activity of CcCCR1 compared to AtCCR1. These findings provide valuable insights for the functional characterization of enzyme-coding genes and hold potential for future engineering of trans-cinnamaldehyde biosynthetic pathways.

Curry-Odorants and Their Metabolites Transfer into Human Milk and Urine.

SCOPE: The excretion of dietary odorants into urine and milk is evaluated and the impact of possible influencing factors determined. Furthermore, the metabolic relevance of conjugates for the excretion into milk is investigated. METHODS AND RESULTS: Lactating mothers (n = 20) are given a standardized curry dish and donated one milk and urine sample each before and 1, 2, 3, 4.5, 6, and 8 h after the intervention. The concentrations of nine target odorants in these samples are determined. A significant transition is observed for linalool into milk, as well as for linalool, cuminaldehyde, cinnamaldehyde, and eugenol into urine. Maximum concentrations are reached within 1 h after the intervention in the case of milk and within 2-3 h in the case of urine. In addition, the impact of glucuronidase treatment on odorant concentrations is evaluated in a sample subset of twelve mothers. Linalool, eugenol, and vanillin concentrations increased 3-77-fold in milk samples after treatment with ß-glucuronidase. CONCLUSION: The transfer profiles of odorants into milk and urine differ qualitatively, quantitatively, and in temporal aspects. More substances are transferred into urine and the transfer needs a longer period compared with milk. Phase II metabolites are transferred into urine and milk.

Mitochondrial DNA is a key driver in cigarette smoke extract-induced IL-6 expression.

Smoking is an independent risk factor for atherosclerosis, the primary pathogenesis of which is inflammation. We recently reported that cigarette smoke extract (CSE) causes cytosolic and extracellular accumulation of both nuclear (n) and mitochondrial (mt) DNA, which leads to inflammation in human umbilical vein endothelial cells (HUVECs). In this study, we examined whether inflammation induction depends more on cytosolic nDNA or mtDNA, and which chemical constituents of CSE are involved. Acrolein (ACR), methyl vinyl ketone (MVK), and 2-cyclopenten-1-one (CPO) were used in the experiments, as these are the major cytotoxic factors in CSE in various cell types. Stimulation with ACR, MVK, or CPO alone resulted in the accumulation of DNA double-strand breaks (DSBs), but not oxidative DNA damage, accumulation of cytosolic DNA, or increased expression of inflammatory cytokines. Simultaneous administration of all three constituents (ALL) resulted in oxidative DNA damage in both the nucleus and mitochondria, accumulation of DSBs, reduced mitochondrial membrane potential, induction of minority mitochondrial outer membrane permeabilization, accumulation of cytosolic free DNA, and increased expression of inflammatory cytokines such as IL-6 and IL-1α. Treatment with N-acetyl-L-cysteine, a reactive oxygen species scavenger, suppressed oxidative DNA damage and the increased expression of IL-6 and IL-1α induced by ALL or CSE. The ALL- or CSE-induced increase in IL-6 expression, but not that of IL-1α, was suppressed by mtDNA depletion. In conclusion, ACR, MVK, and CPO may strongly contribute to CSE-induced inflammation. More importantly, cytosolic free mtDNA is thought to play an important role in IL-6 expression, a central mediator of inflammation.

Bulk and In Situ Quantification of Coniferaldehyde Residues in Lignin.

Lignin is a group of cell wall localised heterophenolic polymers varying in the chemistry of the aromatic and aliphatic parts of its units. The lignin residues common to all vascular plants have an aromatic ring with one para hydroxy group and one meta methoxy group, also called guaiacyl (G). The terminal function of the aliphatic part of these G units, however, varies from alcohols, which are generally abundant, to aldehydes, which represent a smaller proportion of lignin monomers. The proportions of aldehyde to alcohol G units in lignin are, nevertheless, precisely controlled to respond to environmental and development cues. These G aldehyde to alcohol unit proportions differ between each cell wall layer of each cell type to fine-tune the cell wall biomechanical and physico-chemical properties. To precisely determine changes in lignin composition, we, herein, describe the various methods to detect and quantify the levels and positions of G aldehyde units, also called coniferaldehyde residues, of lignin polymers in ground plant samples as well as in situ in histological cross-sections.

The mechanism of acrolein exposure inhibited the release of neutrophil extracellular traps: By reducing respiratory burst and Raf/MEK/ERK pathway and promote cell apoptosis.

Acrolein (AC) is a highly toxic volatile substance in the environment, and studies have found that excessive AC had a toxic effect on the immune system. Neutrophils are the first line of defense against pathogen invasion. The release of neutrophil extracellular traps (NETs) is a protective mechanism for neutrophils, and its release is affected by environmental pollutants. However, the effect of AC on NETs release and its mechanism remains unclear. In this study, chicken peripheral blood neutrophils were pretreated with 20 µM AC and treated with 5 µM Phorbol 12-myristate 13-acetate (PMA) to stimulate the release of NETs. The results showed that AC exposure significantly inhibited the release of NETs induced by PMA, respiratory burst, and the expression levels of phospho-rapidly accelerated fibrosarcoma (p-Raf), phospho-mitogen-activated extracellular signal-regulated kinase (p-MEK) and phospho-extracellular regulated protein kinases (p-ERK). In addition, AC exposure significantly inhibited the expression of B-cell lymphoma-2 (Bcl-2) and promoted the expression of apoptotic factors Bcl2-Associated X (Bax), cytochrome c (Cyt C), cysteinyl aspartate specific proteinase 9 (Casp 9) and cysteinyl aspartate specific proteinase 3 (Casp 3). Further inhibition of neutrophil apoptosis significantly improved the release of NETs. The above results indicated that AC exposure led to a decrease in the formation of NETs, which is caused by excessive AC-induced neutrophil apoptosis. Our study clarified the immune toxicity mechanism of AC on chickens, which is of great significance and reference value for protecting the ecological environment and poultry health.

Hydralazine Promotes Central Nervous System Recovery after Spinal Cord Injury by Suppressing Oxidative Stress and Inflammation through Macrophage Regulation.

OBJECTIVE: This study aims to investigate the effects of hydralazine on inflammation induced by spinal cord injury (SCI) in the central nervous system (CNS) and its mechanism in promoting the structural and functional recovery of the injured CNS. METHODS: A compressive SCI mouse model was utilized for this investigation. Immunofluorescence and quantitative real-time polymerase chain reaction were employed to examine the levels of acrolein, acrolein-induced inflammation-related factors, and macrophages at the injury site and within the CNS. Western blotting was used to evaluate the activity of the phosphoinositide 3-kinase (PI3K)/AKT pathway to study macrophage regulation. The neuropathic pain and motor function recovery were evaluated by glutamic acid decarboxylase 65/67 (GAD65/67), vesicular glutamate transporter 1 (VGLUT1), paw withdrawal response, and Basso Mouse Scale score. Nissl staining and Luxol Fast Blue (LFB) staining were performed to investigate the structural recovery of the injured CNS. RESULTS: Hydralazine downregulated the levels of acrolein, IL-1ß, and TNF-α in the spinal cord. The downregulation of acrolein induced by hydralazine promoted the activation of the PI3K/AKT pathway, leading to M2 macrophage polarization, which protected neurons against SCI-induced inflammation. Additionally, hydralazine promoted the structural recovery of the injured spinal cord area. Mitigating inflammation and oxidative stress by hydralazine in the animal model alleviated neuropathic pain and altered neurotransmitter expression. Furthermore, hydralazine facilitated motor function recovery following SCI. Nissl staining and LFB staining indicated that hydralazine promoted the structural recovery of the injured CNS. CONCLUSION: Hydralazine, an acrolein scavenger, significantly mitigated SCI-induced inflammation and oxidative stress in vivo, modulated macrophage activation, and consequently promoted the structural and functional recovery of the injured CNS.

Toxicological effects of ocular acrolein exposure to eyelids in rabbits in vivo.

Acrolein is a highly reactive volatile toxic chemical that injures the eyes and many organs. It has been used in wars and terrorism for wounding masses on multiple occasions and is readily accessible commercially. Our earlier studies revealed acrolein's toxicity to the cornea and witnessed damage to other ocular tissues. Eyelids play a vital role in keeping eyes mobile, moist, lubricated, and functional utilizing a range of diverse lipids produced by the Meibomian glands located in the upper and lower eyelids. This study sought to investigate acrolein's toxicity to eyelid tissues by studying the expression of inflammatory and lipid markers in rabbit eyes in vivo utilizing our reported vapor-cap model. The study was approved by the institutional animal care and use committees and followed ARVO guidelines. Twelve New Zealand White Rabbits were divided into 3 groups: Naïve (group 1), 1-min acrolein exposure (group 2), or 3-min acrolein exposure (group 3). The toxicological effects of acrolein on ocular health in live animals were monitored with regular clinical eye exams and intraocular pressure measurements and eyelid tissues post-euthanasia were subjected to H&E and Masson's trichrome histology and qRT-PCR analysis. Clinical eye examinations witnessed severely swollen eyelids, abnormal ocular discharge, chemosis, and elevated intraocular pressure (p < 0.001) in acrolein-exposed eyes. Histological studies supported clinical findings and exhibited noticeable changes in eyelid tissue morphology. Gene expression studies exhibited significantly increased expression of inflammatory and lipid mediators (LOX, PAF, Cox-2, and LTB4; p < 0.001) in acrolein-exposed eyelid tissues compared to naïve eyelid tissues. The results suggest that acrolein exposure to the eyes causes acute damage to eyelids by altering inflammatory and lipid mediators in vivo.

Acrolein produced by glioma cells under hypoxia inhibits neutrophil AKT activity and suppresses anti-tumoral activities.

Acrolein, which is the most reactive aldehyde, is a byproduct of lipid peroxidation in a hypoxic environment. Acrolein has been shown to form acrolein-cysteine bonds, resulting in functional changes in proteins and immune effector cell suppression. Neutrophils are the most abundant immune effector cells in circulation in humans. In the tumor microenvironment, proinflammatory tumor-associated neutrophils (TANs), which are termed N1 neutrophils, exert antitumor effects via the secretion of cytokines, while anti-inflammatory neutrophils (N2 neutrophils) support tumor growth. Glioma is characterized by significant tissue hypoxia, immune cell infiltration, and a highly immunosuppressive microenvironment. In glioma, neutrophils exert antitumor effects early in tumor development but gradually shift to a tumor-supporting role as the tumor develops. However, the mechanism of this anti-to protumoral switch in TANs remains unclear. In this study, we found that the production of acrolein in glioma cells under hypoxic conditions inhibited neutrophil activation and induced an anti-inflammatory phenotype by directly reacting with Cys310 of AKT and inhibiting AKT activity. A higher percentage of cells expressing acrolein adducts in tumor tissue are associated with poorer prognosis in glioblastoma patients. Furthermore, high-grade glioma patients have increased serum acrolein levels and impaired neutrophil functions. These results suggest that acrolein suppresses neutrophil function and contributes to the switch in the neutrophil phenotype in glioma.

The role of acrolein for E-cigarette vapour condensate mediated activation of NADPH oxidase in cultured endothelial cells and macrophages.

Electronic cigarettes (E-cigarettes) have recently become a popular alternative to traditional tobacco cigarettes. Despite being marketed as a healthier alternative, increasing evidence shows that E-cigarette vapour could cause adverse health effects. It has been postulated that degradation products of E-cigarette liquid, mainly reactive aldehydes, are responsible for those effects. Previously, we have demonstrated that E-cigarette vapour exposure causes oxidative stress, inflammation, apoptosis, endothelial dysfunction and hypertension by activating NADPH oxidase in a mouse model. To better understand oxidative stress mechanisms, we have exposed cultured endothelial cells and macrophages to condensed E-cigarette vapour (E-cigarette condensate) and acrolein. In both endothelial cells (EA.hy 926) and macrophages (RAW 264.7), we have observed that E-cigarette condensate incubation causes cell death. Since recent studies have shown that among toxic aldehydes found in E-cigarette vapour, acrolein plays a prominent role, we have incubated the same cell lines with increasing concentrations of acrolein. Upon incubation with acrolein, a translocation of Rac1 to the plasma membrane has been observed, accompanied by an increase in oxidative stress. Whereas reactive oxygen species (ROS) formation by acrolein in cultured endothelial cells was mainly intracellular, the release of ROS in cultured macrophages was both intra- and extracellular. Our data also demonstrate that acrolein activates the nuclear factor erythroid 2-related factor 2 (Nrf2) antioxidant pathway and, in general, could mediate E-cigarette vapour-induced oxidative stress and cell death. More mechanistic insight is needed to clarify the toxicity associated with E-cigarette consumption and the possible adverse effects on human health.

Inhibitive effect and mechanism of cinnamaldehyde on growth and OTA production of Aspergillus niger in vitro and in dried red chilies.

Mould and mycotoxin contamination is an ongoing issue in agriculture and food industry. Production by Aspergillus niger DTZ-12 in Guizhou dried red chilies was found, leading to significant economic losses. In this study, the inhibitive efficacy (Effective Concentration, EC) of cinnamaldehyde (CIN), eugenol (EUG), carvacrol (CAR), and linalool (LIN) against A. niger DTZ-12 were evaluated. CIN with the best antifungal capacity was then investigated for the comprehensive inhibitory activity against A. niger DTZ-12 including mycelia, spores, and physiological activities. Results showed that CIN can effectively retard mycelial growth, spore germination, and OTA production of A. niger DTZ-12 in vitro and in dried red chilies during storage. At physiological level, CIN can increase cell membrane permeability by reducing the ergosterol, decrease ATP content and ATPase activity, and promote the accumulation of reactive oxygen species (ROS) and malondialdehyde (MDA) in cell. These results suggested that CIN displayed a great potential to be employed as a natural and effective alternative preservative during dried red chili storage.

Hydralazine plays an immunomodulation role of pro-regeneration in a mouse model of spinal cord injury.

Spinal cord injury (SCI) results in severe motor and sensory dysfunction with no effective therapy. Spinal cord debris (sp) from injured spinal cord evokes secondary SCI continuously. We and other researchers have previously clarified that it is mainly bone marrow derived macrophages (BMDMs) infiltrating in the lesion epicenter to clear sp, rather than local microglia. Unfortunately, the pro-inflammatory phenotype of these infiltrating BMDMs is predominant which impairs wound healing. Hydralazine, as a potent vasodilator and scavenger of acrolein, has protective effects in many diseases. Hydralazine is also confirmed to promote motor function and hypersensitivity in SCI rats through scavenging acrolein. However, few studies have explored the effects of hydralazine on immunomodulation, as well as spontaneous pain and emotional response, the important syndromes in clinical patients. It remains unclear whether hydralazine affects infiltrating BMDMs after SCI. In this study, we targeted BMDMs to explore the influence of hydralazine on immune cells in a mouse model of SCI, and also investigated the contribution of polarized BMDMs to hydralazine-induced neurological function recovery after SCI in male mice. The adult male mice underwent T10 spinal cord compression. The results showed that in addition to improving motor function and hypersensitivity, hydralazine relieved SCI-induced spontaneous pain and emotional response, which is a newly discovered function of hydralazine. Hydralazine inhibited the recruitments of pro-inflammatory BMDMs and educated infiltrated BMDMs to a more reparative phenotype involving in multiple biological processes associated with SCI pathology, including immune/inflammation response, neurogenesis, lipid metabolism, oxidative stress, fibrosis formation, and angiogenesis, etc. As an overall effect, hydralazine-treated BMDMs loaden with sp partially rescued neurological function after SCI. It is concluded that hydralazine plays an immunomodulation role of educating pro-inflammatory BMDMs to a more reparative phenotype; and hydralazine-educated BMDMs contribute to hydralazine-induced improvement of neurological function in SCI mice, which provides support for drug and cell treatment options for SCI therapy.

Molecular Characteristics of Toxicity of Acrolein Produced from Spermine.

Acrolein (CH2=CH-CHO), an unsaturated aldehyde produced from spermine, is one of the major contributors to oxidative stress. Acrolein has been found to be more toxic than reactive oxygen species (H2O2 and •OH), and it can be easily conjugated with proteins, bringing about changes in nature of the proteins. Acrolein is detoxified by glutathione in cells and was found to be mainly produced from spermine through isolating two cell lines of acrolein-resistant Neuro2a cells. The molecular characteristics of acrolein toxicity and tissue damage elicited by acrolein were investigated. It was found that glyceraldehyde-3-phosphate dehydrogenase (GAPDH); cytoskeleton proteins such as vimentin, actin, α- and ß-tubulin proteins; and apolipoprotein B-100 (ApoB100) in LDL are strongly damaged by acrolein conjugation. In contrast, activities of matrix metalloproteinase-9 (MMP-9) and proheparanase (proHPSE) are enhanced, and antibody-recognizing abilities of immunoglobulins are modified by acrolein conjugation, resulting in aggravation of diseases. The functional changes of these proteins by acrolein have been elucidated at the molecular level. The findings confirmed that acrolein is the major contributor causing tissue damage in the elderly.

Urinary Amino Acid-Conjugated Acrolein and Taurine as New Biomarkers for Detection of Dementia.

BACKGROUND: Dementia, including Alzheimer's disease (AD), is one of the serious diseases at advanced age, and its early detection is important for maintaining quality of life (QOL). OBJECTIVE: In this study, we sought novel biomarkers for dementia in urine. METHODS: Samples of urine were collected from 57 control subjects without dementia, 62 mild cognitive impairment (MCI) patients, and 42 AD patients. Mini-Mental State Examination (MMSE) was evaluated when subjects were examined by medical doctors. Urinary amino acid (lysine)-conjugated acrolein (AC-Acro) was measured using N ɛ-(3-formyl-3, 4-dehydropiperidine) lysine (FDP-Lys) ELISA kit, and taurine content was measured using a taurine assay kit. Values were normalized by creatinine content which was measured with the colorimetric assay kit. RESULTS: We found that urinary amino acid (lysine)-conjugated acrolein (AC-Acro) and taurine negatively correlated with MMSE score and are significantly lower in dementia patients compared to the normal subjects. When AC-Acro and taurine were evaluated together with age using an artificial neural network model, median relative risk values for subjects with AD, subjects with mild cognitive impairment, and control subjects were 0.96, 0.53, and 0.06, respectively. CONCLUSION: Since urine is relatively easy to collect, our findings provide a novel biomarker for dementia without invasiveness.

Disruption of the Molecular Regulation of Mitochondrial Metabolism in Airway and Lung Epithelial Cells by Cigarette Smoke: Are Aldehydes the Culprit?

Chronic obstructive pulmonary disease (COPD) is a devastating lung disease for which cigarette smoking is the main risk factor. Acetaldehyde, acrolein, and formaldehyde are short-chain aldehydes known to be formed during pyrolysis and combustion of tobacco and have been linked to respiratory toxicity. Mitochondrial dysfunction is suggested to be mechanistically and causally involved in the pathogenesis of smoking-associated lung diseases such as COPD. Cigarette smoke (CS) has been shown to impair the molecular regulation of mitochondrial metabolism and content in epithelial cells of the airways and lungs. Although it is unknown which specific chemicals present in CS are responsible for this, it has been suggested that aldehydes may be involved. Therefore, it has been proposed by the World Health Organization to regulate aldehydes in commercially-available cigarettes. In this review, we comprehensively describe and discuss the impact of acetaldehyde, acrolein, and formaldehyde on mitochondrial function and content and the molecular pathways controlling this (biogenesis versus mitophagy) in epithelial cells of the airways and lungs. In addition, potential therapeutic applications targeting (aldehyde-induced) mitochondrial dysfunction, as well as regulatory implications, and the necessary required future studies to provide scientific support for this regulation, have been covered in this review.

New insights into the persistent effect of transient cinnamaldehyde vapor treatment on the growth and aflatoxin synthesis of Aspergillus flavus.

The antimicrobial effects of continuous treatment with essential oils (EOs) in both liquid and gaseous phases have been intensively studied. Due to their rapid volatility, the effects of EOs on microorganisms after transient treatment are also worth exploring. In this work, the persistent effects of cinnamaldehyde (CA) vapor on Aspergillus flavus were detected by a series of biochemical analyses. Transcriptome analysis was also conducted to study the gene expression changes between recovered and normal A. flavus. When CA vapor was removed, biochemical analyses showed that the oxidative stress induced by the antimicrobial atmosphere was alleviated, and almost all the damaged functions were restored apart from mitochondrial function. Remarkably, the suppressed aflatoxin production intensified, which was confirmed by the up-regulation of most genes in the aflatoxin synthetic gene cluster, the velvet-related gene FluG and the aflatoxin precursor acetyl-CoA. Transcriptomic analysis also demonstrated significant changes in secondary metabolism, energy metabolism, oxidative stress, and amino acid metabolism in the recovery group. Taken together, these findings provide new insights into the mechanisms underlying the response of A. flavus to CA vapor treatment and will guide the rational application of EOs.

Increased Levels of the Acrolein Metabolite 3-Hydroxypropyl Mercapturic Acid in the Urine of e-Cigarette Users.

Carcinogen and toxicant uptake by e-cigarette users have not been fully evaluated. In the study reported here, we recruited 30 e-cigarette users, 63 nonsmokers, and 33 cigarette smokers who gave monthly urine samples over a period of 4-6 months. Their product use status was confirmed by measurements of exhaled CO, urinary total nicotine equivalents, cyanoethyl mercapturic acid (CEMA), and total 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol. Urinary biomarkers of exposure to the carcinogens acrolein (3-hydroxypropyl mercapturic acid, 3-HPMA), benzene (S-phenyl mercapturic acid, SPMA), acrylonitrile (CEMA), and a combination of crotonaldehyde, methyl vinyl ketone, and methacrolein (3-hydroxy-1-methylpropyl mercapturic acid, HMPMA) were quantified at each visit. Data from subject visits with CEMA > 27 pmol/mL were excluded from the statistical analysis of the results because of possible unreported exposures to volatile combustion products such as secondhand cigarette smoke or marijuana smoke exposure; this left 22 e-cigarette users with 4 or more monthly visits and all 63 nonsmokers. Geometric mean levels of 3-HPMA (1249 versus 679.3 pmol/mL urine) were significantly higher (P = 0.003) in e-cigarette users than in nonsmokers, whereas levels of SPMA, CEMA, and HMPMA did not differ between these two groups. All analytes were significantly higher in cigarette smokers than in either e-cigarette users or nonsmokers. The results of this unique multimonth longitudinal study demonstrate consistent significantly higher uptake of the carcinogen acrolein in e-cigarette users versus nonsmokers, presenting a warning signal regarding e-cigarette use.