CLDN5: From structure and regulation to roles in tumors and other diseases beyond CNS disorders.

Claudin-5 (CLDN5) is an essential component of tight junctions (TJs) and is critical for the integrity of the blood-brain barrier (BBB), ensuring homeostasis and protection from damage to the central nervous system (CNS). Currently, many researchers have summarized the role and mechanisms of CLDN5 in CNS diseases. However, it is noteworthy that CLDN5 also plays a significant role in tumor growth and metastasis. In addition, abnormal CLDN5 expression is involved in the development of respiratory diseases, intestinal diseases, cardiac diseases, and diabetic ocular complications. This paper aims to review the structure, expression, and regulation of CLDN5, focusing on its role in tumors, including its expression and regulation, effects on malignant phenotypes, and clinical significance. Furthermore, this paper will provide an overview of the role and mechanisms of CLDN5 in respiratory diseases, intestinal diseases, cardiac diseases, and diabetic ocular complications.

Puerarin alleviates acrolein-induced atherosclerosis by activating the MYH9-mediated SIRT1/Nrf2 cascade to inhibit the activation of inflammasome.

Puerarin (Pue) has significant antioxidant and anti-inflammatory properties. This work was designed to clarify and investigate the potential mechanisms of Pue in atherosclerosis (AS) progression. In vivo, acrolein (Acr) was inhaled through drinking water to construct AS model. In vitro, CCK-8 assay and lactate dehydrogenase (LDH) assay kit were used to detect cell viability. Apoptosis was detected by flow cytometry. The content of malondialdehyde (MDA) was determined by commercial kit, the level of inflammatory factors was detected by ELISA, and proteins were determined by western blot. Pue administration could effectively reduce blood lipid level in Acr-fed mice. Pue suppressed oxidative stress, the formation of atherosclerotic plaques, and the process of aortic histological changes. Pue pretreatment decreased MDA in HUVECs and maintained the activity of antioxidant enzymes. Pue upregulated SIRT1/Nrf2 cascade in HUVECs. Pue increased MYH9 and inhibited NLRP3 inflammasome-related proteins, and the inhibition of MYH9 significantly impaired Pue-induced Nrf2 activation. Moreover, HUVEC cytotoxicity and apoptosis are alleviated by Pue, in addition to NLRP3-mediated pyroptosis in HUVECs induced by Acr. MYH9 inhibitors effectively suppressed the pyroptosis induced by Acr and prevented injury to HUVECs. In addition, Pue promoted SIRT1/Nrf2 cascade activation in HUVECs. Pue may alleviate Acr-induced AS by activating the MYH9-mediated SIRT1/Nrf2 cascade to inhibit inflammasome activation.

How renal toxins respond to renal function deterioration and oral toxic adsorbent in pH-controlled releasing capsule.

The number of patients with chronic kidney disease (CKD) is increasing. Oral toxin adsorbents may provide some value. Several uremic toxins, including indoxyl sulfate (IS), p-cresol (PCS), acrolein, per- and poly-fluoroalkyl substances (PFAS), and inflammation markers (interleukin 6 [IL-6] and tumor necrosis factor [TNF]-alpha) have been shown to be related to CKD progression. A total of 81 patients taking oral activated charcoal toxin adsorbents (AC-134), which were embedded in capsules that dissolved in the terminal ileum, three times a day for 1 month, were recruited. The renal function, hemoglobulin (Hb), inflammation markers, three PFAS (PFOA, PFOS, and PFNA), and acrolein were quantified. Compared with the baseline, an improved glomerular filtration rate (GFR) and significantly lower acrolein were noted. Furthermore, the CKD stage 4 and 5 group had significantly higher concentrations of IS, PCS, IL-6, and TNF but lower levels of Hb and PFAS compared with the CKD Stage 3 group at baseline and after the intervention. Hb was increased only in the CKD Stage 3 group after the trial (p = .032). Acrolein did not differ between the different CKD stage groups. Patients with improved GFR (responders) (about 77%) and nonresponders had similar baseline GFR. Responders had higher acrolein and PFOA levels throughout the study and a more significant reduction in acrolein, indicating a better digestion function. Both the higher PFOA and lower acrolein may be related to improved eGFR (and possibly to improvements in proteinuria, which we did not measure. Proteinuria is associated with PFAS loss in the urine), AC-134 showed the potential to improve the GFR and decrease acrolein, which might better indicate renal function change. Future studies are needed with longer follow-ups.

Singlet-Oxygen-Mediated Regulation of Photosynthesis-Specific Genes: A Role for Reactive Electrophiles in Signal Transduction.

During photosynthesis, reactive oxygen species (ROS) are formed, including hydrogen peroxide (H2O2) and singlet oxygen (1O2), which have putative roles in signalling, but their involvement in photosynthetic acclimation is unclear. Due to extreme reactivity and a short lifetime, 1O2 signalling occurs via its reaction products, such as oxidised poly-unsaturated fatty acids in thylakoid membranes. The resulting lipid peroxides decay to various aldehydes and reactive electrophile species (RES). Here, we investigated the role of ROS in the signal transduction of high light (HL), focusing on GreenCut2 genes unique to photosynthetic organisms. Using RNA seq. data, the transcriptional responses of Chlamydomonas reinhardtii to 2 h HL were compared with responses under low light to exogenous RES (acrolein; 4-hydroxynonenal), ß-cyclocitral, a ß-carotene oxidation product, as well as Rose Bengal, a 1O2-producing photosensitiser, and H2O2. HL induced significant (p < 0.05) up- and down-regulation of 108 and 23 GreenCut2 genes, respectively. Of all HL up-regulated genes, over half were also up-regulated by RES, including RBCS1 (ribulose bisphosphate carboxylase small subunit), NPQ-related PSBS1 and LHCSR1. Furthermore, 96% of the genes down-regulated by HL were also down-regulated by 1O2 or RES, including CAO1 (chlorophyllide-a oxygnease), MDH2 (NADP-malate dehydrogenase) and PGM4 (phosphoglycerate mutase) for glycolysis. In comparison, only 0-4% of HL-affected GreenCut2 genes were similarly affected by H2O2 or ß-cyclocitral. Overall, 1O2 plays a significant role in signalling during the initial acclimation of C. reinhardtii to HL by up-regulating photo-protection and carbon assimilation and down-regulating specific primary metabolic pathways. Our data support that this pathway involves RES.

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.

MgO Modified by X2, HX, or Alkyl Halide (X = Cl, Br, or I) Catalytic Systems and Their Activity in Chemoselective Transfer Hydrogenation of Acrolein into Allyl Alcohol.

A new type of catalyst containing magnesium oxide modified with various modifiers ranging from bromine and iodine, to interhalogen compounds, hydrohalogenic acids, and alkyl halides have been prepared using chemical vapor deposition (CVD) and wet impregnation methods. The obtained systems were characterized using a number of methods: determination of the concentration of X- ions, surface area determination, powder X-ray diffraction (PXRD), surface acid-base strength measurements, TPD of probe molecules (acetonitrile, pivalonitrile, triethylamine, and n-butylamine), TPD-MS of reaction products of methyl iodide with MgO, and Fourier transform infrared spectroscopy (FTIR). The catalysts' activity and chemoselectivity during transfer hydrogenation from ethanol to acrolein to allyl alcohol was measured. A significant increase in the activity of modified MgO (up to 80% conversion) in the transfer hydrogenation of acrolein was found, while maintaining high chemoselectivity (>90%) to allyl alcohol. As a general conclusion, it was shown that the modification of MgO results in the suppression of strong basic sites of the oxide, with a simultaneous appearance of Brønsted acidic sites on its surface. Independently, extensive research on the reaction progress of thirty alkyl halides with MgO was also performed in order to determine its ability to neutralize chlorinated wastes.

Intermolecular Interactions between Aldehydes and Alcohols: Conformational Equilibrium and Rotational Spectra of Acrolein-Methanol Complex.

The rotational spectra of the 1:1 complex formed by acrolein and methanol and its deuterated isotopologues have been analyzed. Two stable conformations in which two hydrogen bonds between the two moieties are formed were detected. The rotational lines show a hyperfine structure due to the methyl group internal rotation in the complex and the V3 barriers hindering the motion were determined as 2.629(5) kJ mol-1 and 2.722(5) kJ mol-1 for the two conformations, respectively. Quantum mechanical calculations at the MP2/aug-cc-pVTZ level and comprehensive analysis of the intermolecular interactions, utilizing NCI and SAPT approaches, highlight the driving forces of the interactions and allow the determination of the binding energies of complex formation.

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.

Acrolein produced during acute kidney injury promotes tubular cell death.

Acute kidney injury is an important global health concern as it is associated with high morbidity and mortality. Polyamines, essential for cell growth and proliferation, are known to inhibit cardiovascular disease. However, under conditions of cellular damage, toxic acrolein is produced from polyamines by the enzyme spermine oxidase (SMOX). We used a mouse renal ischemia-reperfusion model and human proximal tubule cells (HK-2) to investigate whether acrolein exacerbates acute kidney injury by renal tubular cell death. Acrolein visualized by acroleinRED was increased in ischemia-reperfusion kidneys, particularly in tubular cells. When HK-2 cells were cultured under 1% oxygen for 24 h, then switched to 21% oxygen for 24 h (hypoxia-reoxygenation), acrolein accumulated and SMOX mRNA and protein levels were increased. Acrolein induced cell death and fibrosis-related TGFB1 mRNA in HK-2 cells. Administration of the acrolein scavenger cysteamine suppressed the acrolein-induced upregulation of TGFB1 mRNA. Cysteamine also inhibited a decrease in the mitochondrial membrane potential observed by MitoTrackerCMXRos, and cell death induced by hypoxia-reoxygenation. The siRNA-mediated knockdown of SMOX also suppressed hypoxia-reoxygenation-induced acrolein accumulation and cell death. Our study suggests that acrolein exacerbates acute kidney injury by promoting tubular cell death during ischemia-reperfusion injury. Treatment to control the accumulation of acrolein might be an effective therapeutic option for renal ischemia-reperfusion injury.

Redox perturbations in yeast cells lacking glutathione reductase.

Cellular redox homeostasis has a major effect on cell functions and its maintenance is supported by glutathione and protein thiols which serve as redox buffers in cells. The regulation of the glutathione biosynthetic pathway is a focus of a lot of scientific research. However, still little is known about how complex cellular networks influence glutathione homeostasis. In this work was used an experimental system based on an S. cerevisiae yeast mutant with a lack of the glutathione reductase enzyme and allyl alcohol as a precursor of acrolein inside the cell to determine the cellular processes influencing glutathione homeostasis. The absence of Glr1p slows down the growth rate of the cell population, especially in the presence of allyl alcohol, but does not lead to complete inhibition of the cell's reproductive capacity. It also amends the GSH/GSSG ratio and the share of NADPH and NADP+ in the total NADP(H) pool. The obtained results show that potential pathways involved in the maintenance of redox homeostasis are based from one side on de novo synthesis of GSH as indicated by increased activity of γ-GCS and increased expression of GSH1 gene in the Δglr1 mutant, from the other hand, on increased the level of NADPH. This is because the lower ratio of GSH/GSSG can be counterbalanced with the NADPH/NADP+ alternative system. The higher level of NADPH can be used by the thioredoxin system and other enzymes requiring NADPH to reduce cytosolic GSSG and maintain glutathione redox potential.

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.

A search for acrolein scavengers among food components.

Brain stroke is a major cause of being bedridden for elderly people, and preventing stroke is important for maintaining quality of life (QOL). Acrolein is a highly reactive aldehyde and causes tissue damage during stroke. Decreasing acrolein toxicity ameliorates tissue injury during brain stroke. In this study, we tried to identify food components which decrease acrolein toxicity. We found that 2-furanmethanethiol, cysteine methyl and ethyl esters, alliin, lysine and taurine decreased acrolein toxicity. These compounds neutralized acrolein by direct interaction. However, the interaction between acrolein and taurine was not so strong. Approximately 30 mM taurine was necessary to interact with 10 µM acrolein, and 2 g/kg taurine was necessary to decrease the size of mouse brain infarction. Taurine also slightly increased polyamine contents, which are involved in decrease in the acrolein toxicity. Mitochondrial potential damage by acrolein was also protected by taurine. Our results indicate that daily intake of foods containing 2-furanmethanethiol, cysteine methyl and ethyl esters, alliin, lysine and taurine may prevent severe injury in brain stroke and improve the quality of life for elderly people.

Acrolein: formation, health hazards and its controlling by dietary polyphenols.

Acrolein, a highly reactive toxic aldehyde, is a common dietary and environmental contaminant which can also be generated endogenously. Exposure to acrolein has been positively associated with some pathological conditions, such as atherosclerosis, diabetes mellitus, stroke, and Alzheimer's disease. At the cellular level, acrolein induces various harmful effects, particularly protein adduction and oxidative damages. Polyphenols are a group of secondary plant metabolites ubiquitously presented in fruits, vegetables, and herbs. Recent evidence has gradually solidified the protective role of polyphenols by working as acrolein scavengers and regulator of acrolein toxicities. This was largely attributed to the ability of polyphenols as antioxidants and sacrificial nucleophiles in trapping acrolein. This review discussed the exposure and toxicity of acrolein, summarized the known and anticipated contribution of polyphenols in ameliorating acrolein contamination and its health hazards.

Impairment of Endothelial Function by Cigarette Smoke Is Not Caused by a Specific Smoke Constituent, but by Vagal Input From the Airway.

BACKGROUND: Exposure to tobacco or marijuana smoke, or e-cigarette aerosols, causes vascular endothelial dysfunction in humans and rats. We aimed to determine what constituent, or class of constituents, of smoke is responsible for endothelial functional impairment. METHODS: We investigated several smoke constituents that we hypothesized to mediate this effect by exposing rats and measuring arterial flow-mediated dilation (FMD) pre- and post-exposure. We measured FMD before and after inhalation of sidestream smoke from research cigarettes containing normal and reduced nicotine level with and without menthol, as well as 2 of the main aldehyde gases found in both smoke and e-cigarette aerosol (acrolein and acetaldehyde), and inert carbon nanoparticles. RESULTS: FMD was reduced by all 4 kinds of research cigarettes, with extent of reduction ranging from 20% to 46% depending on the cigarette type. While nicotine was not required for the impairment, higher nicotine levels in smoke were associated with a greater percent reduction of FMD (41.1±4.5% reduction versus 19.2±9.5%; P=0.047). Lower menthol levels were also associated with a greater percent reduction of FMD (18.5±9.8% versus 40.5±4.8%; P=0.048). Inhalation of acrolein or acetaldehyde gases at smoke-relevant concentrations impaired FMD by roughly 50% (P=0.001). However, inhalation of inert carbon nanoparticles at smoke-relevant concentrations with no gas phase also impaired FMD by a comparable amount (P<0.001). Bilateral cervical vagotomy blocked the impairment of FMD by tobacco smoke. CONCLUSIONS: There is no single constituent or class of constituents responsible for acute impairment of endothelial function by smoke; rather, we propose that acute endothelial dysfunction by disparate inhaled products is caused by vagus nerve signaling initiated by airway irritation.

Acrolein Exposure Impaired Glucose Homeostasis and Increased Risk of Type 2 Diabetes: An Urban Adult Population-Based Cohort Study with Repeated Measures.

Acrolein is an identified high-priority hazardous air pollutant ubiquitous in daily life and associated with cardiometabolic risk that attracts worldwide attention. However, the etiology role of acrolein exposure in glucose dyshomeostasis and type 2 diabetes (T2D) is unclear. This repeated-measurement prospective cohort study included 3522 urban adults. Urine/blood samples were repeatedly collected for determinations of acrolein metabolites (N-acetyl-S-(3-hydroxypropyl)-l-cysteine, N-acetyl-S-(2-carboxyethyl)-l-cysteine; acrolein exposure biomarkers), glucose homeostasis, and T2D at baseline and a three-year follow-up. We found that each 3-fold increment in acrolein metabolites was cross-sectionally associated with 5.91-6.52% decrement in homeostasis model assessment-insulin sensitivity (HOMA-IS) and 0.07-0.14 mmol/L, 4.02-4.57, 5.91-6.52, 19-20, 18-19, and 23-31% increments in fasting glucose (FPG), fasting insulin (FPI), HOMA-insulin resistance (HOMA-IR), risks of prevalent IR, impaired fasting glucose (IFG), and T2D, respectively; longitudinally, participants with sustained-high acrolein metabolite levels had increased risks of incident IR, IFG, and T2D by 63-80, 87-99, and 120-154%, respectively (P < 0.05). In addition, biomarkers of heme oxygenase-1 activity (exhaled carbon monoxide), lipid peroxidation (8-iso-prostaglandin-F2α), protein carbonylation (protein carbonyls), and oxidative DNA damage (8-hydroxy-deoxyguanosine) mediated 5.00-38.96% of these associations. Our study revealed that acrolein exposure may impair glucose homeostasis and increase T2D risk via mediating mechanisms of heme oxygenase-1 activation, lipid peroxidation, protein carbonylation, and oxidative DNA damage.

Acrolein increases the concentration of intracellular Zn2⁺ by producing mitochondrial reactive oxygen species in A549 cells.

Smoking or occupational exposure leads to low concentrations of acrolein on the surface of the airways. Acrolein is involved in the pathophysiological processes of various respiratory diseases. Reports showed that acrolein induced an increase in mitochondrial reactive oxygen species (mROS). Furthermore, exogenous H2O2 was found to increase intracellular Zn2⁺ concentration ([Zn2⁺]ᵢ). However, the specific impact of acrolein on changes in intracellular Zn2⁺ levels has not been fully investigated. Therefore, this study aimed to investigate the effects of acrolein on mROS and [Zn2⁺]ᵢ in A549 cells. We used Mito Tracker Red CM-H2Xros (MitoROS) and Fluozin-3 fluorescent probes to observe changes in mROS and intracellular Zn2⁺. The results revealed that acrolein increased [Zn2⁺]ᵢ in a time- and dose-dependent manner. Additionally, the production of mROS was observed in response to acrolein treatment. Subsequent experiments showed that the intracellular Zn2⁺ chelator TPEN could inhibit the acrolein-induced elevation of [Zn2⁺]ᵢ but did not affect the acrolein-induced mROS production. Conversely, the acrolein-induced elevation of mROS and [Zn2⁺]ᵢ were significantly decreased by the inhibitors of ROS formation (NaHSO3, NAC). Furthermore, external oxygen free radicals increased both [Zn2⁺]ᵢ levels and mROS production. These results demonstrated that acrolein-induced elevation of [Zn2⁺]ᵢ in A549 cells was mediated by mROS generation, rather than through a pathway where [Zn2⁺]ᵢ elevation leads to mROS production.

Inhibition of Polyamine Catabolism Reduces Cellular Senescence.

The aging of the global population has necessitated the identification of effective anti-aging technologies based on scientific evidence. Polyamines (putrescine, spermidine, and spermine) are essential for cell growth and function. Age-related reductions in polyamine levels have been shown to be associated with reduced cognitive and physical functions. We have previously found that the expression of spermine oxidase (SMOX) increases with age; however, the relationship between SMOX expression and cellular senescence remains unclear. Therefore, we investigated the relationship between increased SMOX expression and cellular senescence using human-liver-derived HepG2 cells. Intracellular spermine levels decreased and spermidine levels increased with the serial passaging of cells (aged cells), and aged cells showed increased expression of SMOX. The levels of acrolein-conjugated protein, which is produced during spermine degradation, also increases. Senescence-associated ß-gal activity was increased in aged cells, and the increase was suppressed by MDL72527, an inhibitor of acetylpolyamine oxidase (AcPAO) and SMOX, both of which are enzymes that catalyze polyamine degradation. DNA damage accumulated in aged cells and MDL72527 reduced DNA damage. These results suggest that the SMOX-mediated degradation of spermine plays an important role in cellular senescence. Our results demonstrate that cellular senescence can be controlled by inhibiting spermine degradation using a polyamine-catabolizing enzyme inhibitor.

Acrolein Induces Retinal Abnormalities of Alzheimer's Disease in Mice.

It is reported that retinal abnormities are related to Alzheimer's disease (AD) in patients and animal models. However, it is unclear whether the retinal abnormities appear in the mouse model of sporadic Alzheimer's disease (sAD) induced by acrolein. We investigated the alterations of retinal function and structure, the levels of ß-amyloid (Aß) and phosphorylated Tau (p-Tau) in the retina, and the changes in the retinal vascular system in this mouse model. We demonstrated that the levels of Aß and p-Tau were increased in the retinas of mice from the acrolein groups. Subsequently, a decreased amplitudes of b-waves in the scotopic and photopic electroretinogram (ERG), decreased thicknesses of the retinal nerve fiber layer (RNFL) in the retina, and slight retinal venous beading were found in the mice induced by acrolein. We propose that sAD mice induced by acrolein showed abnormalities in the retina, which may provide a valuable reference for the study of the retina in sAD.

Transient Receptor Potential Ankyrin 1 (TRPA1) Channel Mediates Acrolein Cytotoxicity in Human Lung Cancer Cells.

Transient receptor potential ankyrin 1 (TRPA1) is a nonselective ion channel implicated in thermosensation and inflammatory pain. It has been reported that expression of the TRPA1 channel is induced by cigarette smoke extract. Acrolein found in cigarette smoke is highly toxic and known as an agonist of the TRPA1 channel. However, the role of TRPA1 in the cytotoxicity of acrolein remains unclear. Here, we investigated whether the TRPA1 channel is involved in the cytotoxicity of acrolein in human lung cancer A549 cells. The IC50 of acrolein in A549 cells was 25 µM, and acrolein toxicity increased in a concentration- and time-dependent manner. When the effect of acrolein on TRPA1 expression was examined, the expression of TRPA1 in A549 cells was increased by treatment with 50 µM acrolein for 24 h or 500 µM acrolein for 30 min. AP-1, a transcription factor, was activated in the cells treated with 50 µM acrolein for 24 h, while induction of NF-κB and HIF-1α was observed in the cells treated with 500 µM acrolein for 30 min. These results suggest that acrolein induces TRPA1 expression by activating these transcription factors. Overexpression of TRPA1 in A549 cells increased acrolein sensitivity and the level of protein-conjugated acrolein (PC-Acro), while knockdown of TRPA1 in A549 cells or treatment with a TRPA1 antagonist caused tolerance to acrolein. These findings suggest that acrolein induces the TRPA1 channel and that an increase in TRPA1 expression promotes the cytotoxicity of acrolein.

The Recycling of Substandard Rocket Fuel N,N-Dimethylhydrazine via the Involvement of Its Hydrazones Derived from Glyoxal, Acrolein, Metacrolein, Crotonaldehyde, and Formaldehyde in Organic Synthesis.

"Heptil" (unsymmetrical dimethylhydrazine-UDMH) is extensively employed worldwide as a propellant for rocket engines. However, UDMH constantly loses its properties as a result of its continuous and uncontrolled absorption of moisture, which cannot be rectified. This situation threatens its long-term usability. UDMH is an exceedingly toxic compound (Hazard Class 1), which complicates its transportation and disposal. Incineration is currently the only method used for its disposal, but this process generates oxidation by-products that are even more toxic than the original UDMH. A more benign approach involves its immediate reaction with a formalin solution to form 1,1-dimethyl-2-methylene hydrazone (MDH), which is significantly less toxic by an order of magnitude. MDH can then be polymerized under acidic conditions, and the resulting product can be burned, yielding substantial amounts of nitrogen oxides. This review seeks to shift the focus of MDH from incineration towards its application in the synthesis of relatively non-toxic and readily available analogs of various pharmaceutical substances. We aim to bring the attention of the international chemical community to the distinctive properties of MDH, as well as other hydrazones (such as glyoxal, acrolein, crotonal, and meta-crolyl), wherein each structural fragment can initiate unique transformations that have potential applications in molecular design, pharmaceutical research, and medicinal chemistry.