Accumulation Of Formaldehyde Research Articles

Metabolic engineering of Komagataella phaffii for the efficient utilization of methanol

BackgroundKomagataella phaffii, a type of methanotrophic yeast, can use methanol, a favorable non-sugar substrate in eco-friendly bio-manufacturing. The dissimilation pathway in K. phaffii leads to the loss of carbon atoms in the form of CO2. However, the ΔFLD strain, engineered to lack formaldehyde dehydrogenase—an essential enzyme in the dissimilation pathway—displayed growth defects when exposed to a methanol-containing medium.ResultsInhibiting the dissimilation pathway triggers an excessive accumulation of formaldehyde and a decline in the intracellular NAD+/NADH ratio. Here, we designed dual-enzyme complex with the alcohol oxidase1/dihydroxyacetone synthase1 (Aox1/Das1), enhancing the regeneration of the formaldehyde receptor xylulose-5-phosphate (Xu5P). This strategy mitigated the harmful effects of formaldehyde accumulation and associated toxicity to cells. Concurrently, we elevated the NAD+/NADH ratio by overexpressing isocitrate dehydrogenase in the TCA cycle, promoting intracellular redox homeostasis. The OD600 of the optimized combination of the above strategies, strain DF02-1, was 4.28 times higher than that of the control strain DF00 (ΔFLD, HIS4+) under 1% methanol. Subsequently, the heterologous expression of methanol oxidase Mox from Hansenula polymorpha in strain DF02-1 resulted in the recombinant strain DF02-4, which displayed a growth at an OD600 4.08 times higher than that the control strain DF00 in medium containing 3% methanol.ConclusionsThe reduction of formaldehyde accumulation, the increase of NAD+/NADH ratio, and the enhancement of methanol oxidation effectively improved the efficient utilization of a high methanol concentration by strain ΔFLD strain lacking formaldehyde dehydrogenase. The modification strategies implemented in this study collectively serve as a foundational framework for advancing the efficient utilization of methanol in K. phaffii.

Organoleptic quality and formaldehyde content of mackerel marketed in Dar es Salaam, Tanzania

BackgroundFish constitutes a nutritious food that deteriorates quickly when poorly preserved. Several biochemicals, including formaldehyde, accumulate naturally in the fish post-mortem. Apart from this natural formaldehyde, reports reveal the deliberate addition of formalin (37% formaldehyde solution) to the stored fish as a preservative. This is risky to consumers since formaldehyde is carcinogenic, genotoxic, and a potentiator of other carcinogens.AimThis study aimed to assess both the organoleptic quality and formaldehyde content of mackerels, the most consumed fish in Dar es Salaam, Tanzania.MethodsA total of 60 mackerel samples were conveniently and equally obtained from the local markets, street vendors, and supermarkets in five districts of the Dar es Salaam region. Organoleptic quality was evaluated based on organoleptic characteristics. Formaldehyde analysis was done by High-Performance Liquid Chromatography (HPLC). Analysis of variance was subsequently run to test the variation of formaldehyde content in mackerel by outlet type and district.ResultsAll analyzed mackerel samples had acceptable levels of organoleptic quality (2.46 ± 0.50) and a mean formaldehyde concentration of 10.89 ± 2.44 mg/kg. On average, the samples from supermarkets had the highest level of organoleptic quality (2.20 ± 0.21) but were also the most contaminated with formaldehyde (16.07 ± 4.68 mg/kg), while those from local markets were the least contaminated (3.91 ± 1.86 mg/kg) (p = 0.000). Moreover, 0% (n = 0), 20% (n = 4), and 35% (n = 7) of samples from local markets, street vendors, and supermarkets, respectively, had formaldehyde concentrations above 20 mg/kg, the previously estimated highest concentration for naturally formed formaldehyde in fish.ConclusionMackerels marketed in Dar es Salaam have acceptable organoleptic quality but are substantially contaminated with formaldehyde. Whether this is natural or artificial formaldehyde, our findings are inconclusive given the conflicting global standards. Nonetheless, the findings reveal the potential exposure of fish consumers to formaldehyde. Future research should explore the dynamics of the accumulation of natural formaldehyde in marketed fish and accurately assess the risk associated with the exposure of consumers to the formaldehyde in fish. The emanating findings will ultimately guide the development of local guidelines for natural and permissible formaldehyde concentrations in fish and fish products in Tanzania.

Green tea marinades can reduce formaldehyde of pan-fried pork via Mannich reaction mechanism

Foods containing proteins or unsaturated fatty acids can generate toxic formaldehyde upon exposure to high thermal. Polyphenol-fortified food has been proved to be has less heat-induced toxic aldehydes formation (including formaldehyde), however, the chemical mechanism underlie such effect has not been fully revealed. In the present research, whether Mannich reaction mechanism is responsible for natural polyphenols's inhibition on formaldehyde production on cooking meat was explored. It is validated that green tea marination can suppress the accumulation of formaldehyde of pan-fried porks. By using HPLC, LC-ESI-MS and LC-ESI-HRMS analysis, members of catechins from tea polyphenols were found has high activity for Mannich addition. Besides, a serial of polyphenol-formaldehyde-amino acid three-component adducts were found in the extract of green tea marinated pork. Herein, we proposed firstly that tea polyphenols' inhibitory effect on formaldehyde was accounted for (at least in part) the formation of Mannich adducts.

Improving Methanol Utilization by Reducing Alcohol Oxidase Activity and Adding Co-Substrate of Sodium Citrate in Pichia pastoris.

Methanol, which produced in large quantities from low-quality coal and the hydrogenation of CO2, is a potentially renewable one-carbon (C1) feedstock for biomanufacturing. The methylotrophic yeast Pichia pastoris is an ideal host for methanol biotransformation given its natural capacity as a methanol assimilation system. However, the utilization efficiency of methanol for biochemical production is limited by the toxicity of formaldehyde. Therefore, reducing the toxicity of formaldehyde to cells remains a challenge to the engineering design of a methanol metabolism. Based on genome-scale metabolic models (GSMM) calculations, we speculated that reducing alcohol oxidase (AOX) activity would re-construct the carbon metabolic flow and promote balance between the assimilation and dissimilation of formaldehyde metabolism processes, thereby increasing the biomass formation of P. pastoris. According to experimental verification, we proved that the accumulation of intracellular formaldehyde can be decreased by reducing AOX activity. The reduced formaldehyde formation upregulated methanol dissimilation and assimilation and the central carbon metabolism, which provided more energy for the cells to grow, ultimately leading to an increased conversion of methanol to biomass, as evidenced by phenotypic and transcriptome analysis. Significantly, the methanol conversion rate of AOX-attenuated strain PC110-AOX1-464 reached 0.364 g DCW/g, representing a 14% increase compared to the control strain PC110. In addition, we also proved that adding a co-substrate of sodium citrate could further improve the conversion of methanol to biomass in the AOX-attenuated strain. It was found that the methanol conversion rate of the PC110-AOX1-464 strain with the addition of 6 g/L sodium citrate reached 0.442 g DCW/g, representing 20% and 39% increases compared to AOX-attenuated strain PC110-AOX1-464 and control strain PC110 without sodium citrate addition, respectively. The study described here provides insight into the molecular mechanism of efficient methanol utilization by regulating AOX. Reducing AOX activity and adding sodium citrate as a co-substrate are potential engineering strategies to regulate the production of chemicals from methanol in P. pastoris.

Autoxidation of glycols used in inhalable daily products: implications for the use of artificial fogs and e-cigarettes.

The use of glycols is seen in various industries and occupations. In the past few decades, the health implications of inhalable glycols have gained public attention. Inhalable glycols may cause adverse health effects, especially for workers in occupations receiving frequent exposure and consumers of glycol-based daily products. Our previous work highlighted the rapid accumulation of formaldehyde and glycolaldehyde in fog juice, thus proposing the occurrence of glycol autoxidation. However, the fundamentals of glycol autoxidation remained unclear and unexplored. Our goal is to investigate the autoxidation of common glycols during indoor storage. Carbonyls were quantified using liquid chromatography-mass spectrometry (LC-MS), and peroxides from autoxidation were monitored via iodometry and UV-Vis spectrometry. The impact of certain factors such as the water mixing ratio and antioxidants (vitamin C) was also investigated. Formation of aldehydes in many glycols was weekly monitored, such as e-cigarette juice and triethylene glycol (TEG). Occurrence of autoxidation was confirmed by the increase in the total peroxide concentration. Additionally, we highlighted the dependence of the carbonyl formation rate on the TEG-water mixing ratio, demonstrating the complex role of water in glycol autoxidation. We have also tested the effectiveness of vitamin C and made suggestions for minimizing the formation of toxic carbonyls in consumer products.

Systematic evaluation of urinary formic acid as a new potential biomarker for Alzheimer's disease.

The accumulation of endogenous formaldehyde is considered a pathogenic factor in Alzheimer's disease (AD). The purpose of this study was to investigate the relationship between urinary formic acid and plasma biomarkers in AD. Five hundred and seventy-four participants were divided into five groups according to their diagnosis: 71 with normal cognitive (NC), 101 with subjective cognitive decline (SCD), 131 with cognitive impairment without mild cognitive impairment (CINM), 158 with mild cognitive impairment (MCI), and 113 with AD. With the progression of the disease, urinary formic acid levels showed an overall upward trend. Urinary formic acid was significantly correlated with Mini-Mental State Examination (MMSE) scores, the Chinese version of Addenbrooke's Cognitive Examination III (ACE-III) scores, and Montreal Cognitive Assessment-Basic (MoCA-B) time. The areas under the receiver operating characteristic curves (AUC) of urinary formic acid in distinguishing NC from AD was 0.797, which was similar to that of plasma neurofilament light chain (NfL; AUC = 0.768) and better than other plasma biomarkers (Aβ40, Aβ42, Aβ42/Aβ40, T-tau, P-tau181, and P-tau181/T-tau). We also found that using urinary formic acid and formaldehyde levels could improve the accuracy of using plasma biomarkers to determine AD disease stage. Our study revealed the possibility of urinary formic acid as a potential novel biomarker for the early diagnosis of AD.

Enhancing monellin production in Pichia pastoris fed-batch fermentation through an efficient on-line methanol/sorbitol co-feeding strategy

Methanol is the sole inducer for driving recombinant protein expression in P. pastoris fed-batch fermentation. However, when adopting methanol-only feeding and controlling its concentration at the optimal level (5–10 g/L) would decrease dissolved oxygen concentration (DO) down to limitation conditions due to its high combustion enthalpy, leading to the severe accumulations of formaldehyde and a limited recombinant protein expression. To solve these problems, with help of the lower combustion enthalpy of sorbitol, an efficient on-line methanol/sorbitol co-feeding strategy was proposed, using monellin production as a prototype. The scheme of this strategy was that the feeding of methanol was controlled by ON-OFF control mode to ensure methanol induction strength via controlling its concentration around 5–10 g/L, while the co-feeding of sorbitol was determined by an improved DO-stat mode to repress the accumulation of formaldehyde via maintaining DO at sufficient levels of 5–15%.When adopting this strategy, 1) DO was maintained at sufficient levels and thus the severe accumulation of formaldehyde was reduced to nearly zero level; 2) the methanol metabolic flux to cells maintenance could be kept at the lowest level (0.011 1/h vs 0.018–0.026 1/h); 3) monellin degradation by proteases was weakened; 4) the major energy regeneration pattern energizing monellin biosynthesis switched from formaldehyde (methanol) dissimilatory pathway to TCA cycle; 5) the maximum monellin expression titer of 2.45 g/L was obtained, which was 2.35–4.53 fold compared with that obtained using methanol-only feeding. In conclusion, the proposed on-line methanol/sorbitol co-feeding strategy could inhibit the severe accumulation of toxic metabolite formaldehyde through maintaining DO at the sufficient level and switching energy regeneration pattern from formaldehyde dissimilatory pathway to TCA cycle, while increasing cells metabolic activities reflected by a lower maintenance coefficient and formation rate of proteases etc., which eventually achieved an effective monellin expression in turn.

Methanol biotransformation toward high-level production of fatty acid derivatives by engineering the industrial yeast Pichia pastoris.

Methanol-based biorefinery is a promising strategy to achieve carbon neutrality goals by linking CO2 capture and solar energy storage. As a typical methylotroph, Pichia pastoris shows great potential in methanol biotransformation. However, challenges still remain in engineering methanol metabolism for chemical overproduction. Here, we present the global rewiring of the central metabolism for efficient production of free fatty acids (FFAs; 23.4 g/L) from methanol, with an enhanced supply of precursors and cofactors, as well as decreased accumulation of formaldehyde. Finally, metabolic transforming of the fatty acid cell factory enabled overproduction of fatty alcohols (2.0 g/L) from methanol. This study demonstrated that global metabolic rewiring released the great potential of P. pastoris for methanol biotransformation toward chemical overproduction.

Unravelling Formaldehyde Metabolism in Bacteria: Road towards Synthetic Methylotrophy.

Formaldehyde metabolism is prevalent in all organisms, where the accumulation of formaldehyde can be prevented through the activity of dissimilation pathways. Furthermore, formaldehyde assimilatory pathways play a fundamental role in many methylotrophs, which are microorganisms able to build biomass and obtain energy from single- and multicarbon compounds with no carbon–carbon bonds. Here, we describe how formaldehyde is formed in the environment, the mechanisms of its toxicity to the cells, and the cell’s strategies to circumvent it. While their importance is unquestionable for cell survival in formaldehyde rich environments, we present examples of how the modification of native formaldehyde dissimilation pathways in nonmethylotrophic bacteria can be applied to redirect carbon flux toward heterologous, synthetic formaldehyde assimilation pathways introduced into their metabolism. Attempts to engineer methylotrophy into nonmethylotrophic hosts have gained interest in the past decade, with only limited successes leading to the creation of autonomous synthetic methylotrophy. Here, we discuss how native formaldehyde assimilation pathways can additionally be employed as a premise to achieving synthetic methylotrophy. Lastly, we discuss how emerging knowledge on regulation of formaldehyde metabolism can contribute to creating synthetic regulatory circuits applied in metabolic engineering strategies.

Opposite Roles of Co-enzyme Q10 and Formaldehyde in Neurodegenerative Diseases.

Most of neurodegenerative diseases (NDD) have no cure. The common etiology of neurodegenerations is unclear. Air pollutant-gaseous formaldehyde is notoriously known to induce demyelination and cognitive impairments. Unexpectedly, an amount of formaldehyde has been detected in the brains. Multiple factors can induce the generation and accumulation of endogenous formaldehyde. Excessive formaldehyde can induce oxidative stress to generate H2O2; in turn, H2O2 promote formaldehyde production. Clinical investigations have shown that an abnormal high level of formaldehyde but low level of coenzyme Q10 (coQ10) was observed in patients with NDD. Further studies have proven that excessive formaldehyde directly inactivates coQ10, reduces the ATP generation, enhances oxidative stress, initiates inflammation storm, induces demyelination; subsequently, it results in neurodegeneration. Although the low water solubility of coQ10 limits its clinical application, nanomicellar water-soluble coQ10 exhibits positive therapeutical effects. Hence, nanopackage of coQ10 may be a promising strategy for treating NDD.

In Situ Imaging of Formaldehyde in Live Mice with High Spatiotemporal Resolution Reveals Aldehyde Dehydrogenase-2 as a Potential Target for Alzheimer's Disease Treatment.

Alterations in formaldehyde (FA) homeostasis are associated with the pathology of Alzheimer's disease (AD). In vivo tracking of FA flux is important for understanding the underlying molecular mechanisms, but is challenging due to the lack of sensitive probes favoring a selective, rapid, and reversible response toward FA. In this study, we re-engineered the promiscuous and irreversible phenylhydrazines to make them selective and reversible toward FA by tuning their nucleophilicity. This effort resulted in PFM309, a selective (selectivity coefficient KFA,methylglyoxal = 0.06), rapid (t1/2 = 32 s at [FA] = 200 μM), and reversible fluorogenic probe (K = 6.24 mM-1) that tracks the FA flux in both live cells and live mice. In vivo tracking of the FA flux was realized by PFM309 imaging, which revealed the gradual accumulation of FA in the live mice brain during normal aging and its further increase in AD mice. We further identified the age-dependent loss of catabolism enzymes ALDH2 and ADH5 as the primary mechanism responsible for formaldehyde excess. Activating ALDH2 with the small molecular activator Alda1 significantly protected neurovascular cells from formaldehyde overload and consequently from impairment during AD progress both in vitro and in vivo. These findings revealed PFM309 as a robust tool to study AD pathology and highlight ALDH2 as a potential target for AD drug development.

Molecular dissection of a dedicated formaldehyde dehydrogenase from Mycobacterium smegmatis.

Accumulation of formaldehyde, a highly reactive molecule, in the cell is toxic, and requires detoxification for the organism's survival. Mycothiol-dependent formaldehyde dehydrogenase or S-nitrosomycothiol reductase (MscR) from Mycobacterium smegmatis and Mycobacterium tuberculosis was previously known for detoxifying formaldehyde and protecting the cell against nitrosative stress. We here show that M. smegmatis MscR exhibits a mycothiol-independent formaldehyde dehydrogenase (FDH) activity in vitro. Presence of zinc in the reaction enhances MscR activity, thus making it a zinc-dependent FDH. Interestingly, MscR utilizes only formaldehyde and no other primary aldehydes as its substrate in vitro, and M. smegmatis lacking mscR (ΔmscR) shows sensitivity exclusively toward formaldehyde. Bioinformatics analysis of MscRs from various bacteria reveals 10 positionally conserved cysteines, whose importance in structural stability and biological activity is not yet investigated. To explore the significance of these cysteines, we generated MscR single Cys variants by systematically replacing each cysteine with serine. All of the Cys variants except C39S and C309S are unable to show a complete rescue of ΔmscR on formaldehyde, show a significant loss of enzymatic activity in vitro, pronounced structural alterations as probed by circular dichroism, and loss of homotetramerization on size exclusion chromatography. Our data thus reveal the importance of intact cysteines in the structural stability and biological activity of MscR, which is a dedicated FDH in M. smegmatis, and shows ~84% identity with M. tuberculosis MscR. We believe that this knowledge will further help in the development of FDH as a potential drug target against M. tuberculosis infections.

Formaldehyde-Crosslinked Nontoxic Aβ Monomers to Form Toxic Aβ Dimers and Aggregates: Pathogenicity and Therapeutic Perspectives.

Alzheimer's disease (AD) is characterized by the presence of senile plaques in the brain. However, medicines targeting amyloid-beta (Aβ) have not achieved the expected clinical effects. This review focuses on the formation mechanism of the Aβ dimer (the basic unit of oligomers and fibrils) and its tremendous potential as a drug target. Recently, age-associated formaldehyde and Aβ-derived formaldehyde have been found to crosslink the nontoxic Aβ monomer to form the toxic dimers, oligomers and fibrils. Particularly, Aβ-induced formaldehyde accumulation and formaldehyde-promoted Aβ aggregation form a vicious cycle. Subsequently, formaldehyde initiates Aβ toxicity in both the early-and late-onset AD. These facts also explain why AD drugs targeting only Aβ do not have the desired therapeutic effects. Development of the nanoparticle-based medicines targeting both formaldehyde and Aβ dimer is a promising strategy for improving the drug efficacy by penetrating blood-brain barrier and extracellular space into the cortical neurons in AD patients.

Accumulation of formaldehyde causes motor deficits in an in vivo model of hindlimb unloading

During duration spaceflight, or after their return to earth, astronauts have often suffered from gait instability and cerebellar ataxia. Here, we use a mouse model of hindlimb unloading (HU) to explore a mechanism of how reduced hindlimb burden may contribute to motor deficits. The results showed that these mice which have experienced HU for 2 weeks exhibit a rapid accumulation of formaldehyde in the gastrocnemius muscle and fastigial nucleus of cerebellum. The activation of semicarbazide-sensitive amine oxidase and sarcosine dehydrogenase induced by HU-stress contributed to formaldehyde generation and loss of the abilities to maintain balance and coordinate motor activities. Further, knockout of formaldehyde dehydrogenase (FDH-/-) in mice caused formaldehyde accumulation in the muscle and cerebellum that was associated with motor deficits. Remarkably, formaldehyde injection into the gastrocnemius muscle led to gait instability; especially, microinfusion of formaldehyde into the fastigial nucleus directly induced the same symptoms as HU-induced acute ataxia. Hence, excessive formaldehyde damages motor functions of the muscle and cerebellum.

Formaldehyde exposure and atmospheric biomonitoring with lichen Cladonia verticillaris in an anatomy laboratory.

Formaldehyde is one of the most toxic contaminants of indoor environments and very common in the anatomy laboratory. In this work, we investigated the level of formaldehyde exposure to staff and students who attended an anatomy lab and in nearby environments in the same university building. We also performed atmospheric biomonitoring of the sites with the lichen Cladonia verticillaris. Quantification samplings were performed over four weeks, on 7 days with and 7 days without practical classes, totaling 70 samples. The samples were collected in five different locations, three points inside the laboratory and two points outside the laboratory, representing nearby and susceptible environments to contamination. The results showed CHOH concentrations from 0.20-3.76 ppmv for days with practical courses and 0.17-3.06 ppmv for days without practical classes. Although the laboratory was more contaminated than the surrounding environments, the concentration of formaldehyde in these areas is not negligible, showing a dispersion of formaldehyde from the laboratory. Potential dose (PD) and cancer risk (CR) were calculated for an individual exposed to the same levels analyzed for 8 h daily and 30 years of work. The study on C. verticillaris lasted 90 days and evaluated the variation of chlorophyll and pheophytin (photosynthetic pigments). The results showed a significant difference in the production of chlorophylls a and b and total chlorophyll when compared to control, and there was also a progressive increase of the total pheophytin/total chlorophyll ratio. The results also showed the correlation between the increase in chlorophylls and the studied environments with less ventilation since these places provided greater accumulation of formaldehyde in the long run. Thus, measurable evidence was obtained of biological disorders in a living organism caused by exposure to formaldehyde.

Radiation-Induced Processes in Diazoquinone–Novolac Resist Films under Irradiation with 60Co γ-Rays

The processes occurring under the irradiation of FP9120 diazoquinone–novolac resist films on silicon with 60Co γ-rays have been studied by attenuated total reflectance (ATR) FTIR spectroscopy. It has been found that a significant modification of the ATR spectra of the photoresist films was noticeable only at absorbed doses above 200 kGy, and it occurred due to the radiation-induced transformations of methyl, methylene, hydroxymethyl, and phenoxyl groups of phenol–formaldehyde resin and o-naphthoquinone diazide (a photosensitive component). At the same time, the ATR spectra exhibited no signs of the destruction of aromatic fragments in the resist at doses to 300 kGy. In the region of the stretching vibrations of C=O bonds, a decrease in the maximum intensity of a band at ~1700 cm–1 was observed upon irradiation with its simultaneous broadening and shift to the high-energy region by ~30 cm–1 due to a change in the nearest environment of the C=O group. An increase in the absorption band intensity at 1650 cm–1 indicated the accumulation of formaldehyde upon the γ-irradiation of the resist as a result of the fragmentation of hydroxymethyl residues in the phenol–formaldehyde resin.

Sonochemical Transformations of Methane and Ethylene in Aqueous Solutions under Conditions of Cavitation

The conversion of methane, ethylene and mixtures of them in aqueous solutions was studied using ultrasonic vibrations with a frequency of 22 kHz under conditions of cavitation. It is found that formaldehyde, the main product, forms even if there is no dissolved oxygen in the initial solution. It is shown that the rate of accumulation of formaldehyde depends on the power of the ultrasound and the amount of molecular oxygen introduced into the system.

Mitochondrial dysfunction and DNA damage accompany enhanced levels of formaldehyde in cultured primary human fibroblasts

Formaldehyde (FA) is a simple biological aldehyde that is produced inside cells by several processes such as demethylation of DNA and proteins, amino acid metabolism, lipid peroxidation and one carbon metabolism (1-C). Although accumulation of excess FA in cells is known to be cytotoxic, it is unknown if an increase in FA level might be associated with mitochondrial dysfunction. We choose to use primary human fibroblasts cells in culture (foreskin, FSK) as a physiological model to gain insight into whether an increase in the level of FA might affect cellular physiology, especially with regard to the mitochondrial compartment. FSK cells were exposed to increasing concentrations of FA, and different cellular parameters were studied. Elevation in intracellular FA level was achieved and was found to be cytotoxic by virtue of both apoptosis and necrosis and was accompanied by both G2/M arrest and reduction in the time spent in S phase. A gene expression assessment by microarray analysis revealed FA affected FSK cells by altering expression of many genes including genes involved in mitochondrial function and electron transport. We were surprised to observe increased DNA double-strand breaks (DSBs) in mitochondria after exposure to FA, as revealed by accumulation of γH2A.X and 53BP1 at mitochondrial DNA foci. This was associated with mitochondrial structural rearrangements, loss of mitochondrial membrane potential and activation of mitophagy. Collectively, these results indicate that an increase in the cellular level of FA can trigger mitochondrial DNA double-strand breaks and dysfunction.

Human Endogenous Formaldehyde as an Anticancer Metabolite: Its Oxidation Downregulation May Be a Means of Improving Therapy.

Malignant cells are characterized by an increased content of endogenous formaldehyde formed as a by-product of biosynthetic processes. Accumulation of formaldehyde in cancer cells is combined with activation of the processes of cellular formaldehyde clearance. These mechanisms include increased ALDH and suppressed ADH5/FDH activity, which oncologists consider poor and favorable prognostic markers, respectively. Here, the sources and regulation of formaldehyde metabolism in cancer cells are reviewed. The authors also analyze the participation of oncoproteins such as fibulins, FGFR1, HER2/neu, FBI-1, and MUC1-C in the control of genes related to formaldehyde metabolism, suggesting the existence of two mutually exclusive processes in cancer cells: 1) production and 2) oxidation and elimination of formaldehyde from the cell. The authors hypothesize that the study of the anticancer properties of disulfiram and alpha lipoic acid - which affect the balance of formaldehyde in the body - may serve as the basis of future anticancer therapy.

Formaldehyde interacts with RNA rather than DNA: Accumulation of formaldehyde by the RNA-inorganic hybrid material

Formaldehyde (HCHO) has been known to react with a nucleobase which possesses an amino group and denatures the nucleic acid, such as RNA and DNA. Therefore, we demonstrated the accumulation of HCHO from an aqueous solution by the water-insoluble nucleic acid-inorganic hybrid materials which were prepared by mixing the nucleic acid with a silane coupling reagent (SiNSi). As a result, the water-insoluble nucleic acid-SiNSi hybrid materials effectively accumulated the HCHO from an aqueous solution. In particular, at the maximum accumulated amount of HCHO, the molar ratios of RNA (ribonucleotide):HCHO and DNA (deoxyribonucleotide):HCHO were 1:0.055 and 1:0.015, respectively. Additionally, the accumulative mechanism of HCHO was related to the reaction between HCHO and the nucleobase with the amino group. Furthermore, the RNA material showed a conformational change at a low HCHO concentration and these conformational changes of RNA were greater than that of DNA. These results suggested that HCHO molecule interacts with RNA rather than DNA.