dichloroacetate

BACKGROUND: Disinfection byproducts (DBPs) have been shown to impair thyroid function in experimental models. However, epidemiological evidence is scarce. METHODS: This study included 1190 women undergoing assisted reproductive technology (ART) treatment from the Tongji Reproductive and Environmental (TREE) cohort from December 2018 to August 2021. Serum thyrotropin (TSH), free triiodothyronine (FT3), and free thyroxine (FT4) were measured as indicators of thyroid function...

Insulin resistance is a risk factor for type 2 diabetes and exercise can improve insulin sensitivity. However, following exercise high circulating fatty acid (FA) levels might counteract this. We hypothesized that such inhibition would be reduced by forcibly increasing carbohydrate oxidation through pharmacological activation of the pyruvate dehydrogenase complex (PDC). Insulin-stimulated glucose uptake was examined with a cross-over design in healthy young men (n = 8) in a previously exercised and a rested leg during a hyperinsulinemiceuglycemic clamp five hours after one-legged exercise with: 1) infusion of saline, 2) infusion of intralipid imitating circulating FA levels during recovery from whole-body exercise, and 3) infusion of intralipid + oral PDC-activator, dichloroacetate (DCA)...

Dichloroacetic acid or trichloroacetic acid are commonly used in the detritylation reaction of the automated solid-phase synthesis of oligonucleotides. Dichloroacetic acid, however, is often contaminated with trichloroacetaldehyde (chloral), leading to the formation of inseparable impurities in the final oligonucleotide product. In this work, three different sequences, namely T18 , d(TAA)6 , and an 18-mer mixed sequence, were used as models to compare the deprotection efficiency of three acids: trichloroacetic acid, dichloroacetic acid, and difluoroacetic acid...

The study presents data on the anti-inflammatory effects of a combination of sodium dichloroacetate and sodium valproate (DCA-VPA) on the expression of inflammation- and immune response-related genes in T lymphocytes of SARS-CoV-2 patients. The study aimed to assess the effects of DCA-VPA on the genes of cytokine activity, chemokine-mediated signaling, neutrophil chemotaxis, lymphocyte chemotaxis, T-cell chemotaxis, and regulation of T-cell proliferation pathways. The study included 21 patients with SARS-CoV-2 infection and pneumonia: 9 male patients with a mean age of 68...

Storm events play a crucial role in organic matter transport within watersheds and can increase the concentration and alter the composition of NOMs and DBP formation potential. To assess the impact that storm events can have on drinking water quality, samples were collected and analyzed across four storm events in the Neversink River, Catskill region, New York in 2019 and 2022. Source water natural organic matter (NOM) was characterized, and the change of NOM quality was evaluated due to storm impacts. During storm events, a high level of NOM mobilization is initiated by heavy precipitation causing overland flow and a rise in the water table...

Tumor malignant cells are characterized by dysregulation of mitochondrial bioenergetics due to the 'Warburg effect'. In the present study, this metabolic imbalance was explored as a potential target for novel cancer chemotherapy. Imatinib (IM) downregulates the expression levels of SCΟ2 and FRATAXIN ( FXN ) genes involved in the heme‑dependent cytochrome c oxidase biosynthesis and assembly pathway in human erythroleukemic IM‑sensitive K‑562 chronic myeloid leukemia cells (K‑562)...

Mitochondrial dysfunction is considered one of the major pathogenic mechanisms of sepsis-induced cardiomyopathy (SIC). Pyruvate dehydrogenase kinase 4 (PDK4), a key regulator of mitochondrial metabolism, is essential for maintaining mitochondrial function. However, its specific role in SIC remains unclear. To investigate this, we established an in vitro model of septic cardiomyopathy using lipopolysaccharide (LPS)-induced H9C2 cardiomyocytes. Our study revealed a significant increase in PDK4 expression in LPS-treated H9C2 cardiomyocytes...

Haloacetic acids (HAAs) are ubiquitous in drinking water and have been associated with impaired male reproductive health. However, epidemiological evidence exploring the associations between HAA exposure and reproductive hormones among males is scarce. In the current study, the urinary concentrations of dichloroacetic acid (DCAA) and trichloroacetic acid (TCAA), the internal exposure markers of HAAs, as well as sex hormones (testosterone [T], progesterone [P], and estradiol [E2 ]) were measured among 449 Chinese men...

The increasing demand for trichloroisocyanuric acid (TCCA) in swimming pool disinfection highlights the need to evaluate its applicability in terms of disinfection by-product (DBP) formation. Nevertheless, there is limited understanding of DBP formation and control during TCCA disinfection, particularly concerning the effects of various management parameters. This study aimed to fill this knowledge gap by comprehensively investigating DBP formation during TCCA chlorination, with a particular focus on assessing the contribution and interaction of influencing factors using Box-Behnken Design and response surface methodology...

The Parsurameswara stone monument, built in the seventh century, is one of the oldest stone monuments in Odisha, India. Metagenomic analysis of the biological crust samples collected from the stone monument revealed 17 phyla in the microbiome, with Proteobacteria being the most dominant phylum, followed by cyanobacteria. Eight cyanobacteria were isolated. Lyngbya corticicola was the dominant cyanobacterium in all crust samples and could tolerate six months of desiccation in vitro . With six months of desiccation, chlorophyll- a decreased; however, carotenoid and cellular carbohydrate contents of this organism increased in the desiccated state...

Amyotrophic lateral sclerosis (ALS) is a devastating neurodegenerative disease characterized by the progressive loss of motor neurons, for which current treatment options are limited. Recent studies have shed light on the role of mitochondria in ALS pathogenesis, making them an attractive therapeutic intervention target. This review contains a very comprehensive critical description of the involvement of mitochondria and mitochondria-mediated mechanisms in ALS. The review covers several key areas related to mitochondria in ALS, including impaired mitochondrial function, mitochondrial bioenergetics, reactive oxygen species, metabolic processes and energy metabolism, mitochondrial dynamics, turnover, autophagy and mitophagy, impaired mitochondrial transport, and apoptosis...

BACKGROUND: Reactive oxygen species (ROS) and inflammation are reported to have a fundamental role in the pathogenesis of ischemia-reperfusion (IR) injury, a leading cause of acute kidney injury. The present study investigated the role of pyruvate dehydrogenase kinase 4 (PDK4) in ROS production and inflammation following IR injury. METHODS: We used a streptozotocin-induced diabetic C57BL6/J mouse model, which was subjected to IR by clamping both renal pedicles. Cellular apoptosis and inflammatory markers were evaluated in NRK-52E cells and mouse primary tubular cells after hypoxia and reoxygenation using a hypoxia work station...

As an oral antidiabetic agent, dichloroacetate (DCA) has been proven to improve diabetes and related complications. However, its functional role in diabetic cataract (DC) remains to be elucidated. This study was to define the role of DCA and its underlying molecular mechanism in DC in vitro and in vivo. In this study, it was shown that DCA dose-dependently ameliorated DC formation and development in DM rats. In addition, DCA significantly increased cell viability, reduced apoptosis, and inhibited EMT and oxidative stress of high glucose (HG)-treated SRA-01/04 cells in a concentration-dependent manner...

Improving the activation capacity of peroxymonosulfate (PMS) to increase radical and non-radical production is critical for antibiotic degradation. However, how to boost reactive oxygen species (ROS) and speed interfacial charge transfer remains an essential challenge. We report a coupling system of 10 %CNNS/CuBi2 O4 photocatalyst and sulfate radical-based advanced oxidation processes (SO4 - -AOPs) to enhance the activation of PMS and improve antibiotic degradation. Owing to highly efficient oxygen activation and interfacial charge transfer, the degradation efficiency of the photo-assisted PMS system was as high as 51...

Pyruvate, the final product of glycolysis, undergoes conversion into acetyl-CoA within the mitochondria of oocytes, serving as a primary fuel source for the tricarboxylic acid (TCA) cycle. The citrate generated in the TCA cycle can be transported to the cytoplasm and converted back into acetyl-CoA. This acetyl-CoA can either fuel lipid synthesis or act as a substrate for histone acetylation. This study aimed to investigate how pyruvate metabolism influences lysine 9 histone 3 acetylation (H3K9ac) dynamics and RNA transcription in bovine oocytes during in vitro maturation (IVM)...

Dichloroacetic acid (DCAA) and trichloroacetic acid (TCAA) are two typical non-volatile disinfection by-products (DBPs) found in drinking water. Increasing evidence has demonstrated that they show reproductive toxicity. However, whether they might have endocrine disrupting properties remains largely unknown. To discover this, we treated male mice or pregnant mice with 0, 1-, 102 -, 103 -, 104 -, or 5 × 104 -fold maximal concentration level (MCL) of DCAA or TCAA in drinking water. In male mice, the levels of testosterone in serum and androgen receptor (AR) in testis were declined with ≥ 103 -fold MCL of DCAA (26...

BACKGROUND: Experimental studies have shown that disinfection byproducts (DBPs) including haloacetic acids (HAAs) can cause liver toxicity, but evidence linking this association in humans is sparse. OBJECTIVES: We aimed to explore the associations between HAA exposures and liver injury. METHODS: We included 922 women between December 2018 and January 2020 from the Tongji Reproductive and Environmental (TREE) cohort study in Wuhan, China. Urinary HAA concentrations including trichloroacetic acid (TCAA) and dichloroacetic acid (DCAA) and serum indicators of liver function, including alanine aminotransferase (ALT), aspartate aminotransferase (AST), and gamma-glutamyltransferase (GGT) were measured...

Here, mitochondria were isolated from mesenchymal stem cells (MSCs) after being treated with mitochondria-stimulating substrates, 50 μM metformin (Met), and 40 μM dichloroacetic acid (DCA). The isolated mitochondria (2 × 107 particles) were characterized and encapsulated inside 100 μl hydrogel composed of alginate (3 % w/v; Alg)/gelatin (Gel; 1 % w/v) enriched with 1 μM pyrrole (Pyr) solidified in the presence of 0...

Heart failure with reduced ejection fraction (HFrEF) is characterized not only by reduced left ventricular ejection fraction (EF) but is also combined with symptoms such as dyspnea, fatigue, and edema. Several pharmacological interventions have been established. However, a treatment targeting a novel pathophysiological mechanism is still needed. Evidence indicating that inhibition of pyruvate dehydrogenase kinase 4 (PDK4) may be cardioprotective has been accumulating. Thus, we focused on vitamin K3 and used its framework as a new PDK4 inhibitor skeleton to synthesize new PDK4 inhibitors that show higher activity than the existing PDK4 inhibitor, dichloroacetic acid, and tested their cardioprotective effects on a mouse heart failure model...

Although studies have shown that olfaction may contribute to the perception of tastant, literature is scarce or circumstantial, especially in humans. This study aims to (a) explore whether humans can perceive solutions of basic prototypical tastants through orthonasal and retronasal olfaction, (b) and to examine what volatile odor compounds (VOCs) underlie this ability. Solutions of five basic tastants (sucrose, sodium chloride, citric acid, monosodium glutamate (MSG), quinine dissolved in water, and two fatty acids (oleic and linoleic acid dissolved in mineral oil were prepared...