Endoplasmic reticulum (ER) stress responses play an important role in neurodegenerative diseases. Sodium 4-phenylbutyrate (4-PBA) is a terminal aromatic substituted fatty acid that has been used for the treatment of urea cycle disorders. 4-PBA possesses in vitro chemical chaperone activity and reduces the accumulation of Parkin-associated endothelin receptor-like receptor (Pael-R), ...

Protons are important signals for neuronal function. In the central nervous system (CNS), proton concentrations change locally when synaptic vesicles release their acidic contents into the synaptic cleft, and globally in ischemia, seizures, traumatic brain injury, and other neurological disorders due to lactic acid accumulation. The finding that protons gate ...

Phosphatidylcholine (PC) is the most abundant component of lipid bilayers and exists in various molecular forms, through combinations of 2 acylated fatty acids. Arachidonic acid (AA)-containing PC (AA-PC) can be a source of AA, which is a crucial mediator of synaptic transmission and intracellular signaling. However, the distribution of AA-PC ...

Credneramides A (1) and B (2), two vinyl chloride-containing metabolites, were isolated from a Papua New Guinea collection of cf. Trichodesmium sp. nov. and expand a recently described class of vinyl chloride-containing natural products. The precursor fatty acid, credneric acid (3), was isolated from both the aqueous and organic fractions ...

Polyphenolic compounds including a number of natural products such as resveretrol, curcumin, catechin derivatives, and nordihydroguaiaretic acid have effects on the assembly of Aβ fibrils and oligomers as well as on fibril morphology. Based on a lead structure obtained from a screen of a small molecule diversity library, simple benzoic ...

Obesity is linked to increased risk of Alzheimer's disease and cognitive impairment. Microglia-mediated neuroinflammation is implicated in neuronal loss. Elevated levels of fatty acids seen in obesity induce inflammation in peripheral tissues. Whether fatty acids promote neuroinflammation is unknown. Using an established neuroinflammation model involving human microglia-like THP-1 cells and ...

The sialic acid of complex N-glycans can be biochemically engineered by substituting the physiological precursor N-acetylmannosamine with non-natural N-acylmannosamines. The Kv3.1 glycoprotein, a neuronal voltage-gated potassium channel, contains sialic acid. Western blots of the Kv3.1 glycoprotein isolated from transfected B35 neuroblastoma cells incubated with N-acylmannosamines verified sialylated N-glycans attached to ...

Clavulanic acid is a CNS-modulating compound with exceptional blood-brain barrier permeability and safety profile. Clavulanic acid has been proposed to have anti-depressant activity and is currently entering Phase IIb clinical trials for the treatment of Major Depressive Disorder (MDD). Studies have also shown that clavulanic acid suppresses anxiety and enhances ...

α-synuclein (α-Syn) is a neuronal protein that accumulates progressively in Parkinson's disease and related synucleinopathies. Attempting to identify cellular factors that affect α-Syn neuropathology, we previously reported that polyunsaturated fatty acids (PUFAs) promote α-Syn oligomerization and aggregation in cultured cells. We now report that docosahexaenoic acid (DHA) a 22:6 PUFA ...

Sialylation is an important carbohydrate modification of glycoconjugates that has been shown to modulate many cellular/molecular interactions in vertebrates. In Drosophila melanogaster (Dm), using sequence homology, several enzymes of the sialylation pathway have been cloned and their function tested in expression systems. Here we investigated whether sialic acid incorporation in ...

Maslinic acid is a triterpenoid compound present in plants of Olea europaea. This compound has been reported to have potent antioxidant, anti-cancer, anti-HIV and anti-inflammatory activities. In this study, we investigated the neuroprotective effect of maslinic acid and its mechanism of action. With presence or absence of maslinic acid, cortical ...

Recent findings demonstrate that epigenetic modifications are required for sexual differentiation of the brain. For example, neonatal administration of the histone deacetylase inhibitor, valproic acid, blocks masculinisation of cell number in the principal nucleus of the bed nucleus of the stria terminalis (BNST). Here we examined effects of valproic acid ...

Amino acids reliably evoke strong responses in fish olfactory system. The molecular olfactory receptors (ORs) are located in the membrane of cilia and microvilli of the olfactory receptor neurons (ORNs). Axons of ORNs converge on specific olfactory bulb (OB) glomeruli and the neural responses of ORNs expressing single Ors activate ...

Arachidonic acid (ARA) and docosahexaenoic acid (DHA), which are the dominant polyunsaturated fatty acids in the brain, have crucial roles in brain development and function. Recent studies have shown that ARA and DHA promote postnatal neurogenesis. However, the direct effects of ARA on neural stem/progenitor cells (NSPCs) and the effects ...

Valproic acid (VPA) has been used for > 30 years in the treatment of epilepsy and is now one of the most frequently prescribed anti-epileptic drugs (AEDs) worldwide. Its chronic use has been associated with hyperandrogenism and polycystic ovaries in women with epilepsy and thus suggests change in normal levels ...

In this study, we attempted to use the neural network to model a quantitative structure-K(m) (Michaelis-Menten constant) relationship for beta-glucosidase, which is an important enzyme to cut the beta-bond linkage in glucose while K(m) is a very important parameter in enzymatic reactions. Eight feedforward backpropagation neural networks with different layers ...

Acetic acid produces an irritating sensation that can be attributed to activation of nociceptors within the trigeminal ganglion that innervate the nasal or oral cavities. These sensory neurons sense a diverse array of noxious agents in the environment, allowing animals to actively avoid tissue damage. Although receptor mechanisms have been ...

Systemic or intracerebral administration of kainic acid in rodents induces neuronal death followed by a cascade of neuroplastic changes in the hippocampus. Kainic acid-induced neuroplasticity is evidenced by alterations in hippocampal neurogenesis, dispersion of the granule cell layer and re-organisation of mossy fibres. Similar abnormalities are observed in patients with ...

To investigate glucose homeostasis and in particular gluconeogenesis in a large animal model of acute liver failure (ALF). Six pigs with paracetamol induced ALF under general anaesthesia were studied over 25 h. Plasma samples were withdrawn every five hours from a central vein. Three animals were used as controls and ...

We have previously found that the weak base 4-aminopyridine induces Brownian motion of acidic organelles around which vacuoles are formed, causing organelle traffic disorder in neurons. Our present study investigated the characteristics of vacuoles induced by weak bases (NH(4)Cl, aminopyridines, and chloroquine) using mouse cells. Individual vacuoles included acidic organelles ...

5-Fluorouracil (5-FU) in combination with its synergistic biomodulator folinic acid maintains a pivotal position in cancer chemotherapy. However, clinical limitations such as phlebitis and catheter blockages persist with the administration of these drugs in combination, and are associated with reduced efficacy and/or quality of life for patients. We have reported ...

Understanding the interactions between nutrition and immune system is crucial for adjusting nutrient allowances in dietary formulations that optimize production efficiency. Among various animal proteins, fish meal (FM) is rich in protein (amino acids), readily available throughout most of the world, and competitively priced against other animal proteins (e.g. milk ...

Folic acid is essential for numerous biological functions, ranging from nucleotide biosynthesis to the remethylation of homocysteine. Folic acid is unable to cross the biological membranes by simple diffusion, so there exists a well-developed epithelial folate transport system for the regulation of normal folate homeostasis in the intestine. Any perturbances ...

Hyperhomocysteinemia, a condition of elevated blood homocysteine (Hcy) levels, is a metabolic disease. It is a common clinical finding in patients with chronic kidney diseases and occurs almost uniformly in patients with end-stage renal disease. Hyperhomocysteinemia is also a risk factor for cardiovascular disease. Our recent studies indicate that hyperhomocysteinemia ...

Levels of antioxidants such as folic acid and selenium decrease in dams exposed to ethanol during gestation and lactation, affecting their antioxidant status, their reproductive function and consequently the health of their progeny. We will study whether a Se (0.5 p.p.m.) plus folic acid (8 p.p.m.) supplemented diet administered to ethanol-exposed dams ...

The folate receptor is a proven target for folate-based diagnosis and treatment of cancer. Several folic acid conjugates have been developed as radiopharmaceuticals, but a suitable (18)F-labeled folic acid derivative for routine clinical use is still lacking. The purpose of this study was to investigate the potential of 2'-(18)F-fluorofolic acid ...

Interaction of nanoparticles with human cells is an interesting topic for understanding toxicity and developing potential drug candidates. Water soluble platinum nanoparticles were synthesized via reduction of hexachloroplatinic acid using sodium borohydride in the presence of capping agents. The bioactivity of folic acid and poly(vinyl pyrrolidone) capped platinum nanoparticles (Pt-nps) ...

Carboxylic acids with known central nervous system and histone deacetylase (HDAC) inhibitory activities were converted to hydroxamic acids and tested using a suite of in vitro biochemical assays with recombinant HDAC isoforms, cell based assays in human cervical carcinoma Hela cells and primary cultures from mouse forebrain, and a whole ...

Folic acid is a vitamin for probably all animals. When converted to folate forms, it is used in DNA synthesis and amino acid metabolism. Literature suggests insects must consume folates, folates do not affect others, is a toxin for some, and that a few insects synthesize it. It has been ...

Young Latina adults require targeted health messages to meet the unique needs of this life stage. Folic acid messages for the prevention of neural tube defects that are effective for other women might not be relevant to this group. The aim of this study was to identify barriers and motivators ...

The importance of unmetabolized folic acid in maternal and fetal blood is not known. We investigated total folate, tetrahydrofolate (THF), 5-methyltetrahydrofolate (5-MTHF), formyl-THF, 5,10-methenylTHF, and folic acid concentrations in women and in umbilical cord blood at delivery. The study included 87 pregnant women and 29 cord blood samples, including 24 ...

Systemic administration of folic acid (FA) in mice was used for studying the pathogenesis associated with acute renal failure (ARF). However, the mechanism by which FA induces ARF remains poorly understood. The present study therefore, was planned to investigate the effect of folic acid administration on prooxidant state and associated ...

Folic acid or 17-β estradiol produces antidepressant effects, either alone or combined with several antidepressants. However, the antidepressant-like actions of folic acid combined with 17-β estradiol in the forced swimming test (FST) have not been tested before. Thus, in the present study, ovariectomized female rats received folic acid (5.0nmol/i.c.v., P<0.05; ...

Nutritional intervention is effective in reducing the risk of neural tube defects (NTDs). To determine the effects of nutritional supplementation on human metabolism, a metabonomic study was carried out on 96 women of reproductive age. Subjects with nutritional intervention were given fortified wheat flour (containing folic acid, vitamin B(1) , ...

Attention has shifted from the treatment of colorectal cancer (CRC) to chemoprevention using aspirin and folic acid as agents capable of preventing the onset of colon cancer. However, no sensitive analytical method exists to simultaneously quantify the two drugs when released from polymer-based nanoparticles. Thus, a rapid, highly sensitive method ...

Methotrexate (MTX), an antifolate, is an anchor drug for the treatment of rheumatoid arthritis (RA). Both folic acid (FA) and folinic acid (FLN) supplements have been shown to reduce the toxicity of MTX when used in RA therapy. The effect of folate supplementation on MTX efficacy still needs to be ...

Periconceptional use of folic acid may effectively reduce the risk of fetal neural tube defects. The objective of the present study was to evaluate the awareness and use of folic acid during periconceptional period in Taiwan. A cross-sectional study was performed at Taiwan Adventist Hospital between March 2008 and December ...

Myocardial infarction (MI) results in significant metabolic derangement, causing accumulation of metabolic by product, such as homocysteine (Hcy). Hcy is a nonprotein amino acid generated during nucleic acid methylation and demethylation of methionine. Folic acid (FA) decreases Hcy levels by remethylating the Hcy to methionine, by 5-methylene tetrahydrofolate reductase (5-MTHFR). ...

The present study investigated the effect of folic acid supplementation on the Notch signaling pathway and cell proliferation in rat embryonic neural stem cells (NSCs). The NSCs were isolated from E14-16 rat brain and grown as neurospheres in serum-free suspension culture. Individual cultures were assigned to one of 3 treatment ...

Women with child wish are advised to take folic acid supplements to reduce the risk for spina bifida. However, there is less evidence for this protective effect in women using valproic acid (VPA). We investigated the effect of folic acid in women exposed to VPA in the first trimester of ...

There is a large body of evidence to suggest that improving periconceptional folate status reduces the risk of neonatal neural tube defects. Thus increased folate intake is now recommended before and during the early stages of pregnancy, through folic acid supplements or fortified foods. Furthermore, there is growing evidence that ...

To examine the relationship between adherence to prescribed folic acid supplements and folic acid intake, serum folate and plasma homocysteine in hemodialysis patients. The effects of change in adherence patterns from enrollment to 1 year later on changes in these same measures were also assessed. Secondary data analysis. Eighty-six hemodialysis ...

In a few countries enriched cereal grains have been fortified with folic acid to reduce the incidence of neural tube defects. The objective of this study was to analyse the effect of folic acid fortified foods on the incidence of neural tube defects in live newborns at Princess Badea Teaching ...

PURPOSE: To examine effectiveness of a Web-based, stage-tailored folic acid intervention compared to non-stage-tailored education to promote folic acid-containing multivitamin use among college women. DESIGN: Pretest/posttest with random assignment to groups. SETTING: Internet-based on college campus. PARTICIPANTS: Female college students (n = 408; mean age +/- SD = 20.8 +/- ...

Unmetabolized serum folic acid (UMFA) has been detected in adults. Previous research indicates that high folic acid intakes may be associated with risk of cancer. The objective was to examine UMFA concentrations in relation to dietary and supplemental folate and status biomarkers in the US population aged > or =60 ...

BACKGROUND: Recent data revealed differences in human absorption kinetics and metabolism between food folates and folic acid supplements and fortificant. OBJECTIVE: The objective was to determine folate bioavailability after ingestion of breads or a breakfast meal fortified with either 5-CH(3)-H(4) folate or folic acid by using a stable-isotope area under ...

Neural tube closure defects are among the most frequent congenital malformations in humans. Supplemental maternal intake of folic acid before and during pregnancy reduces their incidence significantly, but the mechanism underlying this preventive effect is unknown. As a number of genes that cause neural tube closure defects encode transcriptional regulators ...

Efficient regioselective syntheses of conjugates of folic acid and cytotoxic agents derived from natural epothilones are described. These folate receptor (FR) targeting compounds are water soluble and incorporate a hydrophilic peptide-based spacer unit and a reducible self-immolative disulfide-based linker system between the FR-targeting ligand and the parent drug.

A series of PEG-epirubicin conjugates with different folic acid contents per polymer chain was synthesized in order to study the influence of polymer/targeting moiety ratio on selective cytotoxicity, cellular uptake and intracellular localization. Analogous carboxyl-terminated conjugates without folic acid were studied as control. The heterobifunctional HO-PEG-COOH was used as polymeric ...

Doxorubicin (DOX) is one of the most effective anticancer drugs. However, its therapeutic effectiveness is greatly hampered by its dose limiting and cumulative cardiotoxic side effects. To overcome these limitations, bioconjugates of DOX were studied using bovine serum albumin (BSA) as a carrier to provide passive tumor targeting by the ...