Search Results (12)

Radiation-induced intestinal injury is a common complication of radiotherapy for abdominal and pelvic malignancies. Due to its rapid proliferation, the small intestine is particularly sensitive to radiation, making it a critical factor limiting treatment. Ferulic acid (FA), a derivative of cinnamic acid, exhibits antioxidant, anti-inflammatory, and anti-radiation properties. In this study, we established a mouse model of radiation-induced intestinal injury using a dose of 11 Gy at a rate of 96.62 cGy/min. Our findings indicate that FA’s protective effects against radiation-induced intestinal injury may be mediated through the parkinsonism-associated deglycase (DJ-1) nuclear factor erythroid 2-related factor 2 (Nrf2) and silent mating type information regulation 2 homolog 1 (Sirt1) nuclear Factor kappa-light-chain-enhancer of activated B cells (NF-κB) NOD-like receptor family, pyrin domain containing 3 (NLRP3). FA was found to mitigate changes in oxidative stress indices and inflammatory factors induced by radiation, as well as to attenuate radiation-induced pathological alterations in the small intestine. Furthermore, FA enhanced the expression of DJ-1 and Nrf2 at both the transcriptional and protein levels, inhibited NLRP3 protein fluorescence intensity, and reduced the expression of NLRP3, interleukin-18 (IL-18), and interleukin-1 beta (IL-1β). Additionally, FA suppressed the transcription and translation of NF-κB, NLRP3, cysteine-aspartic acid protease-1 (Caspase-1), IL-18, and IL-1β by upregulating Sirt1, thereby alleviating radiation-induced inflammatory injury in the small intestine. Thus, FA holds promise as an effective therapeutic agent for ameliorating radiation-induced intestinal injury. Full article

Derangement of the epidermal barrier lipids and dysregulated immune responses are key pathogenic features of atopic dermatitis (AD). The Th2-type cytokines interleukin IL-4 and IL-13 play a prominent role in AD by activating the Janus Kinase/Signal Transduction and Activator of Transcription (JAK/STAT) intracellular signaling axis. This study aimed to investigate the role of JAK/STAT in the lipid perturbations induced by Th2 signaling in 3D epidermal equivalents. Tofacitinib, a low-molecular-mass JAK inhibitor, was used to screen for JAK/STAT-mediated deregulation of lipid metabolism. Th2 cytokines decreased the expression of elongases 1, 3, and 4 and serine-palmitoyl-transferase and increased that of sphingolipid delta(4)-desaturase and carbonic anhydrase 2. Th2 cytokines inhibited the synthesis of palmitoleic acid and caused depletion of triglycerides, in association with altered phosphatidylcholine profiles and fatty acid (FA) metabolism. Overall, the ceramide profiles were minimally affected. Except for most sphingolipids and very-long-chain FAs, the effects of Th2 on lipid pathways were reversed by co-treatment with tofacitinib. An increase in the mRNA levels of CPT1A and ACAT1, reduced by tofacitinib, suggests that Th2 cytokines promote FA beta-oxidation. In conclusion, pharmacological inhibition of JAK/STAT activation prevents the lipid disruption caused by the halted homeostasis of FA metabolism. Full article

Fanconi anemia (FA) is a rare genetic disease characterized by a dysfunctional DNA repair and an oxidative stress accumulation due to defective mitochondrial energy metabolism, not counteracted by endogenous antioxidant defenses, which appear down-expressed compared to the control. Since the antioxidant response lack could depend on the hypoacetylation of genes coding for detoxifying enzymes, we treated lymphoblasts and fibroblasts mutated for the FANC-A gene with some histone deacetylase inhibitors (HDACi), namely, valproic acid (VPA), beta-hydroxybutyrate (OHB), and EX527 (a Sirt1 inhibitor), under basal conditions and after hydrogen peroxide addition. The results show that VPA increased catalase and glutathione reductase expression and activity, corrected the metabolic defect, lowered lipid peroxidation, restored the mitochondrial fusion and fission balance, and improved mitomycin survival. In contrast, OHB, despite a slight increase in antioxidant enzyme expressions, exacerbated the metabolic defect, increasing oxidative stress production, probably because it also acts as an oxidative phosphorylation metabolite, while EX527 showed no effect. In conclusion, the data suggest that VPA could be a promising drug to modulate the gene expression in FA cells, confirming that the antioxidant response modulation plays a pivotal in FA pathogenesis as it acts on both oxidative stress levels and the mitochondrial metabolism and dynamics quality. Full article

The anti-oxidant and anti-inflammatory effect of beta-glucogallin (BGG), a plant-derived natural product, was evaluated in both in vitro and in vivo studies. For the in vitro study, the ability of BGG pre-treatment to quench LPS-induced effects compared to LPS alone in macrophages was investigated. It was found that BGG pre-treatment showed a significant decrease in ROS, NO, superoxide, and pro-inflammatory cytokines (TNF-alpha, IL-4, IL-17, IL-1β, and IL-6) and increased reduced glutathione coupled with the restoration of mitochondrial membrane potential. Gene profiling and further validation by qPCR showed that BGG pre-treatment downregulated the LPS-induced expression of c-Fos, Fas, MMP-9, iNOS, COX-2, MyD88, TRIF, TRAF6, TRAM, c-JUN, and NF-κB. We observed that BGG pre-treatment reduced nuclear translocation of LPS-activated NF-κB and thus reduced the subsequent expressions of NLRP3 and IL-1β, indicating the ability of BGG to inhibit inflammasome formation. Molecular docking studies showed that BGG could bind at the active site of TLR4. Finally, in the LPS-driven sepsis mouse model, we showed that pre-treatment with BGG sustained toxic shock, as evident from their 100% survival. Our study clearly showed the therapeutic potential of BGG in toxic shock syndrome. Full article

Beta-oxidation(β-oxidation) is an important metabolic process involving multiple steps by which fatty acid molecules are broken down to produce energy. The very long-chain fatty acids (VLCFAs), a type of fatty acid (FA), are usually highly toxic when free in vivo, and their oxidative metabolism depends on the peroxisomal β-oxidation. For a long time, although β-oxidation takes place in both mitochondria and peroxisomes, most studies have been keen to explore the mechanism of β-oxidation in mitochondria while ignoring the importance of peroxisomal β-oxidation. However, current studies indicate that it is hard to provide effective treatment for diseases caused by the disorder of peroxisomal β-oxidation, such as X-ALD, SCOX deficiency, and D-BP deficiency; thus, actions should be taken to solve this problem. Based on existing research results, this review will summarize the importance of peroxisomal β-oxidation and help further learning. Full article

The beneficial properties of the flavanones hesperidin and naringin as feed additives in poultry have lately been under investigation. In broilers, both flavanones have been shown to exhibit antioxidant properties while their individual effects on fatty acid (FA) composition and the underlying molecular mechanisms of their activity have not been explored. Here, we studied their effects on broiler meats’ FA profiles and on the expression of genes related to lipid metabolism, antioxidant defense and anti-inflammatory function. The experimental design comprised six treatment groups of broilers, each supplemented from day 11 until slaughter at 42 days with hesperidin, naringin or vitamin E, as follows: the E1 group received 0.75 g of hesperidin per kg of feed, E2 received 1.5 g hesperidin/kg feed, N1 received 0.75 g naringin/kg feed, N2 received 1.5 g naringin/kg feed, vitamin E (VE) received 0.2 g a-tocopheryl acetate/kg feed, and the control group was not provided with a supplemented feed. The VE treatment group served as a positive control for antioxidant activity. An analysis of the FA profiles of the abdominal adipose tissue (fat pad), major pectoralis (breast) and biceps femoris (thigh) muscles showed that both hesperidin and naringin had significant effects on saturated FA (SFA), polyunsaturated FA (PUFA) and omega n-6 content. Both compounds reduced SFA and increased PUFA and n-6 content, as well as reducing the atherogenicity and thrombogenicity indices in the breast muscle and fat pad. The effects on the thigh muscle were limited. An analysis of gene expression in the liver revealed that naringin significantly increased peroxisome proliferator-activated receptor alpha (PPARα), Acyl-CoA oxidase 1 (ACOX1) and glutathione disulfide reductase (GSR) expression. In the breast muscle, both hesperidin and naringin increased fatty acid synthase (FASN) expression and hesperidin increased the expression of adiponectin. In brief, both hesperidin and naringin supplementation beneficially affected FA profiles in the breast meat and fat pad of broiler chicken. These effects could be attributed to an increase in FA β-oxidation since the increased expression of related genes (PPARα and ACOX1) was observed in the liver. Furthermore, the antioxidant activity of hesperidin and naringin previously observed in the meat of broilers could be attributed, at least partly, to the regulation of antioxidant defense genes, as evidenced by the increased GSR expression in response to naringin supplementation. Full article

Altered lipid metabolic pathways including hydrolysis of triglycerides are key players in the pathogenesis of nonalcoholic fatty liver disease (NAFLD). Whether adiponutrin (patatin-like phospholipase domain containing protein-3—PNPLA3) and monoacylglycerol lipase (MGL) synergistically contribute to disease progression remains unclear. We generated double knockout (DKO) mice lacking both Mgl and Pnpla3; DKO mice were compared to Mgl^−/− after a challenge by high-fat diet (HFD) for 12 weeks to induce steatosis. Serum biochemistry, liver transaminases as well as histology were analyzed. Fatty acid (FA) profiling was assessed in liver and adipose tissue by gas chromatography. Markers of inflammation and lipid metabolism were analyzed. Bone marrow derived macrophages (BMDMs) were isolated and treated with oleic acid. Combined deficiency of Mgl and Pnpla3 resulted in weight gain on a chow diet; when challenged by HFD, DKO mice showed increased hepatic FA synthesis and diminished beta-oxidation compared to Mgl^−/−.DKO mice exhibited more pronounced hepatic steatosis with inflammation and recruitment of immune cells to the liver associated with accumulation of saturated FAs. Primary BMDMs isolated from the DKO mice showed increased inflammatory activities, which could be reversed by oleic acid supplementation. Pnpla3 deficiency aggravates the effects of Mgl deletion on steatosis and inflammation in the liver under HFD challenge. Full article

To investigate the anti-obesity effects and underlying mechanism of BS21, a combination of Phyllostachys pubescens leaves and Scutellaria baicalensis roots was used to investigate the effects of BS21 on adipogenesis, lipogenesis, and browning in 3T3-L1 adipocytes. The expression of adipocyte-specific genes was observed via Western blot, and the BS21 chemical profile was analyzed using ultra-performance liquid chromatography (UPLC). BS21 treatment inhibited adipocyte differentiation and reduced the expression of the adipogenic proteins peroxisome proliferator-activated receptor γ (PPAR-γ), CCAAT/enhancer-binding protein (C/EBP-α), and adipocyte protein 2 (aP2), as well as the lipogenic proteins sterol regulatory element-binding protein 1c (SREBP-1c) and fatty-acid synthase (FAS). BS21 enhanced protein levels of the beta-oxidation genes carnitine palmitoyltransferase (CPT1) and phospho-acetyl-coA carboxylase (p-ACC). BS21 also induced protein expressions of the browning marker genes PR domain containing 16 (PRDM16), peroxisome proliferator-activated receptor gamma co-activator 1-alpha (PGC1α), and uncoupling protein (UCP) 1, and it induced the expression of the thermogenic gene UCP2. Furthermore, BS21 increased adenosine monophosphate-activated protein kinase (AMPK) activation. UPLC analysis showed that BS21 contains active constituents such as chlorogenic acid, orientin, isoorientin, baicalin, wogonoside, baicalein, tricin, wogonin, and chrysin. Our findings demonstrate that BS21 plays a modulatory role in adipocytes by reducing adipogenesis and lipogenesis, increasing fat oxidation, and inducing browning. Full article

Lipid biosynthesis produces glycerol, which is important in fueling turgor pressure necessary for germination and penetration of plant host by fungi. As the relationship between pathogenicity and the lipid biosynthetic pathway is not fully understood, we have elucidated the role of the fatty acid synthase beta subunit dehydratase (FAS1) gene in lipid biosynthesis. The FAS1 gene was silenced through homologous double crossover in Magnaporthe oryzae strain S6 to study the effect on lipid biosynthesis. The vegetative growth of Δfas1 mutants show the highest drop on oleic acid (between 10 and 50%), while the mycelial dry weight of mutants dropped significantly on all media. Conidiation of FAS1 mutants show a ~10- and ~5-fold reduction on oatmeal and Potato Dextrose Agar (PDA), respectively. Mutants formed mycelium that were mildly pigmented, indicating that the deletion of FAS1 may have affected melanin biosynthesis. Biochemical and gene expression studies concluded that the fatty acid degradation pathway might have been interrupted by FAS1 deletion. FAS1 mutants showed no enzyme activity on glucose or olive oil, suggesting that the mutants may lack functional peroxisomes and be defective in β-oxidation of fatty acids, hence explaining the reduced lipid deposits in the spores. Full article

The cross-talk between skeletal muscle and adipose tissue is involved in the development of insulin resistance (IR) in skeletal muscle, leading to the decrease in the anabolic effect of insulin. We investigated if the long chain polyunsaturated n-3 fatty acids (LCn-3PUFA), eicosapentaenoic and docosapentaenoic acids (EPA and DPA, respectively) could (1) regulate the development of IR in 3T3-L1 adipocytes and C2C12 muscle cells and (2) inhibit IR in muscle cells exposed to conditioned media (CM) from insulin-resistant adipocytes. Chronic insulin (CI) treatment of adipocytes and palmitic acid (PAL) exposure of myotubes were used to induce IR in the presence, or not, of LCn-3PUFA. EPA (50 µM) and DPA (10 µM) improved PAL-induced IR in myotubes, but had only a partial effect in adipocytes. CM from adipocytes exposed to CI induced IR in C2C12 myotubes. Although DPA increased the mRNA levels of genes involved in fatty acid (FA) beta-oxidation and insulin signaling in adipocytes, it was not sufficient to reduce the secretion of inflammatory cytokines and prevent the induction of IR in myotubes exposed to adipocyte’s CM. Treatment with DPA was able to increase the release of adiponectin by adipocytes into CM. In conclusion, DPA is able to protect myotubes from PAL-induced IR, but not from IR induced by CM from adipocytes. Full article

The aim of this study was to investigate the effects of 6-week beta-hydroxy-beta methylbutyrate-free acid (HMB-FA) supplementation on oxidative stress and biochemical variables in responses to resistance training. Sixteen healthy young males participated in this study and were randomly assigned to a HMB-FA supplementation group (n = 8) or a placebo supplementation group (n = 8). The resistance training program was applied for 6 weeks with two sessions per week. Blood samples were collected before and after training, and 8-hydroxy-2-deoxyguanosine (8-OHdG), malondialdehyde (MDA), protein carbonyl (PC), and biochemical variables, such as alanine transaminase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), and the numbers of total white blood cells (WBC), neutrophils, lymphocytes, and monocytes were analyzed. Following intervention, both the HMB-FA and placebo supplementation groups showed significant decreases in MDA (effect size [ES]; −0.39, −0.33) and PC (ES; −1.37, −1.41), respectively. However, 8-OHdG did not change after 6 weeks of training in any of the groups. In addition, both groups showed similar training effects on biochemical variables after 6 weeks of intervention. It was concluded that HMB-FA supplementation during resistance training did not add further adaptive changes related to oxidative stress markers. Full article

Alzheimer’s disease (AD) is a neurodegenerative disorder characterized by the deposition of extracellular amyloid-beta peptide (Aβ) and intracellular neurofibrillar tangles, associated with loss of neurons in the brain and consequent learning and memory deficits. Aβ is the major component of the senile plaques and is believed to play a central role in the development and progress of AD both in oligomer and fibril forms. Inhibition of the formation of Aβ fibrils as well as the destabilization of preformed Aβ in the Central Nervous System (CNS) would be an attractive therapeutic target for the treatment of AD. Moreover, a large number of studies indicate that oxidative stress and mitochondrial dysfunction may play an important role in AD and their suppression or reduction via antioxidant use could be a promising preventive or therapeutic intervention for AD patients. Many antioxidant compounds have been demonstrated to protect the brain from Aβ neurotoxicity. Ferulic acid (FA) is an antioxidant naturally present in plant cell walls with anti-inflammatory activities and it is able to act as a free radical scavenger. Here we present the role of FA as inhibitor or disaggregating agent of amyloid structures as well as its effects on biological models. Full article