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AIMS: Renal fibrosis is a common feature in various chronic kidney diseases (CKD). Tubular cell damage is a main characterization which results from dysregulated fatty acid oxidation (FAO) and lipid accumulation. Cannabinoid Receptor 2 (CB2) contributes to renal fibrosis, however, its role in FAO dysregulation in tubular cells is not clarified. In this study, we found CB2 plays a detrimental role in lipid metabolism in tubular cells. METHODS: CB2 knockout mice were adopted to establish a folic acid-induced nephropathy (FAN) model. CB2-induced FAO dysfunction, lipid deposition, and fibrogenesis were assessed in vivo and vitro. To explore molecular mechanisms, ß-catenin inhibitors and peroxisome proliferator-activated receptor alpha (PPARα) activators were also used in CB2-overexpressed cells. The mediative role of ß-catenin in CB2-inhibited PPARα and peroxisome proliferator-activated receptor gamma coactivator-1 alpha (PGC-1α) activation was analyzed. RESULTS: CB2 activates ß-catenin signaling, resulting in the suppression of PPARα/PGC-1α axis. This decreased FAO functions and led to lipid droplet formation in tubular cells. CB2 gene ablation effectively mitigated FAO dysfunction, lipid deposition and uremic toxins accumulation in FAN mice, consequently retarding renal fibrosis. Additionally, inhibition to ß-catenin or PPARα activation could greatly inhibit lipid accumulation and fibrogenesis induced by CB2. CONCLUSIONS: This study highlights CB2 disrupts FAO in tubular cells through ß-catenin activation and subsequent inhibition on PPARα/PGC-1α activity. Targeted inhibition on CB2 offers a perspective therapeutic strategy to fight against renal fibrosis.
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BACKGROUND: Flexible cavovarus deformity is prevalent and the Coleman block test is frequently used to assess the first ray plantarflexion malpositioning in the overall deformity as well as the flexibility of the hindfoot. The objective was to assess and compare the weightbearing computed tomography (WBCT) 3-dimensional (3D) changes in clinical and bone alignment in flexible cavovarus deformity patients when performing the Coleman block test when compared to normal standing position and to controls. METHODS: Twenty patients (40 feet) with flexible cavovarus deformity and 20 volunteer controls (40 feet) with normal foot alignment underwent WBCT imaging of the foot and ankle. Cavovarus patients were assessed in normal orthostatic and Coleman block test positions. Foot and ankle offset (FAO), hindfoot alignment angle (HAA), talocalcaneal angle (TCA), subtalar vertical angle (SVA) and talonavicular coverage angle (TNCA) and a CT-simulated soft tissue envelope image, WBCT clinical hindfoot alignment angle (WBCT-CHAA), were evaluated by 2 readers. Measurements were compared between cavovarus nonstressed and stressed positions and to controls. P values of .05 or less were considered significant. RESULTS: The intra- and interobserver intraclass correlation coefficient were good or excellent for all WBCT measurements. Cavovarus patients demonstrated significant correction of WBCT-CHAA (9.7 ± 0.4 degrees), FAO (2.6 ± 0.4%), and TNCA (8.8 ± 1.8 degrees) when performing the Coleman block test (all P values <.0001). However, WBCT-CHAA and FAO measurements were still residually deformed and significantly different from controls (P values of .001 and <.0001, respectively). TNCA values corrected to values similar to healthy controls (P = .29). No differences were observed in cavovarus patients during Coleman block test for the coronal measures: HAA, TCA, and SVA measurements. CONCLUSION: In this study, we observed improvement in the overall 3D WBCT alignment (FAO), axial plane adduction deformity (TNCA), as well as CT simulated clinical hindfoot alignment (WBCT-CHAA) in flexible cavovarus deformity patients when performing a Coleman block test. However, we did not find improvement in measures of coronal alignment of the hindfoot, indicating continued varus positioning of the hindfoot in these patients. LEVEL OF EVIDENCE: Level III, retrospective comparative study.
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Background: Accurate estimation of reference crop evapotranspiration (ET0) is crucial for farmland hydrology, crop water requirements, and precision irrigation decisions. The Penman-Monteith (PM) model has high accuracy in estimating ET0, but it requires many uncommon meteorological data inputs. Therefore, an ideal method is needed that minimizes the number of input data variables without compromising estimation accuracy. This study aims to analyze the performance of various methods for estimating ET0 in the absence of some meteorological indicators. The Penman-Monteith (PM) model, known for its high accuracy in ET0 estimation, served as the standard value under conditions of adequate meteorological indicators. Comparative analyses were conducted for the Priestley-Taylor (PT), Hargreaves (H-A), McCloud (M-C), and FAO-24 Radiation (F-R) models. The Bayesian estimation method was used to improve the ET estimation model. Results: Results indicate that, compared to the PM model, the F-R model performed best with inadequate meteorological indicators. It demonstrates higher average correlation coefficients (R2) at daily, monthly, and 10-day scales: 0.841, 0.937, and 0.914, respectively. The corresponding root mean square errors (RMSE) are 1.745, 1.329, and 1.423, and mean absolute errors (MAE) are 1.340, 1.159, and 1.196, with Willmott's Index (WI) values of 0.843, 0.862, and 0.859. Following Bayesian correction, R2 values remained unchanged, but significant reductions in RMSE were observed, with average reductions of 15.81%, 29.51%, and 24.66% at daily, monthly, and 10-day scales, respectively. Likewise, MAE decreased significantly, with average reductions of 19.04%, 34.47%, and 28.52%, respectively, and WI showed improvement, with average increases of 5.49%, 8.48%, and 10.78%, respectively. Conclusion: Therefore, the F-R model, enhanced by the Bayesian estimation method, significantly enhances the estimation accuracy of ET0 in the absence of some meteorological indicators.
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Cellular metabolism is a crucial determinant of immune cell fate and function. Extensive studies have demonstrated that metabolic decisions influence immune cell activation, differentiation, and cellular capacity, in the process impacting an organism's ability to stave off infection or recover from injury. Conversely, metabolic dysregulation can contribute to the severity of multiple disease conditions including autoimmunity, alloimmunity, and cancer. Emerging data also demonstrate that metabolic cues and profiles can influence the success or failure of adoptive cellular therapies. Importantly, immunometabolism is not one size fits all; and different immune cell types, and even subdivisions within distinct cell populations utilize different metabolic pathways to optimize function. Metabolic preference can also change depending on the microenvironment in which cells are activated. For this reason, understanding the metabolic requirements of different subsets of immune cells is critical to therapeutically modulating different disease states or maximizing cellular function for downstream applications. Fatty acid oxidation (FAO), in particular, plays multiple roles in immune cells, providing both pro- and anti-inflammatory effects. Herein, we review the major metabolic pathways available to immune cells, then focus more closely on the role of FAO in different immune cell subsets. Understanding how and why FAO is utilized by different immune cells will allow for the design of optimal therapeutic interventions targeting this pathway.
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Ácidos Graxos , Oxirredução , Humanos , Ácidos Graxos/metabolismo , AnimaisRESUMO
Gas chromatography with electron capture negative ion mass spectrometry (GC/ECNI-MS) was used to quantify and compare halogenated natural products (HNPs) and selected anthropogenic persistent organic pollutants (POPs) in individual samples of 17 fish species from the Seychelles (Western Indian Ocean). The sum-HNP amounts (9.5-1100 ng/g lipid mass (lm)) were between 1 and 2 orders of magnitude higher than those of the sum of seven abundant polychlorinated biphenyl (PCB) congeners (0.2-15 ng/g lm) and dichlorodiphenyltrichloroethane-related compounds (DDTs) (<1.1-43 ng/g lm). Within the group of HNPs, the two tetrabrominated phenoxyanisoles (aka methoxylated diphenyl ethers, MeO-BDEs), 2'-MeO-BDE 68 â« 6-MeO-BDE 47, were predominant in most cases. Pearson correlation analysis showed that MeO-BDE levels were positively correlated with less abundant HNPs (2,2'-diMeO-BB 80, 2',6-diMeO-BDE 68, and Br6-DBP) (p < 0.01). Accordingly, HNPs, rather than PCBs and DDTs, were the predominant polyhalogenated contaminants in the current species.
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Produtos Biológicos , Peixes , Bifenilos Policlorados , Poluentes Químicos da Água , Animais , Peixes/metabolismo , Poluentes Químicos da Água/metabolismo , Poluentes Químicos da Água/química , Poluentes Químicos da Água/análise , Produtos Biológicos/metabolismo , Produtos Biológicos/química , Bifenilos Policlorados/metabolismo , Bifenilos Policlorados/análise , Bifenilos Policlorados/química , Oceano Índico , Seicheles , Bioacumulação , Cromatografia Gasosa-Espectrometria de Massas , Recifes de CoraisRESUMO
Mycobacterium tuberculosis (Mtb) successfully thrives in the host by adjusting its metabolism and manipulating the host environment. In this study, we investigated the role of Rv0547c, a protein that carries mitochondria-targeting sequence (MTS), in mycobacterial persistence. We show that Rv0547c is a functional oxidoreductase that targets host-cell mitochondria. Interestingly, the localization of Rv0547c to mitochondria was independent of the predicted MTS but depended on specific arginine residues at the N- and C-terminals. As compared to the mitochondria-localization defective mutant, Rv0547c-2SDM, wild-type Rv0547c increased mitochondrial membrane fluidity and spare respiratory capacity. To comprehend the possible reason, comparative lipidomics was performed that revealed a reduced variability of long-chain and very long-chain fatty acids as well as altered levels of phosphatidylcholine and phosphatidylinositol class of lipids upon expression of Rv0547c, explaining the increased membrane fluidity. Additionally, the over representation of propionate metabolism and ß-oxidation intermediates in Rv0547c-targeted mitochondrial fractions indicated altered fatty acid metabolism, which corroborated with changes in oxygen consumption rate (OCR) upon etomoxir treatment in HEK293T cells transiently expressing Rv0547c, resulting in enhanced mitochondrial fatty acid oxidation capacity. Furthermore, Mycobacterium smegmatis over expressing Rv0547c showed increased persistence during infection of THP-1 macrophages, which correlated with its increased expression in Mtb during oxidative and nutrient starvation stresses. This study identified for the first time an Mtb protein that alters mitochondrial metabolism and aids in survival in host macrophages by altering fatty acid metabolism to its benefit and, at the same time increases mitochondrial spare respiratory capacity to mitigate infection stresses and maintain cell viability.
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The complex pathogenesis of kidney disease is closely related to the diversity of kidney intrinsic cells. In this study, single-cell transcriptome sequencing technology was used to sequence and analyze blood and kidney tissue cells in normal control rats and rats with chronic kidney disease (CKD), focusing on key cell populations and functional enrichment to explore the pathogenesis of CKD. Oil red O staining and enzyme-linked immunosorbent assay (ELISA) were used to detect lipid droplets and free fatty acid (FFA). Quantitative real-time polymerase chain reaction (RT-PCR), western blot (WB) were used to verify the differential gene hydroxyacid oxidase 2 (HAO2) and fatty acid metabolic process in tissue to ensure the reliability of single-cell sequencing results. We successfully established a single-cell transcriptome atlas of blood and kidney tissue in rats with CKD, which were annotated into 14 cell subsets (MPCs, PT, Tc, DCT, B-IC, A-IC, CNT, ALOH, BC, Neu, Endo, Pla, NKT, Baso) according to marker gene, and the integrated single-cell atlas of rats showed a significant increase and decrease of MPCs and PTs in the CKD group, respectively. Functional analysis found extensive enrichment of metabolic-related pathways in PT cells, includes fatty acid metabolic process, cellular amino acid metabolic process and generation of precursor metabolites and energy. Immunohistochemical experiments determined that the differential gene HAO2 was localized in the renal tubules, and its expression was significantly reduced in CKD group compared with control, and oil red O staining showed that lipid droplets increased in the CKD group, after overexpression of HAO2 the lipid droplets was inhibited. ELISA assay showed that ATP content decreased in the CKD group and FFA increased in the CKD group. Moreover, the mitochondrial membrane potential of the cells in the OE-HAO2 group was significantly increased compared with OE-NC. The acyl-CoA oxidase 1(ACOX1), peroxisome proliferator-activated receptor alpha (PPARα), peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC1α) were decreased in the CKD group, while genes and proteins were increased after overexpression of HAO2, and the AMP-activated protein kinase (AMPK) phosphorylated proteins were increased, the acetyl-CoA carboxylase (ACC) phosphorylated proteins were decreased, reversely. Therefore, HAO2 may be an important regulator of fatty acid metabolic processes in CKD, and overexpression of HAO2 can enhance fatty acid metabolism by promoting fatty acid oxidation (FAO) pathway.
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Ácidos Graxos , Túbulos Renais Proximais , Insuficiência Renal Crônica , Animais , Ratos , Insuficiência Renal Crônica/metabolismo , Insuficiência Renal Crônica/patologia , Insuficiência Renal Crônica/genética , Túbulos Renais Proximais/metabolismo , Túbulos Renais Proximais/patologia , Masculino , Ácidos Graxos/metabolismo , Ratos Sprague-Dawley , Transcriptoma , Modelos Animais de DoençasRESUMO
Mitochondrial metabolism plays a central role in the regulation of hematopoietic stem cell (HSC) biology. Mitochondrial fatty acid oxidation (FAO) is pivotal in controlling HSC self-renewal and differentiation. Herein, we discuss recent evidence suggesting that NADPH generated in the mitochondria can influence the fate of HSCs. Although NADPH has multiple functions, HSCs show high levels of NADPH that are preferentially used for cholesterol biosynthesis. Endogenous cholesterol supports the biogenesis of extracellular vesicles (EVs), which are essential for maintaining HSC properties. We also highlight the significance of EVs in hematopoiesis through autocrine signaling. Elucidating the mitochondrial NADPH-cholesterol axis as part of the metabolic requirements of healthy HSCs will facilitate the development of new therapies for hematological disorders.
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ETHNOPHARMACOLOGICAL RELEVANCE: 2,3,5,4'-tetrahydroxy-stilbene-2-O-ß-D-glucoside (TSG) is the principal bioactive compound contained in Polygonum multiflorum Thunb. (PMT), which is traditionally recorded to possess tonic and anti-aging efficacy. AIM OF THE STUDY: To identify the TSG-provided promotion on liver regeneration (LR) following partial hepatectomy (PHx) in mice and to explicate its involved mechanism. MATERIALS AND METHODS: The promotion of TSG on LR was evaluated by hematoxylin and eosin (H&E), 5-bromodeoxyuridinc (BrdU) and Ki-67 staining, and measuring the level of proliferating cell nuclear antigen (PCNA) and Cyclin D1 in mice with PHx at different time points. Gene Expression Omnibus (GEO, GSE15239) database and the label-free quantitative proteomics from liver of mice at 24 h after PHx were integrated to identify potential involved critical proteins, which were verified by Western-blot, Real-time polymerase chain reaction (RT-PCR), molecular docking and luciferase activity assay. Primary hepatocytes isolated from mice were used to investigate the TSG-provided promotion on proliferation in vitro. RESULTS: TSG (20 mg/kg) promoted LR in mice after PHx. Results from RNA expression data from clinical samples and proteomic analysis from liver tissues indicated that peroxisome proliferator-activated receptor α (PPARα)-mediated fatty acid metabolism pathway were crucially associated with the TSG-provided promotion on LR. TSG enhanced the nuclear translocation of PPARα and the mRNA expression of a series of PPARα-regulated downstream genes. In addition, TSG lowered hepatic triglyceride (TG) and non-esterified fatty acid (NEFA) amounts and increased hepatic adenosine triphosphate (ATP) level in mice after PHx. TSG up-regulated the transcriptional activity of PPARα in vitro. Next results displayed that TSG promoted cell proliferation as well as ATP level in mice primary hepatocytes, which were abolished when PPARα was suppressed. Meanwhile, the cell viability was also elevated in mice primary hepatocytes treated with ATP. CONCLUSION: Activating PPARα-mediated fatty acid ß-oxidation (FAO) pathway led to the production of ATP, which contributed to the TSG-provided promotion on LR after PHx in mice.
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Ácidos Graxos , Glucosídeos , Hepatectomia , Regeneração Hepática , PPAR alfa , Estilbenos , Animais , PPAR alfa/metabolismo , PPAR alfa/genética , Glucosídeos/farmacologia , Masculino , Regeneração Hepática/efeitos dos fármacos , Camundongos , Estilbenos/farmacologia , Ácidos Graxos/metabolismo , Proliferação de Células/efeitos dos fármacos , Fígado/efeitos dos fármacos , Fígado/metabolismo , Camundongos Endogâmicos C57BL , Hepatócitos/efeitos dos fármacos , Hepatócitos/metabolismoRESUMO
Heavy metal contamination in leafy vegetables poses significant health risks, highlighting the urgent need for stringent monitoring and intervention measures to ensure food safety and mitigate potential adverse effects on public health. This study investigates the levels of heavy metals, including cadmium (Cd), chromium (Cr), nickel (Ni), lead (Pb), zinc (Zn), and copper (Cu), in locally grown and commercially available leafy vegetables, comparing them to the safety limits established by WHO/FAO. The results revealed that levels of Cd, Cr, Ni, and Pb in the vegetables exceeded WHO/FAO limits, while Zn and Cu remained within permissible bounds. Marketed vegetables exhibited higher metal concentrations than those from nearby farms. For Cu (0.114-0.289 mg/kg) and Zn (0.005-0.574 mg/kg), the daily intake of metals (DIM) was below the dietary intake (DI) and upper limit (UL). Cd's DIM (0.031-0.062 mg/kg) remained below the UL but exceeded the DI. Marketed kale and mint surpassed both DI and UL limits for Ni, while local produce only exceeded the DI. All vegetables had DIM below the DI, except for mint and kale. For Pb, every vegetable exceeded DI limits, with market samples contributing significantly. Cr's DIM ranged from 0.028 to 1.335 mg/kg, for which no set maximum daily intake exists. The health risk index (HRI) values for Zn, Cd, Cu, Ni, and Pb suggested potential health risks associated with leafy greens, while Cr's HRI was below 1. The study underscores the need for stringent monitoring and intervention measures to mitigate the health risks posed by heavy metal contamination in leafy vegetables. These findings suggest that consuming these leafy greens may put consumers at considerable risk for health problems related to Cd, Cu, Ni, Pb, and Zn exposure.
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Monitoramento Ambiental , Contaminação de Alimentos , Metais Pesados , Saúde Pública , Poluentes do Solo , Verduras , Metais Pesados/análise , Verduras/química , Contaminação de Alimentos/análise , Poluentes do Solo/análise , Humanos , Medição de RiscoRESUMO
Reference evapotranspiration (ETo) has a significant role in water resource planning and management as well as analysis of crop production and other agricultural tasks. Methods for estimating ETo may require diurnal/monthly assessments to perceive the consequences of climatic changes on local regions. The spatial and temporal patterns of ETo were analyzed in the current work using data from 340 weather stations in Iran. The entropy theory was used to assess the uncertainty of the utilized variables and the modified Kendall test was applied for temporal trend analysis. The interpolation (e.g., kriging) and ordinary least squares (OLS) methods were used for spatio-temporal ETo classification/modeling. The spatial analysis demonstrated that the OLS method with a good fit measure (R2 = 0.985) successfully simulated the spatial relationships of ETo with climatic parameters. After examining error indices, the cokriging method with an exponential variogram was introduced as the best method of seasonal and annual ETo classification in Iran. Spatially and temporally calculated ETo patterns using modified Hargreaves (MHGR) and MODIS methods closely resembled the standard FAO Penman-Monteith (FPM-56) method, all indicating a gradual increase in ETo. MHGR and MODIS methods serve as suitable alternatives for estimating ETo in various climatic regions of Iran, provided data availability.
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Estações do Ano , Irã (Geográfico) , Agricultura , ClimaRESUMO
Oxidative stress plays a pivotal role in the development of diabetic cardiomyopathy (DCM). Previous studies have revealed that inhibition of mitochondrial fission suppressed oxidative stress and alleviated mitochondrial dysfunction and cardiac dysfunction in diabetic mice. However, no research has confirmed whether mitochondria fission accentuates hyperglycemia-induced cardiomyoblast oxidative stress through regulating fatty acid oxidation (FAO). We used H9c2 cardiomyoblasts exposed to high glucose (HG) 33 mM to simulate DCM in vitro. Excessive mitochondrial fission, poor cell viability, and lipid accumulation were observed in hyperglycemia-induced H9c2 cardiomyoblasts. Also, the cells were led to oxidative stress injury, lower adenosine triphosphate (ATP) levels, and apoptosis. Dynamin-related protein 1 (Drp1) short interfering RNA (siRNA) decreased targeted marker expression, inhibited mitochondrial fragmentation and lipid accumulation, suppressed oxidative stress, reduced cardiomyoblast apoptosis, and improved cell viability and ATP levels in HG-exposed H9c2 cardiomyoblasts, but not in carnitine palmitoyltransferase 1 (CPT1) inhibitor etomoxir treatment cells. We also found subcellular localization of CPT1 on the mitochondrial membrane, FAO, and levels of nicotinamide adenine dinucleotide phosphate (NADPH) were suppressed after exposure to HG treatment, whereas Drp1 siRNA normalized mitochondrial CPT1, FAO, and NADPH. However, the blockade of FAO with etomoxir abolished the above effects of Drp1 siRNA in hyperglycemia-induced H9c2 cardiomyoblasts. The preservation of mitochondrial function through the Drp1/CPT1/FAO pathway is the potential mechanism of inhibited mitochondria fission in attenuating oxidative stress injury of hyperglycemia-induced H9c2 cardiomyoblasts.
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Ácidos Graxos , Hiperglicemia , Dinâmica Mitocondrial , Oxirredução , Estresse Oxidativo , Animais , Dinâmica Mitocondrial/efeitos dos fármacos , Hiperglicemia/metabolismo , Ratos , Linhagem Celular , Ácidos Graxos/metabolismo , Apoptose/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Dinaminas/metabolismo , Miócitos Cardíacos/metabolismo , Miócitos Cardíacos/patologia , Carnitina O-Palmitoiltransferase/metabolismo , Carnitina O-Palmitoiltransferase/genética , Cardiomiopatias Diabéticas/metabolismo , Cardiomiopatias Diabéticas/patologia , Mitocôndrias/metabolismo , Mioblastos Cardíacos/metabolismo , Mioblastos Cardíacos/efeitos dos fármacos , Glucose/farmacologia , Trifosfato de Adenosina/metabolismoRESUMO
Peripheral artery disease (PAD) is an atherosclerotic disease impacting over 200 million individuals and the prevalence increases with age. PAD occurs when plaque builds up within the peripheral arteries, leading to reduced blood flow and oxygen supply to the outer extremities. Individuals who experience PAD suffer from ischemia, which is typically accompanied by significant damage to skeletal muscles. Additionally, this tissue damage affects mitochondria, causing them to become dysregulated and dysfunctional, resulting in decreased metabolic rates. As there is no known cure for PAD, researchers are exploring potential therapeutic targets by examining coexisting cardiovascular conditions and metabolic risk factors, such as the aging process. Among these comorbidities, type-two diabetes mellitus and obesity are particularly common in PAD cases. These conditions, along with aging itself, are associated with an elevated accumulation of ectopic lipids within skeletal muscles, similar to what is observed in PAD. Researchers have attempted to reduce excess lipid accumulation by increasing the rate of fatty acid beta oxidation. Manipulating acetyl coenzyme A carboxylase 2, a key regulatory protein of fatty acid beta oxidation, has been the primary focus of such research. When acetyl coenzyme A carboxylase 2 is inhibited, it interrupts the conversion of acetyl-CoA into malonyl-CoA, resulting in an increase in the rate of fatty acid beta oxidation. By utilizing samples from PAD patients and applying the pharmacological strategies developed for acetyl coenzyme A carboxylase 2 in diabetes and obesity to PAD, a potential new therapeutic avenue may emerge, offering hope for improved quality of life for individuals suffering from PAD.
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The ocular surface is a mucosal barrier tissue colonized by commensal microbes, which tune local immunity by eliciting IL-17 from conjunctival γδ T cells to prevent pathogenic infection. The commensal Corynebacterium mastitidis (C. mast) elicits protective IL-17 responses from conjunctival Vγ4 T cells through a combination of γδ TCR ligation and IL-1 signaling. Here, we identify Vγ6 T cells as a major C. mast-responsive subset in the conjunctiva and uncover its unique activation requirements. We demonstrate that Vγ6 cells require not only extrinsic (via dendritic cells) but also intrinsic TLR2 stimulation for optimal IL-17A response. Mechanistically, intrinsic TLR2 signaling was associated with epigenetic changes and enhanced expression of genes responsible for metabolic shift to fatty acid oxidation to support Il17a transcription. We identify one key transcription factor, IκBζ, which is upregulated by TLR2 stimulation and is essential for this program. Our study highlights the importance of intrinsic TLR2 signaling in driving metabolic reprogramming and production of IL-17A in microbiome-specific mucosal γδ T cells.
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BACKGROUND: Despite the positive impact of trade liberalization on food availability in India, severe inequality in nutrition consumption at the district level persists. Empirical evidence on the relationship between trade liberalization and nutrition consumption inequality often offers a country-level perspective and generates disputed outcomes. The study aimed to explore the effects of trade liberalization on inequality in nutrition consumption at the district level in India and to examine the heterogeneity of the impact on different nutrition consumption. METHODS: Our study employed the Gini Index to measure nutrition consumption inequality of 2 macronutrients and 5 micronutrients at the district level in India during 2009-2011, utilizing the comprehensive FAO/WHO individual food consumption data. The import tariff was adopted as a proxy for trade liberalization, as its externally imposed nature facilitates a causal interpretation. We further identified the direct causal relationship between food trade liberalization and inequality in nutrition consumption using a fixed effects model. RESULTS: The results show that more than 50% of the individuals in the survey districts did not meet the dietary standards for both macronutrients and micronutrients. Food trade liberalization hindered the improvement of inequality in nutrition consumption. As import tariffs were reduced by 1%, the inequality in intake of calories, zinc, vitamin B1, and vitamin B2 increased significantly by 0.45, 0.56, 0.48, and 0.66, respectively, which might be related to food market performance. The results also highlight the positive role of the gender gap, female-headed households, and caste culture on inequality in nutrition consumption in India. CONCLUSIONS: To ease the shock of liberalization and minimize its inequality effects, complementary measures should be adopted, such as improving food logistic conditions in poor areas, and nutrition relief schemes.
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Comércio , Humanos , Índia , Feminino , Masculino , Adulto , Comércio/estatística & dados numéricos , Micronutrientes , Adolescente , Abastecimento de Alimentos/estatística & dados numéricos , Adulto Jovem , Dieta/estatística & dados numéricos , Política , Fatores Socioeconômicos , Pessoa de Meia-Idade , Criança , Estado NutricionalRESUMO
Evapotranspiration (ETo) is an important component of the hydrological cycle and reliable estimates of ETo are essential for assessing crop water requirements and irrigation management. Direct measurement of evapotranspiration is both costly and involves complex and intricate procedures. Hence, empirical models are commonly utilized to estimate ETo using accessible meteorological data. Given that empirical methods operate on various assumptions, it is essential to assess their performance to pinpoint the most suitable methods for ETo calculation based on the availability of input data and the specific climatic conditions of a region. This study aims to evaluate different empirical methods of ETo in the tropical highland Udhagamandalam region of Tamil Nadu, India, utilizing sixty years of meteorological data from 1960-2020. In this study, 8 temperature-based and 10 radiation-based empirical models are evaluated against ETo estimates derived from pan evaporation observation and the FAO Penman-Monteith method (FAO-PM), respectively. Statistical error metrics indicate that both temperature and radiation-based models perform better for the Udhagamandalam region. However, radiation-based models performed better than the temperature based models. This is possibly due to the high humidity of the study region throughout the year. The results suggest that simple temperature and radiation-based models using minimum meteorological information are adequate to estimate ETo and thus find potential application in agricultural water practices, hydrological processes, and irrigation management.
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Triple-negative breast cancer (TNBC), the most aggressive subtype of breast cancer, has a poor prognosis and lacks effective treatment strategies. Here, the study discovered that TNBC shows a decreased expression of epithelial transcription factor ovo-like 2 (OVOL2). The loss of OVOL2 promotes fatty acid oxidation (FAO), providing additional energy and NADPH to sustain stemness characteristics, including sphere-forming capacity and tumor initiation. Mechanistically, OVOL2 not only suppressed STAT3 phosphorylation by directly inhibiting JAK transcription but also recruited histone deacetylase 1 (HDAC1) to STAT3, thereby reducing the transcriptional activation of downstream genes carnitine palmitoyltransferase1 (CPT1A and CPT1B). PyVT-Ovol2 knockout mice develop a higher number of primary breast tumors with accelerated growth and increased lung-metastases. Furthermore, treatment with FAO inhibitors effectively reduces stemness characteristics of tumor cells, breast tumor initiation, and metastasis, especially in OVOL2-deficient breast tumors. The findings suggest that targeting JAK/STAT3 pathway and FAO is a promising therapeutic strategy for OVOL2-deficient TNBC.
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Ácidos Graxos , Oxirredução , Fator de Transcrição STAT3 , Neoplasias de Mama Triplo Negativas , Neoplasias de Mama Triplo Negativas/genética , Neoplasias de Mama Triplo Negativas/metabolismo , Neoplasias de Mama Triplo Negativas/patologia , Animais , Camundongos , Feminino , Ácidos Graxos/metabolismo , Humanos , Fator de Transcrição STAT3/metabolismo , Fator de Transcrição STAT3/genética , Camundongos Knockout , Carnitina O-Palmitoiltransferase/genética , Carnitina O-Palmitoiltransferase/metabolismo , Linhagem Celular Tumoral , Modelos Animais de Doenças , Células-Tronco Neoplásicas/metabolismo , Células-Tronco Neoplásicas/patologiaRESUMO
Commensal gut bacteria use oleate hydratase to release a spectrum of hydroxylated fatty acids using host-derived unsaturated fatty acids. These compounds are thought to attenuate the immune response, but the underlying signaling mechanism(s) remain to be established. The pathogen Staphylococcus aureus also expresses an oleate hydratase and 10-hydroxyoctadecanoic acid (h18:0) is the most abundant oleate hydratase metabolite found at Staphylococcal skin infection sites. Here, we show h18:0 stimulates the transcription of a set of lipid metabolism genes associated with the activation of peroxisome proliferator activated receptor (PPAR) in the RAW 264.7 macrophage cell line and mouse primary bone marrow-derived macrophages. Cell-based transcriptional reporter assays show h18:0 selectively activates PPARα. Radiolabeling experiments with bone marrow-derived macrophages show [1-14C]h18:0 is not incorporated into cellular lipids, but is degraded by ß-oxidation, and mass spectrometry detected shortened fragments of h18:0 released into the media. The catabolism of h18:0 was >10-fold lower in bone marrow-derived macrophages isolated from Ppara -/- knockout mice, and we recover 74-fold fewer S. aureus cells from the skin infection site of Ppara -/- knockout mice compared to wildtype mice. These data identify PPARα as a target for oleate hydratase-derived hydroxy fatty acids and support the existence of an oleate hydratase-PPARα signaling axis that functions to suppress the innate immune response to S. aureus.
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PPAR alfa , Staphylococcus aureus , Camundongos , Animais , PPAR alfa/metabolismo , Staphylococcus aureus/metabolismo , Ácido Oleico , Ácidos Graxos/metabolismo , Camundongos KnockoutRESUMO
Transboundary animal diseases are defined by the Food and Agriculture Organization (FAO) of the United Nation's Emergency Prevention System as those diseases that are of significant economic, trade and/or food security importance, which can easily spread to other countries and reach epidemic proportions, and where control/management including exclusion requires cooperation among several countries. The Global Framework for the Progressive Control of Transboundary Animal Diseases represents a platform of the FAO and World Organisation for Animal Health to engage regional sub-regional organizations and national veterinary authorities in developing and monitoring progress in animal disease management efforts.
Assuntos
Doenças dos Animais , Animais , Doenças dos Animais/prevenção & controle , Doenças dos Animais/terapia , Controle de Doenças Transmissíveis , Saúde Global , Medicina Veterinária/organização & administração , Cooperação Internacional , Doenças Transmissíveis/veterinária , Doenças Transmissíveis/terapiaRESUMO
Background: As one of the major metabolic reprogramming pathways, fatty acid oxidation (FAO) contributes to rapid progression in tumor cells. Nevertheless, the genomic patterns of patients' FAO levels in colorectal cancer (CRC) remain unknown. Hence, it is crucial to identify the interplay mechanisms of molecular biochemical features of FAO in CRC. Methods: Data of patients with CRC were accessed from The Cancer Genome Atlas (TCGA). Unsupervised consensus clustering related to FAO sores was conducted. The differentially expressed genes (DEGs) were screened by clustering according to FAO status polarized in TCGA, followed by the construction of the scores of genes related to FAO (GFAO_Score). Enrichment of FAO and carcinogenesis at the cell level were calculated based on the single-cell RNA (scRNA) sequencing analysis. The clinical values and drug analysis of GFAO_Score were evaluated by external validation cohorts from Gene Expression Omnibus (GEO) datasets. Results: We classified patients into two distinct FAO clusters which indicated those with lower FAO levels had poor prognosis and high enrichment of carcinogenic-gene pathways. Further, the high FAO-enriched subtypes in epithelial cells revealed carcinogenesis. Three FAO-related genes (ZFHX4, AQP8, and AKR1B10) were screened to construct the GFAO_Score. The high GFAO_Score group leaned toward advanced CRC and unfavorable survival outcomes in the validation cohort. The low GFAO_Score group possessed a better response to immunotherapy and exhibited lower IC50 (50% inhibition concentration) values for certain chemotherapy drugs, such as 5-fluorouracil, irinotecan, oxaliplatin, paclitaxel, and camptothecin. Conclusions: FAO patterns vary in patients with CRC. The GFAO_Score might contribute to the precise screening of patients according to metabolism reprogramming and optimization of strategies in clinical practice.