The pathogenesis of liver fibrosis requires activation of hepatic stellate cells (HSCs); once activated, HSCs lose intracellular fatty acids but the role of fatty acid oxidation and carnitine ...palmitoyltransferase 1A (CPT1A) in this process remains largely unexplored.
CPT1A was found in HSCs of patients with fibrosis. Pharmacological and genetic manipulation of CPT1A were performed in human HSC cell lines and primary HCSs. Finally, we induced fibrosis in mice lacking CPT1A specifically in HSCs.
Herein, we show that CPT1A expression is elevated in HSCs of patients with non-alcoholic steatohepatitis, showing a positive correlation with the fibrosis score. This was corroborated in rodents with fibrosis, as well as in primary human HSCs and LX-2 cells activated by transforming growth factor β1 (TGFβ1) and fetal bovine serum (FBS). Furthermore, both pharmacological and genetic silencing of CPT1A prevent TGFβ1- and FBS-induced HSC activation by reducing mitochondrial activity. The overexpression of CPT1A, induced by saturated fatty acids and reactive oxygen species, triggers mitochondrial activity and the expression of fibrogenic markers. Finally, mice lacking CPT1A specifically in HSCs are protected against fibrosis induced by a choline-deficient high-fat diet, a methionine- and choline-deficient diet, or treatment with carbon tetrachloride.
These results indicate that CPT1A plays a critical role in the activation of HSCs and is implicated in the development of liver fibrosis, making it a potentially actionable target for fibrosis treatment.
We show that the enzyme carnitine palmitoyltransferase 1A (CPT1A) is elevated in hepatic stellate cells (HSCs) in patients with fibrosis and mouse models of fibrosis, and that CPT1A induces the activation of these cells. Inhibition of CPT1A ameliorates fibrosis by preventing the activation of HSCs.
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•CPT1A is overexpressed in HSCs from patients with fibrosis and positively correlates with fibrosis and NAFLD activity score.•Fatty acid oxidation is increased in activated HSCs and CPT1A inhibition blunts HSC activation by reducing mitochondrial activity.•In experimental models, CPT1A-induced fibrogenesis is dependent on ATP availability.•The specific deletion of CPT1A in mouse HSCs protects against fibrosis.
According to previous research, the incidence of necrotising enterocolitis (NEC) decreases after supplementation with probiotics. However, few studies have considered the equivalence or otherwise of ...different strains of probiotics in this respect. Accordingly, this prospective observational study was conducted in a cohort of 245 very-low-birth-weight (VLBW) new-borns to assess the prevalence of NEC after supplementation with the probiotic Inforan
(Berna Biotech, Madrid, Spain) 250 mg capsules containing 10
cfu of
(ATCC 4356) and 10
cfu of
(ATCC 15696); or with Bivos
(Ferring, Madrid, Spain) containing
(formerly
)
(LGG) (ATCC 53103) (10
cfu); or with no probiotic supplementation. Statistical analysis was performed using multivariant regression for the duration of parenteral nutrition, length of neonatal intensive care unit stay, use of oxygen therapy and presence of chorioamnionitis. Of the VLBW new-borns in the study group, 65 received Infloran, 108 received Bivos and 72 received no probiotic. A significant association was observed between a reduced presence of NEC Stage ≥2 and probiotic supplementation. The odds risk (OR) obtained was 0.174 (95% confidence interval (CI): 0.032-0.936) for Infloran and 0.196 (95%CI: 0.053-0.732) for Bivos. Therefore, both probiotics are associated with a lower prevalence of NEC in VLBW new-borns, with no significant differences.
Objetive: The present study aimed to compare the efficacy of three separate strengths training-based interventions - Gratitude, Savoring, and Optimism - in older adults.
Method: The sample comprised ...124 older adults, namely, 74 women and 50 men, non-institutionalized individuals who regularly attend day centers in the provinces of Jaén and Córdoba, southern Spain. Their ages ranged between 60 and 89 years. The measures used were Anxiety, Depression, Life Satisfaction, Positive and Negative Affect, Subjective Happiness, and Resilience.
Results: Training in Gratitude and Savoring increased scores in Life Satisfaction, Positive Affect, Subjective Happiness and Resilience, and reduced Negative Affect, whereas training in Optimism failed to produce a significant change in these variables. The Savoring and Optimism interventions decreased scores in Depression but, contrary to hypothesis, this was not the case for Gratitude.
Conclusion: These results represent an important step in understanding what type of strengths work best when it comes to enhancing well-being in older adults and consequently helping them tackle the challenges of everyday life and recover as quickly as possible from the adverse situations and events that may arise.
Different agri-food wastes (brewer´s spent grain (BSG), spent coffee ground (SCG) and kale stems) have been proposed as excellent sources of protein-enriched extracts with an antioxidant capacity. ...The optimization of the microwave-assisted hydrothermal and alkali extraction has been compared in this study. From a technical and economic point of view, the extraction of BSG under optimal conditions (110 ºC, 10 min and 0.5 M NaOH) provided the best extract with a content of 14.6 kg protein/100 kg BSG (dry matter), 13.8 g/L of total sugars and an antioxidant activity (DPPH method) of 17.1 mg trolox equivalents (TE)/g BSG. This extract had the lowest production cost (29.9 €/kg) and a minimum selling price of 51.7 €/kg, estimated for an extraction pilot plant of 15 kg/h of BSG. The microwave-assisted hydrothermal extraction of kale stems, a novel waste in the biorefinery context, also provides bioactive and green extracts of commercial interest. There is a need for specific research studies related to biorefining of agri-food wastes to produce proteins for food, contributing to the development of a future sustainable and climate-neutral agriculture. The proposed techno-economic assessment represents an important advance in research and scaling-up of microwave-assisted extraction processes for protein recovery from agri-food wastes.
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•Protein recovery from brewer´s spent grain, spent coffee grounds and kale stems.•Techno-economic comparison of microwave-assisted protein extraction processes.•Maximum protein recovery got of 14.6 kg/100 kg BSG at 110 ºC, 10 min and 0.5 M NaOH.•MW-hydrothermal extraction of kale stems is a promising process for scaling-up.•Protein enriched-extracts with antioxidant activity for comercial applications.
The use of molecular biomarkers for COVID-19 remains unconclusive. The application of a molecular biomarker in combination with clinical ones that could help classifying aggressive patients in first ...steps of the disease could help clinician and sanitary system a better management of the disease. Here we characterize the role of ACE2, AR, MX1, ERG, ETV5 and TMPRSS2 for trying a better classification of COVID-19 through knowledge of the disease mechanisms.
A total of 329 blood samples were genotyped in ACE2, MX1 and TMPRSS2. RNA analyses were also performed from 258 available samples using quantitative polymerase chain reaction for genes: ERG, ETV5, AR, MX1, ACE2, and TMPRSS2. Moreover, in silico analysis variant effect predictor, ClinVar, IPA, DAVID, GTEx, STRING and miRDB database was also performed. Clinical and demographic data were recruited from all participants following WHO classification criteria.
We confirm the use of ferritin (p < 0.001), D-dimer (p < 0.010), CRP (p < 0.001) and LDH (p < 0.001) as markers for distinguishing mild and severe cohorts. Expression studies showed that MX1 and AR are significantly higher expressed in mild vs severe patients (p < 0.05). ACE2 and TMPRSS2 are involved in the same molecular process of membrane fusion (p = 4.4 × 10
), acting as proteases (p = 0.047).
In addition to the key role of TMPSRSS2, we reported for the first time that higher expression levels of AR are related with a decreased risk of severe COVID-19 disease in females. Moreover, functional analysis demonstrates that ACE2, MX1 and TMPRSS2 are relevant markers in this disease.
Artificial neural networks (ANNs) have become key methods for achieving global climate goals. The aim of this review is to carry out a detailed analysis of the applications of ANNs to the energy ...transition all over the world. Thus, the applications of ANNs to renewable energies such as solar, wind, and tidal energy or for the prediction of greenhouse gas emissions were studied. This review was conducted through keyword searches and research of publishers and research platforms such as Science Direct, Research Gate, Google Scholar, IEEE Xplore, Taylor and Francis, and MDPI. The dates of the most recent research were 2018 for wind energy, 2022 for solar energy, 2021 for tidal energy, and 2021 for the prediction of greenhouse gas emissions. The results obtained were classified according to the type of structure and the architecture used, the inputs/outputs used, the region studied, the activation function used, and the algorithms used as the main methods for synthesizing the results. To carry out the present review, 96 investigations were used, and among them, the predominant structure was that of the multilayer perceptron, with Purelin and Sigmoid as the most used activation functions.
Abstract
Objectives
It is widely acknowledged that the experience of pain is promoted by both genetic susceptibility and environmental factors such as engaging in physical activity (PA), and that ...pain-related cognitions are also important. Thus, the purpose of the present study was to test the association of 64 polymorphisms (34 candidate genes) and the gene–gene, gene–PA and gene–sedentary behaviour interactions with pain and pain-related cognitions in women with FM.
Methods
Saliva samples from 274 women with FM mean (s.d.) age 51.7 (7.7) years were collected for extracting DNA. We measured PA and sedentary behaviour by accelerometers for a week, pain with algometry and questionnaires, and pain-related cognitions with questionnaires. To assess the robustness of the results, a meta-analysis was also performed.
Results
The rs6311 and rs6313 polymorphisms (5-hydroxytryptamine receptor 2A, HTR2A) were individually related to algometer scores. The interaction of rs4818 (catechol-O-methyltransferase, COMT) and rs1799971 (opioid receptor μ gene, OPRM1) was related to pain catastrophizing. Five gene–behaviour interactions were significant: the interactions of sedentary behaviour with rs1383914 (adrenoceptor alpha 1A, ADRA1A), rs6860 (charged multivesicular body protein 1A, CHMP1A), rs4680 (COMT), rs165599 (COMT) and rs12994338 (SCN9A) on bodily pain subscale of the Short Form 36. Furthermore, the meta-analysis showed an association between rs4680 (COMT) and severity of FM symptoms (codominant model, P-value 0.032).
Conclusion
The HTR2A gene (individually), COMT and OPRM1 gene–gene interaction, and the interactions of sedentary behaviour with ADRA1A, CHMP1A, COMT and SCN9A genes were associated with pain-related outcomes. Collectively, findings from the present study indicate a modest contribution of genetics and gene–sedentary behaviour interaction to pain and pain catastrophizing in women with FM. Future research should examine whether reducing sedentary behaviour is particularly beneficial for reducing pain in women with genetic susceptibility to pain.
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