Search Results (4,366)

Individual susceptibility to pulmonary oxygen toxicity (PO₂tox) is highly variable and currently lacks a reliable biomarker for predicting pulmonary hyperoxic stress. As nitric oxide (NO) is involved in many respiratory system processes and functions, we aimed to determine if expired nitric oxide (F_ENO) levels can provide an indication of PO₂tox susceptibility in humans. Eight U.S. Navy-trained divers volunteered as subjects. The hyperoxic exposures consisted of six- and eight-hour hyperbaric chamber dives conducted on consecutive days in which subjects breathed 100% oxygen at 202.65 kPa. Subjects’ individual variability in pulmonary function and F_ENO was measured twice daily over five days and compared with their post-dive values to assess susceptibility to PO₂tox. Only subjects who showed no decrements in pulmonary function following the six-hour exposure conducted the eight-hour dive. F_ENO decreased by 55% immediately following the six-hour oxygen exposure (n = 8, p < 0.0001) and by 63% following the eight-hour exposure (n = 4, p < 0.0001). Four subjects showed significant decreases in pulmonary function immediately following the six-hour exposure. These subjects had the lowest baseline F_ENO, had the lowest post-dive F_ENO, and had clinical symptoms of PO₂tox. Individuals with low F_ENO were the first to develop PO₂tox symptoms and deficits in pulmonary function from the hyperoxic exposures. These data suggest that endogenous levels of NO in the lungs may protect against the development of PO₂tox. Full article

Stress caused by noise is becoming widespread globally. Noise may lead to deafness, endocrine disorders, neurological diseases, and a decline in mental health. The mechanism behind noise-induced neurodevelopmental abnormalities is unclear, but apoptosis and pro-inflammatory signals may play an important role. In this study, weaned piglets were used as a model to explore noise-induced neurodevelopmental abnormalities. We hypothesized that long-term noise exposure would induce anxiety and cause acute stress, exhibited by alterations in neurotransmission in the amygdala. A total of 72 hybrid piglets (Large White × Duroc × Min Pig) were randomly divided into three groups, including noise (exposed to mechanical noise, 80–85 dB), control (blank, exposed to natural background sound, <40 dB), and music (positive control, exposed to Mozart K.448, 60–70 dB) groups. The piglets were exposed to 6 h of auditory noise daily (10:00–16:00) for 28 days. Compared with the control group, piglets exposed to noise showed more aggressive behavior. The expression of Caspase3, Caspase9, Bax, NF-κB (p56), TLR4, MYD88, I κ B α, IL-1 β, TNF-α, and IL-12RB2 was significantly upregulated in the amygdala, while the expression of Nrf2, HO-1, CAT, and SOD was downregulated in piglets in the noise group. Cell death occurred, and numerous inflammatory cells accumulated in the amygdala of piglets in the noise group. Targeted metabolomics showed that the content of inhibitory neurotransmitter GABA was higher in the amygdala of piglets in the noise group. Compared with the noise group, piglets in the music group displayed more positive emotion-related behaviors. Compared with the noise group, the expression of genes related to apoptosis, inflammation, and oxidative damage was lower in the music group. Cells of the amygdala in the music group were also of normal morphology. Our results show that noise-induced stress causes apoptosis and neuroinflammation in the amygdala and induces anxiety during the early neonatal neural development of piglets. In contrast, to some extent, music alleviates noise-induced anxiety. Full article

Non-alcoholic fatty liver disease is a multifaceted disease that progresses through multiple phases; it involves metabolic as well as structural changes. These alterations can be measured directly or indirectly through blood, non-invasive imaging, and/or tissue analyses. While some studies have evaluated the correlations between two sets of measurements (e.g., histopathology with cross-sectional imaging or blood biomarkers), the interrelationships, if any, among histopathology, clinical blood profiles, cross-sectional imaging, and metabolomics in a pediatric cohort remain unknown. We created a multiparametric clinical MRI–histopathologic NMR network map of pediatric NAFLD through multimodal correlation networks, in order to gain insight into how these different sets of measurements are related. We found that leptin and other blood markers were correlated with many other measurements; however, upon filtering out the blood biomarkers, the network was decomposed into three independent hubs centered around histopathological features, each with associated MRI and plasma metabolites. These multi-modality maps could serve as a framework for characterizing disease status and progression and could potentially guide medical interventions. Full article

As the quality of life improves, there is an increasing demand for nutrition-rich marine organisms like fish, shellfish, and cephalopods. To address this, artificial cultivation of these organisms is being explored along with ongoing research on their growth and development. A case in point is Amphioctopus fangsiao, a highly valued cephalopod known for its tasty meat, nutrient richness, and rapid growth rate. Despite its significance, there is a dearth of studies on the A. fangsiao growth mechanism, particularly of its larvae. In this study, we collected A. fangsiao larvae at 0, 4, 12, and 24 h post-hatching and conducted transcriptome profiling. Our analysis identified 4467, 5099, and 4181 differentially expressed genes (DEGs) at respective intervals, compared to the 0 h sample. We further analyzed the expression trends of these DEGs, noting a predominant trend of continuous upregulation. Functional exploration of this trend entailed GO and KEGG functional enrichment along with protein–protein interaction network analyses. We identified GLDC, DUSP14, DPF2, GNAI1, and ZNF271 as core genes, based on their high upregulation rate, implicated in larval growth and development. Similarly, CLTC, MEF2A, PPP1CB, PPP1R12A, and TJP1, marked by high protein interaction numbers, were identified as hub genes and the gene expression levels identified via RNA-seq analysis were validated through qRT-PCR. By analyzing the functions of key and core genes, we found that the ability of A. fangsiao larvae to metabolize carbohydrates, lipids, and other energy substances during early growth may significantly improve with the growth of the larvae. At the same time, muscle related cells in A. fangsiao larvae may develop rapidly, promoting the growth and development of larvae. Our findings provide preliminary insights into the growth and developmental mechanism of A. fangsiao, setting the stage for more comprehensive understanding and broader research into cephalopod growth and development mechanisms. Full article

Orchard grass cultivation management is an effective measure to safeguard the sustainable development of the fruit industry in China. However, details of the influence of natural sod culture management on carbon (C)–nitrogen (N) nutrition of trees and fruit quality in Hanfu apple orchards are lacking. Therefore, a field experiment was conducted, which consisted of two treatments: clean tillage (CT) and natural grass cultivation (NG). Results revealed that NG treatment contributed to the increases in soil organic matter (SOM), total N, and soil NH₄⁺-N at depths of 0–20 cm and 20–40 cm, while the soil NO₃⁻-N concentration under NG treatment was significantly decreased at the same depth, within the range of 0–200 cm of the soil profile, compared with CT. NG treatment also significantly promoted leaf photosynthesis and enhanced leaf N and fruit sugar metabolism. The results of isotope labeling showed that NG treatment obviously elevated the ¹³C accumulation and distribution rate in fruits, as well as the ¹⁵N accumulation in the whole tree, whereas the ¹⁵N accumulation in fruits decreased. Furthermore, NG treatment significantly increased the fruit anthocyanin content. These results provide theoretical references for the feasibility of natural sod culture management to improve fruit quality in Hanfu apple orchards. Full article

Introduction: the objective of our study was to systematically review the current literature and perform a meta-analysis to evaluate the effect of the level of adherence to the DASH diet on blood pressure. Methods: The identification of relevant studies, data extraction and critical appraisal of the included studies were performed independently by two reviewers. A random-effects model was employed to synthesize the available evidence using the standardized mean difference (SMD) as the appropriate effect size. Results: A total of 37 and 29 articles were included in the qualitative and quantitative analysis, respectively. The pooled effect for systolic blood pressure was SMD = −0.18 (95%CI: −0.32 to −0.04; I² = 94%; PI: −0.93 to 0.57) and for diastolic blood pressure it was SMD = −0.13 (95%CI: −0.19 to −0.06; I² = 94%; PI: −0.42 to 0.17). Conclusions: Our findings showed that greater adherence to the DASH diet has a beneficial effect on blood pressure compared to the lowest adherence. Increased compliance with DASH diet recommendations might also have a positive effect on cardiometabolic factors and overall health status. Future studies should aim to standardize the tools of adherence to the DASH diet and utilize rigorous study designs to establish a clearer understanding of the potential benefits of the level of adherence to the DASH diet in blood pressure management. Full article

The untargeted approach to mass spectrometry-based metabolomics has a wide potential to investigate health and disease states, identify new biomarkers for diseases, and elucidate metabolic pathways. All this holds great promise for many applications in biological and chemical research. However, the complexity of instrumental parameters on advanced hybrid mass spectrometers can make the optimization of the analytical method immensely challenging. Here, we report a strategy to optimize the selected settings of a hydrophilic interaction liquid chromatography-tandem mass spectrometry method for untargeted metabolomics studies of human plasma, as a sample matrix. Specifically, we evaluated the effects of the reconstitution solvent in the sample preparation procedure, the injection volume employed, and different mass spectrometry-related operating parameters including mass range, the number of data-dependent fragmentation scans, collision energy mode, duration of dynamic exclusion time, and mass resolution settings on the metabolomics data quality and output. This study highlights key instrumental variables influencing the detection of metabolites along with suggested settings for the IQ-X tribrid system and proposes a new methodological framework to ensure increased metabolome coverage. Full article

The twigs of sea buckthorn, blackcurrant, gooseberries, quince, and grapes were evaluated as a promising source of biologically active compounds—proanthocyanidins (PACs). Sea buckthorn twigs had the highest content of PACs (9.2% on dry biomass). Preliminary pretreatment of biomass with freon R134a did not allow an increase in PACs content in the composition of hydrophilic extract but confirmed the value of freon extract as an antibacterial agent against P. aeruginosa and B. cereus. The content of PACs was used as an indicator for assessment of the influence of hydrophilic extracts on pancreatic lipase activity. Under normal physiological conditions, in the presence of bile, the extract, which contained 42.4% of PACs was more effective compared to the extract which contained 17.5% of PACs. At all concentrations (0.2–40 mg of sample/g of pancreatic lipase), it inhibited lipase activity by 33%. Purified PACs were the most effective in inhibiting lipase activity (by 36%). However, in pathological physiological conditions (without bile), the opposite effect on lipase activity was observed. Thus, PACs and extracts can be used as inhibitors of pancreatic lipase only under normal physiological conditions. Full article

To gain confidence in results of omic-data acquisitions, methods must be benchmarked using validated quality control materials. We report data combining both untargeted and targeted metabolomics assays for the analysis of four new human fecal reference materials developed by the U.S. National Institute of Standards and Technologies (NIST) for metagenomics and metabolomics measurements. These reference grade test materials (RGTM) were established by NIST based on two different diets and two different samples treatments, as follows: firstly, homogenized fecal matter from subjects eating vegan diets, stored and submitted in either lyophilized (RGTM 10162) or aqueous form (RGTM 10171); secondly, homogenized fecal matter from subjects eating omnivore diets, stored and submitted in either lyophilized (RGTM 10172) or aqueous form (RGTM 10173). We used four untargeted metabolomics assays (lipidomics, primary metabolites, biogenic amines and polyphenols) and one targeted assay on bile acids. A total of 3563 compounds were annotated by mass spectrometry, including 353 compounds that were annotated in more than one assay. Almost half of all compounds were annotated using hydrophilic interaction chromatography/accurate mass spectrometry, followed by the lipidomics and the polyphenol assays. In total, 910 metabolites were found in at least 4-fold different levels in fecal matter from vegans versus omnivores, specifically for peptides, amino acids and lipids. In comparison, only 251 compounds showed 4-fold differences between lyophilized and aqueous fecal samples, including DG O-34:0 and methionine sulfoxide. A range of diet-specific metabolites were identified to be significantly different between vegans and omnivores, exemplified by citrinin and C17:0-acylcarnitine for omnivores, and curcumin and lenticin for vegans. Bioactive molecules like acyl alpha-hydroxy-fatty acids (AAHFA) were differentially regulated in vegan versus omnivore fecal materials, highlighting the importance of diet-specific reference materials for dietary biomarker studies. Full article

Early detection in the development of a Major Depressive Disorder (MDD) could guide earlier clinical interventions. Although MDD can begin at a younger age, most people have their first episode in young adulthood. The underlying pathophysiological mechanisms relating to such an increased risk are not clear. The posterior cingulate cortex (PCC), exhibiting high levels of brain connectivity and metabolic activity, plays a pivotal role in the pathological mechanism underlying MDD. In the current study, we used the (F-18) fluorodeoxyglucose (FDG) positron emission tomography (PET) to measure metabolic covariance connectivity of the PCC and investigated its association with depression symptomatology evaluated by the Centre for Epidemiological Studies Depression Inventory—Revised (CESD-R) among 27 healthy individuals aged between 18 and 23 years. A significant negative correlation has been observed between CESD-R scale scores and the PCC metabolic connectivity with the anterior cingulate, medial prefrontal cortex, inferior and middle frontal gyrus, as well as the insula. Overall, our findings suggest that the neural correlates of depressive symptomatology in healthy young adults without a formal diagnosis involve the metabolic connectivity of the PCC. Our findings may have potential implications for early identification and intervention in people at risk of developing depression. Full article

Carotid artery stenosis (CAS), an atherosclerotic disease of the carotid artery, is one of the leading causes of transient ischemic attacks (TIA) and cerebrovascular attacks (CVA). The atherogenic process of CAS affects a wide range of physiological processes, such as inflammation, endothelial cell function, smooth muscle cell migration and many more. The current gold-standard test for CAS is Doppler ultrasound; however, there is yet to be determined a strong, clinically validated biomarker in the blood that can diagnose patients with CAS and/or predict adverse outcomes in such patients. In this comprehensive literature review, we evaluated all of the current research on plasma and serum proteins that are current contenders for biomarkers for CAS. In this literature review, 36 proteins found as potential biomarkers for CAS were categorized in to the following nine categories based on protein function: (1) Inflammation and Immunity, (2) Lipid Metabolism, (3) Haemostasis, (4) Cardiovascular Markers, (5) Markers of Kidney Function, (6) Bone Health, (7) Cellular Structure, (8) Growth Factors, and (9) Hormones. This literature review is the most up-to-date and current comprehensive review of research on biomarkers of CAS, and the only review that demonstrated the several pathways that contribute to the initiation and progression of the disease. With this review, future studies can determine if any new markers, or a panel of the proteins explored in this study, may be contenders as diagnostic or prognostic markers for CAS. Full article

In children with obesity, insulin hypersecretion is proposed to precede insulin resistance. We investigated if metformin could be used to attenuate insulin secretion from palmitate-treated isolated islets and its implication for children with obesity. Human islets were exposed to palmitate for 0.5 or 1 day, when metformin was introduced. After culture, glucose-stimulated insulin secretion (GSIS) was measured. Children with obesity, who had received metformin for over six months (n = 21, age 13.9 ± 1.8), were retrospectively evaluated. Children were classified as either “reducing” or “increasing” based on the difference between AUC_0–120 of insulin during OGTT before and after metformin treatment. In human islets, GSIS increased after culture in palmitate for up to 1 day but declined with continued palmitate exposure. Whereas adding metformin after 1 day of palmitate exposure increased GSIS, adding metformin after 0.5 days reduced GSIS. In children with “reducing” insulin AUC_0–120 (n = 9), 2 h glucose and triglycerides decreased after metformin treatment, which was not observed in patients with “increasing” insulin AUC_0–120 (n = 12). In isolated islets, metformin attenuated insulin hypersecretion if introduced when islet secretory capacity was maintained. In children with obesity, improved glycemic and lipid levels were accompanied by reduced insulin levels during OGTT after metformin treatment. Full article

Overfeeding and a lack of exercise are increasingly causing obesity in dogs, which has become a big problem threatening the health of dogs. Therefore, it is necessary to investigate how dietary regulations can help to improve dogs’ body conditions and minimize obesity. This study was carried out to investigate the effects of dietary mulberry leaf powder (MLP) supplementation on the growth performance, lipid metabolism parameters, and gut microbiota of Chinese indigenous dogs. Fifteen Chinese indigenous dogs (6.34 ± 0.56 kg) were randomly assigned to three treatment groups and received either the control diet (CON), high-fat diet (HF), or high-fat diet containing 6% Mulberry leaf powder (MLP) for four weeks. The CON group received a basal diet, the HF group received a basal diet supplemented with 10% lard, and the MLP group received a basal diet supplemented with 10% lard and 6% MLP. The trial lasted for four weeks. The growth performance, lipid metabolism parameters, immune globulins, cytokines, and fecal microbiota were measured. Results showed that there was no significant difference in growth performance. The MLP group appeared to have decreased (p < 0.05) the serum level of low-density lipoprotein cholesterol (LDL-C) and apoliprotein-A1(APO-A1) in serum. The MLP group appeared to have higher (p < 0.05) serum immune globulin A (IgA) levels. UPGMA results showed that the MLP group was closer to the CON group than to the HF group. LEfSe analysis showed that dietary supplementation with MLP contributed to an alteration in the genus Alloprevotella, Sarcina, and species belonging to the Bacteroides and Lactobacillus genus. Overall, the dietary supplementation of 6% MLP can improve lipid metabolism conditions and immunity in high-fat-diet-fed dogs, and can alter the gut microbial composition of dogs. Full article

It has been consistently demonstrated that circulating lipids and particularly low-density lipoprotein cholesterol (LDL-C) play a significant role in the development of coronary artery disease (CAD). Several trials have been focused on the reduction of LDL-C values in order to interfere with atherothrombotic progression. Importantly, for patients who experience acute coronary syndrome (ACS), there is a 20% likelihood of cardiovascular (CV) event recurrence within the two years following the index event. Moreover, the mortality within five years remains considerable, ranging between 19 and 22%. According to the latest guidelines, one of the main goals to achieve in ACS is an early improvement of the lipid profile. The evidence-based lipid pharmacological strategy after ACS has recently been enhanced. Although novel lipid-lowering drugs have different targets, the result is always the overexpression of LDL receptors (LDL-R), increased uptake of LDL-C, and lower LDL-C plasmatic levels. Statins, ezetimibe, and PCSK9 inhibitors have been shown to be safe and effective in the post-ACS setting, providing a consistent decrease in ischemic event recurrence. However, these drugs remain largely underprescribed, and the consistent discrepancy between real-world data and guideline recommendations in terms of achieved LDL-C levels represents a leading issue in secondary prevention. Although the cost-effectiveness of these new therapeutic advancements has been clearly demonstrated, many concerns about the cost of some newer agents continue to limit their use, affecting the outcome of patients who experienced ACS. In spite of the fact that according to the current recommendations, a stepwise lipid-lowering approach should be adopted, several more recent data suggest a "strike early and strike strong" strategy, based on the immediate use of statins and, eventually, a dual lipid-lowering therapy, reducing as much as possible the changes in lipid-lowering drugs after ACS. This review aims to discuss the possible lipid-lowering strategies in post-ACS and to identify those patients who might benefit most from more powerful treatments and up-to-date management. Full article