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This study aimed to investigate the mechanism of quercetin increasing growth performance and decreasing incidence of diarrhea in weaned piglets. Forty-eight Duroc × Landrace × Large White weaned piglets with similar body weight (7.48 ± 0.20 kg, 28 days of age) were randomly divided into four treatments (control, 250 mg/kg quercetin, 500 mg/kg quercetin, and 750 mg/kg quercetin treatments) and fed with basal diet or experimental diet supplemented with quercetin. Performance, diarrhea rate and index, and content of serum anti-inflammatory factors were determined and calculated in weaned piglets; colonic flora and signaling pathways related to anti-inflammation were measured using 16S rDNA sequencing and RNA-seq, respectively. The results showed that compared with control, feed-to-gain ratio and content of serum interferon gamma (IFN-γ) were significantly decreased in the 500 and 750 mg/kg quercetin treatments (P < 0.05); quercetin significantly decreased diarrhea rate and diarrhea index (P < 0.05) and significantly increased the content of serum transforming growth factor (TGF-ß) in weaned piglets (P < 0.05); the content of serum NF-κB was significantly decreased in the 750 mg/kg quercetin treatment (P < 0.05); moreover, quercetin significantly increased diversity of colonic flora (P < 0.05), and at the phylum level, the relative abundance of Actinobacteria in the 500 and 750 mg/kg treatments was significantly increased (P < 0.05), and the relative abundance of Proteobacteria in the three quercetin treatments were significantly decreased (P < 0.05) in the colon of weaned piglets; at the genus level, the relative abundance of Clostridium-sensu-stricto-1, Turicibacter, unclassified_f_Lachnospiraceae, Phascolarctobacterium, and Family_XIII _AD3011_group was significantly increased (P < 0.05); the relative abundance of Subdollgranulum and Blautia was significantly decreased in the 500 and 750 mg/kg treatments (P < 0.05); the relative abundance of Eschericha-Shigella, Terrisporobacter, and Eubacterium-coprostanoligenes was significantly increased (P < 0.05); the relative abundance of Streptocococcus, Sarcina, Staphylococcus, and Ruminococcaceae_UCG-008 was significantly decreased in the three quercetin treatments (P < 0.05); the relative abundance of Ruminococcaceae_UCG_014 was significantly increased in the 250 mg/kg quercetin treatment in the colon of weaned piglets (P < 0.05). The results of Gene Ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis showed that differentially expressed genes (DEGs) from the quercetin treatments were significantly enriched in nuclear transcription factor-κB (NF-κB) signal pathway (P < 0.05); mRNA expression of tumor necrosis factor-α (TNF-α), interleukin-1R1 (IL-1R1), conserved helix-loop-helix ubiquitous kinase (CHUK), toll-like receptor 4 (TLR4), and IL-1ß from quercetin treatments were significantly decreased in colonic mucosa of weaned piglets (P < 0.05). In summary, quercetin increased feed conversion ratio and decreased diarrhea through regulating NF-κB signaling pathway, controlling the balance between anti-inflammatory and proinflammatory factors, and modulating intestinal flora, thus promoting the absorption of nutrients in weaned piglets. These results provided the theoretical foundation for applying quercetin in preventing weaning piglets' diarrhea and animal husbandry practices.
Subject(s)
Diarrhea , Quercetin , Weaning , Animals , Quercetin/pharmacology , Quercetin/therapeutic use , Swine , Diarrhea/veterinary , Diarrhea/drug therapy , Gastrointestinal Microbiome/drug effects , Swine Diseases/microbiology , Swine Diseases/drug therapy , IncidenceABSTRACT
Yu Liu, Zhengyang Zhang, Yongting Luo, Peng An, Jingyi Qi, Xu Zhang, Shuaishuai Zhou, Yongzhi Li, Chong Xu, Junjie Luo, and Jiaping Wang. Product of traditional Chinese medicine longgui yangxinwan protects the human body from altitude sickness damage by reducing oxidative stress and preventing mitochondrial dysfunction. High Alt Med Biol. 00:00-00, 2024. Background: Plateau reaction, caused by high-altitude exposure, results in symptoms like headaches, dyspnea, palpitations, fatigue, shortness of breath, and insomnia due to reduced oxygen levels. Mitochondria are crucial for high-altitude acclimatization as they regulate oxygen metabolism and cellular energy, reducing oxidative stress and maintaining bodily functions. Methods: The study participants were randomly divided into placebo group, Rhodiola group and longgui yangxinwan (Original name: taikong yangxinwan) group, with 20 people in each group. Three groups of subjects were sampled at three time points (PI: pre-intervention; P-D1: high-altitude day 1; P-D7: high-altitude day 7), and blood pressure, blood oxygen, heart rate, hemoglobin, and red blood cell count were measured. The ATP content, mitochondrial DNA copy number, expression of mitochondria-related genes, reactive oxygen species (ROS), glutathione peroxidase (GSH-PX) and malondialdehyde (MDA) levels, and mitochondrial morphology were measured in blood at each time point. Results: Our study results demonstrate that longgui yangxinwan keeps the selected human physiological indicators stable and prevents mitochondrial dysfunction in the high altitude. Mechanically, longgui yangxinwan decreases the level of ROS in human serum, whereas increases the activity of the antioxidant enzyme GSH-PX. At high-altitude day 1 (P-D1) and high-altitude day 7 (P-D7), ROS in the placebo group were 1.5 and 2.2-fold higher than those of the longgui yangxinwan group, respectively. In addition, longgui yangxinwan enhances ATP production capacity, restores the levels of mitochondrial respiratory chain complexes, and effectively maintains mitochondrial morphology and integrity. At P-D1 and P-D7, the ATP levels in the longgui yangxinwan group were 19-fold and 26-fold higher than those in the placebo group, respectively. Conclusions: Our study highlights longgui yangxinwan as a potential drug for protecting humans from high-altitude damage by reducing oxidative stress and preventing mitochondrial dysfunction.
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BACKGROUND: Uncertainties still existed about the effect of high-quality protein supplementation on cardiovascular disease (CVD) risk factors, although high-quality proteins such as soy and milk proteins have proposed to be beneficial for cardiometabolic health. METHODS: A systematic search in PubMed, Web of Science, Cochrane Library, Scopus, and Embase was conducted to quantify the impact of high-quality protein on CVD risk factors. RESULTS: 63 RCTs on 4 types of high-quality protein including soy protein, milk protein, whey, and casein were evaluated. Soy protein supplementation decreased systolic blood pressure (SBP, -1.42 [-2.68, -0.17] mmHg), total cholesterol (TC, -0.18 [-0.30, -0.07] mmol/L), and low-density lipoprotein cholesterol (LDL-C, -0.16 [-0.27, -0.05] mmol/L). Milk protein supplementation decreased SBP (-2.30 [-3.45, -1.15] mmHg) and total cholesterol (-0.27 [-0.51, -0.03] mmol/L). Whey supplementation decreased SBP (-2.20 [-3.89, -0.51] mmHg), diastolic blood pressure (DBP, -1.07 [-1.98, -0.16] mmHg), triglycerides (-0.10 [-0.17, -0.03] mmol/L), TC (-0.18 [-0.35, -0.01] mmol/L), LDL-C (-0.09 [-0.16, -0.01] mmol/L) and fasting blood insulin (FBI, -2.02 [-3.75, -0.29] pmol/L). Casein supplementation decreased SBP (-4.10 [-8.05, -0.14] mmHg). In the pooled analysis of four high-quality proteins, differential effects were seen in individuals with different health status. In hypertensive individuals, high-quality proteins decreased both SBP (-2.69 [-3.50, -1.87] mmHg) and DBP (-1.34 [-2.09, -0.60] mmHg). In overweight/obese individuals, high-quality proteins improved SBP (-1.40 [-2.22, -0.59] mmHg), DBP (-2.59 [-3.20, -1.98] mmHg), triglycerides (-0.09 [-0.15, -0.02] mmol/L), TC (-0.14 [-0.22, -0.05] mmol/L), LDL-C (-0.12 [-0.16, -0.07] mmol/L), and HDL-C levels (0.02 [0.01, 0.04] mmol/L). According to the benefits on CVD risks factors, whey ranked top for improving cardiometabolic health in hypertensive or overweight/obese individuals. CONCLUSION: Our study supports a beneficial role of high-quality protein supplementation to reduce CVD risk factors. Further studies are still warranted to investigate the effects of different high-quality proteins on CVD risks in individuals with cardiometabolic disorders.
Subject(s)
Cardiovascular Diseases , Dietary Supplements , Heart Disease Risk Factors , Metabolic Diseases , Randomized Controlled Trials as Topic , Humans , Cardiovascular Diseases/prevention & control , Metabolic Diseases/prevention & control , Dietary Proteins/administration & dosage , Soybean Proteins/administration & dosage , Milk Proteins/administration & dosage , Blood Pressure/drug effects , Whey Proteins/administration & dosage , Risk FactorsABSTRACT
BACKGROUND: The discovery of traditional plants' medicinal and nutritional properties has opened up new avenues for developing pharmaceutical and dietary strategies to prevent atherosclerosis. However, the effect of the antioxidant Dendrobium officinale polysaccharide (DOP) on atherosclerosis is still not elucidated. PURPOSE: This study aims to investigate the inhibitory effect and the potential mechanism of DOP on high-fat diet-induced atherosclerosis in Apolipoprotein E knockout (ApoE-/-) mice. STUDY DESIGN AND METHODS: The identification of DOP was measured by high-performance gel permeation chromatography (HPLC) and Fourier transform infrared spectroscopy (FTIR). We used high-fat diet (HFD)-induced atherosclerosis in ApoE-/- mice as an animal model. In the DOP intervention stage, the DOP group was treated by gavage with 200 µL of 200 mg/kg DOP at regular times each day and continued for eight weeks. We detected changes in serum lipid profiles, inflammatory factors, anti-inflammatory factors, and antioxidant capacity to investigate the effect of the DOP on host metabolism. We also determined microbial composition using 16S rRNA gene sequencing to investigate whether the DOP could improve the structure of the gut microbiota in atherosclerotic mice. RESULTS: DOP effectively inhibited histopathological deterioration in atherosclerotic mice and significantly reduced serum lipid levels, inflammatory factors, and malondialdehyde (F/B) production. Additionally, the levels of anti-inflammatory factors and the activity of antioxidant enzymes, including superoxide dismutase (SOD) and glutathione peroxidase (GSH-PX), were significantly increased after DOP intervention. Furthermore, we found that DOP restructures the gut microbiota composition by decreasing the Firmicutes/Bacteroidota (F/B) ratio. The Spearman's correlation analysis indicated that serum lipid profiles, antioxidant activity, and pro-/anti-inflammatory factors were associated with Firmicutes, Bacteroidota, Allobaculum, and Coriobacteriaceae_UCG-002. CONCLUSIONS: This study suggests that DOP has the potential to be developed as a food prebiotic for the treatment of atherosclerosis in the future.
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The development of low-cost, high-efficiency, and stable electrocatalysts for the alkaline hydrogen evolution reaction (HER) is a key challenge because the alkaline HER kinetics is slowed by an additional water dissociation step. Herein, we report an interfacial engineering strategy for polyoxometalate (POM)-stabilized nickel (Ni) quantum dots decorated on the surface of porous titanium mesh (POMs-Ni@PTM) for high-rate and stable alkaline hydrogen production. Benefiting from the strong interfacial interactions among POMs, Ni atoms, and PTM substrates, as well as unique POM-Ni quantum dot structures, the optimized POMs-Ni@PTM electrocatalyst exhibits a remarkable alkaline HER performance with an overpotential (η10) of 30.1 mV to reach a current density of 10 mA cm-2, which is much better than those of bare Ni decorated porous titanium mesh (Ni@PTM) (η10 = 171.1 mV) and POM decorated porous titanium mesh (POMs@PTM) electrocatalysts (η10 = 493.6 mV), comparable to that of the commercial 20 wt% platinum/carbon (20% Pt/C) electrocatalyst (η10 = 20 mV). Moreover, the optimized POMs-Ni@PTM electrocatalyst demonstrates excellent stability under continuous alkaline water-splitting at a current density of â¼100 mA cm-2 for 100 h, demonstrating great potential for its practical application.
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According to research, shock, the most common complication of extremely severe burns, is also the leading cause of mortality among patients with such burns. The case fatality rate reaches 83.45% when the total burn area exceeds 90%. The American Heart Association in 2020 recommended the intraosseous (IO) access after the peripheral access and prior to the central venous access when venous cannulation is either difficult or delayed. The use and experience with intraosseous infusion in extremely severe burns are still limited. We report efficacy and safety results from 19 burn patients treated with IO infusion between June 2020 and December 2022. In these patients, the mean injury time of burns was 1.55 ± 1.10 hours, the mean burn surface area was 86.24% ± 11.33%, the mean catheterization time was 49.68 ± 10.11 seconds, and the mean emergency retention time was 2.75 ± 1.74 hours, the mean actual fluid supplement amount was 5,533.68 ± 3,077.19 mL, the mean hourly urine volume of the patient was 93.31 ± 60.94 mL, the mean emergency detention time was 4.16 ± 2.97 hours, and the mean duration of hospitalization was 34.50 ± 25.38 days. The results demonstrated a clinically meaningful improvement and higher response rate vs peripheral venous cannulation and an acceptable safety profile in those patients.
Subject(s)
Burns , Shock , Humans , Burns/therapy , Infusions, Intraosseous , Fluid Therapy/methods , Resuscitation/methodsABSTRACT
BACKGROUND AND AIMS: Stanford type A aortic dissection (AD) is a degenerative aortic remodelling disease marked by an exceedingly high mortality without effective pharmacologic therapies. Smooth muscle cells (SMCs) lining tunica media adopt a range of states, and their transformation from contractile to synthetic phenotypes fundamentally triggers AD. However, the underlying pathomechanisms governing this population shift and subsequent AD, particularly at distinct disease temporal stages, remain elusive. METHODS: Ascending aortas from nine patients undergoing ascending aorta replacement and five individuals undergoing heart transplantation were subjected to single-cell RNA sequencing. The pathogenic targets governing the phenotypic switch of SMCs were identified by trajectory inference, functional scoring, single-cell regulatory network inference and clustering, regulon, and interactome analyses and confirmed using human ascending aortas, primary SMCs, and a ß-aminopropionitrile monofumarate-induced AD model. RESULTS: The transcriptional profiles of 93 397 cells revealed a dynamic temporal-specific phenotypic transition and marked elevation of the activator protein-1 (AP-1) complex, actively enabling synthetic SMC expansion. Mechanistically, tumour necrosis factor signalling enhanced AP-1 transcriptional activity by dampening mitochondrial oxidative phosphorylation (OXPHOS). Targeting this axis with the OXPHOS enhancer coenzyme Q10 or AP-1-specific inhibitor T-5224 impedes phenotypic transition and aortic degeneration while improving survival by 42.88% (58.3%-83.3% for coenzyme Q10 treatment), 150.15% (33.3%-83.3% for 2-week T-5224), and 175.38% (33.3%-91.7% for 3-week T-5224) in the ß-aminopropionitrile monofumarate-induced AD model. CONCLUSIONS: This cross-sectional compendium of cellular atlas of human ascending aortas during AD progression provides previously unappreciated insights into a transcriptional programme permitting aortic degeneration, highlighting a translational proof of concept for an anti-remodelling intervention as an attractive strategy to manage temporal-specific AD by modulating the tumour necrosis factor-OXPHOS-AP-1 axis.
Subject(s)
Aortic Diseases , Aortic Dissection , Benzophenones , Isoxazoles , Vascular Diseases , Humans , Transcription Factor AP-1 , Aminopropionitrile , Cross-Sectional Studies , Aortic Dissection/genetics , Aortic Diseases/pathology , Vascular Diseases/pathology , Myocytes, Smooth Muscle/pathology , Myocytes, Smooth Muscle/physiology , Tumor Necrosis FactorsABSTRACT
To improve the output flow characteristics of the piezoelectric pump in one direction, a new valveless piezoelectric pump with a crescent dune bluff body has been proposed. The pump can achieve low damage to the active substance on the premise that the active cell can guarantee the transport volume. By comparing with the hemispherically deficient and imitated meniscus resistance fluid, the barchan dune resistance fluid which can effectively improve the unidirectional output of the piezoelectric pump is obtained. Combined with the pump theoretical flow calculation formula, these influencing parameters, the degree of inclination, the sand ridge radius and the order of the crescent dune were analyzed. Finally, an experimental prototype of a valveless piezoelectric pump has been fabricated by 3D printing technology, and the pump flow test is being conducted. The relationship between frequency, voltage and output flow has been obtained. The test results show that with a dune inclination of 37.5, a sand ridge radius of 6.75â mm and a dune order of 4, the flow rate of the piezoelectric pump is best at 194.7â mL/min. The experimental results agree with the simulation results, showing the effectiveness of the valveless piezoelectric pump structure.
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Dandelion (Taraxacum officinale), a member of the Asteraceae (Compositae) family, is well known as the traditional medical plant. Dandelion polysaccharides, a natural active ingredient extracted from the dandelion, possess immune regulation, anti-inflammatory, antioxidant, and anti-aggregation properties. These properties suggest that dandelion polysaccharides might alleviate atherosclerosis. Using an ApoE-/- atherosclerotic mice model fed a high-fat diet, we investigated the impact and potential mechanism of dandelion polysaccharides on atherosclerosis. We observed that dandelion polysaccharides significantly reduced the levels of triglyceride, total cholesterol, and low-density lipoprotein-cholesterol in serum, while elevated the high-density lipoprotein-cholesterol level. Concomitantly, dandelion polysaccharides reduced the area of atherosclerotic lesions and necrotic core of the aortic sinus, and increased the collagen content. Mechanistic studies showed that dandelion polysaccharides were effective in reducing serum malondialdehyde levels while elevating the enzymatic activities of superoxide dismutase and glutathione peroxidase. Furthermore, dandelion polysaccharides reduced the expression of chemotactic factor Mcp-1 and pro-inflammatory cytokines (Tnf-α, Il-1ß, and Il-6) in atherosclerotic lesions. Overall, these results indicated that dandelion polysaccharides may take an important part in the attenuation of atherosclerosis via its antioxidant and anti-inflammatory properties.
Subject(s)
Atherosclerosis , Taraxacum , Mice , Animals , Antioxidants/pharmacology , Antioxidants/therapeutic use , Diet, High-Fat/adverse effects , Atherosclerosis/drug therapy , Atherosclerosis/etiology , Atherosclerosis/metabolism , Anti-Inflammatory Agents/pharmacology , Anti-Inflammatory Agents/therapeutic use , Cholesterol, LDL , Polysaccharides/pharmacology , Polysaccharides/therapeutic useABSTRACT
Cervical cancer is one of the leading causes of cancer death in women. Mitochondrial-mediated ferroptosis (MMF) is a recently discovered form of cancer cell death. However, the role and the underlying mechanism of MMF in cervical cancer remain elusive. Here, using an unbiased screening for mitochondrial transmembrane candidates, we identified mitochondrial carrier 1 (MTCH1) as a central mediator of MMF in cervical cancers. MTCH1-deficiency disrupted mitochondrial oxidative phosphorylation while elevated mitochondrial reactive oxygen species (ROS) by decreasing NAD+ levels. This mitochondrial autonomous event initiated a mitochondria-to-nucleus retrograde signaling involving reduced FoxO1 nuclear translocation and subsequently downregulation of the transcription and activity of a key anti-ferroptosis enzyme glutathione peroxidase 4 (GPX4), thereby elevating ROS and ultimately triggering ferroptosis. Strikingly, targeting MTCH1 in combination with Sorafenib effectively and synergistically inhibited the growth of cervical cancer in a nude mouse xenograft model by actively inducing ferroptosis. In conclusion, these findings enriched our understanding of the mechanisms of MMF in which MTCH1 governed ferroptosis though retrograde signaling to FoxO1-GPX4 axis, and provided a potential therapeutic target for treating cervical cancer.
Subject(s)
Ferroptosis , Uterine Cervical Neoplasms , Female , Mice , Animals , Humans , Uterine Cervical Neoplasms/drug therapy , Uterine Cervical Neoplasms/genetics , Phospholipid Hydroperoxide Glutathione Peroxidase/metabolism , Reactive Oxygen Species/metabolism , Cell Death/physiology , Membrane Proteins/pharmacology , Mitochondrial ProteinsABSTRACT
BACKGROUND: Sarcoplasmic reticulum calcium ATPase 2a (SERCA2a) is a key protein that maintains myocardial Ca 2+ homeostasis. The present study aimed to investigate the mechanism underlying the SERCA2a-SUMOylation (small ubiquitin-like modifier) process after ischemia/reperfusion injury (I/RI) in vitro and in vivo . METHODS: Calcium transient and systolic/diastolic function of cardiomyocytes isolated from Serca2a knockout (KO) and wild-type mice with I/RI were compared. SUMO-relevant protein expression and localization were detected by quantitative real-time PCR (RT-qPCR), Western blotting, and immunofluorescence in vitro and in vivo . Serca2a-SUMOylation, infarct size, and cardiac function of Senp1 or Senp2 overexpressed/suppressed adenovirus infected cardiomyocytes, were detected by immunoprecipitation, triphenyltetrazolium chloride (TTC)-Evans blue staining, and echocardiography respectively. RESULTS: The results showed that the changes of Fura-2 fluorescence intensity and contraction amplitude of cardiomyocytes decreased in the I/RI groups and were further reduced in the Serca2a KO + I/RI groups. Senp1 and Senp2 messenger ribose nucleic acid (mRNA) and protein expression levels in vivo and in cardiomyocytes were highest at 6 h and declined at 12 h after I/RI. However, the highest levels in HL-1 cells were recorded at 12 h. Senp2 expression increased in the cytoplasm, unlike that of Senp1. Inhibition of Senp2 protein reversed the I/RI-induced Serca2a-SUMOylation decline, reduced the infarction area, and improved cardiac function, while inhibition of Senp1 protein could not restore the above indicators. CONCLUSION: I/RI activated Senp1 and Senp2 protein expression, which promoted Serca2a-deSUMOylation, while inhibition of Senp2 expression reversed Serca2a-SUMOylation and improved cardiac function.
Subject(s)
Myocardial Reperfusion Injury , Myocytes, Cardiac , Animals , Mice , Calcium/metabolism , Cysteine Endopeptidases/genetics , Cysteine Endopeptidases/metabolism , Myocardial Reperfusion Injury/genetics , Myocardial Reperfusion Injury/metabolism , Myocardium/metabolism , Myocytes, Cardiac/metabolism , Proteins/metabolism , Sarcoplasmic Reticulum Calcium-Transporting ATPases/geneticsABSTRACT
Copper is an essential micronutrient for human body and plays a vital role in various biological processes including cellular respiration and free radical detoxification. Generally, copper metabolism in the body is in a stable state, and there are specific mechanisms to regulate copper metabolism and maintain copper homeostasis. Dysregulation of copper metabolism may have a great connection with various types of diseases, such as Wilson disease causing copper overload and Menkes disease causing copper deficiency. Cancer presents high mortality rates in the world due to the unlimited proliferation potential, apoptosis escape and immune escape properties to induce organ failure. Copper is thought to have a great connection with cancer, such as elevated levels in cancer tissue and serum. Copper also affects tumor progression by affecting angiogenesis, metastasis and other processes. Notably, cuproptosis is a novel form of cell death that may provide novel targeting strategies for developing cancer therapy. Copper chelators and copper ionophores are two copper coordinating compounds for the treatment of cancer. This review will explore the relationship between copper metabolism and cancers, and clarify copper metabolism and cuproptosis for cancer targeted therapy.
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This study aims to compare the effect of quercetin and daidzein on production performance, anti-oxidation, hormones, and cecal microflora in laying hens during the late laying period. A total of 360 53-week-old healthy Hyline brown laying hens were randomly divided into 3 groups (control, 0.05% quercetin, and 0.003% daidzein). Diets were fed for 10 wk, afterwards 1 bird per replicate (6 replicates) were euthanized for sampling blood, liver and cecal digesta. Compared with the control, quercetin significantly increased laying rate and decreased feed-to-egg weight ratio from wk 1 to 4, wk 5 to 10, and wk 1 to 10 (P < 0.05). Quercetin significantly increased the activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) and decreased catalase (CAT) activity and malondialdehyde (MDA) content in serum and liver (P < 0.05) and increased content of total antioxidant capacity (T-AOC) in liver (P < 0.05). Quercetin increased content of estradiol (E2), luteinizing hormone (LH), follicle-stimulating hormone (FSH), growth hormone (GH), insulin-like growth factor 1 (IGF-1), triiodothyronine (T3) and thyroxine (T4) in serum (P < 0.05). Quercetin significantly decreased the relative abundance of Bacteroidaceae and Bacteroides (P < 0.01) and significantly increased the relative abundance of Lactobacillaceae and Lactobacillus (P < 0.05) at family and genus levels in cecum. Daidzein did not significantly influence production performance from wk 1 to 10. Daidzein significantly increased SOD activity and decreased CAT activity and MDA content in serum and liver (P < 0.05), and increased T-AOC content in liver (P < 0.05). Daidzein increased content of FSH, IGF-1, T3 in serum (P < 0.05). Daidzein increased the relative abundance of Rikenellaceae RC9 gut group at genus level in cecum (P < 0.05). Quercetin increased economic efficiency by 137.59% and 8.77%, respectively, compared with daidzein and control. In conclusion, quercetin improved production performance through enhancing antioxidant state, hormone levels, and regulating cecal microflora in laying hens during the late laying period. Quercetin was more effective than daidzein in improving economic efficiency.
Subject(s)
Gastrointestinal Microbiome , Quercetin , Female , Animals , Quercetin/pharmacology , Antioxidants/metabolism , Insulin-Like Growth Factor I , Chickens/physiology , Diet/veterinary , Luteinizing Hormone , Follicle Stimulating Hormone , Superoxide Dismutase , Cecum/metabolism , Animal Feed/analysis , Dietary Supplements/analysisABSTRACT
As a novel anticancer therapy, chimeric antigen receptor T (CAR T) cell therapy may lead to cardiotoxic reactions. However, the exact incidence remains unclear. Our study aimed to preliminarily assess the prevalence of cardiotoxicity after CAR T cell treatment using a systematic review and meta-analysis. PubMed, Embase, Web of Science, and Cochrane databases were searched for potentially relevant studies. All types of relevant clinical studies were screened and assessed for risk bias. In most instances, random-effect models were used for data analysis, and heterogeneity between studies was evaluated. Standard quality assessment tools were used to assess quality. The study was registered with PROSPERO (CRD42022304611). Eight eligible studies comprising 3567 patients, including seven observational studies and one controlled study, were identified. The incidence of cardiovascular events was 16.7% [95% confidence interval (CI) 0.138-0.200, P < 0.01)]. Arrhythmia was the most common disorder, with an incidence of 6.5% (95% CI 0.029-0.115, P < 0.01). The occurrence of cardiotoxicity was associated with cytokine release syndrome (CRS), with a prevalence of 18.7% (95% CI 0.107-0.315, P < 0.01). Moreover, such adverse reactions were more common when CRS > 2 (OR = 0.07, 95% CI 0.02-0.29, P < 0.01). The risk of cardiotoxicity was not notably higher in patients receiving CAR T cell therapy than in those receiving traditional anticancer treatment. However, sufficient attention should be paid to this. And further evidence from large-scale clinical trials are needed.
Subject(s)
Immunotherapy, Adoptive , Receptors, Chimeric Antigen , Humans , Immunotherapy, Adoptive/adverse effects , Cardiotoxicity/complications , Cardiotoxicity/drug therapy , T-Lymphocytes , Cytokine Release Syndrome/drug therapy , Cytokine Release Syndrome/etiology , Cell- and Tissue-Based Therapy/adverse effectsABSTRACT
Objectives: To analyze the trends in mortality and causes of death among children under 5 years of age in Xuzhou, China between 2016 and 2020, in order to protect children's health and provide a basis for formulating child survival, development, and protection strategies. Methods: A population-based epidemiological study was conducted. Data were obtained from the Xuzhou Center for Disease Control Prevention. We input the data into the excel database and analyzed with SPSS20.0. Results: There were 1,949 children under 5 years of age died in Xuzhou, The number of deaths from 2016 to 2020 were 573 (29.40%), 577 (29.60%), 371 (19.04%), 334 (17.14%), and 94 (4.82%) respectively, mortality in children showed a downward trend. The number of deaths was relatively high in January (195 cases, 10.01%), February (190 cases, 9.75%), and May (180 cases, 9.24%), while was relatively small in July (147 cases, 7.54%), August (139 cases, 7.13%), and September (118 cases, 6.05%). The leading causes of death (COD) in children under 5 years of age were neonatal suffocation and hypoxia (323 cases, 16.57%). Pizhou (528 cases, 27.09%) showed the highest number of deaths in children under 5 years of age in China, and the Kaifa (25 cases, 1.28%) zone showed the lowest death toll. Conclusions: Our research suggested that the current strategies for reducing child mortality should prioritize the actions on neonatal deaths and conduct targeted interventions for the main cause.
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BACKGROUND: In recent years, heart failure with preserved ejection fraction (HFpEF) has received increasing clinical attention. To investigate the diagnostic value of diastolic function parameters derived from planar gated blood-pool imaging (MUGA) for detecting HFpEF in coronary atherosclerotic heart disease (coronary artery disease, CAD) patients. METHODS: Ninety-seven CAD patients with left ventricular ejection fraction ≥ 50% were included in the study. Based on the left ventricular end-diastolic pressure (LVEDP), the patients were divided into the HFpEF group (LVEDP ≥ 16 mmHg, 47 cases) and the normal LV diastolic function group (LVEDP < 16 mmHg, 50 cases). Diastolic function parameters obtained by planar MUGA include peak filling rate (PFR), filling fraction during the first third of diastole (1/3FF), filling rate during the first third of diastole (1/3FR), mean filling rate during diastole (MFR), and peak filling time (TPF). Echocardiographic parameters include left atrial volume index (LAVI), peak tricuspid regurgitation velocity (peak TR velocity), transmitral diastolic early peak inflow velocity (E), average early diastolic velocities of mitral annulars (average e'), average E/e' ratio. The diastolic function parameters obtained by planar MUGA were compared with those obtained by echocardiography to explore the clinical value of planar MUGA for detecting HFpEF. RESULTS: The Receiver-operating characteristic curve analysis of diastolic function parameters obtained from planar MUGA and echocardiography to detect HFpEF showed that: among the parameters examined by planar MUGA, the area under the curve (AUC) of PFR, 1/3FF, 1/3FR, MFR and TPF were 0.827, 0.662, 0.653, 0.663 and 0.809, respectively. Among the echocardiographic parameters, the AUCs for average e', average E/e' ratio, peak TR velocity, and LAVI values were 0.747, 0.706, 0.735, and 0.633. The combination of PFR and TPF showed an AUC of 0.856. PFR combined with TPF value demonstrated better predictive value than average e' (Z = 2.020, P = 0.043). CONCLUSION: Diastolic function parameters obtained by planar MUGA can be used to diagnose HFpEF in CAD patients. PFR combined with TPF was superior to the parameters obtained by echocardiography and showed good sensitivity and predictive power for detecting HFpEF.
Subject(s)
Coronary Artery Disease , Heart Failure , Ventricular Dysfunction, Left , Humans , Stroke Volume , Heart Failure/diagnostic imaging , Heart Failure/etiology , Ventricular Function, Left , Coronary Artery Disease/diagnosis , Coronary Artery Disease/diagnostic imaging , Gated Blood-Pool Imaging , DiastoleABSTRACT
In this study, the effects of quercetin and daidzein on egg quality, lipid metabolism, and cecal short-chain fatty acids (SCFAs) were compared in layers. Hyline brown layers at 385 days of age with a similar laying rate (81.36% ± 0.62%) and body weight (2.10 kg ± 0.04 kg) were randomly divided into three treatments, six replicates per treatment, and 20 layers per replicate. Layers in control, quercetin, and daidzein treatment were fed by a basal diet supplemented with 0 mg/kg, 500 mg/kg quercetin, and 30 mg/kg of daidzein for 10 weeks. Results showed that eggshell strength and albumen height in week 4, egg yolk diameter in week 10, and eggshell thickness and egg yolk height in weeks 4 and 10 were significantly increased in the quercetin treatment (P ≤ 0.05); contents of phospholipid (PL) and lecithin (LEC) in egg yolk and high-density lipoprotein (HDL) content in serum were significantly increased; however, contents of malondialdehyde (MDA), total cholesterol (TC), and triglyceride (TG) in egg yolk, contents of TC, TG, low-density lipoprotein (LDL), and very-low-density lipoprotein (VLDL) in serum, and contents of TC and TG in the liver were significantly decreased in the quercetin treatment (P ≤ 0.05); contents of isobutyric acid and valeric acid were significantly increased in the cecum of the quercetin treatment (P ≤ 0.05), compared with control. Moreover, egg yolk height in week 10 and eggshell thickness in weeks 4 and 10 were significantly increased in the daidzein treatment (P ≤ 0.05); contents of MDA, TC, and TG in egg yolk, TC, TG, and VLDL in serum, and TC and TG in liver were significantly decreased in the daidzein treatment (P ≤ 0.05); and HDL content was significantly increased in serum of the daidzein treatment (P ≤ 0.05) compared with control. However, daidzein did not affect SCFA content in the cecum. In conclusion, egg quality was improved by quercetin and daidzein by increasing the antioxidant ability of egg yolk and by regulating lipid metabolism in layers. Quercetin worked better than daidzein in improving egg quality under this experimental condition.
ABSTRACT
BACKGROUND: Healthy dietary patterns are rich in micronutrients, but their influence on cardiovascular disease (CVD) risks has not been systematically quantified. OBJECTIVES: The goal of this study was to provide a comprehensive and most up-to-date evidence-based map that systematically quantifies the impact of micronutrients on CVD outcomes. METHODS: This study comprised a systematic review and meta-analysis of randomized controlled intervention trials of micronutrients on CVD risk factors and clinical events. RESULTS: A total of 884 randomized controlled intervention trials evaluating 27 types of micronutrients among 883,627 participants (4,895,544 person-years) were identified. Supplementation with n-3 fatty acid, n-6 fatty acid, l-arginine, l-citrulline, folic acid, vitamin D, magnesium, zinc, α-lipoic acid, coenzyme Q10, melatonin, catechin, curcumin, flavanol, genistein, and quercetin showed moderate- to high-quality evidence for reducing CVD risk factors. Specifically, n-3 fatty acid supplementation decreased CVD mortality (relative risk [RR]: 0.93; 95% CI: 0.88-0.97), myocardial infarction (RR: 0.85; 95% CI: 0.78-0.92), and coronary heart disease events (RR: 0.86; 95% CI: 0.80-0.93). Folic acid supplementation decreased stroke risk (RR: 0.84; 95% CI: 0.72-0.97), and coenzyme Q10 supplementation decreased all-cause mortality events (RR: 0.68; 95% CI: 0.49-0.94). Vitamin C, vitamin D, vitamin E, and selenium showed no effect on CVD or type 2 diabetes risk. ß-carotene supplementation increased all-cause mortality (RR: 1.10; 95% CI: 1.05-1.15), CVD mortality events (RR: 1.12; 95% CI: 1.06-1.18), and stroke risk (RR: 1.09; 95% CI: 1.01-1.17). CONCLUSIONS: Supplementation of some but not all micronutrients may benefit cardiometabolic health. This study highlights the importance of micronutrient diversity and the balance of benefits and risks to promote and maintain cardiovascular health in diverse populations. (Antioxidant Supplementation in the Prevention and Treatment of Cardiovascular Diseases; CRD42022315165).
Subject(s)
Cardiovascular Diseases , Diabetes Mellitus, Type 2 , Stroke , Humans , Cardiovascular Diseases/epidemiology , Cardiovascular Diseases/prevention & control , Risk Factors , Heart Disease Risk Factors , Vitamin D , Folic Acid/therapeutic useABSTRACT
This study was conducted to investigate the effects and mechanism of quercetin on chicken quality in broilers. We selected 480 AA broilers (1 day old) and randomly allotted those to four treatments (negative control and 0.2, 0.4, or 0.6 g of quercetin per kg of diet) for 42 days. Compared with the control group, the supplementation with 0.4 g of quercetin significantly increased the pH45min and L * value of the thigh muscle and decreased the shearing force of the thigh muscle and breast muscle and drip loss of the thigh muscle (P < 0.05). The supplementation with 0.6 g/kg of quercetin significantly increased the pH45min and L * value of the thigh muscle, and pH45min of breast muscle and decreased the drip loss of the thigh muscle (P < 0.05). Sensory scores of meat color, tenderness, and juiciness also were improved with increasing quercetin concentration (P < 0.05). The inosinic acid (IMP) content of the breast and thigh muscles of broilers was significantly increased by supplementation with 0.6 g/kg of quercetin (P < 0.05). Supplementation with 0.2, 0.4, and 0.6 g of quercetin significantly reduced mRNA expression of L-FABP (P < 0.05, P < 0.05, and P < 0.05); supplementation with 0.4 and 0.6 g/kg of quercetin significantly increased mRNA expression of PKB and AMPKα1 (P < 0.05 and P < 0.05); supplementation with 0.6 g/kg of quercetin in the diet significantly reduced mRNA expression of SREBP1 and HMGR (P < 0.05 and P < 0.05) and significantly increased mRNA expression of CPT1 and PPARγ (P < 0.05 and P < 0.05); and supplementation with 0.2, 0.4, and 0.6 g/kg of quercetin significantly increased mRNA expression of PI3K, LPL, and Apo A1 and significantly reduced mRNA expression of ACC and FATP1 in the breast muscle of broilers (P > 0.05). PI3k, PKB, AMPK, SREBP1, and L-FABP were significantly and positively correlated with pH45min (P < 0.05); PPARγ was significantly and positively correlated with shear force (P < 0.05); CPT1 was significantly and positively correlated with the L * value (P < 0.05); and HMGR was significantly and positively correlated with drip loss (P < 0.05). In conclusion, quercetin improved the meat quality, protecting it against lipid oxidation and deposition by regulating the PI3K/PKB/AMPKα1 signaling pathway in the breast muscle of broilers.
ABSTRACT
Casein hydrolysate has various biological functional activities, especially prominent are angiotensin I-converting enzyme inhibitory activities. Increasing evidence has reported the prominent hypotensive effect of casein hydrolysate. However, the effects of casein hydrolysate on cardiovascular risk factors remain unclear and require more comprehensive and detailed studies. Here, we conducted a systematic review and meta-analysis on eligible randomized controlled trials (RCTs) to summarize the effects of casein hydrolysate supplementation on blood pressure, blood lipids, and blood glucose. In the pooled analyses, casein hydrolysate significantly reduced systolic blood pressure by 3.20 mmHg (-4.53 to -1.87 mmHg) and diastolic blood pressure by 1.50 mmHg (-2.31 to -0.69 mmHg). Supplementation of casein hydrolysate displayed no effect on total cholesterol (-0.07 mmol/L; -0.17 to 0.03 mmol/L), low-density lipoprotein cholesterol (-0.04 mmol/L; -0.15 to 0.08 mmol/L), high-density lipoprotein cholesterol (-0.01 mmol/L; -0.06 to 0.03 mmol/L), triglycerides (-0.05 mmol/L, -0.14 to 0.05 mmol/L), or fasting blood glucose (-0.01 mmol/L; -0.10 to 0.09 mmol/L) compared with the placebo diets. Collectively, this study indicated that supplementation of casein hydrolysate displayed decreasing effect on blood pressure without affecting blood lipids or glycemic status.