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The generally nonpolar SrTiO3 has attracted more attention recently because of its possibly induced novel polar states and related paraelectric-ferroelectric phase transitions. By using controlled pulsed laser deposition, high-quality, ultrathin, and strained SrTiO3 layers were obtained. Here, transmission electron microscopy and theoretical simulations have unveiled highly polar states in SrTiO3 films even down to one unit cell at room temperature, which were stabilized in the PbTiO3/SrTiO3/PbTiO3 sandwich structures by in-plane tensile strain and interfacial coupling, as evidenced by large tetragonality (â¼1.05), notable polar ion displacement (0.019 nm), and thus ultrahigh spontaneous polarization (up to â¼50 µC/cm2). These values are nearly comparable to those of the strong ferroelectrics as the PbZrxTi1-xO3 family. Our findings provide an effective and practical approach for integrating large strain states into oxide films and inducing polarization in nonpolar materials, which may broaden the functionality of nonpolar oxides and pave the way for the discovery of new electronic materials.
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Aqueous aluminum-ion batteries are attractive post-lithium battery technologies for large-scale energy storage in virtue of abundant and low-cost Al metal anode offering ultrahigh capacity via a three-electron redox reaction. However, state-of-the-art cathode materials are of low practical capacity, poor rate capability, and inadequate cycle life, substantially impeding their practical use. Here layered manganese oxide that is pre-intercalated with benzoquinone-coordinated aluminum ions (BQ-AlxMnO2) as a high-performance cathode material of rechargeable aqueous aluminum-ion batteries is reported. The coordination of benzoquinone with aluminum ions not only extends interlayer spacing of layered MnO2 framework but reduces the effective charge of trivalent aluminum ions to diminish their electrostatic interactions, substantially boosting intercalation/deintercalation kinetics of guest aluminum ions and improving structural reversibility and stability. When coupled with Zn50Al50 alloy anode in 2 m Al(OTf)3 aqueous electrolyte, the BQ-AlxMnO2 exhibits superior rate capability and cycling stability. At 1 A g-1, the specific capacity of BQ-AlxMnO2 reaches ≈300 mAh g-1 and retains ≈90% of the initial value for more than 800 cycles, along with the Coulombic efficiency of as high as ≈99%, outperforming the AlxMnO2 without BQ co-incorporation.
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Placental chorion/labyrinth trophoblasts are energy demanding which is met by the mitochondrial oxidative phosphorylation. Exercise enhances placental development and mitochondrial biogenesis, but the underlying mechanisms remain poorly understood. To address, female C57BL/6 J mice were randomly assigned into two groups: a control group and an exercise (EX) group. All animals were acclimated to treadmill exercise for 1 week before mating, but only the EX group was subjected to daily exercise during pregnancy from embryonic day (E) 1.5 to E16.5. Placenta were collected at E18.5 for biochemical and histochemical analyses, and primary trophoblast cells were isolated from the E18.5 placenta for further analyses. The data showed that exercise during pregnancy promoted the expression of syncytiotrophoblast cell markers, indicating trophoblast cell differentiation, which was closely associated with elevated mitochondrial biogenesis and oxidative metabolism in the E18.5 placenta. In addition, exercise during pregnancy activated peroxisome proliferator-activated receptor γ coactivator-1 α (PGC-1α), which was associated with upregulated placental α-ketoglutarate and the expression of isocitrate dehydrogenases and ten-eleven translocations, facilitating DNA demethylation of the Pgc1a promoter. Furthermore, exercise upregulated fibronectin type III domain containing 5 expression and the secretion of its cleaved form, irisin, which is known to activate PGC-1α. These data suggest that exercise-induced activation of PGC-1α, via epigenetic modifications, is responsible for promoting mitochondrial energy metabolism and chorion/labyrinth trophoblast development.
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Fibronectinas , Placentação , Animais , Feminino , Camundongos , Gravidez , Fibronectinas/genética , Fibronectinas/metabolismo , Camundongos Endogâmicos C57BL , Músculo Esquelético/metabolismo , Placenta/metabolismo , Fatores de Transcrição/genética , Trofoblastos/metabolismoRESUMO
High prevalence and metastasis rates are characteristics of lung cancer. Glycolysis provides energy for the development and metastasis of cancer cells. The 1,25-dihydroxy vitamin D3 (1,25(OH)2 D3 ) has been linked to reducing cancer risk and regulates various physiological functions. We hypothesized that 1,25(OH)2 D3 could be associated with the expression and activity of Na+ /H+ exchanger isoform 1 (NHE1) of Lewis lung cancer cells, thus regulating glycolysis as well as migration by actin reorganization. Followed by online public data analysis, Vitamin D3 receptor, the receptor of 1,25(OH)2 D3 has been proved to be abundant in lung cancers. We demonstrated that 1,25(OH)2 D3 treatment suppressed transcript levels, protein levels, and activity of NHE1 in LLC cells. Furthermore, 1,25(OH)2 D3 treatment resets the metabolic balance between glycolysis and OXPHOS, mainly including reducing glycolytic enzymes expression and lactate production. In vivo experiments showed the inhibition effects on tumor growth as well. Therefore, we concluded that 1,25(OH)2 D3 could amend the NHE1 function, which leads to metabolic reprogramming and cytoskeleton reconstruction, finally inhibits the cell migration.
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Neoplasias Pulmonares , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , Movimento CelularRESUMO
OBJECTIVE: Epstein-Barr virus (EBV)-associated gastric cancer (EBVaGC) is a distinct molecular subtype of gastric cancer (GC). At present, the clinical characteristics and prognostic implications of EBV infection and the potential clinical benefits of immune checkpoint blockade in GC remain to be clarified. Hence, this study was designed to analyze the clinical and pathological characteristics of GC patients with varying EBV infection states and compare their overall survival (OS). METHODS: A retrospective study was performed on 1031 consecutive GC patients who underwent gastrectomy at the Affiliated Hospital of Xuzhou Medical University from February 2018 to November 2022. EBV-encoded RNA (EBER) in situ hybridization (ISH) was used for EBV assessment, and immunohistochemical staining was used for evaluation of human epidermal growth factor receptor 2 (HER2), programmed death ligand 1 (PD-L1), and Ki67 expression. EBVaGC was defined as tumors with EBV positivity. In addition, EBV-negative GC (EBVnGC) patients were matched with EBVaGC patients based on seven clinicopathological parameters (age, gender, anatomic subsite, tumor size, Lauren classification, degree of differentiation, and tumor-node-metastasis [TNM] stage). The correlations of clinical features with HER2, PD-L1, and Ki67 expression were evaluated statistically. The survival of patients was assessed through medical records, telephone, or WeChat communication, and prognostic analysis was performed using the logrank test as well as univariable and multivariable regression analysis. RESULTS: Out of 1031 GC patients tested, 35 (3.4%) were diagnosed with EBVaGC. Notably, the EBVaGC group exhibited a distinct predominance of males and younger patients, significantly higher Ki67 and PD-L1 expression levels, and a lower prevalence of pericancerous nerve invasion than the EBVnGC group (P < 0.01). In the 35 EBVaGC cases, Ki67 expression was negatively correlated with age (P < 0.05), suggesting that a younger onset age was associated with higher Ki67 expression. In addition, PD-L1 expression was correlated with the degree of differentiation, T-stage, and clinical stage of the patient. Furthermore, PD-L1 expression was elevated in tumors with lower differentiation or at later stages (P < 0.05). Using univariate analysis, Ki67, PD-L1, and clinical stage were identified as significant factors influencing the overall survival (OS) of EBVaGC patients (P < 0.05). Moreover, multivariate survival analysis revealed that clinical stage and Ki67 expression were independent risk factors for the OS of the patients (P < 0.05), and the three-year OS rate of EBVaGC patients was 64.2%. CONCLUSION: EBV-ISH is a practical and valuable method to identify EBVaGC. Owing to its unique etiological, pathological, and clinical characteristics, patients with EBVaGC might benefit from immune checkpoint blockade therapy.
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Infecções por Vírus Epstein-Barr , Herpesvirus Humano 4 , Neoplasias Gástricas , Humanos , Neoplasias Gástricas/virologia , Neoplasias Gástricas/patologia , Masculino , Feminino , Infecções por Vírus Epstein-Barr/virologia , Infecções por Vírus Epstein-Barr/complicações , Infecções por Vírus Epstein-Barr/mortalidade , Pessoa de Meia-Idade , Herpesvirus Humano 4/genética , Prognóstico , Estudos Retrospectivos , Idoso , Adulto , Antígeno B7-H1/metabolismo , Antígeno B7-H1/genética , Receptor ErbB-2/metabolismo , Receptor ErbB-2/genética , Antígeno Ki-67/metabolismo , RNA Viral/genética , GastrectomiaRESUMO
AIMS: The survival of inoculated Escherichia coli on Fuji apples in Washington State orchards was studied, considering evaporative cooling, canopy location, year, and region, with the examination of sunlight exposure and inoculation levels in year 2. METHODS AND RESULTS: Rifampicin-resistant E. coli was applied to Fuji apples. Initial concentrations for the high-inoculation study were 7.4 ± 0.3 log10 CFU per apple and 3.4 ± 0.3 log10 CFU per apple for the low-inoculation study. Enumeration of E. coli was conducted at 0, 2, 10, 18, 34, 42, 58, 82, 106, and 154 h after inoculation. Results were analyzed using Tukey's honest significance difference test and a log-linear model. Log-linear, Weibull, and Biphasic models characterized E. coli die-off patterns for high and low inoculations. The application of evaporative overhead cooling water did not significantly influence E. coli survival on Fuji apples; inoculation level and sunlight exposure were significant factors in a log-linear model. E. coli decreased by 5.5 ± 1.3 and 3.3 ± 0.4 log10 CFU per apple for high and low inoculated apples, respectively, by 154 h. The Biphasic model best explained the die-off pattern for high and low-inoculated Fuji apples. CONCLUSIONS: Overhead evaporative cooling, a useful fruit quality practice, did not impact the survival of generic E. coli on Fuji apple surfaces. The significant impact of sunlight exposure and inoculation levels on die-off highlights the importance of ultraviolet radiation in risk reduction and the need for various inoculum concentrations in preharvest field studies.
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The effect of changes in microbial community structure on the migration and release of toxic heavy metal (loid)s is often ignored in ecological restoration. Here, we investigated a multi-metal (mercury and thallium, Tl) mine waste slag. With particular focus on its strong acidity, poor nutrition, and high toxicity pollution characteristics, we added fish manure and carbonate to the slag as environmental-friendly amendments. On this basis, ryegrass, which is suitable for the remediation of metal waste dumps, was then planted for ecological restoration. We finally explored the influence of changes in microbial community structure on the release of Tl and As in the waste slag during vegetation reconstruction. The results show that the combination of fish manure and carbonate temporarily halted the release of Tl, but subsequently promoted the release of Tl and arsenic (As), which was closely related to changes in the microbial community structure in the waste slag after fish manure and carbonate addition. The main reason for these patterns was that in the early stage of the experiment, Bacillaceae inhibited the release of Tl by secreting extracellular polymeric substances; with increasing time, Actinobacteriota became the dominant bacterium, which promoted the migration and release of Tl by mycelial disintegration of minerals. In addition, the exogenously added organic matter acted as an electron transport medium for reducing microorganisms and thus helped to reduce nitrate or As (â ¤) in the substrate, which reduced the redox potential of the waste slag and promoted As release. At the same time, the phylum Firmicutes, including specific dissimilatory As-reducing bacteria that are capable of converting As into a more soluble form, further promoted the release of As. Our findings provide a theoretical basis for guiding the ecological restoration of relevant heavy-metal (loid) mine waste dumps.
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Mercúrio , Mineração , Tálio , Mercúrio/análise , Mercúrio/metabolismo , Poluentes do Solo/análise , Poluentes do Solo/química , Metais Pesados/análise , Microbiota/efeitos dos fármacos , Resíduos Industriais/análise , Recuperação e Remediação Ambiental/métodos , Microbiologia do SoloRESUMO
OBJECTIVE: This study aimed to investigate the structure of the mitral valve in patients undergoing mitral valvuloplasty (MVP) using real-time three-dimensional transesophageal echocardiography (RT-3D-TEE). The main objective was to study the relationship between intraoperative annuloplasty ring size and mitral valve structure dimensions, with a focus on exploring the application value of RT-3D-TEE in MVP. METHODS: A total of 28 patients with degenerative mitral regurgitation (DMR), who underwent MVP between February and September 2022, as well as 12 normal control cases, were enrolled in this study. The MV annulus and leaflets were quantitatively analyzed using MVN software. RESULTS: The DMR group exhibited significantly greater dimensions in various parameters of the mitral valve, including the anterolateral-to-posteromedial diameter (DAlPm ), anterior-to-posterior diameter (DAP ), annulus height (HA ), three-dimensional annulus circumference (CA3D ), two-dimensional annulus area (AA2D ), anterior leaflet area (Aant ), posterior leaflet area (Apost ), anterior leaflet length (Lant ), posterior leaflet length (Lpost ), and tenting volume (Vtent ) compared to the control group. CONCLUSION: Real-time three-dimensional transesophageal echocardiography provides valuable insights into the morphological structure of the mitral valve and lesion location. It can aid in surgical decision-making, validate the success of MVP, and potentially reduce mortality and complications associated with mitral valve repair procedures.
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Valvuloplastia com Balão , Ecocardiografia Tridimensional , Ecocardiografia Transesofagiana , Insuficiência da Valva Mitral , Humanos , Ecocardiografia Tridimensional/métodos , Ecocardiografia Transesofagiana/métodos , Eletrocardiografia , Valva Mitral/diagnóstico por imagem , Valva Mitral/cirurgia , Insuficiência da Valva Mitral/diagnóstico por imagem , Insuficiência da Valva Mitral/cirurgiaRESUMO
BACKGROUND: Ferroptosis is emerging as a critical pathway in ischemia/reperfusion (I/R) injury, contributing to compromised cardiac function and predisposing individuals to sepsis and myocardial failure. The study investigates the underlying mechanism of dexmedetomidine (DEX) in hypoxia/reoxygenation (H/R)-induced ferroptosis in cardiomyocytes, aiming to identify novel targets for myocardial I/R injury treatment. METHODS: H9C2 cells were subjected to H/R and treated with varying concentrations of DEX. Additionally, H9C2 cells were transfected with miR-141-3p inhibitor followed by H/R treatment. Levels of miR-141-3p, long noncoding RNA (lncRNA) taurine upregulated 1 (TUG1), Fe2+, glutathione (GSH), and malondialdehyde were assessed. Reactive oxygen species (ROS) generation was measured via fluorescent labeling. Expression of ferroptosis-related proteins glutathione peroxidase 4 (GPX4) and acyl-CoA synthetase long-chain family member 4 (ACSL4) was determined using Western blot. The interaction between miR-141-3p and lncRNA TUG1 was evaluated through RNA pull-down assay and dual-luciferase reporter gene assays. The stability of lncRNA TUG1 was assessed using actinomycin D. RESULTS: DEX ameliorated H/R-induced cardiomyocyte injury and elevated miR-141-3p expression in cardiomyocytes. DEX treatment increased cell viability, Fe2+, and ROS levels while decreasing ACSL4 protein expression. Furthermore, DEX upregulated GSH and GPX4 protein levels. miR-141-3p targeted lncRNA TUG1, reducing its stability and overall expression. Inhibition of miR-141-3p or overexpression of lncRNA TUG1 partially reversed the inhibitory effect of DEX on H/R-induced ferroptosis in cardiomyocytes. CONCLUSION: DEX mitigated H/R-induced ferroptosis in cardiomyocytes by upregulating miR-141-3p expression and downregulating lncRNA TUG1 expression, unveiling a potential therapeutic strategy for myocardial I/R injury.
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Antiferroelectrics characterized by voltage-driven reversible transitions between antiparallel and parallel polarity are promising for cutting-edge electronic and electrical power applications. Wide-ranging explorations revealing the macroscopic performances and microstructural characteristics of typical antiferroelectric systems have been conducted. However, the underlying mechanism has not yet been fully unraveled, which depends largely on the atomistic processes. Herein, based on atomic-resolution transmission electron microscopy, the deterministic phase transition pathway along with the underlying lattice-by-lattice details in lead zirconate thin films was elucidated. Specifically, we identified a new type of ferrielectric-like dipole configuration with both angular and amplitude modulations, which plays the role of a precursor for a subsequent antiferroelectric to ferroelectric transformation. With the participation of the ferrielectric-like phase, the phase transition pathways driven by the phase boundary have been revealed. We provide new insights into the consecutive phase transformation in low-dimensional lead zirconate, which thus would promote potential antiferroelectric-based multifunctional devices.
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Listeria monocytogenes biofilms formed on food-contact surfaces within food-processing facilities pose a significant challenge, serving as persistent sources of cross-contamination. In this review, we examined documented cases of foodborne outbreaks and recalls linked to L. monocytogenes contamination on equipment surfaces and in the food production environment, provided an overview of the prevalence and persistence of L. monocytogenes in different food-processing facilities, and discussed environmental factors influencing its biofilm formation. We further delved into antimicrobial interventions, such as chemical sanitizers, thermal treatments, biological control, physical treatment, and other approaches for controlling L. monocytogenes biofilms on food-contact surfaces. This review provides valuable insights into the persistent challenge of L. monocytogenes biofilms in food processing, offering a foundation for future research and practical strategies to enhance food safety.
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Biofilmes , Microbiologia de Alimentos , Listeria monocytogenes , Listeria monocytogenes/fisiologia , Biofilmes/crescimento & desenvolvimento , Manipulação de Alimentos/métodos , Contaminação de Alimentos/prevenção & controle , Contaminação de Equipamentos/prevenção & controleRESUMO
BACKGROUND: While growing evidence suggests a relationship between migraine and cardiovascular disease, the genetic evidence for a causal relationship between migraine and cardiovascular disease is still scarce. Investigating the causal association between migraine and cardiovascular disease is vital. METHODS: We carried out a bidirectional Mendelian randomization (MR) study including discovery samples and replication samples using publicly available genome-wide association study (GWAS) summary datasets and stringent screening instrumental variables. Four different MR techniques-Inverse variance weighted (IVW), MR âEgger, weighted median, and weighted mode-as well as various sensitivity analyses-Cochran's Q, IVW radial, leave-one-out (LOO), and MR-PRESSO-were utilized to investigate the causal relationship between cardiovascular disease and migraine. RESULTS: The protective causal effects of genetically predicted migraine on coronary artery disease (OR, 0.881; 95% CI 0.790-0.982; p = 0.023) and ischemic stroke (OR, 0.912; 95% CI 0.854-0.974; p = 0.006) were detected in forward MR analysis but not in any other cardiovascular disease. Consistently, we also discovered protective causal effects of coronary atherosclerosis (OR, 0.865; 95% CI 0.797-0.940; p = 0.001) and myocardial infarction (OR, 0.798; 95% CI 0.668-0.952; p = 0.012) on migraine in reverse MR analysis. CONCLUSION: We found a potential protective effect of migraine on coronary artery disease and ischemic stroke and a potential protective effect of coronary atherosclerosis and myocardial infarction on migraine. We emphasised epidemiological and genetic differences and the need for long-term safety monitoring of migraine medications and future research to improve cardiovascular outcomes in migraine patients.
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Doenças Cardiovasculares , Estudo de Associação Genômica Ampla , Análise da Randomização Mendeliana , Transtornos de Enxaqueca , Humanos , Transtornos de Enxaqueca/genética , Transtornos de Enxaqueca/epidemiologia , Doenças Cardiovasculares/genética , Doenças Cardiovasculares/epidemiologia , Causalidade , Polimorfismo de Nucleotídeo Único , Predisposição Genética para DoençaRESUMO
Intestinal remodelling is dynamically regulated by energy metabolism. Exercise is beneficial for gut health, but the specific mechanisms remain poorly understood. Intestine-specific apelin receptor (APJ) knockdown (KD) and wild-type male mice were randomly divided into two subgroups, with/without exercise, to obtain four groups: WT, WT with exercise, APJ KD and APJ KD with exercise. Animals in the exercise groups were subjected to daily treadmill exercise for 3 weeks. Duodenum was collected at 48 h after the last bout of exercise. AMP-activated protein kinase (AMPK) α1 KD and wild-type mice were also utilized for investigating the mediatory role of AMPK on exercise-induced duodenal epithelial development. AMPK and peroxisome proliferator-activated receptor γ coactivator-1 α were upregulated by exercise via APJ activation in the intestinal duodenum. Correspondingly, exercise induced permissive histone modifications in the PR domain containing 16 (PRDM16) promoter to activate its expression, which was dependent on APJ activation. In agreement, exercise elevated the expression of mitochondrial oxidative markers. The expression of intestinal epithelial markers was downregulated due to AMPK deficiency, and AMPK signalling facilitated epithelial renewal. These data demonstrate that exercise-induced activation of the APJ-AMPK axis facilitates the homeostasis of the intestinal duodenal epithelium. KEY POINTS: Apelin receptor (APJ) signalling is required for improved epithelial homeostasis of the small intestine in response to exercise. Exercise intervention activates PRDM16 through inducing histone modifications, enhanced mitochondrial biogenesis and fatty acid metabolism in duodenum. The morphological development of duodenal villus and crypt is enhanced by the muscle-derived exerkine apelin through the APJ-AMP-activated protein kinase axis.
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Proteínas Quinases Ativadas por AMP , Transdução de Sinais , Camundongos , Masculino , Animais , Proteínas Quinases Ativadas por AMP/metabolismo , Receptores de Apelina , Transdução de Sinais/fisiologia , Fatores de Transcrição/metabolismo , Homeostase , Mucosa Intestinal/metabolismoRESUMO
Substance addiction causes anxiety, which in turn reinforces the maintaining of substance use, resulting in a vicious circle. And this circle is one of the reasons why addiction is so hard to cure. However, there is no treatment involved in addiction-induced anxiety at present. We tested whether VNS (vagus nerve stimulation) can improve heroin-induced anxiety, and made a comparison between nVNS (transcervical vagus nerve stimulation) and taVNS (transauricular vagus nerve stimulation) on therapeutic effect. Mice were subjected to nVNS or taVNS before heroin administration. By observing c-Fos expression in the NTS (nucleus of the solitary tract), we assessed vagal fiber activation. Using the OFT (open field test) and the EPM (elevated cross maze test), we evaluated the anxiety-like behaviors of the mice. Using immunofluorescence, we observed the proliferation and activation of microglia in the hippocampus. And ELISA was used to measure the levels of proinflammatory factors in the hippocampus. Both nVNS and taVNS significantly increased the expression of c-Fos in the nucleus of solitary tract, suggesting the feasibility of nVNS and taVNS. The anxiety level of heroin-treated mice was significantly increased, microglia in the hippocampus was significantly proliferated and activated, and the proinflammatory factors (IL-1ß, IL-6, TNF-α) in the hippocampus were significantly up-regulated. Crucially, both nVNS and taVNS reversed the above changes caused by heroin addiction. SIGNIFICANCE: It was confirmed that the therapeutic effect of VNS on heroin-induced anxiety may be an effective treatment method to break the "addiction-anxiety" cycle and provides some insights for subsequent treatment of addiction.
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Heroína , Estimulação do Nervo Vago , Camundongos , Animais , Estimulação do Nervo Vago/métodos , Próteses e Implantes , Hipocampo , Ansiedade , Nervo Vago/fisiologiaRESUMO
The innate immune system has developed sophisticated strategies to defense against infections. Host cells utilize the recognition machineries such as toll-like receptors and nucleotide binding and oligomerization domain-like receptors to identify the pathogens and alert immune system. However, some pathogens have developed tactics to evade host defenses, including manipulation of host inflammatory response, interference with cell death pathway, and highjack of phagocytosis signaling for a better survival and colonization in host. Enterohemorrhagic Escherichia coli (EHEC) is a notorious foodborne pathogen that causes severe tissue damages and gastrointestinal diseases, which has been reported to disturb host immune responses. Diverse bioactive compounds such as flavonoids, phenolic acids, alkaloids, saccharides, and terpenoids derived from food varieties and probiotics have been discovered and investigated for their capability of combating bacterial infections. Some of them serve as novel antimicrobial agents and act as immune boosters that harness host immune system. In this review, we will discuss how EHEC, specifically E. coli O157:H7, hijacks the host immune system and interferes with host signaling pathway; and highlight the promising role of food-derived bioactive compounds and probiotics in harnessing host innate immunity and eliminating E. coli O157:H7 infection with multiple strategies.
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Escherichia coli Êntero-Hemorrágica , Infecções por Escherichia coli , Escherichia coli O157 , Enteropatias , Probióticos , Humanos , Escherichia coli O157/fisiologia , Infecções por Escherichia coli/prevenção & controle , Infecções por Escherichia coli/microbiologia , Imunidade InataRESUMO
The prevalence of inflammatory bowel disease (IBD) is increasing, which is concerning because IBD is a known risk factor for the development of colorectal cancer. Emerging evidence highlights environmental factors, particularly dietary factors and gut microbiota dysbiosis, as pivotal inducers of IBD onset. Goji berry, an ancient tonic food and a nutraceutical supplement, contains a range of phytochemicals such as polysaccharides, carotenoids, and polyphenols. Among these phytochemicals, L. barbarum polysaccharides (LBPs) are the most important functional constituents, which have protective effects against oxidative stress, inflammation, and neurodegeneration. Recently, the beneficial effects of goji berry and associated LBPs consumption were linked to prebiotic effects, which can prevent dysbiosis associated with IBD. This review assessed pertinent literature on the protective effects of goji berry against IBD focusing on the gut microbiota and their metabolites in mediating the observed beneficial effects.
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Doenças Inflamatórias Intestinais , Lycium , Humanos , Prebióticos , Disbiose/prevenção & controle , Doenças Inflamatórias Intestinais/tratamento farmacológico , Doenças Inflamatórias Intestinais/prevenção & controle , Polissacarídeos/farmacologia , Compostos Fitoquímicos/farmacologiaRESUMO
A novel benzene sulfonamide compound named IMB16-4 exhibits excellent anti-hepatic fibrosis activity in a recent study. To develop potential anti-hepatic fibrosis agents, a series of benzene sulfonamide derivatives were designed and synthesized based on the scaffold of the lead compound IMB16-4. As it turned out, most of the derivatives displayed potential anti-hepatic fibrosis activity, among which, compounds 11a, 11b, 11d, 13a, 36b, and 47b exhibited inhibition rates of 42.3%, 48.7%, 42.4%, 40.0%, 39.4%, and 49.3%, respectively, which were equivalent to the control IMB16-4 with an inhibition rate of 35.9%, Costunolide with an inhibition rate of 45.4%, and much more potent than that of Epigallocatechin gallate (EGCG) with an inhibition rate of 25.3%. Especially, compounds 46a, 46b, and 46c exhibited excellent anti-hepatic fibrosis activity with inhibition rates of 61.7%, 54.8%, and 60.7%, which were almost 1.5-fold inhibition rates of IMB16-4. In addition, compounds 46a, 46b, and 46c exhibited remarkable inhibitory activity in the gene expression of COL1A1, MMP-2, and the protein expression of COL1A1, FN, α-SMA, and TIMP-1 by inhibiting the JAK1-STAT1/3 pathway. These findings furnished valuable inspiration for the further development of anti-hepatic fibrosis agents.
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Antifibróticos , Benzeno , Humanos , Derivados de Benzeno , Cirrose Hepática/tratamento farmacológico , Cirrose Hepática/metabolismo , Sulfonamidas/farmacologia , Relação Estrutura-AtividadeRESUMO
Extracellular communication within the tumor microenvironment exerts critical functions in tumor progression. Moreover, exosomes are capable of packaging into long non-coding RNAs (lncRNAs) to regulate extracellular communication. We tried to discuss the role of exosomal lncRNA TTN-AS1 and its molecular mechanism on gastric cancer (GC) progression. Bioinformatics analysis depicted increased TTN-AS1 in GC which shared correlation with poor prognosis. Clinical tissue and cellular experiments also confirmed the elevation of TTN-AS1 in GC tissues and cells. GC cell (AGS)-derived Exo could be uptake by NCI-N87 cells to induce malignant features of GC cells. Functionally, TTN-AS1 could upregulate ZEB1 expression by binding to miR-499a-5p. In addition, in vitro experiments demonstrated that ZEB1 targeted and activated CDX2 transcription and promoted CDX2 expression; silencing CDX2 inhibited malignant phenotypes of AGS and NCI-N87 cells. Furthermore, Exo-TTN-AS1 promoted GC cell growth and migration by promoting CDX2 expression. Exosomal TTN-AS1 from GC cells could also promote metastasis of GC in vivo. In conclusion, our findings provided evidence describing that exosomes derived from GC cells transferred TTN-AS1 to GC cells, which aggravate GC through the miR-499a-5p/ZEB1/CDX2 axis. 1. Exo derived from GC cells promotes the growth and metastasis of GC cells by carrying TTN-AS1. 2. TTN-AS1 acts as a ceRNA to adsorb miR-499a-5p to regulate the expression of ZEB1. 3. ZEB1 targets and activates CDX2 transcription. 4. GC cell-derived Exo-TTN-AS1 enhances the growth and metastasis of GC cell xenografts in vivo.
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Exossomos , MicroRNAs , RNA Longo não Codificante , Neoplasias Gástricas , Humanos , Neoplasias Gástricas/metabolismo , MicroRNAs/genética , MicroRNAs/metabolismo , Exossomos/genética , Exossomos/metabolismo , Linhagem Celular Tumoral , Transformação Celular Neoplásica/genética , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , Regulação Neoplásica da Expressão Gênica , Proliferação de Células/genética , Movimento Celular/genética , Microambiente Tumoral , Conectina/genética , Conectina/metabolismoRESUMO
The current study evaluated the efficacy and safety of a denosumab biosimilar, QL1206 (60 mg), compared to placebo in postmenopausal Chinese women with osteoporosis and high fracture risk. At 31 study centers in China, a total of 455 postmenopausal women with osteoporosis and high fracture risk were randomly assigned to receive QL1206 (60 mg subcutaneously every 6 months) or placebo. From baseline to the 12-month follow-up, the participants who received QL1206 showed significantly increased bone mineral density (BMD) values (mean difference and 95% CI) in the lumbar spine: 4.780% (3.880%, 5.681%), total hip :3.930% (3.136%, 4.725%), femoral neck 2.733% (1.877%, 3.589%) and trochanter: 4.058% (2.791%, 5.325%) compared with the participants who received the placebo. In addition, QL1206 injection significantly decreased the serum levels of C-terminal crosslinked telopeptides of type 1 collagen (CTX): -77.352% (-87.080%, -66.844%), and N-terminal procollagen of type l collagen (P1NP): -50.867% (-57.184%, -45.217%) compared with the placebo over the period from baseline to 12 months. No new or unexpected adverse events were observed. We concluded that compared with placebo, QL1206 effectively increased the BMD of the lumbar spine, total hip, femoral neck and trochanter in postmenopausal Chinese women with osteoporosis and rapidly decreased bone turnover markers. This study demonstrated that QL1206 has beneficial effects on postmenopausal Chinese women with osteoporosis and high fracture risk.
Assuntos
Medicamentos Biossimilares , Conservadores da Densidade Óssea , Osteoporose Pós-Menopausa , Osteoporose , Feminino , Humanos , Medicamentos Biossimilares/efeitos adversos , Densidade Óssea , Conservadores da Densidade Óssea/uso terapêutico , Remodelação Óssea , Denosumab/uso terapêutico , Denosumab/farmacologia , Método Duplo-Cego , População do Leste Asiático , Osteoporose/tratamento farmacológico , Osteoporose Pós-Menopausa/complicações , Osteoporose Pós-Menopausa/tratamento farmacológico , Pós-MenopausaRESUMO
BACKGROUND: Thalassemia trait (TT) and iron deficiency anemia (IDA) are the most common conditions of microcytic hypochromic anemia (MHA) in pregnant women. Accurate discrimination between TT and IDA is an important issue, and better methods are urgently needed. Although considerable RBC formulas and indices have been developed since 1973, distinguishing between IDA and TT is still a challenging problem due to the diversity of various anemic populations. To address this problem, we assessed the diagnostic function of 43 different differential formulas in patients with microcytic anemia by using accuracy measures and recommending a new log-based differential formula. METHODS: The data of 430 pregnant women (229 with TT and 201 with IDA) were enrolled, and 44 formula performances were evaluated with receiver operating characteristic (ROC) analysis. RESULTS: The newly introduced logarithm-based formula XS-1 performs better than the general discriminant index with sensitivity and specificity of 82.10 and 89.05, which are better than other formulas. In the pregnant population, the Shine and Lal and Roth..SVM. formulas have shown excellent performance, while other formulas showed poorer discriminative abilities in our study than in the original authors. CONCLUSION: The logarithm-based formula XS-1 can be used to screen thalassemia and iron deficiency anemia during the first trimester. Considering the particularity of pregnancy, medical personnel in different regions should choose a screening formula similar to that of the local region and population when identifying thalassemia in pregnancy. Any formula should be independently verified locally before use. For the convenience of the health care team and experimental scientists, a web-based tool has been established at http://yyy.yiyiy.top/XS-1/ by which users can easily get their desired screening test result without going through the underlying mathematical and computational details.